Sample records for long-term enzyme replacement

  1. Modelling Gaucher disease progression: long-term enzyme replacement therapy reduces the incidence of splenectomy and bone complications.

    van Dussen, Laura; Biegstraaten, Marieke; Dijkgraaf, Marcel Gw; Hollak, Carla Em


    Long-term complications and associated conditions of type 1 Gaucher Disease (GD) can include splenectomy, bone complications, pulmonary hypertension, Parkinson disease and malignancies. Enzyme replacement therapy (ERT) reverses cytopenia and reduces organomegaly. To study the effects of ERT on long-term complications and associated conditions, the course of Gaucher disease was modelled.

  2. Long Term Treatment with Enzyme Replacement Therapy in Patients with Fabry Disease.

    Oder, Daniel; Nordbeck, Peter; Wanner, Christoph


    Anderson-Fabry disease is a potentially life-threatening hereditary lysosomal storage disorder taking origin in over 1,000 known pathogenic mutations in the alpha-galactosidase A encoding gene. Over the past 15 years, intravenous replacement therapy of the deficient alpha agalsidase A enzyme has been well-established retarding the progression of a multisystemic disease and organ involvement. Despite this innovative treatment approach, premature deaths still do occur. The response to enzyme replacement therapy (ERT) varies considerably and appears to depend on gender, genotype (classic or later onset/non-classic), stage of disease or age and agalsidase inhibition by anti-agalsidase antibodies. Early ERT treatment at young age, a personalized approach, and adjunctive therapies for specific disease manifestations appear to impact on prognosis and are currently favored with the expectance of more effective intravenous and oral treatments in the short future.

  3. Bone marrow involvement in Gaucher disease at MRI: what long-term evolution can we expect under enzyme replacement therapy?

    Fedida, Benjamin; Touraine, Sebastien; Laredo, Jean-Denis [Hopital Lariboisiere, AP-HP, Department of Musculoskeletal Imaging, Paris (France); Stirnemann, Jerome [Universite Paris-Diderot Hopital Bichat, AP-HP, Department of Biostatistics and Medical Data Processing, INSERM UMR 738, Paris (France); Geneva University Hospital, Division of General Internal Medicine, Faculty of Medicine, Geneva (Switzerland); Belmatoug, Nadia [Hopital Beaujon, AP-HP, Referral Center for Lysosomal Diseases (RCLD), Clichy (France); Hopital Beaujon, AP-HP, Department of Internal Medicine, Clichy (France); Petrover, David [Hopital Lariboisiere, AP-HP, Department of Musculoskeletal Imaging, Paris (France); Hopital Beaujon, AP-HP, Referral Center for Lysosomal Diseases (RCLD), Clichy (France)


    To study the long-term evolution of the bone marrow burden (BMB) score at MRI in patients with Gaucher disease (GD) under enzyme replacement therapy (ERT). Forty patients treated for GD were retrospectively studied in a referral centre. BMB scores were assessed on spine and femur MR examinations performed between January 2003 and June 2014. The long-term evolution of the BMB scores was analyzed using a linear mixed model. A total of 121 MRI examinations were performed during the study period with a mean follow-up of 7.1 years ± 5.6, an average rate of 3.1 MR examinations ± 1.7 per patient and an interval of 2.3 years ± 1.1 between examinations. Patients had received ERT during 12 years on average ± 6.7. The trend of BMB scores with time decreased significantly by 15 % (P = 0.008) during the total study period and 39 % (P = 0.01) during the first 5 years of treatment. No changes in BMB scores were observed after five years of treatment. In Gaucher patients, the trend of MRI BMB scores with time decreased significantly under ERT the first 5 years of treatment before a long-term stabilization. (orig.)

  4. Enzyme-replacement Therapy in Classic Infantile Pompe Disease: Long-term outcome, dosing and the role of antibodies

    C.M. Van Gelder (Carin)


    textabstract__Abstract__ The introduction of enzyme-replacement therapy (ERT) in 2006 has dramatically increased the interest in Pompe disease. In the three decades following the discovery of acid a-glucosidase deficiency as cause of the disease by H.G. Hers in 1963 only very few research

  5. Long-term endurance and safety of elosulfase alfa enzyme replacement therapy in patients with Morquio A syndrome.

    Hendriksz, Christian J; Parini, Rossella; AlSayed, Moeenaldeen D; Raiman, Julian; Giugliani, Roberto; Solano Villarreal, Martha L; Mitchell, John J; Burton, Barbara K; Guelbert, Norberto; Stewart, Fiona; Hughes, Derralynn A; Berger, Kenneth I; Slasor, Peter; Matousek, Robert; Jurecki, Elaina; Shaywitz, Adam J; Harmatz, Paul R


    Long-term efficacy and safety of elosulfase alfa enzyme replacement therapy were evaluated in Morquio A patients over 96weeks (reaching 120weeks in total from pre-treatment baseline) in an open-label, multi-center, phase III extension study. During this extension of a 24-week placebo-controlled phase III study, all patients initially received 2.0mg/kg elosulfase alfa either weekly or every other week, prior to establishment of 2.0mg/kg/week as the recommended dose, at which point all patients received weekly treatment. Efficacy measures were compared to baseline of the initial 24-week study, enabling analyses of changes over 120weeks. In addition to performing analyses for the entire intent-to-treat (ITT) population (N=173), analyses were also performed for a modified per-protocol (MPP) population (N=124), which excluded patients who had orthopedic surgery during the extension study or were non-compliant with the study protocol (as determined by ≥20% missed infusions). Six-minute walk test (6MWT) was the primary efficacy measure; three-minute stair climb test (3MSCT) and normalized urine keratan sulfate (uKS) were secondary efficacy measures. Mean (SE) change from baseline to Week 120 in 6MWT distance was 32.0 (11.3)m and 39.9 (10.1)m for patients receiving elosulfase alfa at 2.0mg/kg/week throughout the study (N=56) and 15.1 (7.1)m and 31.7 (6.8)m in all patients combined, regardless of dosing regimen, for the ITT and MPP populations, respectively. Further analyses revealed that durability of 6MWT improvements was not impacted by baseline 6MWT distance, use of a walking aid, or age. Mean (SE) change at Week 120 in the 3MSCT was 5.5 (1.9) and 6.7 (2.0)stairs/min for patients receiving elosulfase alfa at 2.0mg/kg/week throughout the study and 4.3 (1.2) and 6.8 (1.3)stairs/min in all patients combined, regardless of dosing regimen, for the ITT and MPP populations, respectively Across all patients, mean (SE) change at Week 120 in normalized uKS was -59.4 (1.8)% and

  6. Magnetic resonance imaging of bone marrow changes in Gaucher disease during enzyme replacement therapy: first German long-term results

    Poll, L.W.; Koch, J.A.; Scherer, A.; Boerner, D.; Moedder, U. [Duesseldorf Univ. (Germany). Inst. fuer Diagnostische Radiologie; Dahl, S. vom; Niederau, C.; Haeussinger, D. [Duesseldorf Univ. (Germany). Medizinische Fakultaet; Willers, R. [Duesseldorf Univ. (Germany). Rechenzentrum


    Objective:. Since 1991, enzyme replacement therapy (ERT) has been available for patients with Gaucher disease in Germany. The aim of this study was to analyse the MR pattern of bone marrow involvement and response to ERT in Gaucher disease type I. Patients and design:. Thirty patients with Gaucher disease type I had MRI examinations prior to initiation of ERT with alglucerase/imiglucerase and during follow-up. Median MR follow-up and duration of ERT were 36 months. Coronal T1- and T2-weighted spin-echo images of the lower extremities were obtained to evaluate changes in the appearance of yellow marrow. MR images were categorized as having either a homogeneous (type A) or non-homogeneous patchy (type B) appearance of bone involvement and response to ERT was assessed by two radiologists. Results:. Overall, 19 of 30 patients (63%) showed an increased signal intensity on T1- and T2-weighted images after 36 months of ERT, consistent with partial reconversion of fatty marrow during treatment. Focal bone lesions surrounded by a low signal intensity (SI) rim did not respond to ERT, suggesting bone infarcts. Of the 11 patients with bone infarcts (low SI rim lesion), 82% had the non-homogeneous type B pattern (P=0.0021). In 86% of patients with splenectomy, bone infarcts were seen (P<0.05). Conclusions:. MRI using T1- and T2-weighted spin-echo sequences is a valuable, non-invasive method for monitoring bone marrow response in patients receiving ERT. A non- homogeneous patchy signal intensity of bone marrow involvement correlates with the presence of bone infarcts (P=0.0021). (orig.)

  7. Cognitive and adaptive functioning of children with infantile Pompe disease treated with enzyme replacement therapy: long-term follow-up.

    Spiridigliozzi, Gail A; Heller, James H; Kishnani, Priya S


    This report documents the long-term cognitive and adaptive outcome of children with infantile Pompe disease. Specifically, we describe the cognitive and adaptive functioning of seven children with classic infantile Pompe disease and two children with atypical infantile Pompe disease who have received enzyme replacement therapy (Myozyme®) for an average of 6 years, 8 months and 4 years, 1. 5 months, respectively. Multiple assessments of cognitive functioning were completed over time by means of individualized intelligence (IQ) testing. Adaptive functioning was measured by means of the Vineland Adaptive Behavior Scales-Second Edition (VABS-II). Consistent with our earlier findings regarding infants treated with ERT, children with classic infantile Pompe disease (ages 4 years, 11 months to 8 years, 11 months) were functioning at the lower end of the average range in comparison to their typical peers on their most recent IQ test. There was no evidence of a decline in their cognitive abilities over time. In contrast, the two children with atypical infantile Pompe disease (ages 5 years, 4 months and 5 years, 11 months) obtained above average IQ scores and demonstrated significant gains in IQ over time. For all children where adaptive functioning was assessed, their overall level of adaptive functioning on the VABS-II was lower than their Full Scale IQ scores on cognitive testing. Motor function appears to be an important factor impacting on reduced adaptive behavior. The implication of these findings on our understanding of a possible relationship between CNS status in children with Pompe and their adaptive and cognitive function is discussed. Copyright © 2012 Wiley Periodicals, Inc.

  8. Early versus late treatment of spinal cord compression with long-term intrathecal enzyme replacement therapy in canine mucopolysaccharidosis type I.

    Dickson, Patricia I; Hanson, Stephen; McEntee, Michael F; Vite, Charles H; Vogler, Carole A; Mlikotic, Anton; Chen, Agnes H; Ponder, Katherine P; Haskins, Mark E; Tippin, Brigette L; Le, Steven Q; Passage, Merry B; Guerra, Catalina; Dierenfeld, Ashley; Jens, Jackie; Snella, Elizabeth; Kan, Shih-Hsin; Ellinwood, N Matthew


    Enzyme replacement therapy (ERT) with intravenous recombinant human alpha-l-iduronidase (IV rhIDU) is a treatment for patients with mucopolysaccharidosis I (MPS I). Spinal cord compression develops in MPS I patients due in part to dural and leptomeningeal thickening from accumulated glycosaminoglycans (GAG). We tested long-term and every 3-month intrathecal (IT) and weekly IV rhIDU in MPS I dogs age 12-15months (Adult) and MPS I pups age 2-23days (Early) to determine whether spinal cord compression could be reversed, stabilized, or prevented. Five treatment groups of MPS I dogs were evaluated (n=4 per group): IT+IV Adult, IV Adult, IT + IV Early, 0.58mg/kg IV Early and 1.57mg/kg IV Early. IT + IV rhIDU (Adult and Early) led to very high iduronidase levels in cervical, thoracic, and lumber spinal meninges (3600-29,000% of normal), while IV rhIDU alone (Adult and Early) led to levels that were 8.2-176% of normal. GAG storage was significantly reduced from untreated levels in spinal meninges of IT + IV Early (pmeninges and histologic absence of storage vacuoles. Lysosomal storage was reduced in spinal anterior horn cells in 1.57mg/kg IV Early and IT + IV Early animals. All dogs in IT + IV Adult and IV Adult groups had compression of their spinal cord at 12-15months of age determined by magnetic resonance imaging and was due to protrusion of spinal disks into the canal. Cord compression developed in 3 of 4 dogs in the 0.58mg/kg IV Early group; 2 of 3 dogs in the IT + IV Early group; and 0 of 4 dogs in the 1.57mg/kg IV Early group by 12-18months of age. IT + IV rhIDU was more effective than IV rhIDU alone for treatment of meningeal storage, and it prevented meningeal GAG accumulation when begun early. High-dose IV rhIDU from birth (1.57mg/kg weekly) appeared to prevent cord compression due to protrusion of spinal disks.

  9. Long-term enzyme replacement therapy is associated with reduced proteinuria and preserved proximal tubular function in women with Fabry disease

    Prabakaran, Thaneas; Birn, Henrik; Bibby, Bo M;


    BACKGROUND: Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the GLA gene. Deficiency of α-galactosidase A (α-Gal A) causes intracellular accumulations of globotriaosylceramide (GL-3) and related glycosphingolipids in all organs, including the kidney, often leading...... to end-stage renal failure. In women with Fabry disease, accumulation of GL-3 in the glomerular podocytes and other renal cells induces progressive, proteinuric nephropathy, but not as severe as in men. Enzyme replacement therapy (ERT) with recombinant α-Gal A reduces cellular GL-3 deposits in podocytes...

  10. Being a long-term user of nicotine replacement therapy

    Borup, Gitte; Nørgaard, Lotte Stig; Tønnesen, Philip;

    Background During recent years a gradual shift in the application of nicotine replacement therapy (NRT) has taken place from NRT-products only being recommended to achieve smoking cessation, to now including smoking reduction, and long-term substitution of tobacco with NRT has taken place. This has...... been promoted as a way of achieving harm-reduction in highly nicotine dependent smokers who are unwilling or incapable of quitting all nicotine products, as continued use of NRT is widely accepted as being far less hazardous than continued smoking. To our knowledge no previous research has been done......, regarding long-term NRT users’ experiences with continuing the use of NRT. Results from a survey study among long-term NRT-users, who had used NRT for 12 months or more, found that out of 92 former smokers 88 % wished to quit using NRT. The primary causes stated for wishing to quit were being tired...

  11. Being a long-term user of nicotine replacement therapy

    Borup, Gitte; Nørgaard, Lotte Stig; Tønnesen, Philip

    Background During recent years a gradual shift in the application of nicotine replacement therapy (NRT) has taken place from NRT-products only being recommended to achieve smoking cessation, to now including smoking reduction, and long-term substitution of tobacco with NRT has taken place. This has...... been promoted as a way of achieving harm-reduction in highly nicotine dependent smokers who are unwilling or incapable of quitting all nicotine products, as continued use of NRT is widely accepted as being far less hazardous than continued smoking. To our knowledge no previous research has been done...... of feeling addicted, cost of NRT products and fear of adverse health consequences. Aim of study • To get a thorough understanding of the lived experiences of nicotine dependent long-term NRT users. • To investigate what motivates or discourages quitting NRT. Method Semi-structured interviews with long...

  12. Factors influencing long-term survival after aortic valve replacement.



    Full Text Available In the aortic stenosis group, the left ventricular (LV muscle mass index was a good parameter for predicting the prognosis. Associated mitral valve disease had no influence on long term survival after aortic valve replacement. In the aortic insufficiency group, associated mitral valve disease had a marked influence on the results of aortic valve replacement. In general, the aortic insufficiency group had less clinical improvement postoperatively than the aortic stenosis group. In the annuloaortic ectasia group, left ventricular enddiastolic pressure (LVEDP might be the predictor to the prognosis. This group had the worst prognosis, of the three groups. Early operation should be considered for patients who have no, or only mild symptoms of, aortic valve disease.

  13. "Enzyme Test Bench," a high-throughput enzyme characterization technique including the long-term stability.

    Rachinskiy, Kirill; Schultze, Hergen; Boy, Matthias; Bornscheuer, Uwe; Büchs, Jochen


    A new high throughput technique for enzyme characterization with specific attention to the long term stability, called "Enzyme Test Bench," is presented. The concept of the Enzyme Test Bench consists of short term enzyme tests in 96-well microtiter plates under partly extreme conditions to predict the enzyme long term stability under moderate conditions. The technique is based on the mathematical modeling of temperature dependent enzyme activation and deactivation. Adapting the temperature profiles in sequential experiments by optimal non-linear experimental design, the long term deactivation effects can be purposefully accelerated and detected within hours. During the experiment the enzyme activity is measured online to estimate the model parameters from the obtained data. Thus, the enzyme activity and long term stability can be calculated as a function of temperature. The engineered instrumentation provides for simultaneous automated assaying by fluorescent measurements, mixing and homogenous temperature control in the range of 10-85 +/- 0.5 degrees C. A universal fluorescent assay for online acquisition of ester hydrolysis reactions by pH-shift is developed and established. The developed instrumentation and assay are applied to characterize two esterases. The results of the characterization, carried out in microtiter plates applying short term experiments of hours, are in good agreement with the results of long term experiments at different temperatures in 1 L stirred tank reactors of a week. Thus, the new technique allows for both: the enzyme screening with regard to the long term stability and the choice of the optimal process temperature regarding such process parameters as turn over number, space time yield or optimal process duration. The comparison of the temperature dependent behavior of both characterized enzymes clearly demonstrates that the frequently applied estimation of long term stability at moderate temperatures by simple activity measurements

  14. Muscle imaging data in late-onset Pompe disease reveal a correlation between the pre-existing degree of lipomatous muscle alterations and the efficacy of long-term enzyme replacement therapy

    Kai Michael Gruhn


    Conclusions: The results demonstrate that fatty muscle degeneration can occur before clinical manifestation of muscle weakness and suggest that mildly affected muscles may respond better to ERT treatment than severely involved muscles. If these findings can be validated by further studies, it should be discussed if muscle alterations detected by muscle MRI may be an objective sign of disease manifestation justifying an early start of ERT in clinically asymptomatic patients in order to improve the long-term outcome.

  15. [Transformation of free radicals of gamma-irradiated enzymes during long-term storage].

    Ryl'tsev, V V; Virnik, R B; Dovbiĭ, E V; Filatov, V N


    The ESR method was used to study free radical processes occurring in gamma-irradiated enzymes upon their long-term storage (up to 4 years) both at room temperature and at 4 degrees C. Simultaneously, studied was the biological activity of gamma-irradiated enzymes subjected to a long-term storage. The immobilization of enzymes on dialdehyde cellulose or polycaproamine was shown to preserve their biological activity during the postirradiation storage.

  16. Influence of long-term fertilization on soil enzyme activities

    Alina Dora SAMUEL


    Full Text Available Soil enzyme activities (actual and potential dehydrogenase, catalase, acid and alkaline phosphatase were determined in the 0–10, 10–20, and 20–30 cm layers of a brown luvic soil submitted to a complex fertilization experiment with different types of green manure. It was found that each activity decreased with increasing sampling depth. It should be emphasized that greenmanuring of maize led to a significant increase in each of the five enzymatic activities determined. The enzymatic indicators of soil quality calculated from the values of enzymatic activities showed the order: lupinus + rape + oat > lupinus > vetch + oat + ryegrass > lupinus + oat + vetch > unfertilized plot. This order means that by determination of enzymatic activities valuable information can be obtained regarding fertility status of soils. There were significant correlations of soil enzyme activities with chemical properties.

  17. Exploratory survey study of long-term users of nicotine replacement therapy in Danish consumers

    Borup, Gitte; Christrup, Lona Louring; Lyngby Mikkelsen, Kim

    Background Long-term use of nicotine replacement therapy (NRT) has been approved in several countries for smokers who are unable or unwilling to quit smoking. However, information on basic characteristics, degree of nicotine dependence, health status and contentment with long-term use of NRT...... is scarce. The aim of this study was to collect information on the characteristics of long-term NRT users, having used NRT for at least 12 months, reasons for, and contentment with, their continued use of NRT including reasons for wishing to quit or sustain use and an estimation of their degree of nicotine...... to estimate nicotine dependence. Linear regression was used to test association between time to first NRT and daily dosage of NRT. Results A total of 92 respondents were included in the data analysis. A majority of 88% wished to quit NRT for the following reasons: costs of NRT, being tired of feeling addicted...

  18. Exploratory survey study of long-term users of nicotine replacement therapy in Danish consumers

    Borup, Gitte; Lyngby Mikkelsen, Kim; Tønnesen, Philip


    Background: Long-term use of nicotine replacement therapy (NRT) has been approved in several countries for smokers who are unable or unwilling to quit smoking. However, information on basic characteristics, degree of nicotine dependence, health status and contentment with long-term use of NRT...... is scarce. The aim of this study was to collect information on the characteristics of long-term NRT users, having used NRT for at least 12 months, reasons for, and contentment with, their continued use of NRT including reasons for wishing to quit or sustain use and an estimation of their degree of nicotine...... to estimate nicotine dependence. Linear regression was used to test association between time to first NRT and daily dosage of NRT. Results: A total of 92 respondents were included in the data analysis. A majority of 88% wished to quit NRT for the following reasons: costs of NRT, being tired of feeling...

  19. Long-term effects of growth hormone (GH) replacement in men with childhood-onset GH deficiency

    Ter Maaten, JC; De Boer, H; Kamp, O; Stuurman, L; Van der Veen, EA


    Short term GH replacement therapy has been shown to improve body composition and exercise capacity. It is not yet known whether GH replacement remains beneficial over the long term. We assessed the effects of long term GH replacement on body composition, bone mineral density, and cardiac function. T

  20. Pros and Cons of Long-Term use of Nicotine Replacement Therapies: A Qualitative Study

    Borup, Gitte; Kaae, Susanne; Nørgaard, Lotte Stig


    In the last decade, harm reduction has been increasingly suggested as a method to reduce the harm caused by smoking in smokers who are unable or unwilling to quit all nicotine products. One of these methods includes long-term substitution of tobacco with nicotine replacement therapies (NRTs......, including perceived pros and cons of using NRTs, the risk of relapse to smoking and their motivation to quit using NRTs. The results identified five major themes that entailed pros and cons of the long-term use of NRTs. These were the non-nicotinic factors of NRTs, health risks of NRTs vs. smoking......, intrapersonal processes, the social environment of smoking vs. NRTs and finances. None of the ex-smokers feared to relapse to smoking, and few were motivated to quit NRTs. Non-nicotinic factors were found to have an important role in developing an addiction to NRTs. The use of NRTs yields some of the expected...

  1. New-onset postoperative atrial fibrillation after aortic valve replacement: Effect on long-term survival.

    Swinkels, Ben M; de Mol, Bas A; Kelder, Johannes C; Vermeulen, Freddy E; Ten Berg, Jurriën M


    There is a paucity of data on long-term survival of new-onset postoperative atrial fibrillation (POAF) after cardiac surgery. Also, mean follow-up in previous studies is confined to a maximum of one decade. This retrospective, longitudinal cohort study was performed to determine the effect on long-term survival of new-onset POAF after aortic valve replacement (AVR) over a mean follow-up of almost 2 decades. Kaplan-Meier survival analysis was used to determine long-term survival after AVR, performed between January 1, 1990, and January 1, 1994, in 569 consecutive patients without a history of atrial fibrillation, divided into 241 patients (42.4%) with and 328 patients (57.6%) without new-onset POAF. New-onset POAF was considered in multivariable analysis for decreased long-term survival. After AVR, patients with new-onset POAF were treated with the aim to restore sinus rhythm within 24 to 48 hours from onset by medication and when medication failed by direct-current cardioversion before discharge home. Mean follow-up after AVR was 17.8 ± 1.9 years. Incidence of new-onset POAF was 42.4%. Kaplan-Meier overall cumulative survival rates at 15 years of follow-up were similar in the patients with new-onset POAF versus those without: 41.5% (95% confidence interval [CI], 35.2-47.7) versus 41.3% (95% CI, 36.0-46.7), respectively. New-onset POAF was not an independent risk factor for decreased long-term survival (hazard ratio 0.815; 95% CI, 0.663-1.001; P = .052). New-onset POAF after AVR does not affect long-term survival when treatment is aimed to restore sinus rhythm before discharge home. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  2. Stable and Continuous Long-term Enzymatic Reaction using an Enzyme-Nanofiber Composite

    Lee, Jin Hyung; Hwang, Ee Taek; Kim, Byoung Chan; Lee, Sun Mi; Sang, Byoung-In; Choi, Yong Su; Kim, Jungbae; Gu, Man Bock


    This study shows the preparation and application of enzyme-nanofiber composites for long-term stable operation. The enzyme-nanofiber composite was prepared by coating an enzyme-aggregate, the esterase from Rhizopus oryzae, on the surface of the nanofibers. The activity and stability of the esterase-nanofiber composite was evaluated by measuring the production of p-nitrophenol from the hydrolysis of p-nitrophenyl butyrate. It was found that enzyme-nanofiber was very stable, even when the fibers were shaken in glasses, preserving 80 % of the initial activity for 100 days. In addition, the enzyme nanofiber composite was repeatedly used in 30 cycles of substrate hydrolysis and still remained active. Consequently, the esterase-nanofiber composite was finally employed to find its feasibility of long-term and stable continuous substrate hydrolysis reaction. In the sample reactor, the production of p-nitrophenol was consistent for 400 hr. Additionally, it was found that the production of p-nitrophenol proportionally decreased as the dilution rate was increased, showing the relationship between the efficiency of hydrolysis and the retention time within the reactor. This study demonstrates that the enzyme-nanofiber composite can be used in both repeated-batch and continuous modes for long-term stable operation.

  3. Pacemaker replacement in nonagenarians: Procedural safety and long-term follow-up.

    Loirat, Aurélie; Fénéon, Damien; Behaghel, Albin; Behar, Nathalie; Le Helloco, Alain; Mabo, Philippe; Daubert, Jean-Claude; Leclercq, Christophe; Martins, Raphaël P


    The rate of pacemaker implantation is rising. Given that the life expectancy of the population is projected to increase, a large number of elderly patients are likely to be implanted in the future. As pacemaker batteries can last for 8-10years, an increasing number of pacemaker recipients will require replacement of their devices when they become nonagenarians. To analyse the short- and long-term outcomes after device replacement in nonagenarians. Patients aged≥90years referred to a tertiary centre for pacemaker replacement from January 2004 to July 2014 were included retrospectively. Clinical follow-up data were obtained from clinical visits or telephone interviews with patients or their families. The primary clinical endpoint was total mortality. Secondary endpoints included early and delayed procedure-related complications and predictive risk factors for total mortality. Sixty-two patients were included (mean age 93.3±2.9years at time of pacemaker replacement). Mean procedure duration was 35.7±17.2minutes. Mean hospital stay was 2.2±1.1days. One patient died from a perioperative complication. Thirty-seven patients (59.7%) died during a median follow-up of 22.1months (interquartile range, 11.8-39.8months). Survival rates were 84.2% (95% confidence interval [CI] 71.8-91.5%) at 1year, 66.9% (95% CI 51.8-78.2%) at 2years and 22.7% (95% CI 10.6-37.7%) at 5years. Atrial fibrillation (hazard ratio 2.47, 95% CI 1.1-5.6) and non-physiological pacing (i.e. VVI pacing in patients in sinus rhythm) (hazard ratio 2.20, 95% CI 1.0-4.9) were predictors of mortality. Pacemaker replacement in nonagenarians is a safe and straightforward procedure. These data suggest that procedures can be performed securely in this old and frail population, with patients living for a median of 30months afterwards. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  4. Long-term implant-bone fixation of the femoral component in total knee replacement.

    Cristofolini, L; Affatato, S; Erani, P; Leardini, W; Tigani, D; Viceconti, M


    Success of total knee replacement (TKR) depends on the prosthetic design. Aseptic loosening of the femoral component is a significant failure mode that has received little attention. Despite the clinical relevance of failures, no protocol is available to test long-term implant-bone fixation of TKR in vitro. The scope of this work was to develop and validate a protocol to assess pre-clinically the fixation of TKR femoral components. An in vitro protocol was designed to apply a simplified but relevant loading profile using a 6-degrees-of-freedom knee simulator for 1,000000 cycles. Implant-bone inducible micromotions and permanent migrations were measured at three locations throughout the test. After test completion, fatigue damage in the cement was quantified. The developed protocol was successfully applied to a commercial TKR. Additional tests were performed to exclude artefacts due to swelling or creep of the composite femur models. The components migrated distally; they tilted towards valgus in the frontal plane and in extension in the sagittal plane. The migration patterns were consistent with clinical roentgen-stereophotogrammetric recordings with TKR. Additional indicators were proposed that could quantify the tendency to loosen/stabilize. The type and amount of damage found in the cement, as well as the migration patterns, were consistent with clinical experience with the specific TKR investigated. The proposed pre-clinical test yielded repeatable results, which were consistent with the clinical literature. Therefore, its relevance and reliability was proved.

  5. [Long-term outcomes of children treated with continuous renal replacement therapy].

    Almarza, S; Bialobrzeska, K; Casellas, M M; Santiago, M J; López-Herce, J; Toledo, B; Carrillo, Á


    The objective of this study is to analyze long-term outcomes and kidney function in children requiring continuous renal replacement therapy (CRRT) after an acute kidney injury episode. A retrospective observational study was performed using a prospective database of 128 patients who required CRRT admitted to the pediatric intensive care unit between years 2006 and 2012. The subsequent outcomes were assessed in those surviving at hospital discharge. Of the 128 children who required RRT in the pediatric intensive care unit, 71 survived at hospital discharge (54.4%), of whom 66 (92.9%) were followed up. Three patients had chronic renal failure prior to admission to the NICU. Of the 63 remaining patients, 6 had prolonged or relapses of renal function disturbances, but only one patient with atypical Hemolytic Uremic Syndrome developed end-stage renal failure. The rest had normal kidney function at the last check-up. Most of surviving children that required CRRT have a positive outcome later on, presenting low mortality rates and recovery of kidney function in the medium term. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

  6. [Long-term results of conventional aortic valve replacement for small aortic annulus].

    Miura, Y; Miyairi, T; Kitamura, T; Kigawa, I; Fukuda, S


    We studied cardiac function, clinical outcome and quality of life (QOL) long after aortic valve replacement for pure aortic stenosis. Forty-four patients in small group [St. Jude Medical (SJM) 17 HP, 19 A], and 69 patients in non-small group (19 HP, 21 A, 23 A) operated on from 1984 to 2004 were enrolled in this study. We assessed the clinical data, aortic pressure gradient, left ventricular mass index (LVMI), and ejection fraction (EF) by preoperative and postoperative echocardiography. Moreover to evaluate QOL after the operation, we performed SF-36 used for the evaluation of health and QOL worldwide. Mean follow-up is 7.1 +/- 4.8 years in small group, and 6.8 +/- 4.6 years in non-small group. There were 2 hospital deaths in small group, and 1 in non-small group. The actual survival rate at 10-year were 89.2% in small group, and 85.6% in non-small group. There was no significant difference in hospital mortality, LVMI, long-term survival rate, and the scores of SF-36 between the 2 groups. The use of small sized prosthetic valves in patients with small aortic annulus might be justified when there is no patient-prosthesis mismatch.

  7. Ankylosing spondylitis: a difficult diagnosis in patients on long-term renal replacement therapy.

    Piccoli, Giorgina B; Quaglia, Marco; Mezza, Elisabetta; Burdese, Manuel; Lacuzzo, Candida; Bechis, Francesca; Biancone, Luigi; Anania, Patrizia; Maddalena, Emanuela; Jeantet, Alberto; Segoloni, Giuseppe P; Salvarani, Carlo


    We report the case of a 48-year-old male, whose musculoskeletal manifestations, previously related to long-term renal replacement therapy (RRT), were diagnosed as ankylosing spondylitis when symptoms changed their pattern on daily hemodialysis (DHD). The patient started RRT in 1981; in 1985 he received a cadaver graft, which failed in 1987. Secondary hyperparathyroidism, amyloid geoids, bilateral carpal tunnel syndrome and high aluminium levels were present. Musculoskeletal pain, reported since 1986, involved feet, heels, hips, shoulders, hands, spine. Symptoms impairing daily life did not improve after parathyroidectomy. He developed chronic hypotension and recurrent atrial fibrillation. In 1994 and 1998, because of thoracic pain, coronarography was performed (normal on both occasions). In June 2000, DHD was started. Equivalent renal clearance increased from 9-12 to 15-17 mL/min. Well-being remarkably improved. In September 2000, musculoskeletal pain worsened and bilateral Achilles tendinitis occurred. The worsening of musculoskeletal symptoms despite the improvements in well-being and other dialysis related symptoms prompted a re-evaluation of the case. The diagnosis of ankylosing spondylitis was based on: history of plantar fasciitis, bilateral Achilles tendinitis, inflammatory spinal pain with limitation of lumbar spine mobility (positive Schober test), radiological evidence of grade 2 bilateral sacroiliitis, presence of HLA-B27. This diagnosis cast light on the episodes of chest pain, explained by enthesopathy at the costosternal and manubriosternal joints and atrial fibrillation, due to HLA-B27 associated impairment in heart conduction. This case exemplifies the difficulty of differential diagnosis of multisystem illness in patients with long RRT follow-up.

  8. Impact of Prosthesis-Patient Mismatch on Long-term Functional Capacity After Mechanical Aortic Valve Replacement

    Petit-Eisenmann, H.; Epailly, E.; Velten, M.; Radojevic, J.; Eisenmann, B.; Kremer, H.; Kindo, M.


    BACKGROUND: The impact of prosthesis-patient mismatch (PPM) after aortic valve replacement (AVR) for aortic stenosis on exercise capacity remains controversial. The aim of this study was to analyze the long-term impact of PPM after mechanical AVR on maximal oxygen uptake (VO2max). METHODS: The study

  9. Long-term follow-up of homograft function after pulmonary valve replacement in patients with tetralogy of Fallot.

    Oosterhof, T.; Meijboom, F.J.; Vliegen, H.W.; Hazekamp, M.G.; Zwinderman, A.H.; Bouma, B.J.; Dijk, A.P.J. van; Mulder, B.J.M.


    AIMS: To analyse the long-term outcomes after pulmonary valve replacement (PVR) in patients with a previous correction for tetralogy of Fallot. METHODS AND RESULTS: In a retrospective study, 158 adult patients with a diagnosis of tetralogy of Fallot, who had undergone a PVR after initial total

  10. Soil Organic Carbon, Black Carbon, and Enzyme Activity Under Long-Term Fertilization

    SHAO Xing-hua; ZHENG Jian-wei


    The present study aims to understand the effects of long-term fertilization on soil organic carbon (SOC), black carbon (BC), enzyme activity, and the relationships among these parameters. Paddy ifeld was continuously fertilized over 30 yr with nine different fertilizer treatments including N, P, K, NP, NK, NPK, 2NPK (two-fold NPK), NPK+manure (NPKM), and CK (no fertilization), N, 90 kg urea-N ha-1 yr-1; P, 45 kg triple superphosphate-P2O5 ha-1 yr-1; K, 75 kg potassium chloride-K2O ha-1 yr-1;and pig manure, 22 500 kg ha-1 yr-1. Soil samples were collected and determined for SOC, BC content, and enzyme activity. The results showed that the SOC in the NPKM treatment was signiifcantly higher than those in the K, P, and CK treatments. The lowest SOC content was found in the CK treatment. SOC content was similar in the N, NP, NK, NPK, 2NPK, and NPKM treatments. There was no signiifcant difference in BC content among different treatments. The BC-to-SOC ratios (BC/SOC) ranged from 0.50 to 0.63, suggesting that BC might originate from the same source. Regarding enzyme activity, NPK treatment had higher urease activity than NPKM treatment. The urease activity of NPKM treatment was signiifcantly higher than that of 2NPK, NP, N, P, K, CK, and NPKM treatment which produced higher activities of acid phosphatase, catalase, and invertase than all other treatments. Our results indicated that long-term fertilization did not signiifcantly affect BC content. Concurrent application of manure and mineral fertilizers increased SOC content and signiifcantly enhanced soil enzyme activities. Correlation analysis showed that catalase activity was signiifcantly associated with invertase activity, but SOC, BC, and enzyme activity levels were not signiifcantly correlated with one another. No signiifcant correlations were observed between BC and soil enzymes. It is unknown whether soil enzymes play a role in the decomposition of BC.

  11. Obesity and long term functional outcomes following elective total hip replacement

    Vincent Heather K


    Full Text Available Abstract Introduction Obesity rates continue to rise and more total hip arthroplasty procedures are being performed in progressively younger, obese patients. Hence, maintenance of long term physical function will become very important for quality of life, functional independence and hip prosthesis survival. Presently, there are no reviews of the long term efficacy of total hip arthroplasty on physical function. This review: 1 synopsized available data regarding obesity effects on long term functional outcomes after total hip arthroplasty, and 2 suggested future directions for research. Methods A literature search was conducted from 1965 to January of 2011 for studies that evaluated long term functional outcomes at one year or longer after THA in obese (body mass index values ≥30 kg/m2 and non-obese patients (body mass index 2. Results Five retrospective studies and 18 prospective studies were identified as those that assessed physical function before surgery out to ≥ one year after total hip arthroplasty. Study sample sizes ranged from 108–18,968 and followed patients from one to twenty years. Total hip arthroplasty confers significant pain reduction and improvement in quality of life irrespective of body mass index. Functional improvement occurred after total hip arthroplasty among all studies, but obese patients generally did not attain the same level of physical function by the follow-up time point. Discussion Uncontrolled obesity after total hip arthroplasty is related to worsening of comorbidities and excessive health care costs over the long term. Aggressive and sustainable rehabilitation strategies that include physical exercise, psychosocial components and behavior modification may be highly useful in maximizing and maintaining weight loss after total hip arthroplasty.

  12. [The transrectal ultrasonography of prostate in men with congenital hypogonadism treated by long term testosterone replacement therapy].

    Heráček, Jiří; El Balouly, Karim; Sobotka, Vladimír; Šnajderová, Marta; Kalvachová, Božena; Urban, Michael


    The aim of the study was to evaluate prostate transrectal ultrasonography findings in men with congenital hypogonadism treated by long term testosterone replacement therapy. We have gradually included 31 men with congenital hypogonadism in period of 2001-2011. The average follow-up was 7.3 years (2 months - 10.8 years). We have used Sustanon® 250 i.m. every 3 weeks or Nebido® i.m. every 3 months for continual testosterone replacement therapy. We performed to all patients the transrectal ultrasonography of prostate and seminal vesicles by biplanar rectal probe every 6 months. During the transrectal ultrasonography we observed in 22 (71.0 %) patients changes in prostatic tissue. In case of 12 patients were diagnosed asymptomatic prostatic cysts, in 9 patients prostatolithiasis and in 5 patients changes in echogenity of prostatic tissue. In 2 patients was found simultaneous occurrence of prostatic cyst and prostolithiasis, in further 2 patients simultaneous occurrence of hyperechogenic prostatic lesion and prostatolithiasis. The above described findings were diagnosed in 5 patients in the treatment lasting from 3 to 5 years, for the other 17 men with hormone replacement therapy longer than 5 years. The study presents long term results of complex treatment in patients with disorders of sexual development, onset and progress of puberty. The long term treatment of these patients in interdisciplinary cooperation of endocrinologist and andrologist may significantly contribute to clarify an impact of testosterone replacement therapy on prostate development.

  13. Immediate and long-term results of emergency aortic valve replacement in acute bacterial endocarditis.

    Alstrup, P; Fröysaker, T


    A surgically treated material comprising 18 patinets with heart failure from aortic insufficiency during acute endocarditis has been reviewed. At the time of operation the mean duration of heart failure was 3 weeks and duration of endocarditis 9 weeks. Blood culture was positive in half of the patients, 39% had predisposing valve disease, 14 (78%) had a preoperative heart catheterization. The peroperatively measured regurgitation averaged 55%. All 18 patients had an artifical valve implanted, and the mean observation time for 13 long-term survivors was 3 1/3 years. There were 3 postoperative and 2 late deaths. A long-term survival rate of 73% strongly supports early surgical treatment in patients with aortic insufficiency and heart failure during acute endocarditis.

  14. Repair or Replacement for Isolated Tricuspid Valve Pathology? Insights from a Surgical Analysis on Long-Term Survival

    Farag, Mina; Arif, Rawa; Sabashnikov, Anton; Zeriouh, Mohamed; Popov, Aron-Frederik; Ruhparwar, Arjang; Schmack, Bastian; Dohmen, Pascal M.; Szabó, Gábor; Karck, Matthias; Weymann, Alexander


    Background Long-term follow-up data concerning isolated tricuspid valve pathology after replacement or reconstruction is limited. Current American Heart Association guidelines equally recommend repair and replacement when surgical intervention is indicated. Our aim was to investigate and compare operative mortality and long-term survival in patients undergoing isolated tricuspid valve repair surgery versus replacement. Material/Methods Between 1995 and 2011, 109 consecutive patients underwent surgical correction of tricuspid valve pathology at our institution for varying structural pathologies. A total of 41 (37.6%) patients underwent tricuspid annuloplasty/repair (TAP) with or without ring implantation, while 68 (62.3%) patients received tricuspid valve replacement (TVR) of whom 36 (53%) were mechanical and 32 (47%) were biological prostheses. Results Early survival at 30 days after surgery was 97.6% in the TAP group and 91.1% in the TVR group. After 6 months, 89.1% in the TAP group and 87.8% in the TVR group were alive. In terms of long-term survival, there was no further mortality observed after one year post surgery in both groups (Log Rank p=0.919, Breslow p=0.834, Tarone-Ware p=0.880) in the Kaplan-Meier Survival analysis. The 1-, 5-, and 8-year survival rates were 85.8% for TAP and 87.8% for TVR group. Conclusions Surgical repair of the tricuspid valve does not show survival benefit when compared to replacement. Hence valve replacement should be considered generously in patients with reasonable suspicion that regurgitation after repair will reoccur. PMID:28236633

  15. Peritoneal dialysis catheter placement as a mode of renal replacement therapy: Long-term results from a tertiary academic institution.

    Haskins, Ivy N; Schreiber, Martin; Prabhu, Ajita S; Krpata, David M; Perez, Arielle J; Tastaldi, Luciano; Tu, Chao; Rosen, Michael J; Rosenblatt, Steven


    Peritoneal dialysis as a mode of renal replacement therapy still has not been embraced widely as an alternative to hemodialysis. Furthermore, there is marked variability in peritoneal dialysis catheter insertion techniques and perioperative management within the United States. After the publication of best-demonstrated practices for peritoneal dialysis catheter placement, the utilization of peritoneal dialysis has increased significantly at our institution. We detail the long-term success of peritoneal dialysis catheter placement after the adoption of best-demonstrated practices. Retrospective chart review was performed on all patients who underwent laparoscopic peritoneal dialysis catheter placement using the best-demonstrated practice technique from January 2005 through December 2015. Preoperative patient demographic information, intraoperative variables, 30-day morbidity and mortality, and long-term catheter durability outcomes were investigated. A total of 457 patients met inclusion criteria. Four (0.9%) patients experienced an immediate postoperative complication requiring return to the operating room. There were no perioperative mortalities. A total of 298 (65.2%) patients were available for long-term follow-up; 221 (74.2%) patients are still alive, 76 (25.6%) patients are still undergoing peritoneal dialysis, 63 (21.1%) patients transitioned from peritoneal dialysis to hemodialysis, and 88 (29.5%) patients have undergone kidney transplantation. Based on Kaplan-Meier survival plots, 30% of patients will transition from peritoneal dialysis to hemodialysis after 5.5 years of peritoneal dialysis and the median time from commencing peritoneal dialysis to kidney transplantation is 5.6 years. Based on our institutional data, the adoption of best-demonstrated practices should provide long-term and reliable access to the peritoneal cavity. We recommend the adoption of these techniques to facilitate long-term peritoneal dialysis catheter survival. Copyright © 2017

  16. Short- and long-term mortality following primary total hip replacement for osteoarthritis: a Danish nationwide epidemiological study

    Pedersen, Alma Becic; Baron, J A; Overgaard, S


    -term mortality in subjects under 60 years old, and among THR patients without comorbidity. Long-term mortality was lower among THR patients than in controls (mortality rate ratio 0.7; 95% confidence interval 0.7 to 0.7). Overall, THR was associated with lower short- and long-term mortality among patients......We evaluated the short-term of 0 to 90 days and the longer term, up to 12.7 years, mortality for patients undergoing primary total hip replacement (THR) in Denmark in comparison to the general population. Through the Danish Hip Arthroplasty Registry we identified all primary THRs undertaken...... for osteoarthritis between 1 January 1995 and 31 December 2006. Each patient (n = 44 558) was matched at the time of surgery with three people from the general population (n = 133 674). We estimated mortality rates and mortality rate ratios with 95% confidence intervals for THR patients compared with the general...

  17. Exploratory survey study of long-term users of nicotine replacement therapy in Danish consumers

    Borup, Gitte; Christrup, Lona Louring; Lyngby Mikkelsen, Kim;

    dependence. Method Through advertisements in three national Danish newspapers, long-term NRT users were recruited to answer a short questionnaire about basic characteristics, health status and satisfaction with using NRT. A modified version of the Heaviness of Smoking Index (HSI) questionnaire was applied...... and fear of adverse health effects. Scoring on the modified HSI scale was 22.0% low, 68.0% moderate and 9.3% high dependent. Of the respondents, 67.0% used NRT within the first 30 min after waking. A validation check found a significant linear association between the two items in the modified HSI....... Conclusion A significant majority of users wished to quit NRT because of the cost of products, being tired of feeling addicted and fear of adverse health consequences. The majority of these users were moderate to high nicotine dependent. The strong association found between time to first NRT and NRT dosages...

  18. Long-Term Survival of Dialysis Patients with Bacterial Endocarditis Undergoing Valvular Replacement Surgery in the United States

    Leither, Maxwell D.; Shroff, Gautam R.; Ding, Shu; Gilbertson, David T.; Herzog, Charles A.


    Background Bacterial endocarditis in dialysis patients is associated with high mortality rates. The literature is limited regarding long-term outcomes of valvular replacement surgery and choice of prosthesis in dialysis patients with bacterial endocarditis. Methods and Results Dialysis patients hospitalized for bacterial endocarditis, 2004-2007, were studied retrospectively using data from the US Renal Data System. Long-term survival of patients undergoing valve replacement surgery with tissue or non-tissue valves was compared using the Kaplan-Meier method. A Cox proportional hazards model was used to identify independent predictors of mortality in patients undergoing valvular replacement surgery. During the study period, 11,156 dialysis patients were hospitalized for bacterial endocarditis and 1267 (11.4%) underwent valvular replacement surgery (tissue valve 44.3%, non-tissue valve 55.7%). In the valve replacement cohort, 60% were men, 50% white, 54% aged 45-64 years, and 36% diabetic. Estimated survival with tissue and non-tissue valves, respectively, at 0.5, 1, 2, and 3 years was 59% and 60%, 48% and 50%, 35% and 37%, and 25% and 30% (log rank P = 0.42). Staphylococcus was the predominant organism (66% of identified organisms). Independent predictors of mortality in patients undergoing valve replacement surgery included older age, diabetes as cause of end-stage renal disease, surgery during index hospitalization, staphylococcus as the causative organism, and dysrhythmias as a comorbid condition. Conclusions Valve replacement surgery is appropriate for well-selected dialysis patients with bacterial endocarditis, but is associated with high mortality rates. Survival does not differ with tissue or non-tissue prosthesis. PMID:23785002

  19. Recombinant Enzyme Replacement Therapy in Hypophosphatasia.

    Hofmann, Christine; Jakob, Franz; Seefried, Lothar; Mentrup, Birgit; Graser, Stephanie; Plotkin, Horacio; Girschick, Hermann J; Liese, Johannes


    Hypophosphatasia (HPP) is a rare monogenetic and multisystemic disease with involvement of different organs, including bone, muscle, kidney, lung, gastrointestinal tract and the nervous system. The exact metabolic mechanisms of the effects of TNAP deficiency in different tissues are not understood in detail. There is no approved specific treatment for HPP; therefore symptomatic treatment in order to improve the clinical features is of major interest. Enzyme replacement therapy (ERT) is a relatively new type of treatment based on the principle of administering a medical treatment replacing a defective or absent enzyme. Recently ERT with a bone targeted recombinant human TNAP molecule has been reported to be efficient in ten severely affected patients and improved survival of life threatening forms. These results are very promising especially with regard to the skeletal phenotype but it is unclear whether ERT also has beneficial effects for craniosynostosis and in other affected tissues in HPP such as brain and kidney. Long-term data are not yet available and further systematic clinical trials are needed. It is also necessary to establish therapeutic approaches to help patients who are affected by less severe forms of HPP but also suffer from a significant reduction in quality of life. Further basic research on TNAP function and role in different tissues and on its physiological substrates is critical to gain a better insight in the pathogenesis in HPP. This and further experiences in new therapeutic strategies may improve the prognosis and quality of life of patients with all forms of HPP.

  20. Two to three years of hormone replacement treatment in healthy women have long-term preventive effects on bone mass and osteoporotic fractures: the PERF study

    Bagger, Yu Z; Tankó, László B; Alexandersen, Peter


    Hormone replacement therapy (HRT) is often prescribed for a few years to suppress menopausal symptoms. Although its long-term use of HRT for the primary prevention of osteoporosis is not currently recommended, the long-term skeletal benefits of the limited therapy are of great interest. To determ......Hormone replacement therapy (HRT) is often prescribed for a few years to suppress menopausal symptoms. Although its long-term use of HRT for the primary prevention of osteoporosis is not currently recommended, the long-term skeletal benefits of the limited therapy are of great interest...

  1. Metallosis with pseudotumour formation: Long-term complication following cementless total hip replacement in a dog

    Volstad, Nicola J.; Schaefer, Susan L.; Snyder, Laura A.; Meinen, Jeffrey B.; Sample, Susannah J.


    Summary Case description A 10-year-old female Belgian Teruven dog was presented to our clinic for total hip revision following a diagnosis of implant (cup) failure with metallosis and abdominal pseudotumour formation. The patient had a cementless metal-on-polyethylene total hip replacement performed nine years prior to presentation. Clinical findings The clinical findings, including pseudotumour formation locally and at sites distant from the implant and pain associated with the joint replacement, were similar to those described in human patients with this condition. Histopathological, surgical, and radiographic findings additionally supported the diagnosis of metallosis and pseudotumour formation. Treatment and outcome Distant site pseudo tumours were surgically removed and the total hip replacement was explanted due to poor bone quality. The patient recovered uneventfully and has since resumed normal activity. Conclusion In veterinary patients with metal-on-polyethylene total hip implants, cup failure leading to metallosis and pseudotumour formation should be considered as a potential cause of ipsilateral hindlimb lameness, intra-pelvic abdominal tumours, or a combination of both. These clinical findings may occur years after total hip replacement surgery. PMID:27189390

  2. Estrogen metabolism genotypes, use of long-term hormone replacement therapy and risk of postmenopausal breast cancer.

    Cerne, Jasmina Ziva; Novakovic, Srdjan; Frkovic-Grazio, Snjezana; Pohar-Perme, Maja; Stegel, Vida; Gersak, Ksenija


    Association between long-term hormone replacement therapy (HRT) use and increased risk of breast cancer is still under debate. Functionally relevant genetic variants within the estrogen metabolic pathway may alter exposure to exogenous sex hormones and affect the risk of postmenopausal breast cancer. We investigated the associations of common polymorphisms in 4 genes encoding key proteins of the estrogen metabolic pathway, duration of HRT use and their interactions with breast cancer risk. We studied 530 breast cancer cases and 270 controls of the same age and ethnicity participating in a case-control study of postmenopausal women. Duration of HRT use was ascertained through a postal questionnaire. Genotyping was conducted for CYP1B1 (rs1056836), COMT (rs4680), GSTP1 (rs1695) and MnSOD (rs4880) polymorphisms by PCR-based RFLP and TaqMan® allelic discrimination method. Adjusted odds ratios and 95% confidence intervals were calculated using logistic regression analysis. HRT use was significantly associated with decreased breast cancer risk (pC and HRT use (pinteraction=0.036); the risk of breast cancer associated with long-term vs. short-term HRT use was decreased in women homozygous for the wild-type allele and increased in women with at least one variant allele of the MnSOD 47T>C polymorphism. Our results suggest that MnSOD 47T>C polymorphism in interaction with long-term HRT use may modify the risk of breast cancer.

  3. Long-term outcomes of tear-oriented ascending/hemiarch replacements for acute type A aortic dissection.

    Aizawa, Kei; Kawahito, Koji; Misawa, Yoshio


    Extended arch repair for acute type A aortic dissection remains controversial. Our strategy for acute type A aortic dissection was primary entry resection and tear-oriented ascending/hemiarch replacement for patients with the intimal tear in the ascending aorta or is not found in the ascending/aortic arch. Extended total/partial arch replacement was performed for patients with the tear located in the aortic arch. Here, we investigated the validity of our strategy from the viewpoints of long-term survival and reoperation. Between 2003 and 2014, 267 acute type A aortic dissection patients (mean age; 65.2 ± 12.9 years, 134 men and 133 women) underwent emergent surgical repair. Ascending/hemiarch replacements were performed in 225 patients (ascending/hemiarch group) and total/partial arch replacements in 42 patients (arch group). Early and late outcomes of both groups were compared. The hospital mortality rates in the ascending/hemiarch and the arch groups were 4.4 and 9.5 %, respectively (p = 0.25). For ascending/hemiarch and arch groups, the actuarial survival rates were 80.7 vs. 84.3 % after 5 years, and 66.4 vs. 74.6 %, respectively, after 10 years (p = 0.94). For ascending/hemiarch and arch groups, reoperation-free survival rates were 72.1 vs. 77.1 % after 5 years, and 62.0 vs. 67.1 %, respectively, after 10 years (p = 0.85). We observed no significant differences in the actuarial survival or reoperation-free survival rates between the groups. These findings suggest that tear-oriented ascending/hemiarch replacement for acute type A aortic dissection does not increase the risk of long-term mortality or reoperation.

  4. Immediate and long term evolution of valve replacement in children less than 12 years old

    Atik Fernando Antibas


    Full Text Available OBJECTIVE: The aim of this work was the follow-up and evaluation of valve replacement in children under 12 years of age. METHODS: Forty-four children less than 12 years old were underwent valve replacement at INCOR-HCFMUSP between January 1986 and December 1992. Forty (91% were rheumatic, 39 (88.7% were in functional classes II or IV, 19 (43.2% were operated upon on an emergency basis, and 6 (13.6% had atrial fibrillation. Biological prostheses (BP were employed in 26 patients (59.1%, and mechanical prostheses (MP in 18 (40.9%. Mitral valves were replaced in 30 (68.7%, aortic valves in 8 (18.2%, a tricuspid valve in 1 (2.3%, and double (aortic and mitral valves in 5 (11.4 of the patients. RESULTS: Hospital mortality was of 4.5% (2 cases. The mean follow-up period was 5.8 years. Re-operations occurred in 63.3% of the patients with BP and in 12.5% of those with MP (p=0.002. Infectious endocarditis was present in 26.3% of the BP, but in none of the cases of MP (p=0.049. Thrombosis occurred in 2 (12.5% and hemorrhage in one (6.5% of the patients with a MP. Delayed mortality occurred in 5 (11.9% of the patients over a mean period of 2.6 years; four had had BP and one had a MP (NS. Actuarial survival and re-operation-free curves after 10 years were respectively, 82.5±7.7 (SD% and 20.6±15.9%. CONCLUSION: Patients with MP required fewer re-operation, had less infectious endocarditis and lower late mortality rates compared with patients with bioprostheses. The former, therefore, appear to be the best valve replacement for pediatric patients.

  5. Long-term hormone replacement therapy preserves bone mineral density in Turner syndrome

    Cleemann, Line; Hjerrild, Britta E; Lauridsen, Anna L;


    at baseline and follow-up (5.9+/-0.7 years). SETTING: Tertiary hospital. PARTICIPANTS: Fifty-four women with TS (43.0+/-9.95 years). Interventions Hormone replacement therapy (HRT) and calcium and vitamin D supplementation. Main outcome measures BMD (g/cm(2)) measured at lumbar spine, hip, and the non.......010+/-0.144, PTestosterone, IGF1, and maximal oxygen uptake was significantly reduced in TS. CONCLUSION: Longitudinal changes in BMD in TS were slight. BMD can be maintained at most sites in well...

  6. Prediction of Long-term Post-operative Testosterone Replacement Requirement Based on the Pre-operative Tumor Volume and Testosterone Level in Pituitary Macroadenoma

    Cheng-Chi Lee; Chung-Ming Chen; Shih-Tseng Lee; Kuo-Chen Wei; Ping-Ching Pai; Cheng-Hong Toh; Chi-Cheng Chuang


    Non-functioning pituitary macroadenomas (NFPAs) are the most prevalent pituitary macroadenomas. One common symptom of NFPA is hypogonadism, which may require long-term hormone replacement. This study was designed to clarify the association between the pre-operative tumor volume, pre-operative testosterone level, intraoperative resection status and the need of long-term post-operative testosterone replacement. Between 2004 and 2012, 45 male patients with NFPAs were enrolled in this prospective...

  7. Long-Term Weight-Loss Maintenance by a Meal Replacement Based Weight Management Program in Primary Care

    Renate Kruschitz


    Full Text Available Objective: Structured obesity treatment programs at primary care level are becoming increasingly important. However, evidence from current treatment approaches in the long term is lacking. In view of this fact we evaluated a standardized, meal replacement-based weight loss program (myLINE®; AENGUS, Graz, Austria according to the currently applicable guidelines. Methods: Data of overweight and obese individuals (n = 70 who participated at least 36 months in the program were analyzed. Data were collected at baseline (T0 as well as after 1, 3, 6, 12, 24, and 36 (T1-T36 months. Body composition was measured by conventional anthropometry and bioelectrical impedance analysis. Results: Compared to T0, a maximum weight, BMI, fat mass, absolute body cell mass (BCM reduction and an increase of relative BCM could be seen at T6. Subsequently, the findings reveal a significant reduction of body weight and body fat and a satisfying development of body cell mass during the observation period of 36 months. Conclusion: The evaluated program complies with national and international guidelines for the therapy of obesity in adults and is efficient and meaningful for a long-term therapeutic use in primary care..

  8. Selected soil enzyme activities in an oak-hickory forest following long-term prescribed burning

    M. R. Bayan; F. Eivazi


    The biochemical reactions within the soil are mediated by soil flora and fauna, and are catalyzed by enzymes. Therefore, enzymes play a significant role in nutrient cycling. Enzymes are specific for the type of chemical reactions in which they participate. Arylsulfatase is the enzyme that catalyzes the hydrolysis of an arylsulfate anion by fission of the oxygen-sulfur...

  9. Long-term in vitro culture of bovine preantral follicles: Effect of base medium and medium replacement methods.

    Araújo, V R; Gastal, M O; Wischral, A; Figueiredo, J R; Gastal, E L


    Two culture media and replacement methods were compared during long-term in vitro culture of secondary follicles of cattle using α-MEM(+) or TCM-199(+) as base media. The medium replacement methods were: Conventional - removal and subsequent addition of the same amount (60μl) in a 100μl aliquot (MEM-C and TCM-C), and Small Supplementation - addition of 5μl of fresh medium to an initial small aliquot (50μl), resulting in a final volume of 125μl on the last day of culture (MEM-S and TCM-S). A total of 207 secondary follicles were cultured individually for 32 days at 38.5°C in 5% CO2 and medium replacement was performed every other day. The MEM-S treatment resulted in a larger (P0.05) the follicular and estradiol end points for TCM-199(+). The expression of the FSHR gene was greater (Pculture of preantral follicles of cattle if progressive addition of medium is used for medium change.

  10. Effect of long-term industrial waste effluent pollution on soil enzyme activities and bacterial community composition.

    Subrahmanyam, Gangavarapu; Shen, Ju-Pei; Liu, Yu-Rong; Archana, Gattupalli; Zhang, Li-Mei


    Although numerous studies have addressed the influence of exogenous pollutants on microorganisms, the effect of long-term industrial waste effluent (IWE) pollution on the activity and diversity of soil bacteria was still unclear. Three soil samples characterized as uncontaminated (R1), moderately contaminated (R2), and highly contaminated (R3) receiving mixed organic and heavy metal pollutants for more than 20 years through IWE were collected along the Mahi River basin, Gujarat, western India. Basal soil respiration and in situ enzyme activities indicated an apparent deleterious effect of IWE on microbial activity and soil function. Community composition profiling of soil bacteria using 16S rRNA gene amplification and denaturing gradient gel electrophoresis (DGGE) method indicated an apparent bacterial community shift in the IWE-affected soils. Cloning and sequencing of DGGE bands revealed that the dominated bacterial phyla in polluted soil were affiliated with Firmicutes, Acidobacteria, and Actinobacteria, indicating that these bacterial phyla may have a high tolerance to pollutants. We suggested that specific bacterial phyla along with soil enzyme activities could be used as relevant biological indicators for long-term pollution assessment on soil quality. Graphical Abstract Bacterial community profiling and soil enzyme activities in long-term industrial waste effluent polluted soils.

  11. Prediction of Long-term Post-operative Testosterone Replacement Requirement Based on the Pre-operative Tumor Volume and Testosterone Level in Pituitary Macroadenoma.

    Lee, Cheng-Chi; Chen, Chung-Ming; Lee, Shih-Tseng; Wei, Kuo-Chen; Pai, Ping-Ching; Toh, Cheng-Hong; Chuang, Chi-Cheng


    Non-functioning pituitary macroadenomas (NFPAs) are the most prevalent pituitary macroadenomas. One common symptom of NFPA is hypogonadism, which may require long-term hormone replacement. This study was designed to clarify the association between the pre-operative tumor volume, pre-operative testosterone level, intraoperative resection status and the need of long-term post-operative testosterone replacement. Between 2004 and 2012, 45 male patients with NFPAs were enrolled in this prospective study. All patients underwent transsphenoidal surgery. Hypogonadism was defined as total serum testosterone levels of testosterone to patients with defined hypogonadism or clinical symptoms of hypogonadism. Hormone replacement for longer than 1 year was considered as long-term therapy. The need for long-term post-operative testosterone replacement was significantly associated with larger pre-operative tumor volume (p = 0.0067), and lower pre-operative testosterone level (p = 0.0101). There was no significant difference between the gross total tumor resection and subtotal resection groups (p = 0.1059). The pre-operative tumor volume and testosterone level impact post-operative hypogonadism. By measuring the tumor volume and the testosterone level and by performing adequate tumor resection, surgeons will be able to predict post-operative hypogonadism and the need for long-term hormone replacement.

  12. Robotic mitral valve replacement: A single center, medium-long term follow-up of 43 cases

    Guo-peng LIU


    Full Text Available Objective To summarize the surgical experience gained from robotic mitral valve replacement (MVR, and demonstrate the long-term clinical follow-up results. Methods From Jan. 2007 to Jan. 2015, more than 700 patients underwent various types of robotic cardiac surgery in the Department the authors served in, and of them 43 patients underwent robotic MVR with da Vinci Surgical System (Intuitive Surgical, USA. Among the 43 patients, the average age was 47±11 years (ranged 19-65 years, and sex ratio (female to male was 0.8:1. Six patients were with heart function of NYHA class Ⅰ, 30 patients were of NYHA class Ⅱ and 7 patients were of NYHA class Ⅲ. The left ventricular ejection fraction (LVEF were 54%-78% (64.0%±7.1%, and 20 patients had atrial fibrillation on admission, and 35 patients were with rheumatic mitral stenosis (MS. Atrial septal defect (0.7cm in size co-existed in 1 case and 1 patient had mild aortic regurgitation. Mechanical or bioprosthetic mitral valve was replaced via left atriotomy by using da Vinci robotic surgical system after cardiopulmonary bypass (CPB set-up. Radiopaque titan clips was employed by Cor-Knot knot-tying device (LSI Solutions, Inc, Victor, NY to anchor the prosthetic valve. Trans-esophageal echocardiography (TEE was performed before and after surgery. The operative data were collected and patients were followed up at outpatient clinic regularly up to 6 years. Results All cases were performed successfully with the same surgery. No conversion to median sternotomy or operative mortality occurred. The average operation time was 292±62 minutes (ranged 140-450 minutes with CPB time of 124±26 minutes and aortic occlusion time of 88±21 minutes. The postoperative mechanical ventilation support time was continued for 15±6 hours, and the average staying length in critical care unit was 4±1 days. No myocardial infarction, ventricular tachycardia or excessive bleeding was complicated. All patients were successfully

  13. Long-term effects of engineered nanoparticles on enzyme activity and functional bacteria in wastewater treatment plants.

    Zheng, Xiong; Huang, Haining; Su, Yinglong; Wei, Yuanyuan; Chen, Yinguang


    The pervasive use of engineered nanoparticles (NPs) in a wide range of fields raises concerns about their potential environmental impacts. Previous studies confirmed that some NPs had already entered wastewater treatment plants (WWTPs). Wastewater nutrient removal depends on the metabolisms of activated sludge bacteria and their related key enzymes. Therefore, this study compared the possible influences of Al2O3, SiO2, TiO2, and ZnO NPs on the key enzymes activities and microbial community structures involved in wastewater treatment facilities. It was found that long-term exposure to these NPs significantly affected the microbial communities and changed the relative abundances of key functional bacteria, such as ammonia-oxidizing bacteria. Also, the gene expressions and catalytic activities of essential enzymes, such as ammonia monooxygenase, nitrite oxidoreductase, nitrate reductase, and nitrite reductase, were decreased, which finally resulted in a lower efficiency of biological nitrogen removal.

  14. Responses of absolute and specific soil enzyme activities to long term additions of organic and mineral fertilizer.

    Zhang, Xinyu; Dong, Wenyi; Dai, Xiaoqin; Schaeffer, Sean; Yang, Fengting; Radosevich, Mark; Xu, Lili; Liu, Xiyu; Sun, Xiaomin


    Long-term phosphorus (P) and nitrogen (N) applications may seriously affect soil microbial activity. A long-term field fertilizer application trial was established on reddish paddy soils in the subtropical region of southern China in 1998. We assessed the effects of swine manure and seven different rates or ratios of NPK fertilizer treatments on (1) the absolute and specific enzyme activities per unit of soil organic carbon (SOC) or microbial biomass carbon (MBC) involved in C, N, and P transformations and (2) their relationships with soil environmental factors and soil microbial community structures. The results showed that manure applications led to increases in the absolute and specific activities of soil β-1,4-glucosidase(βG), β-1,4-N-acetylglucosaminidase (NAG), and leucine aminopeptidase (LAP). The absolute and specific acid phosphatase (AP) activities decreased as mineral P fertilizer application rates and ratios increased. Redundancy analysis (RDA) showed that there were negative correlations between absolute and specific AP activities, pH, and total P contents, while there were positive correlations between soil absolute and specific βG, NAG, and LAP enzyme activities, and SOC and total N contents. RDA showed that the contents of actinomycete and Gram-positive bacterium PLFA biomarkers are more closely related to the absolute and specific enzyme activities than the other PLFA biomarkers (Pfertilizer application rates to subtropical paddy soils should not exceed 44 kg P ha(-1) year(-1).

  15. Long-term follow-up of mobile-bearing total ankle replacement in patients with inflammatory joint disease.

    Kraal, T; van der Heide, H J L; van Poppel, B J; Fiocco, M; Nelissen, R G H H; Doets, H C


    Little is known about the long-term outcome of mobile-bearing total ankle replacement (TAR) in the treatment of end-stage arthritis of the ankle, and in particular for patients with inflammatory joint disease. The aim of this study was to assess the minimum ten-year outcome of TAR in this group of patients. We prospectively followed 76 patients (93 TARs) who underwent surgery between 1988 and 1999. No patients were lost to follow-up. At latest follow-up at a mean of 14.8 years (10.7 to 22.8), 30 patients (39 TARs) had died and the original TAR remained in situ in 28 patients (31 TARs). The cumulative incidence of failure at 15 years was 20% (95% confidence interval (CI) 11 to 28). The mean American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score of the surviving patients at latest follow-up was 80.4 (95% CI 72 to 88). In total, 21 patients (23 TARs) underwent subsequent surgery: three implant exchanges, three bearing exchanges and 17 arthrodeses. Neither design of TAR described in this study, the LCS and the Buechel-Pappas, remains currently available. However, based both on this study and on other reports, we believe that TAR using current mobile-bearing designs for patients with end-stage arthritis of the ankle due to inflammatory joint disease remains justified.

  16. Long term end-stage renal disease and death following acute renal replacement therapy in the ICU

    Lohse, R.; Damholt, M. B.; Wiis, J.


    INTRODUCTION: In ICU the need for acute renal replacement therapy (RRT) associates with high mortality and risk of end-stage renal disease (ESRD), but there are limited long-term data. We investigated these outcomes and their risk factors. METHODS: Retrospective analysis of all adult patients...... admitted to a general, university hospital ICU 2005-2012, excluding chronic dialysis patients. ESRD was defined as need of RRT > 90 days or kidney transplant. RESULTS: Of 5766 patients included, 1004 (16%) received acute RRT; their 30-day mortality was 42% vs. 16% for those not requiring acute RRT...... (adjusted hazard ratio (HR) 1.13 (0.96-1.32)). The 90-day mortality was 55% for patients receiving acute RRT vs. 22% for those who did not (adjusted HR 1.32 (1.15-1.51)) and 1-year mortality was 63% vs. 30%, respectively, (adjusted HR 1.31 (1.16-1.48)). The 7-year risk of ESRD for ICU patients surviving 90...

  17. Sonographic assessment of carotid artery in postmenopausal women receiving long-term low-dose hormone replacement therapy

    Wang Hong-yan; Jiang Yu-xin; Meng Hua; Ge Qin-sheng


    Objective: The aim of this study was to determine the influence of long-term low-dose hor mone replacement therapy (HRT) on the intima-media wall of the carotid artery in postmenopa usal women by ultrasound.Methods: 146 postmenopausal women were divided into the HRT group(n= 68, HRT over 5years after menopause) and the control group(n= 78, no HRT). The intima-media thickness (IMT) of the carotid arteries was measured bilaterally, the characteristics of the atherosclerotic plaques were described, the peak systolic velocity (PSV) and resistance index (RI) were measured by ultrasound examination.Results: The IMT of HRT group was significantly smaller than that of the control group,(0. 089±0. 22) cm vs (0. 093±0.29) cm, (P<0. 01). The occurrence of plaques was reduced in HRT group than the control group (7.7% vs 12.7%, P<0. 05). The plaques were most frequently found at the bifurcation of the arteries. The soft and mixed plaques in HRT group were found significantly less than that of the control group (soft 1.7% vs 4. 5%, mixed 3.1% vs 6. 7%, both P<0.05), while the hard plaques in HRT group were more than those of the control group(2.6% vs 1.3%, P<0. 05). The maximum plaque thickness of HRT group was less than that of control group (0. 191±0. 057) cm vs (0. 226±0. 073) cm, (P<0.05). The internal carotid artery PSV and RI in the two groups were similar [PSV (65.61±26.55) cm/s vs (64.82±27. 22) cm/s, RI (0.67±0. 082) vs (0. 68±0. 075), both P>0.05].Conclusion: Our study indicated that HRT may has an effect to reduce the carotid IMT thickness, inhibit the plaque formation, and make the plaques harder and more stable. The long-term low-dose HRT may protect the postmenopausal women against the artherosclerosis of the carotid artery.

  18. Elaboration of Method of Long-Term Culturing and Selection of Enzyme Producers

    Blieva Raushan


    Full Text Available On the basis of the conducted researches on pectin lyase and proteolytic enzyme biosynthesis by Penicillium and Asperaillus micromycetes we have developed efficient methods for their cultivation and selection. We theoretically substantiated and experimentally confirmed an advantage of growing micromycetes in a new filament-spongy immobilized growth structure on the substrate relative to the traditional method of deep cultivation of free cells in the form of pellets. When comparing a traditional with our innovative method of cultivation, many advantages of the latter are revealed, above all being the possibility of the formation of new highly selective cultures in the long process of their growth with modified culturally - morphological properties.


    Ling Hu; Yun Yue; Ping-ping Zuo; Zheng-yu Jin; Feng Feng; Hui You; Ming-li Li; Qin-sheng Ge


    Objective To investigate the effects of long-term low dose hormone replacement therapy (HRT) on postmenopausal women in hormone level,cognition score,hippocampus volume,and magnetic resonance spectroscopy (MRS) parameters.Methods A total of 182 postmenopausal women aged 50-87 years were chosen at Peking Union Medical College Hospital and assigned to HRT group and control group.The volunteers of HRT group had taken low dose hormone [estradiol (E2) 0.5-1.0 mg and progesterone 0.5-2.0 mg,once a day] for 4-33 years.The concentrations of E2,progesterone,and testosterone were measured using enzyme-linked immunosorbent assay (ELISA).The gene types of apolipoprotein E (ApoE) were measured by polymerase chain reaction,and the subjects with susceptible genes (ApoE ε3/ε4) of Alzheimer's disease (AD) were screened.Their hippocampus volumes and MRS parameters were obtained through magnetic resonance imaging (MRI),and results in two groups were analyzed by statistical method.Results Compared with control group,the concentrations of E2 at each age stage in HRT group were significantly higher (P<0.05) except the 80-89 years old subgroup;yet,there were no statistical differences in the concentrations of progesterone and testosterone between the two groups.There was no obvious difference in ApoE subtypes distribution between the two groups.The results of hippocampus MRI for the subjects with susceptible genes ApoE ε3/ε4 (HRT group 14 cases,control group 11 cases) showed that the ratio of bilateral hippocampus volume to whole brain volume in HRT group (0.406±0.028) was significantly higher than control group (0.369±0.031,P<0.05).The results of 1H MRS for the subjects with susceptible genes ApoE ε3/ε4 (HRT group 12 cases,control group 11 cases) showed that the N-acetylaspartate/total creatine at the area of hippocampus in HRT group (1.54±0.08) were significantly higher than control group (1.45±0.13,P<0.05).Conclusions For postmenopausal women,long-term low dose HRT can

  20. Reconstructed ancestral enzymes suggest long-term cooling of Earth's photic zone since the Archean

    Garcia, Amanda K.; Schopf, J. William; Yokobori, Shin-ichi; Akanuma, Satoshi; Yamagishi, Akihiko


    Paleotemperatures inferred from the isotopic compositions (δ18O and δ30Si) of marine cherts suggest that Earth’s oceans cooled from 70 ± 15 °C in the Archean to the present ˜15 °C. This interpretation, however, has been subject to question due to uncertainties regarding oceanic isotopic compositions, diagenetic or metamorphic resetting of the isotopic record, and depositional environments. Analyses of the thermostability of reconstructed ancestral enzymes provide an independent method by which to assess the temperature history inferred from the isotopic evidence. Although previous studies have demonstrated extreme thermostability in reconstructed archaeal and bacterial proteins compatible with a hot early Earth, taxa investigated may have inhabited local thermal environments that differed significantly from average surface conditions. We here present thermostability measurements of reconstructed ancestral enzymatically active nucleoside diphosphate kinases (NDKs) derived from light-requiring prokaryotic and eukaryotic phototrophs having widely separated fossil-based divergence ages. The ancestral environmental temperatures thereby determined for these photic-zone organisms--shown in modern taxa to correlate strongly with NDK thermostability--are inferred to reflect ancient surface-environment paleotemperatures. Our results suggest that Earth's surface temperature decreased over geological time from ˜65-80 °C in the Archean, a finding consistent both with previous isotope-based and protein reconstruction-based interpretations. Interdisciplinary studies such as those reported here integrating genomic, geologic, and paleontologic data hold promise for providing new insight into the coevolution of life and environment over Earth history.

  1. Alterations in antioxidant enzyme activities and proline content in pea leaves under long-term drought stress.

    Karataş, Ilhami; Öztürk, Lokman; Demir, Yavuz; Unlükara, Ali; Kurunç, Ahmet; Düzdemir, Oral


    The effects of long-term drought stress on chlorophyll, proline, protein and hydrogen peroxide (H2O2) contents, malondialdehyde (MDA) in terms of lipid peroxidation and on the changes in the activities of antioxidant enzymes such as superoxide dismutase (SOD, EC, ascorbate peroxidase (APX, EC, catalase (CAT, EC and peroxidase (POX; EC in the leaves of pea (Pisum sativum L.) were studied in field conditions. Chlorophyll and protein contents in leaves decreased significantly with increased drought stress. The proline content increased markedly under water deficit. MDA amounts were elevated as a result of water shortage, whereas H(2)O(2) content changed slightly in pea leaves exposed to drought stress. Drought stress markedly enhanced the activities of SOD, CAT and POX but slightly changed the activity of APX. We conclude that in field conditions, long-term water shortage increased the susceptibility to drought in peas.

  2. Long-term Administration of Angiotension-Converting Enzyme Inhibitor Improves the Outcome of Chronic Heart Failure in Senile Patients

    陈学林; 张劲农; 柯琴梅; 张银环; 刘承云


    Summary: One hundred and sixteen senile patients (older than 65 years) with chronic heart failure (CHF) were analyzed retrospectively in order to verify if old patients with CHF would benefit from long-term (one year) angiotension-converting enzyme inhibitor (ACEI) treatment. The frequency of drugs (including ACEI, digitalis and diuretic) used was stratified into four degrees accordingly. Development of the CHF was scored with regard to relapse rate and severity of this disease. Stepwise regression analysis was applied to explore the relationship between the scored outcome of CHF and the frequency of individual drug administra tion. A significant relationship of the scored outcome of CHF to the frequency of ACEI usage but not to digitalis nor to diuretics was found (partial coefficient of the correlation r=0. 42, P=0. 002). It was concluded that the longterm administration of ACEI improves the outcome of CHF in senile patients.

  3. Long-term follow-up of bioprosthetic aortic valve replacement in patients aged ≤60 years.

    Anselmi, Amedeo; Flecher, Erwan; Chabanne, Celine; Ruggieri, Vito Giovanni; Langanay, Thierry; Corbineau, Hervé; Leguerrier, Alain; Verhoye, Jean-Philippe


    To address the long-term durability of bioprostheses used for aortic valve replacement (AVR) in adult patients aged ≤60 years at the time of surgery. Through a retrospective review of a prospectively collected database, we identified 416 bioprosthetic AVRs performed between 1977 and 2013. A prospective follow-up of valve-related and non-valve-related events was performed. Follow-up was 98.5% complete (2423.1 patient-years; average, 6 ± 5.5 years). At 15 years, overall survival was 62.1 ± 4.4%; freedom from valve-related death was 97.1 ± 1.6%. There were 68 SVD events (11.9 ± 28.8 years after surgery). Freedom from SVD at 15 years was 48.7 ± 5.5% for Kaplan-Meier analysis and 61.4 ± 4.3% for competing-risks analysis. After stratification into age subgroups (SVD (P = .50). The average delay to SVD was not statistically different among subgroups (P = .30). There were 57 reoperations for SVD (11.8 ± 5.2 years after implantation). The 15 year freedom from reoperation for SVD was 55.4 ± 5.6% by Kaplan-Meier analysis and 67.1 ± 4.2% by competing-risks analysis. After stratification by age, freedom from reoperation for SVD was comparable (P = .13). Freedom from any valve-related complication or death was 42 ± 5% by Kaplan-Meier analysis and 54.4 ± 4.1% by competing-risks analysis. The lifetime risk of SVD is considerable in patients aged ≤60 years at the time of bioprosthesis implantation. Nonetheless, durability remains consistent during the first decade; additional data are required for the second decade. Patients' information is pivotal for valve choice (competing-risks method). Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  4. Does preservation of the sub-valvular apparatus during mitral valve replacement affect long-term survival and quality of life? A Microsimulation Study

    Murtuza Bari


    Full Text Available Abstract Background Techniques to preserve the sub-valvular apparatus in order to reduce morbidity and mortality following mitral valve replacement have been frequently reported. However, it is uncertain what impact sub-valvular apparatus preservation techniques have on long-term outcomes following mitral valve replacement. This study investigated the effect of sub-valvular apparatus preservation on long-term survival and quality of life following mitral valve replacement. Methods A microsimulation model was used to compare long-term survival and quality-adjusted life years following mitral valve replacement after conventional valve replacement and sub-valvular apparatus preservation. Probabilistic sensitivity analysis and alternative analysis were performed to investigate uncertainty associated with the results. Results Our Analysis suggests that patients survive longer if the sub-valvular apparatus are preserved (65.7% SD 1.5%, compared with 58.1% SD 1.6% at 10 years. The quality adjusted life years gained over a 10 year period where also greater after sub-valvular apparatus preservation. (6.54 QALY SD 0.07 QALY, compared with 5.61 QALY, SD 0.07 QALY. The superiority of preservation techniques was insensitive to patient age, parameter or model uncertainty. Conclusion This study suggests that long-term outcomes may be improved when the sub-valvular apparatus are preserved. Given the lack of empirical data further research is needed to investigate health-related quality of life after mitral valve replacement, and to establish whether outcomes differ between preservation techniques.

  5. Digestive Enzyme Replacement Therapy: Pancreatic Enzymes and Lactase.

    Felicilda-Reynaldo, Rhea Faye D; Kenneally, Maria


    Maldigestion occurs when digestive enzymes are lacking to help break complex food components into absorbable nutrients within the gastrointestinal tract. Education is needed to help patients manage the intricacies of digestive enzyme replacement therapies and ensure their effectiveness in reducing symptoms of maldigestion.

  6. Donor Selection in Flow Replacement Bypass Surgery for Cerebral Aneurysms: Quantitative Analysis of Long-term Native Donor Flow Sufficiency.

    Rustemi, Oriela; Amin-Hanjani, Sepideh; Shakur, Sophia F; Du, Xinjian; Charbel, Fady T


    Graft selection in extracranial-intracranial bypass surgery for cerebral aneurysms has traditionally been based on clinical impression and operator preference. However, decision making can be optimized with a donor selection algorithm based on intraoperative flow data. To present long-term follow-up and quantitative assessment of flow sufficiency for native donors selected in this manner. Patients with bypass for anterior circulation intracranial aneurysms using only a native donor (superficial temporal artery) selected on the basis of an intraoperative flow algorithm over a 10-year period were retrospectively studied. Intracranial hemispheric and bypass flows were assessed preoperatively and postoperatively when available with quantitative magnetic resonance angiography. Twenty-two patients with flow data were included (median aneurysm size, 22 mm). The intraoperative flow offer (cut flow) of the superficial temporal artery was sufficient in these cases relative to the flow demand in the sacrificed vessel (59 vs 28 mL/min) to warrant its use. Bypass flow averaged 81 mL/min postoperatively (n = 19). Bypass flows were highest in the immediate postoperative period but remained stable between the intermediate and final follow-up (40 vs 52 mL/min; P = .39; n = 8). Mean ipsilateral hemisphere flows were maintained after bypass (299 vs 335 mL/min; P = .42; n = 7), and remained stable over intermediate and long-term follow-up. Ipsilateral hemispheric flows remained similar to contralateral flows at all time points. Despite a relative reduction in bypass flow over time, hemispheric flows were maintained, indicating that simple native donors can carry sufficient flow for territory demand long term when an intraoperative flow-based algorithm is used for donor selection.

  7. Enzyme replacement therapy for alpha-mannosidosis

    Borgwardt, Line Gutte; Dali, Christine I.; Fogh, J


    Alpha-mannosidosis (OMIM 248500) is a rare lysosomal storage disease (LSD) caused by alpha-mannosidase deficiency. Manifestations include intellectual disabilities, facial characteristics and hearing impairment. A recombinant human alpha-mannosidase (rhLAMAN) has been developed for weekly intrave...... intravenous enzyme replacement therapy (ERT). We present the preliminary data after 12 months of treatment....

  8. The Scandinavian total ankle replacement: long-term, eleven to fifteen-year, survivorship analysis of the prosthesis in seventy-two consecutive patients.

    Brunner, Samuel; Barg, Alexej; Knupp, Markus; Zwicky, Lukas; Kapron, Ashley L; Valderrabano, Victor; Hintermann, Beat


    The objective of this study was to determine the long-term survivorship and clinical and radiographic results of the Scandinavian Total Ankle Replacement (STAR). From February 1996 to March 2000, seventy-seven ankles in seventy-two patients (thirty-seven female and thirty-five male patients, with an average age of fifty-six years) underwent total ankle replacement using the STAR prosthesis with a single coating of hydroxyapatite. Two patients were lost to follow-up, and twelve patients with thirteen ankle replacements died. The average duration of follow-up for the patients without revision was 12.4 years (range, 10.8 to 14.9 years). Sixty-two of the seventy-seven ankles were available for final follow-up. Twenty-nine (38%) of the seventy-seven ankles had a revision of at least one of the metallic components. The probability of implant survival was 70.7% at ten years and 45.6% at fourteen years. The main reasons for revision were aseptic loosening, subsidence of the talar component, and progressive cyst formation. Polyethylene insert fractures were observed in eleven ankles. While the midterm to short-term results for patients managed with the STAR prosthesis have been encouraging at 3.7 years, the long-term survivorship of the same cohort was considerably inferior. The subjective and clinical results of the patients with retained prostheses are generally good and comparable with results reported in the current literature.

  9. Effects of Long-term Growth Hormone Replacement in Adults With Growth Hormone Deficiency Following Cure of Acromegaly

    Tritos, Nicholas A; Johannsson, Gudmundur; Korbonits, Márta


    CONTEXT: GH deficiency (GHD) may occur in adults with cured acromegaly (acroGHD). OBJECTIVE: Our objective was to examine the effectiveness and safety of GH replacement in acroGHD. DESIGN: This study was a retrospective analysis of data from KIMS (Pfizer International Metabolic Database). SETTING...

  10. Long-term Clinical Outcome of Antibody Replacement Therapy in Humoral Immunodeficient Adults With Respiratory Tract Infections

    van Kessel, Diana A; Hoffman, Thijs W; van Velzen-Blad, Heleen; Zanen, Pieter|info:eu-repo/dai/nl/173876412; Grutters, Jan|info:eu-repo/dai/nl/258116129; Rijkers, Ger T

    In severe humoral immunodeficiency the indication for antibody replacement therapy (ART) is clear, and supported by several large studies. However, for milder forms of humoral immunodeficiency, the indication for ART is less clear. This is a retrospective cohort study of 87 adults with recurrent

  11. In situ replacement of infected vascular prosthesis with fresh arterial homograft: Early and long-term results in 18 patients

    Pejkić Siniša


    Full Text Available Introduction. Graft infection is rightly considered one of the severest complications of vascular reconstruction. Treatment is non­standardized and associated with high mortality and morbidity rates. The choice of therapeutic modality depends upon variety of factors. One increasingly used option is in situ replacement of the infected prosthesis with the arterial allograft. Objective. The aim of this prospective nonrandomized study was to evaluate the effectiveness and durability of fresh arterial allograft as in situ substitute for the infected vascular prosthesis. Methods. During period of 2002-2005, 18 patients with the synthetic vascular graft infection underwent partial or complete prosthesis removal and secondary in situ reconstruction using the fresh arterial allograft, preserved under hypothermic conditions in buffered saline solution with an addition of antibiotics. Results. In 14 male and 4 female patients, meanaged 62 years, 8 aortic and 10 peripheral arterial infected prostheses were partially or completely replaced with the allograft. Operative mortality was 27.8% and amputation rate was 22.2%. Systemic sepsis at initial presentation and highly virulent nature of causative microorganisms were identified as significant negative prognostic factors (χ² test, p<0.05. During the long­term follow­up (mean 47 months, allograft aneurysm developed in three patients, requiring allograft explantation, followed in two cases by tertiary prosthetic reconstruction. Conclusion. Substitution of the infected prosthesis with the arterial allograft could be successful if used selectively - for less virulent and localized infections of extracavitary grafts. Close follow­up is mandatory for timely diagnosis of late homograft lesions and its eventual replacement with more durable prosthetic material.

  12. Vision-based approach for long-term mobility monitoring: Single case study following total hip replacement

    Elham Dolatabadi, MSc


    Full Text Available This article presents a single case study on the feasibility of using a low-cost and portable vision-based system (a Microsoft Kinect sensor to monitor changes in movement patterns before and after a total hip replacement surgery. The primary subject was an older male adult with total hip replacement who performed two different functional tasks: walking and sit-to-stand. The tasks were recorded with a Kinect multiple times, starting from 1 d before the surgery until 9 wk after the surgery. An automated algorithm has been developed to extract the important spatiotemporal characteristics from the video recorded functional tasks (walking and sit-to-stand. Statistical analysis was then performed by TryonC statistic to study changes in spatiotemporal characteristics between different stages before and after the surgery. The statistical analysis indicated significant difference and slight improvement between all measures from the presurgery to each postsurgery date. The study confirmed that the Kinect sensor and an automated algorithm have the potential to be integrated into a patient’s home to monitor changes in mobility during the recovery period.

  13. [Augmented anterior cruciate ligament replacement with the Kennedy-LAD (ligament augmentation device)--long term outcome].

    Riel, K A


    The ligament augmentation device (Kennedy-LAD) is used to protect tendon grafts during the posttransplantation decrease in strength in anterior cruciate ligament (acl) reconstructions. The augmentation with the LAD is based on the concept of load sharing. Since 1983 we used the LAD in acl-reconstructions in 856 patients. In 63 cases we had to treat complications like infection (8), recurrent effusions (21), arthrofibrosis (34). The overall results are good with respect to stability, regain of strength and sports activity. In 73 cases resurgery was necessary because of synovitis (7), LAD-rupture due to re-injury (9), fatigue-rupture of the LAD (22), meniscal tears (35), 2.7 +/- 2.3 years (range: 2 months to 10 years) after LAD implantation. Modern techniques in acl reconstruction lead to comparable results without synthetic augmentation. Therefore, we now recommend the use of a LAD only in cases of repeated acl replacement with week tendon grafts, to avoid an allograft.

  14. [Severe tricuspid insufficiency and primary carcinoid tumor of the ovary. Long term success after valve replacement. Apropos of a case].

    Herreman, F; Vernant, P; Cachera, J P; Monier, P


    The case is reported of carcinoid heart disease in a lady of 70 with intractable congestive cardiac failure 5 years after the removal of a primary carcinoid tumour of the ovary. The special features of primary carcinoid tumours of the ovary are recalled, with emphasis on their rarity and of the absence of liver metastases. The various features of carcinoid syndrome are recalled in the light of current knowledge of the pathogenesis. A review of the literature on cardiac involvement in primary carcinoid tumours of the ovary, amounting to 10 cases, is included. The possibility of surgical cure of the heart lesions in carcinoid tumour by a prosthetic tricuspid valve are discussed, in the light of the 6 reported cases and the present one. Our report is the first one of replacement of the valve after removal of a primary ovarien carcinoid tumour, and the excellent result has been maintained after three years.

  15. Enzyme Activity in Water-Stable Soil Aggregates as Affected by Long-Term Application of Organic Manure and Chemical Fertiliser

    LIU Yi-Ren; LI Xiang; SHEN Qi-Rong; XU Yang-Chun


    The activities of invertase,protease,urease,acid phosphomonoesterase,dehydrogenase,and catalase in different fractions of waterstable aggregates (WSA) were examined in long-term (26 years) fertilised soils.The long-term application of organic manure (OM) with chemical fertiliser (CF) significantly increased macroaggregate and decreased microaggregate percentages,enhanced the mean weight diameter,and significantly increased soil total carbon (TC) and total nitrogen (TN) contents of WSA in different size fractions.Combined fertilisation with OM and CF also increased invertase,protease,urease,acid phosphomonoesterase,dehydrogenase,and catalase activities of WSA in different size fractions.Enzyme activities were higher in macroaggregates than in microaggregates.The distribution of enzyme activities generally followed the distribution of TC and TN in WSA.The geometric mean of the enzyme activities in different WSA of OM-treated soils was significantly higher than that in soils treated with 100% CF or no fertiliser.The results indicated that the long-term combined application of OM with CF increased the aggregate stability and enzyme activity of different WSA sizes,and consequently,improved soil physical structure and increased soil microbial activity.

  16. Long-term results of the use of autogenous cortical bone columellas to replace the stapes at stapedectomy.

    Bauer, Miklós; Pytel, József; Vóna, Ida; Gerlinger, Imre


    The first author has been using an autogenous cortical bone columella to replace the stapes removed during stapedectomy since 1965. The audiograms of 21 of the 271 patients operated on with this method between 1965 and 1989 (i.e. 7.7% of the possible candidates) were available 20-35 (average 26.8) years postoperatively. The operation could be regarded as successful in 20 and unsuccessful in 1 patient in the long run. The audiological data are presented individually as averages of the values obtained at 0.5, 1, 2 and 3 kHz. The averaged data (n = 21): preoperative air conduction, 58.27; bone conduction, 24.46; and air-bone gap, 33.81 dB. Postoperative best air conduction, 19.07; bone conduction, 14.10; and air-bone gap, 4.97 dB. Postoperative recent air conduction, 45.77; bone conduction, 38.45; and air-bone gap, 7.32 dB. The best values were measured 1-8 (average 1.57) years postoperatively. In relation to the postoperative best value, the recent value of the air-bone gap had deteriorated by 2.35 dB, and that of the bone conduction by 24.35 dB. The small air-bone gap indicates that the deterioration of the hearing is mainly caused by the deterioration of the function of the inner ear and not by that of the conductive apparatus. The progression of the deterioration differs individually (0.3-1.6, average 0.93 dB/year) and accelerates with age. This finding seems to be a problem that does not depend on the operative technique. The data show that the autogenous bone columella ensures the same good and lasting results as the alloplastic solutions; moreover, there is no problem with the incus-prosthesis connection.

  17. [Early and long term results of mechanical aortic valve replacement at the Instituto Nacional del Torax in Chile].

    Villavicencio, Mauricio; Turner, Eduardo; Naranjo, Lorenzo


    Mechanical aortic valve replacement (AVR) results have been published extensively in industrialized countries. To assess our immediate and late results in patients subjected to AVR. We retrospectively studied 194 patients subjected to isolated AVR between 1995 and 2003. Mean age was 57 +/- 13 years and 119 (61%) were male. One hundred thirty nine (73%) were in functional class III-IV, 20 (10%) had a previous cardiac operation and 25 (13%) were operated as an emergency. Surgical indication was stenosis in 110 (58%), regurgitation in 49 (26%) and stenosis/regurgitation in 31 (16%). Etiology was bicuspid valve 56 (29%), degenerative lesions 55 (28%), rheumatic valve disease 38 (20%) and endocarditis 27 (14%). Medtronic Hall was the most common prosthesis used in 157 patients (81%). Mean cardiopulmonary bypass time 97 +/- 29 min and mean cross clamp time was 69 +/- 21 min. Operative mortality was 4.6% (3% in elective surgery, 16% in emergency surgery and 0% in reoperations). Follow-up was complete in 100% of cases, totalizing 636 patients-year. Survival was 91 +/- 2%, 80 +/- 4% and 73 +/- 6%, at 1, 5 and 7 years, respectively. Multivariate risk analysis identified renal failure and endocarditis as predictors of early and late mortality. During follow up, the linear incidence rate for hemorrhage was 3.29% /patients-year, thromboembolism 2.04% patients-year and endocarditis 1.1% patients-year. AVR has low overall and elective mortality. Midterm survival is good but linear event rates related to anticoagulant treatment are higher than those previously published in industrialized countries. Renal failure and endocarditis were risk factors for early and late death.

  18. Improvement with ongoing Enzyme Replacement Therapy in advanced late-onset Pompe disease: a case study.

    Case, Laura E; Koeberl, Dwight D; Young, Sarah P; Bali, Deeksha; DeArmey, Stephanie M; Mackey, Joanne; Kishnani, Priya S


    Benefits of enzyme replacement therapy with Myozyme (alglucosidase alfa), anecdotally reported in late-onset Pompe disease, range from motor and pulmonary improvement in less severely affected patients, to stabilization with minimal improvement in those with advanced disease. We report a case of a 63-year-old patient with significant morbidity who made notable motor and pulmonary function gains after two years on therapy. Thus, improvements in those with advanced disease may be possible after long-term treatment.

  19. Mathematical modelling long-term effects of replacing Prevnar7 with Prevnar13 on invasive pneumococcal diseases in England and Wales.

    Yoon Hong Choi

    Full Text Available INTRODUCTION: England and Wales recently replaced the 7-valent pneumococcal conjugate vaccine (PCV7 with its 13-valent equivalent (PCV13, partly based on projections from mathematical models of the long-term impact of such a switch compared to ceasing pneumococcal conjugate vaccination altogether. METHODS: A compartmental deterministic model was used to estimate parameters governing transmission of infection and competition between different groups of pneumococcal serotypes prior to the introduction of PCV13. The best-fitting parameters were used in an individual based model to describe pneumococcal transmission dynamics and effects of various options for the vaccination programme change in England and Wales. A number of scenarios were conducted using (i different assumptions about the number of invasive pneumococcal disease cases adjusted for the increasing trend in disease incidence prior to PCV7 introduction in England and Wales, and (ii a range of values representing serotype replacement induced by vaccination of the additional six serotypes in PCV13. RESULTS: Most of the scenarios considered suggest that ceasing pneumococcal conjugate vaccine use would cause an increase in invasive pneumococcal disease incidence, while replacing PCV7 with PCV13 would cause an overall decrease. However, the size of this reduction largely depends on the level of competition induced by the additional serotypes in PCV13. The model estimates that over 20 years of PCV13 vaccination, around 5000-62000 IPD cases could be prevented compared to stopping pneumococcal conjugate vaccination altogether. CONCLUSION: Despite inevitable uncertainty around serotype replacement effects following introduction of PCV13, the model suggests a reduction in overall invasive pneumococcal disease incidence in all cases. Our results provide useful evidence on the benefits of PCV13 to countries replacing or considering replacing PCV7 with PCV13, as well as data that can be used to

  20. A proposal of "core enzyme" bioindicator in long-term Pb-Zn ore pollution areas based on topsoil property analysis.

    Yang, JinShui; Yang, FengLong; Yang, Yang; Xing, GuanLan; Deng, ChunPing; Shen, YaTing; Luo, LiQiang; Li, BaoZhen; Yuan, HongLi


    To study the effects of long-term mining activities on the agricultural soil quality of Mengnuo town in Yunnan province, China, the heavy metal and soil enzyme activities of soil samples from 47 sites were examined. The results showed that long-term mining processes led to point source heavy metal pollution and Pb, Cd, Zn and As were the primary metal pollutants. Polyphenoloxidase was found the most sensitive soil enzyme activity and significantly correlated with almost all the metals (P < 0.05). Amylase (for C cycling), acid phosphatase (for P cycling) and catalase (for redox reaction) activities showed significantly positive correlations (P < 0.05) with Pb, Cd, Zn and As contents. The correlations between soil enzymes activities and Cd, Pb and Zn contents were verified in microcosm experiments, it was found that catalase activity had significant correlations (P < 0.05) with these three metals in short-term experiments using different soils under different conditions. Based on both field investigation and microcosm simulation analysis, oxidoreductases activities (rather than a specific enzyme activity) were suggested to be used as "core enzyme", which could simply and universally indicate the heavy metal pollution degrees of different environments. And hydrolases (for C, N, P and S recycling) could be used as a supplement to improve correlation accuracy for heavy metal indication in various polluted environments.

  1. Long-term effects of growth hormone (GH) replacement therapy on hematopoiesis in a large cohort of children with GH deficiency.

    Esposito, Andrea; Capalbo, Donatella; De Martino, Lucia; Rezzuto, Martina; Di Mase, Raffaella; Pignata, Claudio; Salerno, Mariacarolina


    The aim of our prospective case-control study was to evaluate long-term effects of GH replacement therapy on erythrocytes parameters, leukocytes, and platelets numbers in a large cohort of children with isolated GH deficiency (GHD). Hemoglobin (Hb) concentration, hematocrit (Hct), mean corpuscular volume, mean corpuscular hemoglobin, red cell distribution width, number of erythrocytes, leukocytes, neutrophils, lymphocytes, monocytes and platelets, ferritin, and C-reactive protein were evaluated in 85 children with isolated GHD (10.20 ± 3.50 years) before and annually during the first 5 years of GH replacement therapy and in 85 healthy children age and sex comparable to patients during 5 years of follow-up. Compared with controls, GHD children at study entry showed lower Hb (-1.18 ± 0.87 vs. -0.40 ± 0.90 SDS, p GH therapy was associated with a significant increase in Hb, Hct, and red cells number which became all comparable to controls within the first 2 years of treatment. Moreover, hemoglobin levels normalized in all anemic GHD patients after 5 years of therapy. No difference between patients and controls was found in leukocytes and platelets numbers neither at baseline nor during the study. GHD in childhood is associated with an impairment of erythropoiesis which causes a normocytic anemia in a considerable percentage of patients. GH replacement therapy exerts a beneficial effect leading to a significant increase of erythrocytes parameters and recovery from anemia. Neither GHD nor GH replacement treatment exerts effects on leukocytes or platelets numbers.

  2. Long-term response on growth, antioxidant enzymes, and secondary metabolites in salicylic acid pre-treated Uncaria tomentosa microplants.

    Sánchez-Rojo, Silvia; Cerda-García-Rojas, Carlos M; Esparza-García, Fernando; Plasencia, Javier; Poggi-Varaldo, Héctor M; Ponce-Noyola, Teresa; Ramos-Valdivia, Ana C


    To obtain micro propagated Uncaria tomentosa plantlets with enhanced secondary metabolites production, long-term responses to salicylic acid (SA) pre-treatments at 1 and 100 µM were evaluated after propagation of the plantlets in a SA-free medium. SA pre-treatments of single node cuttings OF U. tomentosa produced long-term responses in microplants grown for 75 days in a SA-free medium. Reduction in survival rate, root formation, and stem elongation were observed only with 100 µM SA pre-treatments with respect to the control (0 + DMSO).Both pre-treatments enhanced H2O2 and inhibited superoxide dismutase and catalase activities, while guaiacol peroxidase was increased only with 1 µM SA. Also, both pre-treatments increased total monoterpenoid oxindole alkaloids by ca. 55 % (16.5 mg g(-1) DW), including isopteropodine, speciophylline, mitraphylline, isomitraphylline, rhynchopylline, and isorhynchopylline; and flavonoids by ca. 21 % (914 μg g(-1) DW), whereas phenolic compounds were increased 80 % (599 μg g(-1) DW) at 1 µM and 8.2 % (359 μg g(-1) DW) at 100 µM SA. Pre-treatment with 1 µM SA of U.tomentosa microplants preserved the survival rate and increased oxindole alkaloids, flavonoids, and phenolic compounds in correlation with H2O2 and peroxidase activity enhancements, offering biotechnological advantages over non-treated microplants.

  3. Effects of long-term estrogen replacement therapy on beta-amyloid precursor protein and mRNA expression in ovariectomized rat hippocampus

    Bo Jiang; Eryuan Liao; Liming Tan; Ruchun Dai; Zhijie Xiao


    of compound nylestriol or 17beta-estradiol did not alter the number of β-APP mRNA-positive neurons. CONCLUSION: The results show that long-term estrogen deficiency results in an increase of expression of β-APP though no changes in the expression of β-APP mRNA are detected. Replacement of estrogen with low-dose 17 beta-estradiol or compound nylestriol tablet inhibits the expression of β-APP in the hippocampus to the same extent.

  4. Long term use of analgesics and risk of osteoarthritis progressions and knee replacement: propensity score matched cohort analysis of data from the Osteoarthritis Initiative.

    Hafezi-Nejad, N; Guermazi, A; Roemer, F W; Eng, J; Zikria, B; Demehri, S


    To determine the association between the long-term use of analgesics and progression of osteoarthritis (OA) as evidenced by up to 3-years follow-up worsening of radiographic Kellgren-Lawrence (KL) grade and incidence of knee replacement (KR). Using nearest neighbor matching of the propensity scores with caliper in the Osteoarthritis Initiative (OAI) cohort, 173 index (Analgesic +) and 173 referent (Analgesic -) subjects were included. Analgesic + and - subjects had analgesics in all and none of their visits, respectively. Analgesic + and - subjects were balanced in their demographics, baseline, first, second and third year body mass index (BMI), Western Ontario and McMaster (WOMAC) total score, Physical and Mental health summary scales (SF-12), Physical Activity Scale for the Elderly (PASE) and Charleston Comorbidity Scale. Analgesic + and - subjects were also matched for baseline radiographic KL grade. Interval increase in the KL grade and incidence of KR were defined as the outcome. Included subjects had average 6.5 years of follow-up. By the third year, 44 subjects had an interval increase in the KL grade; 29 in Analgesic + and 15 among Analgesic - subjects (P = 0.024). By the eighth-year, 41 subjects had their first KR; 29 in Analgesic + and 12 among Analgesic - subjects (P = 0.005). Hazard Ratio (HR) of OA progression and KR for Analgesic + subjects was 1.91 (1.02-3.57) and 2.57 (1.31-5.04), respectively. Long-term use of analgesics may be associated with radiographic progression of knee OA and increased risk of future KR. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  5. Effects of long-term, low-dose sex hormone replacement therapy on hippocampus and cognition of postmenopausal women of different apoE genotypes

    Yun YUE; Ping-ping ZUO; Ling HU; Qin-jie TIAN; Jing-mei JIANG; Yi-long DONG; Zheng-yu JIN; Yu-hang CHENG; Xia HONG; Qin-sheng GE


    Aim: To study the effects of long-term, low-dose sex hormone replacement therapy (HRT) on the volume and biochemical changes of the hippocampus in postmeno-pausal women carrying apolipoprotein E (apoE) gene ε3 or ε4. Methods: Eighty-three postmenopausal women who had used a low dose of HRT for over 4 years were selected as the HRT group, and 99 postmenopausal women with matched age and education were enrolled as the control group. ApoE alleles were analyzed by PCR. Magnetic resonance imaging was performed to determine the volume of the brain hippocampus. Proton magnetic resonance spectroscopy was used to detect the biochemical changes in the anterior cingulate cortex and hippocampus in apoE ε4 and ε3 carriers. Six common cognitive tests were used to make an overall evaluation of cognitive function. Results: Analysis with the apoE ε4 carriers showed that the volume of the hippocampus of the control group were significantly lower than those of the HRT group. The biochemical analysis showed that there was an increase of N-acetylaspartate (NAA)/total creatine (tCr) and a decrease of myoinositol (mI)/tCr in the hippocampus of apoE ε4 carriers in the HRT group, compared with the control group. For the apoE ε3 carriers, the least squares means (LSMEAN) of the HRT group was higher than that of the control group. Conclusion: This study showed that long-term, low dose HRT might be beneficial for reducing the risk of AD development in vulnerable postmenopausal women. Meanwhile, HRT could increase the LSMEAN of apoE ε3 carriers.

  6. Aortic valve replacement with autologous pericardium: long-term follow-up of 15 patients and in vivo histopathological changes of autologous pericardium.

    Liu, Xiaohong; Han, Lin; Song, Zhigang; Tan, Mengwei; Gong, Dejun; Xu, Zhiyun


    The study aimed to assess the long-term follow-up of patients with an autologous pericardial aortic valve (APAV) replacement and to analyse in vivo histopathological changes in implanted APAVs. From 1996 to 1997, 15 patients (mean age, 34 years) underwent aortic valve replacement with the glutaraldehyde-treated autologous pericardium. All patients were followed up after discharge. The excised APAVs were processed for haematoxylin-eosin, Victoria blue-van Gieson and immunohistochemical staining. The mean clinical follow-up was 11.43 ± 4.50 years. APAV-related in-hospital and late mortalities were both 0%. Five (33%) patients required reoperation because of a prolapse of the right coronary cusp (n = 1), infective endocarditis (n = 1) or fibrocalcific degeneration (n = 3). Freedom from endocarditis, fibrocalcific degeneration and reoperation at the end of follow-up was 93, 80 and 67%, respectively. The remaining 10 patients were alive and well with a mean New York Heart Association class of 1.10 ± 0.32 and normally functioning aortic valves (peak pressure gradient: 7.70 ± 3.41 mmHg; mean pressure gradient: 1.79 ± 0.64 mmHg). Histopathology revealed that (i) a thin factor VIII-positive layer (endothelialization) was found on all non-endocarditis APAVs; (ii) pericardial cells in all APAVs were positive for α-smooth muscle actin (myofibroblast phenotype) and some cells in the fibrocalcific APAVs were positive for alkaline phosphatase (osteoblast phenotype) and (iii) an elastic band was found in 3 cases (in vivo >9 years). APAV replacement is a procedure with a low mortality. APAVs adapt to new environmental demands by producing an elastic band and by endothelialization, whereas myofibroblast/osteoblast transdifferentiation seems to be responsible for the fibrocalcification of APAVs.

  7. Long-term Mortality Predictors in Patients with Small Aortic Annulus Undergoing Aortic Valve Replacement with a 19- or 21-mm Bioprosthesis

    Jenny Lourdes Rivas de Oliveira

    Full Text Available Abstract Introduction: Replacement of the aortic valve in patients with a small aortic annulus is associated with increased morbidity and mortality. A prosthesis-patient mismatch is one of the main problems associated with failed valves in this patient population. Objective: To evaluate the long-term mortality predictors in patients with a small aortic annulus undergoing aortic valve replacement with a bioprosthesis. Methods: In this retrospective observational study, a total of 101 patients undergoing aortic valve replacement from January 2000 to December 2010 were studied. There were 81 (80.19% women with a mean age of 52.81±18.4 years. Severe aortic stenosis was the main indication for surgery in 54 (53.4% patients. Posterior annulus enlargement was performed in 16 (15.8% patients. Overall, 54 (53.41% patients underwent concomitant surgery: 28 (27.5% underwent mitral valve replacement, and 13 (12.7% underwent coronary artery bypass graft surgery. Results: Mean valve index was 0.82±0.08 cm2/m2. Overall, 17 (16.83% patients had a valve index lower than 0.75 cm2/m2, without statistical significance for mortality (P=0.12. The overall 10-year survival rate was 83.17%. The rate for patients who underwent isolated aortic valve replacement was 91.3% and 73.1% (P=0.02 for patients who underwent concomitant surgery. In the univariate analysis, the main predictors of mortality were preoperative ejection fraction (P=0.02; HR 0.01 and EuroSCORE II results (P=0.00000042; HR 1.13. In the multivariate analysis, the main predictors of mortality were age (P=0.01, HR 1.04 and concomitant surgery (P=0.01, HR 5.04. Those relationships were statistically significant. Conclusion: A valve index of < 0.75 cm2/m2 did not affect 10-year survival. However, concomitant surgery and age significantly affected mortality.

  8. Artificial-enzyme gel membrane-based biosurveillance sensor with high reproducibility and long-term storage stability.

    Ikeno, Shinya; Yoshida, Tetsuya; Haruyama, Tetsuya


    We propose that the most sophisticated strategy for primary biosurveillance is to exploit structural commonality through the detection of biologically relevant phosphoric substances. A novel assay, an artificial-enzyme membrane was designed and synthesized for sensor fabrication. This artificial-enzyme catalyzes the hydrolysis of the diphosphoric acid anhydride structure. This structure-selective, albeit not molecule-selective, catalytic hydrolysis was successfully coupled with amperometric detection. Since the catalytic reaction produces a dephosphorylation product (PO(4)(3-)), it can be reduced by an electrode potential of -250 mV vs. Ag/AgCl. Owing to the structural selectivity of the artificial-enzyme membrane, the sensor can detect biological phosphoric substances comprehensively that have the diphosphoric acid anhydride structure. The sensor successfully determined various biological phosphoric substances at concentrations in the micromolar (microM) to millimolar (mM) range, and it showed good functional stability and reproducibility in terms of sensor responses. This sensor was used to detect Escherichia coli lysed by heat treatment, and the response increased with increasing bacterial numbers. This unique technique for analyzing molecular commonality can be applied to the surveillance of biocontaminants, e.g. microorganisms, spores and viruses. Artificial-enzyme-based detection is a novel strategy for practical biosurveillance in the front line.

  9. Effects of long-term hormone replacement therapy on QT and corrected QT dispersion during resting and peak exercise electrocardiography in post-menopausal women.

    Altunkeser, Bülent B; Ozdemir, Kurtulus; Içli, Abdullah; Celik, Cetin; Akyürek, Cemalettin; Gök, Hasan


    It is known that the QT interval is longer in women than men. Estrogen is reported to account for the QT interval prolongation in several studies conducted with hormone replacement therapy (HRT) in postmenopausal women. Along with this, there are conflicting data as regards the effects of HRT on QT interval and dispersion. Moreover, there is no evidence about the effect of HRT on exercise QT parameters. We compared QT parameters obtained from surface electrocardiograms during resting and peak exercise before and after 6 months of HRT consisting of estrogen plus progesterone in healthy postmenopausal women. Twenty-four healthy postmenopausal women were given 0.625 mg/day conjugated estrogens and 2.5 mg/day medroxyprogesterone acetate for 6 months. Exercise stress testing using the Bruce protocol was performed before and after HRT. QT maximum, minimum, dispersion and corrected QT maximum, minimum and dispersion were calculated during resting and peak exercise. HRT resulted in a significant increase in estradiol plasma levels from 24+/-10 pg/mL to 117+/-66 pg/mL (Pexercise (20+/-7 versus 25+/-10 ms; Pexercise QT parameters were unchanged. The resting QT parameters are not affected by long term HRT consisting of estrogen plus progesterone, which leads to an increase in QT dispersion and corrected QT dispersion during peak exercise.

  10. Early weight loss predicts the reduction of obesity in men with erectile dysfunction and hypogonadism undergoing long-term testosterone replacement therapy.

    Salman, Mahmoud; Yassin, Dany-Jan; Shoukfeh, Huda; Nettleship, Joanne Elisabeth; Yassin, Aksam


    We and others have previously shown that testosterone replacement therapy (TRT) results in sustained weight loss in the majority of middle-aged hypogonadal men. Previously, however, a small proportion failed to lose at least 5% of their baseline weight. The reason for this is not yet understood. In the present study, we sought to identify early indicators that may predict successful long-term weight loss, defined as a reduction of at least 5% of total body weight relative to baseline weight (T0), in men with hypogonadism undergoing TRT. Eight parameters measured were assessed as potential predictors of sustained weight loss: loss of 3% or more of baseline weight after 1 year of TU treatment, severe hypogonadism, BMI, waist circumference, International Prostate Symptom Score (IPSS), glycated hemoglobin (HbA1C), age and use of vardenafil. Among the eight measured parameters, three factors were significantly associated with sustained weight loss over the entire period of TU treatment: (1) a loss of 3% of the baseline body weight after 1 year of TRT; (2) baseline BMI over 30; and (3) a waist circumference >102 cm. Age was not a predictor of weight loss.

  11. The effects of long-term low-dose hormone replacement therapy on blood pressure and vasoactive factors in postmenopausal women

    Nie Min; Sun Mei-li; Song Ai-ling; Ge Qin-sheng


    Objective: To investigate the effects of long-term low-dose hormone replacement therapy (HRT) on blood pressure, the plasma renin activity (PRA), plasma angiotensin Ⅱ (Ang Ⅱ) level and serum nitric oxide (NO) concentration in postmenopausal women.Methods: A total of 140 postmenopausal women were selected from the medical staff of the Peking Union Medical College Hospital. Of these, 63 subjects who had been treated with low-dose sex hormone for over 5 (5-32) years were set up as HRT group, and 77 age-matched subjects who had never received HRT were designed as control group. The levels of serum estradiol (E2), follicle stimulating hormone (FSH) and nitric oxide (NO), the concentration of plasma angiotensin Ⅱ (Ang Ⅱ), plasma rennin activity (PRA) and the blood pressure were evaluated in these two groups.Results: The serum level of estradiol in HRT group was significantly higher than that in control group(median,interquartile range; 124.0 pmol/L,113.4 vs. 78.2 pmol/L,121.8)(P<0.05)and systolic blood pressure in HRT groups was significantly lower than that in control group [(126.7±14.4) mmHg vs. (132.4±19.8) mmHg] (P<0.05). Diastolic blood pressure [(79.7±7.9) mmHg vs. (79.6±10.4) mmHg], the serum level of FSH [(54.4±18.9) IU/L vs. (60.4±24.4) IU/L], the plasma level of PRA(median,interquartile range; 0.14 pg/L/hr,0.11 vs. 0.12 pg/L/hr,0.10), Ang Ⅱ(median,interquartile range; 46.0,31.1 pg/ml vs. 44.4,33.0 pg/ml)and serum level of NO(median,interquartile range;63.8 μmol/L,58.9 vs. 56.0 μmol/L,94.8)showed no significant difference between HRT and control groups (P>0.05).Conclusions: Long-term low-dose HRT decreased the systolic blood pressure, but showed no effects on the diastolic blood pressure, plasma level of Ang Ⅱ, PRA, and serum level of NO in postmenopausal women.

  12. Patient-related predictors of implant failure after primary total hip replacement in the initial, short- and long-terms. A nationwide Danish follow-up study including 36,984 patients

    Johnsen, S.P.; Sørensen, H.T.; Lucht, Ulf


    We examined the association between patient-related factors and the risk of initial, short- and long-term implant failure after primary total hip replacement. We used data from the Danish Hip Arthroplasty Registry between 1 January 1995 and 31 December 2002, which gave us a total of 36 984 patients....... Separate analyses were carried out for three follow-up periods: 0 to 30 days, 31 days to six months (short term), and six months to 8.6 years after primary total hip replacement (long term). The outcome measure was defined as time to failure, which included re-operation with open surgery for any reason...

  13. STAR假体踝关节置换的中长期疗效分析%Intermediate and long term outcomes of Scandinavian total ankle replacment

    赵宏谋; 俞光荣; 杨云峰


    [Objective]The purpose of this study was to provide cumulative data about the intermediate and long term outcome of Scandinavian total ankle replacement (STAR)in the literature,and to provide a summary of survival rate,implant failure rate and reasons. [ Method] A comprehensive search for all relevant articles published in English from January 1995 to December 2010 was conducted. Two reviewers evaluated each study to determine whether it was eligible for inclusion and collected the data of interest. The intermediate and long term outcomes were concluded. Evidence based meta-analytic pooling of results across the studies was performed for the survival rate and failure rate. [Result]Twelve primary studies with 2005 implants were identified. The mean AOFAS score was 77.6. The pooled mean five-year survival was 84.7 % ( 95 % CI:80.0 to 89. 3) ,and the pooled mean ten-year survival was 72.5% (95 % CI: 62.3 to 82.5). The pooled mean failure rate was 14. 2% (95% CI:10.6tol7. 8). The first three reasons associated with implant failure were aseptic loosening (6.8%), malalignment (2. 8% ) and pain (2. 5% ). [Conclusion]We have found that total ankle arthroplasty achieved encouraging results about intermediate and long term outcomes. The five-year and ten-year survival rates are acceptable. The first reason for implant failure is aseptic loosening.%[目的]通过对已发表的文献进行汇总分析,总结Scandinavian (STAR)假体踝关节置换术的中长期疗效,并对假体生存率、失败率和失败原因进行汇总分析.[方法]通过系统检索1995年1月~2010年12月以英文发表的关于STAR假体踝关节置换中长期疗效的文献.2名作者全文阅读并决定是否符合纳入标准或排除标准,收集相关结果和数据,总结中长期疗效;通过循证医学Meta分析方法,加权汇总STAR假体的5、10年生存率,总结假体失败率和失败原因.[结果]有12篇文献纳入研究,共包括2 005例假体.平均AOFAS得分为77.6

  14. Long-term compliance with beta-blockers, angiotensin-converting enzyme inhibitors, and statins after acute myocardial infarction

    Gislason, Gunnar H; Rasmussen, Jeppe N; Abildstrøm, Steen Z


    AIMS: To study initiation, dosages, and compliance with beta-blockers, angiotensin-converting enzyme (ACE)-inhibitors, and statins in patients after acute myocardial infarction (AMI) and to identify likely targets for improvement. METHODS AND RESULTS: Patients admitted with first AMI between 1995...... and 2002 were identified by linking nationwide administrative registers. A total of 55 315 patients survived 30 days after discharge and were included; 58.3% received beta-blockers, 29.1% ACE-inhibitors, and 33.5% statins. After 1, 3, and 5 years, 78, 64, and 58% of survivors who had started therapy were...... still receiving beta-blockers, 86, 78, and 74% were receiving ACE-inhibitors, and 85, 80, and 82% were receiving statins, respectively. Increased age and female sex were associated with improved compliance. The dosages prescribed were generally 50% or less of the dosages used in clinical trials...

  15. Long-term effects of a novel phosphorothionate (RPR-II) on detoxifying enzymes in brain, lung, and kidney rats.

    Mahboob, M; Siddiqui, M K J


    The effects of a phosphorothionate, 2-butenoic acid-3-(diethoxyphosphinothioyl) methyl ester (RPR-II), on the activities of glutathione S-transferase (GST) and UDP-glucuronyltransferase (UDPGT) and the level of glutathione (GSH) were evaluated in rats after administration of RPR-II at 0.014 (low), 0.028 (medium), and 0.042 (high) mgkg(-1)day(-1) for 90 days and also at 28 days (withdrawal) after stopping treatment. Brain GST activity and GSH level decreased significantly at the high dose on the 45th and 90th days of treatment. Dose- and time-dependent decreases in GST activity and GSH was level were observed in lung at medium and high doses and in kidneys at all three doses on both the 45th and 90th days. UDPGT activity increased significantly in kidneys at the medium and high doses at 45 and 90 days. Brain and lung did not display any significant variations in UDPGT activity when compared with the control. Interestingly, the withdrawal study revealed that the effect was reversible within 28 days of cessation of treatment, when enzyme activity reverted to levels close to those of controls. The study revealed that RPR-II affected the GSH- and GST-dependent detoxification system of the treated tissues of rat and its potential to modulate the enzymes is in the order kidneys>lung>brain. The present subacute study suggests that RPR-II may bring about physiological upsets by altering GSH- and GST-dependent events in different tissues of exposed organisms.

  16. Long-term feeding a plant-based diet devoid of marine ingredients strongly affects certain key metabolic enzymes in the rainbow trout liver.

    Véron, Vincent; Panserat, Stéphane; Le Boucher, Richard; Labbé, Laurent; Quillet, Edwige; Dupont-Nivet, Mathilde; Médale, Françoise


    Incorporation of a plant blend in the diet can affect growth parameters and metabolism in carnivorous fish. We studied for the first time the long-term (1 year) metabolic response of rainbow trout fed from first feeding with a plant-based diet totally devoid of marine ingredients. Hepatic enzymes were analyzed at enzymatic and molecular levels, at 3, 8 and 24 h after the last meal to study both the short-term effects of the last meal and long-term effects of the diet. The results were compared with those of fish fed a control diet of fish meal and fish oil. Growth, feed intake, feed efficiency and protein retention were lower in the group fed the plant-based diet. Glucokinase and pyruvate kinase activity were lower in the livers of trout fed the plant-based diet which the proportion of starch was lower than in the control diet. Glutamate dehydrogenase was induced by the plant-based diet, suggesting an imbalance of amino acids and a possible link with the lower protein retention observed. Gene expression of delta 6 desaturase was higher in fish fed the plant-based diet, probably linked to a high dietary level of linolenic acid and the absence of long-chain polyunsaturated fatty acids in vegetable oils. Hydroxymethylglutaryl-CoA synthase expression was also induced by plant-based diet because of the low rate of cholesterol in the diet. Changes in regulation mechanisms already identified through short-term nutritional experiments (<12 weeks) suggest that metabolic responses are implemented at short term and remain in the long term.

  17. Changes in soil carbon and enzyme activity as a result of different long-term fertilization regimes in a greenhouse field.

    Lili Zhang

    Full Text Available In order to discover the advantages and disadvantages of different fertilization regimes and identify the best management practice of fertilization in greenhouse fields, soil enzyme activities involved in carbon (C transformations, soil chemical characteristics, and crop yields were monitored after long-term (20-year fertilization regimes, including no fertilizer (CK, 300 kg N ha-1 and 600 kg N ha-1 as urea (N1 and N2, 75 Mg ha-1 horse manure compost (M, and M with either 300 or 600 kg N ha-1 urea (MN1 and MN2. Compared with CK, fertilization increased crop yields by 31% (N2 to 69% (MN1. However, compared with CK, inorganic fertilization (especially N2 also caused soil acidification and salinization. In the N2 treatment, soil total organic carbon (TOC decreased from 14.1±0.27 g kg-1 at the beginning of the long-term experiment in 1988 to 12.6±0.11 g kg-1 (P<0.05. Compared to CK, N1 and N2 exhibited higher soil α-galactosidase and β-galactosidase activities, but lower soil α-glucosidase and β-glucosidase activities (P<0.05, indicating that inorganic fertilization had different impacts on these C transformation enzymes. Compared with CK, the M, MN1 and MN2 treatments exhibited higher enzyme activities, soil TOC, total nitrogen, dissolved organic C, and microbial biomass C and N. The fertilization regime of the MN1 treatment was identified as optimal because it produced the highest yields and increased soil quality, ensuring sustainability. The results suggest that inorganic fertilizer alone, especially in high amounts, in greenhouse fields is detrimental to soil quality.

  18. Effects of long-term tea polyphenols consumption on hepatic microsomal drug-metabolizing enzymes and liver function in Wistar rats

    Tao-Tao Liu; Ning-Sheng Liang; Yan Li; Fan Yang; Yi Lu; Zi-Qing Meng; Li-Sheng Zhang,


    AIM: To investigate the effects of long-term tea polyphenols (TPs) consumption on hepatic microsomal drug-metabolizing enzymes and liver function in rats.METHODS: TPs were administered intragastrically to rats at the doses of 833 (n=20) and 83.3 (n=20) respectively for six months. Controlled group (n=20)was given same volume of saline solution. Then the contents of cytochrome P450, bS, enzyme activities of aminopyrine N-demethylase (ADM), glutathione S-trasferase (GST) and the biochemical liver function of serum were determined.RESULTS: The contents of cytochrome P450 and b5 in the livers of male rats in high dose groups (respectively 2.66±0.55,10.43±2.78 MS pro-1) were significantly increased compared with the control group (1.08±1.04, 5.51± MS pro-1; P<0.01, respectively). The enzymatic activities of ADM in the livers of female rats in high dose groups (0.91±0.08 mmol@mg MS pro-1min-1) were increased compared with the control group (0.82±0.08 MS pro-1.min-1; P<0.05). The GST activity was unchanged in all treated groups, and the function of liver was not obviously changed.CONCLUSION: The antidotal capability of rats' livers can be significantly improved after long-term consumption of TPs.There are differences in changes of drug-metabolizing enzymes between the sexes induced by TPs and normal condition.

  19. Long-term effect of municipal solid waste amendment on microbial abundance and humus-associated enzyme activities under semiarid conditions.

    Bastida, Felipe; Kandeler, Ellen; Hernández, Teresa; García, Carlos


    Microbial ecology is the key to understanding the function of soil biota for organic matter cycling after a single amendment of organic waste in semiarid soils. Therefore, in this paper, the long-term effect (17 years) of adding different doses of a solid municipal waste to an arid soil on humus-enzyme complexes, a very stable and long-lasting fraction of soil enzymes, as well as on microbial and plant abundance, was studied. Humic substances were extracted by 0.1 M pH 7 sodium pyrophosphate from soil samples collected in experimental plots amended with different doses of a solid municipal waste (0, 65, 130, 195, and 260 t/ha) 17 years before. The activity of different hydrolases related with the C (beta-glucosidase), N (urease), and P (alkaline phosphatase) cycles and with the formation of humic substances (o-diphenol oxidase) were determined in this extract. The density and diversity of plant cover in the plots, as well as the fungal and bacterial biomass (by analyzing phopholipid fatty acids) were also determined. In general, the amended plots showed greater humic substance-related enzymatic activity than the unamended plots. This activity increased with the dose but only up to a certain level, above which it leveled off or even diminished. Plant diversity and cover density followed the same trend. Fungal and bacterial biomass also benefited in a dose-dependent manner. Different signature molecules representing gram+ and gram- bacteria, and those corresponding to monounsaturated and saturated fatty acids showed a similar behavior. The results demonstrate that organic amendment had a noticeable long-term effect on the vegetal development, humic substances-related enzyme activity and on the development of bacteria and fungi in semiarid conditions.

  20. Studies on the effect of long-term exposure to nitrogen dioxide on serum and liver proteins level and enzyme activity in guinea pigs.

    Drozdz, M; Kucharz, E; Ludyga, K; Molska-Drozda, T


    Forty male guinea pigs were exposed to nitrogen dioxide in a concentration of 2 mg/m3, 8 hours daily for a period of 180 days. Forty male animals were used as a control group. The following changes were found in intoxicated animals: the decrease of total protein and seromucoid concentration in blood serum and the decrease of total protein, perchloric acid-soluble proteins, protein-bound hexosamines and sialic acids content, in liver tissue. Electrophoretic examination of the serum proteins showed the increase of alpha 1- and beta 2-globulins and the decrease of albumin concentration. Changes in the level of glycoproteins fractions and protein-bound carbohydrates in blood serum were described also. Estimation of enzymes activity showed the decrease of alanine and aspartate transaminase activity in blood serum caused by the strong decrease of the cytoplasmic fraction of these enzymes. However the simultaneous increase of the mitochondrial fraction of transaminases activity was observed. The decrease of the activity of choline esterase was found also. Similar changes of enzymes activity were found in liver tissue. Histopathological studies were done for the further clearing the influenze of nitrogen dioxide on serum and liver proteins concentration and enzymes activity. It was found that after long-term exposure to nitrogen dioxide the destruction processes may be observed in the liver. The possible mechanism of the nitrogen dioxide-induced damage of protein metabolism is discussed.

  1. Changes in soil carbon and enzyme activity as a result of different long-term fertilization regimes in a greenhouse field.

    Zhang, Lili; Chen, Wei; Burger, Martin; Yang, Lijie; Gong, Ping; Wu, Zhijie


    In order to discover the advantages and disadvantages of different fertilization regimes and identify the best management practice of fertilization in greenhouse fields, soil enzyme activities involved in carbon (C) transformations, soil chemical characteristics, and crop yields were monitored after long-term (20-year) fertilization regimes, including no fertilizer (CK), 300 kg N ha-1 and 600 kg N ha-1 as urea (N1 and N2), 75 Mg ha-1 horse manure compost (M), and M with either 300 or 600 kg N ha-1 urea (MN1 and MN2). Compared with CK, fertilization increased crop yields by 31% (N2) to 69% (MN1). However, compared with CK, inorganic fertilization (especially N2) also caused soil acidification and salinization. In the N2 treatment, soil total organic carbon (TOC) decreased from 14.1±0.27 g kg-1 at the beginning of the long-term experiment in 1988 to 12.6±0.11 g kg-1 (Pbiomass C and N. The fertilization regime of the MN1 treatment was identified as optimal because it produced the highest yields and increased soil quality, ensuring sustainability. The results suggest that inorganic fertilizer alone, especially in high amounts, in greenhouse fields is detrimental to soil quality.

  2. Effect of long term exposure of low doses of lambda- cyhalothrin on the level of lipid peroxidation and antioxidant enzymes of the pregnant rats and their offspring

    Kadir Tukhtaev


    Full Text Available Lambda- cyhalothrin (LCT is a pyrethroid insecticide class, which is widely used for pest control in agriculture, public health, home and garden. In the present study we investigated the effect of long term exposure of low doses of the LCT on the state of lipid peroxidation and antioxidant protection of pregnant rats and their offspring. It was revealed, that prolonged exposure of lambda-cyhalothrin leads to the development of oxidative stress in both of pregnant females and their offspring. The highest level of lipid peroxidation detected on 14-21 days of pregnancy, which was accompanied by a reduction in activity of antioxidant enzymes. In the offspring highest level of oxidative stress observed on 7-14 days of lactation. The degree of oxidative stress in offspring decreases as the cessation of receipt of a pesticide or its toxic metabolites in breast milk.

  3. H2O2 Distribution and its Relationship with Antioxidant Enzymes during Germination in Dianthus Chinensis L. under Long-Term Salt Stress

    Xue-qin He


    Full Text Available Dianthus chinensis L. is a very ornamental plant and widely used in landscaping. It can be tolerant to some level of salt stress. In order to study H2O2 distribution and activities of antioxidant enzymes under salt stress, seeds of Dianthus chinensis L. were treated with different NaCl concentrations. The results suggested that H2O2 initially produced in root and then transferred to leaf via stem xylem and leaf vein during seed germination under long-term salt stress. Same phenomena were observed in seedlings under short-term salt stress. However, the distribution varied with time under different NaCl. H2O2 was quickly scavenged with 100 mM NaCl. POD and CAT obviously dropped, as well as SOD significantly rose under NaCl. In the meantime, APX and GR seemed to be no associated with salt stress.

  4. [Effects of different long-term fertilization on the activities of enzymes related to carbon, nitrogen, and phosphorus cycles in a red soil].

    Fan, Miao-zhen; Yin, Chang; Fan, Fen-liang; Song, A-lin; Wang, Bo-ren; Li, Dong-chu; Liang, Yong-chao


    Using a microplate fluorimetric assay method, five fertilization treatments, i.e. no-fertilizer control (CK) , sole application of nitrogen (N), balanced application of nitrogen, phosphorus, and potassium fertilizer (NPK), application of pig manure (M), and combination of pig manure with balanced chemical fertilizer (MNPK) were selected to investigate the effects of different long-term fertilization regimes on the activity of five enzymes (β-1, 4-glucosidase, βG; cellobiohydrolase, CBH; β-1, 4-xylosidase, βX; β-1, 4-N-acetylglucosaminidase, NAG; acid phosphatase, AP) in a red soil sampled from Qiyang, Hunnan Province. The results showed that compared with CK treatment, N treatment had no impact on βG, βX, CBH, and NAG activities but reduced AP activity, while NPK, M and MNPK treatments increased the activities of all the five enzymes. Correlation analysis indicated that all the five enzyme activities were positively correlated with the content of nitrate (r=0.465-0.733) , the content of available phosphorus (r=0.612-0.947) , soil respiration (r=0.781-0.949) and crop yield (r=0.735-0.960), while βG, CBH and AP were positively correlated with pH (r= 0.707-0.809), only AP was significantly correlated with dissolvable organic carbon (r = -0.480). These results suggested that the activities of the measured enzymes could be used as indicators of red soil fertility under different fertilization regimes, but the five enzymes tested provided limited information on the degree of acidification induced by application of mineral nitrogen.

  5. Human growth hormone replacement in adult hypopituitary patients: long-term effects on body composition and lipid status--3-year results from the HypoCCS Database.

    Attanasio, Andrea F; Bates, Peter C; Ho, Ken K Y; Webb, Susan M; Ross, Richard J; Strasburger, Christian J; Bouillon, Roger; Crowe, Brenda; Selander, Keith; Valle, Domenico; Lamberts, Steven W J


    The Hypopituitary Control and Complications Study is an international surveillance study evaluating efficacy and safety of GH therapy of adult GH-deficient patients in clinical practice. The present report examined baseline data from 1,123 adult onset (AO) and 362 childhood onset (CO) patients, as well as efficacy in 242 patients who had completed 3 yr of GH treatment. At study entry, mean height, body mass index, waist to hip ratio, and lean body mass were significantly (P body mass was significantly increased in AO males and females and CO males but not CO females, whereas fat mass was significantly decreased in AO males only. Serum total cholesterol was decreased in females (-0.32 +/- 1.00 mmol/liter; P = 0.045) and males (-0.36 +/- 0.96 mmol/liter; P = 0.004). High-density lipoprotein (HDL) cholesterol was increased for females (0.10 +/- 0.26 mmol/liter; P = 0.026) and males (0.10 +/- 0.34 mmol/liter; P = 0.022). The low-density lipoprotein/HDL ratio was decreased in AO males (-0.93 +/- 2.00; P = 0.003), AO females (-0.65 +/- 0.74; P body mass increase from baseline was greatest in the those younger than 40 yr old, less but still significant in the middle group (40-60 yr) and unchanged in older (>60 yr) patients; conversely, decreases in the low-density lipoprotein/HDL ratio were small and not significant in the younger patients but greater and significant in the middle and older age groups. During the 3-yr treatment, 114 (7.7%) patients discontinued, including 9 (0.6%) for tumor recurrences, 9 (0.6%) for neoplasia, and 9 (0.6%) for side effects. Therefore, these observational data showed significant long-term efficacy of adult GH replacement therapy on body composition and lipid profiles and indicate that age is an important predictor of response.

  6. Effects of Long-Term Combined Application of Organic and Mineral Fertilizers on Microbial Biomass, Soil Enzyme Activities and Soil Fertility

    LI Juan; ZHAO Bing-qiang; LI Xiu-ying; JIANG Rui-bo; So Hwat Bing


    Soil health is important for the sustainable development of terrestrial ecosystem.In this paper,we studied the relationship between soil quality and soil microbial properties such as soil microbial biomass and soil enzyme activities in order to illustrate the function of soil microbial properties as bio-indicators of soil health.In this study,microbial biomass C and N contents(Cmic&Nmic),soil enzyme activities,and soil fertility with different fertilizer regimes were carried out based on a 15-year long-term fertilizer experiment in Drab Fluvo-aquic soil in Changping County,Beijing,China.At this site,7 different treatments were established in 1991.They were in a wheat-maize rotation receiving either no fertilizer(CK),mineral fertilizers(NPK),mineral fertilizers with wheat straw incorporated(NPKW),mineral fertilizers with incremental wheat straw incorporated(NPKW+),mineral fertilizers plus swine manure(NPKM),mineral fertilizers plus incremental swine manure(NPKM+)or mineral fertilizers with maize straw incorporated(NPKS).In different fertilization treatments Cmic changed from 96.49 to 500.12 mg kg-1,and Nmic changed from 35.89 to 101.82 mg kg-1.Compared with CK,the other treatments increased Cmic&Nmic,Cmic/Corg(organic C)ratios,Cmic/Nmic,urease activity,soil organic matter(SOM),soil total nitrogen(STN),and soil total phosphorus(STP).All these properties in treatment with fertilizers input NPKM+ were the highest.Meantime,long-term combined application of mineral fertilizers with organic manure or crop straw could significantly decrease the soil pH in Fluvo-aquic soil(the pH around 8.00 in this experimental soil).Some of soil microbial properties(Cmic/Nmic,urease activity)were positively correlated with soil nutrients.Cmic/Nmic was significantly correlated with SOM and STN contents.The correlation between catalase activity and soil nutrients was not significant.In addition,except of catalase activity,the soil pH in this experiment was negatively correlated with soil

  7. Mitral valve replacement via right thoracotomy approach for prevention of mediastinitis in a female patient with long-term uncontrolled diabetes mellitus: a case report

    Fujiwara Hiroshi


    Full Text Available Abstract A 76-year-old woman with a history of percutaneous transvenous mitral commissurotomy and repeated hospital admissions due to heart failure was referred for an operation for severe mitral valve stenosis. She presented with hypertension, hyperlipidemia and cerebral infarction with stenosis of right internal carotid artery, retinopathy, neuropathy and nephropathy caused by long-term uncontrolled diabetes mellitus, hemoglobin A1c of 9.4%, and New York Heart Association (NYHA functional classification of 3/4. Echocardiography revealed severe mitral valve stenosis with mitral valve area of 0.6 cm2, moderate tricuspid valve regurgitation, and dilatation of the left atrium. Taking into consideration the NYHA functional classification and severe mitral valve stenosis, an immediate surgical intervention designed to prevent mediastinitis was performed. The approach was via the right 4th thoracotomy, as conventional sternotomy would raise the risk of mediastinitis. Postoperative antibiotics were administered intravenously for 2 days, and signs of infection were not recognized. In patients with long-term uncontrolled diabetes mellitus, mid-line sternotomy can easily cause mediastinitis. The choice of operative approach plays an important role in preventing this complication. In this report, the importance of the conventional right thoracotomy for prevention for mediastinitis is reviewed.

  8. Cardiac metaiodobenzylguanidine activity can predict the long-term efficacy of angiotensin-converting enzyme inhibitors and/or beta-adrenoceptor blockers in patients with heart failure

    Nakata, Tomoaki; Wakabayashi, Takeru; Kyuma, Michifumi; Takahashi, Toru; Tsuchihashi, Kazufumi; Shimamoto, Kazuaki [Sapporo Medical University School of Medicine, Second Department of Internal Medicine (Cardiology), Sapporo (Japan)


    Although the benefits of treatment with angiotensin-converting enzyme (ACE) inhibitors and beta-blockers are well known, no method has as yet been established to predict the efficacy of drug therapy. This study tested whether cardiac{sup 123}I-metaiodobenzylguanidine (MIBG) activity is of prognostic value and can predict the improvement in heart failure patients resulting from treatment with ACE inhibitors and/or beta-blockers. Following quantification of the heart-to-mediastinum ratio (HMR) of MIBG activity, 88 patients with heart failure who were treated with ACE inhibitors and/or beta-blockers (treated group) and 79 patients with heart failure who were treated conventionally without the aforementioned agents, and who served as controls, were followed up for 43 months with a primary endpoint of cardiac death. The treated group had a significantly lower prevalence of cardiac death and a significantly lower mortality at 5 years compared with the control group (15% vs 37% and 21% vs 42%, p<0.05, respectively). Multivariate analysis revealed that significant predictors were HMR, age, nitrate use and ventricular tachycardia for the treated group, and HMR, nitrate use and NYHA class for the control group. The drug treatment significantly reduced mortality from 36% to 12% when HMR was 1.53 or more and from 53% to 37% when HMR was less than 1.53. The reduction in risk of mortality within 5 years in patients without a severe MIBG defect (67%) was twice that in patients with such a defect (32%) (p<0.05). The reduction in mortality risk achieved by using ACE inhibitors and/or beta-blockers is associated with the severity of impairment of cardiac MIBG uptake. Cardiac MIBG activity can consequently be of long-term prognostic value in predicting the effectiveness of such treatment in patients with heart failure. (orig.)

  9. Plasma levels of nitric oxide and related vasoactive factors following long-term treatment with angiotensin-converting enzyme inhibitor in patients with essential hypertension.

    Kohno, M; Yokokawa, K; Minami, M; Yasunari, K; Maeda, K; Kano, H; Hanehira, T; Yoshikawa, J


    Several mechanisms other than the inhibition of systemic and local formation of angiotensin II (Ang II) have been proposed to play a role in mediating the hypotensive effects of angiotensin-converting enzyme (ACE) inhibitors. In the present study, we measured plasma levels of nitric oxide (NO) and the related vasoactive factors bradykinin, 6-keto prostaglandin F1alpha (6-keto PGF1alpha) a stable metabolite of prostacyclin, and cyclic guanosine-3',5'-monophosphate (cGMP) before and after a 4-week treatment with the ACE inhibitor lisinopril in 17 patients with essential hypertension. Plasma NO levels were measured by the Griess method after conversion of nitrate to nitrite. Long-term lisinopril treatment significantly reduced blood pressure and increased plasma NO and 6-keto PGF1alpha. The treatment also tended to increase plasma levels of bradykinin and cGMP, but not to a significant extent. The posttreatment NO level was inversely correlated with posttreatment systolic, diastolic, and mean blood pressure (n = 17, r= -.68, P< .01, n = 17, r= -.54, P < .05, and n = 17, r= -.66, P< .01, respectively). The posttreatment bradykinin level was also modestly correlated with posttreatment systolic and mean blood pressure (n = 17, r = -.51, P < .05 and n = 17, r = -.55, P < .05, respectively). In contrast, posttreatment 6-keto PGF1alpha and cGMP levels were not correlated with posttreatment systolic, diastolic, or mean blood pressure. These findings raise the possibility that increased formation of NO and bradykinin, as well as inhibition of the renin-angiotensin system, contribute to the hypotensive effect of the ACE inhibitor observed in our hypertensive patients.

  10. Long-term collections

    Collectes à long terme


    The Committee of the Long Term Collections (CLT) asks for your attention for the following message from a young Peruvian scientist, following the earthquake which devastated part of her country a month ago.

  11. Replacing tedium with transformation: Why the US Department of Energy needs to change the way it conducts long-term R and D

    Sovacool, Benjamin K. [Energy Governance Program, Centre on Asia and Globalisation, National University of Singapore, Lee Kuan Yew School of Public Policy, 469C Bukit Timah Road, Singapore 259772 (Singapore)


    To avoid promoting technologies that merely produce incremental change, the US Department of Energy needs to establish a new organization designed to focus on transformational R and D projects. From its inception in 1977, the US Department of Energy (DOE) has been responsible for maintaining the nation's nuclear stockpile, leading the country in terms of basic research, setting national energy goals, and managing thousands of individual programs. Despite these responsibilities, however, the DOE research and development (R and D) model does not appear to offer the nation an optimal strategy for assessing long-term energy challenges. American energy policy continues to face constraints related to an overly rigid management structure and loss of mission within the DOE, layers of stove-piping within and between the national laboratories, and inadequate public and private funding for energy R and D. To address these concerns, an independent organization dedicated to transformative, creative energy R and D is required. (author)

  12. Mid- to long-term outcome comparison of the Medtronic Hancock II and bi-leaflet mechanical aortic valve replacement in patients younger than 60 years of age: a propensity-matched analysis.

    Wang, Yin; Chen, Si; Shi, Jiawei; Li, Geng; Dong, Nianguo


    This study aims to compare mid-long-term clinical outcomes between patients younger than 60 years of age undergoing bioprosthetic and mechanical aortic valve replacement. From January 2002 to December 2009, patients younger than 60 years of age who received Medtronic Hancock II porcine bioprostheses were selected and compared with those who received mechanical bi-leaflet valves in the aortic position. A stepwise logistic regression propensity score identified a subset of 112 evenly matched patient-pairs. Mid-long-term outcomes of survival, valve-related reoperations, thromboembolic events and bleeding events were assessed. The follow-up was only 95.1% complete. Fourteen measurable variables were statistically similar for the matched cohort. Postoperative in-hospital mortality was 3.6% (bioprosthetic valves) and 2.7% (mechanical valves) (P = 0.700). Survival at 5 and 10 years was 96.3 and 88.7% for patients receiving bioprosthetic valve replacement versus 96.3 and 87.9% for patients receiving mechanical valve replacement (P = 0.860), respectively. At 5 and 10 years after operations, freedom from valve-related reoperation was 97.2 and 94.8% for patients receiving mechanical valve replacement, and 96.3 and 90.2% for patients receiving bioprosthetic valve replacement (P = 0.296), respectively. There was no difference between freedom from thromboembolic events (P = 0.528) and bleeding events (P = 0.128) between the matched groups during the postoperative 10 years. In patients younger than 60 years of age undergoing aortic valve replacement, mid-long-term survival rate was similar for patients receiving bioprosthetic versus mechanical valve replacement. Bioprosthetic valves were associated with a trend for a lower risk of anticoagulation treatment and did not have significantly greater likelihood of a reoperation. These findings suggest that a bioprosthetic valve may be a reasonable choice for AVR in patients younger than 60 years of age. © The Author 2015. Published by

  13. Modeling chronic hepatitis B or C virus infection during antiviral therapy using an analogy to enzyme kinetics: long-term viral dynamics without rebound and oscillation.

    Takayanagi, Toshiaki


    The basic model for chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection during therapy enables us to analyze short-term viral kinetics. However, the model is not useful for analyzing long-term viral kinetics. Here, I suggest a new model that was obtained by introducing Michaelis-Menten kinetics into the basic model. The new model can exhibit long-term viral kinetics without rebound and oscillation, unlike the basic model. The value of the parameter K in the new model is analogous to the Michaelis constant Km and is predicted to be approximately less than 10(10)/ml.

  14. China's far below replacement fertility and its long-term impact: Comments on the preliminary results of the 2010 census

    Zhongwei Zhao


    Full Text Available The Chinese government conducted its sixth national census in 2010 and released its major results in April 2011. According to the National Bureau of Statistics the quality of the census was very high. Although the currently released census results consist of limited statistics only, they shed new light on China's recent fertility levels, which have been debated among scholars and policy makers for more than a decade. The 2010 census results, however, also show considerable inconsistencies with those published by the United Nations Population Division recently. This paper will, on the basis of newly published census results and other available evidence, further examine China's recent fertility decline and its impact on the country's long-term development. It will also comment on the major discrepancies between the results of Chinese government recent population projection, the United Nations' World Population Prospects, the 2010 Revision and China's 2010 census, and investigate the underlying causes that have led to these differences.

  15. Long-term replacement of a mutated nonfunctional CNS gene: reversal of hypothalamic diabetes insipidus using an EIAV-based lentiviral vector expressing arginine vasopressin.

    Bienemann, Alison S; Martin-Rendon, Enca; Cosgrave, Anna S; Glover, Colin P J; Wong, Liang-Fong; Kingsman, Susan M; Mitrophanous, Kyriacos A; Mazarakis, Nicholas D; Uney, James B


    Due to the complexity of brain function and the difficulty in monitoring alterations in neuronal gene expression, the potential of lentiviral gene therapy vectors to treat disorders of the CNS has been difficult to fully assess. In this study, we have assessed the utility of a third-generation equine infectious anemia virus (EIAV) in the Brattleboro rat model of diabetes insipidus, in which a mutation in the arginine vasopressin (AVP) gene results in the production of nonfunctional mutant AVP precursor protein. Importantly, by using this model it is possible to monitor the success of the gene therapy treatment by noninvasive assays. Injection of an EIAV-CMV-AVP vector into the supraoptic nuclei of the hypothalamus resulted in expression of functional AVP peptide in magnocellular neurons. This was accompanied by a 100% recovery in water homeostasis as assessed by daily water intake, urine production, and urine osmolality lasting for a 1-year measurement period. These data show that a single gene defect leading to a neurological disorder can be corrected with a lentiviral-based strategy. This study highlights the potential of using viral gene therapy for the long-term treatment of disorders of the CNS.

  16. Long-term soil microbial community and enzyme activity responses to an integrated cropping-livestock system in a semi-arid region

    This study is part of a larger long-term project to develop and evaluate integrated crop and livestock systems in order to reduce dependence on underground water sources by optimizing cotton (Gossypium hirsutum) production in the Texas High Plains of U.S. Microbial communities and activities were e...

  17. Risk factors for long-term renal survival after renal transplantation : A role for angiotensin-converting enzyme (insertion/deletion) polymorphism?

    Broekroelofs, J.; Stegeman, Coen; Navis, Ger Jan; Tegzess, Adam; De Jong, P.E.; de Zeeuw, Dick


    Chronic progressive renal function loss is a main cause of long-term graft loss after initially successful renal transplantation. Transplanted kidneys share some risk factors for renal function loss, such as hypertension or proteinuria, with diseased native kidneys. Recently, it has been shown that

  18. Long-Term Collections

    Comité des collectes à long terme


    It is the time of the year when our fireman colleagues go around the laboratory for their traditional calendars sale. A part of the money of the sales will be donated in favour of the long-term collections. We hope that you will welcome them warmly.

  19. Enzyme replacement therapy for pancreatic insufficiency: present and future

    Fieker A


    Full Text Available Aaron Fieker1, Jessica Philpott1, Martine Armand21Division of Digestive Diseases, University of Oklahoma, OKC, OK, USA; 2INSERM, U476 "Nutrition Humaine et Lipides", Marseille, F-13385 France; Univ Méditerranée Aix-Marseille 2, Faculté de Médecine, IPHM-IFR 125, Marseille, F-13385 FranceAbstract: Pancreatic enzyme replacement therapy is currently the mainstay of treatment for nutrient malabsorption secondary to pancreatic insufficiency. This treatment is safe and has few side effects. Data demonstrate efficacy in reducing steatorrhea and fat malabsorption. Effective therapy has been limited by the ability to replicate the physiologic process of enzyme delivery to the appropriate site, in general the duodenum, at the appropriate time. The challenges include enzyme destruction in the stomach, lack of adequate mixing with the chyme in the duodenum, and failing to deliver and activate at the appropriate time. Treatment is begun when clinically significant malabsorption occurs resulting in steatorrhea and weight loss. Treatment failure is addressed in a sequential fashion. Current research is aimed at studying new enzymes and delivery systems to improve the efficiency of action in the duodenum along with developing better means to monitor therapy.Keywords: exocrine pancreatic insufficiency, chronic pancreatitis, cystic fibrosis, pancreatic enzyme replacement therapy, lipase, lipids

  20. Model for Quantitative Evaluation of Enzyme Replacement Treatment

    Radeva B.


    Full Text Available Gaucher disease is the most frequent lysosomal disorder. Its enzyme replacement treatment was the new progress of modern biotechnology, successfully used in the last years. The evaluation of optimal dose of each patient is important due to health and economical reasons. The enzyme replacement is the most expensive treatment. It must be held continuously and without interruption. Since 2001, the enzyme replacement therapy with Cerezyme*Genzyme was formally introduced in Bulgaria, but after some time it was interrupted for 1-2 months. The dose of the patients was not optimal. The aim of our work is to find a mathematical model for quantitative evaluation of ERT of Gaucher disease. The model applies a kind of software called "Statistika 6" via the input of the individual data of 5-year-old children having the Gaucher disease treated with Cerezyme. The output results of the model gave possibilities for quantitative evaluation of the individual trends in the development of the disease of each child and its correlation. On the basis of this results, we might recommend suitable changes in ERT.

  1. Long-term effects of oral tea polyphenols and Lactobacillus brevis M8 on biochemical parameters, digestive enzymes, and cytokines expression in broilers

    Hua-li LI; Zong-jun LI; Zhong-shan WEI; Ting LIU; Xiao-zuo ZOU; Yong LIAO; Yu LUO


    This study investigates the long-term effects of oral tea polyphenols (TPs) and Lactobacillus brevis M8 (LB) on biochemical parameters, digestive enzymes, and cytokines expression in broilers. In experiment 1, 240 broiler chickens were selected to investigate the effects of 0.06 g/kg body weight (BW) TP and 1.0 ml/kg BW LB on broilers;in experiment 2, 180 broiler chickens were assigned randomly to three groups to investigate the effects of different dosages of TP (0.03, 0.06, and 0.09 g/kg BW) combined with 1.0 ml/kg BW LB on broilers;in experiment 3, 180 broiler chickens were assigned randomly to three groups to investigate the effects of different dosages of LB (0.5, 1.0, and 1.5 ml/kg BW) combined with 0.06 g/kg BW TP on broilers. The results showed that TP and LB affected serum bio-chemical parameters, and TP reduced serum cholesterol (CHO) and low-density lipoprotein cholesterol (LDL-C) abundances in a dosage-dependent manner (P  目的:茶多酚和乳酸菌在动物营养上的作用已经得到广泛的验证,但是关于二者联合作用的研究鲜有报道。本文采用肉鸡作为试验模型,研究了茶多酚和乳酸菌联合灌喂对肉鸡血液生化、消化酶以及肠道细胞因子表达的影响。  创新点:本研究首次采用联合灌喂茶多酚和乳酸菌,探讨了二者联合作用对肉鸡的影响,并通过模拟生产,长期观察了茶多酚和乳酸菌对肉鸡的影响。  方法:对肉仔鸡灌喂不同浓度的茶多酚和乳酸菌,在第56和84天随机屠宰取样。收集血液检查血液生化指标,并测定消化酶活性。取肠道样品提取RNA,采用反转录聚合酶链反应(RT-PCR)检测细胞因子的表达以及相关信号通路的激活。  结论:长期灌喂茶多酚和乳酸菌改善了肉鸡脂质代谢、消化酶活性以及炎症反应,其机制可能是通过影响了NF-κB信号通路。

  2. Positive impact of hormone replacement therapy on the fibrinolytic system: a long-term randomized controlled study in healthy postmenopausal women

    Madsen, J S; Kristensen, S R; Bladbjerg, E M;


    be of importance. OBJECTIVES: To investigate the prolonged effect of HRT on the fibrinolytic system and to determine whether two common polymorphisms in the plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t-PA) genes modulate this effect. Methods: Healthy postmenopausal women (n......BACKGROUND: The mechanisms by which postmenopausal hormone replacement therapy (HRT) may influence risk of cardiovascular disease are still unclear. Impaired fibrinolytic function is associated with an enhanced risk of cardiovascular disease and therefore the effect of HRT on fibrinolysis may...... of smoking and without influence from the two common polymorphisms PAI-1 -675(4G/5G) and t-PA intron8ins311. Furthermore, no difference between opposed estrogen (with norethisterone acetate as the gestagen component) and unopposed estrogen therapy was found. Both an intention-to-treat and a per...

  3. Transcatheter Mitral Valve Replacement: Long-Term Outcomes of First-In-Man Experience with an Apically Tethered Device - A Case Series from a Single Centre.

    Duncan, Alison; Daqa, Anan; Yeh, James; Davies, Simon; Uebing, Anselm; Quarto, Cesare; Moat, Neil


    Transcatheter mitral valve replacement (TMVR) is a novel technique for treating mitral regurgitation. We report 18-month/2-year outcomes of the 5 first-in-man patients undergoing chronic TMVR with the Tendyne device. Five patients (STS score 14%-23%) underwent TMVR using a Tendyne system under compassionate use at a single centre. 1 patient (who was noncompliant with anti-coagulation) died 9 months after TMVR following a cerebrovascular accident. Whilst some of the remaining patients experienced recognised post-TMVR complications (left ventricular outflow tract obstruction, paravalvular leak, stent thrombosis), all patients alive at 18-months/2-years after TMVR reported significant reduction in NYHA Class and increase in exercise capacity compared to baseline. Transthoracic echocardiography demonstrated valve stability, absent transvalvular mitral regurgitation, and significant reductions in tricuspid regurgitation severity and systolic pulmonary arterial pressure. Eighteen months/2 years after compassionate use of Tendyne TMVR in a highrisk surgical group, the majority of patients were alive, patient symptoms improved, and the device was stable with good haemodynamic function and no late migration. Continued follow-up of patients treated with Tendyne TMVR are required to further describe its safety and efficacy.

  4. Effects of intermission and resumption of long-term testosterone replacement therapy on body weight and metabolic parameters in hypogonadal in middle-aged and elderly men.

    Yassin, Aksam; Almehmadi, Yousef; Saad, Farid; Doros, Gheorghe; Gooren, Louis


    In addition to primary and secondary ('classical') hypogonadism, hypogonadism occurring in middle-aged and elderly men has been recognized. There is evidence that restoring T levels to normal improves body weight, serum lipids and glucose levels. Observational registry study. Two hundred and sixty-two hypogonadal, middle-aged and elderly, men received testosterone replacement treatment (TRT). After having been on TRT for a mean duration of 65·5 months, TRT was temporarily intermitted in 147 patients for a mean of 16·9 months (Group I) due to cost reimbursement issues and in seven men due to prostate cancer. All these men resumed TRT for a mean period of 14·5 months. Of the cohort, 115 men were treated continuously (designated as Group C). To compare on-treatment to off-treatment periods, three periods of equal duration were defined: pre-intermission (on TRT), during intermission (off TRT) and post-intermission (on TRT after resumption of TRT). For proper comparison, the same periods were analysed for those patients who continued TRT throughout (Group C). Variables of body weight, glucose metabolism, lipids, blood pressure and C-reactive protein (CRP). In Group C there was a continuous improvement of body weight, serum lipids, glucose, HbA1c , blood pressure and CRP. In Group I there was a similar initial improvement which was reversed upon intermission of T administration but which appeared again when T treatment was reinstated. Our observation indicates that T administration improves body weight and metabolic factors in men with hypogonadism but withdrawal of T reverses these beneficial effects to appear again when TRT is resumed. © 2015 John Wiley & Sons Ltd.

  5. [Long-term results of closed mitral commissurotomy--comparative study of closed mitral commissurotomy (CMC), open mitral commissurotomy (OMC) and mitral valve replacement (MVR)].

    Suzuki, S; Kondo, J; Imoto, K; Kajiwara, H; Tobe, M; Sakamoto, A; Isoda, S; Yamazaki, I; Noishiki, Y; Matsumoto, A


    As the technique of open heart surgery has improved, CMC has been abandoned in favor of OMC and MVR. We evaluated and compared the results of CMC, OMC and MVR. METHOD. Between 1965 and 1978, 141 patients with mitral stenosis (MS) underwent CMC, and late follow-up obtained in 117 (83%) of them (CMC group). Between 1980 and 1989, 72 patients and 37 patients underwent OMC (OMC group) and MVR (MVR group), respectively. Cumulative follow-up periods were 1982, 632 and 200 patient-years in the CMC, OMC and MVR groups, respectively. RESULTS. (1) Survival rate; In the CMC group there were 2 operative deaths due to severe mitral regurgitation (MR). There were 17 late deaths, due to reoperations in 4 patients, cerebral infarction in 4 patients, congestive heart failure in 3 patients, myocardial infarction in 2 patients and unknown causes in 4 patients. The survival rate was 95%, 91% and 86% at 5, 10 and 15 years, respectively, in the CMC group. In the OMC and MVR groups there was no death. (2) The event free rate was 89%, 79% and 58% at 5, 10 and 15 years, respectively, in the CMC group, 97% and 97% at 5 and 10 years in the OMC group, and 95% and 90% at 4 and 5 years in the MVR group. (3) Reoperations; In the CMC group of 40 patients (34%) required reoperations in an average of 10.4 years after the initial operation, due to re-MS in 22 patients, MR in 10 patients and MRS in the 8 patients. Reoperative findings consisted of clefts in the mitral leaflets in 7 patients. There were pulmonary hypertension in 15 patients and tricuspid regurgitation in 22 patients. Fourteen patients underwent tricuspid anuloplasty and one patient underwent a tricuspid valve replacement. In the OMC group one patient required a reoperation due to MR; in the MVR group one patient required a reoperation due to a thrombosed valve. CONCLUSION. In the CMC group the survival rate and the event free rate were lower, and the rate of reoperation was higher than in the other two groups.

  6. La eficacia a largo plazo de los reemplazos dietéticos en la pérdida de peso: revisión sistemática Meal replacement efficacy on long-term weight loss: a systematic review

    G. López Barrón


    Full Text Available Introducción: Los reemplazos dietéticos (RD se han utilizado para substituir una o dos comidas al día. Sin embargo, pocos estudios aleatorios han valorado su eficacia a largo plazo. Objetivo: Valorar el efecto de los RD sobre la pérdida de peso a largo plazo (≥ 1 año, en personas con sobrepeso y obesidad, con y sin diabetes. Metodología: Se realizó una revisión de todos los ensayos clínicos aleatorios de uno o más años de intervención, publicados hasta Noviembre del 2010, y registrados en las siguientes bases de datos: Pubmed, EBSCO host y SciELO. Los términos MeSH utilizados fueron "weight loss", "overweight", "obesity" y "diabetes", además del término "meal replacement". Para evaluar la calidad de los estudios, se utilizó la escala de GRADE. Resultados: Se encontraron siete ensayos clínicos aleatorios que cumplieron con los criterios de inclusión. Sólo cuatro de los estudios mostraron mayor pérdida de peso con las dietas con RD, en tres no se observaron diferencias significativas. Los dos estudios de mayor calidad presentaron resultados inconsistentes. Conclusión: No existe evidencia suficiente que respalde la eficacia del uso de RD sobre la pérdida de peso a largo plazo. Por lo que se requiere estudios mejor diseñados, con seguimiento a largo plazo.Meal replacement (MR has been frequently used to substitute one or more meals during the day. However, few randomized long-term studies have assessed its efficacy. Objective: To asses meal replacement use and its effectiveness on long-term weight loss (> 1 year in overweight and obese people with or without diabetes. Methods: A search of randomized clinical trials with an intervention period equal to or more than a year, published on Pubmed, EBSCO host and SciELO through November 2010 was performed. Mesh terms such as "meal replacement", "weight loss," "overweight," "obesity" and "diabetes" were used, plus the term "meal replacement." GRADE scale was used to assess the

  7. Long-Term Collections

    Staff Association


    45 years helping in developing countries! CERN personnel have been helping the least fortunate people on the planet since 1971. How? With the Long-Term Collections! Dear Colleagues, The Staff Association’s Long-Term Collections (LTC) Committee is delighted to share this important milestone in the life of our Laboratory with you. Indeed, whilst the name of CERN is known worldwide for scientific discoveries, it also shines in the many humanitarian projects which have been supported by the LTC since 1971. Several schools and clinics, far and wide, carry its logo... Over the past 45 years, 74 projects have been supported (9 of which are still ongoing). This all came from a group of colleagues who wanted to share a little of what life offered them here at CERN, in this haven of mutual understanding, peace and security, with those who were less fortunate elsewhere. Thus, the LTC were born... Since then, we have worked as a team to maintain the dream of these visionaries, with the help of regular donat...

  8. Long-Term Collection

    Staff Association


    Dear Colleagues, As previously announced in Echo (No. 254), your delegates took action to draw attention to the projects of the Long-Term Collections (LTC), the humanitarian body of the CERN Staff Association. On Tuesday, 11 October, at noon, small Z-Cards were widely distributed at the entrances of CERN restaurants and we thank you all for your interest. We hope to have achieved an important part of our goal, which was to inform you, convince you and find new supporters among you. We will find out in the next few days! An exhibition of the LTC was also set up in the Main Building for the entire week. The Staff Association wants to celebrate the occasion of the Long-Term Collection’s 45th anniversary at CERN because, ever since 1971, CERN personnel have showed great support in helping the least fortunate people on the planet in a variety of ways according to their needs. On a regular basis, joint fundraising appeals are made with the Directorate to help the victims of natural disasters around th...

  9. Collectes à long terme

    Collectes à long terme


    En cette fin d’année 2014 qui approche à grands pas, le Comité des Collectes à Long Terme remercie chaleureusement ses fidèles donatrices et donateurs réguliers pour leurs contributions à nos actions en faveur des plus démunis de notre planète. C’est très important, pour notre Comité, de pouvoir compter sur l’appui assidu que vous nous apportez. Depuis plus de 40 ans maintenant, le modèle des CLT est basé principalement sur des actions à long terme (soit une aide pendant 4-5 ans par projet, mais plus parfois selon les circonstances), et sa planification demande une grande régularité de ses soutiens financiers. Grand MERCI à vous ! D’autres dons nous parviennent au cours de l’année, et ils sont aussi les bienvenus. En particulier, nous tenons à remercier...

  10. The Effects of Long-Term Feeding of Rodent Food Bars on Lipid Peroxidation And Antioxidant Enzyme Levels In Fisher Rats

    Ramirez, Joel; Zirkle-Yoshida, M.; Piert, S.; Barrett, J.; Yul, D.; Dalton, B.; Girten, B.


    A specialized rodent food bar diet has been developed and utilized successfully for short-duration shuttle missions. Recent tests conducted in preparation for experiments aboard the International Space Station (ISS) indicated that long-term food bar feeding for three months induced hyperlipidemia in rats. This study examined oxidative stress status in livers of these same animals. Spectrophotometric analysis of 79 Fischer rat livers (40 female and 39 male) for lipid peroxidation (LPO) and superoxide dismutase (SOD) was conducted using Bioxytech LPO-587(TM) assay kit and SOD-525(Tm) assay kit, respectively. The treatment groups consisted of 20 male CHOW and 19 male FOOD BAR rats and 20 female CHOW and 20 female FOOD BAR rats. Statistical analysis to compare differences between groups was performed by standard analysis of variance procedures. The male FOOD BAR group LPO mean (3.6 +/- 0.2 mmol/g) was significantly (p less than or equal to 0.05) greater than that of the male CHOW group (2.1 +/-0.1 mmol/g). Moreover the female FOOD BAR group LPO mean (2.9 +/-0.1 mmol/g) was also significantly greater than the female CHOW group mean (2.2 +/-0.1 mmol/g). The mean values for SOD in both male and female groups showed no significant differences between CHOW and FOOD BAR groups. These results show that LPO levels were significantly higher in both the male and female FOOD BAR groups compared to CHOW groups and that there was no concomitant increase in SOD levels across the group. In addition, males showed a greater difference than females in terms of LPO levels. These findings suggest a need for further investigation into the use of the current food bar formulation for long-term experiments such as those planned for the ISS.

  11. Long-Term Ownership by Industrial Foundations

    Børsting, Christa Winther; Kuhn, Johan Moritz; Poulsen, Thomas


    Short-termism has become a serious concern for businesses and policy makers and this has inspired a search for governance arrangement to promote long term decision making. In this paper we study a particularly long-term ownership structure, which is fairly common in Northern Europe, particularly...... in Denmark. Industrial foundations are independent legal entities without owners or members typically with the dual objective of preserving the company and using excess profits for charity. We use a unique Danish data set to examine the governance of foundation-owned companies. We show that they are long-term...... in several respects. Foundations hold on to their shares for longer. Foundation-owned companies replace managers less frequently. They have more conservative capital structures with less leverage. Their companies survive longer. Their business decisions appear to be more long term. This paper supports...

  12. Long circulating enzyme replacement therapy rescues bone pathology in mucopolysaccharidosis VII murine model.

    Rowan, Daniel J; Tomatsu, Shunji; Grubb, Jeffrey H; Haupt, Bisong; Montaño, Adriana M; Oikawa, Hirotaka; Sosa, Angela C; Chen, Anping; Sly, William S


    Mucopolysaccharidosis (MPS) type VII is a lysosomal storage disease caused by deficiency of the lysosomal enzyme β-glucuronidase (GUS), leading to accumulation of glycosaminoglycans (GAGs). Enzyme replacement therapy (ERT) effectively clears GAG storage in the viscera. Recent studies showed that a chemically modified form of GUS (PerT-GUS), which escaped clearance by mannose 6-phosphate and mannose receptors and showed prolonged circulation, reduced CNS storage more effectively than native GUS. Clearance of storage in bone has been limited due to the avascularity of the growth plate. To evaluate the effectiveness of long-circulating PerT-GUS in reducing the skeletal pathology, we treated MPS VII mice for 12 weeks beginning at 5 weeks of age with PerT-GUS or native GUS and used micro-CT, radiographs, and quantitative histopathological analysis for assessment of bones. Micro-CT findings showed PerT-GUS treated mice had a significantly lower BMD. Histopathological analysis also showed reduced storage material and a more organized growth plate in PerT-GUS treated mice compared with native GUS treated mice. Long term treatment with PerT-GUS from birth up to 57 weeks also significantly improved bone lesions demonstrated by micro-CT, radiographs and quantitative histopathological assay. In conclusion, long-circulating PerT-GUS provides a significant impact to rescue of bone lesions and CNS involvement.

  13. Enzyme replacement therapy in a mouse model of aspartylglycosaminuria.

    Dunder, U; Kaartinen, V; Valtonen, P; Väänänen, E; Kosma, V M; Heisterkamp, N; Groffen, J; Mononen, I


    Aspartylglycosaminuria (AGU), the most common lysosomal disorder of glycoprotein degradation, is caused by deficient activity of glycosylasparaginase (AGA). AGA-deficient mice share most of the clinical, biochemical and histopathologic characteristics of human AGU disease. In the current study, recombinant human AGA administered i.v. to adult AGU mice disappeared from the systemic circulation of the animals in two phases predominantly into non-neuronal tissues, which were rapidly cleared from storage compound aspartylglucosamine. Even a single AGA injection reduced the amount of aspartylglucosamine in the liver and spleen of AGU mice by 90% and 80%, respectively. Quantitative biochemical analyses along with histological and immunohistochemical studies demonstrated that the pathophysiologic characteristics of AGU were effectively corrected in non-neuronal tissues of AGU mice during 2 wk of AGA therapy. At the same time, AGA activity increased to 10% of that in normal brain tissue and the accumulation of aspartylglucosamine was reduced by 20% in total brain of the treated animals. Immunohistochemical studies suggested that the corrective enzyme was widely distributed within the brain tissue. These findings suggest that AGU may be correctable by enzyme therapy.-Dunder, U., Kaartinen, V., Valtonen, P., Väänänen, E., Kosma, V.-M., Heisterkamp, N., Groffen, J., Mononen, I. Enzyme replacement therapy in a mouse model of aspartylglycosaminuria.

  14. Changes in Soil Carbon and Enzyme Activity As a Result of Different Long-Term Fertilization Regimes in a Greenhouse Field: e0118371

    Lili Zhang; Wei Chen; Martin Burger; Lijie Yang; Ping Gong; Zhijie Wu


      In order to discover the advantages and disadvantages of different fertilization regimes and identify the best management practice of fertilization in greenhouse fields, soil enzyme activities involved in carbon (C...

  15. A Newly Defined and Xeno-Free Culture Medium Supports Every-Other-Day Medium Replacement in the Generation and Long-Term Cultivation of Human Pluripotent Stem Cells.

    Ahmadian Baghbaderani, Behnam; Tian, Xinghui; Scotty Cadet, Jean; Shah, Kevan; Walde, Amy; Tran, Huan; Kovarcik, Don Paul; Clarke, Diana; Fellner, Thomas


    Human pluripotent stem cells (hPSCs) present an unprecedented opportunity to advance human health by offering an alternative and renewable cell resource for cellular therapeutics and regenerative medicine. The present demand for high quality hPSCs for use in both research and clinical studies underscores the need to develop technologies that will simplify the cultivation process and control variability. Here we describe the development of a robust, defined and xeno-free hPSC medium that supports reliable propagation of hPSCs and generation of human induced pluripotent stem cells (hiPSCs) from multiple somatic cell types; long-term serial subculturing of hPSCs with every-other-day (EOD) medium replacement; and banking fully characterized hPSCs. The hPSCs cultured in this medium for over 40 passages are genetically stable, retain high expression levels of the pluripotency markers TRA-1-60, TRA-1-81, Oct-3/4 and SSEA-4, and readily differentiate into ectoderm, mesoderm and endoderm. Importantly, the medium plays an integral role in establishing a cGMP-compliant process for the manufacturing of hiPSCs that can be used for generation of clinically relevant cell types for cell replacement therapy applications.




    ACKNOWLEDGMENTS The Long-Term Collections (CLT) committee would like to warmly thank its faithful donors who, year after year, support our actions all over the world. Without you, all this would not be possible. We would like to thank, in particular, the CERN Firemen’s Association who donated 5000 CHF in the spring thanks to the sale of their traditional calendar, and the generosity of the CERN community. A huge thank you to the firemen for their devotion to our cause. And thank you to all those who have opened their door, their heart, and their purses! Similarly, we warmly thank the CERN Yoga Club once again for its wonderful donation of 2000 CHF we recently received. We would also like to tell you that all our projects are running well. Just to remind you, we are currently supporting the activities of the «Réflexe-Partage» Association in Mali; the training centre of «Education et Développement» in Abomey, Benin; and the orphanage and ...

  17. Effects of long-term androgen replacement therapy on the physical and mental statuses of aging males with late-onset hypogonadism: a multicenter randomized controlled trial in Japan (EARTH Study

    Hiroyuki Konaka


    Full Text Available Androgen replacement therapy (ART efficacy on late-onset hypogonadism (LOH has been widely investigated in Western countries; however, it remains controversial whether ART can improve health and prolong active lifestyles. We prospectively assessed long-term ART effects on the physical and mental statuses of aging men with LOH in Japan. The primary endpoint was health-related quality of life assessed by questionnaires. Secondary endpoints included glycemic control, lipid parameters, blood pressure, waist circumference, body composition, muscular strength, International Prostate Symptom Scores (IPSS, International Index of Erectile Function-5 (IIEF-5 scores, and serum prostate-specific antigen levels. Of the 1637 eligible volunteers, 334 patients > 40 years with LOH were randomly assigned to either the ART (n = 169 or control groups (n = 165. Fifty-two weeks after the initial treatment, ART significantly affected the role physical subdomain of the short form-36 health survey (SF-36 scale (P = 0.0318. ART was also associated with significant decreases in waist circumstance (P = 0.002 and serum triglyceride (TG (P = 0.013 and with significant increases in whole-body and leg muscle mass volumes (P = 0.071 and 0.0108, respectively, serum hemoglobin (P < 0.001, IPSS voiding subscore (P = 0.0418, and the second question on IIEF-5 (P = 0.0049. There was no significant difference between the groups in terms of severe adverse events. In conclusion, in patients with LOH, long-term ART exerted beneficial effects on Role Physical subdomain of the SF-36 scale, serum TG, waist circumstance, muscle mass volume, voiding subscore of IPSS, and the second question of IIEF-5. We hope our study will contribute to the future development of this area.

  18. Effects of long-term treatment with angiotensin-converting-enzyme inhibitors in the presence or absence of aspirin: a systematic review

    Teo, Koon K; Yusuf, Salim; Pfeffer, Marc


    BACKGROUND: Results from a retrospective analysis of the Studies of Left Ventricular Dysfunction (SOLVD) study suggest that angiotensin-converting-enzyme (ACE) inhibitors may be less effective in patients receiving aspirin. We aimed to confirm or refute this theory. METHODS: We used the Peto-Yusu...

  19. Long-term effect of inhibition of the angiotensin-converting enzyme (ACE) on cavernosal perfusion in men with atherosclerotic erectile dysfunction: a pilot study.

    Speel, T.G.M.; Kiemeney, L.A.L.M.; Thien, Th.; Smits, P.; Meuleman, E.J.H.


    INTRODUCTION: Impaired perfusion of the corpora cavernosa is considered an important causal factor of erectile dysfunction (ED) in the aging male with atherosclerosis. Aim. On the basis of this notion, we hypothesized that inhibition of angiotensin-converting enzyme (ACE) may have a structural benef

  20. Enzyme replacement therapy in newborn mucopolysaccharidosis IVA mice: early treatment rescues bone lesions?

    Tomatsu, Shunji; Montaño, Adriana M; Oikawa, Hirotaka; Dung, Vu Chi; Hashimoto, Amiko; Oguma, Toshihiro; Gutiérrez, Monica L; Takahashi, Tatsuo; Shimada, Tsutomu; Orii, Tadao; Sly, William S


    We treated mucopolysaccharidosis IVA (MPS IVA) mice to assess the effects of long-term enzyme replacement therapy (ERT) initiated at birth, since adult mice treated by ERT showed little improvement in bone pathology [1]. To conduct ERT in newborn mice, we used recombinant human N-acetylgalactosamine-6-sulfate sulfatase (GALNS) produced in a CHO cell line. First, to observe the tissue distribution pattern, a dose of 250units/g body weight was administered intravenously in MPS IVA mice at day 2 or 3. The infused enzyme was primarily recovered in the liver and spleen, with detectable activity in the bone and brain. Second, newborn ERT was conducted after a tissue distribution study. The first injection of newborn ERT was performed intravenously, the second to fourth weekly injections were intraperitoneal, and the remaining injections from 5th to 14th weeks were intravenous into the tail vein. MPS IVA mice treated with GALNS showed clearance of lysosomal storage in the liver and spleen, and sinus lining cells in bone marrow. The column structure of the growth plate was organized better than that in adult mice treated with ERT; however, hyaline and fibrous cartilage cells in the femur, spine, ligaments, discs, synovium, and periosteum still had storage materials to some extent. Heart valves were refractory to the treatment. Levels of serum keratan sulfate were kept normal in newborn ERT mice. In conclusion, the enzyme, which enters the cartilage before the cartilage cell layer becomes mature, prevents disorganization of column structure. Early treatment from birth leads to partial remission of bone pathology in MPS IVA mice. Copyright © 2014 Elsevier Inc. All rights reserved.


    O.I. Simonova


    Full Text Available In the past years we have gained enormous success not only in the field of understanding of pathologic basis and genetics of cystic fibrosis, but we have also developed new therapeutic approach to this disease. Enzyme therapy is one of the main parts of a complex treatment of cystic fibrosis. Correct therapeutic decision upon medication and treatment regimen allows to reach dramatic amelioration o patient’s condition, and significantly decrease the risk of complications of the disease itself and side-effects of the treatment given. This article contains guidelines of enzyme therapy in cystic fibrosis and clinical mistakes analysis that occur while deciding upon therapy. Key words: chronic pancreatic failure, replacement enzyme therapy, kreon, cystic fibrosis, children. (Voprosy sovremennoi pediatrii — Current Pediatrics. — 2011; 10 (5: 152–156.

  2. Long-term results after mechanical valve replacement in patients with small aortic root%小主动脉瓣环者行瓣膜置换手术后远期疗效随访

    张春曦; 罗兆榴; 吴戴红


    目的 探讨小主动脉瓣环者接受机械瓣膜置换术后的远期疗效.方法 2003年7月-2005年12月间,对36例成人小主动脉瓣环(直径≤19 mm)者行人工机械瓣膜置换术,其中主动脉瓣置换25例,主动脉瓣、二尖瓣双瓣置换11例.主动脉瓣置换采用改良Manougnian法瓣环扩大后植入23 mm CarboMedics 瓣14例(CM组);采用瓣环上瓣膜置换法植入19 mm CarboMedics Top Hat Supra-Annular Aortic瓣22例(CMSA 组),分析两组术前和术后第6年的临床及超声心动图资料.结果 与术前比较,术后第6年两组患者的心功能明显改善,左心室的射血分数、短轴缩短率明显上升,舒张末内径、主动脉跨瓣压差明显降低,CM组的室间隔厚度、左心室后壁厚度明显缩小,差异具有显著性(P<0.05);组间比较,CM组的主动脉跨瓣压差较CMSA组降低更加明显(P<0.05),而室间隔厚度和左心室后壁厚度的均数值也小于CMSA组,已达健康成年人水平.结论 小主动脉瓣环者机械瓣膜置换术后远期左心室功能恢复良好,行瓣环扩大而植入较大内径瓣膜者,更有利于左心室形态的逆转.%Objective To evaluate the long-term effect after mechanical valve replacement in adult patients with small aortic root, and guide clinical practice. Methods From July 2003 to December 2005, 36 patients with small aortic root (diameter ≤ 19 mm) received aortic prostheses; among which 25 cases underwent aortic valve replacement alone, and the other received mitral valve replacement besides aortic valve replacement. 23mm CarboMedics valve were implantated in 14 patients(CM group) by using of Manougnian's annulus enlarging technique; 22 patients received implantation of 19mmCarboMedics Top Hat Supra-Annular valve(CMSA group). All of patients were followed up with echocardiography and cardiac functions Pre-operation ang 6th Year post-operation. Results Comparing with those before operation, cardiac function(NYHA) improved obviously

  3. 长期肠内营养患者造瘘管置换术临床应用进展%Gastric fistula tube replacement in long-term enteral nutrition patients’ clinical application

    李思静; 庾艳军; 卢杰夫


    For swallowing dysfunction or dysphagia patients but with normal gastrointestinal function, we can indwell a gastric fistula, reconstruction of gastrointestinal nutrition pathway, make it get better nutrition and drug suppot. However, gastrostomy tube fistula is not permanent, for patients with long-term enteral nutrition,the tube is the need to change regularly. This article will be introducing several aspects of the peg replacement technology research from its development, clinical applications,complications, prevention, and prospects.%对于无法正常吞咽,而具有正常的消化功能的患者,通常医生进行肠内营养,使患者更好的得到营养及药物支持。然而造瘘管并不是永久性的,对于行造瘘术进行肠内营养的患者,多种原因使造瘘管需要进行更换。文章将从造瘘管置换术方法、适应症、并发症及其预防、前景与展望等几方面阐述长期肠内营养患者行造瘘管置换术的现状及最新研究进展。

  4. Mortality benefit of long-term angiotensin-converting enzyme inhibitors or angiotensin receptor blockers after successful percutaneous coronary intervention in non-ST elevation acute myocardial infarction.

    González-Cambeiro, María Cristina; López-López, Andrea; Abu-Assi, Emad; Raposeiras-Roubín, Sergio; Peña-Gil, Carlos; García-Acuña, José; González-Juanatey, Ramón


    Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been shown to reduce mortality after myocardial infarction (MI). Current guidelines recommend their prescription in all patients after MI. Limited data are available on whether ACEIs/ARBs still improve prognosis in the contemporary era of non-ST elevation MI (NSTEMI) management. We aimed to evaluate the mortality benefit of ACEIs/ARBs in NSTEMI patients treated successfully with percutaneous coronary intervention (PCI). We analyzed 2784 patients with NSTEMI treated successfully with in-hospital PCI. Two groups were formed based on ACEI/ARB prescription at discharge. Two propensity score (PS) analyses were performed to control for differences in covariates: one with adjustment among the entire cohort, and the other with PS matching (n=1626). The outcome variable was all-cause mortality at four-year follow-up. There were 1902 (68.3%) patients prescribed ACEIs/ARBs at discharge. When adjusted by PS, ACEI/ARB use was associated with a hazard ratio (HR) for mortality of 0.75 (0.60-0.94; absolute risk reduction [ARR] 4.0%) in the whole cohort (p=0.01). After one-to-one PS matching (n=813 in each group), the mortality rate was significantly lower in patients prescribed ACEIs/ARBs, with HR of 0.77 (0.63-0.94; ARR 3.8%) (p=0.03). In this observational study of patients with NSTEMI, all of them treated successfully by PCI, the use of ACEIs/ARBs was significantly associated with a lower risk of four-year all-cause mortality. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  5. Long-term urethral catheterisation.

    Turner, Bruce; Dickens, Nicola

    This article discusses long-term urethral catheterisation, focusing on the relevant anatomy and physiology, indications for the procedure, catheter selection and catheter care. It is important that nurses have a good working knowledge of long-term catheterisation as the need for this intervention will increase with the rise in chronic health conditions and the ageing population.

  6. 晋南长期免耕褐土肥力和酶活性的关系%Relationship between Soil Fertilities and Soil Enzyme Activities of Long-term No-tillage in Cinnamon Soil in South Shanxi

    王恒飞; 张永清; 张水利; 景小元


    traditional Effects of long-term no-tillage on tillage and Long-term no-tillage District of Linfen total K, alkaline traditional tillage soil fertility, enzyme activities and their correlation were studied by using soil in ChengHuang experiment wheat field,which is located in Yaodu City in the loess plateau. The result indicated that N, available P, and available K soil were increased contents of soil organic matter, total N, total P, in the long-term no-l:illage soil, compared with soil. Activities of catalase, urease and invertase of the no-tillage soil were above the traditional tillage soil significantly. Soil enzyme activities correlates closely on fertility of long-term no-tillage soil,so the activities of catalase, urease and inverease of the no-tillage soil may be used for evaluating component analysis indicated that the years of no-tillage had significant impacted the soil fertility on the activities well. Principal and fertility of no-tillage soil. Long-term no-tillage is beneficial to soil fertility and sustainable development of agriculture. It is a feasible tillage pattern in arid and semiarid areas in the north of China%临汾市尧都区机械化保护性耕作试验示范区连续18年免耕覆盖(NTCS18)、连续12年免耕覆盖(NTCS12)、连续10年免耕覆盖(NTCS10)和传统耕作(CK)对土壤肥力和酶活性的影响研究结果表明,长期免耕提高了表层土壤有机质、碱解氮、速效磷、速效钾、全氮、全磷、全钾含量,并使表层土壤脲酶、蔗糖酶、过氧化氢酶活性显著增加;相关分析研究表明,长期免耕条件下土壤肥力与土壤酶活性间关系密切,蔗糖酶、过氧化氢酶、脲酶可以用来评价长期免耕土壤肥力状况;主成分分析法研究表明,长期免耕土壤肥力和酶活性信息系统主成分得分由高到低顺序为:NTCS18〉NTCS12〉NTCS10〉CK,说明长期免耕利于土壤肥力水平和酶活性提高,而且肥力水平和酶活

  7. 长期施肥对薄层黑土酶活性及土壤肥力的影响%Effect of long-term fertilization on enzyme activities and soit fertility in the black thin-layer soil

    焦晓光; 隋跃宇; 魏丹


    Soil enzyme activities and soil fertility were studied to explore the long-term fertilization on soil enzyme activities and its relationship with soil fertility on the basis of 29-years long-term site-specific experiment with different fertilization methods. The results showed that combined application of chemical fertilizers and organic manure could significantly increase the soil organic matter, total nitrogen, total phosphorus, alkali-soluble nitrogen, available phosphorus content and enhance the soil urease, phosphatase, invertase, catalase, dehydrogenase activity. The results of correlation analysis showed that soil urease, phosphatase, invertase catalase and dehydrogenase activity positively corrected with organic matter, total nitrogen, total phosphorus and alkali-soluble nitrogen significantly, and the integrated activities of soil urease, phosphatase, invertase, catalase dehydrogenase activity could reflect the changing trend of black thin-layer soil quality in the farmland after long-term fertilization.%利用29年的长期定位试验,对不同的施肥方式下薄层黑土酶活性及肥力进行了研究,探讨长期施肥对土壤酶活性及与土壤肥力的影响.结果表明,化肥与有机肥配合施用能明显提高土壤有机质、全氮、全磷、碱解氮、有效磷含量,增强土壤脲酶、磷酸酶、转化酶、过氧化氢酶、脱氢酶活性.相关分析结果显示,土壤脲酶、磷酸酶、转化酶、过氧化氢酶、脱氢酶活性与有机质、全氮、全磷、有效磷、碱解氮呈显著正相关.土壤脲酶、磷酸酶、转化酶、过氧化氢酶、脱氢酶综合活性可以反映长期施肥后薄层黑土质量的变化趋势.

  8. Temporal and spatial dynamics of enzyme activities under long-term fertilization in a maize growing brown soil%长期不同施肥棕壤玉米地酶活性的时空变化

    兰宇; 韩晓日; 杨劲峰; 王月; 房大伟; 李娜


    为揭示长期不同施肥对棕壤玉米地酶活性时空变化的影响,利用31年长期肥料定位试验研究了玉米生育期内3种主要土壤酶活性的时空变化及其与土壤理化性质的关系。结果表明,棕壤上各种酶活性随玉米生育期推进而有规律地变化。土壤脲酶、转化酶活性高峰出现在玉米拔节期,酸性磷酸酶活性高峰出现在玉米大喇叭口期;玉米收获后,土壤转化酶、脲酶均高于播前或与播前相当,而酸性磷酸酶活性则低于播前。在同样化肥水平卜增施有机肥能增加脲酶、转化酶活性,而降低酸性磷酸酶活性;3种酶活性的空间分布均遵循随土层深度加深而不断减小的规律,长期培肥对深层土壤酶活性亦有影响。相关分析结果显示,土壤脲酶与转化酶呈极显著正相关(r=0.636^**);脲酶、转化酶与土壤有机碳、pH、含水量、碱解氮、速效磷基本呈极显著正相关;酸性磷酸酶与各因子无显著相关关系。土壤酶与土壤肥力因素关系密切,可作为衡量土壤肥力的敏感指标。%A long-term fertilizer location experiment (31 years) was carried out to study the temporal and spatial dynamics of enzyme activities under long-term fertilization in a maize growing brown soil. Results showed that enzyme activities changed regularly with the growing of maize. The highest urease and invertase activities were observed at jointing stage, while the highest acid phosphatase activity at the huge bellbottom period. Urease and invertase activities were higher after harvest than before sowing, however acid phosphatase activity was lower after harvest. With same application rate of chemical fertilizer, application of organic fertilizer could increase urease and invertase activities, but decrease acid phosphatase activity. All of the three enzyme activities decreased with the depth soil profile. Long-term fertilization could also affect

  9. The right ventricle in Fabry disease: natural history and impact of enzyme replacement therapy.

    Niemann, Markus; Breunig, Frank; Beer, Meinrad; Herrmann, Sebastian; Strotmann, Jörg; Hu, Kai; Emmert, Andrea; Voelker, Wolfram; Ertl, Georg; Wanner, Christoph; Weidemann, Frank


    Storage of globotriaosylceramides is present in the left and right ventricles of patients with Fabry disease. Improvement of left ventricular morphology and function during enzyme replacement therapy (ERT) has previously been reported. To analyse the effects of long term ERT on right ventricular morphology and function. This was a prospective follow-up of 75 genetically confirmed consecutive Fabry patients for 3.1±1.8 years. According to treatment guidelines the natural history was followed in 18 patients, whereas 57 patients received ERT. Standard echocardiography, strain rate imaging for regional deformation of the right and left ventricle, and magnetic resonance tomography with late enhancement (LE) imaging for the detection of fibrosis were all performed at yearly intervals. Right ventricular hypertrophy was evident in 53 patients (71%) at baseline. A significant positive correlation was found between left and right ventricular wall thickness (r=0.76; pright ventricle. Patients with LE in the left ventricle presented with the lowest right ventricular deformation properties. In contrast to the left ventricle, there was no change in right ventricular wall thickness (baseline 6.9±1.6 mm vs follow-up 6.7±1.5 mm; p=0.44) or systolic strain rate (2.2±0.7/s vs 2.1±0.8/s; p=0.31) during follow-up with ERT. The degree of right ventricular involvement in Fabry disease is related to the left ventricular cardiomyopathy stage. ERT seems to have no direct impact on right ventricular morphology and function.

  10. Taliglucerase alfa: an enzyme replacement therapy using plant cell expression technology.

    Grabowski, Gregory A; Golembo, Myriam; Shaaltiel, Yoseph


    Gaucher disease (GD) is a rare, genetic lysosomal storage disorder caused by functional defects of acid β-glucosidase that results in multiple organ dysfunction. Glycosylation of recombinant acid human β-glucosidase and exposure of terminal mannose residues are critical to the success of enzyme replacement therapy (ERT) for the treatment of visceral and hematologic manifestations in GD. Three commercially available ERT products for treatment of GD type 1 (GD1) include imiglucerase, velaglucerase alfa, and taliglucerase alfa. Imiglucerase and velaglucerase alfa are produced in different mammalian cell systems and require production glycosylation modifications to expose terminal α-mannose residues, which are needed for mannose receptor-mediated uptake by target macrophages. Such modifications add to production costs. Taliglucerase alfa is a plant cell-expressed acid β-glucosidase approved in the United States and other countries for ERT in adults with GD1. A plant-based expression system, using carrot root cell cultures, was developed for production of taliglucerase alfa and does not require additional processing for postproduction glycosidic modifications. Clinical trials have demonstrated that taliglucerase alfa is efficacious, with a well-established safety profile in adult, ERT-naïve patients with symptomatic GD1, and for such patients previously treated with imiglucerase. These included significant improvements in organomegaly and hematologic parameters as early as 6months, and maintenance of achieved therapeutic values in previously treated patients. Ongoing clinical trials will further characterize the long-term efficacy and safety of taliglucerase alfa in more diverse patient populations, and may help to guide clinical decisions for achieving optimal outcomes for patients with GD1.

  11. The Daily Practice of Pancreatic Enzyme Replacement Therapy After Pancreatic Surgery: A Northern European Survey: Enzyme Replacement After Surgery

    E.C.M. Sikkens (Edmée); D.L. Cahen (Djuna); C.H.J. van Eijck (Casper); E.J. Kuipers (Ernst); M.J. Bruno (Marco)


    textabstractIntroduction: After pancreatic surgery, up to 80 % of patients will develop exocrine insufficiency. For enzyme supplementation to be effective, prescribing an adequate dose of pancreatic enzymes is mandatory but challenging because the required dose varies. Data on the practice of enzyme

  12. The Daily Practice of Pancreatic Enzyme Replacement Therapy After Pancreatic Surgery: A Northern European Survey: Enzyme Replacement After Surgery

    E.C.M. Sikkens (Edmée); D.L. Cahen; C.H.J. van Eijck (Casper); E.J. Kuipers (Ernst); M.J. Bruno (Marco)


    textabstractIntroduction: After pancreatic surgery, up to 80 % of patients will develop exocrine insufficiency. For enzyme supplementation to be effective, prescribing an adequate dose of pancreatic enzymes is mandatory but challenging because the required dose varies. Data on the practice of enzyme

  13. Short-term effects on antioxidant enzymes and long-term genotoxic and carcinogenic potential of CuO nanoparticles compared to bulk CuO and ionic copper in mussels Mytilus galloprovincialis.

    Ruiz, Pamela; Katsumiti, Alberto; Nieto, Jose A; Bori, Jaume; Jimeno-Romero, Alba; Reip, Paul; Arostegui, Inmaculada; Orbea, Amaia; Cajaraville, Miren P


    The aim of this work was to study short-term effects on antioxidant enzyme activities and long-term genotoxic and carcinogenic potential of CuO nanoparticles (NPs) in comparison to bulk CuO and ionic copper in mussels Mytilus galloprovincialis after 21 days exposure to 10 μg Cu L(-1). Then, mussels were kept for up to 122 days in clean water. Cu accumulation depended on the form of the metal and on the exposure time. CuO NPs were localized in lysosomes of digestive cells, as confirmed by TEM and X ray microanalysis. CuO NPs, bulk CuO and ionic copper produced different effects on antioxidant enzyme activities in digestive glands, overall increasing antioxidant activities. CuO NPs significantly induced catalase and superoxide dismutase activities. Fewer effects were observed in gills. Micronuclei frequency increased significantly in mussels exposed to CuO NPs and one organism treated with CuO NPs showed disseminated neoplasia. However, transcription levels of cancer-related genes did not vary significantly. Thus, short-term exposure to CuO NPs provoked oxidative stress and genotoxicity, but further studies are needed to determine whether these early events can lead to cancer development in mussels.

  14. 成年人小主动脉瓣环者机械瓣膜置换术后远期疗效%Long-term effect after mechanical valve replacement in adult patients with small aortic root

    张春曦; 罗兆榴; 黄达德; 吴戴红


    Objective To evaluate the long-term effect after mechanical valve replacement in adult patients with small aortic root,and guide clinical practice.Methods From July 2003 to February 2005,36adult patients with small amtic root(diameter≤ 19 mm)received mechanical valve replacement,23 mm CarboMedics valve were implanted in 14 patients by using of Manougnian annulus enlargiW; technique(CM group),19 mm CarboMedics Top Hat Supra-Annular Aortic valve were implanted in 22 patients(CMSA group).All of the patients were examined for cardiac functions(CF),left ventricular end-diastolic diameter (LVDD),interventricular septal thickness(IVST),left ventricular posterior wall thickness(LVPWT),pressure gradients across aortic valve(PGav),and left ventricular fractional shortening(LVFS),calculating left ventricular ejection fraction(LVEF)before operation and 6 years after operation.Twenty healthy adults were as control group.Results Compared to the preoperation,there was no statistical difference in CMSA group in IVST[(10.37 ± 2.06)mm vs.(11.03 ± 2.45)mm]and LVPWT[(10.53 ± 2.18)mm vs.(11.24 ±degrees(P< 0.01 or < 0.05).PGav in CM group was lower significantly than that in CMSA group after 6 years [(9.24 ±5.93)mm Hg(1 mm Hg =0.133 kPa)vs.(24.30 ± 12.50)mm Hg],the difference was statistically significant(P < 0.05).The indicators in CM group were not statistically significant compared to control group,while CMSA group in IVST,LVPWT,PGav was significant difference(P <0.05).Conclusions The long-term effect after mechanical valve replacement is satisfied in adult patients with small aortic root,especially in left ventricular function.Line valve ring augmentation larger diameter valves implanted will help reverse the left vehicular morphology.%目的 探讨成年人小主动脉瓣环者机械瓣膜置换术后的远期疗效,以指导临床实践.方法 2003年7月至2005年2月对36例小主动脉瓣环(直径≤19mm)的成年患者行人工机械瓣膜置换术.分别采

  15. Impact of enzyme replacement therapy and hematopoietic stem cell transplantation in patients with Morquio A syndrome.

    Tomatsu, Shunji; Sawamoto, Kazuki; Alméciga-Díaz, Carlos J; Shimada, Tsutomu; Bober, Michael B; Chinen, Yasutsugu; Yabe, Hiromasa; Montaño, Adriana M; Giugliani, Roberto; Kubaski, Francyne; Yasuda, Eriko; Rodríguez-López, Alexander; Espejo-Mojica, Angela J; Sánchez, Oscar F; Mason, Robert W; Barrera, Luis A; Mackenzie, William G; Orii, Tadao


    Patients with mucopolysaccharidosis IVA (MPS IVA) can present with systemic skeletal dysplasia, leading to a need for multiple orthopedic surgical procedures, and often become wheelchair bound in their teenage years. Studies on patients with MPS IVA treated by enzyme replacement therapy (ERT) showed a sharp reduction on urinary keratan sulfate, but only modest improvement based on a 6-minute walk test and no significant improvement on a 3-minute climb-up test and lung function test compared with the placebo group, at least in the short-term. Surgical remnants from ERT-treated patients did not show reduction of storage materials in chondrocytes. The impact of ERT on bone lesions in patients with MPS IVA remains limited. ERT seems to be enhanced in a mouse model of MPS IVA by a novel form of the enzyme tagged with a bone-targeting moiety. The tagged enzyme remained in the circulation much longer than untagged native enzyme and was delivered to and retained in bone. Three-month-old MPS IVA mice treated with 23 weekly infusions of tagged enzyme showed marked clearance of the storage materials in bone, bone marrow, and heart valves. When treatment was initiated at birth, reduction of storage materials in tissues was even greater. These findings indicate that specific targeting of the enzyme to bone at an early stage may improve efficacy of ERT for MPS IVA. Recombinant N-acetylgalactosamine-6-sulfate sulfatase (GALNS) in Escherichia coli BL21 (DE3) (erGALNS) and in the methylotrophic yeast Pichia pastoris (prGALNS) has been produced as an alternative to the conventional production in Chinese hamster ovary cells. Recombinant GALNS produced in microorganisms may help to reduce the high cost of ERT and the introduction of modifications to enhance targeting. Although only a limited number of patients with MPS IVA have been treated with hematopoietic stem cell transplantation (HSCT), beneficial effects have been reported. A wheelchair-bound patient with a severe form of MPS

  16. Effect of enzyme replacement therapy on isokinetic strength for all major muscle groups in four patients with Pompe disease-a long-term follow-up

    Andreassen, Christer Swan; Schlütter, Jacob Mørup; Vissing, John


    Pompe disease is a rare, inherited metabolic myopathy characterized by progressive weakness of the proximal limb and respiratory muscles. We report the findings from four patients with late-onset Pompe disease treated with α-glucosidase (Myozyme) for 2 (n=2) and 6 (n=2) years, and monitored...... with isokinetic dynamometry, 6-minute walking test (6MWT), and vital capacity. Patients were evaluated after 6, 12, 24, 36, 48, 60, and 72months. In two patients, muscle size estimated by MRI and DXA scanning was also performed prior to and following 6months of treatment. After 2years of α-glucosidase treatment......, maximal isokinetic muscle strength increased by 11% (0%-50%) [median (range)] and 6MWT improved by 18% (2%-40%). In the two patients treated for 6years, the increase in muscle strength stabilized at 40% and 6MWT stabilized at 32%. The improvements primarily occurred during the first 6months of treatment...

  17. Effect of enzyme replacement therapy on isokinetic strength for all major muscle groups in four patients with Pompe disease-a long-term follow-up.

    Andreassen, Christer Swan; Schlütter, Jacob Mørup; Vissing, John; Andersen, Henning


    Pompe disease is a rare, inherited metabolic myopathy characterized by progressive weakness of the proximal limb and respiratory muscles. We report the findings from four patients with late-onset Pompe disease treated with α-glucosidase (Myozyme) for 2 (n=2) and 6 (n=2) years, and monitored with isokinetic dynamometry, 6-minute walking test (6MWT), and vital capacity. Patients were evaluated after 6, 12, 24, 36, 48, 60, and 72months. In two patients, muscle size estimated by MRI and DXA scanning was also performed prior to and following 6months of treatment. After 2years of α-glucosidase treatment, maximal isokinetic muscle strength increased by 11% (0%-50%) [median (range)] and 6MWT improved by 18% (2%-40%). In the two patients treated for 6years, the increase in muscle strength stabilized at 40% and 6MWT stabilized at 32%. The improvements primarily occurred during the first 6months of treatment. Interestingly, the weakest muscle groups seemed to benefit more than those less affected, and greater improvements occurred for flexor muscles compared to extensor muscles. Vital capacity did not improve on treatment.

  18. 人工心脏瓣膜置换手术的随访和中远期疗效分析%Follow-up of the artificial heart valve replacement and analyze the long-term curative effect

    马浩; 王奇; 石海燕; 王立新; 马振海; 张晓


    related to age,cardiac function before operation ( P < 0.05 ).One patient died during the follow-up period.The statistics analysis showed that the long-term incidence of complication was related to the type of heart valve prosthesis ( P < 0.05 ).Conclusion The therapeutic effect of artificial heart valve replacement surgery appears satisfactory.Heart function is improved significantly and the survival rate is high.Reasonable timing of surgery,appropriate type of prosthetic valve and intensified clinical follow-up can help to reduce the occurrence of postoperative complication.

  19. Development of nanoparticle-bound arylsulfatase B for enzyme replacement therapy of mucopolysaccharidosis VI

    Mühlstein, A; Gelperina, S; Kreuter, J


    .... Even though an enzyme replacement therapy (ERT) of recombinant arylsulfatase B (ASB) is available for MPS VI, the administration cannot positively affect the neurologic manifestations such as spinal cord compression...

  20. 长期不同施肥处理对华北潮土酶活性的影响%Soil Enzyme Levels in Fluvo-auic Soil with Different Long-term Fertilization in North China Plain

    李芳; 张佳宝; 信秀丽; 张丛志; 宁琪; 赵金花; 吴其聪; 赵占辉; 蔡太义; 聂广森


    酶产生显著影响。%Soil enzyme activities, as an important biological indicator of soil fertility, can quickly reflect the change of soil properties. In order to improve the fertility of fluvo-auic soil, we assessed the effects of long-term fertilization on Soil enzyme activities. Based on two long-term fertilization experiments located in Zhengzhou and Fengqiu, the activities of urease, alkaline phospahtase, catalase, protease and invertase under different fertilization treatments in plough layer soil (0~15 cm) were investigated, as well as the correlations between soil enzyme activities and soil chemical properties were analyzed. The results showed that: (1) Although both of topsoil types at two field experiments were fluvo-auic soil, the effects of different fertilization on soil enzyme activities were very different. Soil catalase activities was not significant influenced by long-term fertilization in Zhengzhou, whereas NK fertilization increased the soil catalase activities by 58.3% compared with control in Fengqiu. (2) Without the application of phosphate fertilizer, protease activity increased by 119% compared with the control when the ratio of nitrogen and potassium was 1∶1; however, protease activity descended by 20% when the ratio was 2∶1. (3) Different fertilization was helpful for the urease enzyme activity, and the highest urease enzyme activity was found in organic compost treated soil, which increased by 41.1% and 106.4% in Zhengzhou and Fengqiu, respectively. (4) Long-term fertilization did not significantly increase the soil alkaline phosphatase activity, nevertheless the straw incorporated treatment dominantly induce the activity of alkaline phosphatase by the percent of 133.5% in comparison with that in the CK plots; (5) Invertase activity of all fertilization treated soil was improved in Zhengzhou, and the increase ranged 95.5% in the NK plots to 439% in straw incorporated fertilizer plots. In Fengqiu, compared to the control, NK,OM fertilization improved the invertase

  1. Analysing long term discursive processes

    Horsbøl, Anders

    What do timescales - the notion that processes take place or can be viewed within a shorter or longer temporal range (Lemke 2005) - mean for the analysis of discourse? What are the methodological consequences of analyzing discourse at different timescales? It may be argued that discourse analysis...... in general has favored either the analysis of short term processes such as interviews, discussions, and lessons, or the analysis of non-processual entities such as (multimodal) texts, arguments, discursive repertoires, and discourses (in a Foucaultian sense). In contrast, analysis of long term processes...... which extend beyond the single interaction, for instance negotiations or planning processes, seems to have played a less important role, with studies such as Iedema 2001 and Wodak 2000 as exceptions. These long term processes, however, are central to the constitution and workings of organizations...

  2. Long-term In Vitro Treatment of Human Glioblastoma Cells with Temozolomide Increases Resistance In Vivo through Up-regulation of GLUT Transporter and Aldo-Keto Reductase Enzyme AKR1C Expression

    Benjamin Le Calvé


    Full Text Available Glioblastoma (GBM is the most frequent malignant glioma. Treatment of GBM patients is multimodal with maximum surgical resection, followed by concurrent radiation and chemotherapy with the alkylating drug temozolomide (TMZ. The present study aims to identify genes implicated in the acquired resistance of two human GBM cells of astrocytic origin, T98G and U373, to TMZ. Resistance to TMZ was induced by culturing these cells in vitro for months with incremental TMZ concentrations up to 1 mM. Only partial resistance to TMZ has been achieved and was demonstrated in vivo in immunocompromised mice bearing orthotopic U373 and T98G xenografts. Our data show that long-term treatment of human astroglioma cells with TMZ induces increased expression of facilitative glucose transporter/solute carrier GLUT/SLC2A family members, mainly GLUT-3, and of the AKR1C family of proteins. The latter proteins are phase 1 drug-metabolizing enzymes involved in the maintenance of steroid homeostasis, prostaglandin metabolism, and metabolic activation of polycyclic aromatic hydrocarbons. GLUT-3 has been previously suggested to exert roles in GBM neovascularization processes, and TMZ was found to exert antiangiogenic effects in experimental gliomas. AKR1C1 was previously shown to be associated with oncogenic potential, with proproliferative effects similar to AKR1C3 in the latter case. Both AKR1C1 and AKR1C2 proteins are involved in cancer pro-proliferative cell chemoresistance. Selective targeting of GLUT-3 in GBM and/or AKR1C proteins (by means of jasmonates, for example could thus delay the acquisition of resistance to TMZ of astroglioma cells in the context of prolonged treatment with this drug.

  3. Long term stability of power systems

    Kundur, P.; Gao, B. [Powertech Labs. Inc., Surrey, BC (Canada)


    Power system long term stability is still a developing subject. In this paper we provide our perspectives and experiences related to long term stability. The paper begins with the description of the nature of the long term stability problem, followed by the discussion of issues related to the modeling and solution techniques of tools for long term stability analysis. Cases studies are presented to illustrate the voltage stability aspect and plant dynamics aspect of long term stability. (author) 20 refs., 11 figs.

  4. Cognitive Development in Infantile-Onset Pompe Disease Under Very Early Enzyme Replacement Therapy.

    Lai, Chih-Jou; Hsu, Ting-Rong; Yang, Chia-Feng; Chen, Shyi-Jou; Chuang, Ya-Chin; Niu, Dau-Ming


    Most patients with infantile-onset Pompe disease die in early infancy before beginning enzyme replacement therapy, which has made it difficult to evaluate the impact of Pompe disease on cognitive development. Patients with infantile-onset Pompe disease can survive with enzyme replacement therapy, and physicians can evaluate cognitive development in these patients. We established an effective newborn screening program with quick clinical diagnostic criteria. Cognitive and motor development were evaluated using the Bayley Scales of Infant and Toddler Development-Third Edition at 6, 12, and 24 months of age. The patients who were treated very early demonstrate normal cognitive development with no significant change in cognition during this period (P = .18 > .05). The cognitive development was positively correlated with motor development (r = 0.533, P = .011). The results indicated that very early enzyme replacement therapy could protect cognitive development in patients with infantile-onset Pompe disease up to 24 months of age.

  5. A Research on Response of Enzyme Activities to Long-term Fertilization in Lime Concretion Black Soil%淮北砂姜黑土酶活性对长期不同施肥模式的响应

    陈欢; 李玮; 张存岭; 乔玉强; 杜世州; 赵竹; 曹承富


    同。【结论】同等施氮水平下,有机肥与化肥配施与单施化肥或单施有机肥相比,能使砂姜黑土脲酶、磷酸酶、过氧化氢酶及蔗糖酶均保持较高的活性,有利于改善土壤生物化学环境,进而提高土壤可持续生产力;土壤酶之间相关关系各有不同,呈显著正相关关系的有脲酶与过氧化氢酶、脲酶与蔗糖酶及过氧化氢酶与蔗糖酶,而磷酸酶与其他3种酶之间均呈显著负相关关系;砂姜黑土酶活性受季节影响的程度因酶种类与施肥方式不同而有所不同。%[Objective]In order to provide a theoretical support for improving soil biochemical environment and soil quality, insuring high and steady yield of crops in view of the characters of“drought, waterlogging, concretion, leanness”in lime concretion black soil, the responsive mechanism of soil enzyme activities to fertilization in black soil was studied by the way of exploring effects of long-term fertilization on soil enzyme activities. [Method] Based on a 31 yeas long-term fertilization experiment in Yangliu of Anhui province, the change trend of activities of urease, acid phosphatase, neutral phosphatase, catalase and invertase in tilth soil (0-20 cm) was investigated with 5 patterns of fertilization (non-fertilization, application of single chemical fertilizer, application of single organic fertilizer, mixed application of organic and chemical fertilizer (with the same amount of nitrogen), mixed application of organic and chemical fertilizer (with the lager amount of nitrogen) in wheat-maize rotation system, as well as the correlation and paired comparison was analyzed to interpret the relationship among soil enzymes and seasonal variation, respectively.[Result]Compared with control, the activities of urease, catalase, and invertase increased significantly by 130.5%and 129.5%, 11.4% and 14.9%, and 31.4% and 12.0%, respectively, after wheat and maize harvested in the situation of

  6. Renal histology before and after effective enzyme replacement therapy in a patient with classical Fabry's disease.

    Hirashio, S; Taguchi, T; Naito, T; Maki, K; Ogata, S; Taniyama, K; Taniguchi, Y; Yorioka, N


    A 38-year-old man underwent renal biopsy because of proteinuria. It revealed swelling and vacuolation of glomerular epithelial cells, as well as myelin-like structures characteristic of Fabry's disease. Detection of decreased plasma activity of alpha-galactosidase A confirmed the diagnosis. Enzyme replacement therapy was provided with recombinant agalsidase-beta, resulting in improvement of his symptoms. When renal biopsy was repeated, specific staining for globotriaosylceramide showed that renal deposits were decreased by enzyme therapy.

  7. Enzyme replacement therapy in type 1 Gaucher disease and a review of the literature

    Gökhan Kabaçam


    Full Text Available Gaucher disease (GD is the most common lysosomal storage disorder. Deficiency of the lysosomal enzyme glucocerebrosidase results in the intracellular accumulation of undegraded substrates in the spleen, liver and bone marrow. Enzyme replacement therapy (ERT is a standard approach for type 1 GD. Here, we present an adult patient with hematological disorders due to type 1 GD, who markedly improved with ERT.

  8. Effects of long-term fertilizer on soil fertility and soil enzyme activities in upland red soils%长期施肥对旱地红壤肥力和酶活性的影响

    邵兴华; 徐金仁; 张建忠; 李海峰; 周同林; 张辉


    In order to understand the relation between soil enzyme activity and soil chemical propertities in upland red soil under different fertilizer treatments, we conducted a study to determine the effects of pig manure, inorganic fertiliser and combination of pig manure and inorganic NPK on soil chemical and biological properties in a more than 30 a long-term fertilization experiment. The treatments as the following: no fertilization(CK), N, NP, NPK, double NPK, pig manure, NPK+pig manure. The results showed, the total N content had no significant difference between different treatments. The only applied N could significantly improve available N in soil. Soil pH, organic matter, total P and available P in manure fertilization treatments ( NPK+pig manure and pig manure) all increased significantly compared with no fertilization (CK) and mineral fertilization treatmets (N, NP, NPK and double NPK). Except for the highest urease activity was double NPK treatment, the soil invertase, dehydrognease, catalase and acid phosphatase activities were all significantly higher than those in other fertilization treatments. Acid phosphatase, catalase, dehydrognease and urease activities were significant and dramatically significant positively correlated with total N, organic matter and available N. So, manure application or co-application of manure and mineral fertilizers not only increased the soil fertility, but also enhanced significantly soil enzymes activities, thus could improve red soil sustainable productivity.%为了明确不同施肥种类对旱地红壤肥力与酶活性的影响,以30年(1981年至今)长期定位试验地为基础,研究不同施肥处理(CK,N,NP,NPK,2倍NPK,猪粪,NPK+猪粪)旱地红壤玉米田耕层(0~20 cm)土壤酶活性与养分的变化趋势及其相关性.结果表明:1)全N含量各处理间差异不显著,单施N肥显著增加土壤速效N,施有机肥处理(NPK+猪粪,猪粪)土壤的pH值、有机质、全P、速效P均显著增加;2)

  9. Children with Pompe disease: clinical characteristics, peculiar features and effects of enzyme replacement therapy

    C.I. van Capelle (Carine)


    markdownabstract__Abstract__ Pompe disease is a metabolic myopathy. Since the first description of the disease in 1932 by J.C. Pompe,1 tremendous progress has been made from discovering the biochemical and genetic basis of the disease to developing enzyme replacement therapy (ERT). With this

  10. Asthma Medicines: Long-Term Control

    ... Size Email Print Share Asthma Medicines: Long-term Control Page Content Article Body Corticosteroids Synthetic versions of ... form, they are used exclusively for long-term control; they are not very effective for acute symptoms. ...

  11. Long term complications after radical cystoprostatectomy with ...

    Long term complications after radical cystoprostatectomy with orthotopic diversion in male ... AFRICAN JOURNALS ONLINE (AJOL) · Journals · Advanced Search · USING ... Objective: To evaluate the long-term outcomes beyond 1 year, both ...

  12. Gratitude in Long Term Care

    Brooke Abrams Sunding


    Full Text Available An exploratory study was conducted to examine the effectiveness of a group gratitude intervention with 29 permanent residents at a long term care/skilled nursing facility in improving elder mood, behavior and well- being over a 3 week time period. The sample included individuals diagnosed with dementia, other cognitive impairment, major depressive disorder, insomnia and generalized anxiety disorder. The gratitude intervention consisted of asking elders to share what they are thankful for at the dinner table each day. Measures included the Elder Well Being Scale and The Dinner Rating Scale. On both measures, higher scores indicated better functioning. To test the hypothesis that post treatment elder well-being will be significantly higher than pretreatment elder well-being ratings, a one-way ANOVA was conducted. Post-hoc tests revealed a statistically significant increase in Elder Well Being Scale scores. An ANOVA of comparing Dinner Ratings demonstrated a nonsignificant increase over the 3 week experiment. Implications are discussed.

  13. The attenuated/late onset lysosomal storage disorders: Therapeutic goals and indications for enzyme replacement treatment in Gaucher and Fabry disease.

    Hollak, Carla E M; Weinreb, Neal J


    Enzyme replacement therapies have been developed and authorized for commercial use for six different lysosomal storage disorders. For Gaucher disease, Fabry disease and mucopolysaccharidosis type 1, disease-specific treatments have been available for more than a decade. Although long term follow-up data are still sparse, therapeutic goals for patients with Gaucher disease and Fabry disease have been formulated and published for both adults and children. Without adaptation or modification, these goals are often applied in clinical research and in routine patient care across the entire phenotypic spectrum of disease, although in practice, patients commonly manifest high variability in clinical presentation and course of the illness. In this context, establishing goals for the follow-up and treatment of late onset/attenuated phenotypes is particularly challenging. In this chapter, we review current therapeutic goals for Gaucher disease and Fabry disease and discuss approaches for those with attenuated disease manifestations.

  14. Replacement of traditional seawater-soluble pigments by starch and hydrolytic enzymes in polishing antifouling coatings

    Olsen, Søren Martin; Pedersen, L. T.; Dam-Johansen, Kim;


    The use of starch and hydrolytic enzymes as replacement for traditional polishing pigments (e.g., Cu2O and ZnO) in antifouling coatings has been investigated. The enzymes facilitate a slow conversion of water-insoluble starch into water-soluble glucose, and dissolution of glucose causes the devel......The use of starch and hydrolytic enzymes as replacement for traditional polishing pigments (e.g., Cu2O and ZnO) in antifouling coatings has been investigated. The enzymes facilitate a slow conversion of water-insoluble starch into water-soluble glucose, and dissolution of glucose causes...... the development of a leached (porous) layer in the wetted, outermost part of the coating. Subsequent water-binder interaction at the pore walls gives rise to polishing, in a manner similar to that of conventional antifouling coatings. Different starch types have been evaluated and classified as potential coating...... the starch-enzyme coatings tested; however, polishing is only detected for two out of four binder systems investigated. Suitable polishing rates of 7-10 mu m/month, based on the enzymatic starch-degradation, have been measured. Controls containing only starch (no enzyme) did not polish....

  15. 儿童心脏瓣膜置换术的近远期疗效分析%Early-and Long-term Clinical Efficacy of Heart Valve Replacement in Children

    陈澍; 孙宗全; 董念国; 蒋雄刚; 孙图成


    Objective To explore the etiologies ,surgical indications and methods ,early‐and long‐term outcomes ,risk fac‐tors of mortality and anti‐coagulation treatment of heart valve replacement in children.Methods Clinical data of 53 patients who received heart valve replacement in Union Hospital ,Tongji Medical College ,Huazhong University of Science and Technolo‐gy ,between Jan.1980 and Dec.2010 ,were retrospectively analyzed.The patients were aged from 2.5 to 12 years.The etiologies included congenital heart disease (n= 41 ,77.3% ) ,rheumatic valve disease (n= 8 ,15.1% ) ,infective endocarditis (n= 2 , 3.8% ) ,endocardial fibroelastosis (n=2 ,3.8% ).Mitral valve replacement was performed in 29 cases ,aortic valve replacement in 18 ,mitral and aortic valve replacement in two ,tricuspid valve replacement in three and pulmonary valve replacement in one.Fifty‐one patients received mechanical valve implantation and 2 patients received bio‐prosthetic valve implantation.Results Overall hospital mortality was 11.3% (6/53).Patients died mainly due to low cardiac output syndrome.Follow‐up was com‐pleted in 40 out of 47 survivors ,with a mean follow‐up of (11.7 ± 3.5) years (2.5-20 years).Cardiac function of most patients was at NYHA class Ⅰ or Ⅱ.Three patients died and three patients suffered a second valve replacement during follow‐up.Conclusion The valve replacement is associated with an increased mortality in children relative to adults.Every effort should be made in the first surgery to preserve the native valve ,although the long‐term outcome can be improved to some extent by using prosthesis with a larger effective orifice area and regularly monitoring and regulating anticoagulation intensity.%目的:探讨儿童心脏瓣膜置换术的病因、手术指征及方法、近远期效果、死亡危险因素及抗凝相关问题。方法回顾性分析1980年1月至2010年12月在华中科技大学同济医学院附属协和医院接受

  16. Long-term Follow up of Tricuspid Valve Function after Mitral Valve Replacement in 28 Cases%二尖瓣置换术对三尖瓣功能的影响28例临床分析

    王荣华; 杨东东; 陈磊; 苏润毅


    目的 探究二尖瓣置换术本身可否引起三尖瓣返流.方法 为了除外肺动脉高压、心功能不全等原因导致的三尖瓣返流,对随访病例进行了挑选.选择标准:术前无肺动脉高压,无心功能不全,无三尖瓣返流;术后无肺部疾患,无心功能减退的28例患者.意在排除除二尖瓣置换之外的其他导致三尖瓣返流的因素,刻意观察二尖瓣置换术本身与三尖瓣返流的关系.结果 选择的这28例患者中,术后均无肺部疾病,心功能较术前相同或较术前有改善.但有3例出现中度返流,10例轻度返流,共计13例,其发生率46%.讨论三尖瓣的返流或与二尖瓣置换有着直接因果关系.%Objective To investigate whether mitral valve replacement can or not lead to tricuspid regurgitation. Methods In order to get rid of the influence of other dieases, like pulmonary hypertension, cardiac dysfunction and so on, we chose 28 patients who were not suffered from these diseases before operation. And then we could easily find the relationship between mitral valve replacement and tricuspid regurgitation. Results Pulmonary diseases were not found in all of the 28 patients and the cardiac function were improved in various degrees at the same time. But tricuspid regurgitation was found in 13 patients (46%) , including 3 moderate and 10 mild regurgitation. Conclusion There is a direct relationship between mitral valve replacement and tricuspid regurgitation.

  17. The long-term impact of the angiotensin-converting enzyme inhibitor trandolapril on mortality and hospital admissions in patients with left ventricular dysfunction after a myocardial infarction: follow-up to 12 years

    Buch, Pernille; Rasmussen, Søren; Abildstrøm, Steen Zabell;


    deaths and hospitalizations until 2002. Mortality was analysed with Cox proportional hazard models and hospitalization with Poisson regression models (models adjusted for observation time). Over 10-12 years of follow-up, a total of 1283 deaths and 9220 hospitalizations were registered. Compared...... congestive heart failure hospitalizations (rate ratio 0.85, 95% CI 0.77-0.93, Pyears has long-term benefits. The beneficial effect on mortality and hospitalization rates is maintained for at least 10-12 years....... (ejection fractionyears. At study closure, all patients were recommended continued ACE-inhibitor use. National registries were used to track...

  18. Effect of Cross-Sex Hormonal Replacement on Antioxidant Enzymes in Rat Retroperitoneal Fat Adipocytes

    Velázquez Espejel, Rodrigo; Cabrera-Orefice, Alfredo; Uribe-Carvajal, Salvador; Pavón, Natalia


    We report the effect of cross-sex hormonal replacement on antioxidant enzymes from rat retroperitoneal fat adipocytes. Eight rats of each gender were assigned to each of the following groups: control groups were intact female or male (F and M, resp.). Experimental groups were ovariectomized F (OvxF), castrated M (CasM), OvxF plus testosterone (OvxF + T), and CasM plus estradiol (CasM + E2) groups. After sacrifice, retroperitoneal fat was dissected and processed for histology. Adipocytes were isolated and the following enzymatic activities were determined: Cu-Zn superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and glutathione reductase (GR). Also, glutathione (GSH) and lipid peroxidation (LPO) were measured. In OvxF, retroperitoneal fat increased and adipocytes were enlarged, while in CasM rats a decrease in retroperitoneal fat and small adipocytes are observed. The cross-sex hormonal replacement in F rats was associated with larger adipocytes and a further decreased activity of Cu-Zn SOD, CAT, GPx, GST, GR, and GSH, in addition to an increase in LPO. CasM + E2 exhibited the opposite effects showing further activation antioxidant enzymes and decreases in LPO. In conclusion, E2 deficiency favors an increase in retroperitoneal fat and large adipocytes. Cross-sex hormonal replacement in F rats aggravates the condition by inhibiting antioxidant enzymes. PMID:27630756

  19. Effects of long-term testosterone replacement therapy, with a temporary intermission, on glycemic control of nine hypogonadal men with type 1 diabetes mellitus - a series of case reports.

    Saad, Farid; Yassin, Aksam; Almehmadi, Yousef; Doros, Gheorghe; Gooren, Louis


    Type 2 diabetes mellitus (T2DM) is often associated with obesity and subnormal serum testosterone (T) levels. Until 5 years ago there was no indication that men with type 1 diabetes mellitus (T1DM) had subnormal serum T. But recent studies indicate that about 10% of men with T1DM suffer from hypogonadism, as a rule aged men and men with obesity. While hypogonadal men with T2DM benefit from normalization of their serum T, this has not been investigated in men with T1DM. Nine men with T1DM, erectile dysfunction and hypogonadism (total testosterone ≤ 12 nmol/L) received testosterone replacement therapy (TRT). In seven men TRT was intermitted: one man with prostate malignancy and six men because of problems of reimbursement. Incidentally, this provided an opportunity to monitor the effects of withdrawal and of the reinstatement of TRT. In all men, glycemic control (serum glucose and HbA1c), weight, waist circumference, lipid profiles and erectile function improved upon TRT. The seven men whose TRT was intermitted showed a deterioration which improved again upon reinstatement of TRT. The data suggest that aging and obese men with T1DM might have subnormal T levels and that their glycemic control, lipid profiles and erectile function might benefit from TRT.


    Ewa Kułagowska


    Full Text Available The considerable proportion of the elderly, the chronically ill and the disabled in community is an economic and organizational challenge for the state social policy. It requires a large, steadily increasing financing from the public funds and creating an optional care model to fulfill the needs of citizens and guarantee high quality services. Development of the long-term care is one of the problems to be solved. This paper presents: – a long-term care forms, organization and tasks; – a role of long-term care but particularly home longterm care to protect health in Poland; – problems related with home long-term care functioning.

  1. Long-term dynamics simulation: Modeling requirements

    Morched, A.S.; Kar, P.K.; Rogers, G.J.; Morison, G.K. (Ontario Hydro, Toronto, ON (Canada))


    This report details the required performance and modelling capabilities of a computer program intended for the study of the long term dynamics of power systems. Following a general introduction which outlines the need for long term dynamic studies, the modelling requirements for the conduct of such studies is discussed in detail. Particular emphasis is placed on models for system elements not normally modelled in power system stability programs, which will have a significant impact in the long term time frame of minutes to hours following the initiating disturbance. The report concludes with a discussion of the special computational and programming requirements for a long term stability program. 43 refs., 36 figs.

  2. Reconstructing the Phylogenetic History of Long-Term Effective Population Size and Life-History Traits Using Patterns of Amino Acid Replacement in Mitochondrial Genomes of Mammals and Birds

    Nabholz, Benoit; Lartillot, Nicolas


    The nearly neutral theory, which proposes that most mutations are deleterious or close to neutral, predicts that the ratio of nonsynonymous over synonymous substitution rates (dN/dS), and potentially also the ratio of radical over conservative amino acid replacement rates (Kr/Kc), are negatively correlated with effective population size. Previous empirical tests, using life-history traits (LHT) such as body-size or generation-time as proxies for population size, have been consistent with these predictions. This suggests that large-scale phylogenetic reconstructions of dN/dS or Kr/Kc might reveal interesting macroevolutionary patterns in the variation in effective population size among lineages. In this work, we further develop an integrative probabilistic framework for phylogenetic covariance analysis introduced previously, so as to estimate the correlation patterns between dN/dS, Kr/Kc, and three LHT, in mitochondrial genomes of birds and mammals. Kr/Kc displays stronger and more stable correlations with LHT than does dN/dS, which we interpret as a greater robustness of Kr/Kc, compared with dN/dS, the latter being confounded by the high saturation of the synonymous substitution rate in mitochondrial genomes. The correlation of Kr/Kc with LHT was robust when controlling for the potentially confounding effects of nucleotide compositional variation between taxa. The positive correlation of the mitochondrial Kr/Kc with LHT is compatible with previous reports, and with a nearly neutral interpretation, although alternative explanations are also possible. The Kr/Kc model was finally used for reconstructing life-history evolution in birds and mammals. This analysis suggests a fairly large-bodied ancestor in both groups. In birds, life-history evolution seems to have occurred mainly through size reduction in Neoavian birds, whereas in placental mammals, body mass evolution shows disparate trends across subclades. Altogether, our work represents a further step toward a more

  3. Long-term efficacy of replanlation vesus prosthetic replacement for complex severed lower legs%复杂小腿离断伤再植与假肢治疗远期疗效分析

    夏志刚; 喻爱喜; 漆白文; 祝少博


    目的 探讨复杂小腿离断伤再植与截肢的指征.方法 25例复杂小腿离断伤患者,再植15例,截肢10例.再植病例在肢体存活后对术后出现的软组织缺损、骨缺损、肢体短缩等并发症以显微外科方法并肢体延长术进行修复.截肢病例在创面愈合后行小腿假肢治疗.结果 术后随访3~10年(平均6.4年),再植15例中肢体存活11例,4例行延期截肢后行假肢治疗,再植成功的患肢有不同程度短缩,参照陈中伟的断肢再植下肢功能评定标准:Ⅰ级1例,Ⅱ级4例,Ⅲ级4例,Ⅳ级2例;假肢治疗14例患肢外观与正常无明显差别,12例可下地负重行走,2例轻度跛行.假肢治疗组患者满意度高于再植组.结论 复杂小腿离断伤是否再植应结合毁损肢体严重程度评分、患肢的局部条件和预后功能情况综合考虑.%Objective To explore indications for replantation and amputation of complex severed lower legs. Methods Fifteen lower legs in 25 cases with complex severed lower limbs were replanted including four finally amputated again, and other 10 legs were amputated directly after trauma. Those with successful replantation were repaired with microsurgical technology and limb lengthening procedure for complications such as soft tissue defect, bone defect and limb shortening. The amputated cases were fitted with prosthetic limb after wound healing. Results All cases were followed-up for three to 10 years (6.4 years in average), and 11 lower legs were survived in 15 replanted cases and other four were finally amputated and fitted with prosthetic replacement. The limbs of those with successfully replantation shortened to varied extent, and one can be categorized as grade Ⅰ, four as grade Ⅱ, four as grade Ⅲ and two as grade Ⅳ, according to Chen's classification of function evaluation for replanted limbs. Appearance of prosthetic limbs in 14 cases had no significant difference from the normal, and 12 of them could walk with


    Stephen P. Farrington; John W. Haas; Neal Van Wyck


    Long-term monitoring (LTM) associated with subsurface contamination sites is a key element of Long Term Stewardship and Legacy Management across the Department of Energy (DOE) complex. However, both within the DOE and elsewhere, LTM is an expensive endeavor, often exceeding the costs of the remediation phase of a clean-up project. The primary contributors to LTM costs are associated with labor. Sample collection, storage, preparation, analysis, and reporting can add a significant financial burden to project expense when extended over many years. Development of unattended, in situ monitoring networks capable of providing quantitative data satisfactory to regulatory concerns has the potential to significantly reduce LTM costs. But survival and dependable operation in a difficult environment is a common obstacle to widespread use across the DOE complex or elsewhere. Deploying almost any sensor in the subsurface for extended periods of time will expose it to chemical and microbial degradation. Over the time-scales required for in situ LTM, even the most advanced sensor systems may be rendered useless. Frequent replacement or servicing (cleaning) of sensors is expensive and labor intensive, offsetting most, if not all, of the cost savings realized with unattended, in situ sensors. To enable facile, remote monitoring of contaminants and other subsurface parameters over prolonged periods, Applied Research Associates, Inc has been working to develop an advanced LTM sensor network consisting of three key elements: (1) an anti-fouling sensor chamber that can accommodate a variety of chemical and physical measurement devices based on electrochemical, optical and other techniques; (2) two rapid, cost effective, and gentle means of emplacing sensor packages either at precise locations directly in the subsurface or in pre-existing monitoring wells; and (3) a web browser-based data acquisition and control system (WebDACS) utilizing field-networked microprocessor-controlled smart

  5. Long-term Effects of Shrub Encroachment and Grazing on Soil Microbial Composition and Function

    Gallery, R. E.; O'Shea, C.; Kwiecien, A.; Predick, K.; Archer, S. R.


    Drylands account for ca. 35% of terrestrial net primary productivity and thus play a significant role in global water and biogeochemical cycles. Replacement of grasses by shrubs has been widespread in these systems and has altered rates of erosion and native plant biodiversity and productivity. The net effect of these changes on biogeochemical cycling is not well understood. Projected warmer and drier conditions may further alter the function and stability of these ecosystems and soil resources through direct effects on soil microbiota and plant-microbe interactions. We quantified microbial community responses to long-term livestock grazing and shrub encroachment in a Sonoran Desert grassland. We sought to characterize tipping points where biotic controls over ecosystem processes shift from being 'grass-driven' to 'shrub-driven.' We asked: How do livestock grazing (the predominant land use in dryland ecosystems) and shrub invasion (a predominant land cover change) interact to influence microbial biomass and the relative abundance of bacteria, archaea, and fungi and their extracellular enzyme activities? Surface soil from bare-ground patches, native and invasive grass rhizospheres, and bole and canopy dripline locations in patches of mature mesquite trees in long-term grazed and long-term (70+ y) protected pastures were collected and analyzed for microbial community composition, biomass, potential exoenzyme activities, and a suite of biogeochemical characteristics. We found no differences in microbial communities or the soils associated with native vs. exotic grasses. Overall, mesquite bole patches differed from other patches in all soil characteristics except potential enzyme activity: soil temperature was significantly lower, and total carbon (C) and soil moisture were significantly higher. Potential activities were lowest for bare ground and highest at shrub dripline patches for all seven exoenzymes tested. Mean potential activities for C and phosphorous (P

  6. Long-term survival after perforated diverticulitis

    J. Vermeulen (Jan); M.P. Gosselink (Martijn Pieter); W.C.J. Hop (Wim); E. van der Harst (Erwin); B.E. Hansen (Bettina); G.H.H. Mannaerts (Guido); P-P. Coene (Peter Paul); W.F. Weidema (Wibo); J.F. Lange (Johan)


    textabstractAim: Short-term survival after emergency surgery for perforated diverticulitis is poor. Less is known about long-term survival. The aims of this study were to evaluate long-term survival after discharge from hospital and to identify factors associated with prognosis. Method: All patients

  7. Virtual Models of Long-Term Care

    Phenice, Lillian A.; Griffore, Robert J.


    Nursing homes, assisted living facilities and home-care organizations, use web sites to describe their services to potential consumers. This virtual ethnographic study developed models representing how potential consumers may understand this information using data from web sites of 69 long-term-care providers. The content of long-term-care web…

  8. Recommendations for initiation and cessation of enzyme replacement therapy in patients with Fabry disease

    Biegstraaten, Marieke; Arngrímsson, Reynir; Barbey, Frederic;


    INTRODUCTION: Fabry disease (FD) is a lysosomal storage disorder resulting in progressive nervous system, kidney and heart disease. Enzyme replacement therapy (ERT) may halt or attenuate disease progression. Since administration is burdensome and expensive, appropriate use is mandatory. We aimed...... to define European consensus recommendations for the initiation and cessation of ERT in patients with FD. METHODS: A Delphi procedure was conducted with an online survey (n = 28) and a meeting (n = 15). Patient organization representatives were present at the meeting to give their views. Recommendations...

  9. Expression and purification of a human, soluble Arylsulfatase A for Metachromatic Leukodystrophy enzyme replacement therapy.

    Martino, Sabata; Consiglio, Antonella; Cavalieri, Cristina; Tiribuzi, Roberto; Costanzi, Egidia; Severini, Giovanni Maria; Emiliani, Carla; Bordignon, Claudio; Orlacchio, Aldo


    The production of active Arylsulfatase A is a key step in the development of enzyme replacement therapy for Metachromatic Leukodystrophy. To obtain large amounts of purified Arylsulfatase A for therapeutic use, we combined a retroviral expression system with a versatile and rapid purification protocol that can easily and reliably be adapted to high-throughput applications. The purification method consists of an initial ion-exchange DEAE-cellulose chromatography step followed by immuno-affinity purification using a polyclonal antibody against a 29-mer peptide of the Arylsulfatase A sequence. Immuno-adsorbed protein was eluted with a combination of acidic pH and an optimal concentration of the 29-mer peptide. This protocol reproducibly yielded approximately 100 microg of >99% pure human Arylsulfatase A, corresponding to 152 mU of enzyme activity, per liter of culture medium with properties similar to those of human non-recombinant protein.

  10. Oral maintenance clinical trial with miglustat for type I Gaucher disease: switch from or combination with intravenous enzyme replacement

    D. Elstein; A. Dweck; D. Attias; I. Hadas-Halpern; S. Zevin; G. Altarescu; J.F.M.G. Aerts; S. van Weely; A. Zimran


    Enzyme replacement therapy (ERT) with imiglucerase reduces hepatosplenomegaly and improves hematologic parameters in Gaucher disease type 1 within 6-24 months. Miglustat reduces organomegaly, improves hematologic parameters, and reverses bone marrow infiltration. This trial evaluates miglustat in pa

  11. The return of the family? Welfare state retrenchment and client autonomy in long-term care

    E. Grootegoed; D. van Dijk


    European welfare states are cutting back their responsibilities for long-term care, emphasising ‘self-reliance’ and replacing care as an entitlement of citizenship with targeted services. But we do not know how former long-term care recipients cope with retrenchment and if they are able to negotiate

  12. Business Students' Choice of Short-Term or Long-Term Study Abroad Opportunities

    Fitzsimmons, Stacey R.; Flanagan, David J.; Wang, Xiaodan


    Recent years have seen a proliferation of short-term study abroad opportunities. Although they are both supplementing and replacing semester-long study abroad programs, research has focused primarily on semester (long-term) programs. We draw on the theory of planned behavior (TPB) to explore factors that predict why students choose long-term and…

  13. Enzyme replacement therapy in late-onset Pompe's disease: a three-year follow-up.

    Winkel, Léon P F; Van den Hout, Johanna M P; Kamphoven, Joep H J; Disseldorp, Janus A M; Remmerswaal, Maaike; Arts, Willem F M; Loonen, M Christa B; Vulto, Arnold G; Van Doorn, Pieter A; De Jong, Gerard; Hop, Wim; Smit, G Peter A; Shapira, Stuart K; Boer, Marijke A; van Diggelen, Otto P; Reuser, Arnold J J; Van der Ploeg, Ans T


    Pompe's disease is an autosomal recessive myopathy. The characteristic lysosomal storage of glycogen is caused by acid alpha-glucosidase deficiency. Patients with late-onset Pompe's disease present with progressive muscle weakness also affecting pulmonary function. In search of a treatment, we investigated the feasibility of enzyme replacement therapy with recombinant human alpha-glucosidase from rabbit milk. Three patients (aged 11, 16, and 32 years) were enrolled in the study. They were all wheelchair-bound and two of them were ventilator dependent with a history of deteriorating pulmonary function. After 3 years of treatment with weekly infusions of alpha-glucosidase, the patients had stabilized pulmonary function and reported less fatigue. The youngest and least affected patient showed an impressive improvement of skeletal muscle strength and function. After 72 weeks of treatment, he could walk without support and finally abandoned his wheelchair. Our findings demonstrate that recombinant human alpha-glucosidase from rabbit milk has a therapeutic effect in late-onset Pompe's disease. There is good reason to continue the development of enzyme replacement therapy for Pompe's disease and to explore further the production of human therapeutic proteins in the milk of mammals.

  14. Long Term Care Minimum Data Set (MDS)

    U.S. Department of Health & Human Services — The Long-Term Care Minimum Data Set (MDS) is a standardized, primary screening and assessment tool of health status that forms the foundation of the comprehensive...

  15. Long Term Care Minimum Data Set (MDS)

    U.S. Department of Health & Human Services — The Long-Term Care Minimum Data Set (MDS) is a standardized, primary screening and assessment tool of health status that forms the foundation of the comprehensive...

  16. Long-Term Care Ombudsman Program

    ... Strategic Plan Federal Initiatives Career Opportunities Contact Us Administration on Aging (AoA) Long-Term Care Ombudsman Program ( ... Prevention HIV/AIDS Nutrition Services Oral Health Elder Justice & Adult Protective Services Elder Justice Coordinating Council Prevention ...

  17. Pituitary diseases : long-term clinical consequences

    Klaauw, Agatha Apolonia van der


    This thesis describes various studies during the long-term follow-up of patients after treatment for pituitary diseases. The focus of this thesis is acromegaly, growth hormone deficiency, sleep and quality of life. Various aspects are described.

  18. Long-term outcome of meniscectomy

    Roos, Ewa M.; Ostenberg, A; Roos, H;


    To describe the long-term influence of meniscectomy on pain, functional limitations, and muscular performance. To assess the effects of radiographic osteoarthritis (OA), gender and age on these outcomes in patients with meniscectomy....

  19. Pituitary diseases : long-term clinical consequences

    Klaauw, Agatha Apolonia van der


    This thesis describes various studies during the long-term follow-up of patients after treatment for pituitary diseases. The focus of this thesis is acromegaly, growth hormone deficiency, sleep and quality of life. Various aspects are described.

  20. Long-term outcomes after severe shock.

    Pratt, Cristina M; Hirshberg, Eliotte L; Jones, Jason P; Kuttler, Kathryn G; Lanspa, Michael J; Wilson, Emily L; Hopkins, Ramona O; Brown, Samuel M


    Severe shock is a life-threatening condition with very high short-term mortality. Whether the long-term outcomes among survivors of severe shock are similar to long-term outcomes of other critical illness survivors is unknown. We therefore sought to assess long-term survival and functional outcomes among 90-day survivors of severe shock and determine whether clinical predictors were associated with outcomes. Seventy-six patients who were alive 90 days after severe shock (received ≥1 μg/kg per minute of norepinephrine equivalent) were eligible for the study. We measured 3-year survival and long-term functional outcomes using the Medical Outcomes Study 36-Item Short-Form Health Survey, the EuroQOL 5-D-3L, the Hospital Anxiety and Depression Scale, the Impact of Event Scale-Revised, and an employment instrument. We also assessed the relationship between in-hospital predictors and long-term outcomes. The mean long-term survival was 5.1 years; 82% (62 of 76) of patients survived, of whom 49 were eligible for follow-up. Patients who died were older than patients who survived. Thirty-six patients completed a telephone interview a mean of 5 years after hospital admission. The patients' Physical Functioning scores were below U.S. population norms (P shock had a high 3-year survival rate. Patients' long-term physical and psychological outcomes were similar to those reported for cohorts of less severely ill intensive care unit survivors. Anxiety and depression were relatively common, but only a few patients had symptoms of posttraumatic stress disorder. This study supports the observation that acute illness severity does not determine long-term outcomes. Even extremely critically ill patients have similar outcomes to general intensive care unit survivor populations.

  1. Anticipating Long-Term Stock Market Volatility

    Conrad, Christian; Loch, Karin


    We investigate the relationship between long-term U.S. stock market risks and the macroeconomic environment using a two component GARCH-MIDAS model. Our results provide strong evidence in favor of counter-cyclical behavior of long-term stock market volatility. Among the various macro variables in our dataset the term spread, housing starts, corporate profits and the unemployment rate have the highest predictive ability for stock market volatility . While the term spread and housing starts are...

  2. First experience with enzyme replacement therapy during pregnancy and lactation in Pompe disease.

    de Vries, Juna M; Brugma, Jan-Dietert C; Ozkan, Lale; Steegers, Eric A P; Reuser, Arnold J J; van Doorn, Pieter A; van der Ploeg, Ans T


    Enzyme replacement therapy (ERT) with alglucosidase alfa was registered as a treatment for Pompe disease in 2006. It is as yet unknown whether ERT can be safely applied during pregnancy and lactation. A primiparous 40-year-old woman diagnosed with Pompe disease continued receiving ERT during pregnancy and lactation. Before pregnancy, she had moderate limb-girdle weakness and used nocturnal ventilation. During pregnancy, her clinical condition remained fairly stable until the 25th gestational week. Thereafter she experienced more problems with mobility and respiration. Fetal growth was normal as monitored by regular ultrasound investigations. A healthy boy was born at a gestational age of 37 weeks and 5 days by elective Cesarean section. There were no maternal complications and the child developed normally. One year after delivery the mother's physical condition was similar as prior to her pregnancy. Pharmacokinetic studies following enzyme infusion showed that alglucosidase alfa was secreted into the breast milk. Activity levels in the milk (245 nmol/ml.h) peaked at 2.5h after the end of the infusion; which was 2h later than in the plasma (80 μmol/ml.h). Twenty-four hours after start of the infusion, the enzyme activity in the breast milk was back to the pre-infusion level. In this case report, the continuation of treatment with alglucosidase alfa during pregnancy and lactation has been safe for the mother and the child.

  3. Towards the development of an enzyme replacement therapy for the metabolic disorder propionic acidemia

    Mahnaz Darvish-Damavandi


    Full Text Available Propionic acidemia (PA is a life-threatening disease caused by the deficiency of a mitochondrial biotin-dependent enzyme known as propionyl coenzyme-A carboxylase (PCC. This enzyme is responsible for degrading the metabolic intermediate, propionyl coenzyme-A (PP-CoA, derived from multiple metabolic pathways. Currently, except for drastic surgical and dietary intervention that can only provide partial symptomatic relief, no other form of therapeutic option is available for this genetic disorder. Here, we examine a novel approach in protein delivery by specifically targeting and localizing our protein candidate of interest into the mitochondrial matrix of the cells. In order to test this concept of delivery, we have utilized cell penetrating peptides (CPPs and mitochondria targeting sequences (MTS to form specific fusion PCC protein, capable of translocating and localizing across cell membranes. In vitro delivery of our candidate fusion proteins, evaluated by confocal images and enzymatic activity assay, indicated effectiveness of this strategy. Therefore, it holds immense potential in creating a new paradigm in site-specific protein delivery and enzyme replacement therapeutic for PA.

  4. Protein synthesis and antioxidant capacity in aging mice: effects of long-term voluntary exercise.

    Vaanholt, Lobke M; Speakman, John R; Garland, Theodore; Lobley, Gerald E; Visser, G Henk


    Exercise increases metabolic rate and the production of reactive oxygen species (ROS) but also elevates protein turnover. ROS cause damage to macromolecules (e.g., proteins) and thereby contribute to aging. Protein turnover removes and replaces damaged proteins. The balance between these two responses may underlie beneficial effects of physical activity on aging. Effects of lifelong exercise on antioxidant enzyme activities and fractional synthesis rate of protein (FSRP) were examined at various ages (2-26 mo) in heart, liver, and muscle of mice that had been selectively bred for high wheel-running activity, housed with (S+) or without (S-) a running wheel, and their random-bred controls (C+) housed with running wheels. FSRP decreased with age and increased in muscle of young, but not old, activity-selected mice. Enzyme activity of superoxide dismutase and glutathione peroxidase decreased with age and showed a peak at 10 mo of age in liver. Selection for wheel-running activity did not affect antioxidant enzyme activity. Daily energy expenditure correlated positively with antioxidant levels in liver. This might indicate that oxidative stress (ROS production) increases with metabolic rate, driving upregulation of antioxidant enzymes. Alternatively, the elevated energy expenditure may reflect the energetic cost of elevated protection, consistent with the disposable-soma hypothesis and with other studies showing positive links between energy expenditure and life span. Long-term elevations in voluntary exercise did not result in elevations in antioxidant enzyme activities or protein synthesis rates.

  5. Preventive Long-Term Effects of a Topical Film-Forming Medical Device with Ultra-High UV Protection Filters and DNA Repair Enzyme in Xeroderma Pigmentosum: A Retrospective Study of Eight Cases

    Sandra Giustini


    Full Text Available Skin cancer is common in xeroderma pigmentosum (XP due to a DNA repair mechanisms genetic defect. Ultraviolet (UV exposure is the main cause of increased incidence of actinic keratosis (AK, basal cell carcinoma (BCC and squamous cell carcinoma (SCC observed in XP subjects. Photoprotection is therefore a mandatory strategy in order to reduce skin damage. A topical DNA repair enzyme has been shown to slow down the development of skin lesions in XP. However, there are no data regarding the effects of photoprotection combined with DNA repair strategies in this clinical setting. A film-forming medical device containing the DNA repair enzyme photolyase and very high-protection UV filters (Eryfotona AK-NMSC, Ery is currently available. We report retrospective data regarding the use of Ery in 8 patients (5 women, 3 men with a diagnosis of XP treated for at least 12 consecutive months, comparing the rate of new skin lesions (AK, BCC and SCC during active treatment with Ery and during 12 months just before the use of the product. New AK, BCC and SCC mean lesion numbers during the 1-year Ery treatment were 5, 3 and 0, respectively in comparison with 14, 6.8 and 3 lesions, respectively during the 1-year pre-treatment period. Ery use was associated with a 65% reduction in appearance of new AK lesions and with 56 and 100% reductions in the incidence of new BCC and SCC lesions, respectively. These data suggest that topical use of photoprotection and DNA repair enzyme could help lower skin cancer lesions in XP. Control prospective trials are advisable in this clinical setting.

  6. 中-重度功能性三尖瓣关闭不全瓣膜置换与成形手术近远期效果的比较研究%Immediate and long-term outcomes of tricuspid valve replacement versus repair for functional tricuspid regurgitation

    苏洁; 程蕊; 张金洲; 刘金成; 王红兵; 程亮; 支伟伟


    Objective Functional tricuspid regurgitation ( FTR) is very common in patients with rheumatic heart valve diseases. For moderate and( or) severe FTR,although heart valve replacement and repair procedures both can correct this heart valve disorder,it remains unclear which one can bring more benefits to patients with FTR. We aimed to examine the immediate and long term outcomes of FTR patients retrospectively. Methods From November, 1998 to December,2009,68 patients admitted to our hospital and underwent tricuspid valve replacement or repair operation, of which 45 patients underwent anuloplasty procedure and 23 patients underwent tricuspid valve replacement. We compared clinical data of these patients retrospectively. Results The average age of patients in repair group were greater than those in replacement group [ ( 43. 7 ± 22. 3 ) years vs. ( 45. 9 ±21.3) years, P = 0. 035 ]. The grade of tricuspid regurgitation in replacement group was much more severer than that in repair group [ (21. 9 ±35. 4)ml vs. ( 19. 8 ±24. 5)ml,P <0. 001 ]. The average time required for aorta clamping,cardiopulmonary bypass in replacement group were much longer than that in repair group [ ( 152. 0 ± 52. 0) min vs. ( 122. 6 ± 57. 6) min, (86. 6 ±20. 6) min vs. (81.5 ± 33. 5) min,P < 0. 001 ,respectively]. Early after surgery, the usage of inotropic agents in replacement group were much more than that in repair group, consequently, the staying time of ICU in replacement group was much longer than that in repair group [ ( 97. 2 ± 75. 3 ) h vs. ( 83. 7 ± 47. 5 ) h, P < 0. 001 ].Although the postoperative complication morbidity showed no difference between these two groups ( 30.4% vs. 17. 8% ,P =0. 234) , the mortality in replacement group was much higher than that in repair group (30. 4% vs. 11. 1% ,P =0. 048) . The follow up time ranged from 17 months to 10 years. The rates of follow-up were 93. 8% and 97. 5% in replacement and repair group respectively. The total rate of recurrence

  7. Replacement

    S. Radhakrishnan


    Full Text Available The fishmeal replaced with Spirulina platensis, Chlorella vulgaris and Azolla pinnata and the formulated diet fed to Macrobrachium rosenbergii postlarvae to assess the enhancement ability of non-enzymatic antioxidants (vitamin C and E, enzymatic antioxidants (superoxide dismutase (SOD and catalase (CAT and lipid peroxidation (LPx were analysed. In the present study, the S. platensis, C. vulgaris and A. pinnata inclusion diet fed groups had significant (P < 0.05 improvement in the levels of vitamins C and E in the hepatopancreas and muscle tissue. Among all the diets, the replacement materials in 50% incorporated feed fed groups showed better performance when compared with the control group in non-enzymatic antioxidant activity. The 50% fishmeal replacement (best performance diet fed groups taken for enzymatic antioxidant study, in SOD, CAT and LPx showed no significant increases when compared with the control group. Hence, the present results revealed that the formulated feed enhanced the vitamins C and E, the result of decreased level of enzymatic antioxidants (SOD, CAT and LPx revealed that these feeds are non-toxic and do not produce any stress to postlarvae. These ingredients can be used as an alternative protein source for sustainable Macrobrachium culture.

  8. European consensus for starting and stopping enzyme replacement therapy in adult patients with Pompe disease

    van der Ploeg, Ans T.; Kruijshaar, Michelle E.; Toscano, A.


    synthesis is presented. RESULTS: Consensus was reached on how the diagnosis of Pompe disease should be confirmed, when treatment should be started, reasons for stopping treatment and the use of ERT during pregnancy. This was based on expert opinion and supported by the literature. One clinical trial and 43......BACKGROUND AND PURPOSE: Pompe disease is a rare inheritable muscle disorder for which enzyme replacement therapy (ERT) has been available since 2006. Uniform criteria for starting and stopping ERT in adult patients were developed and reported here. METHODS: Three consensus meetings were organized...... through the European Pompe Consortium, a network of experts from 11 European countries in the field of Pompe disease. A systematic review of the literature was undertaken to determine the effectiveness of ERT in adult patients on a range of clinical outcome measures and quality of life. A narrative...

  9. Soil enzyme activities under long-term tillage and crop rotation systems in subtropical agro-ecosystems Atividade enzimática em solo sob plantio direto e rotações de culturas em agro-ecossistema subtropical

    Elcio Liborio Balota


    Full Text Available Agricultural practices that reduce soil degradation and improve agricultural sustainability are needed particularly for tropical/subtropical soils. No-tillage planting causes minimal soil disturbance and combined with crop rotation may hold potential to meet these goals. Soil enzyme activities can provide information on how soil management is affecting the potential to perform the processes in soils such as decomposition and nutrient cycling. Soil enzyme activities were investigated in a split-plot experiment (3 replications where tillage (no till and conventional was the main plot and crop rotation (soybean/wheat, S/W; maize/wheat, M/W or cotton/wheat, C/W was the subplot. The experiment was established in 1976 in southern Brazil. Soil samples were taken at 0-5, 5-10 and 10-20 cm depths in 1997 and 1998. The 0-5 cm layer under NT system showed increases up 68% for amylase, 90% for cellulase, 219% for arylsulfatase, 46% for acid phosphatase, and 61% for alkaline phosphatase. There were significant correlations of soil enzyme activities with total organic C, and C and N microbial biomass. These results showed that NT increased microbial activity and that soil enzyme activity is a sensitive indicator of alteration soil quality by management.Práticas agrícolas que reduzam a degradação do solo e promovam sustentabilidade são importantes para os agrossistemas tropicais/subtropicais. O plantio direto (PD diminui as perdas de solo e, se combinado com rotação de culturas pode proteger o solo da degradação físico-química provocada pela agricultura intensiva. A atividade enzimática do solo pode fornecer importantes informações de como o manejo do solo está afetando a decomposição da material orgânica e a ciclagem dos nutrientes. Assim, avaliou-se a atividade das enzimas amilase, celulose, arilsulfatase, fosfatase ácida e fosfatase alcalina em um experimento a campo, instalado em 1976 em Londrina, PR, que tem como tratamentos o preparo

  10. Long-term follow-up study and long-term care of childhood cancer survivors

    Hyeon Jin Park


    Full Text Available The number of long-term survivors is increasing in the western countries due to remarkable improvements in the treatment of childhood cancer. The long-term complications of childhood cancer survivors in these countries were brought to light by the childhood cancer survivor studies. In Korea, the 5-year survival rate of childhood cancer patients is approaching 70%; therefore, it is extremely important to undertake similar long-term follow-up studies and comprehensive long-term care for our population. On the basis of the experiences of childhood cancer survivorship care of the western countries and the current Korean status of childhood cancer survivors, long-term follow-up study and long-term care systems need to be established in Korea in the near future. This system might contribute to the improvement of the quality of life of childhood cancer survivors through effective intervention strategies.

  11. Long-term fasting in the anadromous Arctic charr is associated with downregulation of metabolic enzyme activity and upregulation of leptin A1 and SOCS expression in the liver.

    Jørgensen, Even Hjalmar; Martinsen, Mads; Strøm, Vidar; Hansen, Kristin Elisa Ruud; Ravuri, Chandra Sekhar; Gong, Ningping; Jobling, Malcolm


    The life strategy of the anadromous Arctic charr (Salvelinus alpinus) includes several months of voluntary fasting during overwintering in freshwater, leading to emaciation prior to seawater migration in spring. In this study we compared changes in condition, substrate utilization and liver metabolism between captive anadromous charr subjected to food deprivation during late winter and spring, and conspecifics fed in excess. In March, nine out of the 10 sampled fed fish had not eaten, indicating that they were in a voluntary anorexic state. In June, the fed fish were eating and all had higher body mass, condition factor and adiposity than in March. In fasted fish there were only small decreases in body mass, condition factor and adiposity between March and May, but all these parameters decreased markedly from May to June. The fasted fish were depleted in fat and glycogen in June, had suppressed activity of hepatic enzymes involved in lipid metabolism (G6PDH and HOAD) and seemed to rely on protein-derived glucose as a major energy source. This was associated with upregulated liver gene expression of leptin A1, leptin A2, SOCS1, SOCS2 and SOCS3, and reduced IGF-I expression. In an in vitro study with liver slices it was shown that recombinant rainbow trout leptin stimulated SOCS1 and SOCS3 expression, but not SOCS2, IGF-I or genes of enzymes involved in lipid (G6PDH) and amino acid (AspAT) metabolism. It is concluded that liver leptin interacts with SOCS in a paracrine fashion to suppress lipolytic pathways and depress metabolism when fat stores are depleted.

  12. Long-term Multiwavelength Observations of Polars

    Santana, Joshua; Mason, Paul A.


    Polars are cataclysmic variables with the highest magnetic field strengths (10-250 MG). Matter is accreted after being funneled by the strong magnetic field of the white dwarf. We perform a meta-study of multi-wavelength data of polars. Many polars have been observed in surveys, such as SDSS, 2MASS, ROSAT, just to name a few. Some polars have now been detected by the JVLA, part of an expanding class of radio CVs. A large subset of polars have long-term optical light curves from CRTS and AAVSO. We suggest that the long term light curves of polars display a variety of signature behaviors and may be grouped accordingly. Additional characteristics such a binary period, magnetic field strengths, X-ray properties, and distance estimates are examined in context with long-term observations.

  13. Risk factors for the long-term prognosis of patients undergoing heart valve replacement and coronary artery bypass grafting%心瓣膜置换术同期行冠状动脉旁路移植术患者长期预后的危险因素探讨



    Objective To investigate the risk factors for the long-term prognosis of patients undergoing heart valve replacement ( HVR ) and coronary artery bypass grafting ( CABG). Methods Fifty-seven patients who underwent HVR combined with CABG in our center were selected as the study objects, CABG combined with aortic operation were performed in 13 cases,CABG combined with double valve replacement were performed in 16 cases and CABG combined with mitral surgery were peformed in 28 cases; The mean number of the graft vessels was ( 1. 97 ?1. 36 ). The follow-up data were collected. Cox proportional hazard model was used to perform the univariate and multivariate analysis of risk factors. Results Fifty-five patients were followed up with the mean time of(57. 37 ?13. 98)months. Two patients were out of follow-up and 7 patients died; Cox proportional hazard model revealed that age > 70 years, pre-existing diabetes,history of myocardical infarction,chronic lung diseases,previous infarction,and left ventricular e-jection fraction (LVEF) =S40% were the independent risk factors for the long-term prognosis in patients undergoing HVR combined with CABG. Conclusion Age, pre-existing diabetes, history of myocardical infarction, chronic lung diseases,previous infarction,and LVEF<40% were the risk factors for the long-term prognosis in patients undergoing HVR combined with CABG.%目的 探讨影响心瓣膜置换术同期行冠状动脉旁路移植术(CABG)患者长期预后的危险因素.方法 57例同期行心脏瓣膜置换术和冠状动脉旁路移植术的患者,同行CABG和主动脉手术13例,同行CABG和双瓣膜手术16例,同行CABG和二尖瓣手术28例;移植血管(1.97±1.36)支.通过随访获取数据,对潜在危险因素先用Cox比例风险模型进行单变量分析,再将有统计学意义(P<0.05)的危险因素纳入Cox多变量回归.结果 失访2例,随访55例,平均随访时间(57.37±13.98)个月,随访期间共7例死亡;高龄(年龄>70岁)、

  14. Development of nanoparticle-bound arylsulfatase B for enzyme replacement therapy of mucopolysaccharidosis VI.

    Mühlstein, A; Gelperina, S; Kreuter, J


    Lysosomal storage disorders like mucopolysaccharidosis (MPS) VI are rare diseases with a lack of well-suited treatments. Even though an enzyme replacement therapy (ERT) of recombinant arylsulfatase B (ASB) is available for MPS VI, the administration cannot positively affect the neurologic manifestations such as spinal cord compression. Since nanoparticles (NP) have shown to be effective drug carriers, the feasibility of arylsulfatase B adsorption onto poly(butyl cyanoacrylate) (PBCA) nanoparticles was investigated in this study. In order to advance the ERT of ASB, the adsorption of the latter on the surface of PBCA NP as well as in vitro release in serum was investigated. With alteration of parameters like temperature, incubation time, pH, and enzyme amount, the adsorption process revealed to be stable with a maximum capacity of 67 microg/mg NP at a pH of 6.3. In vitro release experiments demonstrated that the adsorption is stable for at least 60 minutes in human blood serum, indicating that the ASB-loaded PBCA nanoparticles represent a promising candidate for ERT of MPS VI.

  15. Morphological changes in muscle tissue of patients with infantile Pompe's disease receiving enzyme replacement therapy.

    Winkel, Léon P F; Kamphoven, Joep H J; van den Hout, Hannerieke J M P; Severijnen, Lies A; van Doorn, Pieter A; Reuser, Arnold J J; van der Ploeg, Ans T


    Pompe's disease (glycogen storage disease type II) is an autosomal recessive myopathy caused by lysosomal alpha-glucosidase deficiency. Enzyme replacement therapy (ERT) is currently under development for this disease. We evaluated the morphological changes in muscle tissue of four children with infantile Pompe's disease who received recombinant human alpha-glucosidase from rabbit milk for 72 weeks. The patients were 2.5-8 months of age at entry. Prior to treatment, all patients showed lysosomal glycogen storage in skeletal and smooth muscle cells, vascular endothelium, Schwann cells, and perineurium. The first response to treatment was noticed in vascular endothelium and in peripheral nerves after 12 weeks of treatment at an enzyme dose of 15-20 mg/kg. Increasing the dose to 40 mg/kg led, after 72 weeks of treatment, to a reduction of glycogen storage and substantial improvement of muscle architecture in the least affected patient. Not all patients responded equally well, possibly due to differences in degree of glycogen storage and concomitant muscle pathology at the start of treatment. We conclude that intravenous administration of recombinant human alpha-glucosidase from rabbit milk can improve muscle morphology in classic infantile Pompe's disease when treatment is started before irreversible damage has occurred.

  16. [Neuropathic Gaucher disease treated with long enzyme replacement therapy. Two clinical cases].

    Correa, Cecilia


    Gaucher disease (GD) is the most common of all inherited lipid storage diseases. It is an autosomal recessive disorder portraying catabolism and cerebroside deposit in the lysosomes, which is due to a lack of glucocerebrosidase enzyme. Though GD shows a panethnic pattern of presentation, it particularly affects the Ashkenazi Jewish population. Several mutations have been defined among GD patients, and some genotypes related to neurologic affection have been described (L444P--most common mutation for neuropathic GD--188S, V394L and G377S). Lipid material storage or deposit exerts multiorganic affection. Enzyme replacement therapy (ERT) has demonstrable efficacy in reversing organic damage related to GD, though its capability to stop neurologic affection is currently under controversy and particular research. This paper portrays two GD cases of Mexican children treated with ERT at general zone hospitals of the Instituto Mexicano del Seguro Social in recent years, both of them depicting characteristic type 3 GD mutations, and comparing their clinical evolution with and without neurological features.

  17. Long-term home care scheduling

    Gamst, Mette; Jensen, Thomas Sejr

    In several countries, home care is provided for certain citizens living at home. The long-term home care scheduling problem is to generate work plans spanning several days such that a high quality of service is maintained and the overall cost is kept as low as possible. A solution to the problem...... provides detailed information on visits and visit times for each employee on each of the covered days. We propose a branch-and-price algorithm for the long-term home care scheduling problem. The pricing problem generates one-day plans for an employee, and the master problem merges the plans with respect...

  18. [Fetal pain: immediate and long term consequences].

    Houfflin Debarge, Véronique; Dutriez, Isabelle; Pusniak, Benoit; Delarue, Eléonore; Storme, Laurent


    Several situations are potentially painful for fetuses, such as malformations and invasive procedures. Nociceptive pathways are known to be functional at 26 weeks. Even if it is not possible to evaluate the fetal experience of pain, it is essential to examine its immediate and long-term consequences. As early as the beginning of the second trimester, hemodynamic and hormonal responses are observed following fetal nociceptive stimulation, In experimental studies, long-term changes have been noted in the corticotrop axis, subsequent responses to pain, and behavior after perinatal nociceptive stimulation.

  19. Keratoprosthesis: a long-term review.

    Barnham, J J; Roper-Hall, M J


    A keratoprosthesis (KP), is an artificial cornea which is inserted into an opacified cornea in an attempt to restore useful vision or, less commonly, to make the eye comfortable in painful keratopathy. Results o a retrospective study of 35 patients, with 55 KP insertions, are reviewed with regard to visual acuity, length of time vision is maintained, retention time, and complication. Overall there were a number of long-term real successes, eith retention of the KP and maintenance of improved vision in eyes not amenable to conventional treatment. Careful long-term follow-up was needed, with further surgical procedures often being necessary.

  20. Consequences of long-term hyperparathyroidism

    Graal, M B; Wolffenbuttel, B H


    We describe a young woman with long-term untreated hyperparathyroidism with a superimposed vitamin D deficiency and an extremely decreased bone mineral density that was complicated by a vertebral fracture. Despite pretreatment with intravenous pamidronate and short-term vitamin D supplementation, se

  1. Long-term prevention of diabetic nephropathy

    Schjoedt, K J; Hansen, H P; Tarnow, L


    AIMS/HYPOTHESIS: In type 1 diabetic patients with microalbuminuria not receiving antihypertensive treatment, an increase in urinary AER (UAER) of 6-14%/year and a risk of developing diabetic nephropathy (DN) of 3-30%/year have been reported. We audited the long-term effect of blocking the renin-a...

  2. Long Term Transfer Effect of Metaphoric Allusion.

    Hayes, David A.; Mateja, John A.

    A study was conducted to investigate the long term transfer effect of metaphoric allusion used to clarify unfamiliar subject matter. Forty-nine high school students were given unfamiliar prose materials variously augmented by metaphoric allusion. The subjects' immediate performance on a transfer task was compared to their performance on an…

  3. Long-Term Memory and Learning

    Crossland, John


    The English National Curriculum Programmes of Study emphasise the importance of knowledge, understanding and skills, and teachers are well versed in structuring learning in those terms. Research outcomes into how long-term memory is stored and retrieved provide support for structuring learning in this way. Four further messages are added to the…

  4. Long-Term Stability of Social Participation

    Hyyppa, Markku T.; Maki, Juhani; Alanen, Erkki; Impivaara, Olli; Aromaa, Arpo


    The long-term stability of social participation was investigated in a representative urban population of 415 men and 579 women who had taken part in the nationwide Mini-Finland Health Survey in the years 1978-1980 and were re-examined 20 years later. Stability was assessed by means of the following tracking coefficients: kappa, proportion of…

  5. The long term characteristics of greenschist

    Jang, Bo-An


    The greenschist in the Jinping II Hydropower Station in southwest China exhibits continuous creep behaviour because of the geological conditions in the region. This phenomenon illustrates the time-dependent deformation and progressive damage that occurs after excavation. In this study, the responses of greenschist to stress over time were determined in a series of laboratory tests on samples collected from the access tunnel walls at the construction site. The results showed that the greenschist presented time-dependent behaviour under long-term loading. The samples generally experienced two stages: transient creep and steady creep, but no accelerating creep. The periods of transient creep and steady creep increased with increasing stress levels. The long-term strength of the greenschist was identified based on the variation of creep strain and creep rate. The ratio of long-term strength to conventional strength was around 80% and did not vary much with confining pressures. A quantitative method for predicting the failure period of greenschist, based on analysis of the stress-strain curve, is presented and implemented. At a confining pressure of 40 MPa, greenschist was predicted to fail in 5000 days under a stress of 290 MPa and to fail in 85 days under the stress of 320 MPa, indicating that the long-term strength identified by the creep rate and creep strain is a reliable estimate.

  6. Pituitary diseases : long-term psychological consequences

    Tiemensma, Jitske


    Nowadays, pituitary adenomas can be appropriately treated, but patients continue to report impaired quality of life (QoL) despite long-term remission or cure. In patients with Cushing’s disease, Cushing’s syndrome or acromegaly, doctors should be aware of subtle cognitive impairments and the

  7. Analysis of mid-long term clinical efficacy and complications of Bryan artificial cervical disc replacement%Bryan人工颈椎椎间盘置换术后中长期临床疗效及相关问题分析

    蒋涛; 任先军; 王卫东; 初同伟; 李长青


    目的 探讨Bryan人工颈椎椎间盘置换术(artificial cervical disc replacement,ACDR)治疗颈椎椎间盘突出症的中长期临床疗效及并发症发生情况.方法 回顾分析13例颈椎椎间盘突出症患者,采用Bryan ACDR治疗,单节段11例,双节段2例,共置换了15个节段.术后定期随访,依照Odom评级和日本骨科学会(Japanese Orthopaedic Association,JOA)评分评定临床疗效和神经功能改善情况,通过影像学资料观察假体位移、假体周围骨吸收、异位骨化、假体活动度及颈椎生理曲度变化.结果 经过5年以上的随访,患者神经症状有明显缓解,Odom评级临床优良率达到92.3%,JOA评分由术前的11.6分增加到的15.6分.术后X线片示假体稳定,没有出现假体前后位移>2mm.术后1例出现自发性融合;1例在置换节段上位椎体前下缘有明显骨吸收,接近2.5mm,并伴椎体后缘的异位骨化.末次随访时置换假体活动度平均为9.2°,邻近节段活动度与术前相当.结论 通过5~7年的中长期随访,Bryan ACDR术治疗颈椎椎间盘突出症具有较好的临床疗效,并发症少,安全可靠.%Objective To evaluate the mid-long term clinical efficacy and complications of Bryan artificial cervical arthro-plasty replacement (ACDR) for treatment of cervical disc herniation. Methods Thirteen cases of cervical disc herniation were retrospectively analyzed. A total of 15 sets of Bryan cervical disc prosthesis were implanted into 13 cases, including single level disc replacement in 11 cases and bi-level in 2 cases. During follow-up, the clinical efficacy and neurological function were evaluated by Odom's criteria and Japanese Orthopaedic Association (JOA)score; the mobility, resorption, heteropic ossification, physiological lordosis and range of motion of the implanted and adjacent segment were observed on dynamic radiograph. Results After more than 5 years of follow-up, all cases showed significant improvement in neurological

  8. Long-Term Monitoring Research Needs: A DOE Perspective

    Moore, B.; Davis, C. B.


    The U.S. Department of Energy's Office of Environmental Management is responsible for dealing with the nation's legacy of Cold War radioactive and hazardous waste and contamination. Major efforts are underway to deal with this legacy; these are expected to last up to decades and cost up to billions of dollars at some sites. At all sites, however, active remediation must eventually cease; if hazards then remain, the site must enter into a long-term stewardship mode. In this talk we discuss aspects of long-term monitoring pertinent to DOE sites, focusing on challenges to be faced, specific goals or targets to be met, and research needs to be addressed in order to enable DOE to meet its long-term stewardship obligations. DOE LTM research needs fall into three major categories: doing what we can do now much more efficiently; doing things we cannot do now; and proving the validity of our monitoring programs. Given the enormity of the DOE obligations, it will be highly desirable to develop much more efficient monitoring paradigms. Doing so will demand developing autonomous, remote monitoring networks of in situ sensors capable of replacing (or at least supplementing to a large extent) conventional groundwater and soil gas sampling and analysis programs. The challenges involved range from basic science (e.g., inventing in situ sensors for TCE that do not demand routine maintenance) to engineering (attaining superior reliability in data reporting in remote networks) to ergonomics (developing decent ways of selecting and presenting the "right" information from the monitoring network) to regulatory affairs (presenting convincing evidence that the more efficient systems actually provide superior monitoring). We explore these challenges in some detail, focusing on the "long" in long-term monitoring as it applies to DOE sites. Monitoring system performance validation and, ultimately, regulator and stakeholder acceptance of site closure and long-term stewardship plans depend

  9. Effects of Long-term Fertilization on Enzyme Activities and Soil Fertility for Black Farmlands Under Different Soil Matter Levels%长期施肥对不同有机质含量农田黑土土壤酶活性及土壤肥力的影响

    陈文婷; 付岩梅; 隋跃宇; 刘晓冰; 李建维


    The research investigated the effects of long-term fertilization on soil enzyme activities and soil fertility for the black farmlands under different soil organic matter levels. This study used the conventional analysis methods to test and analyze the activity of soil urease, phosphatase, invertase, protease and the contents of soil organic matter, total nitrogen, total phosphorus, available nitrogen, available phosphorus in five black farmlands soil with different soil matter content of soil spatial shift long-term experiments in National Observation Station of Hailun Agro-ecology System. The results showed that, the application of chemical fertilizers could increase the nutrient content in different degree and soil enzyme activities of black soil. The order of the raise was Bei'an (SOM11)>Nenjiang (SOM6)>Helen (SOM5)>Dehui (SOM3) > Lishu (SOM1.7). Compared to other four soils, Bei'an (SOM11) reached significant difference level(P嫩江(SOM6)>海伦(SOM5)>德惠(SOM3)>梨树(SOM1.7),北安黑土与其他4种土壤之间达到了差异显著水平(P<0.05)。相关分析结果显示:土壤脲酶、磷酸酶、蛋白酶、蔗糖酶与土壤有机质、全氮、全磷、碱解氮显著相关,土壤脲酶、蔗糖酶可以反映不同有机质含量农田黑土长期施肥后土壤质量变化趋势。

  10. Impact of enzyme replacement therapy and hematopoietic stem cell transplantation in patients with Morquio A syndrome

    Tomatsu S


    -targeting moiety. The tagged enzyme remained in the circulation much longer than untagged native enzyme and was delivered to and retained in bone. Three-month-old MPS IVA mice treated with 23 weekly infusions of tagged enzyme showed marked clearance of the storage materials in bone, bone marrow, and heart valves. When treatment was initiated at birth, reduction of storage materials in tissues was even greater. These findings indicate that specific targeting of the enzyme to bone at an early stage may improve efficacy of ERT for MPS IVA. Recombinant N-acetylgalactosamine-6-sulfate sulfatase (GALNS in Escherichia coli BL21 (DE3 (erGALNS and in the methylotrophic yeast Pichia pastoris (prGALNS has been produced as an alternative to the conventional production in Chinese hamster ovary cells. Recombinant GALNS produced in microorganisms may help to reduce the high cost of ERT and the introduction of modifications to enhance targeting. Although only a limited number of patients with MPS IVA have been treated with hematopoietic stem cell transplantation (HSCT, beneficial effects have been reported. A wheelchair-bound patient with a severe form of MPS IVA was treated with HSCT at 15 years of age and followed up for 10 years. Radiographs showed that the figures of major and minor trochanter appeared. Loud snoring and apnea disappeared. In all, 1 year after bone marrow transplantation, bone mineral density at L2–L4 was increased from 0.372 g/cm2 to 0.548 g/cm2 and was maintained at a level of 0.48±0.054 for the following 9 years. Pulmonary vital capacity increased approximately 20% from a baseline of 1.08 L to around 1.31 L over the first 2 years and was maintained thereafter. Activity of daily living was improved similar to the normal control group. After bilateral osteotomies, a patient can walk over 400 m using hip–knee–ankle–foot orthoses. This long-term observation of a patient shows that this treatment can produce clinical improvements although bone deformity remained

  11. Enzyme replacement therapy for Fabry disease: some answers but more questions

    Majid Alfadhel


    Full Text Available Majid Alfadhel1, Sandra Sirrs21Division of Biochemical Diseases, Department of Paediatrics, BC Children’s and Women’s Hospital, University of British Columbia, Vancouver, BC, Canada; 2Adult Metabolic Diseases Clinic, Division of Endocrinology, Department of Medicine, Vancouver Hospital and Health Sciences Centre, University of British Columbia, Vancouver, BC, CanadaAbstract: Fabry disease (FD is a multisystem, X-linked disorder of glycosphingolipid metabolism caused by enzyme deficiency of α-galactosidase A. Affected patients have symptoms including acroparesthesias, angiokeratomas, and hypohidrosis. More serious manifestations include debilitating pain and gastrointestinal symptoms, proteinuria and gradual deterioration of renal function leading to end-stage renal disease, hypertrophic cardiomyopathy, and stroke. Heterozygous females may have symptoms as severe as males with the classic phenotype. Before 2001, treatment of patients with FD was supportive. The successful development of enzyme replacement therapy (ERT has been a great advancement in the treatment of patients with FD and can stabilize renal function and cardiac size, as well as improve pain and quality of life of patients with FD. In this review, we have provided a critical appraisal of the literature on the effects of ERT for FD. This analysis shows that data available on the treatment of FD are often derived from studies which are not controlled, rely on surrogate markers, and are of insufficient power to detect differences on hard clinical endpoints. Further studies of higher quality are needed to answer the questions that remain concerning the efficacy of ERT for FD.Keywords: Fabry disease, agalsidase α, agalsidase β, Replagal, Fabrazyme, critical appraisal, evidence-based medicine

  12. Structure-based chemical modification strategy for enzyme replacement treatment of phenylketonuria.

    Wang, Lin; Gamez, Alejandra; Sarkissian, Christineh N; Straub, Mary; Patch, Marianne G; Han, Gye Won; Striepeke, Steve; Fitzpatrick, Paul; Scriver, Charles R; Stevens, Raymond C


    Structure-based protein engineering coupled with chemical modifications (e.g., pegylation) is a powerful combination to significantly improve the development of proteins as therapeutic agents. As a test case, phenylalanine ammonia-lyase (PAL, EC was selected for enzyme replacement therapy in phenylketonuria [C.R. Scriver, S. Kaufman, Hyperphenylalaninemia:phenylalanine Hydroxylase Deficiency. The Metabolic and Molecular Bases of Inherited Disease, McGraw-Hill, New York, 2001, Chapter 77], an inherited metabolic disorder (OMIM 261600) causing mental retardation due to deficiency of the enzyme l-phenylalanine hydroxylase (EC Previous in vivo studies of recombinant PAL demonstrated a lowering of blood l-phenylalanine levels; yet, the metabolic effect was not sustained due to protein degradation and immunogenicity [C.N. Sarkissian, Z. Shao, F. Blain, R. Peevers, H. Su, R. Heft, T.M. Chang, C.R. Scriver, A different approach to treatment of phenylketonuria:phenylalanine degradation with recombinant phenylalanine ammonia lyase, Proc. Natl. Acad. Sci. USA 96 (1999) 2339; J.A. Hoskins, G. Jack, H.E. Wade, R.J. Peiris, E.C. Wright, D.J. Starr, J. Stern, Enzymatic control of phenylalanine intake in phenylketonuria, Lancet 1 (1980) 392; C.M. Ambrus, S. Anthone, C. Horvath, K. Kalghatgi, A.S. Lele, G. Eapen, J.L. Ambrus, A.J. Ryan, P. Li, Extracorporeal enzyme reactors for depletion of phenylalanine in phenylketonuria, Ann. Intern. Med. 106 (1987) 531]. Here, we report the 1.6A three-dimensional structure of Rhodosporidium toruloides PAL, structure-based molecular engineering, pegylation of PAL, as well as in vitro and in vivo PKU mouse model studies on pegylated PAL formulations. Our results show that pegylation of R. toruloides PAL leads to promising therapeutic efficacy after subcutaneous injection by enhancing the in vivo activity, lowering plasma phenylalanine, and leading to reduced immunogenicity. The three-dimensional structure of PAL provides a

  13. Pancreatic enzyme replacement therapy in cystic fibrosis: dose, variability and coefficient of fat absorption.

    Calvo-Lerma, Joaquim; Martínez-Barona, Sandra; Masip, Etna; Fornés, Victoria; Ribes-Koninckx, Carmen


    Pancreatic enzyme replacement therapy (PERT) remains a backbone in the nutritional treatment of cystic fibrosis. Currently, there is a lack of an evidence-based tool that allows dose adjustment. To date, no studies have found an association between PERT dose and fat absorption. Therefore, the aim of the study was to assess the influence of both the PERT dose and the variability in this dose on the coefficient of fat absorption (CFA). This is a retrospective longitudinal study of 16 pediatric patients (192 food records) with three consecutive visits to the hospital over a twelve-month period. Dietary fat intake and PERT were assessed via a four-day food record and fat content in stools was determined by means of a three-day stool sample collection. A beta regression model was built to explain the association between the CFA and the interaction between the PERT dose (lipase units [LU]/g dietary fat) and the variability in the PERT dose (standard deviation [SD]). The coefficient of fat absorption increased with the PERT dose when the variability in the dose was low. In contrast, even at the highest PERT dose values, the CFA decreased when the variability was high. The confidence interval suggested an association, although the analysis was not statistically significant. The variability in the PERT dose adjustment should be taken into consideration when performing studies on PERT efficiency. A clinical goal should be the maintenance of a constant PERT dose rather than trying to obtain an optimal value.

  14. Deleterious effects of interruption followed by reintroduction of enzyme replacement therapy on a lysosomal storage disorder.

    Schneider, Ana Paula; Matte, Ursula; Pasqualim, Gabriela; Tavares, Angela Maria Vicente; Mayer, Fabiana Quoos; Martinelli, Barbara; Ribas, Graziela; Vargas, Carmen Regla; Giugliani, Roberto; Baldo, Guilherme


    Temporary interruption of enzyme replacement therapy (ERT) in patients with different lysosomal storage disorders may happen for different reasons (adverse reactions, issues with reimbursement, logistic difficulties, and so forth), and the impact of the interruption is still uncertain. In the present work, we studied the effects of the interruption of intravenous ERT (Laronidase, Genzyme) followed by its reintroduction in mice with the prototypical lysosomal storage disorder mucopolysaccharidosis type I, comparing to mice receiving continuous treatment, untreated mucopolysaccharidosis type I mice, and normal mice. In the animals which treatment was temporarily interrupted, we observed clear benefits of treatment in several organs (liver, lung, heart, kidney, and testis) after reintroduction, but a worsening in the thickness of the aortic wall was detected. Furthermore, these mice had just partial improvements in behavioral tests, suggesting some deterioration in the brain function. Despite worsening is some disease aspects, urinary glycosaminoglycans levels did not increase during interruption, which indicates that this biomarker commonly used to monitor treatment in patients should not be used alone to assess treatment efficacy. The deterioration observed was not caused by the development of serum antienzyme antibodies. All together our results suggest that temporary ERT interruption leads to deterioration of function in some organs and should be avoided whenever possible.

  15. Continuous infusion of enzyme replacement therapy is inferior to weekly infusions in MPS I dogs.

    Passage, M B; Krieger, A W; Peinovich, M C; Lester, T; Le, S Q; Dickson, P I; Kakkis, E D


    Intravenous enzyme replacement therapy with recombinant human α-L-iduronidase (rhIDU) is used weekly to treat mucopolysaccharidosis (MPS) I. We tested continuous administration of rhIDU at two dosing levels (0.58 mg/kg per week and 2 mg/kg per week) in MPS I dogs, and compared the efficacy of continuous infusion with the clinically used 0.58 mg/kg weekly three-hour infusion. Peak plasma concentrations of rhIDU were much higher in weekly-treated dogs (mean 256 units/ml) than steady-state concentrations in dogs treated with continuous infusion (mean 1.97 units/ml at 0.58 mg/kg per week; 8.44 units/ml at 2 mg/kg per week). Dogs receiving continuous IV rhIDU, even at a higher (2 mg/kg per week) dose, had consistently lower iduronidase levels in tissues than dogs receiving a weekly (0.58 mg/kg per week) dose. GAG storage was also less improved by continuous intravenous infusion. Adverse events were similar in all dosing groups. We found that continuous administration of 2 mg/kg per week rhIDU to MPS I dogs was insufficient to achieve GAG storage reduction comparable to 0.58 mg/kg weekly dosing.

  16. Respiratory mechanics in an infant with perinatal lethal hypophosphatasia treated with human recombinant enzyme replacement therapy.

    Rodriguez, Elena; Bober, Michael B; Davey, Lauren; Zamora, Arlene; Li Puma, Annelise B; Chidekel, Aaron; Shaffer, Thomas H


    Hypophosphatasia is a rare autosomal recessive disorder caused by deficient activity of tissue nonspecific alkaline phosphatase (TNSALP) and characterized by defective bone mineralization. In the perinatal lethal form, respiratory complications due to rachitic deformities of the thoracic cage and associated hypoplastic lungs are present. ENB-0040 is a bone-targeted human recombinant TNSALP fusion protein that aims to restore skeletal mineralization. The goal of this study was to characterize pulmonary and thoracic cage mechanics in an infant with the perinatal lethal form of hypophosphatasia under enzyme replacement therapy. Pulmonary function testing was performed on a preterm, 8-week-old patient with hypophosphatasia who was mechanically ventilated since birth because of severe chest wall insufficiency. The measurements consisted of respiratory impulse oscillation measurements (resistance and reactance), ventilatory mechanics (compliance and resistance), and thoracoabdominal motion (TAM) analysis. At baseline, chest wall compliance was 50% of normal, and the TAM indicated predominantly abdominal displacement. After 12 weeks of treatment, a consistent decrease in ventilator requirements and improvement in lung function and chest wall mechanics were observed and correlated with thoracic cage radiologic findings. Measurable changes in chest wall dynamics and respiratory mechanics using noninvasive technology were useful for respiratory management and therapeutic guidance of ENB-0040 treatment in this patient.

  17. A technique for long term continent gastrostomy.

    Locker, D L; Foster, J E; Craun, M L; Torma, M J


    The use of the continent gastrostomy described herein offers several advantages: 1, the elimination of an indwelling catheter; 2, prevention of soiling at skin level; 3, long term access to the normal gastrointestinal track for alimentation without fear of tube erosion; 4, little compromise to gastric volume, and 5, ease of stoma care. We recommend this operation in instances when long term tube feedings are indicated either because of damage to the central nervous system or as a palliative treatment for patients with higher obstructing gastrointestinal malignant disease. The procedure may also be useful for patients in whom esophagogastric continuity has been interrupted (surgically or traumatically) and in whom reconstruction of the gastrointestinal tract would not seem feasible within a three to six month interval.

  18. Long-term opioid therapy in Denmark

    Birke, H; Ekholm, O; Sjøgren, P


    BACKGROUND: Longitudinal population-based studies of long-term opioid therapy (L-TOT) in chronic non-cancer pain (CNCP) patients are sparse. Our study investigated incidence and predictors for initiating L-TOT and changes in self-rated health, pain interference and physical activities in long......-term opioid users. METHODS: Data were obtained from the national representative Danish Health and Morbidity Surveys and The Danish National Prescription Registry. Respondents with no dispensed opioids the year before the survey were followed from 2000 and from 2005 until the end of 2012 (n = 12...... defined as those who were dispensed at least one opioid prescription in six separate months within a year. RESULTS: The incidence of L-TOT was substantially higher in CNCP patients at baseline than in others (9/1000 vs. 2/1000 person-years). Smoking behaviour and dispensed benzodiazepines were...

  19. Case presentation: long-term treatment.

    Glucksman, Myron L


    The long-term (14 years) psychodynamic psychotherapy and pharmacotherapy of a depressed, suicidal, self-mutilating female patient is described. Her diagnoses included Chronic Posttraumatic Stress Disorder, Borderline Personality Disorder, and Recurrent Major Depression. Treatment was punctuated with repeated hospitalizations for self-mutilation (cutting) and suicidal ideation. A major determinant for her psychopathology was sexual abuse by her father from ages 6 to 14. This resulted in feelings of guilt and rage that she repressed and acted out through self-mutilating and suicidal behavior. A prolonged negative transference gradually became ambivalent, then positive. This was associated with her internalization of the healing qualities of the therapeutic relationship. She also gained insight into the reasons for her need to punish herself. Her initial self-representation as unworthy and bad was transformed into perceiving herself as a worthwhile, loving person. This case illustrates the role of long-term treatment for a complex, life-threatening, psychiatric disorder.

  20. Ophthalmic experience over 10 years in an observational nationwide Danish cohort of Fabry patients with access to enzyme replacement

    Fledelius, Hans C.; Sandfeld, Lisbeth; Rasmussen, Åse Krogh


    PURPOSE: Enzyme replacement therapy (ERT) was offered from year 2001 to patients with Fabry disease. The ophthalmic experience was analysed, as part of a general 10-year status. METHODS: A retrospective observational series comprising 39 patients (25 females, 14 males) closely followed by the end...

  1. Cost-effectiveness of enzyme replacement therapy with alglucosidase alfa in classic-infantile patients with Pompe disease

    T.A. Kanters (Tim A.); I Hoogenboom-Plug (Iris); M.P.M.H. Rutten-van Mölken (Maureen); W.K. Redekop (Ken); A.T. van der Ploeg (Ans); L. van Hakkaart-van Roijen (Leona)


    textabstractBackground: Infantile Pompe disease is a rare metabolic disease. Patients generally do not survive the first year of life. Enzyme replacement therapy (ERT) has proven to have substantial effects on survival in infantile Pompe disease. However, the costs of therapy are very high. In this

  2. Impact of enzyme replacement therapy on survival in adults with Pompe disease: Results from a prospective international observational study

    D. Güngör (Deniz); M.E. Kruijshaar (Michelle); I. Plug (Iris); R.B. D'Agostino (Ralph); M.L.C. Hagemans (Marloes); P.A. van Doorn (Pieter); A.J.J. Reuser (Arnold); A.T. van der Ploeg (Ans)


    textabstractBackground: Pompe disease is a rare metabolic myopathy for which disease-specific enzyme replacement therapy (ERT) has been available since 2006. ERT has shown efficacy concerning muscle strength and pulmonary function in adult patients. However, no data on the effect of ERT on the survi

  3. Pancreatic Enzyme Therapy and Coefficient of Fat Absorption in Children and AdolReplacement escents With Cystic Fibrosis

    Woestenenk, Janna W; van der Ent, Cornelis K.; Houwen, Roderick H J; van der Ent, CK


    Objectives: Pancreatic enzyme replacement therapy (PERT) is the proven therapy to substantially reduce fat malabsorption in patients with cystic fibrosis (CF). Few details of the daily practice regarding PERT and the resulting coefficient of fat absorption (CFA) are known. We therefore recorded the

  4. Pancreatic Enzyme Therapy and Coefficient of Fat Absorption in Children and AdolReplacement escents With Cystic Fibrosis

    Woestenenk, Janna W; van der Ent, Cornelis K.; Houwen, Roderick H J; van der Ent, CK

    Objectives: Pancreatic enzyme replacement therapy (PERT) is the proven therapy to substantially reduce fat malabsorption in patients with cystic fibrosis (CF). Few details of the daily practice regarding PERT and the resulting coefficient of fat absorption (CFA) are known. We therefore recorded the

  5. Cost-effectiveness of enzyme replacement therapy with alglucosidase alfa in classic-infantile patients with Pompe disease

    T.A. Kanters (Tim A.); I Hoogenboom-Plug (Iris); M.P.M.H. Rutten-van Mölken (Maureen); W.K. Redekop (Ken); A.T. van der Ploeg (Ans); L. van Hakkaart-van Roijen (Leona)


    markdownabstract__Abstract__ Background: Infantile Pompe disease is a rare metabolic disease. Patients generally do not survive the first year of life. Enzyme replacement therapy (ERT) has proven to have substantial effects on survival in infantile Pompe disease. However, the costs of therapy

  6. Long-Term Hearing Results After Ossiculoplasty.

    Cox, Matthew D; Trinidade, Aaron; Russell, James Shep; Dornhoffer, John L


    To determine if the OOPS index is predictive of long-term hearing results after ossiculoplasty. Case series with retrospective chart review. Tertiary care otology practice. Adult and pediatric patients (3-88 years of age). Ossiculoplasty with cartilage tympanoplasty, with or without mastoidectomy. Primary outcome measures included short-term hearing results (pure-tone average air-bone gap [PTA-ABG] measured between 60 days and 1 year after surgery), long-term hearing results (PTA-ABG measured ≥5 years after surgery), and the rate of successful ABG closure to ≤20 dB. Secondary measures included the need for revision surgery, delayed tympanic membrane graft failure, worsening conductive hearing loss (after an initially satisfactory hearing result), and recurrence of cholesteatoma. There was no significant difference between adults and children for short-term hearing results (average post-op PTA-ABG was 18.9 dB vs. 19.8 dB, respectively; p = 0.544), long-term hearing results (average final PTA-ABG was 19.3 dB vs. 19.4 dB, respectively; p = 0.922), or rate of ABG closure to less than 20 dB (63.1% vs. 58.0%, p = 0.282). Spearman's rank-order correlation (ρ) identified a strong positive correlation between OOPS index score and average post-operative PTA-ABG (ρ = 0.983; p hearing outcomes in adult and pediatric patients undergoing ossiculoplasty in both the short term and the long term.

  7. Timber joints under long-term loading

    Feldborg, T.; Johansen, M.

    This report describes tests and results from stiffness and strength testing of splice joints under long-term loading. During two years of loading the spicimens were exposed to cyclically changing relative humidity. After the loading period the specimens were short-term tested. The connectors were...... integral nail-plates and nailed steel and plywood gussets. The report is intended for designers and researchers in timber engineering....

  8. Cutaneous oxalosis after long-term hemodialysis.

    Abuelo, J G; Schwartz, S T; Reginato, A J


    A 27-year-old woman undergoing long-term hemodialysis developed cutaneous calcifications on her fingers. A skin biopsy specimen showed that the deposits were calcium oxalate. To our knowledge, only one previous article has reported pathologic and crystallographic studies on calcifications of the skin resulting from dialysis oxalosis. We speculate that vitamin C supplements, liberal tea consumption, an increased serum ionized calcium concentration, and the long duration of hemodialysis contributed to the production of these deposits.

  9. Long term evolution 4G and beyond

    Yacoub, Michel; Figueiredo, Fabrício; Tronco, Tania


    This book focus on Long Term Evolution (LTE) and beyond. The chapters describe different aspects of research and development in LTE, LTE-Advanced (4G systems) and LTE-450 MHz such as telecommunications regulatory framework, voice over LTE, link adaptation, power control, interference mitigation mechanisms, performance evaluation for different types of antennas, cognitive mesh network, integration of LTE network and satellite, test environment, power amplifiers and so on. It is useful for researchers in the field of mobile communications.

  10. Consequences of long-term hyperparathyroidism.

    Graal, M B; Wolffenbuttel, B H


    We describe a young woman with long-term untreated hyperparathyroidism with a superimposed vitamin D deficiency and an extremely decreased bone mineral density that was complicated by a vertebral fracture. Despite pretreatment with intravenous pamidronate and short-term vitamin D supplementation, severe and long-standing hypocalcaemia ('hungry bone syndrome') developed after parathyroidectomy. We discuss the consequences of hyperparathyroidism, especially the effects on bone, the complications of parathyroidectomy and the possibilities of preoperative treatment with bisphosphonates.

  11. Long-term behaviour of GRP pipes

    Faria, H; A Vieira; Reis, J; Marques, A. T.; Guedes, R.M.; Ferreira, A. J. M.


    The main objective of the research programme /1/ described is the study of creep and relaxation behaviour of glass-rein forced thermosetting (GRP) pipes, in order to find alternative methods to predict the long-term properties, rendering a considerable reduction of the time needed for testing and assuring, as far as possible, equivalent reliability when compared to the existing methods. Experimental procedures were performed and are presented here, together with discussion of results, as well...

  12. Early Life Environments and Long Term Outcomes

    Bolbocean, Corneliu


    A large literature has linked “in utero” environment to health and socio-economic outcomes in adulthood. We consider the effect of early life environments on health and skill formation outcomes. We first evaluate the impact of perinatal-neonatal level of technology at birth, which varies across delivery institutions, on the long-term neurodevelopmental outcomes of children with Cerebral Palsy. The level of technology at delivery determines the type of therapy newborns receive immediately afte...

  13. Long term economic relationships from cointegration maps

    Vicente, Renato; Pereira, Carlos de B.; Leite, Vitor B. P.; Caticha, Nestor


    We employ the Bayesian framework to define a cointegration measure aimed to represent long term relationships between time series. For visualization of these relationships we introduce a dissimilarity matrix and a map based on the sorting points into neighborhoods (SPIN) technique, which has been previously used to analyze large data sets from DNA arrays. We exemplify the technique in three data sets: US interest rates (USIR), monthly inflation rates and gross domestic product (GDP) growth rates.

  14. Fat malabsorption in cystic fibrosis patients receiving enzyme replacement therapy is due to impaired intestinal uptake of long-chain fatty acids

    Kalivianakis, M; Minich, DM; Bijleveld, CMA; van Aalderen, WMC; Stellaard, F; Vonk, RJ; Verkade, HJ


    Background: Pancreatic enzyme replacement therapy frequently fails to correct intestinal fat malabsorption completely in cystic fibrosis (CF) patients. The reason for this failure is unknown. Objective: We investigated whether fat malabsorption in CF patients treated with pancreatic enzymes is cause

  15. Enzyme replacement therapy for Mucopolysaccharidosis Type I among patients followed within the MPS Brazil Network.

    Dornelles, Alícia Dorneles; de Camargo Pinto, Louise Lapagesse; de Paula, Ana Carolina; Steiner, Carlos Eduardo; Lourenço, Charles Marques; Kim, Chong Ae; Horovitz, Dafne Dain Gandelman; Ribeiro, Erlane Marques; Valadares, Eugênia Ribeiro; Goulart, Isabela; Neves de Souza, Isabel C; da Costa Neri, João Ivanildo; Santana-da-Silva, Luiz Carlos; Silva, Luiz Roberto; Ribeiro, Márcia; de Oliveira Sobrinho, Ruy Pires; Giugliani, Roberto; Schwartz, Ida Vanessa Doederlein


    Mucopolysaccharidosis type I (MPS I) is a rare lysosomal disorder caused by deficiency of alpha-L-iduronidase. Few clinical trials have assessed the effect of enzyme replacement therapy (ERT) for this condition. We conducted an exploratory, open-label, non-randomized, multicenter cohort study of patients with MPS I. Data were collected from questionnaires completed by attending physicians at the time of diagnosis (T1; n = 34) and at a median time of 2.5 years later (T2; n = 24/34). The 24 patients for whom data were available at T2 were allocated into groups: A, no ERT (9 patients; median age at T1 = 36 months; 6 with severe phenotype); B, on ERT (15 patients; median age at T1 = 33 months; 4 with severe phenotype). For all variables in which there was no between-group difference at baseline, a delta of ≥ ± 20% was considered clinically relevant. The following clinically relevant differences were identified in group B in T2: lower rates of mortality and reported hospitalization for respiratory infection; lower frequency of hepatosplenomegaly; increased reported rates of obstructive sleep apnea syndrome and hearing loss; and stabilization of gibbus deformity. These changes could be due to the effect of ERT or of other therapies which have also been found more frequently in group B. Our findings suggest MPS I patients on ERT also receive a better overall care. ERT may have a positive effect on respiratory morbidity and overall mortality in patients with MPS I. Additional studies focusing on these outcomes and on other therapies should be performed.

  16. Long-Term Recency in Anterograde Amnesia.

    Deborah Talmi

    Full Text Available Amnesia is usually described as an impairment of a long-term memory (LTM despite an intact short-term memory (STM. The intact recency effect in amnesia had supported this view. Although dual-store models of memory have been challenged by single-store models based on interference theory, this had relatively little influence on our understanding and treatment of amnesia, perhaps because the debate has centred on experiments in the neurologically intact population. Here we tested a key prediction of single-store models for free recall in amnesia: that people with amnesia will exhibit a memory advantage for the most recent items even when all items are stored in and retrieved from LTM, an effect called long-term recency. People with amnesia and matched controls studied, and then free-recalled, word lists with a distractor task following each word, including the last (continual distractor task, CDFR. This condition was compared to an Immediate Free Recall (IFR, no distractors and a Delayed Free Recall (DFR, end-of-list distractor only condition. People with amnesia demonstrated the full long-term recency pattern: the recency effect was attenuated in DFR and returned in CDFR. The advantage of recency over midlist items in CDFR was comparable to that of controls, confirming a key prediction of single-store models. Memory deficits appeared only after the first word recalled in each list, suggesting the impairment in amnesia may emerge only as the participant's recall sequence develops, perhaps due to increased susceptibility to output interference. Our findings suggest that interference mechanisms are preserved in amnesia despite the overall impairment to LTM, and challenge strict dual-store models of memory and their dominance in explaining amnesia. We discuss the implication of our findings for rehabilitation.

  17. Long-Term Recency in Anterograde Amnesia.

    Talmi, Deborah; Caplan, Jeremy B; Richards, Brian; Moscovitch, Morris


    Amnesia is usually described as an impairment of a long-term memory (LTM) despite an intact short-term memory (STM). The intact recency effect in amnesia had supported this view. Although dual-store models of memory have been challenged by single-store models based on interference theory, this had relatively little influence on our understanding and treatment of amnesia, perhaps because the debate has centred on experiments in the neurologically intact population. Here we tested a key prediction of single-store models for free recall in amnesia: that people with amnesia will exhibit a memory advantage for the most recent items even when all items are stored in and retrieved from LTM, an effect called long-term recency. People with amnesia and matched controls studied, and then free-recalled, word lists with a distractor task following each word, including the last (continual distractor task, CDFR). This condition was compared to an Immediate Free Recall (IFR, no distractors) and a Delayed Free Recall (DFR, end-of-list distractor only) condition. People with amnesia demonstrated the full long-term recency pattern: the recency effect was attenuated in DFR and returned in CDFR. The advantage of recency over midlist items in CDFR was comparable to that of controls, confirming a key prediction of single-store models. Memory deficits appeared only after the first word recalled in each list, suggesting the impairment in amnesia may emerge only as the participant's recall sequence develops, perhaps due to increased susceptibility to output interference. Our findings suggest that interference mechanisms are preserved in amnesia despite the overall impairment to LTM, and challenge strict dual-store models of memory and their dominance in explaining amnesia. We discuss the implication of our findings for rehabilitation.

  18. Replacement of the human topoisomerase linker domain with the plasmodial counterpart renders the enzyme camptothecin resistant

    Arnò, Barbara; D'Annessa, Ilda; Tesauro, Cinzia;


    , but it is characterized by a much faster religation rate. The hybrid enzyme is also camptothecin resistant. A 3D structure of the hybrid enzyme has been built and its structural-dynamical properties have been analyzed by molecular dynamics simulation. The analysis indicates that the swapped plasmodial linker samples......A human/plasmodial hybrid enzyme, generated by swapping the human topoisomerase IB linker domain with the corresponding domain of the Plasmodium falciparum enzyme, has been produced and characterized. The hybrid enzyme displays a relaxation activity comparable to the human enzyme...... in the modulation of the topoisomerase IB activity....

  19. Long-term policy on gas composition

    Verhagen, M.J.M.


    This letter sets out the policy of the Dutch cabinet on the long-term change to the composition of low calorific gas that is distributed via the public gas grid. The title of a separate attachment to this letter is 'The composition of low calorific gas in the more distant future and the requirements for gas appliances covered by the Gas Appliances Directive'. The attachment sets out the composition of low calorific gas as network operators can distribute it via the public gas grid from 2021 (or from a later date). This relates to the changes in the 'exit specification' of the gas.

  20. Safety of long-term PPI therapy

    Reimer, Christina


    Proton pump inhibitors have become the mainstay of medical treatment of acid-related disorders. Long-term use is becoming increasingly common, in some cases without a proper indication. A large number of mainly observational studies on a very wide range of possible associations have been published...... is based on a relevant indication. The concern for complications should primarily be directed at elderly, malnourished with significant co-morbidity. In this population an increased risk for enteric infections, fractures and nutritional deficiencies might have clinical consequences and should lead...

  1. Long-term space flights - personal impressions

    Polyakov, V. V.

    During a final 4-month stage of a 1-year space flight of cosmonauts Titov and Manarov, a physician, Valery Polyakov was included on a crew for the purpose of evaluating their health, correcting physical status to prepare for the spacecraft reentry and landing operations. The complex program of scientific investigations and experiments performed by the physician included an evaluation of adaptation reactions of the human body at different stages of space mission using clinicophysiological and biochemical methods; testing of alternative regimes of exercise and new countermeasures to prevent an unfavourable effect of long-term weightlessness.

  2. The long term stability of lidar calibrations

    Courtney, Michael; Gayle Nygaard, Nicolai

    Wind lidars are now used extensively for wind resource measurements. One of the requirements for the data to be accepted in support of project financing (so-called ‘banka-bility’) is to demonstrate the long-term stability of lidar cali-brations. Calibration results for six Leosphere WindCube li-dars......-ters pertaining in the different calibration periods. This is supported by sliding-window analyses of one lidar at one location where the same order of variation is observed as between pre-service and post-service calibrations....

  3. Long-term effects of sibling incest.

    Daie, N; Witztum, E; Eleff, M


    Although sexual abuse of children is recognized as a serious problem, sibling incest has received relatively little attention. A distinction has been made between power-oriented sibling incest and nurturance-oriented incest. The authors review the relevant literature and present four clinical examples. The cases illustrate the broad range of sibling incest and demonstrate its effects, including the long-term consequences for the perpetrator. Lasting difficulties in establishing and maintaining close relationships, especially sexual ones, are prominent features of each case. Without denying the occurrences of benign sex-play between siblings, the authors emphasize exploitation and abuse as pathogenic aspects of sibling incest.

  4. Long Term Analysis for the BAM device

    Bonino, D.; Gardiol, D.


    Algorithms aimed at the evaluation of critical quantities are based on models with many parameters, which values are estimated from data. The knowledge, with high accuracy, of these values and the control of their temporal evolution are important features. In this work, we focus on the latter subject, and we show a proposed pipeline for the BAM (Basic Angle Monitoring) Long Term Analysis, aimed at the study of the calibration parameters of the BAM device and of the Basic Angle variation, searching for unwanted trends, cyclic features, or other potential unexpected behaviours.

  5. Long-Term Wind Power Variability

    Wan, Y. H.


    The National Renewable Energy Laboratory started collecting wind power data from large commercial wind power plants (WPPs) in southwest Minnesota with dedicated dataloggers and communication links in the spring of 2000. Over the years, additional WPPs in other areas were added to and removed from the data collection effort. The longest data stream of actual wind plant output is more than 10 years. The resulting data have been used to analyze wind power fluctuations, frequency distribution of changes, the effects of spatial diversity, and wind power ancillary services. This report uses the multi-year wind power data to examine long-term wind power variability.

  6. Terminating a long-term clinical trial.

    Klimt, C R


    Long-term clinical trials often include more than one active treatment group. These may be discontinued independently if found to be ineffective or possibly harmful. Certain subgroups of patients may be discovered, in the course of a clinical trial, who do not respond satisfactorily and are, therefore, excluded during the course of a trial. Yet another kind of termination comes when we have a therapeutic breakthrough or when hope has to be abandoned for demonstrating beneficial effects for one, several, or all treatments included in a trial. Examples from the authors' experience are presented, as are successful and unsuccessful techniques in managing terminations of various types.

  7. Long-term outcomes following Medtronic Open Pivot valved conduit.

    Naidoo, Rishendran; Pearse, Bronwyn; Tesar, Peter J; Yap, Su-Ann; Barnett, Adrian G; Fayers, Trevor


    Aortic root replacement is a complex procedure, though subsequent modifications of the original Bentall procedure have made surgery more reproducible. The study aim was to examine the outcomes of a modified Bentall procedure, using the Medtronic Open PivotTM valved conduit. Whilst short-term data on the conduit and long-term data on the valve itself are available, little is known of the long-term results with the valved conduit. Patients undergoing aortic root replacement between February 1999 and February 2010, using the Medtronic Open Pivot valved conduit were identified from the prospectively collected Cardiothoracic Register at The Prince Charles Hospital, Brisbane, Australia. All patients were followed up echocardiographically and clinically. The primary end-point was death, and a Cox proportional model was used to identify factors associated.with survival. Secondary end-points were valve-related morbidity (as defined by STS guidelines) and postoperative morbidity. Predictors of morbidity were identified using logistic regression. A total of 246 patients (mean age 50 years) was included in the study. The overall mortality was 12%, with actuarial 10-year survival 79% and a 10-year estimate of valve-related death of 0.04 (95% CI: 0.004, 0.07). Preoperative myocardial infarction (p = 0.004, HR 4.74), urgency of operation (p = 0.038, HR 2.8) and 10% incremental decreases in ejection fraction (p = 0.046, HR 0.69) were predictive of mortality. Survival was also affected by the valve gradients, with a unit increase in peak gradient reducing mortality (p = 0.021, HR 0.93). Valve-related morbidity occurred in 11 patients. Urgent surgery (p Medtronic Open Pivot valved conduit is a safe and durable option for aortic root replacement, and is associated with low morbidity and 10-year survival of 79%. However, further studies are required to determine the effect of valve gradient on survival.

  8. Effects of Different Long-term Fertilization Models on Culturable Microbial Quantity and Enzyme Activities of Lime Concretion Black Soil%长期不同施肥模式对砂姜黑土可培养微生物数量和酶活性的影响

    张向前; 陈欢; 乔玉强; 曹承富; 杜世州; 李玮; 赵竹


    Based on long-term located fertilization experiment (year 1981—) in lime concretion black soil area, we studied the effects of without fertilizer application CK, long-term application of single chemical fertilizer NPK, long-term application of single organic fertilizer M, long-term mixed application of organic and chemical fertilizer MNPK (with the same amount of nitrogen) and HMNPK (with the larger amount of nitrogen) on culturable microbial quantity and enzyme activities in soil, in order to reveal the response mechanism of soil microbial quantity and enzyme activities to different fertilization models, and to provide scientific basis and theoretical help for improving lime concretion black soil fertility and quality. The quantity of bacteria, fungi, actinomycetes and Azotobacter of CK was lower than that of other fertilization treatments, and the quantity of bacteria, actinomycetes and Azotobacter of M was significantly higher than that of NPK at middle of filling stage, while the difference in the quantity of fungi between M and NPK was insignificant. The quantity of bacteria, fungi and actinomycetes of MNPK and HMNPK was higher than that of NPK and M, compared to NPK and M, MNPK increased the quantity of bacteria, fungi and actinomycetes by 47.0%, 21.1%, 32.1% and 23.2%, 11.7%, 20.2%, respectively. The difference in the quantity of bacteria, fungi and actinomycetes between MNPK and HMNPK was insignificant at middle of filling stage, while the quantity of Azotobacter of MNPK was higher than that of HMNPK. The activities of invertase, dehydrogenase, acidic and neutral phosphatase and protease of M were higher than that of NPK at middle of filling stage, and increased by 20.9%, 22.1%, 17.7%, 18.4%, 10.0%, respectively. When compared to long-term application of single chemical fertilizer and organic fertilizer, the treatment of long-term mixed application of organic and chemical fertilizer obviously increased the activities of soil invertase, dehydrogenase

  9. 绝经后妇女长期低剂量激素替代疗法中外周血内吗啡肽1和2的分析研究%Analysis of Endomorphin-1 and Endomorphin-2 in Peripheral Blood of Postmenpausal Women with Long-term Low-dose Hormone Replacement Therapy

    王涛; 任志丽; 纪超; 杨楠; 刘雁勇; 左萍萍


    Objective To investigate the levels of EM-1 and EM-2 in peripheral blood with long-term low dose HRT therapy and analyze the relationship between endomorphins and estradiol.Methods169 female medical staff in Peking Union Medical College Hospital were included in our study. Based on age, participants were divided into 4 groups, including 50~59 , 60~64 , 65~69 and over 70 years old , HRT group and control group were included in each age group. Plasma hormones including estradiol (E2), progesterone (P) and testosterone (T) were detected by using Bio-RAD 550 Model ELISA(enzyme-linked immunosorbent assay) device, and levels of EM-1 and EM-2 were examined by radioimmunoassay methods.ResultsCompared to control group at each age, plasma estrodiol (E2) levels obviously increased in HRT groups (P<0.05). The levels of EM-1 and EM-2 in HRT group of each age decreased compared to control group, meanwhile, pearson correlation analysis showed that the level of endomorphin-1 (EM-1) on all subjects was correlated with their individual estradiol(P<0.01).ConclusionThis is the ifrst observation of the relationship between endomorphins and estradiol in a long-term low-dose HRT therapy, which providing clinical signiifcance of protecting brain cognition in postmenpausal women.%目的:在长期低剂量激素替代疗法(HRT)下,观察绝经后妇女外周血中内吗啡肽1(EM-1)和内吗啡肽2(EM-2)的变化,并对内吗啡呔与雌激素进行相关性分析。方法研究对象系北京协和医院已绝经女职工共169人,全员根据年龄共分为4组,包括50~59岁,60~64岁,65~69岁,70岁以上,每年龄段内均包括HRT组和对照组。用酶联免疫反应测试仪测定受试者血浆性激素水平,用放射免疫法检测血浆内EM-1和EM-2的含量。结果各年龄段HRT治疗组E2的水平均显著高于对照组(P<0.05);各年龄段HRT治疗组EM-1和EM-2的水平均低于对照组,且全体受试者血浆雌激素E2的水平与EM-1具

  10. Long term effects of Escherichia coli mastitis.

    Blum, Shlomo E; Heller, Elimelech D; Leitner, Gabriel


    Escherichia coli is one of the most frequently diagnosed causes of bovine mastitis, and is typically associated with acute, clinical mastitis. The objective of the present study was to evaluate the long term effects of intramammary infections by E. coli on milk yield and quality, especially milk coagulation. Twenty-four Israeli Holstein cows diagnosed with clinical mastitis due to intramammary infection by E. coli were used in this study. Mean lactation number, days in milk (DIM) and daily milk yield (DMY) at the time of infection was 3.3 ± 1.3, 131.7 days ± 78.6 and 45.7 L ± 8.4, respectively. DMY, milk constituents, somatic cells count (SCC), differential leukocytes count and coagulation parameters were subsequently assessed. Two patterns of inflammation were identified: 'short inflammation', characterized by 15% decrease in DMY and >30 days to reach a new maximum DMY (n = 19). The estimated mean loss of marketable milk during the study was 200 L/cow for 'short inflammation' cases, and 1,500 L/cow for 'long inflammation' ones. Significant differences between 'short' and 'long inflammation' effects were found in almost all parameters studied. Long-term detrimental effects on milk quality were found regardless of clinical or bacteriological cure of affected glands.

  11. Long term perfusion system supporting adipogenesis.

    Abbott, Rosalyn D; Raja, Waseem K; Wang, Rebecca Y; Stinson, Jordan A; Glettig, Dean L; Burke, Kelly A; Kaplan, David L


    Adipose tissue engineered models are needed to enhance our understanding of disease mechanisms and for soft tissue regenerative strategies. Perfusion systems generate more physiologically relevant and sustainable adipose tissue models, however adipocytes have unique properties that make culturing them in a perfusion environment challenging. In this paper we describe the methods involved in the development of two perfusion culture systems (2D and 3D) to test their applicability for long term in vitro adipogenic cultures. It was hypothesized that a silk protein biomaterial scaffold would provide a 3D framework, in combination with perfusion flow, to generate a more physiologically relevant sustainable adipose tissue engineered model than 2D cell culture. Consistent with other studies evaluating 2D and 3D culture systems for adipogenesis we found that both systems successfully model adipogenesis, however 3D culture systems were more robust, providing the mechanical structure required to contain the large, fragile adipocytes that were lost in 2D perfused culture systems. 3D perfusion also stimulated greater lipogenesis and lipolysis and resulted in decreased secretion of LDH compared to 2D perfusion. Regardless of culture configuration (2D or 3D) greater glycerol was secreted with the increased nutritional supply provided by perfusion of fresh media. These results are promising for adipose tissue engineering applications including long term cultures for studying disease mechanisms and regenerative approaches, where both acute (days to weeks) and chronic (weeks to months) cultivation are critical for useful insight.

  12. Long-term environmental behaviour of radionuclides

    Brechignac, F.; Moberg, L.; Suomela, M


    The radioactive pollution of the environment results from the atmospheric nuclear weapons testing (during the mid-years of twentieth century), from the development of the civilian nuclear industry and from accidents such as Chernobyl. Assessing the resulting radiation that humans might receive requires a good understanding of the long-term behaviour of radionuclides in the environment. This document reports on a joint European effort to advance this understanding, 3 multinational projects have been coordinated: PEACE, EPORA and LANDSCAPE. This report proposes an overview of the results obtained and they are presented in 6 different themes: (i) redistribution in the soil-plant system, (ii) modelling, (iii) countermeasures, (iv) runoff (v) spatial variations, and (vi) dose assessment. The long term behaviour of the radionuclides {sup 137}Cs, {sup 90}Sr and {sup 239-240}Pu is studied through various approaches, these approaches range from in-situ experiments designed to exploit past contamination events to laboratory simulations. A broad scope of different ecosystems ranging from arctic and boreal regions down to mediterranean ones has been considered. (A.C.)

  13. Long term testing of PSI-membranes

    Huslage, J.; Brack, H.P.; Geiger, F.; Buechi, F.N.; Tsukada, A.; Scherer, G.G. [Paul Scherrer Inst. (PSI), Villigen (Switzerland)


    Long term tests of PSI membranes based on radiation-grafted FEP and ETFE films were carried out and FEP-based membranes were evaluated by monitoring the in-situ membrane area resistance measured by a current pulse method. By modifying our irradiation procedure and using the double crosslinking concept we obtain reproducible membrane cell lifetimes (in term of in-situ membrane resistance) of greater than 5000 hours at 60-65{sup o}C. Preliminary tests at 80-85{sup o}C with lifetimes of greater than 2500 demonstrate the potential long term stability of PSI proton exchange membranes based on FEP over the whole operating temperature range of low-temperature polymer electrolyte fuel cells. Radiation grafted PSI membranes based on ETFE have better mechanical properties than those of the FEP membranes. Mechanical properties are particularly important in large area cells and fuel cell stacks. ETFE membranes have been tested successfully for approximately 1000 h in a 2-cell stack (100 cm{sup 2} active area each cell). (author) 4 figs., 4 refs.

  14. Long Term Changes in the Polar Vortices

    Braathen, Geir O.


    As the amount of halogens in the stratosphere is slowly declining and the ozone layer slowly recovers it is of interest to see how the meteorological conditions in the vortex develop over the long term since such changes might alter the foreseen ozone recovery. In conjunction with the publication of the WMO Antarctic and Arctic Ozone Bulletins, WMO has acquired the ERA Interim global reanalysis data set for several meteorological parameters. This data set goes from 1979 - present. These long time series of data can be used for several useful studies of the long term development of the polar vortices. Several "environmental indicators" for vortex change have been calculated, and a climatology, as well as trends, for these parameters will be presented. These indicators can act as yardsticks and will be useful for understanding past and future changes in the polar vortices and how these changes affect polar ozone depletion. Examples of indicators are: vortex mean temperature, vortex minimum temperature, vortex mean PV, vortex "importance" (PV*area), vortex break-up time, mean and maximum wind speed. Data for both the north and south polar vortices have been analysed at several isentropic levels from 350 to 850 K. A possible link between changes in PV and sudden stratospheric warmings will be investigated, and the results presented. The unusual meteorological conditions of the 2015 south polar vortex and the 2010/11 and 2015/16 north polar vortices will be compared to other recent years.

  15. Climate Predictability and Long Term Memory

    Zhu, X.; Blender, R.; Fraedrich, K.; Liu, Z.


    The benefit of climate Long Term Memory (LTM) for long term prediction is assessed using data from a millennium control simulation with the atmosphere ocean general circulation model ECHAM5/MPIOM. The forecast skills are evaluated for surface temperature time series at individual grid points. LTM is characterised by the Hurst exponent in the power-law scaling of the fluctuation function which is determined by detrended fluctuation analysis (DFA). LTM with a Hurst exponent close to 0.9 occurs mainly in high latitude oceans, which are also characterized by high potential predictability. Climate predictability is diagnosed in terms of potentially predictable variance fractions. Explicit prediction experiments for various time steps are conducted on a grid point basis using an auto-correlation (AR1) predictor: in regions with LTM, prediction skills are beyond that expected from red noise persistence; exceptions occur in some areas in the southern oceans and over the northern hemisphere continents. Extending the predictability analysis to the fully forced simulation shows large improvement in prediction skills.

  16. Long-term Caspian Sea level change

    Chen, J. L.; Pekker, T.; Wilson, C. R.; Tapley, B. D.; Kostianoy, A. G.; Cretaux, J.-F.; Safarov, E. S.


    Caspian Sea level (CSL) has undergone substantial fluctuations during the past several hundred years. The causes over the entire historical period are uncertain, but we investigate here large changes seen in the past several decades. We use climate model-predicted precipitation (P), evaporation (E), and observed river runoff (R) to reconstruct long-term CSL changes for 1979-2015 and show that PER (P-E + R) flux predictions agree very well with observed CSL changes. The observed rapid CSL increase (about 12.74 cm/yr) and significant drop ( -6.72 cm/yr) during the periods 1979-1995 and 1996-2015 are well accounted for by integrated PER flux predictions of +12.38 and -6.79 cm/yr, respectively. We show that increased evaporation rates over the Caspian Sea play a dominant role in reversing the increasing trend in CSL during the past 37 years. The current long-term decline in CSL is expected to continue into the foreseeable future, under global warming scenarios.

  17. Pediatric HIV Long-Term Nonprogressors

    B. H. Rimawi


    Full Text Available Patients infected with HIV are best categorized along a continuum from rapid progressors to HIV long-term nonprogressors. Long-term nonprogressors (LTNPs are those in which AIDS develop many years after being infected with HIV, often beyond the 10-year mark, and represent 15–20% of the HIV infected patients. Many of these patients are able to control their infection and maintain undetectable viral loads for long periods of time without antiretroviral therapy. After a comprehensive literature search, we found extensive data related to HIV LTNPs in the adult population; however, very limited data was available related to LTNPs within the pediatric population. We present a case of pediatric HIV LTNPs, perinatally infected patient with undetectable viral loads, despite never receiving ART. Although there are not many instances of LTNPs among children, this child may be one, though she had intermittent viremia. She has continued to manifest serologic evidence of infection, with yearly ELISA and western blot positive tests. Based on the viral fitness studies that were performed, this case exemplifies an adolescent LTNP.

  18. Sleep facilitates long-term face adaptation.

    Ditye, Thomas; Javadi, Amir Homayoun; Carbon, Claus-Christian; Walsh, Vincent


    Adaptation is an automatic neural mechanism supporting the optimization of visual processing on the basis of previous experiences. While the short-term effects of adaptation on behaviour and physiology have been studied extensively, perceptual long-term changes associated with adaptation are still poorly understood. Here, we show that the integration of adaptation-dependent long-term shifts in neural function is facilitated by sleep. Perceptual shifts induced by adaptation to a distorted image of a famous person were larger in a group of participants who had slept (experiment 1) or merely napped for 90 min (experiment 2) during the interval between adaptation and test compared with controls who stayed awake. Participants' individual rapid eye movement sleep duration predicted the size of post-sleep behavioural adaptation effects. Our data suggest that sleep prevented decay of adaptation in a way that is qualitatively different from the effects of reduced visual interference known as 'storage'. In the light of the well-established link between sleep and memory consolidation, our findings link the perceptual mechanisms of sensory adaptation--which are usually not considered to play a relevant role in mnemonic processes--with learning and memory, and at the same time reveal a new function of sleep in cognition.

  19. Institutionalization and Organizational Long-term Success

    Denise L. Fleck


    Full Text Available Institutionalization processes have an ambivalent effect on organizational long-term success. Even though they foster organizational stability and permanence, they also bring about rigidity and resistance to change. As a result, successful organizations are likely to lose their competitive advantage over time. The paper addresses this issue through the investigation of the institutionalization processes of two long-lived companies: General Electric, a firm that has been a long-term success and its rival, Westinghouse, which was broken up after eleven decades of existence. The longitudinal, multilevel analysis of firms and industry has identified two different modes of organizational institutionalization. The reactive mode gives rise to rigidity and change resistance, much like institutional theory predicts; the proactive mode, on the other hand, neutralizes those negative effects of institutionalization processes. In the reactive mode, structure predominates. In the proactive mode, agency plays a major role in organizational institutionalization, and in managing the organization’s relations with the environment, clearly contributing to environmental institutionalization.

  20. Effect of Long-term Different Fertilization Ways on Soil Enzyme Activities and Fertility in Dryland Black Humus Soil in the Loess Plateau%长期不同施肥方式对黄土高原旱地黑垆土土壤酶活性及其肥力的影响

    张平良; 王淑英; 姜小凤; 苏敏; 李倩


    以30 a(1979~2008)肥料长期定位试验为基础,分析探讨长期不同施肥方式对旱地黑垆土耕层(0~20 cm)土壤酶活性及其肥力的影响.结果表明:土壤脲酶活性M处理显著高于其他处理,MNP和SNP处理效果优于NP处理;土壤多酚氧化酶活性N和NP处理增加效果显著,M、MNP、SNP处理效果均不明显;土壤蛋白酶活性N处理效果最佳,显著高于其他处理;MNP、SNP处理能显著增加土壤有机质和全磷含量,有利于全氮含量的积累,表明有机-无机肥配施是旱地中低产田培肥土壤的有效措施.%By a 30-year (1979~2008) long-term located fertilizer experiment, effect of long-term different fertilization ways on soil enzyme activities and fertility in dryland black humus soil was analyzed. The results showed that, effect of M treatment generate on soil urease activity is obviously higher than other treatments, and the effect of MNP and SNP treatments generate surpass that of NP treatment; The effect of N and NP treatments generate increasing on soil polyphenoloxidase activity is remarkable, and effect of M, MNP and SNP treatments generate is not to be obvious. The effect of N treatment way on soil protein enzyme activity is very best, which obviously is higher than others; MNP and SNP treatments can obviously increase soil organic and total phosphorus contents, which is advantage to accumulate total nitrogen content, which indicated that organic-inorganic matches executes is a effective measure of the cultivating soil fertility in dryland of middle-low yielding.

  1. The observation and clinical significance of the long-term anticoagulation status in patients after mechanical heart valve replacement.%机械瓣膜置换术后远期抗凝状态观察及临床意义

    王永亮; 张伟; 万俊哲; 李少民; 裴斐; 张军


    Objective To investigate the long-term anticoagulation starus and relation of INR and complica-tion,best anticoagulation range and clinical significance in patients after mechanical heart valve replacement. Meth-ods The data of blood clotting test series(containing PT,PT% ,PTR,INR,Fbg,APTT) for patients after 6 months of mechanical heart valve replacement were collected, then the cases were divided into 4 groups according to their INR levels( group Ⅰ : INR 2.5 ). Results Group Ⅰ contained 28 person-times, with their dosage of warfarin for (3.61 ± 1.44 ) mg, INR 1.38 ± 0. 12, core-bral embolism occurred for 4 person-times,with a inception rate of 14%. Group Ⅱ contained 92 person-times,with their dosage of warfarin for (3.5±1.37)mg,INR 1.65±0. 14,hemorrhinia occurred for 2 person-times,with a in-ception rate of 2%. Group Ⅲ contained 80 person-times, with their dosage of warfarin for (3.18±1.63 )mg, INR 2.23±0.19 ,bematuria occurred for 2 person-times, bemorrhinia occurred for 2 person-times, with a total inception rate of 5% ; Group Ⅳ contained 16 person-times, with their dosage of warfarin for ( 2.32 ± 1. 23 ) mg, INR 2.80± 0.19, hemorrhinia occurred for 2 person-times and hemoptysis occurred for 1 person-times, with a total inception rate of 18.7%. The person-times in group Ⅱ and Ⅲ accounted for 79.6% and the complication rate was the lowest when INR was between 1.5-2.5. Conclusions INR levels between 1.5-2.5 is the most secure, which is the best antico-agu]ation range in our region. Since the anticoagulation strength dynamically changes, the long-term anticoagulation status in patients after mechanical heart valve replacement should be deeply concerned.%目的 了解机械心脏瓣膜置换术后远期国际标准化比值(INR)与并发症的关系,最佳抗凝强度范围及临床意义.方法 对行机械心脏瓣膜置换术后出院6个月以上的患者在门诊检查凝血三项(PT、PT%、PTR、INR、Fbg、APTY)216例

  2. Problems of long-term preservation of web pages

    Mitja Dečman


    Full Text Available The World Wide Web is a distributed collection of web sites available on the Internet anywhere in the world. Its content is constantly changing: old data are being replaced which causes constant loss of a huge amount of information and consequently the loss of scientific, cultural and other heritage. Often, unnoticeably even legal certainty is questioned. In what way the data on the web can be stored and how to preserve them for the long term is a great challenge. Even though some good practices have been developed, the question of final solution on the national level still remains. The paper presents the problems of long-term preservation of web pages from technical and organizational point of view. It includes phases such as capturing and preserving web pages, focusing on good solutions, world practices and strategies to find solutions in this area developed by different countries. The paper suggests some conceptual steps that have to be defined in Slovenia which would serve as a framework for all document creators in the web environment and therefore contributes to the consciousness in this field, mitigating problems of all dealing with these issues today and in the future.

  3. [Femoral angioplasty. Long-term results].

    Foucart, H; Carlier, C; Baudrillard, J C; Joffre, F; Cécile, J P


    A study on the long-term efficacy of femoral-popliteal angioplasty was carried out on 185 angioplasty cases over a 5 year follow-up period. A classification of data according to the type of lesion treated, revealed that results were favorable in case of stenosis (87%), short obstruction (70%) and long obstruction (35%). A special study of the outcome of treatments for stage IV arteritis was carried out. After comparing results with those obtained by other teams, the authors list the complications encountered, hematomas, and thromboses, and show their current tendency for regression. Lastly, the authors stress the advantages of angioscopy, which permits to identify the nature of the treated lesions and to predict possible complications, which are usually underrated by angiography.

  4. Technology for long-term care.

    Tak, Sunghee H; Benefield, Lazelle E; Mahoney, Diane Feeney


    Severe staff shortages in long-term care (LTC) make it difficult to meet the demands of the growing aging population. Further, technology-savvy Baby Boomers are expected to reshape the current institutional environments toward gaining more freedom and control in their care and lives. Voices from business, academia, research, advocacy organizations, and government bodies suggest that innovative technological approaches are the linchpin that may prepare society to cope with these projected demands. In this article, we review the current state of aging-related technology, identify potential areas for efficacy testing on improving the quality of life of LTC residents in future research, and discuss barriers to implementation of LTC technology. Finally, we present a vision of future technology use that could transform current care practices.

  5. Emotional behavior in long-term marriage.

    Carstensen, L L; Gottman, J M; Levenson, R W


    In exploring the emotional climate of long-term marriages, this study used an observational coding system to identify specific emotional behaviors expressed by middle-aged and older spouses during discussions of a marital problem. One hundred and fifty-six couples differing in age and marital satisfaction were studied. Emotional behaviors expressed by couples differed as a function of age, gender, and marital satisfaction. In older couples, the resolution of conflict was less emotionally negative and more affectionate than in middle-aged marriages. Differences between husbands and wives and between happy and unhappy marriages were also found. Wives were more affectively negative than husbands, whereas husbands were more defensive than wives, and unhappy marriages involved greater exchange of negative affect than happy marriages.

  6. Long-Term Stability of Horseshoe Orbits

    Ćuk, Matija; Holman, Matthew J


    Unlike Trojans, horseshoe coorbitals are not generally considered to be long-term stable (Dermott and Murray, 1981; Murray and Dermott, 1999). As the lifetime of Earth's and Venus's horseshoe coorbitals is expected to be about a Gyr, we investigated the possible contribution of late-escaping inner planet coorbitals to the lunar Late Heavy Bombardment. Contrary to analytical estimates, we do not find many horseshoe objects escaping after first 100 Myr. In order to understand this behaviour, we ran a second set of simulations featuring idealized planets on circular orbits with a range of masses. We find that horseshoe coorbitals are generally long lived (and potentially stable) for systems with primary-to-secondary mass ratios larger than about 1200. This is consistent with results of Laughlin and Chambers (2002) for equal-mass pairs or coorbital planets and the instability of Jupiter's horseshoe companions (Stacey and Connors, 2008). Horseshoe orbits at smaller mass ratios are unstable because they must approa...

  7. [Enteral nutrition through long-term jejunostomy].

    Fernández, T; Neira, P; Enríquez, C


    We present the case of a female patient suffering a peritonitis episode after subtotal gastrectomy due to gastric neoplasm in relation to lesser curvature necrosis extending to the anterior esophageal wall. This an uncommon andsevere complication that made mandatory further aggressive surgery: transection of the abdominal esophagus, transection of the gastric stump, and cervical esophagostomy with creation of a jejunostomy with a needle catheter for feeding. This digestive tube access technique is generally used during major abdominal post-surgery until oral intake is reestablished. Our patient has been 187 days with this therapy since reconstruction of the GI tract was ruled out due to tumoral infiltration of the colon and tumor recurrence at the gastrohepatic omentum. To date, there has been no complication from permanence and/or long-term use of this technique.

  8. Long-term variations of solar activity


    Using the Lomb-Scargle periodogram we analyzed two sunspot series: the one over the past 11000 years at the 10-year interval based upon the survey data of 14C concentration in tree-rings, reconstructed by Solanki et al.; and the sunspot number over the past 7000 years, derived from geomagnetic variations by Usoskin et al. We found the periods and quasi-periods in solar activity, such as about 225, 352, 441, 522 and 561 a, and near 1000 and 2000 a. An approach of wavelet transform was applied to check the two sunspot time series, with emphasis on investigating time-varying characteristics in the long-term fluctuations of solar activity. The results show that the lengths and amplitudes of the periods have changed with time, and large variations have taken place during some periods.

  9. Autobiographical reasoning in long-term fandom

    C. Lee Harrington


    Full Text Available We explore the social psychological processes through which fan-based experiences become situated in fans' larger life narratives. Drawing on original survey data with long-term U.S. soap opera fans, we examine how the psychological mechanism of autobiographical reasoning functions in fans' construction of self-narratives over time. The case study presented here is a subset of a larger investigation into the age-related structure of fans' activities, identities, and interpretive capacities. Situated at the intersections of gerontological (life span/life course theory and contemporary fan studies, our project mines relatively uninvestigated theoretical terrain. We conclude with a brief discussion of implications for future fan studies.

  10. Brodie's abscess. A long-term review.

    Stephens, M M; MacAuley, P


    In 20 patients with 21 Brodie's abscesses, a long-term review revealed that 13 occurred in the second decade of life. All had local symptoms for six weeks or more. The tibia was involved in 11 cases and seven of these were in the proximal metaphysis. The erythrocyte sedimentation rate (ESR) was elevated in only six cases. When the ESR was more than 40 mm per hour, recurrence was more likely. Staphylococcus aureus was cultured from 11 abscesses. Curettage and antibiotics for six weeks were adequate for treatment in most cases. However, lesions larger than 3 cm in diameter should be grafted, and patients with an elevated ESR require more aggressive decompression and prolonged antibiotic therapy. Lesions within the neck of the femur pose particular anatomic problems and should not be approached laterally. All cases were followed to full bone maturity. No significant leg length inequality was clinically or roentgenologically apparent. If an abscess was juxtaphyseal, deformity of the epiphysis could develop.

  11. Vertebral sarcoidosis: long-term follow-up with MRI

    Lefere, M. [University Hospitals Gasthuisberg, Department of Radiology, Leuven (Belgium); Larbi, A.; Malghem, J.; Vande Berg, B.; Dallaudiere, B. [University Hospitals St Luc, Department of Radiology, Brussels (Belgium)


    Vertebral involvement in sarcoidosis is rare and its clinical and imaging features are non-specific. Indeed, because the lesions are hard to differentiate from metastatic disease based on imaging alone, a histological confirmation is advised. Fatty replacement is a well-known finding indicating stabilization and healing in both benign and malignant conditions. It can be used as an indicator of a favorable disease course and response to treatment. We report the case of a 43-year-old woman with multifocal vertebral sarcoidosis lesions and long-term follow-up showing progressive and gradual fatty involution on magnetic resonance imaging (MRI) during 4 years of steroid treatment with a final favorable outcome. (orig.)

  12. Long-term dynamics of Typha populations

    Grace, J.B.; Wetzel, R.G.


    The zonation of Typha populations in an experimental pond in Michigan was re-examined 15 years after the original sampling to gain insight into the long-term dynamics. Current distributions of Typha populations were also examined in additional experimental ponds at the site that have been maintained for 23 years. The zonation between T. latifolia and T. angustifolia in the previously studied pond 15 years after the initial sampling revealed that the density and distribution of shoots had not changed significantly. Thus, it appears that previously reported results (based on 7- year old populations) have remained consistent over time. Additional insight into the interaction between these two taxa was sought by comparing mixed and monoculture stands in five experimental ponds that have remained undisturbed for their 23-year history. The maximum depth of T. latifolia, the shallow- water species, was not significantly reduced when growing in the presence of the more flood tolerant T. angustifolia. In contrast, the minimum depth of T. angustifolia was reduced from 0 to 37 cm when in the presence of T. latifolia. When total populations were compared between monoculture and mixed stands, the average density of T. angustifolia shoots was 59.4 percent lower in mixed stands while the density of T. latifolia was 32 percent lower, with T. angustifolia most affected at shallow depths (reduced by 92 percent) and T. latifolia most affected at the deepest depths (reduced by 60 percent). These long-term observations indicate that competitive displacement between Typha taxa has remained stable over time.

  13. Long-term reductions in tinnitus severity

    Folmer Robert L


    Full Text Available Abstract Background This study was undertaken to assess long-term changes in tinnitus severity exhibited by patients who completed a comprehensive tinnitus management program; to identify factors that contributed to changes in tinnitus severity within this population; to contribute to the development and refinement of effective assessment and management procedures for tinnitus. Methods Detailed questionnaires were mailed to 300 consecutive patients prior to their initial appointment at the Oregon Health & Science University Tinnitus Clinic. All patients were then evaluated and treated within a comprehensive tinnitus management program. Follow-up questionnaires were mailed to the same 300 patients 6 to 36 months after their initial tinnitus clinic appointment. Results One hundred ninety patients (133 males, 57 females; mean age 57 years returned follow-up questionnaires 6 to 36 months (mean = 22 months after their initial tinnitus clinic appointment. This group of patients exhibited significant long-term reductions in self-rated tinnitus loudness, Tinnitus Severity Index scores, tinnitus-related anxiety and prevalence of current depression. Patients who improved their sleep patterns or Beck Depression Inventory scores exhibited greater reductions of tinnitus severity scores than patients who continued to experience insomnia and depression at follow-up. Conclusions Individualized tinnitus management programs that were designed for each patient contributed to overall reductions in tinnitus severity exhibited on follow-up questionnaires. Identification and treatment of patients experiencing anxiety, insomnia or depression are vital components of an effective tinnitus management program. Utilization of acoustic therapy also contributed to improvements exhibited by these patients.

  14. Long term results of pneumatic retinopexy

    Ellakwa AF


    Full Text Available Amin F EllakwaMenoufiya University, Shibin el Kom, Al-Menoufiya, EgyptBackground: Rhegmatogenous retinal detachment is a commonly encountered retinal problem where rapid treatment can prevent irreversible vision loss. Pneumatic retinopexy (PR is a simple, minimally invasive procedure for retinal reattachment.Purpose: This study aimed to assess the long-term anatomical and functional outcome of pneumatic retinopexy in primary rhegmatogenous retinal detachment.Patients and methods: A prospective interventional study was performed. Subjects with rhegmatogenous retinal detachment who underwent pneumatic retinopexy from May 2006 to May 2007 at Menoufiya University Hospital were included in this study with at least 3 years follow-up.Results: A total of 40 cases were included in the study. The mean age of patients was 44.25 ± 10.85 years. Reattachment of the retina was achieved in 100% of cases. In 75% of cases, the primary intervention was successful. However, the retina redetached in 20% of these during the first 6 months, requiring reinjection or another procedure. Three years after the first intervention, follow-up measurement of the mean visual acuity of the eyes without reoperation was 0.40 ± 0.21 while the mean visual acuity of the eyes which needed additional operations was 0.22 ± 0.13.Conclusion: Sixty percent of the cases obtained long-term retinal reattachment with a single operation success (SOS, with good visual recovery and less morbidity than other more invasive procedures like scleral buckling or pars plana vitrectomy, translating to higher productivity for the patient. This procedure, being quicker than the alternatives, also saves the surgeon's time, making PR a good choice for managing primary rhegmatogenous retinal detachment in developing countries.Keywords: pneumatic, retinopexy, rhegmatogenous, retinal detachment

  15. Study on the Long-term Effect of LPS NexGen in High Flexion Knee Prosthesis Replacement%NexGen LPS高屈曲型膝关节假体置换术后中远期效果的研究

    方源; 王兰凤


    目的:用普通膝关节假体行TKA后,膝关节安全活动曲度约为100°~110°,如要完成包括下跪、下蹲等高度屈曲动作,必须选用高屈曲度设计假体。本文研究观察为膝关节高度屈曲而设计的NexGen LPS高屈曲型人工全膝关节假体置换术后中远期效果。方法回顾性分析我院106例(120膝)接受NexGen LPS高屈曲型人工全膝关节假体置换术后8~11年的患者的相关数据,包括术前、术后测量的膝关节屈曲度,及根据KSS膝关节评分系统进行评分。结果获随访106例(120膝),平均随访时间(123.5±3.2)个月(96~134个月),KSS术前膝评分平均为(46.3±15.6)分、功能评分平均为(49.5±18.6)分,术后末次随访膝评分平均为(92.7±6.1)分、功能评分平均为(81.6±17.8)分,术前膝屈曲度为<90°、90°~100°、>100°的三组患者术后屈曲度平均增加(37.6°±7.2°),(25.8°±1.9°)和(6.9°±2.1°),1例出现假体无菌性松动,1例发生感染。结论 NexGen LPS高屈曲型人工膝关节假体通过设计上的改进使理论上能达到高度屈曲,但膝关节假体置换后的屈曲度受术前屈曲度等多因素影响,术前活动度较差的患者术后获益更大,并且假体松动、感染等并发症发生率较低,术后总体中远期临床效果满意。%Objective After used the common knee prosthesis in TKA,the knee range of security activities from 100° to 110°. It was including kneeling and squatting high flexion,it must be used a high flexion prosthesis design. Our study aimed to investigate the long-term effect of LPS NexGen high flexion total knee prosthesis replacement in the design of knee joint with high flexion.Methods A retrospective analysis of 106 cases of our hospital (120 knees)received NexGen LPS high flexion type artificial total knee arthroplasty 8 to 11 years of patient related data, including preoperative and

  16. Mid-long-term Clinical Results and Hemodynamic Evaluation of Aortic Valve Replacement with 17 mm St. Jude Medical Regent Valve%17 mm St.Jude Regent瓣术后中远期临床效果和在体血流动力学评价

    刘勇; 张尔永; 方智; 古君; 钱宏


    Objective To investigate the mid-long-term clinical results of aortic valve replacement with 17 mm St. Jude medical regent valve with hemodynamic evaluation including the measurement of effective orifice area, the occurrence of prosthesis-patient mismatch (PPM) and its affect on heart function. Methods There were 44 patients accepted aortic valve replacement with 17 mm St. Jude medical regent valve because of small aortic annulus. Before the operation and during the postoperative follow-up, color doppler echocardiography was used to measure the hemodynamic parameters, such as left ventricular mass (LVmass), effective orifice area (EOA) and effective orifice area index (EOAI), etc.. Results Transthoracic echocardiographic data were obtained from 39 of 44 patients (88. 6%)at 12-55 months after surgery. One (2. 27%) died of heart failure in 1 year. According to the current standard of PPM (EOAI≤0. 85 cm2/m2) , 33 cases (82. 1%) had PPM, 13 cases (30. 8%) had severe PPM with an EOAI ≤0. 65 cm2/m2. After the operation, there were significant decreases in LVAo-PG (19 ± 8) mmHg and left ventricular mass index (LVmass I ) (86. 6 ± 23. 3) g/m2(P<0. 05). The assessment for physical capacity according to NYHA classification: 41 patients improved to class II or better and 2 patients improved to class Ⅲ (P<0. 05). Conclusion The patients with small aortic annulus may obtain satisfactory clinical results after AVR with 17 mm St. Jude medical regent valve, PPM seems not affect the mid-long-term results.%目的 观察17 mm St.Jude Regent机械瓣置入人体后中远期临床效果,测量其有效瓣口面积,评价是否发生瓣膜-患者不匹配(prosthesis-patient mismatch,PPM)现象,并探索PPM现象对术后患者心功能的影响.方法 44例心脏瓣膜病患者接受二尖瓣及主动脉瓣置换术,所有患者因主动脉瓣环小而置入17 mm St.Jude Regent机械瓣.对该组患者进行随访研究,分别于术前及术后12~55月,运用心

  17. High prevalence of long-term cardiovascular, neurological and psychosocial morbidity after treatment for craniopharyngioma.

    Pereira, Alberto M; Schmid, Eva M; Schutte, Pieter J; Voormolen, Joan H C; Biermasz, Nienke R; van Thiel, Sjoerd W; Corssmit, Eleonora P M; Smit, Jan W A; Roelfsema, Ferdinand; Romijn, Johannes A


    The treatment of craniopharyngiomas is associated with long-term morbidity. To assess the long-term functional outcome and mortality rates after treatment for craniopharyngiomas, we audited our data with special focus on cardiovascular, neurological and psychosocial morbidity. Between 1965 and 2002, 54 consecutive patients underwent surgery for craniopharyngiomas at the Leiden University Medical Centre (LUMC). Fifteen patients (25%) received additional postoperative radiation therapy. The median follow-up period was 10 years (range 1-37 years). Long-term cure rate was 82% and long-term recurrence rate 18%. Visual fields/visual acuity stabilized or improved in 74% of cases. The long-term prevalence rate of hypopituitarism was 89%. In addition, long-term cardiovascular, neurological and psychosocial morbidity rates were high: 22% (risk factors 57%), 49% and 47%, respectively. Female sex was an independent predictor of increased cardiovascular, neurological and psychosocial morbidity (odds ratio 3.78, P = 0.031). Ten patients (18%) died during an 828 person-year follow-up. The actuarial patient survival rates 5, 10 and 20 years after the initial operation were 95, 85 and 85%, respectively. The standardized mortality ratio (SMR) was 2.88 [95% confidence interval (CI) 1.35-4.99]. Craniopharyngioma is associated with excessive long-term multisystem morbidity and mortality, especially in female patients, despite a high cure rate. These observations indicate that dedicated long-term follow-up of these patients is required. The purpose of the follow-up should be: first, to look for recurrences and to ensure appropriate endocrine replacement, especially oestrogen replacement in premenopausal females; and second, to achieve intensive control of glucose, lipids, blood pressure and weight, as in any other patient with increased risk for cardiovascular disease.

  18. Preeclampsia: long-term consequences for vascular health

    Amaral LM


    Full Text Available Lorena M Amaral, Mark W Cunningham Jr, Denise C Cornelius, Babbette LaMarca Department of Pharmacology, University of Mississippi Medical Center, Jackson, MS, USA Abstract: Preeclampsia (PE is a pregnancy-specific syndrome and one of the leading causes of preterm birth, neonatal and maternal morbidity and mortality. This disease is characterized by new onset hypertension usually in the third trimester of pregnancy and is sometimes associated with proteinuria, although proteinuria is not a requirement for the diagnosis of PE. In developing countries, women have a higher risk of death due to PE than more affluent countries and one of the most frequent causes of death is high blood pressure and stroke. Although PE only affects approximately 2%–8% of pregnancies worldwide it is associated with severe complications such as eclampsia, hemorrhagic stroke, hemolysis, elevated liver enzymes and low platelets (HELLP syndrome, renal failure and pulmonary edema. Importantly, there is no “cure” for the disease except for early delivery of the baby and placenta, leaving PE a health care risk for babies born from PE moms. In addition, PE is linked to the development of cardiovascular disease and stroke in women after reproductive age, leaving PE a risk factor for long-term health in women. This review will highlight factors implicated in the pathophysiology of PE that may contribute to long-term effects in women with preeclamptic pregnancies. Keywords: preeclampsia, endothelial dysfunction, AT1-AA, CD4+ T helper cells

  19. Long-Term Care Facilities: A Cornucopia of Viral Pathogens

    Falsey, Ann R.; Dallal, Gerard E.; Formica, Maria A.; Andolina, Gloria G.; Hamer, Davidson H.; Leka, Lynette L.; Meydani, Simin Nikbin


    Objectives To determine the frequency and types of respiratory viruses circulating in Boston long-term care facilities (LTCFs) during a 3-year period. Design Observational. Setting Thirty-three Boston-area LTCFs over a 3-year period. Participants Residents of long-term care who had previously participated in a trial of vitamin E supplementation and had paired serum samples available for viral analysis. Measurements Viral antibody titers to eight respiratory viruses (influenza A and B, respiratory syncytial virus (RSV), parainfluenza virus serotype three (PIV-3), PIV-2, human metapneumovirus (hMPV), and coronaviruses 229E and OC43) were measured using enzyme immunoassay at baseline and 53 weeks. Infection was defined as a more than quadrupling of viral titers. Clinical data on respiratory illnesses were collected throughout the study period. Results A total of 617 persons were enrolled in the trial. Of these, 382 (62%) had sera available for viral analysis. A total of 204 viral infections were documented in 157 subjects. Serological responses to all eight viruses were documented, with hMPV (12.8%) and coronavirus 229E (10.5%) being the most common and PIV-2 (2.4%) the least common. The occurrence of bronchitis (P = .007), pneumonia (P = .02), and any lower respiratory tract infection (P = .002) was significantly associated with having a viral diagnosis. Conclusion A wide range of respiratory viruses cocirculates in LTCFs and contributes to respiratory illness morbidity in these populations. PMID:18557966

  20. Long-term potentiation and long-term depression: a clinical perspective

    Timothy V.P. Bliss


    Full Text Available Long-term potentiation and long-term depression are enduring changes in synaptic strength, induced by specific patterns of synaptic activity, that have received much attention as cellular models of information storage in the central nervous system. Work in a number of brain regions, from the spinal cord to the cerebral cortex, and in many animal species, ranging from invertebrates to humans, has demonstrated a reliable capacity for chemical synapses to undergo lasting changes in efficacy in response to a variety of induction protocols. In addition to their physiological relevance, long-term potentiation and depression may have important clinical applications. A growing insight into the molecular mechanisms underlying these processes, and technological advances in non-invasive manipulation of brain activity, now puts us at the threshold of harnessing long-term potentiation and depression and other forms of synaptic, cellular and circuit plasticity to manipulate synaptic strength in the human nervous system. Drugs may be used to erase or treat pathological synaptic states and non-invasive stimulation devices may be used to artificially induce synaptic plasticity to ameliorate conditions arising from disrupted synaptic drive. These approaches hold promise for the treatment of a variety of neurological conditions, including neuropathic pain, epilepsy, depression, amblyopia, tinnitus and stroke.

  1. Enhancement of drug delivery: enzyme-replacement therapy for murine Morquio A syndrome.

    Tomatsu, Shunji; Montaño, Adriana M; Dung, Vu Chi; Ohashi, Amiko; Oikawa, Hirotaka; Oguma, Toshihiro; Orii, Tadao; Barrera, Luis; Sly, William S


    Mucopolysaccharidosis IVA (MPS IVA, Morquio A disease) is an inherited lysosomal storage disorder that features skeletal chondrodysplasia caused by deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS). Human GALNS was bioengineered with the N-terminus extended by the hexaglutamate sequence (E6) to improve targeting to bone (E6-GALNS). We initially assessed blood clearance and tissue distribution. Next, to assess the effectiveness of storage clearance and reversal of pathological phenotype, a dose of 250 U/g of enzyme was given weekly to Morquio A mice (adults: 12 or 24 weeks, newborn: 8 weeks). Sulfatase modifier factor 1 (SUMF1) was co-transfected to activate the enzyme fully. The E6-GALNS tagged enzyme had markedly prolonged clearance from circulation, giving over 20 times exposure time in blood, compared to untagged enzyme. The tagged enzyme was retained longer in bone, with residual enzyme activity demonstrable at 48 hours after infusion. The pathological findings in adult mice treated with tagged enzyme showed substantial clearance of the storage materials in bone, bone marrow, and heart valves, especially after 24 weekly infusions. Mice treated from the newborn period showed marked reduction of storage materials in tissues investigated. These findings indicate the feasibility of using tagged enzyme to enhance delivery and pathological effectiveness in Morquio A mice.

  2. Assimilation of wheat starch in patients with chronic pancreatitis. Positive effect of enzyme replacement

    Nordgaard, I; Rumessen, J J; Gudmand-Høyer, E


    of the Western diet. We studied the absorption of wheat starch and the effect of pancreatic enzyme substitution in seven patients with chronic pancreatitis and steathorrea. The malabsorption was determined from hydrogen breath tests with lactulose standards as reference. Without enzyme substitution, wheat starch...

  3. Enhancement of Drug Delivery: Enzyme-replacement Therapy for Murine Morquio A Syndrome

    Tomatsu, Shunji; Montaño, Adriana M; Dung, Vu Chi; Ohashi, Amiko; Oikawa, Hirotaka; Oguma, Toshihiro; Orii, Tadao; Barrera, Luis; Sly, William S


    Mucopolysaccharidosis IVA (MPS IVA, Morquio A disease) is an inherited lysosomal storage disorder that features skeletal chondrodysplasia caused by deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS). Human GALNS was bioengineered with the N-terminus extended by the hexaglutamate sequence (E6) to improve targeting to bone (E6-GALNS). We initially assessed blood clearance and tissue distribution. Next, to assess the effectiveness of storage clearance and reversal of pathological phenotype, a dose of 250 U/g of enzyme was given weekly to Morquio A mice (adults: 12 or 24 weeks, newborn: 8 weeks). Sulfatase modifier factor 1 (SUMF1) was co-transfected to activate the enzyme fully. The E6-GALNS tagged enzyme had markedly prolonged clearance from circulation, giving over 20 times exposure time in blood, compared to untagged enzyme. The tagged enzyme was retained longer in bone, with residual enzyme activity demonstrable at 48 hours after infusion. The pathological findings in adult mice treated with tagged enzyme showed substantial clearance of the storage materials in bone, bone marrow, and heart valves, especially after 24 weekly infusions. Mice treated from the newborn period showed marked reduction of storage materials in tissues investigated. These findings indicate the feasibility of using tagged enzyme to enhance delivery and pathological effectiveness in Morquio A mice. PMID:20332769

  4. Abdominal Pain (Stomach Pain), Long-Term

    ... MALABSORPTION, an inability to absorb some foods, or LACTOSE INTOLERANCE or WHEAT INTOLERANCE (CELIAC DISEASE).Self CareAvoid the ... beverages that cause your symptoms. People who have lactose intolerance can use lactose enzyme tablets or drops to ...

  5. Elevated rheumatoid factor and long term risk of rheumatoid arthritis

    Nielsen, Sune F; Bojesen, Stig E; Schnohr, Peter;


    To test whether elevated concentration of rheumatoid factor is associated with long term development of rheumatoid arthritis.......To test whether elevated concentration of rheumatoid factor is associated with long term development of rheumatoid arthritis....

  6. Long term hypolipidaemic and anti-atherogenic effects of Carica ...

    Long term hypolipidaemic and anti-atherogenic effects of Carica papaya Linn. ... AFRICAN JOURNALS ONLINE (AJOL) · Journals · Advanced Search · USING ... This study was designed to assess the long term (24 weeks) effects of daily oral ...

  7. Seasonal And Long Term Rainfall Trends In Calabar, Nigeria ...

    Seasonal And Long Term Rainfall Trends In Calabar, Nigeria. ... AFRICAN JOURNALS ONLINE (AJOL) · Journals · Advanced Search ... Both seasonal and long term trends of rain fall in Calabar between 1985 and 2003 have been examined.

  8. Memory Vocabulary Learning Strategies and Long-Term Retention ...

    Memory Vocabulary Learning Strategies and Long-Term Retention. ... AFRICAN JOURNALS ONLINE (AJOL) · Journals · Advanced Search · USING ... The results were reflected in the students' short-term and long-term memory retention.

  9. IPO-related organizational change and long-term performance

    Eije, J.H. von; Witte, M.C. de; Zwaan, A.H. van der


    Mainstream literature on long-term performance of initial public offerings focuses on long-term underperformance. Because underperformance is an anomalous phenomenon, many authors search for explanations based on financial market imperfections. More recently, however, the attention shifts from

  10. A homeobox protein Phx1 regulates long-term survival and meiotic sporulation in Schizosaccharomyces pombe

    Kim Ji-Yoon


    Full Text Available Abstract Background In the fission yeast Schizosaccharomyces pombe, the phx1+ (pombe homeobox gene was initially isolated as a multi-copy suppressor of lysine auxotrophy caused by depletion of copper/zinc-containing superoxide dismutase (CuZn-SOD. Overproduction of Phx1 increased the synthesis of homocitrate synthase, the first enzyme in lysine biosynthetic pathway, which is labile to oxidative stress. Phx1 has a well conserved DNA-binding domain called homeodomain at the N-terminal region and is predicted to be a transcription factor in S. pombe. However, its role has not been revealed in further detail. Here we examined its expression pattern and the phenotype of its null mutant to get clues on its function. Results Fluorescence from the Phx1-GFP expressed from a chromosomal fusion gene demonstrated that it is localized primarily in the nucleus, and is distinctly visible during the stationary phase. When we replaced the N-terminal homeobox domain of Phx1 with the DNA binding domain of Pap1, a well-characterized transcription factor, the chimeric protein caused the elevation of transcripts from Pap1-dependent genes such as ctt1+ and trr1+, suggesting that Phx1 possesses transcriptional activating activity when bound to DNA. The amount of phx1+ transcripts sharply increased as cells entered the stationary phase and was maintained at high level throughout the stationary phase. Nutrient shift down to low nitrogen or carbon sources caused phx1+ induction during the exponential phase, suggesting that cells need Phx1 for maintenance function during nutrient starvation. The Δphx1 null mutant showed decreased viability in long-term culture, whereas overproduction of Phx1 increased viability. Decrease in long-term survival was also observed for Δphx1 under N- or C-starved conditions. In addition, Δphx1 mutant was more sensitive to various oxidants and heat shock. When we examined sporulation of the Δphx1/Δphx1 diploid strain, significant decrease

  11. Long-term outcome of neuroparacoccidioidomycosis treatment

    Fabio Francesconi


    Full Text Available INTRODUCTION: Neuroparacoccidioidomycosis (NPCM is a term used to describe the invasion of the central nervous system by the pathogenic fungus Paracoccidioides brasiliensis. NPCM has been described sporadically in some case reports and small case series, with little or no focus on treatment outcome and long-term follow-up. METHODS: All patients with NPCM from January 1991 to December 2006 were analyzed and were followed until December 2009. RESULTS: Fourteen (3.8% cases of NPCM were identified out of 367 patients with paracoccidioidomycosis (PCM. A combination of oral fluconazole and sulfamethoxazole/trimethoprim (SMZ/TMP was the regimen of choice, with no documented death due to Paracoccidioides brasiliensis infection. Residual neurological deficits were observed in 8 patients. Residual calcification was a common finding in neuroimaging follow-up. CONCLUSIONS: All the patients in this study responded positively to the association of oral fluconazole and sulfamethoxazole/trimethoprim, a regimen that should be considered a treatment option in cases of NPCM. Neurological sequela was a relatively common finding. For proper management of these patients, anticonvulsant treatment and physical therapy support were also needed.

  12. Long-Term Soft Denture Lining Materials

    Chladek, Grzegorz; Żmudzki, Jarosław; Kasperski, Jacek


    Long-term soft denture lining (LTSDL) materials are used to alleviate the trauma associated with wearing complete dentures. Despite their established clinical efficacy, the use of LTSDLs has been limited due to the unfavorable effects of the oral environment on some of their mechanical and performance characteristics. The unresolved issue of LTSDL colonization by Candida albicans is particularly problematic. Silicone-based LTSDL (SLTSDL) materials, which are characterized by more stable hardness, sorption and solubility than acrylic-based LTSDLs (ALTSDLs), are currently the most commonly used LTSDLs. However, SLTSDLs are more prone to debonding from the denture base. Moreover, due to their limitations, the available methods for determining bond strength do not fully reflect the actual stability of these materials under clinical conditions. SLTSDL materials exhibit favorable viscoelastic properties compared with ALTSDLs. Furthermore, all of the lining materials exhibit an aging solution-specific tendency toward discoloration, and the available cleansers are not fully effective and can alter the mechanical properties of LTSDLs. Future studies are needed to improve the microbiological resistance of LTSDLs, as well as some of their performance characteristics. PMID:28788163

  13. Long-term predictions using natural analogues

    Ewing, R.C. [Univ. of New Mexico, Albuquerque, NM (United States)


    One of the unique and scientifically most challenging aspects of nuclear waste isolation is the extrapolation of short-term laboratory data (hours to years) to the long time periods (10{sup 3}-10{sup 5} years) required by regulatory agencies for performance assessment. The direct validation of these extrapolations is not possible, but methods must be developed to demonstrate compliance with government regulations and to satisfy the lay public that there is a demonstrable and reasonable basis for accepting the long-term extrapolations. Natural systems (e.g., {open_quotes}natural analogues{close_quotes}) provide perhaps the only means of partial {open_quotes}validation,{close_quotes} as well as data that may be used directly in the models that are used in the extrapolation. Natural systems provide data on very large spatial (nm to km) and temporal (10{sup 3}-10{sup 8} years) scales and in highly complex terranes in which unknown synergisms may affect radionuclide migration. This paper reviews the application (and most importantly, the limitations) of data from natural analogue systems to the {open_quotes}validation{close_quotes} of performance assessments.

  14. Long-term corrosion testing pan.

    Wall, Frederick Douglas; Brown, Neil R. (Los Alamos National Laboratory, Los Alamos, NM)


    This document describes the testing and facility requirements to support the Yucca Mountain Project long-term corrosion testing needs. The purpose of this document is to describe a corrosion testing program that will (a) reduce model uncertainty and variability, (b) reduce the reliance upon overly conservative assumptions, and (c) improve model defensibility. Test matrices were developed for 17 topical areas (tasks): each matrix corresponds to a specific test activity that is a subset of the total work performed in a task. A future document will identify which of these activities are considered to be performance confirmation activities. Detailed matrices are provided for FY08, FY09 and FY10 and rough order estimates are provided for FY11-17. Criteria for the selection of appropriate test facilities were developed through a meeting of Lead Lab and DOE personnel on October 16-17, 2007. These criteria were applied to the testing activities and recommendations were made for the facility types appropriate to carry out each activity. The facility requirements for each activity were assessed and activities were identified that can not be performed with currently available facilities. Based on this assessment, a total of approximately 10,000 square feet of facility space is recommended to meet all future testing needs, given that all testing is consolidated to a single location. This report is a revision to SAND2007-7027 to address DOE comments and add a series of tests to address NWTRB recommendations.

  15. Long-term corrosion testing plan.

    Wall, Frederick Douglas; Brown, Neil R. (Los Alamos National Laboratory, Los Alamos, NM)


    This document describes the testing and facility requirements to support the Yucca Mountain Project long-term corrosion testing program. The purpose of this document is to describe a corrosion testing program that will (a) reduce model uncertainty and variability, (b) reduce the reliance upon overly conservative assumptions, and (c) improve model defensibility. Test matrices were developed for 17 topical areas (tasks): each matrix corresponds to a specific test activity that is a subset of the total work performed in a task. A future document will identify which of these activities are considered to be performance confirmation activities. Detailed matrices are provided for FY08, FY09 and FY10 and rough order estimates are provided for FY11-17. Criteria for the selection of appropriate test facilities were developed through a meeting of Lead Lab and DOE personnel on October 16-17, 2007. These criteria were applied to the testing activities and recommendations were made for the facility types appropriate to carry out each activity. The facility requirements for each activity were assessed and activities were identified that can not be performed with currently available facilities. Based on this assessment, a total of approximately 10,000 square feet of facility space is recommended to accommodate all future testing, given that all testing is consolidated to a single location. This report is a revision to SAND2008-4922 to address DOE comments.

  16. Downlink Scheduling in Long Term Evolution

    Anwar Hossain


    Full Text Available This is an investigated research article on resource block scheduling of Long Term Evolution (LTE. LTE is one of the evolutions of the Universal Mobile Telecommunication System (UMTS. It provides internet access to mobile users through smart phone, laptop and other android devices. LTE offers a high speed data and multimedia services. It supports data rates up to 100 Mbps in the downlink and 50 Mbps in the uplink transmission. Our research investigation was aim to the downlink scheduling. We have considered The Best CQI scheduling algorithm and the Round Robin scheduling algorithm. The implementation, analysis and comparison of these scheduling algorithms have been performed through MATLAB simulator. We have analyzed the impact of the scheduling schemes on the throughput and the fairness of both scheduling schemes. Here we have proposed a new scheduling algorithm that achieves a compromise between the throughput and the fairness. Orthogonal Frequency Division Multiplexing (OFDM has been adopted as the downlink transmission scheme. We have considered the impact of the channel delay on the throughput. In addition, MIMO transceiver systems have been implemented to increase the throughput

  17. Long Term Evolution of Plasma Wakefields

    Sahai, Aakash A; Tsung, F S; Mori, W B


    We study the long-term evolution (LTE) of plasma wakefields over multiple plasma-electron periods and few plasma-ion periods, much less than a recombination time. The evolution and relaxation of such a wakefield-perturbed plasma over these timescales has important implications for the upper limits of repetition-rates in plasma colliders. Intense fields in relativistic lasers (or intense beams) create plasma wakefields (modes around {\\omega}pe) by transferring energy to the plasma electrons. Charged-particle beams in the right phase may be accelerated with acceleration/focusing gradients of tens of GeV/m. However, wakefields leave behind a plasma not in equilibrium, with a relaxation time of multiple plasma-electron periods. Ion motion over ion timescales, caused by energy transfer from the driven plasma-electrons to the plasma-ions can create interesting plasma states. Eventually during LTE, the dynamics of plasma de-coheres (multiple modes through instability driven mixing), thermalizing into random motion (...

  18. Long term results of mandibular distraction

    Batra Puneet


    Full Text Available Mandibular distraction osteogenesis has become a popular surgical modality due to its many advantages over conventional orthognathic surgical procedures. However, in spite of the technique having been used for over 15 years, no concrete long term results are available regarding the stability of results. We discuss the various studies which have reported either in favour or against the stablility of results after distraction. We report a series of 6 cases (3 unilateral and 3 bilateral distraction where distraction was carried out before puberty and followed them up to seven years after removal of distractors. This case series shows that results achieved by distraction osteogenesis are unstable or best unpredictable with respect to producing a permanent size increase in the mandible. The role of the distraction osteogenesis in overcoming the pterygomassetric sling is questionable. We suggest a multicenter study with adequate patient numbers treated with a similar protocol and documented after growth cessation to have meaningful conclusions on the debate of distraction osteogenesis versus orthognathic surgery.

  19. Long-term data storage in diamond

    Dhomkar, Siddharth; Henshaw, Jacob; Jayakumar, Harishankar; Meriles, Carlos A.


    The negatively charged nitrogen vacancy (NV−) center in diamond is the focus of widespread attention for applications ranging from quantum information processing to nanoscale metrology. Although most work so far has focused on the NV− optical and spin properties, control of the charge state promises complementary opportunities. One intriguing possibility is the long-term storage of information, a notion we hereby introduce using NV-rich, type 1b diamond. As a proof of principle, we use multicolor optical microscopy to read, write, and reset arbitrary data sets with two-dimensional (2D) binary bit density comparable to present digital-video-disk (DVD) technology. Leveraging on the singular dynamics of NV− ionization, we encode information on different planes of the diamond crystal with no cross-talk, hence extending the storage capacity to three dimensions. Furthermore, we correlate the center’s charge state and the nuclear spin polarization of the nitrogen host and show that the latter is robust to a cycle of NV− ionization and recharge. In combination with super-resolution microscopy techniques, these observations provide a route toward subdiffraction NV charge control, a regime where the storage capacity could exceed present technologies.


    Hegde Nidarsh D.


    Full Text Available Oral ulcers is a very common disorder of the oral mucosa. Patients with signs or symptoms of oral ulcers are sometimes referred to gastroenterology clinics, however, in most instances the ulcers does not reflect gastrointestinal disease, some with a chronic non- healing ulcer are advised biopsy. Indeed, a spectrum of disorders can give rise to oral mucosal ulcers ranging from minor local trauma to significant local disease such as malignancy or systemic illness. Lesions of the tongue have a broad differential diagnosis ranging from benign idiopathic processes to infections, cancers, and infiltrative disorders. This article will focus on common ulcerative disorders of the tongue in aspects of their clinical features and differential diagnosis, two case reports with the diagnosis and conservative management for long-term chronic ulcers. The two cases which are reported in this article had a differential diagnosis of Squamous cell carcinoma of the tongue. The clinical picture was craterlike lesion, having a velvety-red base and a rolled, indurated border and most important painless in both cases. Removal of the irritant which was the tooth, rehabilitation of the oral mucosa by lubrication with Cocus Nucifera resulted in the healing of the ulcers. Functional components of Cocus Nucifera are Squaline, tocopherol, phytosterols and other sterols which are all plant steroids.

  1. Long-Term Soft Denture Lining Materials

    Grzegorz Chladek


    Full Text Available Long-term soft denture lining (LTSDL materials are used to alleviate the trauma associated with wearing complete dentures. Despite their established clinical efficacy, the use of LTSDLs has been limited due to the unfavorable effects of the oral environment on some of their mechanical and performance characteristics. The unresolved issue of LTSDL colonization by Candida albicans is particularly problematic. Silicone-based LTSDL (SLTSDL materials, which are characterized by more stable hardness, sorption and solubility than acrylic-based LTSDLs (ALTSDLs, are currently the most commonly used LTSDLs. However, SLTSDLs are more prone to debonding from the denture base. Moreover, due to their limitations, the available methods for determining bond strength do not fully reflect the actual stability of these materials under clinical conditions. SLTSDL materials exhibit favorable viscoelastic properties compared with ALTSDLs. Furthermore, all of the lining materials exhibit an aging solution-specific tendency toward discoloration, and the available cleansers are not fully effective and can alter the mechanical properties of LTSDLs. Future studies are needed to improve the microbiological resistance of LTSDLs, as well as some of their performance characteristics.

  2. CERN Services for Long Term Data Preservation

    Shiers, Jamie; Blomer, Jakob; Ganis, Gerardo; Dallmeier-Tiessen, Sunje; Simko, Tibor; Cancio Melia, German; CERN. Geneva. IT Department


    In this paper we describe the services that are offered by CERN for Long Term preservation of High Energy Physics (HEP) data, with the Large Hadron Collider (LHC) as a key use case. Data preservation is a strategic goal for European High Energy Physics (HEP), as well as for the HEP community worldwide and we position our work in this global content. Specifically, we target the preservation of the scientific data, together with the software, documentation and computing environment needed to process, (re-)analyse or otherwise (re-)use the data. The target data volumes range from hundreds of petabytes (PB – 10^15 bytes) to hundreds of exabytes (EB – 10^18 bytes) for a target duration of several decades. The Use Cases driving data preservation are presented together with metrics that allow us to measure how close we are to meeting our goals, including the possibility for formal certification for at least part of this work. Almost all of the services that we describe are fully generic – the exception being A...

  3. 40 CFR 52.29 - Visibility long-term strategies.


    ...-term strategy. (1) A long-term strategy is a 10- to 15-year plan for making reasonable progress toward... every 3 years from November 24, 1987. (3) During the long-term strategy review process, the... 40 Protection of Environment 3 2010-07-01 2010-07-01 false Visibility long-term strategies. 52.29...

  4. TIA and Stroke: the long-term perspective

    Wijk, I. van


    Background Survival after stroke has improved, but little is known about the long-term risk of new vascular events and the functioning of long-term survivors. The main objective of this thesis was to evaluate the long-term perspective of these patients. Methods Two longitudinal studies were carried


    Daniela-Emanuela Danacica; Raluca Mazilescu


    The aim of this paper is to analyze characteristics of long-term unemployment spells in Romania and to estimate the effect of factors influencing long-term unemployment spells. The study period is in between January 1st 2008 and December 31st 2010. 468159 long-term spells registered in the specified period at the National Agency of Employment are analyzed.

  6. 有机肥和化肥长期施用对土壤活性有机氮组分及酶活性的影响%Long-term effects of mineral versus organic fertilizers on soil labile nitrogen fractions and soil enzyme activities in agricultural soil

    宋震震; 李絮花; 李娟; 林治安; 赵秉强


    本文以中国农业科学院山东禹城长期定位施肥试验为平台,研究了长期施用有机肥和化肥26年后对土壤活性氮库不同组分[颗粒有机氮(POM-N)、可溶性有机氮(DON)、微生物量氮(SMBN)及轻组有机氮(LFOM-N)]及土壤酶活性的影响。结果表明,与不施肥相比,长期施肥显著提高了土壤全氮、颗粒有机氮、可溶性有机氮、微生物量氮以及轻组有机氮的含量,长期施有机肥效果好于化肥,施用高量有机肥效果好于施用常量有机肥。常量施用量下,50%有机肥和50%化肥配施处理其土壤全氮和活性有机氮库各组分含量与高量化肥处理的相当。长期施化肥处理土壤全氮及活性有机氮库各组分含量随施肥量的增加而显著增高。 POM-N对土壤全氮的贡献率最高,且明显受施肥方式的影响,LFOM-N对土壤全氮的贡献率不随施肥方式的改变而变化。长期施肥处理土壤脲酶、碱性磷酸酶和蔗糖酶活性显著增加,它们之间及与土壤全氮、速效磷及有机碳含量间呈现显著或极显著相关性,脲酶活性与土壤各活性氮组分间也存在显著或极显著相关性;但长期施肥后土壤过氧化氢酶的活性低于不施肥处理。%In this paper, the effects of long-term application of organic fertilizer and chemical fertilizer on soil labile nitrogen fractions and some kinds of soil enzyme activities ( urease, catalase, alkaline phosphatase and sucrase ) were studied based on a 26-year long-term field experiment in Chinese Academy of Agricultural Sciences Research Station in Yucheng City, Shandong province, China.The results show that, compared with CK, long term fertilization significantly increases soil total nitrogen , particle organic nitrogen ( POM-N ) , dissolved organic nitrogen ( DON ) , microbial biomass nitrogen ( MBN ) and light fraction organic nitrogen ( LFON ) contents . Treatments of applying organic

  7. 自体听骨与人工听骨在听骨链重建术中远期疗效的对比观察%Contradistinction of Long-term Effect between Self-incus and Partial Ossicular Replacement Prosthesis in Reconstruction of Ossicular Chain

    张社江; 习国平; 马喆; 郝艳芳; 蔡爱军


    Objective To observe long-term effect of self-incus and partial ossicular replacement prosthesis( PORP ) in reconstruction of ossicular chain, to seek preferable materials of reconstruction of ossicular chain. Methods The efficacy of ossicular reconstruction with PORP and self-incus were retrospectively summed up in 58 ears and 69 ears. All patients were followed up for six months to 3 years. All patients were examined by audiometric measurement( the average hearing threshold at 0.5,1.0,2.0 kHz ) before and after reconstruction of ossicular chain. We also compared the influence of different inserts. Results Hearing improvement between two different inserts had no statistical difference( P > 0.05 ). All patients healed well at one month. 6 ears were discovered prolapsed auricular bone in PORP group at 3 month to 3 year, while no patients were discovered bone resorption or prolapse in self-incus group. Only 1 case of eardrum reperfotation occurred in self-incus group( cholesteatoma tympanitis ). Conclusion Self-incus could be a useful and ideal materials in reconstruction of ossicular chain. with an advantage over PORP.%目的 通过自体听骨与人工听骨在听骨链重建术中远期疗效的对比观察,寻求听骨链重建术更好的材料.方法 对接受人工听骨(PORP)植入进行陈旧性中耳炎听骨链重建的患者及接受自体听骨植入进听骨链重建的患者,随访半年以上、资料完整的病例进行回顾性总结,进行疗效对比分析.计算语言频率(分别为0.5、1、2 kHz)平均听力,比较PORP植入及自体听骨植入的疗效.结果 两组植入物鼓膜修补术后纯音测听语言频率,听力提高情况间差异无统计学意义(P>0.05).1个月复查所有患者均愈合良好,术后3个月至3年PORP植入组发现6例听骨脱出,自体听骨植入组未发现听骨吸收及排出现象,仅1例鼓膜再穿孔(胆脂瘤型中耳炎).结论 自体听骨是听骨链重建中理想的材料,优于PORP.

  8. Biochemical Characterization of Porphobilinogen Deaminase–Deficient Mice During Phenobarbital Induction of Heme Synthesis and the Effect of Enzyme Replacement

    Johansson, Annika; Möller, Christer; Fogh, Jens; Harper, Pauline


    Acute intermittent porphyria (AIP) is a genetic disorder caused by a deficiency of porphobilinogen deaminase (PBGD), the 3rd enzyme in heme synthesis. It is clinically characterized by acute attacks of neuropsychiatric symptoms and biochemically by increased urinary excretion of the porphyrin precursors porphobilinogen (PBG) and 5-aminolevulinic acid (ALA). A mouse model that is partially deficient in PBGD and biochemically mimics AIP after induction of the hepatic ALA synthase by phenobarbital was used in this study to identify the site of formation of the presumably toxic porphyrin precursors and study the effect of enzyme-replacement therapy by using recombinant human PBGD (rhPBGD). After 4 d of phenobarbital administration, high levels of PBG and ALA were found in liver, kidney, plasma, and urine of the PBGD-deficient mice. The administration of rhPBGD intravenously or subcutaneously after a 4-d phenobarbital induction was shown to lower the PBG level in plasma in a dose-dependent manner with maximal effect seen after 30 min and 2 h, respectively. Injection of rhPBGD subcutaneously twice daily during a 4-d phenobarbital induction reduced urinary PBG excretion to 25% of the levels found in PBGD-deficient mice administered with only phenobarbital. This study points to the liver as the main producer of PBG and ALA in the phenobarbital-induced PBGD-deficient mice and demonstrates efficient removal of accumulated PBG in plasma and urine by enzyme-replacement therapy. PMID:15208740

  9. Scientific Understanding from Long Term Observations: Insights from the Long Term Ecological Research (LTER) Program

    Gosz, J.


    The network dedicated to Long Term Ecological Research (LTER) in the United States has grown to 24 sites since it was formed in 1980. Long-term research and monitoring are performed on parameters thatare basic to all ecosystems and are required to understand patterns, processes, and relationship to change. Collectively, the sites in the LTER Network provide opportunities to contrast marine, coastal, and continental regions, the full range of climatic gradients existing in North America, and aquatic and terrestrial habitats in a range of ecosystem types. The combination of common core areas and long-term research and monitoring in many habitats have allowed unprecedented abilities to understand and compare complex temporal and spatial dynamics associated with issues like climate change, effects of pollution, biodiversity and landuse. For example, McMurdo Dry Valley in the Antarctic has demonstrated an increase in glacier mass since 1993 which coincides with a period of cooler than normal summers and more than average snowfall. In contrast, the Bonanza Creek and Toolik Lake sites in Alaska have recorded a warming period unprecedented in the past 200 years. Nitrogen deposition effects have been identified through long-term watershed studies on biogeochemical cycles, especially at Coweeta Hydrological Lab, Harvard Forest, and the Hubbard Brook Experimental Forest. In aquatic systems, such as the Northern Temperate Lakes site, long-term data revealed time lags in effects of invaders and disturbance on lake communities. Biological recovery from an effect such as lake acidification was shown to lag behind chemical recovery. The long-term changes documented over 2 decades have been instrumental in influencing management practices in many of the LTER areas. In Puerto Rico, the Luquillo LTER demonstrated that dams obstruct migrations of fish and freshwater shrimp and water abstraction at low flows can completely obliterate downstream migration of juveniles and damage

  10. Modeling Maintenance of Long-Term Potentiation in Clustered Synapses: Long-Term Memory without Bistability

    Paul Smolen


    Full Text Available Memories are stored, at least partly, as patterns of strong synapses. Given molecular turnover, how can synapses maintain strong for the years that memories can persist? Some models postulate that biochemical bistability maintains strong synapses. However, bistability should give a bimodal distribution of synaptic strength or weight, whereas current data show unimodal distributions for weights and for a correlated variable, dendritic spine volume. Thus it is important for models to simulate both unimodal distributions and long-term memory persistence. Here a model is developed that connects ongoing, competing processes of synaptic growth and weakening to stochastic processes of receptor insertion and removal in dendritic spines. The model simulates long-term (>1 yr persistence of groups of strong synapses. A unimodal weight distribution results. For stability of this distribution it proved essential to incorporate resource competition between synapses organized into small clusters. With competition, these clusters are stable for years. These simulations concur with recent data to support the “clustered plasticity hypothesis” which suggests clusters, rather than single synaptic contacts, may be a fundamental unit for storage of long-term memory. The model makes empirical predictions and may provide a framework to investigate mechanisms maintaining the balance between synaptic plasticity and stability of memory.

  11. Nutritional deficit and Long Term Potentiation alterations

    M. Petrosino


    Full Text Available In the present work we examined the ability of prenatally malnourished offspring to produce and maintain long-term potentiation (LTP of the perforant path/dentate granule cell synapse in freely moving rats at 15,30, and 90 days of age. Population spike amplitude (PSA was calculated from dentate field potential recordings prior to and at 15, 30, 60 min. and 3, 5, 18 and 24 h following tetanization of the perforant pathway. All animals of both malnourished and well-nourished diet groups at 15 days of age showed potentiation of PSA measures but the measures obtained from 15-day-old prenatally malnourished animals were significantly less than that of age-matched, well-nourished controls. At 30 days of age, remarkable effect of tetanization was likely observed from PSA measures for this age group followed much the same pattern. At 90 days of age, PSA measures obtained from malnourished animals decreased from pretetanization levels immediately following tetanization. At this age, however, at three hours time recordings, this measure growing up to a level which did not differ significantly from that of the control group. These results indicate that the width of tetanization induced enhancement of dentate granule cell response in preweanling rats (15-day-old animals is signifacantly affected fromgestational protein malnutrition and this trend is kept in animals tested at 30 and 90 days of age. The fact, however, that considerable limitation in LTP generation was gained from prenatally malnourished animals at 90 days of age, implying that dietary rehabilitation starting at birth is an intervention strategy not capable to imbrove the effects of the gestational stress.

  12. A new long-term care manifesto.

    Kane, Robert L


    This article argues for a fresh look at how we provide long-term care (LTC) for older persons. Essentially, LTC offers a compensatory service that responds to frailty. Policy debate around LTC centers on costs, but we are paying for something we really don't want. Building societal enthusiasm (or even support) for LTC will require re-inventing and re-branding. LTC has three basic components: personal care, housing, and health care (primarily chronic disease management). They can be delivered in a variety of settings. It is rare to find all three done well simultaneously. Personal care (PC) needs to be both competent and compassionate. Housing must provide at least minimal amenities and foster autonomy; when travel time for PC raises costs dramatically, some form of clustered housing may be needed. Health care must be proactive, aimed at preventing exacerbations of chronic disease and resultant hospitalizations. Enhancing preferences means allowing taking informed risks. Payment incentives should reward both quality of care and quality of life, but positive outcomes must be defined as slowing decline. Paying for services but not for housing under Medicaid would automatically level the playing field between nursing homes (NH) and community-based services. Regulations should achieve greater parity between NH and community care and include both positive and negative feedback. Providing post-acute care should be separate from LTC. Using the tripartite LTC framework, we can create innovative flexible approaches to providing needed services for frail older persons in formats that are both desirable and affordable. Such care will be more socially desirable and hence worth paying for.

  13. Long term cultivation of larger benthic Foraminifera

    Wöger, Julia; Eder, Wolfgang; Kinoshita, Shunichi; Antonino, Briguglio; Carles, Ferrandes-Cañadell; Hohenegger, Johann


    Benthic Foraminifera are used in a variety of applications employing numerous different methods, i.e. ecological monitoring, studying the effects of ocean acidification, reconstructing palaeo-bathymetry or investigating palaeo-salinity and palaeo-temperature to name only a few. To refine our understanding of ecological influences on larger benthic foraminiferal biology and to review inferences from field observations, culture experiments have become an indispensable tool. While culture experiments on smaller benthic foraminifera have become increasingly frequent in the past century, reports of the cultivation of symbiont bearing larger Foraminifera are rare. Generally, cultivation experiments can be divided into two groups: Culturing of populations and cultivation of single specimens allowing individual investigation. The latter differ form the former by several restrictions resulting from the need to limit individual motility without abridging microenvironmental conditions in the Foraminiferans artificial habitat, necessary to enable the individual to development as unfettered as possible. In this study we present first experiences and preliminary results of the long-term cultivation of larger benthic Foraminifera conducted at the 'Tropical Biosphere Research Station Sesoko Island, University of the Ryukyus', Japan, trying to reproduce natural conditions as closely as possible. Individuals of three species of larger benthic Foraminifera (Heterostegina depressa, Palaeonummulites venosus and Operculina complanata) have been cultured since April 2014. At the time of the general assembly the cultivation experiments will have been going on for more than one year, with the aim to investigate growth rates, longevities and reproduction strategies for comparison with results statistically inferred from application of the of the 'natural laboratory' method. The most important factor influencing foraminiferal health and development was found to be light intensity and light

  14. Hormonal changes during long-term isolation.

    Custaud, M A; Belin de Chantemele, E; Larina, I M; Nichiporuk, I A; Grigoriev, A; Duvareille, M; Gharib, C; Gauquelin-Koch, G


    Confinement and inactivity induce considerable psychological and physiological modifications through social and sensory deprivation. The aim of the SFINCSS-99 experiment was to determine the cardiovascular and hormonal pattern of blood volume regulation during long-term isolation and confinement. Simulation experiments were performed in pressurized chambers similar in size to the volumes of modern space vehicles. Group I consisted of four Russian male volunteers, who spent 240 days in a 100-m(3 )chamber. Group II included four males (one German and three Russians) who spent 110 days in isolation (200-m(3) module). The blood samples, taken before, during and after the isolation period, were used to determine haematocrit (Ht), growth hormone (GH), active renin, aldosterone, and osmolality levels. From the urine samples, electrolytes, osmolality, nitrites, nitrates, cortisol, antidiuretic hormone (ADH), aldosterone, normetanephrine and metanephrine levels were determined. The increase in plasma volume (PV) that is associated with a tendency for a decrease in plasma active renin is likely to be due to decreased sympathetic activity, and concords with the changes in urinary catecholamine levels during confinement. Urinary catecholamine levels were significantly higher during the recovery period than during confinement. This suggests that the sympathoadrenal system was activated, and concords with the increase in heart rate. Vascular resistance is determined by not only the vasoconstrictor but also vasodilator systems. The ratio of nitrite/nitrate in urine, as an indicator of nitric oxide release, did not reveal any significant changes. Analysis of data suggests that the duration of the isolation was a main factor involved in the regulation of hormones.

  15. Perinatal respiratory infections and long term consequences

    Luciana Indinnimeo


    Full Text Available Respiratory syncytial virus (RSV is the most important pathogen in the etiology of respiratory infections in early life. 50% of children are affected by RSV within the first year of age, and almost all children become infected within two years. Numerous retrospective and prospective studies linking RSV and chronic respiratory morbidity show that RSV bronchiolitis in infancy is followed by recurrent wheezing after the acute episod. According to some authors a greater risk of wheezing in children with a history of RSV bronchiolitis would be limited to childhood, while according to others this risk would be extended into adolescence and adulthood. To explain the relationship between RSV infection and the development of bronchial asthma or the clinical pathogenetic patterns related to a state of bronchial hyperreactivity, it has been suggested that RSV may cause alterations in the response of the immune system (immunogenic hypothesis, activating directly mast cells and basophils and changing the pattern of differentiation of immune cells present in the bronchial tree as receptors and inflammatory cytokines. It was also suggested that RSV infection can cause bronchial hyperreactivity altering nervous airway modulation, acting on nerve fibers present in the airways (neurogenic hypothesis.The benefits of passive immunoprophylaxis with palivizumab, which seems to represent an effective approach in reducing the sequelae of RSV infection in the short- and long-term period, strengthen the implementation of prevention programs with this drug, as recommended by the national guidelines of the Italian Society of Neonatology. Proceedings of the 11th International Workshop on Neonatology and Satellite Meetings · Cagliari (Italy · October 26th-31st, 2015 · From the womb to the adultGuest Editors: Vassilios Fanos (Cagliari, Italy, Michele Mussap (Genoa, Italy, Antonio Del Vecchio (Bari, Italy, Bo Sun (Shanghai, China, Dorret I. Boomsma (Amsterdam, the

  16. Long-term outcomes of treatment of hyperthyroidism in Ireland.

    Leary, A C


    We investigated the long-term outcome of treatment in 159 patients with hyperthyroidism first seen between 1979 and 1992. Median duration of follow-up was 10 1\\/2 years. We also inquired into current practice for the follow-up of hyperthyroidism by other endocrinologists in Ireland. Seven cases of unrecognised hyperthyroidism (4 per cent) and one of unrecognised hypothyroidism were identified. Among patients with Graves\\' disease, of those treated with an antithyroid drug, 28 per cent were in remission, 68 per cent had relapsed and 4 per cent had become hypothyroid. Of those treated by sub-total thyroidectomy, 31 per cent were in remission, 19 per cent had relapsed, 19 per cent were hypothyroid and 31 per cent were sub-clinically hypothyroid. Among patients treated with radioiodine, 19 per cent were euthyroid, 3 per cent were still hyperthyroid and three-quarters had become hypothyroid. In contrast, after radioiodine for toxic nodular goitre, 63 per cent were euthyroid and only 32 per cent had become hypothyroid (Chi Squared v. Graves\\' disease, P = 0.001). Of 73 patients receiving thyroxine replacement, plasma TSH was normal in only 41 per cent, although 82 per cent of patients had been seen by the family doctor within the previous 12 months. Seven of 17 other endocrinologists undertook long-term follow-up of hyperthyroid patients in their specialist clinics but none was using a computerised system to co-ordinate this. The findings confirm that careful follow-up is required for all hyperthyroid patients. The family doctor is well positioned to undertake this, but education and auditing are required.

  17. Enzyme Replacement Therapy With Elosulfase Alfa Decreases Storage of Glycosaminoglycan in White Blood Cells of Patients With Morquio A Syndrome

    Guilherme Baldo PhD


    Full Text Available Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome is a lysosomal storage disorder caused by a deficient N-acetylgalactosamine-6-sulfate sulfatase activity, leading to cellular storage of undegraded keratan sulfate. Recently enzyme replacement therapy (ERT was approved for MPS IVA, but some of ERT effects are still unknown. In the present study, we aimed to evaluate the efficacy of elosulfase alfa upon glycosaminoglycan (GAG storage in peripheral blood white blood cells of patients with MPS IVA treated for 6 months, comparing samples from patients who received weekly infusions of enzyme (ERT-W versus infusions every other week (ERT-EOW versus placebo. A significant reduction in GAG storage was observed in both ERT-treated groups, with weekly ERT showing slightly better performance than ERT-EOW.

  18. Survival, Quality of Life and Effects of Enzyme Replacement Therapy in Adults with Pompe Disease

    D. Güngör (Deniz)


    textabstractPompe disease, or glycogen storage disorder type II, is a rare inherited metabolic disorder caused by deficiency of the lysosomal enzyme acid α-glucosidase. This results in accumulation of glycogen in cells throughout the body, particularly muscle cells. The disease presents

  19. Survival, Quality of Life and Effects of Enzyme Replacement Therapy in Adults with Pompe Disease

    D. Güngör (Deniz)


    textabstractPompe disease, or glycogen storage disorder type II, is a rare inherited metabolic disorder caused by deficiency of the lysosomal enzyme acid α-glucosidase. This results in accumulation of glycogen in cells throughout the body, particularly muscle cells. The disease presents with (progre

  20. Replacing corn with pearl millet (raw and sprouted) with and without enzyme in chickens' diet.

    Afsharmanesh, M; Ghorbani, N; Mehdipour, Z


    An experiment was conducted to compare a commercial corn-soya bean meal diet with a pearl millet (raw and sprouted) diet containing less soya bean meal, alone or in combination with exogenous enzyme, on growth performance and ileal villus development of chicks. Two-hundred-and-forty-one-day-old male broilers (10/pen) were randomly allocated to one of the following dietary treatments: (i) a standard corn-soya bean meal control diet (CTL); (ii) a raw pearl millet-soya bean meal diet (PM); (iii) a sprouted pearl millet-soya bean meal diet (SPM); (iv) CTL + exogenous enzymes (CE); (v) PM + exogenous enzymes (PE); and (vi) SPM + exogenous enzymes (SPE) with four replicate pens/treatment. Body weight of birds at day 21 did not differ between those fed the CTL, and SPM and PE diets. In comparison with feeding broilers the CTL diet, feeding the PE and SPM diets caused significant decrease in feed intake, but with equivalent growth and feed efficiency. However, at day 21, feed conversion ratio did not differ between birds fed the CTL diet and those fed the PM, PE and SPM diets. At day 21, broilers fed the PM and PE diets had longer villi (p diet. At day 21, villi width was reduced (p diet. It is concluded that, in comparison with corn, broiler diets formulated with sprouted pearl millet or pearl millet with enzyme require less soya bean meal and can be used to improve growth performance traits and villus development.

  1. Partial resolution of bone lesions. A child with severe combined immunodeficiency disease and adenosine deaminase deficiency after enzyme-replacement therapy

    Yulish, B.S.; Stern, R.C.; Polmar, S.H.


    A child with severe combined immunodeficiency disease and adenosine deaminase deficiency, with characteristic bone dysplasia, was treated with transfusions of frozen irradiated RBCs as a means of enzyme replacement. This therapy resulted in restoration of immunologic competence and partial resolution of the bone lesions. Although the natural history of these lesions without therapy is not known, enzyme-replacement therapy may have played a role in the resolution of this patient's bone lesions.

  2. Anti-BlyS antibody reduces the immune reaction against enzyme and enhances the efficacy of enzyme replacement therapy in Fabry disease model mice.

    Sato, Yohei; Ida, Hiroyuki; Ohashi, Toya


    Formation of antibodies against a therapeutic enzyme is an important complication during enzyme replacement therapy (ERT) for lysosomal storage diseases. Fabry disease (FD) is caused by a deficiency of alpha-galactosidase (GLA), which results in the accumulation of globotriaosylceramide (GL-3). We have shown immune tolerance induction (ITI) during ERT in FD model mice by using an anti-B lymphocyte stimulator (anti-BlyS) antibody (belimumab). A single dose of the anti-BlyS antibody temporarily lowered the percentage of B cells and IgG antibody titer against recombinant human GLA. Administration of a low maintenance dose of the anti-BlyS antibody suppressed the B cell population and immunotolerance was induced in 20% of mice, but antibody formation could not be prevented. We then increased the maintenance dose of the anti-BlyS antibody and immunotolerance was induced in 50% of mice. Therapeutic enzyme distribution and clearance of GL-3 were also enhanced by a high maintenance dose of the anti-BlyS antibody.

  3. Administrative Circular No. 22B (Rev. 2) - Compensation for hours of long-term shift work

    Department Head Office - HR Department


    Administrative Circular No. 22B (Rev. 2) entitled "Compensation for hours of long-term shift work",  approved by the Director-General following discussion in the Standing Concertation Committee meeting on 22 March 2016, will be available on 1st September 2016 via the following link:   This revised circular cancels and replaces Administrative Circular No. 22B (Rev. 1) also entitled "Compensation for hours of long-term shift work" of March 2011. This document contains minor changes to reflect the new career structure. This circular will enter into force on 1st September 2016.


    Kwok, J. H.


    The Long-Term Orbit Predictor (LOP) trajectory propagation program is a useful tool in lifetime analysis of orbiting spacecraft. LOP is suitable for studying planetary orbit missions with reconnaissance (flyby) and exploratory (mapping) trajectories. Sample data is included for a geosynchronous station drift cycle study, a Venus radar mapping strategy, a frozen orbit about Mars, and a repeat ground trace orbit. LOP uses the variation-of-parameters method in formulating the equations of motion. Terms involving the mean anomaly are removed from numerical integrations so that large step sizes, on the order of days, are possible. Consequently, LOP executes much faster than programs based on Cowell's method, such as the companion program ASAP (the Artificial Satellite Analysis Program, NPO-17522, also available through COSMIC). The program uses a force model with a gravity field of up to 21 by 21, lunisolar perturbation, drag, and solar radiation pressure. The input includes classical orbital elements (either mean or oscillating), orbital elements of the sun relative to the planet, reference time and dates, drag coefficients, gravitational constants, planet radius, rotation rate. The printed output contains the classical elements for each time step or event step, and additional orbital data such as true anomaly, eccentric anomaly, latitude, longitude, periapsis altitude, and the rate of change per day of certain elements. Selected output is additionally written to a plot file for postprocessing by the user. LOP is written in FORTRAN 77 for batch execution on IBM PC compatibles running MS-DOS with a minimum of 256K RAM. Recompiling the source requires the Lahey F77 v2.2 compiler. The LOP package includes examples that use LOTUS 1-2-3 for graphical displays, but any graphics software package should be able to handle the ASCII plot file. The program is available on two 5.25 inch 360K MS-DOS format diskettes. The program was written in 1986 and last updated in 1989. LOP is

  5. Northern European long term climate archives

    Hohl, Veronica [Stockholm Univ. (Sweden)


    The Swedish Nuclear Fuel and Waste Management Company is responsible for the management and disposal of Sweden's radioactive waste. It is intended to deposit the spent nuclear fuel in a deep geological repository. This repository shall keep the radiotoxic material separated from humans and the environment for extended periods, from decades to millennia and possibly to geological timescales. During this time perspective climate induced changes such as shore-level displacement and evolution of permafrost and ice sheets are expected to occur which may affect the repository. The possible occurrence, extent and duration of these long-term changes, are therefore of interest when considering the assessment of repository performance and safety. The main climate parameters determining both surface and subsurface conditions are temperature and precipitation. As a result of the last advance of the Weichselian ice sheet only few geological archives exist, which contain information on past climatic conditions in Sweden before c 16,000 years BP. The purpose of this literature review is to compile and evaluate available information from Scandinavian, Northern and Central European geological archives, which record climatic conditions during the Weichselian time period. The compilation provides paleotemperature data sets, which may be used to explore the possible evolution of periglacial permafrost in Sweden. This report is a synopsis of 22 publications detailing climatic and environmental changes during the Weichselian time period in Northwestern Europe based on quantified paleotemperature records. Some of the data is presented as temperature curves which were digitised specifically for this report. The time range covered by the different publications varies considerably. Only few authors dealt with the whole Weichselian period and the majority cover only a few thousand years. This however is not considered to influence the reliability of the archives. The reason for the

  6. Enhanced Polyhydroxybutyrate Production for Long-Term Spaceflight Applications

    Putman, Ryan J.; Rahman, Asif; Miller, Charles D.; Hadi, Masood Z.


    Synthetic biology holds the promise of advancing long term space fight by the production of medicine, food, materials, and energy. One such application of synthetic biology is the production of biomaterials, specifically polyhydroxyalkanoates (PHAs), using purposed organisms such as Escherichia coli. PHAs are a group of biodegradable bioplastics that are produced by a wide variety of naturally occurring microorganisms, mainly as an energy storage intermediate. PHAs have similar melting point to polypropylene and a Youngs modulus close to polystyrene. Due to limited resources and cost of transportation, large-scale extraction of biologically produced products in situ is extremely cumbersome during space flight. To that end, we are developing a secretion systems for exporting PHA from the cell in order to reduce unit operations. PHAs granules deposited inside bacteria are typically associated with proteins bound to the granule surface. Phasin, a granule bound protein, was targeted for type I secretion by fusion with HlyA signal peptide for indirect secretion of PHAs. In order to validate our secretion strategy, a green fluorescent protein (GFP) was tagged to the PHA polymerase enzyme (phaC), this three part gene cassette consists of phaA and phaB and are required for PHA production. Producing PHAs in situ during space flight or planet colonization will enable mission success by providing a valuable source of biomaterials that can have many potential applications thereby reducing resupply requirements. Biologically produced PHAs can be used in additive manufacturing such as three dimensional (3D) printing to create products that can be made on demand during space flight. After exceeding their lifetime, the PHAs could be melted and recycled back to 3D print other products. We will discuss some of our long term goals of this approach.

  7. Changes of the eye during long-term spaceflight. Review

    I. A. Makarov


    Full Text Available The review includes the publications of the scientific literature on the eye change during long-term spaceflight. The any eye changes such as visual impairment, hyperopic shift in refraction, changes in the intraocular pressure, increased the intracranial pressure, globe flattening, choroidal folding, optic disc edema, and optic nerve kinking and other changes were reported. The main cause of eye disorders, in all probability, is the increase of the intracranial pressure during long-term spaceflight. The reasons of the increased intracranial pressure are a collection of various factors of adaptation mechanisms in the body to weightless conditions. The leading role in the development of intracranial hypertension takes a redistribution of the body fluids (blood and lymph in the direction of the head, but the opportunities and the effect of other factors are present. Also the displacement and increase of the internal organs volume of the chest can cause external compression of the jugular veins, increasing the pressure of the blood in them, and as the result to lead to the increase of the intracranial pressure. The role of trigger such mechanisms in the development of the intracranial hypertension in the microgravity environment as anatomical predisposition of the body, race, metabolic changes under the influence of high carbon dioxide content in the different compartments of the station, high sodium intake, the enzyme dysfunction, weight exercises of the astronauts was discussed. However, the pathogenic mechanisms is currently still under investigation. An important role in the study of the adaptation mechanisms is given to research not only before and after the flight, but also during the space flight. The accumulated knowledge and experience about the changes in organs and systems in the conditions of human adaptation to microgravity will help answer many questions related to the implementation of the long spaceflights.

  8. 长期定位施肥对黄土旱塬黑垆土土壤酶活性的影响%Effect of Long-term Fertilization on Soil Enzyme Activities in Dryland Black Humus Soil in the Loess Plateau

    王淑英; 樊庭录; 丁宁平; 姜小凤; 张平良; 苏敏


    以30年(1979~2008年)肥料长期定位试验为基础,探讨长期定位施肥对黄土旱塬黑垆土土壤酶活性的影响及不同土壤酶间相关性.结果表明:SNP和MNP处理可提高土酶蔗糖酶活性,比不施肥对照分别增加19.98%、19.14%;土壤脲酶活性单施M效果最佳,较对照提高30.72%,MNP和SNP处理优于其它处理;MNP提高碱性磷酸酶活性的效果最好、增幅196.5%,单施M和SNP效果次之;单施N可提高土壤蛋白酶活性,较对照增加28.3%,而施P有抑制黄土旱塬黑垆土蛋白酶活性的作用.脲酶与碱性磷酸酶呈显著正相关,相关系数为0.7241,过氧化氢酶与碱性磷酸酶、脲酶呈显著负相关.综合考虑,长期有机-无机NP肥配施是促进黄土旱塬黑垆土土壤良性循环、提高耕地质量的有效施肥管理措施.%Effects of long-term fertilization on soil enzyme activities in dryland black humus soil in the Loess Plateau was studied based on the long-term fertilization experiment from 1979 to 2008. The results showed that nitrogen and phosphorus with farmer manure (MNP), nitrogen and phosphorus with straw (SNP) could improve the soil invertase activity compared with no fertilizer (control) increased by 19.98%, 19.14%. Farmer manure (M) had a great effect on soil urease activities increased by 30.72% compared to the control, next to MNP and SNP. MNP could increase alkaline phos- phatase activities by 196.5% compared with the control, next to M and SNP. Only application of N could increase soil protease activities by 28.3% compared with control, while P could inhibit soil protease activities in dryland black humus soil in the Loess Plateau. There was a significant positive correlation between soil urease and alkaline phosphatase with correlation coefficient of 0.7241, while there was significantly negative correlation between catalase and alkaline phosphatase, urease. Organic-fertilizer (M and S) with NP was an effective practice for dryland black

  9. Mucopolysaccharidosis: cardiologic features and effects of enzyme-replacement therapy in 24 children with MPS I, II and VI.

    Brands, Marion M M G; Frohn-Mulder, Ingrid M; Hagemans, Marloes L C; Hop, Wim C J; Oussoren, Esmee; Helbing, Wim A; van der Ploeg, Ans T


    We determined the cardiologic features of children with MPS I, II and VI, and evaluated the effect of enzyme-replacement therapy (ERT) on cardiac disease. Twenty-four children aged 1-18 years with MPS I, II or VI were prospectively evaluated with echocardiogram and electrocardiogram from the start of enzyme-replacement therapy up to 6 years of treatment. At start of therapy, 66% had abnormal cardiac geometric features. Left-ventricular mass index (LVMI) was increased in half of the patients, due mainly to concentric hypertrophy in MPS I and II and to eccentric hypertrophy in MPS VI. Regurgitation was most severe in a subgroup of young MPS VI patients ( 2. LVMI Z-scores decreased significantly in patients with MPS I and MPS II (p = 0.04 and p = 0.032). Despite ERT, valve regurgitation increased in 60% of the patients. We conclude that all our MPS patients have cardiac abnormalities. The most severe cardiac disease was observed in a subgroup of young MPS VI patients. While ERT had an effect on LVMI and IVSd, it apparently had little or none on valve regurgitation.

  10. Long-term outcomes in idiopathic membranous nephropathy using a restrictive treatment strategy.

    van den Brand, Jan A J G; van Dijk, Peter R; Hofstra, Julia M; Wetzels, Jack F M


    Recently published Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend limiting the use of immunosuppressive drugs in idiopathic membranous nephropathy to patients at the highest risk of kidney failure. However, recommendations are based on natural history rather than direct assessment of a restrictive treatment strategy. Here, we describe the long-term outcomes of treating a large cohort of patients with idiopathic membranous nephropathy according to a restrictive treatment policy. We analyzed data for 254 patients who visited our outpatient clinic between 1995 and 2009. All patients were treated with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers. Immunosuppressive therapy was recommended in cases of deteriorating renal function or untreatable nephrotic syndrome. Primary outcomes for the present study were renal replacement therapy and death. Secondary outcomes included adverse events during follow-up and remission of proteinuria. In total, 124 patients (49%) received immunosuppressive therapy, which predominantly consisted of cyclophosphamide combined with steroids. Ten-year cumulative incidence rates were 3% for renal replacement therapy and 10% for death. Partial remission rates were 39%, 70%, and 83% after 1, 3, and 5 years, respectively; complete remission rates were 5%, 24%, and 38% at 1, 3, and 5 years, respectively. A serious adverse event occurred in 23% of all patients. The most notable complications were infections (17%), leukopenia (18%), cardiovascular events (13%), and malignancies (8%). In conclusion, the use of a restrictive treatment strategy in this cohort of patients with idiopathic membranous nephropathy yielded favorable outcomes while limiting the number of patients exposed to toxic drugs. These results support current KDIGO guidelines.



    It is necessary to study the tropical western Pacific SST in association with variations of other parts of the globe. Two basic compositions are revealed of long-term variation in SST over three major tropical oceans since the 1950's (linear warming and ElNi(n)o-La Ni(n)a oscillations) and typical patterns with which they are displayed over the oceans are compared. On the basis of it, difference in long-term variation of SST over western, central and eastern tropical Pacific is analyzed in details. It is pointed out that the ElNi(n)o-La Ni(n)a oscillations are relatively weak in the long-term variation of SST in the tropical western Pacific and linear warming trend there is replaced by interdecadal oscillations. Further understanding of the peculiarity over the region helps improve short-term climatic predictions in China.

  12. Autoimmune hepatitis as an adverse effect of long-term methotrexate therapy

    Kamilia Ksouda


    Full Text Available Methotrexate (MTX is one of the most commonly used medicines in the treatment of psoriatic arthritis. The drug can produce steatosis and cirrhosis. Autoimmune hepatitis is a rare and serious adverse effect. We describe the case of a 53-year-old woman who developed autoimmune hepatitis after a long-term use of MTX for psoriatic arthritis. Hepatitis was completely resolved 4 months after stopping this drug. The pathophysiologic mechanisms of a drug-induced autoimmunity are unclear and complex. This report confirms the need to monitor liver enzymes carefully in patients using long-term treatment with MTX for psoriasis or rheumatoid arthritis.

  13. Long term behaviour of singularly perturbed parabolic degenerated equation

    Ibrahima Faye


    Full Text Available In this paper we consider models built in [4] for short-term, mean-term and long-term morphodynamics of dunes and megariples. We give an existence and uniqueness result for long term dynamics of dunes. This result is based on a periodic-in-time-and-space solution existence result for degenerated parabolic equation that we set out. Finally the mean-term and long-term models are homogenized.


    Daniela-Emanuela Dănăcică


    Full Text Available The aim of this paper is to analyze characteristics of long-term unemployment spells in Romania and to estimate the effect of factors influencing long-term unemployment spells. The study period is in between January 1st 2008 and December 31st 2010. 468159 long-term spells registered in the specified period at the National Agency of Employment are analyzed.

  15. Quantification of long term emission potential from landfills

    Heimovaara, T.J.


    Novel approaches for the after-care of Municipal Solid Waste (MSW) landfills are based on technological measures to reduce the long term emission potential in a short time period. Biological degradation in landfills is a means to significantly reduce the long term emission potential. Leachate emission to the groundwater is considered to be one of the largest long-term impacts related to landfilling. Currently we are starting up a research program, partly subsidized by the Dutch Technology fou...

  16. A cost of long-term memory in Drosophila

    Mery, Frederic; Kawecki, Tadeusz J.


    Two distinct forms of consolidated associative memory are known in Drosophila: long-term memory and so-called anesthesia-resistant memory. Long-term memory is more stable, but unlike anesthesia-resistant memory, its formation requires protein synthesis. We show that flies induced to form long-term memory become more susceptible to extreme stress (such as desiccation). In contrast, induction of anesthesia-resistant memory had no detectable effect on desiccation resistance. This finding may hel...

  17. Long term behaviour of singularly perturbed parabolic degenerated equation

    Faye, Ibrahima; Seck, Diaraf


    In this paper we consider models for short-term, mean-term and long-term morphodynamics of dunes and megariples. We give an existence and uniqueness result for long term dynamics of dunes. This result is based on a time-space periodic solution existence result for degenerated parabolic equation that we set out. Finally the mean-term and long-term models are homogenized.

  18. Aptamers as a replacement for antibodies in enzyme-linked immunosorbent assay.

    Toh, Saw Yi; Citartan, Marimuthu; Gopinath, Subash C B; Tang, Thean-Hock


    The application of antibodies in enzyme-linked immunosorbent assay (ELISA) is the basis of this diagnostic technique which is designed to detect a potpourri of complex target molecules such as cell surface antigens, allergens, and food contaminants. However, development of the systematic evolution of Ligands by Exponential Enrichment (SELEX) method, which can generate a nucleic acid-based probe (aptamer) that possess numerous advantages compared to antibodies, offers the possibility of using aptamers as an alternative molecular recognition element in ELISA. Compared to antibodies, aptamers are smaller in size, can be easily modified, are cheaper to produce, and can be generated against a wide array of target molecules. The application of aptamers in ELISA gives rise to an ELISA-derived assay called enzyme-linked apta-sorbent assay (ELASA). As with the ELISA method, ELASA can be used in several different configurations, including direct, indirect, and sandwich assays. This review provides an overview of the strategies involved in aptamer-based ELASA.

  19. Multi-isomorphous replacement phasing of the earthworm fibrinolytic enzyme component A from Eisenia fetida

    汤涌; 江涛; 张季平; 樊蓉; 吴骋; 梁栋材; 常文瑞


    Earthworm fibrinolytic enzyme component A (EFEa) from Eisenia fetida, a protein functioning not only as a direct fibrinolytic enzyme, but also as a plasminogen activator, has been crystallized in P212121 space group with 3 proteinmolecules per asymmetric unit. Four heavy atom derivatives were prepared using a mother liquor containing 1.4 mol@L-1 Li2SO4 and 0.1 mol@L-1 MOPS buffer (pH7.2) and used to solve the protein's diffraction phase. The heavy atom binding sites in the derivative crystals were determined using difference Patterson and difference Fourier methods and were refined in combination to yield the initial protein's structure phase at 0.25 nm resolution. The non-crystallographic symmetryrelationship of the three independent protein molecules in the asymmetric unit was determined using the correlative heavy atom sites and used for the averagingof the initial electron density. As a result, the electron density was significantly improved, providing a solid foundation for subsequent structure determination.

  20. Consider long-term care as service alternative.

    Loria, L S


    The increasing demand for elderly care services, pressures on inpatient average length of stay and payment levels, and potential financial rewards from providing additional services, makes long-term care look attractive to hospitals. Long-term care, however, is not for every hospital. Before deciding to establish long-term care services, management should examine how the service fits within the hospital's strategic plan. The action plan below provides guidance in evaluating a decision to use hospital facilities for long-term care. Examine how long-term care services fit within the hospital's strategic plan. Study area demographics and competitors to assess the need and supply of long-term care services. Survey the medical staff, consumers and payers to determine attitudes, perceptions and interests regarding long-term care services. Develop a facility plan that identifies areas of excess capacity that can be most easily converted into long-term care with minimal effects on hospital operations. Prepare a financial feasibility analysis of the contribution margin and return on investment attributable to long-term care services. Include an impact analysis on hospital operations. Establish a management task force to develop a detailed implementation plan including assigned individual responsibilities and related timetable. Develop an effective marketing plan designed to generate increased patient market share.

  1. Hydrodilatation (distension arthrography): a long-term clinical outcome series

    Watson, Lyn; Bialocerkowski, Andrea; Dalziel, Rodney; Balster, Simon; Burke, Frank; Finch, Caroline


    To describe and compare the medium to long-term effectiveness of hydrodilatation and post-hydrodilatation physiotherapy in patients with primary and secondary glenohumeral joint contracture associated...

  2. The long-term stability of cement - Leaching tests

    Engkvist, I.; Albinsson, Y.; Johansson Engkvist, W. [Chalmers Univ. of Technology, Goeteborg (Sweden)


    The concrete construction in the Swedish repository for long-lived low and intermediate level waste will give a stable chemical near field environment for 10{sup 5} years. The pH is expected to exceed 12 for the life time for most of the radionuclides in the repository in both saline and non-saline groundwaters. This is shown by static leaching experiments performed in saline and non-saline granitic groundwater conditions. Five gram portions of crushed ordinary Portland cement paste were equilibrated with 20 ml of synthetic saline or non-saline groundwater in a nitrogen atmosphere. Each week 12 ml (60%) of the water was replaced. The withdrawn water was used for chemical analyses and the results were used to monitor the degradation of the cement paste. After eighty weeks, some samples were analysed for mineral composition and compared with the original unleached paste. The results indicated no secondary ettringite or calcite formation. The results also supported the conclusion that the salinity of the contacting water is of minor importance for the long-term performance of the cement paste. 18 refs, 32 figs.

  3. Long-term Stability of 9- to 12 % Cr Steels

    Hald, John


    of Mo with 1.8 % W combined with a slight amount of Boron led to steel P 92. The creep rupture strength of these new alloys are now secured with long-term tests up to 100,000 hours, which demonstrate improvements of 50% (P 91), 75 % (E 911) and 100 % (P 92) in strength compared to X 20CrMoV12 1....... and pressures. Newly developed steam pipe steels are based on modifications of well-established steels like the X 20CrMoV12 1. Balanced addition of V, Nb and N to a 9Cr 1 Mo steel led to the Modified 9 Cr steel P 91. Addition of 1% W to a 9Cr 1 MoVNbN base composition led to steel E 911 and partial replacement......In the recent 25 years creep rupture strength of 9- to 12 %Cr steels for steam pipes and turbines has been doubled by development of new alloys. This development has formed a basis for improved efficiency of fossil fired steam power plants by introduction of advanced steam temperatures...

  4. Arylsulfatase A bound to poly(butyl cyanoacrylate) nanoparticles for enzyme replacement therapy--physicochemical evaluation.

    Mühlstein, A; Gelperina, S; Shipulo, E; Maksimenko, O; Kreuter, J


    Arylsulfatase A (ASA) deficiency is the cause of metachromatic leucodystrophy (MLD), a lysosomal storage disease associated with severe neurological disorders. Poly(butyl cyanoacrylate) (PBCA) nanoparticles overcoated with polysorbate 80 enabled the delivery of several drugs across the blood-brain barrier to the brain suggesting that these nanoparticles also may transport ASA across this barrier. The objective of this research, therefore, was to evaluate the feasibility of loading ASA onto PBCA nanoparticles. A stable ASA-loaded PBCA nanoparticle formulation was developed that could be easily freeze-dried and stored over a period of more than 8 weeks. The maximum loading capacity for this enzyme was -59 microg per 1 mg of PBCA. In the presence of 3% sucrose as a lyoprotector the activity of freeze-dried ASA was found to be 100% recoverable.

  5. Enzyme replacement therapy (ERT) procedure for mucopolysaccharidosis type II (MPS II) by intraventricular administration (IVA) in murine MPS II.

    Higuchi, Takashi; Shimizu, Hiromi; Fukuda, Takahiro; Kawagoe, Shiho; Matsumoto, Juri; Shimada, Yohta; Kobayashi, Hiroshi; Ida, Hiroyuki; Ohashi, Toya; Morimoto, Hideto; Hirato, Tohru; Nishino, Katsuya; Eto, Yoshikatsu


    Mucopolysaccharidosis type II (MPS II), or Hunter syndrome, is a lysosomal storage disorder caused by a deficiency of iduronate-2-sulfatase (IDS) and is characterized by the accumulation of glycosaminoglycans (GAGs). MPS II has been treated by hematopoietic stem cell therapy (HSCT)/enzyme replacement therapy (ERT), but its effectiveness in the central nervous system (CNS) is limited because of poor enzyme uptake across the blood-brain barrier (BBB). To increase the efficacy of ERT in the brain, we tested an intraventricular ERT procedure consisting of repeated administrations of IDS (20 μg/mouse/3 weeks) in IDS-knockout, MPS II model mice. The IDS enzyme activity and the accumulation of total GAGs were measured in mouse brains. The IDS activity was significantly increased, and the accumulation of total GAGs was decreased in the MPS II mouse brains treated with multiple administrations of IDS via intraventricular ERT. Additionally, a high level of IDS enzyme activity was appreciated in other MPS II mouse tissues, such as the liver, spleen, testis and others. A Y-maze was used to test learning and memory after repeated intraventricular ERT with IDS. The IDS-treated mouse groups recovered the capacity for short-term memory and activity. Although large and small vacuoles were found at the margin of the cerebellar Purkinje cells in the disease-control mice, these vacuoles disappeared upon treated with IDS. Loss of vacuoles was also observed in other tissues (liver, kidney and testis). These results demonstrate the possible efficacy of an ERT procedure with intraventricular administration of IDS for the treatment of MPS II. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

  6. Slow, continuous enzyme replacement via spinal CSF in dogs with the paediatric-onset neurodegenerative disease, MPS IIIA.

    King, Barbara; Marshall, Neil R; Hassiotis, Sofia; Trim, Paul J; Tucker, Justin; Hattersley, Kathryn; Snel, Marten F; Jolly, Robert D; Hopwood, John J; Hemsley, Kim M


    Intra-cerebrospinal fluid (CSF) injection of recombinant human lysosomal enzyme is a potential treatment strategy for several neurodegenerative lysosomal storage disorders including Sanfilippo syndrome (Mucopolysaccharidosis type IIIA; MPS IIIA). Here we have utilised the MPS IIIA Huntaway dog model to compare the effectiveness of the repeated intermittent bolus injection strategy being used in the trials with an alternate approach; slow, continual infusion of replacement enzyme (recombinant human sulphamidase; rhSGSH) into the spinal CSF using a SynchroMed II® pump attached to a spinal infusion cannula. The ability of each enzyme delivery strategy to ameliorate lesions in MPS IIIA brain was determined in animals treated from ∼three- to six-months of age. Controls received buffer or no treatment. Significant reductions in heparan sulphate (primary substrate) were observed in brain samples from dogs treated via either cisternal or lumbar spinal CSF bolus injection methods and also in slow intra-spinal CSF infusion-treated dogs. The extent of the reduction differed regionally. Pump-delivered rhSGSH was less effective in reducing secondary substrate (GM3 ganglioside) in deeper aspects of cerebral cortex, and although near-amelioration of microglial activation was seen in superficial (but not deep) layers of cerebral cortex in both bolus enzyme-treated groups, pump-infusion of rhSGSH had little impact on microgliosis. While continual low-dose infusion of rhSGSH into MPS IIIA dog CSF reduces disease-based lesions in brain, it was not as efficacious as repeated cisternal or spinal CSF bolus infusion of rhSGSH over the time-frame of these experiments.

  7. Evaluation of the efficacy and safety of three dosing regimens of agalsidase alfa enzyme replacement therapy was underpowered

    Ortiz A


    Full Text Available Alberto Ortiz,1,2 Maria Dolores Sanchez-Niño1,2 1Department of Nephrology, IIS-Fundacion Jimenez Diaz, School of Medicine, Universidad Autónoma de Madrid, 2Department of Nephrology, Instituto Reina Sofia de Investigación Nefrológica, Madrid, Spain We read with interest the report by Goláň et al on the “Evaluation of the efficacy and safety of three dosing regimens of agalsidase alfa enzyme replacement therapy in adults with Fabry disease”.1 Based on the reported results, the authors conclude that no efficacy or safety differences were found when the approved every-other-week (EOW dosage of agalsidase alfa was increased to weekly administration. However, the key question is whether the study, as designed and performed, could have had a different outcome. View original article by Goláň et al.

  8. Psychological symptoms as long-term consequences of war experiences

    Priebe, S.; Jankovic Gavrilovic, J.; Bremner, S.; Ajdukovic, D.; Franciskovic, T.; Galeazzi, G.M.; Kucukalic, A.; Lecic-Tosevski, D.; Morina, N.; Popovski, M.; Schützwohl, M.; Bogic, M.


    Background/Aims: War experiences can affect mental health, but large-scale studies on the long-term impact are rare. We aimed to assess long-term mental health consequences of war in both people who stayed in the conflict area and refugees. Method: On average 8 years after the war in former

  9. Factors associated with long-term mortality in acute pancreatitis

    Nøjgaard, Camilla; Matzen, Peter; Bendtsen, Flemming


    Knowledge of the long-term prognosis of acute pancreatitis (AP) is limited. The aims were to investigate: (1) prognostic factors associated with long-term mortality in patients with AP; (2) whether or not the level of serum (S-)amylase at admission had an impact on the prognosis; (3) causes...

  10. Pediatric polytrauma : Short-term and long-term outcomes

    vanderSluis, CK; Kingma, J; Eisma, WH; tenDuis, HJ


    Objective: To assess the short-term and long-term outcomes of pediatric polytrauma patients and to analyze the extent to which short-term outcomes can predict long-term outcomes. Materials and Methods: Ail pediatric polytrauma patients (Injury Severity Score of greater than or equal to 16, less than

  11. Determinants and consequences of long-term benzodiazepine use

    Manthey, Leonie


    The main objective of this thesis is to describe the epidemiology of long term BZD use as well as its long term consequences. This thesis is structured into three sections: In section one, the correlates of BZD use, new use, chronic use, inappropriate use, and BZD dependence severity are investigate

  12. Quantification of long term emission potential from landfills

    Heimovaara, T.J.


    Novel approaches for the after-care of Municipal Solid Waste (MSW) landfills are based on technological measures to reduce the long term emission potential in a short time period. Biological degradation in landfills is a means to significantly reduce the long term emission potential. Leachate emissi

  13. [Developing the core competencies of long-term care professionals].

    Chen, Huey-Tzy; Lee, Kuang-Ting


    Longer average life expectancies and an ageing society have made long-term care an urgent and important issue in Taiwan. Although the implementation of Long-Term Care Ten-year Project four years ago has begun showing success in terms of assessing Taiwan's needs in terms of long-term care services and resources, there has been little forward progress in terms of training, recruiting and maintaining more competent professionals in the long-term care sector. This paper explores the current state of long-term care competency in Taiwan and educational strategies in place to improve the competency of long-term care professionals. Results indicate that the term geriatric competency embraces sub-competencies in direct care, communication, assessment, teamwork, cultural sensitivities and career care competencies. The term long-term care competency embraces the sub-competencies of supervision, management, information technology, resource management, and organizational skill. As a main contributor to effective long-term care, the nursing profession must employ effective strategies to develop competency-based education. Also, the profession must have an adequate supply of competent manpower to effectively respond to Taiwan's aging society.

  14. Long Term Incentives for Residential Customers Using Dynamic Tariff

    Huang, Shaojun; Wu, Qiuwei; Nielsen, Arne Hejde


    This paper reviews several grid tariff schemes, including flat tariff, time-of-use, time-varying tariff, demand charge and dynamic tariff (DT), from the perspective of the long term incentives. The long term incentives can motivate the owners of flexible demands to change their energy consumption...

  15. IPO-related organizational change and long-term performance

    Eije, J.H. von; Witte, M.C. de; Zwaan, A.H. van der


    Mainstream literature on long-term performance of initial public offerings focuses on long-term underperformance. Because underperformance is an anomalous phenomenon, many authors search for explanations based on financial market imperfections. More recently, however, the attention shifts from under

  16. Psychological symptoms as long-term consequences of war experiences

    S. Priebe; J. Jankovic Gavrilovic; S. Bremner; D. Ajdukovic; T. Franciskovic; G.M. Galeazzi; A. Kucukalic; D. Lecic-Tosevski; N. Morina; M. Popovski; M. Schützwohl; M. Bogic


    Background/Aims: War experiences can affect mental health, but large-scale studies on the long-term impact are rare. We aimed to assess long-term mental health consequences of war in both people who stayed in the conflict area and refugees. Method: On average 8 years after the war in former Yugoslav

  17. Developmental Dyslexia and Explicit Long-Term Memory

    Menghini, Deny; Carlesimo, Giovanni Augusto; Marotta, Luigi; Finzi, Alessandra; Vicari, Stefano


    The reduced verbal long-term memory capacities often reported in dyslexics are generally interpreted as a consequence of their deficit in phonological coding. The present study was aimed at evaluating whether the learning deficit exhibited by dyslexics was restricted only to the verbal component of the long-term memory abilities or also involved…

  18. Standards for Psychological Services in Long-Term Care Facilities.

    Morrow-Howell, Nancy; Lichtenberg, Peter A.; Smith, Michael; Frazer, Deborah; Molinari, Victor; Rosowsky, Erlene; Crose, Royda; Stillwell, Nick; Kramer, Nanette; Hartman-Stein, Paula; Qualls, Sara; Salamon, Michael; Duffy, Michael; Parr, Joyce; Gallagher-Thompson, Dolores


    Describes the development of standards for psychological practice in long-term care facilities. The standards, which were developed by Psychologists in Long-Term Care, address provider characteristics, methods of referral, assessment practices, treatment, and ethical issues. Offers suggestions for use of the standards. (MKA)

  19. The Effect of Modality on Long-Term Recognition Memory.

    Dean, Raymond S.; And Others


    The effects of visual and auditory modes of input on long-term memory were examined in two experiments, each with 40 and 80 undergraduates, respectively. In both experiments, visual stimulus attributes were a more salient dimension than were auditory features in the long-term encoding and retrieval process. (SLD)

  20. A new image for long-term care.

    Wager, Richard; Creelman, William


    To counter widely held negative images of long-term care, managers in the industry should implement quality-improvement initiatives that include six key strategies: Manage the expectations of residents and their families. Address customers' concerns early. Build long-term customer satisfaction. Allocate resources to achieve exceptional outcomes in key areas. Respond to adverse events with compassion. Reinforce the facility's credibility.

  1. Long-term effects of a preoperative smoking cessation programme

    Villebro, Nete Munk; Pedersen, Tom; Møller, Ann M;


    Preoperative smoking intervention programmes reduce post-operative complications in smokers. Little is known about the long-term effect upon smoking cessation.......Preoperative smoking intervention programmes reduce post-operative complications in smokers. Little is known about the long-term effect upon smoking cessation....

  2. Long-Term Dynamics of Autonomous Fractional Differential Equations

    Liu, Tao; Xu, Wei; Xu, Yong; Han, Qun

    This paper aims to investigate long-term dynamic behaviors of autonomous fractional differential equations with effective numerical method. The long-term dynamic behaviors predict where systems are heading after long-term evolution. We make some modification and transplant cell mapping methods to autonomous fractional differential equations. The mapping time duration of cell mapping is enlarged to deal with the long memory effect. Three illustrative examples, i.e. fractional Lotka-Volterra equation, fractional van der Pol oscillator and fractional Duffing equation, are studied with our revised generalized cell mapping method. We obtain long-term dynamics, such as attractors, basins of attraction, and saddles. Compared with some existing stability and numerical results, the validity of our method is verified. Furthermore, we find that the fractional order has its effect on the long-term dynamics of autonomous fractional differential equations.

  3. Experimental Researches on Long-Term Strength of Granite Gneiss

    Lin Liu


    Full Text Available It is important to confirm the long-term strength of rock materials for the purpose of evaluating the long-term stability of rock engineering. In this study, a series of triaxial creep tests were conducted on granite gneiss under different pore pressures. Based on the test data, we proposed two new quantitative methods, tangent method and intersection method, to confirm the long-term strength of rock. Meanwhile, the isochronous stress-strain curve method was adopted to make sure of the accuracy and operability of the two new methods. It is concluded that the new methods are suitable for the study of the long-term strength of rock. The effect of pore pressure on the long-term strength of rock in triaxial creep tests is also discussed.

  4. Environmental Management Long-Term Stewardship Transition Guidance

    Kristofferson, Keith


    Long-term stewardship consists of those actions necessary to maintain and demonstrate continued protection of human health and the environment after the completion of facility cleanup. Long-term stewardship is administered and overseen by the U.S. Department of Energy Environmental Management Office of Science and Technology. This report describes the background of long-term stewardship and gives general guidance about considerations when ownership and/or responsibility of a site should be transferred to a long-term stewardship program. This guidance document will assist the U.S. Department of Energy in: (a) ensuring that the long-term stewardship program leads transition planning with respect to facility and site areas, and (b) describing the classes and types of criteria and data required to initiate transition for areas and sites where the facility mission has ended and cleanup is complete.

  5. Long-term weight-loss maintenance in obese patients with knee osteoarthritis

    Christensen, Pia; Henriksen, Marius; Bartels, Else Marie


    % weight-loss and 1-y maintenance, additional use of daily meal replacements or intermittent LED resulted in weight-loss maintenance for 3 y. These results challenge the commonly held assumption that weight regain in the long term is inevitable. This trial was registered at as NCT......Background: A formula low-energy diet (LED) reduces weight effectively in obese patients with knee osteoarthritis, but the role of LED in long-term weight-loss maintenance is unclear.Objective: We aimed to determine the effect of intermittent LED compared with daily meal replacements on weight...... in Frederiksberg, Denmark; they had previously completed a 68-wk lifestyle intervention trial and achieved an average weight loss of 10.5 kg (10% of initial body weight). Participants were randomly assigned to either the intermittent treatment (IN) group with LED for 5 wk every 4 mo for 3 y or to daily meal...

  6. Enzyme

    Enzymes are complex proteins that cause a specific chemical change in all parts of the body. For ... use them. Blood clotting is another example of enzymes at work. Enzymes are needed for all body ...

  7. Enteral refeeding syndrome after long-term total parenteral nutrition

    REN Jian-an; MAO Yao; WANG Ge-fei; WANG Xing-bo; FAN Chao-gang; WANG Zhi-ming; LI Jie-shou


    Background Early enteral feeding (EF) may result in fever, elevated white blood cell count, increased serum levels of liver enzymes, and diarrhea. We name the complications "enteral refeeding syndrome", as a subtype of refeeding syndrome, because they are likely to result from long-term lack of lumen nutrition. The aim of this study was to investigate the characteristics of enteral refeeding syndrome after long-term total parenteral nutrition(TPN), and the solution for the disease.Methods We collected the clinical data of 100 patients with gastrointestinal fistula, who were cured from Apirl2001 to July 2002. Their fasting time, daily stool frequency, body temperature, heart rate, respiratory rate, levels of transaminases, alkaline phosphatase (AKP), and γ-glutamylcyclotransferase (γ-GT), white blood cell count,and systemic inflammatory reaction syndrome (SIRS) score were recorded before and 1, 3, 5, 10, and 15 days after EF. Student's t test and analysis of variance were used to analyze the data.Results Of the 100 patients, 56 were cured after selective resection of intestinal fistula, 15 were cured by emergency operation, and 29 recovered spontaneously. The levels of AKP and γ-GT increased significantly on the 3rd day after EF [On the 3rd day after EF, (243.0± 121.6) U/L and (177.2± 109.9) U/L vs. before EF (181.5± 127.5) U/L and (118.4±94.2) U/L, P<0.05], and decreased gradually afterwards. The SIRS scores on the 1st day (1.05±1.08) and 3rd day (0.96± 1.11) after EF were significantly higher than that before EF (0.72±0.84),then decreased to 0.83±0.91, 0.49±0.73 and 0.32±0.60 on the 5th, 10th and 15th days after EF. The number of patients with diarrhea at 1, 3, 5, 10 and 15 days post-EF were 31, 26, 12, 13, and 7, respectively.Conclusions The longer the TPN lasts, the more severe the enteral refeeding syndrome becomes. Continuous EF is effective for the syndrome. Early enteral nutrition is useful in preventing it.

  8. Issues in long-term protein delivery using biodegradable microparticles.

    Ye, Mingli; Kim, Sungwon; Park, Kinam


    Recently, a variety of bioactive protein drugs have been available in large quantities as a result of advances in biotechnology. Such availability has prompted development of long-term protein delivery systems. Biodegradable microparticulate systems have been used widely for controlled release of protein drugs for days and months. The most widely used biodegradable polymer has been poly(d,l-lactic-co-glycolic acid) (PLGA). Protein-containing microparticles are usually prepared by the water/oil/water (W/O/W) double emulsion method, and variations of this method, such as solid/oil/water (S/O/W) and water/oil/oil (W/O/O), have also been used. Other methods of preparation include spray drying, ultrasonic atomization, and electrospray methods. The important factors in developing biodegradable microparticles for protein drug delivery are protein release profile (including burst release, duration of release, and extent of release), microparticle size, protein loading, encapsulation efficiency, and bioactivity of the released protein. Many studies used albumin as a model protein, and thus, the bioactivity of the release protein has not been examined. Other studies which utilized enzymes, insulin, erythropoietin, and growth factors have suggested that the right formulation to preserve bioactivity of the loaded protein drug during the processing and storage steps is important. The protein release profiles from various microparticle formulations can be classified into four distinct categories (Types A, B, C, and D). The categories are based on the magnitude of burst release, the extent of protein release, and the protein release kinetics followed by the burst release. The protein loading (i.e., the total amount of protein loaded divided by the total weight of microparticles) in various microparticles is 6.7+/-4.6%, and it ranges from 0.5% to 20.0%. Development of clinically successful long-term protein delivery systems based on biodegradable microparticles requires

  9. Comparative impact of AAV and enzyme replacement therapy on respiratory and cardiac function in adult Pompe mice

    Darin J Falk


    Full Text Available Pompe disease is an autosomal recessive genetic disorder characterized by a deficiency of the enzyme responsible for degradation of lysosomal glycogen (acid α-glucosidase (GAA. Cardiac dysfunction and respiratory muscle weakness are primary features of this disorder. To attenuate the progressive and rapid accumulation of glycogen resulting in cardiorespiratory dysfunction, adult Gaa−/− mice were administered a single systemic injection of rAAV2/9-DES-hGAA (AAV9-DES or bimonthly injections of recombinant human GAA (enzyme replacement therapy (ERT. Assessment of cardiac function and morphology was measured 1 and 3 months after initiation of treatment while whole-body plethysmography and diaphragmatic contractile function was evaluated at 3 months post-treatment in all groups. Gaa−/− animals receiving either AAV9-DES or ERT demonstrated a significant improvement in cardiac function and diaphragmatic contractile function as compared to control animals. AAV9-DES treatment resulted in a significant reduction in cardiac dimension (end diastolic left ventricular mass/gram wet weight; EDMc at 3 months postinjection. Neither AAV nor ERT therapy altered minute ventilation during quiet breathing (eupnea. However, breathing frequency and expiratory time were significantly improved in AAV9-DES animals. These results indicate systemic delivery of either strategy improves cardiac function but AAV9-DES alone improves respiratory parameters at 3 months post-treatment in a murine model of Pompe disease.

  10. Effects of Long-term Right Ventricular Apical Pacing on Left Ventricular Remodeling and Cardiac Function


    Objective: To investigate the impacts of long-term right ventricular apical pacing on the ventricular remodeling and cardiac functions of patients with high-grade and third-degree atrioventricular blockage with normal heart structures and cardiac functions. In addition, we provide many evidences for choosing an optimal electrode implantation site.Methods: Study participants included patients who were admitted for pacemaker replacements and revisited for examinations of implanted pacemakers at outpatient. Pa...

  11. Long-term use of stimulants in children with attention deficit hyperactivity disorder: safety, efficacy, and long-term outcome.

    Hechtman, Lily; Greenfield, Brian


    The purpose of this review is to summarize existing data on the long-term safety and efficacy of stimulant treatment, and how long-term stimulant treatment of children with attention deficit hyperactivity disorder (ADHD) affects their outcome. Existing controlled studies of children with ADHD treated and untreated with stimulants, as well as long-term prospective follow-up studies, are reviewed. Children with ADHD treated with stimulants for as long as 2 years continue to benefit from the treatment, with improvements observed in ADHD symptoms, comorbid oppositional defiant disorder, and academic and social functioning, with no significant problems of tolerance or adverse effects. Long-term, prospective follow-up studies into adulthood show that stimulant treatment in childhood has slight benefits regarding social skills and self-esteem. Long-term adverse effects from stimulant treatment in childhood regarding adult height or future substance abuse have not been supported by existing studies.

  12. Long-term Metformin Therapy and Monitoring for Vitamin B12 Deficiency Among Older Veterans.

    Kancherla, Vijaya; Elliott, John L; Patel, Birju B; Holland, N Wilson; Johnson, Theodore M; Khakharia, Anjali; Phillips, Lawrence S; Oakley, Godfrey P; Vaughan, Camille P


    To examine the association between long-term metformin therapy and serum vitamin B12 monitoring. Retrospective cohort study. A single Veterans Affairs Medical Center (VAMC), 2002-2012. Veterans 50 years or older with either type 2 diabetes and long-term metformin therapy (n = 3,687) or without diabetes and no prescription for metformin (n = 13,258). We determined diabetes status from outpatient visits, and defined long-term metformin therapy as a prescription ≥500 mg/d for at least six consecutive months. We estimated the proportion of participants who received a serum B12 test and used multivariable logistic regression, stratified by age, to evaluate the association between metformin use and serum B12 testing. Only 37% of older adults with diabetes receiving metformin were tested for vitamin B12 status after long-term metformin prescription. The mean B12 concentration was significantly lower in the metformin-exposed group (439.2 pg/dL) compared to those without diabetes (522.4 pg/dL) (P = .0015). About 7% of persons with diabetes receiving metformin were vitamin B12 deficient (vitamin B12 testing compared to those without metformin exposure, after adjusting for sex, race and ethnicity, body mass index, and number of years treated at the VAMC. Long-term metformin therapy is significantly associated with lower serum vitamin B12 concentration, yet those at risk are often not monitored for B12 deficiency. Because metformin is first line therapy for type 2 diabetes, clinical decision support should be considered to promote serum B12 monitoring among long-term metformin users for timely identification of the potential need for B12 replacement. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

  13. Technical and Clinical Success and Long-Term Durability of Endovascular Treatment for Atherosclerotic Aortic Arch Branch Origin Obstruction : Evaluation of 144 Procedures

    van de Weijer, M. A. J.; Vonken, E. J. P. A.; de Vries, J-P. P. M.; Moll, F. L.; Vos, J. A.; de Borst, G. J.


    Objectives: Endovascular treatment of atherosclerotic obstruction of aortic arch branch origins (AABO) has largely replaced open surgery, but long-term outcome data are lacking. This study evaluated mid-term and long-term results of these procedures. Design: Retrospective cohort study. Materials and

  14. Long-term employment and health inequalities in Canadian communities.

    Safaei, Jalil


    This study examines the long-term unemployment rate and various health outcomes across Canadian communities to estimate employment-related health inequalities in these communities. The study uses cross-sectional community-level health data along with data on the long-term employment rate for various communities across Canada to quantify health inequalities among these communities. The health outcomes that are considered in this study include total and disease specific mortality rates; health conditions such as high blood pressure, diabetes, injuries, and self rated health; and life expectancies at birth and at age 65. Health inequalities are estimated using the concentration index, which is used to measure health inequalities along socioeconomic dimensions. The concentration index is estimated by a regression of weighted relative health (ill health) over weighted cumulative relative rank of the populations. All the estimates are provided separately for males and females. The findings of the study support the existence of inequalities in community health outcomes as related to the long-term employment rates in those communities. Communities with lower long term employment rates (higher unemployment rates) have poorer health outcomes in terms of higher mortality rates, worse health conditions, and shorter life expectancies. Health inequalities related to long-term employment have important policy implications. They call for policies that would increase and maintain long term employment rates as part of a broader socioeconomic approach to health. Long term employment ensures income security and prevents the psychosocial experiences leading to mental and physical ill health.

  15. Long-Term Stewardship Baseline Report and Transition Guidance

    Kristofferson, Keith


    Long-term stewardship consists of those actions necessary to maintain and demonstrate continued protection of human health and the environment after facility cleanup is complete. As the Department of Energy’s (DOE) lead laboratory for environmental management programs, the Idaho National Engineering and Environmental Laboratory (INEEL) administers DOE’s long-term stewardship science and technology efforts. The INEEL provides DOE with technical, and scientific expertise needed to oversee its long-term environmental management obligations complexwide. Long-term stewardship is administered and overseen by the Environmental Management Office of Science and Technology. The INEEL Long-Term Stewardship Program is currently developing the management structures and plans to complete INEEL-specific, long-term stewardship obligations. This guidance document (1) assists in ensuring that the program leads transition planning for the INEEL with respect to facility and site areas and (2) describes the classes and types of criteria and data required to initiate transition for areas and sites where the facility mission has ended and cleanup is complete. Additionally, this document summarizes current information on INEEL facilities, structures, and release sites likely to enter long-term stewardship at the completion of DOE’s cleanup mission. This document is not intended to function as a discrete checklist or local procedure to determine readiness to transition. It is an overarching document meant as guidance in implementing specific transition procedures. Several documents formed the foundation upon which this guidance was developed. Principal among these documents was the Long-Term Stewardship Draft Technical Baseline; A Report to Congress on Long-Term Stewardship, Volumes I and II; Infrastructure Long-Range Plan; Comprehensive Facility Land Use Plan; INEEL End-State Plan; and INEEL Institutional Plan.

  16. The activity of antioxidant enzymes in blood platelets in different types of renal replacement therapy: a cross-sectional study.

    Stępniewska, Joanna; Dołęgowska, Barbara; Cecerska-Heryć, Elżbieta; Gołembiewska, Edyta; Malinowska-Jędraszczyk, Alicja; Marchelek-Myśliwiec, Małgorzata; Ciechanowski, Kazimierz


    The changes in redox status characterise physiological platelet activation. Increased oxidative stress in chronic kidney disease (CKD) associated with uremic toxicity and procedures of renal replacement therapy leads to the impairment of antioxidant properties of platelets. It may contribute to thrombosis and cardiovascular complications increasing morbidity and mortality among the CKD patients. The object of the research was to assess the influence of conservative treatment, peritoneal dialysis and haemodialysis on platelet prooxidative-antioxidative balance. The examined group consisted of 122 patients: 37 on regular haemodialysis (HD), 23 on peritoneal dialysis (PD) and 62 on conservative treatment with CKD stages 3-5 (CKD3-5). The activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione transpherase (GST) in platelets were obtained using kinetic methods. The spectrophotometric method established the concentrations of reduced glutathione (GSH). SOD activity in PD differs significantly from CKD3-5 (4.96 vs 1.66; p activity assessed in PD and CKD3-5 was significantly different from HD (0.82 and 0.8 vs 0.52 before and 0.35 after HD, respectively). GST activity reached the highest value in PD (1.62), and it was significantly different from CKD3-5 (0.23) and HD before haemodialysis (0.11). During haemodialysis therapy, there was a considerable increase in GST activity (0.11 vs 0.3; p = 0.02) and decrease in SOD activity (from 3.41 to 2.27; p = 0.01). The highest GSH concentrations were obtained in CKD3-5 and differ significantly from HD (4.12 vs 2.01; p = 0.02). The type of treatment, age and duration of renal replacement therapy determined significant changes in platelet antioxidative enzymes activities and concentration of GSH, which may enhance the thrombotic complications. PD is associated with lower platelet oxidative stress.

  17. Long-term clinical outcome of fetal cell transplantation for Parkinson disease: two case reports.

    Kefalopoulou, Zinovia; Politis, Marios; Piccini, Paola; Mencacci, Niccolo; Bhatia, Kailash; Jahanshahi, Marjan; Widner, Håkan; Rehncrona, Stig; Brundin, Patrik; Björklund, Anders; Lindvall, Olle; Limousin, Patricia; Quinn, Niall; Foltynie, Thomas


    Recent advances in stem cell technologies have rekindled an interest in the use of cell replacement strategies for patients with Parkinson disease. This study reports the very long-term clinical outcomes of fetal cell transplantation in 2 patients with Parkinson disease. Such long-term follow-up data can usefully inform on the potential efficacy of this approach, as well as the design of trials for its further evaluation. Two patients received intrastriatal grafts of human fetal ventral mesencephalic tissue, rich in dopaminergic neuroblasts, as restorative treatment for their Parkinson disease. To evaluate the very long-term efficacy of the grafts, clinical assessments were performed 18 and 15 years posttransplantation. Motor improvements gained gradually over the first postoperative years were sustained up to 18 years posttransplantation, while both patients have discontinued, and remained free of any, pharmacological dopaminergic therapy. The results from these 2 cases indicate that dopaminergic cell transplantation can offer very long-term symptomatic relief in patients with Parkinson disease and provide proof-of-concept support for future clinical trials using fetal or stem cell therapies.

  18. Long-term monitoring for nanomedicine implants and drugs

    Kendall, Michaela; Lynch, Iseult


    Increasing globalization means that traditional occupational epidemiological approaches may no longer apply, suggesting a need for an alternative model to assess the long-term impact of nanomaterial exposure on health.

  19. Long-term memory, sleep, and the spacing effect.

    Bell, Matthew C; Kawadri, Nader; Simone, Patricia M; Wiseheart, Melody


    Many studies have shown that memory is enhanced when study sessions are spaced apart rather than massed. This spacing effect has been shown to have a lasting benefit to long-term memory when the study phase session follows the encoding session by 24 hours. Using a spacing paradigm we examined the impact of sleep and spacing gaps on long-term declarative memory for Swahili-English word pairs by including four spacing delay gaps (massed, 12 hours same-day, 12 hours overnight, and 24 hours). Results showed that a 12-hour spacing gap that includes sleep promotes long-term memory retention similar to the 24-hour gap. The findings support the importance of sleep to the long-term benefit of the spacing effect.

  20. Assisted Living Facilities - MO 2010 Long Term Care Facilities (SHP)

    NSGIC GIS Inventory (aka Ramona) — Long Term Care facilities (nursing homes) in Missouri - Data will not be made available for download via MSDIS. Interested parties should send an email inquiry to...

  1. Long-term intrathecal administration of midazolam and clonidine

    Borg, PAJ; Krijnen, HJ


    Objective: To determine the clinical usefulness of the long-term intrathecal administration of midazolam and clonidine in patients with refractory neurogenic and musculoskeletal pain. Setting: Pain Centre, Academic Hospital Groningen, Groningen, The Netherlands. Patients: Four patients with chronic

  2. Modelled long term trends of surface ozone over South Africa

    Naidoo, M


    Full Text Available timescale seeks to provide a spatially comprehensive view of trends while also creating a baseline for comparisons with future projections of air quality through the forcing of air quality models with modelled predicted long term meteorology. Previous...

  3. Office of Disability, Aging and Long-Term Care Policy

    ... Publications Data and Tools Evaluation Database Office of Disability, Aging and Long-Term Care Policy (DALTCP) Home About Offices Disability, Aging, and Long-Te... DALTCP provides leadership on ...

  4. The market for long-term care services.

    Grabowski, David C


    Although a large literature has established the importance of market and regulatory forces within the long-term care sector, current research in this field is limited by a series of data, measurement, and methodological issues. This paper provides a comprehensive review of these issues with an emphasis on identifying initiatives that will increase the volume and quality of long-term care research. Recommendations include: the construction of standard measures of long-term care market boundaries, the broader dissemination of market and regulatory data, the linkage of survey-based data with market measures, the encouragement of further market-based studies of noninstitutional long-term care settings, and the standardization of Medicaid cost data.

  5. Long-term outcome of Tunisian children with primary ciliary ...

    Objective: To study the long-term outcome of PCD in Tunisian children with ciliary ultra-structure defects detected by electron .... the mirror image arrangement of the internal organs. The sputum culture was .... A rotating antibiotic therapy.

  6. Long-term Outcomes of Childhood Onset Nephrotic Syndrome.

    Hjorten, Rebecca; Anwar, Zohra; Reidy, Kimberly Jean


    There are limited studies on long-term outcomes of childhood onset nephrotic syndrome (NS). A majority of children with NS have steroid-sensitive nephrotic syndrome (SSNS). Steroid-resistant nephrotic syndrome (SRNS) is associated with a high risk of developing end-stage renal disease. Biomarkers and analysis of genetic mutations may provide new information for prognosis in SRNS. Frequently relapsing and steroid-dependent NS is associated with long-term complications, including dyslipidemia, cataracts, osteoporosis and fractures, obesity, impaired growth, and infertility. Long-term complications of SSNS are likely to be under-recognized. There remain many gaps in our knowledge of long-term outcomes of childhood NS, and further study is indicated.

  7. Long-term patient survival in ANCA-associated vasculitis

    Flossmann, Oliver; Berden, Annelies; de Groot, Kirsten; Hagen, Chris; Harper, Lorraine; Heijl, Caroline; Hoglund, Peter; Jayne, David; Luqmani, Raashid; Mahr, Alfred; Mukhtyar, Chetan; Pusey, Charles; Rasmussen, Niels; Stegeman, Coen; Walsh, Michael; Westman, Kerstin


    Background Wegener's granulomatosis and microscopic polyangiitis are antineutrophil cytoplasm antibodies (ANCA)-associated vasculitides with significant morbidity and mortality. The long-term survival of patients with ANCA associated vasculitis treated with current regimens is uncertain. Objective T

  8. Managerial Long-Term Responsibility in Family-Controlled Firms

    Dietmar Sternad


    Full Text Available Evidence suggests that long-term orientation (LTO as a dominantstrategic logic contributes to the sustainable performance offamily-controlled firms (FCFS. Combining a review of the literatureon lto with stewardship theory and upper echelons theoryreasoning, this article presents a typology of managerial responsibilityand introduces the concept of long-term responsibility as amanagerial characteristic constituting a major driving force behindcreating lto. The antecedents of long-term responsibilityunder family firm-specific conditions (stemming from the familysystem, the governance system, and family-firm managers’ personalcharacteristics are also identified and presented in an integratedmodel. The paper contributes to a more comprehensiveunderstanding of intertemporal choice in fcfs and explains whythey tend to be more long-term oriented than other types of firms.

  9. Biogeochemistry: Long-term effects of permafrost thaw

    Zona, Donatella


    Carbon emissions from the Arctic tundra could increase drastically as global warming thaws permafrost. Clues now obtained about the long-term effects of such thawing on carbon dioxide emissions highlight the need for more data.


    P Selvam; N Punitavati


      A Fundamental study on Capital Budgeting has been viewed with the intention of providing fundamental knowledge to investors whose inclination is making a profit by investing in long term securities...

  11. The long-term consequences of anaesthetic management | Sessler ...

    The long-term consequences of anaesthetic management. ... AFRICAN JOURNALS ONLINE (AJOL) · Journals · Advanced Search · USING AJOL · RESOURCES ... of age.1 In other words, mortality in the year after surgery is approximately 10 ...

  12. Long-term intrathecal administration of midazolam and clonidine

    Borg, PAJ; Krijnen, HJ

    Objective: To determine the clinical usefulness of the long-term intrathecal administration of midazolam and clonidine in patients with refractory neurogenic and musculoskeletal pain. Setting: Pain Centre, Academic Hospital Groningen, Groningen, The Netherlands. Patients: Four patients with chronic

  13. Long-Term Ecological Monitoring Field Sampling Plan for 2007

    T. Haney


    This field sampling plan describes the field investigations planned for the Long-Term Ecological Monitoring Project at the Idaho National Laboratory Site in 2007. This plan and the Quality Assurance Project Plan for Waste Area Groups 1, 2, 3, 4, 5, 6, 7, 10, and Removal Actions constitute the sampling and analysis plan supporting long-term ecological monitoring sampling in 2007. The data collected under this plan will become part of the long-term ecological monitoring data set that is being collected annually. The data will be used t determine the requirements for the subsequent long-term ecological monitoring. This plan guides the 2007 investigations, including sampling, quality assurance, quality control, analytical procedures, and data management. As such, this plan will help to ensure that the resulting monitoring data will be scientifically valid, defensible, and of known and acceptable quality.

  14. Nutrition in children with long-term health conditions | Westwood ...

    Long-term health conditions (LTHCs) in children may affect nutrition and growth by means of ... Both undernutrition and overweight/obesity are risk factors. Direct effects of the condition that may cause undernutrition include increased resting ...

  15. Intrathecal enzyme replacement therapy reduces lysosomal storage in the brain and meninges of the canine model of MPS I.

    Kakkis, E; McEntee, M; Vogler, C; Le, S; Levy, B; Belichenko, P; Mobley, W; Dickson, P; Hanson, S; Passage, M


    Enzyme replacement therapy (ERT) has been developed for several lysosomal storage disorders, including mucopolysaccharidosis I (MPS I), and is effective at reducing lysosomal storage in many tissues and in ameliorating clinical disease. However, intravenous ERT does not adequately treat storage disease in the central nervous system (CNS), presumably due to effects of the blood-brain barrier on enzyme distribution. To circumvent this barrier, we studied whether intrathecal (IT) recombinant human alpha-L-iduronidase (rhIDU) could penetrate and treat the brain and meninges. An initial dose-response study showed that doses of 0.46-4.14 mg of IT rhIDU successfully penetrated the brain of normal dogs and reached tissue levels 5.6 to 18.9-fold normal overall and 2.7 to 5.9-fold normal in deep brain sections lacking CSF contact. To assess the efficacy and safety in treating lysosomal storage disease, four weekly doses of approximately 1 mg of IT rhIDU were administered to MPS I-affected dogs resulting in a mean 23- and 300-fold normal levels of iduronidase in total brain and meninges, respectively. Quantitative glycosaminoglycan (GAG) analysis showed that the IT treatment reduced mean total brain GAG to normal levels and achieved a 57% reduction in meningeal GAG levels accompanied by histologic improvement in lysosomal storage in all cell types. The dogs did develop a dose-dependent immune response against the recombinant human protein and a meningeal lymphocytic/plasmacytic infiltrate. The IT route of ERT administration may be an effective way to treat the CNS disease in MPS I and could be applicable to other lysosomal storage disorders.

  16. Seamless Long Term Learning in Agile Teams for Sustainable Leadership

    Qureshi, M R J


    Seamless and continuous support for long term organizational learning needs is essential for long lasting progress of the organization. Agile process model provides an excellent opportunity to cater that specific problem and also helps in motivation, satisfaction, coordination, presentation and technical skills enhancement of agile teams. This long term learning process makes organization to sustain their current successes and lead both organization and team members to successful and dynamic market leaders.

  17. Preclinical rodent toxicity studies for long term use of ceftriaxone

    Elena Ratti


    Ceftriaxone showed rapid absorption with half-life values ranging between 1 and 1.5 h. Additionally, there was no evidence of accumulation and a virtually complete elimination by 16 h after the last dose. Overall there were no toxicologically meaningful drug-related animal findings associated with the long-term administration (6 months of ceftriaxone. These results support safety of long-term use of ceftriaxone in human clinical trials.

  18. Long-term plasticity in interneurons of the dentate gyrus

    Ross, Stephen T.; Soltesz, Ivan


    Single interneurons influence thousands of postsynaptic principal cells, and the control of interneuronal excitability is an important regulator of the computational properties of the hippocampus. However, the mechanisms underlying long-term alterations in the input–output functions of interneurons are not fully understood. We report a mechanism of interneuronal plasticity that leads to the functional enhancement of the gain of glutamatergic inputs in the absence of long-term potentiation of ...

  19. Long-term care: a substantive factor in financial planning.

    Willis, D A


    More than 50 percent of women will enter a nursing home at some point in their lives. About one-third of men living to age 65 will also need nursing home care. Planning for long-term care is even more important since Medicare covers very little of the cost of such care. The Indiana Partnership Plan is one program designed to help fund the long-term care costs while allowing individuals protect other financial assets.

  20. Cyclical Long-term Unemployment, Skill Loss, and Monetary Policy


    Movements in long-term unemployment (LTU) exhibit a substantial cyclical component. I develop a business cycle model featuring labor market frictions and skill loss during unemployment to capture various stylized facts about the cyclical behavior of long-term unemployment. I find that the skill loss mechanism helps reproduce negative duration dependence, high persistence in unemployment and output, volatility patterns across macroeconomic variables and the behavior of the incidence of LTU aro...

  1. Comparison of Long-term World Energy Studies

    Schade, Burkhard; WIESENTHAL TOBIAS


    The POLES (Prospective Outlook for the Long-term Energy System) model is a global sectoral simulation model for the development of long-term energy supply and demand scenarios until 2050. The model is used to calculate global energy scenarios, such as the World Energy, Technology and Climate Policy Outlook (WETO) and the WETO-H2 update. In addition, dedicated greenhouse gas emission reduction scenarios are increasingly produced to support the assessment of climate change policies and measures...

  2. Long-term mortality after Staphylococcus aureus spondylodiscitis

    Aagaard, Theis; Larsen, Anders R; Roed-Petersen, Casper;


    Patients diagnosed with Staphylococcus aureus spondylodiscitis have increased long-term mortality compared with the background population mainly due to infectious, endocrine, cardiovascular, gastrointestinal and alcohol and drug abuse-related diseases.......Patients diagnosed with Staphylococcus aureus spondylodiscitis have increased long-term mortality compared with the background population mainly due to infectious, endocrine, cardiovascular, gastrointestinal and alcohol and drug abuse-related diseases....

  3. Long-term Outcomes of Childhood Onset Nephrotic Syndrome

    Hjorten, Rebecca; Anwar, Zohra; Reidy, Kimberly Jean


    There are limited studies on long-term outcomes of childhood onset nephrotic syndrome (NS). A majority of children with NS have steroid-sensitive nephrotic syndrome (SSNS). Steroid-resistant nephrotic syndrome (SRNS) is associated with a high risk of developing end-stage renal disease. Biomarkers and analysis of genetic mutations may provide new information for prognosis in SRNS. Frequently relapsing and steroid-dependent NS is associated with long-term complications, including dyslipidemia, ...

  4. Long-term patient survival in ANCA-associated vasculitis

    Flossmann, Oliver; Berden, Annelies; de Groot, Kirsten


    Wegener's granulomatosis and microscopic polyangiitis are antineutrophil cytoplasm antibodies (ANCA)-associated vasculitides with significant morbidity and mortality. The long-term survival of patients with ANCA associated vasculitis treated with current regimens is uncertain.......Wegener's granulomatosis and microscopic polyangiitis are antineutrophil cytoplasm antibodies (ANCA)-associated vasculitides with significant morbidity and mortality. The long-term survival of patients with ANCA associated vasculitis treated with current regimens is uncertain....

  5. Teacher Cultural Competency and Long-Term English Language Learners

    Wilson, Jannis


    Students that have been designated English Language Learners for five or more years are Long-Term English Learners. The literature review addresses some typical characteristics and experiences of students that are Long- Term English Language Learners, and the need for culturally responsive practices to meet their needs. Teacher attitudes, perceptions about English Language Learners, positionality, and opportunities to learn are integrated into the review. The author discusses linguistic aware...

  6. Commentary: The Broader Context of Long-Term Care Ethics.

    Lesandrini, Jason; O'Connell, Carol


    Ethical issues in long-term care settings, although having received attention in the literature, have not in our opinion received the appropriate level they require. Thus, we applaud the Cambridge Quarterly for publishing this case. We can attest to the significance of ethical issues arising in long-term care facilities, as Mr. Hope's case is all too familiar to those practicing in these settings. What is unique about this case is that an actual ethics consult was made in a long-term care setting. We have seen very little in the published literature on the use of ethics structures in long-term care populations. Our experience is that these healthcare settings are ripe for ethical concerns and that providers, patients, families, and staff need/desire ethics resources to actively and preventively address ethical concerns. The popular press has begun to recognize the ethical issues involved in long-term care settings and the need for ethics structures. Recently, in California a nurse refused to initiate CPR for an elderly patient in a senior residence. In that case, the nurse was quoted as saying that the facility had a policy that nurses were not to start CPR for elderly patients. 1 Although this case is not exactly the same as that of Mr. Hope, it highlights the need for developing robust ethics program infrastructures in long-term care settings that work toward addressing ethical issues through policy, education, and active consultation.

  7. Planning long-term vegetation studies at landscape scales

    Stohlgren, Thomas J.


    Long-term ecological research is receiving more attention now than ever before. Two recent books, Long-term Studies in Ecology: Approaches and Alternatives, edited by Gene Likens (1989), and Long-term Ecological Research: An International Perspective, edited by Paul Risser (1991), prompt the question, “Why are these books so thin?” Except for data from paleoecological, retrospective studies (see below), there are exceptionally few long-term data sets in terrestrial ecology (Strayer et al. 1986; Tilman 1989; this volume). In a sample of 749 papers published in Ecology, Tilman (1989) found that only 1.7% of the studies lasted at least five field seasons. Only one chapter in each of the review books dealt specifically with expanding both the temporal and the spatial scales of ecological research (Berkowitz et al. 1989; Magnuson et al. 1991). Judging by the growing number of landscape-scale long-term studies, however, such as the Long-Term Ecological Research (LTER) Program (Callahan 1991), the U.S. Environmental Protection Agency’s Environmental Monitoring and Assessment Program (EMAP; Palmer et al. 1991), the U.S. Army’s Land Condition-Trend Analysis (LCTA) Program (Diersing et al. 1992), and various agencies’ global change research programs (CEES 1993), there is a growing interest to expand ecological research both temporally and spatially.

  8. 30 months follow-up of an early enzyme replacement therapy in a severe Morquio A patient: About one case.

    Do Cao, J; Wiedemann, A; Quinaux, T; Battaglia-Hsu, S F; Mainard, L; Froissart, R; Bonnemains, C; Ragot, S; Leheup, B; Journeau, P; Feillet, F


    Patients under 5 years were not evaluated in the phase-3 study for enzyme replacement therapy (ERT) in MPS IV A. Here we describe the evolution of a severe Morquio A pediatric patient who was diagnosed at 19 months old and treated by ERT at 21 months old for the next 30 months. Applying the standard ERT protocol on this very young patient appeared to reduce his urinary excretion of glycosaminoglycans (GAGs); the improvements in both the 6 minute-walk test (6MWT) and the stair climb test, however, were no different than those reported in the nature history study. Additionally, this young patient experienced many ERT-associated side effects, and as a result a specific corticosteroid protocol (1 mg/kg of betamethasone the day before and 1 h before the ERT infusion) was given to avoid adverse events. Under these treatments, the height of this patient increased during the first year of the ERT although no more height gain was observed thereafter for 18 months. However, despite of ERT, his bone deformities (including severe pectus carinatum) actually worsened and his medullar cervical spine compression showed no improvement (thus needed decompression surgery).

  9. One Year of Enzyme Replacement Therapy Reduces Globotriaosylceramide Inclusions in Podocytes in Male Adult Patients with Fabry Disease

    Najafian, Behzad; Tøndel, Camilla; Svarstad, Einar; Sokolovkiy, Alexey; Smith, Kelly; Mauer, Michael


    Fabry nephropathy is associated with progressive accumulation of globotriaosylceramide (GL3) in podocytes. Reducing this GL3 burden may reduce podocyte injury. Sensitive methods to quantify podocyte GL3 content may determine whether a given strategy can benefit podocytes in Fabry disease. We developed an unbiased electron microscopic stereological method to estimate the average volume of podocytes and their GL3 inclusions in 6 paired pre- and post-enzyme replacement therapy (ERT) biopsies from 5 men with Fabry disease. Podocyte GL3 content was regularly reduced (average 73%) after 11–12 months of ERT. This was not detectable using a semi-quantitative approach. Parallel to GL3 reduction, podocytes became remarkably smaller (average 63%). These reductions in podocyte GL3 content or size were not significantly correlated with changes in foot process width (FPW). However, FPW after ERT was significantly correlated with the magnitude of the decrease in podocyte GL3 content from baseline to 11–12 months of ERT. Also podocytes exocytosed GL3 inclusions, a phenomenon correlated with their reduction in their GL3 content. Demonstrable after11–12 months, reduction in podocyte GL3 content allows for early assessment of treatment efficacy and shorter clinical trials in Fabry disease. PMID:27081853

  10. Amelioration of serum 8-OHdG level by enzyme replacement therapy in patients with Fabry cardiomyopathy.

    Chen, Kuan-Hsuan; Chou, Yueh-Ching; Hsiao, Chen-Yuan; Chien, Yueh; Wang, Kang-Ling; Lai, Ying-Hsiu; Chang, Yuh-Lih; Niu, Dau-Ming; Yu, Wen-Chung


    The level of 8-hydroxy-2-deoxyguanosise (8-OHdG) is a marker of oxidative stress. The objective of this study was to evaluate the effect of enzyme replacement therapy (ERT) on the level of 8-OHdG in patients with Fabry cardiomyopathy and the clinical evolution of Fabry cardiomyopathy. We measured the serum levels of 8-OHdG in 20 healthy control and 22 patients with Fabry cardiomyopathy before and after ERT. The mean lysoGb3 and 8-OHdG levels was significantly increased in patients with Fabry cardiomyopathy compared with that of control subjects (lysoGb3, 3.6 ± 1.1 nM vs. 0.4 ± 0.1 nM, p cardiomyopathy (FC) and that successful management of FC with ERT is associated with a decrease in this oxidative stress marker. Serum 8-OHdG levels can be used not only as a noninvasive biomarker of oxidative stress in patients with FC but also an objective and quantitative parameter in the follow-up of patients during ERT. Copyright © 2017. Published by Elsevier Inc.

  11. Histological characterisation of visceral changes in a patient with type 2 Gaucher disease treated with enzyme replacement therapy.

    Tezuka, Yuko; Fukuda, Mitsumasa; Watanabe, Shohei; Nakano, Takeshi; Okamoto, Kentaro; Kuzume, Kazuyo; Yano, Yoshiaki; Eguchi, Mariko; Ishimae, Minenori; Ishii, Eiichi; Miyazaki, Tatsuhiko


    Gaucher disease is a lysosomal storage disease caused by deficiency of glucocerebrosidase and accumulation of glucocerebroside. Three major sub-types have been described, type 2 is an acute neurological form that exhibits serious general symptoms and poor prognosis, compared with the other types. This case was a girl diagnosed with type 2 Gaucher disease at 12months of age who presented with poor weight gain from infancy, stridor, hypertonia, hepatosplenomegaly, trismus and an eye movement disorder. Enzyme replacement therapy (ERT) was administered, but she had frequent myoclonus and developmental regression. She needed artificial ventilation because of respiratory failure. She died at 11years of age. An autopsy demonstrated infiltrating CD68-positive large cells containing abundant lipids in alveoli, while in the liver, kidney and bone marrow CD68-positive cells were small and round. In the bone marrow, myelodysplastic changes were present without Gaucher cells. The infiltration of Gaucher cells in alveoli was marked, suggesting that ERT was relatively ineffective in pulmonary involvement, particularly intra-alveolar. Additional treatments are necessary to improve the neurological and pulmonary prognosis of type 2Gaucher disease.

  12. Nicotine uses neuron-glia communication to enhance hippocampal synaptic transmission and long-term memory.

    López-Hidalgo, Mónica; Salgado-Puga, Karla; Alvarado-Martínez, Reynaldo; Medina, Andrea Cristina; Prado-Alcalá, Roberto A; García-Colunga, Jesús


    Nicotine enhances synaptic transmission and facilitates long-term memory. Now it is known that bi-directional glia-neuron interactions play important roles in the physiology of the brain. However, the involvement of glial cells in the effects of nicotine has not been considered until now. In particular, the gliotransmitter D-serine, an endogenous co-agonist of NMDA receptors, enables different types of synaptic plasticity and memory in the hippocampus. Here, we report that hippocampal long-term synaptic plasticity induced by nicotine was annulled by an enzyme that degrades endogenous D-serine, or by an NMDA receptor antagonist that acts at the D-serine binding site. Accordingly, both effects of nicotine: the enhancement of synaptic transmission and facilitation of long-term memory were eliminated by impairing glial cells with fluoroacetate, and were restored with exogenous D-serine. Together, these results show that glial D-serine is essential for the long-term effects of nicotine on synaptic plasticity and memory, and they highlight the roles of glial cells as key participants in brain functions.

  13. Nicotine uses neuron-glia communication to enhance hippocampal synaptic transmission and long-term memory.

    Mónica López-Hidalgo

    Full Text Available Nicotine enhances synaptic transmission and facilitates long-term memory. Now it is known that bi-directional glia-neuron interactions play important roles in the physiology of the brain. However, the involvement of glial cells in the effects of nicotine has not been considered until now. In particular, the gliotransmitter D-serine, an endogenous co-agonist of NMDA receptors, enables different types of synaptic plasticity and memory in the hippocampus. Here, we report that hippocampal long-term synaptic plasticity induced by nicotine was annulled by an enzyme that degrades endogenous D-serine, or by an NMDA receptor antagonist that acts at the D-serine binding site. Accordingly, both effects of nicotine: the enhancement of synaptic transmission and facilitation of long-term memory were eliminated by impairing glial cells with fluoroacetate, and were restored with exogenous D-serine. Together, these results show that glial D-serine is essential for the long-term effects of nicotine on synaptic plasticity and memory, and they highlight the roles of glial cells as key participants in brain functions.

  14. Study of enzyme replacement therapy for Gaucher Disease: comparative analysis of clinical and laboratory parameters at diagnosis and after two, five and ten years of treatment

    Ana Maria Almeida Souza


    Full Text Available Objective: To evaluate the impact of enzyme replacement therapy for Gaucher Disease on clinical and laboratory parameters after two, five and ten years of treatment. Methods: Data were collected from patient records and analyzed using BioEstat software (version 5.0. Student's t-test, Analysis of Variance (ANOVA, Wilcoxon test and Kruskal–Wallis test were used for statistical analysis. Hepatomegaly and splenomegaly were analyzed using the Kappa test. Results: There was a significant increase in hemoglobin levels (p-value <0.01 and platelet counts (p-value = 0.01 within two years of therapy. At the same time, the frequencies of splenomegaly (p-value <0.01 and hepatomegaly (p-value <0.05 reduced. These results were similar at five and ten years of enzyme replacement therapy. Conclusions: There are substantial and quick (within two years laboratory and clinical responses to enzyme replacement therapy. These improvements continue as long as enzyme replacement therapy is administered every two weeks, as recommended by the literature.

  15. Comparison of long-term care in an acute care institution and in a long-term care institution.

    Friedman, R; Kalant, N


    Acute care hospitals in Quebec are required to reserve 10% of their beds for patients receiving long-term care while awaiting transfer to a long-term care facility. It is widely believed that this is inefficient because it is more costly to provide long-term care in an acute care hospital than in one dedicated to long-term care. The purpose of this study was to compare the quality and cost of long-term care in an acute care hospital and in a long-term care facility. A concurrent cross-sectional study was conducted of 101 patients at the acute care hospital and 102 patients at the long-term care hospital. The 2 groups were closely matched in terms of age, sex, nursing care requirements and major diagnoses. Several indicators were used to assess the quality of care: the number of medical specialist consultations, drugs, biochemical tests and radiographic examinations; the number of adverse events (reportable incidents, nosocomial infections and pressure ulcers); and anthropometric and biochemical indicators of nutritional status. Costs were determined for nursing personnel, drugs and biochemical tests. A longitudinal study was conducted of 45 patients who had been receiving long-term care at the acute care hospital for at least 5 months and were then transferred to the long-term care facility where they remained for at least 6 months. For each patient, the number of adverse events, the number of medical specialist consultations and the changes in activities of daily living status were assessed at the 2 institutions. In the concurrent study, no differences in the number of adverse events were observed; however, patients at the acute care hospital received more drugs (5.9 v. 4.7 for each patient, p cost per patient-year was $7580 higher at the acute care hospital, attributable to the higher cost of drugs ($42), the greater use of laboratory tests ($189) and, primarily, the higher cost of nursing ($7349). For patients requiring 3.00 nursing hours/day, the acute care

  16. Enzyme replacement in a human model of mucopolysaccharidosis IVA in vitro and its biodistribution in the cartilage of wild type mice.

    Melita Dvorak-Ewell

    Full Text Available Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome is a lysosomal storage disorder caused by deficiency of N-acetylgalactosamine-6-sulfatase (GALNS, an enzyme that degrades keratan sulfate (KS. Currently no therapy for MPS IVA is available. We produced recombinant human (rhGALNS as a potential enzyme replacement therapy for MPS IVA. Chinese hamster ovary cells stably overexpressing GALNS and sulfatase modifying factor-1 were used to produce active ( approximately 2 U/mg and pure (>or=97% rhGALNS. The recombinant enzyme was phosphorylated and was dose-dependently taken up by mannose-6-phosphate receptor (K(uptake = 2.5 nM, thereby restoring enzyme activity in MPS IVA fibroblasts. In the absence of an animal model with a skeletal phenotype, we established chondrocytes isolated from two MPS IVA patients as a disease model in vitro. MPS IVA chondrocyte GALNS activity was not detectable and the cells exhibited KS storage up to 11-fold higher than unaffected chondrocytes. MPS IVA chondrocytes internalized rhGALNS into lysosomes, resulting in normalization of enzyme activity and decrease in KS storage. rhGALNS treatment also modulated gene expression, increasing expression of chondrogenic genes Collagen II, Collagen X, Aggrecan and Sox9 and decreasing abnormal expression of Collagen I. Intravenous administration of rhGALNS resulted in biodistribution throughout all layers of the heart valve and the entire thickness of the growth plate in wild-type mice. We show that enzyme replacement therapy with recombinant human GALNS results in clearance of keratan sulfate accumulation, and that such treatment ameliorates aberrant gene expression in human chondrocytes in vitro. Penetration of the therapeutic enzyme throughout poorly vascularized, but clinically relevant tissues, including growth plate cartilage and heart valve, as well as macrophages and hepatocytes in wild-type mouse, further supports development of rhGALNS as enzyme replacement therapy for

  17. Enzyme replacement in a human model of mucopolysaccharidosis IVA in vitro and its biodistribution in the cartilage of wild type mice.

    Dvorak-Ewell, Melita; Wendt, Dan; Hague, Chuck; Christianson, Terri; Koppaka, Vish; Crippen, Danielle; Kakkis, Emil; Vellard, Michel


    Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is a lysosomal storage disorder caused by deficiency of N-acetylgalactosamine-6-sulfatase (GALNS), an enzyme that degrades keratan sulfate (KS). Currently no therapy for MPS IVA is available. We produced recombinant human (rh)GALNS as a potential enzyme replacement therapy for MPS IVA. Chinese hamster ovary cells stably overexpressing GALNS and sulfatase modifying factor-1 were used to produce active ( approximately 2 U/mg) and pure (>or=97%) rhGALNS. The recombinant enzyme was phosphorylated and was dose-dependently taken up by mannose-6-phosphate receptor (K(uptake) = 2.5 nM), thereby restoring enzyme activity in MPS IVA fibroblasts. In the absence of an animal model with a skeletal phenotype, we established chondrocytes isolated from two MPS IVA patients as a disease model in vitro. MPS IVA chondrocyte GALNS activity was not detectable and the cells exhibited KS storage up to 11-fold higher than unaffected chondrocytes. MPS IVA chondrocytes internalized rhGALNS into lysosomes, resulting in normalization of enzyme activity and decrease in KS storage. rhGALNS treatment also modulated gene expression, increasing expression of chondrogenic genes Collagen II, Collagen X, Aggrecan and Sox9 and decreasing abnormal expression of Collagen I. Intravenous administration of rhGALNS resulted in biodistribution throughout all layers of the heart valve and the entire thickness of the growth plate in wild-type mice. We show that enzyme replacement therapy with recombinant human GALNS results in clearance of keratan sulfate accumulation, and that such treatment ameliorates aberrant gene expression in human chondrocytes in vitro. Penetration of the therapeutic enzyme throughout poorly vascularized, but clinically relevant tissues, including growth plate cartilage and heart valve, as well as macrophages and hepatocytes in wild-type mouse, further supports development of rhGALNS as enzyme replacement therapy for MPS IVA.

  18. Cyclosporine withdrawal improves long-term graft survival in renal transplantation.

    Gallagher, Martin; Jardine, Meg; Perkovic, Vlado; Cass, Alan; McDonald, Stephen; Petrie, James; Eris, Josette


    The reduction in renal transplant rejection rates achieved over the last 20 years have not translated into a commensurate improvement in long-term graft survival. Cyclosporine has been central to immunosuppressive regimens throughout this period but its effect on long-term transplant outcomes remains unclear. This randomized controlled trial allocated first cadaveric renal transplant recipients in seven centers around Australia to three immunosuppressive regimens: azathioprine and prednisolone (AP), long-term cyclosporine alone (Cy), or cyclosporine initiation followed by withdrawal at 3 months and azathioprine and prednisolone replacement (WDL). Between 1983 and 1986, 489 patients were randomized with 98% follow-up to a median of 20.6 years. Mean graft survival (censoring deaths) was superior in the WDL group (14.8 years) when compared with both AP (12.4 years, P=0.01 log-rank test) and Cy (12.5 years, P=0.01 log-rank test) groups by intention-to-treat. Without death censoring, graft survival with WDL was superior to AP (9.5 years vs. 6.7 years, P=0.04) and of borderline superiority to Cy (9.5 years vs. 8.5 years, P=0.06). Patient survival was not different between the three groups. Renal function was superior in AP (at 1, 10, and 15 years posttransplant) and WDL (at 1, 5, 10, 15, and 20 years) groups when compared with Cy. This study illustrates superior long-term renal transplant survival and preservation of renal function with a protocol using cyclosporine withdrawal. If long-term renal transplant outcomes are to improve, we should reconsider guidelines recommending universal maintenance use of cyclosporine.

  19. [Reform of long-term care in the Netherlands: solidarity maintained?].

    van der Aa, Maartje J; Evers, Silvia M A A; Klosse, Saskia; Maarse, J A M Hans


    The reform of long-term care (LTC) in the Netherlands is a much debated topic. The reform essentially comes down to a shift in healthcare claims and a cutback. As of 1 January 2015, the Long-Term Care Act (WLZ) shall replace the Exceptional Medical Expenses Act (AWBZ). In doing so, parts of the AWBZ will shift to the Health Care Insurance Act (ZVW) and the renewed Social Support Act (WMO 2015), which will be carried out by municipalities. This is a significant change: whereas the AWBZ provides a right to care, the WMO commands delivery of tailor-made support. Care that falls under the WMO is only awarded if the capacity of persons seeking care, among others their financial resources and social network, are insufficient. Higher contributions than in the AWBZ may also be requested. These developments influence the experienced level of solidarity.

  20. Minimally Invasive Long-Term Management of Direct Restorations: the '5 Rs'.

    Green, David; Mackenzie, Louis; Banerjee, Avijit


    The assessment and operative long-term management of direct restorations is a complex and controversial subject in conservative dentistry. Employing a minimally invasive (MI) approach helps preserve natural tooth structure and maintain endodontic health for as long as possible during the restorative cycle. This paper discusses how minimally invasive techniques may be applied practically to reviewing, resealing, refurbishing, repairing or replacing deteriorating/failed direct coronal restorations (the'5 Rs') and provides an update of contemporary MI clinical procedures. CPD/CLINICAL RELEVANCE: The assessment and long-term clinical management of deteriorating/failing direct restorations is a major component of the general dental practice workload and NHS UK budget expenditure for operative dentistry.


    Skidmore, E.; Hoffman, E.; Daugherty, W.


    The Model 9975 shipping package specifies the materials of construction for its various components. With the loss of availability of material for two components (cane fiberboard overpack and Viton{reg_sign} GLT O-rings), alternate materials of construction were identified and approved for use for transport (softwood fiberboard and Viton{reg_sign} GLT-S O-rings). As these shipping packages are part of a long-term storage configuration at the Savannah River Site, additional testing is in progress to verify satisfactory long-term performance of the alternate materials under storage conditions. The test results to date can be compared to comparable results on the original materials of construction to draw preliminary conclusions on the performance of the replacement materials.

  2. Mesozoic long-term eustatic cycles and their uncertain hierarchy

    Dmitry A.Ruban


    Global sea-level has changed in a cyclic manner through geologic history, but the regularities of these changes are yet to be fully understood. Despite certain (and sometimes significant) differences, the available Mesozoic eustatic curves permit the outlining of long-term eustatic cycles, which are provi-sionally defined as cycles recognizable at the stage level and higher. Interpretation of the Triassic eustatic curves indicates two orders of long-term cycles and a 1st-order sea-level rise throughout the entire period. The Jurassic eustatic curves imply cyclicity of one or two orders, and a 1st-order eustatic rise during the entire period is also evident. Most challenges are interpretations for the Cretaceous; two to four orders of long-term eustatic cycles can be established for this period. Generally, the hierarchy of the long-term eustatic cycles might have changed through the Mesozoic. If so, and if one considers differ-ences of cycles of the same order between the periods of this era, it is difficult to apply “standard”hi-erarchical classifications to the documented cycles. The hypothetical uncertainty of the hierarchy of the Mesozoic long-term eustatic cycles is an important challenge for modern researchers.

  3. The Commonwealth Fund Survey of Long-Term Care Specialists.

    Miller, Edward Alan; Weissert, William G


    The Commonwealth Fund Survey of Long-Term Care of Specialists was administered via the World Wide Web from September 2007 through March 2008. The primary purpose was to characterize the views of those with known or demonstrable experience and expertise with at least one aspect of long-term care. Among 2,577 potential respondents, 1,147 completed the entire survey for an overall response rate of 44.5%. This special supplement of Medical Care Research and Review uses data collected from the survey to explore several issue areas, namely, reforming long-term care financing, improving government oversight, adopting nursing home culture change, and rebalancing long-term care away from institutions toward home- and community-based services. Analyses documenting the opinion networks of long-term care specialists and the relationship between network characteristics and attitudes toward reform are also reported. Two leading experts provide commentary as well. Details of the study's methodology and issue content are described.

  4. Short- and long-term (trophic) purinergic signalling.

    Burnstock, Geoffrey


    There is long-term (trophic) purinergic signalling involving cell proliferation, differentiation, motility and death in the development and regeneration of most systems of the body, in addition to fast purinergic signalling in neurotransmission, neuromodulation and secretion. It is not always easy to distinguish between short- and long-term signalling. For example, adenosine triphosphate (ATP) can sometimes act as a short-term trigger for long-term trophic events that become evident days or even weeks after the original challenge. Examples of short-term purinergic signalling during sympathetic, parasympathetic and enteric neuromuscular transmission and in synaptic transmission in ganglia and in the central nervous system are described, as well as in neuromodulation and secretion. Long-term trophic signalling is described in the immune/defence system, stratified epithelia in visceral organs and skin, embryological development, bone formation and resorption and in cancer. It is likely that the increase in intracellular Ca(2+) in response to both P2X and P2Y purinoceptor activation participates in many short- and long-term physiological effects.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'.

  5. Method for Water Management Considering Long-term Probabilistic Forecasts

    Hwang, J.; Kang, J.; Suh, A. S.


    This research is aimed at predicting the monthly inflow of the Andong-dam basin in South Korea using long-term probabilistic forecasts to apply long-term forecasts to water management. Forecasted Cumulative Distribution Functions (CDFs) of monthly precipitation are plotted by combining the range of monthly precipitation based on proper Probability Density Function (PDF) in past data with probabilistic forecasts in each category. Ensembles of inflow are estimated by entering generated ensembles of precipitation based on the CDFs into the 'abcd' water budget model. The bias and RMSE between averages in past data and observed inflow are compared to them in forecasted ensembles. In our results, the bias and RMSE of average precipitation in the forecasted ensemble are bigger than in past data, whereas the average inflow in the forecasted ensemble is smaller than in past data. This result could be used for reference data to apply long-term forecasts to water management, because of the limit in the number of forecasted data for verification and differences between the Andong-dam basin and the forecasted regions. This research has significance by suggesting a method of applying probabilistic information in climate variables from long-term forecasts to water management in Korea. Original data of a climate model, which produces long-term probabilistic forecasts should be verified directly as input data of a water budget model in the future, so that a more scientific response in water management against uncertainty of climate change could be reached.

  6. Child maltreatment: pathway to chronic and long-term conditions?

    Taylor, Julie; Bradbury-Jones, Caroline; Lazenbatt, Anne; Soliman, Francesca


    The manifesto Start Well, Live Better by the UK Faculty of Public Health (Start Well, Live Better-A Manifesto for the Public's Health. London: UK Faculty of Public Health, 2014) sets out 12 compelling priorities for the protection of people's health. The focus of this document is preventative, calling for a comprehensive strategy to target a wide-ranging set of challenges to public health; however, it fails to mention child maltreatment and its negative impact on long-term health outcomes. In this article, we explore the long-term negative consequences of child maltreatment and how these can be conceptually aligned with four different characteristics of long-term health conditions. We suggest that situating child maltreatment within a long-term conditions framework could have significant advantages and implications for practice, policy and research, by strengthening a commitment across disciplines to apply evidence-based principles linked with policy and evaluation and recognizing the chronic effects of maltreatment to concentrate public, professional and government awareness of the extent and impact of the issue. We argue that a public health approach is the most effective way of focusing preventative efforts on the long-term sequelae of child maltreatment and to foster cooperation in promoting children's rights to grow and develop in a safe and caring environment free from violence and abuse. © The Author 2015. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail:

  7. Long-Term Stewardship Program Science and Technology Requirements

    Joan McDonald


    Many of the United States’ hazardous and radioactively contaminated waste sites will not be sufficiently remediated to allow unrestricted land use because funding and technology limitations preclude cleanup to pristine conditions. This means that after cleanup is completed, the Department of Energy will have long-term stewardship responsibilities to monitor and safeguard more than 100 sites that still contain residual contamination. Long-term stewardship encompasses all physical and institutional controls, institutions, information, and other mechanisms required to protect human health and the environment from the hazards remaining. The Department of Energy Long-Term Stewardship National Program is in the early stages of development, so considerable planning is still required to identify all the specific roles and responsibilities, policies, and activities needed over the next few years to support the program’s mission. The Idaho National Engineering and Environmental Laboratory was tasked with leading the development of Science and Technology within the Long-Term Stewardship National Program. As part of that role, a task was undertaken to identify the existing science and technology related requirements, identify gaps and conflicts that exist, and make recommendations to the Department of Energy for future requirements related to science and technology requirements for long-term stewardship. This work is summarized in this document.

  8. Long-term greenhouse gas measurements from aircraft

    Karion, A.; Sweeney, C.; Wolter, S.; Newberger, T.; Chen, H.; Andrews, A.; Kofler, J.; Neff, D.; Tans, P.


    In March 2009 the NOAA/ESRL/GMD Carbon Cycle and Greenhouse Gases Group collaborated with the US Coast Guard (USCG) to establish the Alaska Coast Guard (ACG) sampling site, a unique addition to NOAA's atmospheric monitoring network. This collaboration takes advantage of USCG bi-weekly Arctic Domain Awareness (ADA) flights, conducted with Hercules C-130 aircraft from March to November each year. NOAA has installed window-replacement inlet plates on two USCG C-130 aircraft and deploys a pallet with NOAA instrumentation on each ADA flight. Flights typically last 8 h and cover a very large area, traveling from Kodiak, AK in the south up to Barrow, AK in the north, and making altitude profiles near the coast as well as in the interior. NOAA instrumentation on each flight includes: a flask sampling system, a continuous CO2/CH4/CO/H2O analyzer, a continuous ozone analyzer, and an ambient temperature and humidity sensor. GPS time and location from the aircraft's navigation system are also collected. Air samples collected in flight are analyzed at NOAA/ESRL for the major greenhouse gases and a variety of halocarbons and hydrocarbons that influence climate, stratospheric ozone, and air quality. Instruments on this aircraft are designed and deployed to be able to collect air samples and data autonomously, so that NOAA personnel visit the site only for installation at the beginning of each season. We present an assessment of the cavity ring-down spectroscopy (CRDS) CO2/CH4/CO/H2O analyzer performance operating on an aircraft over a three-year period. We describe the overall system for making accurate greenhouse gas measurements using a CRDS analyzer on an aircraft with minimal operator interaction. Short and long-term stability of the CRDS analyzer over a seven-month deployment period is better than 0.15 ppm, 2 ppb, and 5 ppb for CO2, CH4, CO respectively, considering differences of on-board reference tank measurements from a laboratory calibration performed prior to

  9. Long-term greenhouse gas measurements from aircraft

    A. Karion


    Full Text Available In March 2009 the NOAA/ESRL/GMD Carbon Cycle and Greenhouse Gases Group collaborated with the US Coast Guard (USCG to establish the Alaska Coast Guard (ACG sampling site, a unique addition to NOAA's atmospheric monitoring network. This collaboration takes advantage of USCG bi-weekly Arctic Domain Awareness (ADA flights, conducted with Hercules C-130 aircraft from March to November each year. NOAA has installed window-replacement inlet plates on two USCG C-130 aircraft and deploys a pallet with NOAA instrumentation on each ADA flight. Flights typically last 8 h and cover a very large area, traveling from Kodiak, AK in the south up to Barrow, AK in the north, and making altitude profiles near the coast as well as in the interior. NOAA instrumentation on each flight includes: a flask sampling system, a continuous CO2/CH4/CO/H2O analyzer, a continuous ozone analyzer, and an ambient temperature and humidity sensor. GPS time and location from the aircraft's navigation system are also collected. Air samples collected in flight are analyzed at NOAA/ESRL for the major greenhouse gases and a variety of halocarbons and hydrocarbons that influence climate, stratospheric ozone, and air quality. Instruments on this aircraft are designed and deployed to be able to collect air samples and data autonomously, so that NOAA personnel visit the site only for installation at the beginning of each season. We present an assessment of the cavity ring-down spectroscopy (CRDS CO2/CH4/CO/H2O analyzer performance operating on an aircraft over a three-year period. We describe the overall system for making accurate greenhouse gas measurements using a CRDS analyzer on an aircraft with minimal operator interaction. Short and long-term stability of the CRDS analyzer over a seven-month deployment period is better than 0.15 ppm, 2 ppb, and 5 ppb for CO2, CH4, CO respectively, considering

  10. Reliability of Modern Scores to Predict Long-Term Mortality After Isolated Aortic Valve Operations.

    Barili, Fabio; Pacini, Davide; D'Ovidio, Mariangela; Ventura, Martina; Alamanni, Francesco; Di Bartolomeo, Roberto; Grossi, Claudio; Davoli, Marina; Fusco, Danilo; Perucci, Carlo; Parolari, Alessandro


    Contemporary scores for estimating perioperative death have been proposed to also predict also long-term death. The aim of the study was to evaluate the performance of the updated European System for Cardiac Operative Risk Evaluation II, The Society of Thoracic Surgeons Predicted Risk of Mortality score, and the Age, Creatinine, Left Ventricular Ejection Fraction score for predicting long-term mortality in a contemporary cohort of isolated aortic valve replacement (AVR). We also sought to develop for each score a simple algorithm based on predicted perioperative risk to predict long-term survival. Complete data on 1,444 patients who underwent isolated AVR in a 7-year period were retrieved from three prospective institutional databases and linked with the Italian Tax Register Information System. Data were evaluated with performance analyses and time-to-event semiparametric regression. Survival was 83.0% ± 1.1% at 5 years and 67.8 ± 1.9% at 8 years. Discrimination and calibration of all three scores both worsened for prediction of death at 1 year and 5 years. Nonetheless, a significant relationship was found between long-term survival and quartiles of scores (p < 0.0001). The estimated perioperative risk by each model was used to develop an algorithm to predict long-term death. The hazard ratios for death were 1.1 (95% confidence interval, 1.07 to 1.12) for European System for Cardiac Operative Risk Evaluation II, 1.34 (95% CI, 1.28 to 1.40) for the Society of Thoracic Surgeons score, and 1.08 (95% CI, 1.06 to 1.10) for the Age, Creatinine, Left Ventricular Ejection Fraction score. The predicted risk generated by European System for Cardiac Operative Risk Evaluation II, The Society of Thoracic Surgeons score, and Age, Creatinine, Left Ventricular Ejection Fraction scores cannot also be considered a direct estimate of the long-term risk for death. Nonetheless, the three scores can be used to derive an estimate of long-term risk of death in patients who undergo

  11. First human treatment with investigational rhGUS enzyme replacement therapy in an advanced stage MPS VII patient.

    Fox, Joyce E; Volpe, Linda; Bullaro, Josephine; Kakkis, Emil D; Sly, William S


    Mucopolysaccharidosis type VII (MPS VII, Sly syndrome) is a very rare lysosomal storage disease caused by a deficiency of the enzyme β-glucuronidase (GUS), which is required for the degradation of three glycosaminoglycans (GAGs): dermatan sulfate, heparan sulfate, and chondroitin sulfate. Progressive accumulation of these GAGs in lysosomes leads to increasing dysfunction in numerous tissues and organs. Enzyme replacement therapy (ERT) has been used successfully for other MPS disorders, but there is no approved treatment for MPS VII. Here we describe the first human treatment with recombinant human GUS (rhGUS), an investigational therapy for MPS VII, in a 12-year old boy with advanced stage MPS VII. Despite a tracheostomy, nocturnal continuous positive airway pressure, and oxygen therapy, significant pulmonary restriction and obstruction led to oxygen dependence and end-tidal carbon dioxide (ETCO2) levels in the 60-80mmHg range, eventually approaching respiratory failure (ETCO2 of 100mmHg) and the need for full-time ventilation. Since no additional medical measures could improve his function, we implemented experimental ERT by infusing rhGUS at 2mg/kg over 4h every 2 weeks for 24 weeks. Safety was evaluated by standard assessments and observance for any infusion associated reactions (IARs). Urinary GAG (uGAG) levels, pulmonary function, oxygen dependence, CO2 levels, cardiac valve function, liver and spleen size, and growth velocity were assessed to evaluate response to therapy. rhGUS infusions were well tolerated. No serious adverse events (SAEs) or IARs were observed. After initiation of rhGUS infusions, the patient's uGAG excretion decreased by more than 50%. Liver and spleen size were reduced within 2 weeks of the first infusion and reached normal size by 24 weeks. Pulmonary function appeared to improve during the course of treatment based on reduced changes in ETCO2 after off-ventilator challenges and a reduced oxygen requirement. The patient regained the

  12. Time of Initiating Enzyme Replacement Therapy Affects Immune Abnormalities and Disease Severity in Patients with Gaucher Disease

    Ioanou, Chidima; Plassmeyer, Matthew; Ryherd, Mark; Kozhaya, Lina; Austin, Lauren; Abidoglu, Cem; Unutmaz, Derya; Alpan, Oral; Goker-Alpan, Ozlem


    Gaucher disease (GD) patients often present with abnormalities in immune response that may be the result of alterations in cellular and/or humoral immunity. However, how the treatment and clinical features of patients impact the perturbation of their immunological status remains unclear. To address this, we assessed the immune profile of 26 GD patients who were part of an enzyme replacement therapy (ERT) study. Patients were evaluated clinically for onset of GD symptoms, duration of therapy and validated outcome measures for ERT. According to DS3 disease severity scoring system criteria, they were assigned to have mild, moderate or severe GD. Flow cytometry based immunophenotyping was performed to analyze subsets of T, B, NK, NKT and dendritic cells. GD patients showed multiple types of immune abnormalities associated to T and B lymphocytes with respect to their subpopulations as well as memory and activation markers. Skewing of CD4 and CD8 T cell numbers resulting in lower CD4/CD8 ratio and an increase in overall T cell activation were observed. A decrease in the overall B cells and an increase in NK and NKT cells were noted in the GD patients compared to controls. These immune alterations do not correlate with GD clinical type or level of biomarkers. However, subjects with persistent immune alterations, especially in B cells and DCs correlate with longer delay in initiation of ERT (ΔTX). Thus, while ERT may reverse some of these immune abnormalities, the immune cell alterations become persistent if therapy is further delayed. These findings have important implications in understanding the immune disruptions before and after treatment of GD patients. PMID:27942037

  13. Right ventricular involvement in patients with Fabry's disease and the effect of enzyme replacement therapy

    Wuest, W. [Universitaetsklinikum Erlangen (Germany). Radiologisches Inst.; Machann, W.; Koestler, H.; Hahn, D.; Beer, M. [Universitaetsklinikum Wuerzburg (Germany). Inst. fuer Roentgendiagnostik; Breunig, F.; Weidemann, F.; Wanner, C. [Universitaetsklinikum Wuerzburg (Germany). Medizinische Klinik I


    According to echocardiography reports, Fabry cardiomyopathy not only affects the left ventricle (LV) but also the right ventricle (RV). Until now no MRI studies about the effect of enzyme replacement therapy (ERT) on the RV are available. We evaluated the effect of ERT on the RV. In this prospective trial 14 patients with genetically proven Fabry's disease were examined using a 1.5 T MR scanner before ERT and after 13 {+-} 1 months of ERT. All patients underwent cardiac MR imaging and the RV/LV cardiac morphology and function were analyzed. At baseline examination the values were as follows: RV mass 31 {+-} 6 g/m{sup 2}, end-diastolic volume (EDV) 88 {+-} 13 ml/m{sup 2}, end-systolic volume (ESV) 39 {+-} 9 ml/m{sup 2}, stroke volume (SV) 49 {+-} 7 ml/m{sup 2} and ejection fraction (EF) 56 {+-} 5 %. The RV mass and EDV decreased significantly after 13 {+-} 1 months on ERT (mass 27 {+-} 7 g/m{sup 2}, p < 0.05, EDV 76 {+-} 24 ml/m{sup 2}, p < 0.05), with no significant change of ESV (33 {+-} 13 ml/m{sup 2}), SV (43 {+-} 12 ml/m{sup 2}) and EF (57 {+-} 7 %). The LV mass (102 {+-} 26 g/m{sup 2} vs. 94 {+-} 27 g/m{sup 2}, p < 0.05), EDV (76 {+-} 13 ml/m{sup 2} vs. 66 {+-} 22 ml/m{sup 2}, p < 0.05) and ESV (29 {+-} 9 ml/m{sup 2} vs. 23 {+-} 9 ml/m{sup 2}, p < 0.05) decreased significantly while the EF (64 {+-} 7 % vs. 66 {+-} 5 %; p < 0.05) increased significantly. Besides the known beneficial effect on the LV, ERT improves RV mass and EDV. (orig.)

  14. Long-term urological outcomes in cloacal anomalies.

    Caldwell, Brian T; Wilcox, Duncan T


    Cloacal anomalies are the most complex and severe form of congenital anorectal malformations (ARM) and urogenital malformations, and it has been well documented that increased severity of ARM leads to worse outcomes. While short-term data on persistent cloaca are available, a paucity of data on long-term outcomes exists, largely because of a lack of uniform terminology, inclusion with other ARM and evolution of the operative technique. On comprehensive review of the published literature on long-term urological outcomes in patients with cloacal anomalies, we found a significant risk of chronic kidney disease and incontinence, however, with improvements in surgical technique, outcomes have improved. Continence often requires intermittent catheterization and in some cases, bladder augmentation. The complexity of cloacal malformations and associated anomalies make long-term multidisciplinary follow-up imperative. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Long-term impact of sales promotion on brand image

    Danijela Mandić


    Full Text Available Sales promotion (SP is an inevitable tool in the marketing communications mix, especially in the FMCG markets, due to pressures such as retailers’ growing demands and increasing competition. This has proven to be an issue for many companies, especially those with a premium brand positioning and those concerned about the impact that SP might have on the long-term image of the company. Despite the fact that literature is replete with research on SP, it seems to be vastly generalized and mostly focused on price reductions. Thus, this paper aims to analyze and discuss the issue of the long-term impact that SP has on companies, especially on premium brands in the FMCG markets. It concludes that, when used properly and strategically, SP may have a positive long-term impact on brands.

  16. Sexuality and Physical Intimacy in Long Term Care

    Lichtenberg, Peter A.


    Sexuality and sexual needs in older adults remains a neglected area of clinical intervention, particularly so in long term care settings. Because older adults in medical rehabilitation and long term care beds present with significant frailties, and often significant neurocognitive disorders it makes it difficult for occupational therapists and other staff to evaluate the capacity of an older adult resident to participate in sexual relationships. The current paper reviews the current literature on sexuality and aging, examines some of the clinical practices and guidelines regarding sexual expression in long term care and presents two case examples. A semi-structured interview and decision tree is presented to assist therapists in making careful and informed decisions and thereby balancing needs for protection with needs for autonomy. PMID:24354331

  17. Winning market positioning strategies for long term care facilities.

    Higgins, L F; Weinstein, K; Arndt, K


    The decision to develop an aggressive marketing strategy for its long term care facility has become a priority for the management of a one-hundred bed facility in the Rocky Mountain West. Financial success and lasting competitiveness require that the facility in question (Deer Haven) establish itself as the preferred provider of long term care for its target market. By performing a marketing communications audit, Deer Haven evaluated its present market position and created a strategy for solidifying and dramatizing this position. After an overview of present conditions in the industry, we offer a seven step process that provides practical guidance for positioning a long term care facility. We conclude by providing an example application.

  18. Using long-term transit timing to detect terrestrial planets

    Heyl, J S; Heyl, Jeremy S.; Gladman, Brett J.


    We propose that the presence of additional planets in extrasolar planetary systems can be detected by long-term transit timing studies. If a transiting planet is on an eccentric orbit then the presence of another planet causes a secular advance of the transiting planet's pericenter over and above the effect of general relativity. Although this secular effect is impractical to detect over a small number of orbits, it causes long-term differences in when future transits occur, much like the long-term decay observed in pulsars. Measuring this transit-timing delay would thus allow the detection of either one or more additional planets in the system or the first measurements of non-zero oblateness ($J_2$) of the central stars.

  19. Long-term visual tracking based on correlation filters

    Wei, Quanlu; Lao, Songyang; Bai, Liang


    In order to accomplish the long term visual tracking task in complex scenes, solve problems of scale variation, appearance variation and tracking failure, a long term tracking algorithm is given based on the framework of collaborative correlation tracking. Firstly, we integrate several powerful features to boost the represent ability based on the kernel correlation filter, and extend the filter by embedding a scale factor into the kernelized matrix to handle the scale variation. Then, we use the Peak-Sidelobe Ratio to decide whether the object is tracked successfully, and a CUR filter for re-detection the object in case of tracking failure is learnt with random sampling. Corresponding experiment is performed on 17 challenging benchmark video sequences. Compared with the 8 existing state-of-the-art algorithms based on discriminative learning method, the results show that the proposed algorithm improves the tracking performance on several indexes, and is robust to complex scenes for long term visual tracking.

  20. Marijuana effects on long-term memory assessment and retrieval.

    Darley, C F; Tinklenberg, J R; Roth, W T; Vernon, S; Kopell, B S


    The ability of 16 college-educated male subjects to recall from long-term memory a series of common facts was tested during intoxication with marijuana extract calibrated to 0.3 mg/kg delta-9-tetrahydrocannabinol and during placebo conditions. The subjects' ability to assess their memory capabilities was then determined by measuring how certain they were about the accuracy of their recall performance and by having them predict their performance on a subsequent recognition test involving the same recall items. Marijuana had no effect on recall or recognition performance. These results do not support the view that marijuana provides access to facts in long-term storage which are inaccessible during non-intoxication. During both marijuana and placebo conditions, subjects could accurately predict their recognition memory performance. Hence, marijuana did not alter the subjects' ability to accurately assess what information resides in long-term memory even though they did not have complete access to that information.


    LI Yu-feng; ZHU Jia-bin; WANG Chun-ling; DING Bang-he; LI Yuan-yuan; XUAN Heng-bao; QIAN Mo-sheng


    Objective: To observe the long-term effect of homoharringtonine (HHT) on chronic granulocytic leukemia (CGL) and its pharmacological mechanism. Methods: 76 patients with newly diagnosed early chronic phase CGL received treatment of merely 1.5 mg/m2 daily HHT for induction remission and long-term maintenance treatment. The apoptosis rate of bone marrow CD34+ cells induced by HHT was assayed with flow cytometer. Results: 86.8% patients achieved CHR, 13.2% patients PHR and 31.8% patients got cytogenetic response in HHT treatment group, which was longer than 31 (8-54) months in hydroxyurea (HU) group (P<0.05). The effect of apoptosis induction HHT was stronger on CGL-CP patients bone marrow CD34+ cells than on normal person bone marrow CD34+ cells. Conclusion: HHT is a very effective drug for remission induction and long-term maintenance treatment in early chronic phase CGL patients.

  2. On the relationship between short- and long-term memory

    Sørensen, Thomas Alrik

    James (1890) divided memory into separate stores; primary and secondary – or short-term and long-term memory. The interaction between the two stores often assumes that information initially is represented in volatile short-term store before entering and consolidating in the more durable long-term......, accepted). Counter to popular beliefs this suggest that long-term memory precedes short-term memory and not vice versa....... memory system (e.g. Atkinson & Shiffrin, 1968). Short-term memory seems to provide a surprising processing bottleneck where only a very limited amount of information can be represented at any given moment (Miller, 1956; Cowan, 2001). A number of studies have investigated the nature of this processing...

  3. Evidence for long-term memory in sea level

    Dangendorf, Sönke; Rybski, Diego; Mudersbach, Christoph; Müller, Alfred; Kaufmann, Edgar; Zorita, Eduardo; Jensen, Jürgen


    Detection and attribution of anthropogenic climate change signals in sea level rise (SLR) has experienced considerable attention during the last decades. Here we provide evidence that superimposed on any possible anthropogenic trend there is a significant amount of natural decadal and multidecadal variability. Using a set of 60 centennial tide gauge records and an ocean reanalysis, we find that sea levels exhibit long-term correlations on time scales up to several decades that are independent of any systematic rise. A large fraction of this long-term variability is related to the steric component of sea level, but we also find long-term correlations in current estimates of mass loss from glaciers and ice caps. These findings suggest that (i) recent attempts to detect a significant acceleration in regional SLR might underestimate the impact of natural variability and (ii) any future regional SLR threshold might be exceeded earlier/later than from anthropogenic change alone.

  4. Long-term drought severity variations in Morocco

    Esper, Jan; Frank, David; Büntgen, Ulf; Verstege, Anne; Luterbacher, Jürg; Xoplaki, Elena


    Cedrus atlantica ring width data are used to reconstruct long-term changes in the Palmer Drought Severity Index (PDSI) over the past 953 years in Morocco, NW Africa. The reconstruction captures the dry conditions since the 1980s well and places this extreme period within a millennium-long context. PDSI values were above average for most of the 1450-1980 period, which let recent drought appear exceptional. However, our results also indicate that this pluvial episode of the past millennium was preceded by generally drier conditions back to 1049. Comparison of PDSI estimates with large-scale pressure field reconstructions revealed steady synoptic patterns for drought conditions over the past 350 years. The long-term changes from initially dry to pluvial to recent dry conditions are similar to PDSI trends reported from N America, and we suggest that they are related to long-term temperature changes, potentially teleconnected with ENSO variability and forced by solar irradiance changes.

  5. Stirling engine - Approach for long-term durability assessment

    Tong, Michael T.; Bartolotta, Paul A.; Halford, Gary R.; Freed, Alan D.


    The approach employed by NASA Lewis for the long-term durability assessment of the Stirling engine hot-section components is summarized. The approach consists of: preliminary structural assessment; development of a viscoplastic constitutive model to accurately determine material behavior under high-temperature thermomechanical loads; an experimental program to characterize material constants for the viscoplastic constitutive model; finite-element thermal analysis and structural analysis using a viscoplastic constitutive model to obtain stress/strain/temperature at the critical location of the hot-section components for life assessment; and development of a life prediction model applicable for long-term durability assessment at high temperatures. The approach should aid in the provision of long-term structural durability and reliability of Stirling engines.

  6. Inflammatory markers in relation to long-term air pollution.

    Mostafavi, Nahid; Vlaanderen, Jelle; Chadeau-Hyam, Marc; Beelen, Rob; Modig, Lars; Palli, Domenico; Bergdahl, Ingvar A; Vineis, Paolo; Hoek, Gerard; Kyrtopoulos, Soterios Α; Vermeulen, Roel


    Long-term exposure to ambient air pollution can lead to chronic health effects such as cancer, cardiovascular and respiratory disease. Systemic inflammation has been hypothesized as a putative biological mechanism contributing to these adverse health effects. We evaluated the effect of long-term exposure to air pollution on blood markers of systemic inflammation. We measured a panel of 28 inflammatory markers in peripheral blood samples from 587 individuals that were biobanked as part of a prospective study. Participants were from Varese and Turin (Italy) and Umea (Sweden). Long-term air pollution estimates of nitrogen oxides (NOx) were available from the European Study of Cohorts for Air Pollution Effects (ESCAPE). Linear mixed models adjusted for potential confounders were applied to assess the association between NOx and the markers of inflammation. Long-term exposure to NOx was associated with decreased levels of interleukin (IL)-2, IL-8, IL-10 and tumor necrosis factor-α in Italy, but not in Sweden. NOx exposure levels were considerably lower in Sweden than in Italy (Sweden: median (5th, 95th percentiles) 6.65 μg/m(3) (4.8, 19.7); Italy: median (5th, 95th percentiles) 94.2 μg/m(3) (7.8, 124.5)). Combining data from Italy and Sweden we only observed a significant association between long-term exposure to NOx and decreased levels of circulating IL-8. We observed some indication for perturbations in the inflammatory markers due to long-term exposure to NOx. Effects were stronger in Italy than in Sweden, potentially reflecting the difference in air pollution levels between the two cohorts.

  7. Long-term use of lithium and risk of colorectal adenocarcinoma

    Pottegård, Anton; Ennis, Zandra Nymand; Hallas, Jesper


    BACKGROUND: Lithium accumulates in the colon and inhibits the enzyme GSK-3β that possesses anti-carcinogenic effects. We therefore examined the association between lithium use and colorectal cancer risk in a nationwide study. METHODS: We used the Danish Cancer Registry to identify all patients...... diagnosed with incident colorectal adenocarcinoma during 2000-2012 (n=36 248). Using a matched case-control approach, we estimated the association between long-term use (⩾5 years) of lithium and risk of colorectal adenocarcinoma using conditional logistic regression. RESULTS: Long-term use of lithium......, 0.66-1.55; distal colon: 1.52 (95% CI, 1.05-2.20); and rectum: 0.80 (95% CI, 0.50-1.30). CONCLUSIONS: Lithium use was not associated with an overall increased risk of colorectal adenocarcinoma. The variation by subsite warrants further investigation....

  8. Prediction of Long Term Degradation of Insulating Materials


    fiberglass, foam, or cellulose insulation in areas where thermal bridges may be formed or used in places where it is not practical to install thicker...ER D C/ CE RL T R- 15 -8 Prediction of Long Term Degradation of Insulating Materials Co ns tr uc tio n En gi ne er in g R es ea rc ERDC/CERL TR-15-8 May 2015 Prediction of Long Term Degradation of Insulating Materials L. D. Stephenson, Andrew

  9. Long-term skeletal findings in Menkes disease

    Amador, Eva [Son Dureta Children' s Hospital, Department of Paediatric Radiology, Palma de Mallorca (Spain); Domene, Ruth; Fuentes, Cristian; Carreno, Juan-Carlos; Enriquez, Goya [Vall d' Hebron Children' s Hospital, Department of Paediatric Radiology, Barcelona (Spain)


    Skeletal findings in infants with Menkes disease, the most characteristic of which are metaphyseal spurs, long-bone fractures and wormian bones, have been widely reported. However, the changes in skeletal features over time are not well known. The long-term findings differ completely from those initially observed and consist of undertubulation and metaphyseal flaring, similar to the findings seen in some types of bone dysplasia. The initial and long-term radiological features in an 8-year-old boy with Menkes disease are illustrated. (orig.)

  10. Long-term outcome in patients with juvenile dermatomyositis

    Mathiesen, P; Hegaard, H; Herlin, Troels


    To evaluate a group of 53 patients with juvenile dermatomyositis (JDM), on average 13.9 years after disease onset, in order to describe the long-term disease outcome and to identify disease-related parameters associated with poor disease outcome.......To evaluate a group of 53 patients with juvenile dermatomyositis (JDM), on average 13.9 years after disease onset, in order to describe the long-term disease outcome and to identify disease-related parameters associated with poor disease outcome....

  11. Long-term stability test of a triple GEM detector

    Adak, R P; Das, S; Ghosal, D; Ghosh, S K; Mondal, A; Nag, D; Nayak, T K; Patra, R N; Prasad, S K; Raha, S; Sahu, P K; Sahu, S; Swain, S


    The main aim of the study is to perform the long-term stability test of gain of the single mask triple GEM detector. A simple method is used for this long- term stability test using a radioactive X-ray source with high activity. The test is continued till accumulation of charge per unit area > 12.0 mC/mm2. The details of the chamber fabrication, the test set-up, the method of measurement and the test results are presented in this paper.

  12. Intrahepatic haematoma in a patient on long-term haemodialysis.

    Lai, K N; Disney, A P; Mathew, T H

    Spontaneous intrahepatic haematoma is an uncommon potentially fatal complication in uraemic patients receiving long-term haemodialysis, particularly in those taking anticoagulant and antiplatelet drugs. Prompt diagnosis, withdrawal of anticoagulant and antiplatelet therapy, cautious transfusion, and careful dialysis with regional heparinisation are essential in the management and may help to avoid surgical intervention in the presence of a tendency to bleed. Noninvasive organ imaging such as ultrasonography and computerised axial tomography are helpful in diagnosis and monitoring of progress. A case of intrahepatic haematoma in a 37-year-old man who had been receiving long-term haemodialysis since 1976 is described.

  13. The long-term consequences of parental alcohol abuse

    Christoffersen, Mogens

    Does parents' long-term abuse of alcohol have an impact on children during their formative years? Yes, several long-term consequences for the children result from this study. The study ascertained an increased mortality and high occurrence of self-destructive behavioural forms (attempted suicide...... unemployment is seen in families with evidence of alcohol abuse. In some respects mothers who are alcohol abusers seem to have a different effect on their children than fathers who are alcohol abusers. So, for example, there is a higher occurence of violence-related crimes and convictions for sexual offences...

  14. Long-term recurrence and death rates after acute pancreatitis

    Lund, Helle; Tønnesen, Hanne; Tønnesen, Maja Hanne


    The aim of this study was to compare long-term recurrence and death rates after a first episode of acute pancreatitis in patients with and without gallstones. Additionally, it was of interest to find out if there were factors predictive of readmission or death.......The aim of this study was to compare long-term recurrence and death rates after a first episode of acute pancreatitis in patients with and without gallstones. Additionally, it was of interest to find out if there were factors predictive of readmission or death....

  15. Long-term recurrence and death rates after acute pancreatitis

    Lund, Helle; Tønnesen, Hanne; Tønnesen, Maja Hanne


    The aim of this study was to compare long-term recurrence and death rates after a first episode of acute pancreatitis in patients with and without gallstones. Additionally, it was of interest to find out if there were factors predictive of readmission or death.......The aim of this study was to compare long-term recurrence and death rates after a first episode of acute pancreatitis in patients with and without gallstones. Additionally, it was of interest to find out if there were factors predictive of readmission or death....

  16. Long-term prognosis and causes of death after spondylodiscitis

    Aagaard, Theis; Roed, Casper; Dahl, Benny;


    BACKGROUND: Data on long-term prognosis after spondylodiscitis are scarce. The purpose of this study was to determine long-term mortality and the causes of death after spondylodiscitis. METHODS: A nationwide, population-based cohort study using national registries of patients diagnosed with non.......62), respiratory (MRR = 1.71), gastrointestinal (MRR = 3.35), musculoskeletal (MRR = 5.39) and genitourinary diseases (MRR = 3.37), but also due to trauma, poisoning and external causes (MRR = 2.78), alcohol abuse-related diseases (MRR = 5.59) and drug abuse-related diseases (6 vs 0 deaths, MRR not calculable...

  17. Abdominal pain in long-term spinal cord injury

    Finnerup, Nanna Brix; Faaborg, Pia Møller; Krogh, Klaus;


    /discomfort. There was no relation of abdominal pain to other types of pain.Conclusion:Chronic pain located in the abdomen is frequent in patients with long-term SCI. The delayed onset following SCI and the relation to constipation suggest that constipation plays an important role for this type of pain in the spinal cord injured.......Objectives:To describe the prevalence and character of chronic abdominal pain in a group of patients with long-term spinal cord injury (SCI) and to assess predictors of abdominal pain.Study design:Postal survey.Setting:Members of the Danish Paraplegic Association.Methods:We mailed a questionnaire...

  18. Long-term Morbidity of Testicular Cancer Treatment.

    Fung, Chunkit; Fossa, Sophie D; Williams, Annalynn; Travis, Lois B


    Second malignant neoplasms, cardiovascular disease, neurotoxicity and ototoxicity, pulmonary complications, hypogonadism, and nephrotoxicity are potentially life-threatening long-term complications of testicular cancer and its therapy. This article describes the pathogenesis, risks, and management of these late effects experienced by long-term testicular cancer survivors, who are defined as individuals who are disease free 5 years or more after primary treatment. Testicular cancer survivors should follow applicable national guidelines for cancer screening and management of cardiovascular disease risk factors. In addition, health care providers should capitalize on the time of cancer diagnosis as a teachable moment to introduce and promote lifestyle changes.

  19. Thiazolidinediones and Risk of Long-Term Dialysis in Diabetic Patients with Advanced Chronic Kidney Disease: A Nationwide Cohort Study.

    Yu-Hsin Chen

    Full Text Available Thiazolidinediones (TZDs reduce urinary albumin excretion and proteinuria in diabetic nephropathy. The effect of TZDs on hard renal outcome in diabetic patients with chronic kidney disease (CKD is unknown. We investigate the association of TZDs and risk of long-term dialysis or death in diabetic patients with advanced CKD. The nationwide population-based cohort study was conducted using Taiwan's National Health Insurance Research Database. From January 2000 to June 2009, 12350 diabetic patients with advanced CKD (serum creatinine levels greater than 6 mg/dL but not yet receiving renal replacement therapy were selected for the study. We used multivariable Cox regression models and a propensity score-based matching technique to estimate hazard ratios (HRs for development of long-term dialysis and the composite outcome of long-term dialysis or death for TZD users (n=1224 as compared to nonusers (n=11126. During a median follow-up of 6 months, 8270 (67.0% patients required long-term dialysis and 2593 (21.0% patients died before starting long-term dialysis. Using propensity score matched analysis, we found TZD users were associated with a lower risk for long-term dialysis (HR, 0.80; 95% confidence interval [CI], 0.74-0.86 and the composite outcome of long-term dialysis or death (HR, 0.85; 95% CI, 0.80-0.91. The results were consistent across most patient subgroups. Use of TZDs among diabetic patients with advanced CKD was associated with lower risk for progression to end-stage renal disease necessitating long-term dialysis or death. Further randomized controlled studies are required to validate this association.

  20. Hippocampal Focal Knockout of CBP Affects Specific Histone Modifications, Long-Term Potentiation, and Long-Term Memory

    Barrett, Ruth M; Malvaez, Melissa; Kramar, Eniko; Matheos, Dina P; Arrizon, Abraham; Cabrera, Sara M; Lynch, Gary; Greene, Robert W; Wood, Marcelo A


    To identify the role of the histone acetyltransferase (HAT) CREB-binding protein (CBP) in neurons of the CA1 region of the hippocampus during memory formation, we examine the effects of a focal homozygous knockout of CBP on histone modifications, gene expression, synaptic plasticity, and long-term memory. We show that CBP is critical for the in vivo acetylation of lysines on histones H2B, H3, and H4. CBP's homolog p300 was unable to compensate for the loss of CBP. Neurons lacking CBP maintained phosphorylation of the transcription factor CREB, yet failed to activate CREB:CBP-mediated gene expression. Loss of CBP in dorsal CA1 of the hippocampus resulted in selective impairments to long-term potentiation and long-term memory for contextual fear and object recognition. Together, these results suggest a necessary role for specific chromatin modifications, selectively mediated by CBP in the consolidation of memories. PMID:21508930

  1. Hippocampal focal knockout of CBP affects specific histone modifications, long-term potentiation, and long-term memory.

    Barrett, Ruth M; Malvaez, Melissa; Kramar, Eniko; Matheos, Dina P; Arrizon, Abraham; Cabrera, Sara M; Lynch, Gary; Greene, Robert W; Wood, Marcelo A


    To identify the role of the histone acetyltransferase (HAT) CREB-binding protein (CBP) in neurons of the CA1 region of the hippocampus during memory formation, we examine the effects of a focal homozygous knockout of CBP on histone modifications, gene expression, synaptic plasticity, and long-term memory. We show that CBP is critical for the in vivo acetylation of lysines on histones H2B, H3, and H4. CBP's homolog p300 was unable to compensate for the loss of CBP. Neurons lacking CBP maintained phosphorylation of the transcription factor CREB, yet failed to activate CREB:CBP-mediated gene expression. Loss of CBP in dorsal CA1 of the hippocampus resulted in selective impairments to long-term potentiation and long-term memory for contextual fear and object recognition. Together, these results suggest a necessary role for specific chromatin modifications, selectively mediated by CBP in the consolidation of memories.

  2. Long-term follow-up of a female with congenital adrenal hyperplasia due to P450-oxidoreductase deficiency.

    Bonamichi, Beatriz D S F; Santiago, Stella L M; Bertola, Débora R; Kim, Chong A; Alonso, Nivaldo; Mendonca, Berenice B; Bachega, Tania A S S; Gomes, Larissa G


    P450 oxidoreductase deficiency (PORD) is a variant of congenital adrenal hyperplasia that is caused by POR gene mutations. The POR gene encodes a flavor protein that transfers electrons from nicotinamide adenine dinucleotide phosphate (NADPH) to all microsomal cytochrome P450 type II (including 21-hydroxylase, 17α-hydroxylase 17,20 lyase and aromatase), which is fundamental for their enzymatic activity. POR mutations cause variable impairments in steroidogenic enzyme activities that result in wide phenotypic variability ranging from 46,XX or 46,XY disorders of sexual differentiation, glucocorticoid deficiency, with or without skeletal malformations similar to Antley-Bixler syndrome to asymptomatic newborns diagnosed during neonatal screening test. Little is known about the PORD long-term evolution. We described a 46,XX patient with mild atypical genitalia associated with severe bone malformation, who was diagnosed after 13 years due to sexual infantilism. She developed large ovarian cysts and late onset adrenal insufficiency during follow-up, both of each regressed after hormone replacement therapies. We also described a late surgical approach for the correction of facial hypoplasia in a POR patient.

  3. Long term structural dynamics of mechanical systems with local nonlinearities

    Fey, R.H.B.; Campen, D.H. van; Kraker, A. de


    This paper deals with the long term behavior of periodically excited mechanical systems consisting of linear components and local nonlinearities. The number of degrees of freedom of the linear components is reduced by applying a component mode synthesis technique. Lyapunov exponents are used to iden

  4. Labor Income and the Demand for Long-term Bonds

    Koijen, R.S.J.; Nijman, T.E.; Werker, B.J.M.


    The riskless nature in real terms of inflation-linked bonds has led to the conclusion that inflation-linked bonds should constitute a substantial part of the optimal investment portfolio of long-term investors.This conclusion is reached in models where investors do not receive labor income during th

  5. Long-term Study of a Quadrivalent Human Papillomavirus Vaccine

    Ferris, Daron; Samakoses, Rudiwilai; Block, Stan L


    BACKGROUND: We present a long-term safety, immunogenicity, and effectiveness study of a quadrivalent human papillomavirus (HPV4) vaccine. METHODS: Sexually naive boys and girls aged 9 to 15 years (N = 1781) were assigned (2:1) to receive HPV4 vaccine or saline placebo at day 1 and months 2 and 6...

  6. Predicting the long-term citation impact of recent publications

    Stegehuis, Clara; Litvak, Nelly; Waltman, Ludo


    A fundamental problem in citation analysis is the prediction of the long-term citation impact of recent publications. We propose a model to predict a probability distribution for the future number of citations of a publication. Two predictors are used: The impact factor of the journal in which a pub

  7. Microfinance and rural development: a long-term perspective

    Moll, H.A.J.


    The long-term perspective on microfinance starts with a discussion of three central issues: first, views and policies, with two opposing views: "credit for target group" and "pushing the financial frontier"; second, the performance of microfinance institutions measured via two objectives: outreach a

  8. Assessing long-term and rare adverse effects of medicines

    Duijnhoven, R.G.


    Clinical studies in the development of new medicines are primarily designed to investigate efficacy. Knowledge of adverse effects is therefore limited at the time of approval of new medicines. In this thesis several studies were conducted to investigate long-term and rare adverse effects of medicine

  9. Long-term outcome in children of patients after stroke

    van de Port, Ingrid G. L.; Visser-Meily, Anne M. A.; Post, Marcel W. M.; Lindeman, Eline


    Objective: To investigate the long-term effects on children of parental stroke, with respect to care-giving tasks, children's behavioural problems and stress, and to study the relationship between stress and child, patient and partner characteristics. Subjects: A total of 44 children (age range 10-2

  10. Long-Term English Learners Writing Their Stories

    Jacobs, C. Lynn


    High school teacher C. Lynn Jacobs noted that the long-term English language learners in her class had improved in reading comprehension but still lacked writing skills. Inspired by a state humanities project, she worked with the students to publish a collection of stories and poems. Writing about their lives provided the motivation, and writing…

  11. Autonomy and Acceptance of Long-Term Care

    Hsu, Hui-Chuan; Ting, Yu-Shan; Jiang, Ting-Wen; Chien, Ming-Chih; Chien, Chih-Hsin


    This study explored the relationship between four types of autonomy (health autonomy, informational autonomy, living autonomy, and financial autonomy) and the acceptance of five types of long-term care (adult day care, respite care, assisted living, unit care, and group home) for the elderly in Taiwan. Data were collected from 167 middle-aged and…

  12. Long-term investing and your bond rating.

    Doody, Dennis


    Days cash on hand is an important measure of a healthcare organization's financial condition--but not the only one. A well-diversified investment portfolio managed against long-term objectives is equally important--and can be a significant asset in the eyes of bond rating agencies.

  13. Long-Term Follow-Up after Treatment of Cryptorchidism

    Thorup, Jorgen; Cortes, Dina


    When considering long-term prognosis and results in adult age following treatment of cryptorchidism in childhood there are three main issues to be discussed: cosmetics, fertility, and malignancy. In the present review, the most recent research on the topics related to summaries of well-known know...

  14. Incidental Biasing of Attention from Visual Long-Term Memory

    Fan, Judith E.; Turk-Browne, Nicholas B.


    Holding recently experienced information in mind can help us achieve our current goals. However, such immediate and direct forms of guidance from working memory are less helpful over extended delays or when other related information in long-term memory is useful for reaching these goals. Here we show that information that was encoded in the past…

  15. Long-term Advertising Effects and Optimal Budgeting

    Hansen, Flemming; Bech Christensen, Lars


    Using pure single-source data, this paper provides evidence for theexistence and magnitude of long-term advertising effects across FMCG productcategories. Furthermore, we focus on the difficulties that arise for wellestablishedbrands when new products are introduced into the market andproduct...

  16. Long-term prevention of diabetic nephropathy: an audit

    Schjoedt, K.J.; Hansen, H.P.; Tarnow, L.


    AIMS/HYPOTHESIS: In type 1 diabetic patients with microalbuminuria not receiving antihypertensive treatment, an increase in urinary AER (UAER) of 6-14%/year and a risk of developing diabetic nephropathy (DN) of 3-30%/year have been reported. We audited the long-term effect of blocking the renin-a...

  17. Long-Term Outcome in Guillain-Barre Syndrome

    J Gordon Millichap


    Full Text Available The long-term sequelae and early predictors of sequelae were determined in a chart review of 47 children with Guillain-Barre syndrome (GBS of whom 30 had been treated with intravenous gammaglobulin (IVIG at The Hospital for Sick Children, Toronto, Canada.

  18. Long-term accumulation of atmospheric dust in rocky deserts

    Goossens, D.; Offer, Z.Y.


    The spatial pattern of long-term (hundreds to thousands of years) accumulation of dust in rocky deserts was investigated in the northern Negev Desert of Israel. The concentration of dust in the desert subsoil was measured at 41 locations in a 53 ha test area for which detailed information exists on

  19. Semi-automatic long-term acoustic surveying

    Andreassen, Tórur; Surlykke, Annemarie; Hallam, John


    Increasing concern about decline in biodiversity has created a demand for population surveys. Acoustic monitoring is an efficient non-invasive method, which may be deployed for surveys of animals as diverse as insects, birds, and bats. Long-term unmanned automatic monitoring may provide unique...... to determine bat behavior and correct for the bias toward loud bats inherent in acoustic surveying....

  20. Medium and long-term perspectives of international bioenergy trade

    Kranzl, Lukas; Daioglou, Vasileios; Faaij, Andre; Junginger, Martin; Keramidas, Kimon; Matzenberger, Julian; Tromborg, Erik


    In the coming decades, huge challenges in the global energy system are expected. Scenarios indicate that bioenergy will play a substantial role in this process. However, up to now there is very limited insight regarding the implication this may have on bioenergy trade in the long term. The objective