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

PubMed Central

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

2017-01-01

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

Role of cardiac MRI in evaluating patients with Anderson-Fabry disease: assessing cardiac effects of long-term enzyme replacement therapy.

PubMed

Messalli, G; Imbriaco, M; Avitabile, G; Russo, R; Iodice, D; Spinelli, L; Dellegrottaglie, S; Cademartiri, F; Salvatore, M; Pisani, A

2012-02-01

Anderson-Fabry disease is a multisystemic disorder of lipid metabolism secondary to X-chromosome alterations and is frequently associated with cardiac manifestations such as left ventricular (LV) hypertrophy, gradually leading to an alteration in cardiac performance. The purpose of this study was to monitor, using magnetic resonance imaging (MRI), any changes produced by enzyme replacement therapy with agalsidase beta at the cardiac level in patients with Anderson-Fabry disease. Sixteen (ten men, six women) patients with genetically confirmed Anderson-Fabry disease underwent cardiac MRI before starting enzyme replacement therapy (baseline study) and after 48 months of treatment with agalsidase beta at the dose of 1 mg/kg (follow-up study). After 48 months of treatment, a significant reduction in LV mass and wall thickness was observed: 187±59 g vs. 149±44 g, and 16±3 mm vs. 13±3 mm, respectively. A significant reduction in T2 relaxation time was noted at the level of the interventricular septum (81±3 ms vs. 67±7 ms), at the apical level (80±8 ms vs. 63±6 ms) and at the level of the lateral wall (82±8 ms vs. 63±10 ms) (p<0.05). No significant variation was observed in ejection fraction between the two studies (65±3% vs. 64±2%; p>0.05) (mean bias 1.0); however, an improvement was noted in the New York Heart Association (NYHA) class of the majority of patients (12/16) (p<0.05). In patients with Anderson-Fabry disease undergoing enzyme replacement therapy with agalsidase beta, MRI documented a significant reduction in myocardial T2 relaxation time, a significant decrease in maximal myocardial thickness and in total LV mass. MRI did not reveal significant improvements in LV global systolic function; however, improvement in NYHA functional class was noted, consistent with improved diastolic function.

Regional analgesia for improvement of long-term functional outcome after elective large joint replacement.

PubMed

Atchabahian, Arthur; Schwartz, Gary; Hall, Charles B; Lajam, Claudette M; Andreae, Michael H

2015-08-13

Regional analgesia is more effective than conventional analgesia for controlling pain and may facilitate rehabilitation after large joint replacement in the short term. It remains unclear if regional anaesthesia improves functional outcomes after joint replacement beyond three months after surgery. To assess the effects of regional anaesthesia and analgesia on long-term functional outcomes 3, 6 and 12 months after elective major joint (knee, shoulder and hip) replacement surgery. We performed an electronic search of several databases (CENTRAL, MEDLINE, EMBASE, CINAHL), and handsearched reference lists and conference abstracts. We updated our search in June 2015. We included randomized controlled trials (RCTs) comparing regional analgesia versus conventional analgesia in patients undergoing total shoulder, hip or knee replacement. We included studies that reported a functional outcome with a follow-up of at least three months after surgery. We used standard methodological procedures expected by Cochrane. We contacted study authors for additional information. We included six studies with 350 participants followed for at least three months. All of these studies enrolled participants undergoing total knee replacement. Studies were at least partially blinded. Three studies had a high risk of performance bias and one a high risk of attrition bias, but the risk of bias was otherwise unclear or low.Only one study assessed joint function using a global score. Due to heterogeneity in outcome and reporting, we could only pool three out of six RCTs, with range of motion assessed at three months after surgery used as a surrogate for joint function. All studies had a high risk of detection bias. Using the random-effects model, there was no statistically significant difference between the experimental and control groups (mean difference 3.99 degrees, 95% confidence interval (CI) - 2.23 to 10.21; P value = 0.21, 3 studies, 140 participants, very low quality evidence).We did not

Regional analgesia for improvement of long-term functional outcome after elective large joint replacement

PubMed Central

Atchabahian, Arthur; Schwartz, Gary; Hall, Charles B; Lajam, Claudette M; Andreae, Michael H

2015-01-01

Background Regional analgesia is more effective than conventional analgesia for controlling pain and may facilitate rehabilitation after large joint replacement in the short term. It remains unclear if regional anaesthesia improves functional outcomes after joint replacement beyond three months after surgery. Objectives To assess the effects of regional anaesthesia and analgesia on long-term functional outcomes 3, 6 and 12 months after elective major joint (knee, shoulder and hip) replacement surgery. Search methods We performed an electronic search of several databases (CENTRAL, MEDLINE, EMBASE, CINAHL), and handsearched reference lists and conference abstracts. We updated our search in June 2015. Selection criteria We included randomized controlled trials (RCTs) comparing regional analgesia versus conventional analgesia in patients undergoing total shoulder, hip or knee replacement. We included studies that reported a functional outcome with a follow-up of at least three months after surgery. Data collection and analysis We used standard methodological procedures expected by Cochrane. We contacted study authors for additional information. Main results We included six studies with 350 participants followed for at least three months. All of these studies enrolled participants undergoing total knee replacement. Studies were at least partially blinded. Three studies had a high risk of performance bias and one a high risk of attrition bias, but the risk of bias was otherwise unclear or low. Only one study assessed joint function using a global score. Due to heterogeneity in outcome and reporting, we could only pool three out of six RCTs, with range of motion assessed at three months after surgery used as a surrogate for joint function. All studies had a high risk of detection bias. Using the random-effects model, there was no statistically significant difference between the experimental and control groups (mean difference 3.99 degrees, 95% confidence interval (CI) �

Enzyme replacement and substrate reduction therapy for Gaucher disease.

PubMed

Shemesh, Elad; Deroma, Laura; Bembi, Bruno; Deegan, Patrick; Hollak, Carla; Weinreb, Neal J; Cox, Timothy M

2015-03-27

adverse events were reported, nearly all deemed unrelated to treatment.There are, as yet, no randomized trials of substrate reduction therapy in treatment-naïve patients that can be evaluated. Miglustat monotherapy appeared as effective as continued enzyme replacement therapy for maintenance of hematological, organ and biomarker responses in people with type 1 Gaucher disease previously treated with imiglucerase for at least two years. In those with neuronopathic Gaucher disease, no significant improvements in haemoglobin concentration, platelet count or organ volumes occurred when enzyme replacement therapy was augmented with miglustat.One randomized controlled study assessing substrate reduction therapy was published immediately prior to producing the final version of this review, and this, along with a further ongoing study (expected to be published in the near future), will be assessed for eligibility in a future update of the review. The results reflect the limitations of analysing evidence restricted to prospective randomized controlled trials, especially when dealing with chronic rare diseases. This analysis suggests that, during the first year of treatment, different recombinant glucocerebrosidases are bio-similar and non-inferior in safety and efficacy for surrogate biological response parameters. Enzyme replacement therapy given at 30 to 45 units/kg body weight every two to four weeks was generally as effective as the 60 unit/kg dose for the assessed clinical outcomes. The analysis emphasise the need to determine whether it is realistic to carry out multi-decade prospective clinical trials for rare diseases such as type 1 Gaucher disease. With large treatment effects on the classical manifestations of the disorder, therapeutic investigations in Gaucher disease mandate innovative trial designs and methodology to secure decisive data concerning long-term efficacy and safety - with the realization that knowledge about disease-modifying actions that are sustained

Enzyme replacement therapy of Fabry disease.

PubMed

Clarke, Joe T R; Iwanochko, R Mark

2005-08-01

Fabry disease is an X-linked lysosomal storage disease caused by deficiency of the enzyme alpha-galactosidase A and results in pain, progressive renal impairment, cardiomyopathy, and cerebrovascular disease. The results of two major randomized, double-blind, placebo-controlled clinical trials and open-label extensions have shown that replacement of the deficient enzyme with either of two preparations of recombinant human alpha-galactosidase A, agalsidase-alfa, and agalsidase-beta is safe. Biweekly i.v. infusions of 0.2 mg/kg of agalsidase-alfa were associated with a significant decrease in pain and stabilization of renal function. Biweekly infusions of 1 mg/kg of agalsidase-beta were associated with virtually complete clearing of accumulated glycolipid substrate from renal and cutaneous capillary endothelial cells. Several smaller, open-label studies, along with observations made in the course of monitoring large numbers of patients on enzyme replacement therapy, indicated that treatment stabilizes renal function and produces significant improvements in myocardial mass and function. Treatment of Fabry disease by enzyme replacement has a significant impact on at least some serious complications of the disease.

Enzyme replacement therapy for Anderson-Fabry disease.

PubMed

El Dib, Regina; Gomaa, Huda; Carvalho, Raíssa Pierri; Camargo, Samira E; Bazan, Rodrigo; Barretti, Pasqual; Barreto, Fellype C

2016-07-25

the optimal dose or frequency of enzyme replacement therapy. With regards to safety, adverse events (i.e., rigors, fever) were more significant in the agalsidase beta as compared to placebo. The long-term influence of enzyme replacement therapy on risk of morbidity and mortality related to Anderson-Fabry disease remains to be established. This review highlights the need for continued research into the use of enzyme replacement therapy for Anderson-Fabry disease.

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

PubMed

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

2016-02-01

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.

Long-term Expectations of Vagus Nerve Stimulation: A Look at Battery Replacement and Revision Surgery.

PubMed

Couch, Jonathan D; Gilman, Arthur M; Doyle, Werner K

2016-01-01

Vagus nerve stimulation (VNS) is an established surgical treatment for medically intractable epilepsy with more than 75 000 devices implanted worldwide. While there are many reports documenting efficacy, complications, and clinical use, there are very few reports concerning VNS battery replacement and revision surgeries. To review our experience with VNS battery replacement and revision surgery. We retrospectively reviewed 1144 consecutive VNS procedures performed by a single surgeon between 1998 and 2012. Six hundred forty-four of those procedures were the initial placement of the VNS device. These patients were then followed to determine when a battery change occurred and what type of revision or removal was necessary. In the study, 46% of patients required at least 1 or more type of battery replacement or revision surgery. The most common types of surgery were for generator battery depletion (27%), poor efficacy (9%), and lead malfunction (8%). Only 2% of patients were noted to have an infection. VNS battery replacement, revisions, and removals account for almost one-half of all VNS procedures. Our findings suggest important long-term expectations for VNS including expected complications, battery life, and other surgical issues. Review of the literature suggests that this is the first large review of VNS revisions by a single center. Our findings are important to better characterize long-term surgical expectations of VNS therapy. A significant portion of patients undergoing VNS therapy will eventually require revision.

Enzyme replacement therapy in Fabry disease: influence on cardiac manifestations.

PubMed

Caballero, L; Climent, V; Hernández-Romero, D; Quintanilla, M A; de la Morena, G; Marín, F

2010-01-01

Fabry disease (FD) is an X-linked glycosphingolipid storage disorder caused by deficient activity of the lysosomal enzyme alpha-galactosidase A. This leads to a progressive accumulation of globotriaosylceramide (Gb3) in the lysosomes of different cells and tissues, causing principally ventricular hypertrophy, renal failure and cerebrovascular accidents, reducing lifespan both in hemizygous males and heterozygous females. Residual enzyme activity might lead to slow progression of the disease and result in the so-called cardiac or renal variants with delayed presentation. Two different forms of alpha-galactosidase A enzyme replacement therapies (ERT) are available for the treatment of FD, one genetically engineered in human cell line (agalsidase alfa, Replagal, Shire) and the other produced in a Chinese hamster ovary cell line (agalsidase beta, Fabrazyme, Genzyme). Although both proteins are structurally and functionally very similar, with the same amino acid sequence as the native human enzyme, they differ in the pattern of glycosilation of the protein depending on the originating cell line. Studies with both preparations have described a reduction in plasma, urinary sediment and tissue levels of Gb3, a decrease in the frequency of pain crisis and a reduction in left ventricular mass and improvement or stabilization of renal function. Studies have generally shown the greatest benefit when treatment is started at an early stage of the disease before extensive fibrosis or other irreversible tissue damage takes place. However, more data are needed to document long-term treatment outcomes. The aim of the present review is to provide an update overview of the two different forms of ERT for FD, their clinical effects in cardiac manifestations and their possible differences in terms of efficacy, side effects and safety profiles.

Long-Term Behavior of Simulated Partial Lead Service Line Replacements

PubMed Central

St. Clair, Justin; Cartier, Clement; Triantafyllidou, Simoni; Clark, Brandi; Edwards, Marc

2016-01-01

Abstract In this 48-month pilot study, long-term impacts of copper:lead galvanic connections on lead release to water were assessed without confounding differences in pipe exposure prehistory or disturbances arising from cutting lead pipe. Lead release was tracked from three lead service line configurations, including (1) 100% lead, (2) traditional partial replacement with 50% copper upstream of 50% lead, and (3) 50% lead upstream of 50% copper as a function of flow rate, connection types, and sampling methodologies. Elevated lead from galvanic corrosion worsened with time, with 140% more lead release from configurations representing traditional partial replacement configurations at 14 months compared to earlier data in the first 8 months. Even when sampled consistently at moderate flow rate (8 LPM) and collecting all water passing through service lines, conditions representing traditional partial service line configurations were significantly worse (≈40%) when compared to 100% lead pipe. If sampled at a high flow rate (32 LPM) and collecting 2 L samples from service lines, 100% of samples collected from traditional partial replacement configurations exceeded thresholds posing an acute health risk versus a 0% risk for samples from 100% lead pipe. Temporary removal of lead accumulations near Pb:Cu junctions and lead deposits from other downstream plastic pipes reduced risk of partial replacements relative to that observed for 100% lead. When typical brass compression couplings were used to connect prepassivated lead pipes, lead release spiked up to 10 times higher, confirming prior concerns raised at bench and field scale regarding adverse impacts of crevices and service line disturbances on lead release. To quantify semirandom particulate lead release from service lines in future research, whole-house filters have many advantages compared to other approaches. PMID:26989344

Enzyme Replacement for Craniofacial Skeletal Defects and Craniosynostosis in Murine Hypophosphatasia

PubMed Central

Liu, Jin; Campbell, Cassie; Nam, Hwa Kyung; Caron, Alexandre; Yadav, Manisha C; Millán, José Luis; Hatch, Nan E.

2015-01-01

Hypophosphatasia (HPP) is an inborn-error-of-metabolism disorder characterized by deficient bone and tooth mineralization due to loss-of function mutations in the gene (Alpl) encoding tissue-nonspecific alkaline phosphatase (TNAP). Alpl−/− mice exhibit many characteristics seen in infantile HPP including long bone and tooth defects, vitamin B6 responsive seizures and craniosynostosis. Previous reports demonstrated that a mineral-targeted form of TNAP rescues long bone, verterbral and tooth mineralization defects in Alpl−/− mice. Here we report that enzyme replacement with mineral-targeted TNAP (asfotase-alfa) also prevents craniosynostosis (the premature fusion of cranial bones) and additional craniofacial skeletal abnormalities in Alpl−/− mice. Craniosynostosis, cranial bone volume and density, and craniofacial shape abnormalities were assessed by microsocopy, histology, digital caliper measurements and micro CT. We found that craniofacial shape defects, cranial bone mineralization and craniosynostosis were corrected in Alpl−/− mice injected daily subcutaneously starting at birth with recombinant enzyme. Analysis of Alpl−/− calvarial cells indicates that TNAP deficiency leads to aberrant osteoblastic gene expression and diminished proliferation. Some but not all of these cellular abnormalities were rescued by treatment with inorganic phosphate. These results confirm an essential role for TNAP in craniofacial skeletal development and demonstrate the efficacy of early postnatal mineral-targeted enzyme replacement for preventing craniofacial abnormalities including craniosynostosis in murine infantile HPP. PMID:25959417

[Effects of long-term fertilization on enzyme activities in black soil of Northeast China].

PubMed

Wang, Shu-Qi; Han, Xiao-Zeng; Qiao, Yun-Fa; Wang, Shou-Yu

2008-03-01

In this paper, black soil samples at the depths of 0-20 cm and 20-40 cm were collected from the Hailun Agricultural Ecology Station of Chinese Academy of Sciences to study the effects of long-term fertilization on their urease, invertase, phosphatase and catalase activities and total C and N contents. The results showed that long-term application of chemical fertilizers and organic manure increased the activities of urease, invertase and phosphatase in 0-20 cm and 20-40 cm soil layers in different degree, and the combined application of them increased the activities of the three enzymes significantly, with an increment of 43.6%-113.2%, 25.9%-79.5% and 14.7%-134.4% in 0-20 cm soil layer and 56.1%-127.2%, 14.5%-113.8% and 16.2%-207.2% in 20-40 cm soil layer, respectively. However, long-term application of chemical fertilizers without organic manure had little effects on catalase activity. The activities of urease, invertase and phosphatase decreased with increasing soil depth. Long-term application of N fertilizer increased urease activity, and P fertilization had obvious positive effect on phosphatase activity. Long-term fertilization also had obvious effects on the soil total C and N contents and C/N ratio.

Enzyme replacement therapy for murine hypophosphatasia.

PubMed

Millán, José Luis; Narisawa, Sonoko; Lemire, Isabelle; Loisel, Thomas P; Boileau, Guy; Leonard, Pierre; Gramatikova, Svetlana; Terkeltaub, Robert; Camacho, Nancy Pleshko; McKee, Marc D; Crine, Philippe; Whyte, Michael P

2008-06-01

Hypophosphatasia (HPP) is the inborn error of metabolism that features rickets or osteomalacia caused by loss-of-function mutation(s) within the gene that encodes the tissue-nonspecific isozyme of alkaline phosphatase (TNALP). Consequently, natural substrates for this ectoenzyme accumulate extracellulary including inorganic pyrophosphate (PPi), an inhibitor of mineralization, and pyridoxal 5'-phosphate (PLP), a co-factor form of vitamin B6. Babies with the infantile form of HPP often die with severe rickets and sometimes hypercalcemia and vitamin B6-dependent seizures. There is no established medical treatment. Human TNALP was bioengineered with the C terminus extended by the Fc region of human IgG for one-step purification and a deca-aspartate sequence (D10) for targeting to mineralizing tissue (sALP-FcD10). TNALP-null mice (Akp2-/-), an excellent model for infantile HPP, were treated from birth using sALP-FcD10. Short-term and long-term efficacy studies consisted of once daily subcutaneous injections of 1, 2, or 8.2 mg/kg sALP-FcD10 for 15, 19, and 15 or 52 days, respectively. We assessed survival and growth rates, circulating levels of sALP-FcD10 activity, calcium, PPi, and pyridoxal, as well as skeletal and dental manifestations using radiography, microCT, and histomorphometry. Akp2-/- mice receiving high-dose sALP-FcD10 grew normally and appeared well without skeletal or dental disease or epilepsy. Plasma calcium, PPi, and pyridoxal concentrations remained in their normal ranges. We found no evidence of significant skeletal or dental disease. Enzyme replacement using a bone-targeted, recombinant form of human TNALP prevents infantile HPP in Akp2-/- mice.

A biochemical and physicochemical comparison of two recombinant enzymes used for enzyme replacement therapies of hunter syndrome.

PubMed

Chung, Yo Kyung; Sohn, Young Bae; Sohn, Jong Mun; Lee, Jieun; Chang, Mi Sun; Kwun, Younghee; Kim, Chi Hwa; Lee, Jin Young; Yook, Yeon Joo; Ko, Ah-Ra; Jin, Dong-Kyu

2014-05-01

Mucopolysaccharidosis II (MPS II, Hunter syndrome; OMIM 309900) is an X-linked lysosomal storage disease caused by a deficiency in the enzyme iduronate-2-sulfatase (IDS), leading to accumulation of glycosaminoglycans (GAGs). For enzyme replacement therapy (ERT) of Hunter syndrome, two recombinant enzymes, idursulfase (Elaprase(®), Shire Human Genetic Therapies, Lexington, MA) and idursulfase beta (Hunterase(®), Green Cross Corporation, Yongin, Korea), are currently available in Korea. To compare the biochemical and physicochemical differences between idursulfase and idursulfase beta, we examined the formylglycine (FGly) content, specific enzyme activity, mannose-6-phosphate (M6P) content, sialic acid content, and in vitro cell uptake activity of normal human fibroblasts of these two enzymes.The FGly content, which determines the enzyme activity, of idursulfase beta was significantly higher than that of idursulfase (79.4 ± 0.9 vs. 68.1 ± 2.2 %, P < 0.001). In accordance with the FGly content, the specific enzyme activity of idursulfase beta was significantly higher than that of idursulfase (42.6 ± 1.1 vs. 27.8 ± 0.9 nmol/min/μg protein, P < 0.001). The levels of M6P and sialic acid were not significantly different (2.4 ± 0.1 vs 2.4 ± 0.3 mol/mol protein for M6P and 12.3 ± 0.7 vs. 12.4 ± 0.4 mol/mol protein for sialic acid). However, the cellular uptake activity of the normal human fibroblasts in vitro showed a significant difference (Kuptake, 5.09 ± 0.96 vs. 6.50 ± 1.28 nM protein, P = 0.017).In conclusion, idursulfase beta exhibited significantly higher specific enzyme activity than idursulfase, resulting from higher FGly content. These biochemical differences may be partly attributed to clinical efficacy. However, long-term clinical evaluations of Hunter syndrome patients treated with these two enzymes will be needed to demonstrate the clinical implications of significant difference of the enzyme activity and the FGly content.

Manipulation under anaesthesia post total knee replacement: long term follow up.

PubMed

Yeoh, David; Nicolaou, Nick; Goddard, Richard; Willmott, Henry; Miles, Kim; East, Debra; Hinves, Barry; Shepperd, John; Butler-Manuel, Adrian

2012-08-01

A reduced range of motion post total knee replacement (TKR) is a recognised problem. Manipulation under anaesthesia (MUA) is commonly performed in the stiff post-operative TKR. Long-term results are variable in the literature. We retrospectively reviewed, prospectively collected data on 48 patients followed up since 1996 from one centre, over an average of 7.5 years, (range 1 to 10 years) and report on the long-term results. During the study period 2.3% of TKRs underwent MUA. The mean time to MUA post TKR was 12.3 weeks (range 3 to 48). Pre MUA, the mean flexion was 53°. The mean immediate passive flexion post MUA was 97°, an improvement of 44° (Range 10° to 90°, p<0.05). By 1year, the mean flexion was 87°, an improvement of 34°, (range -15° to 70°, p<0.05). At 10 years the mean flexion was 86°, (range 55° to 100°, p<0.05). We found no difference in the gain in range of motion (ROM) between knees manipulated before or after 12 weeks. Additionally, the gain was no different in stiff knees with a pre TKR ROM <90°, compared to a pre TKR ROM >90°. There were no complications as a result of MUA. However, one patient was eventually revised at 2 years secondary to low grade infection. Our findings show that MUA is a safe and effective method at improving the ROM in a stiff post-operative TKR. The improvement is maintained in the long term irrespective of time to MUA and range of motion pre TKR. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

Clinical response to long term enzyme replacement treatment in children, adolescent and adult patients with Hunter syndrome.

PubMed

Dalmau Serra, Jaime; Vitoria Miñana, Isidro; Calderón Fernández, Rafael; Cortell Aznar, Isidoro

2015-11-06

Since enzyme replacement treatment (ERT) with idursulfase is available for Hunter syndrome (HS; mucopolysaccharidosis type II), for the first time, disease progression can be limited and organ damage reduced or prevented. We described retrospectively the clinical evolution of eight HS males, treated with ERT and followed in routine clinical practice in Hospital Infantil La Fe (Valencia, Spain). We studied three children, three adolescents and two adults. Time from diagnosis to ERT ranged from 13.7 to 0.2 years, and duration of ERT ranged from 24 to 77.1 months. From the start of ERT, weight and height increased in children and adolescents and remained stable in adults. Glycosaminoglycans (GAG) decreased in all patients; in patient 5 (aged 23 years), we observed the highest reduction (86%) with recovery of carpal tunnel syndrome, splenomegaly and a decrease in nocturnal oxygen dependence. Our results show that ERT improve respiratory impairment and organomegalies and decrease GAGs levels in all patients including children, adolescent and adults. While cardiac manifestations and facial features stabilized, responses in other parameters were heterogeneous. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Long-term outcome in dogs undergoing mitral valve repair with suture annuloplasty and chordae tendinae replacement.

PubMed

Mizuno, T; Mizukoshi, T; Uechi, M

2013-02-01

Mitral valve repair under cardiopulmonary bypass was performed in three dogs with clinical signs associated with mitral regurgitation that were not controlled by medication. Mitral valve repair comprised circumferential annuloplasty and chordal replacement with expanded polytetrafluoroethylene. One dog died 2 years after surgery because of severe mitral regurgitation resulting from partial circumferential suture detachment. The others survived for over 5 years, but mild mitral valve stenosis persisted in one. The replaced chordae did not rupture in any dog. Mitral valve repair appears to be an effective treatment for mitral regurgitation in dogs. Chordal replacement with expanded polytetrafluoroethylene is a feasible technique, demonstrating long-term durability in dogs. However, mitral annuloplasty techniques need improvement. © 2012 British Small Animal Veterinary Association.

Long-term results after aortic valve replacement with the Biocor PSB stentless xenograft in the elderly.

PubMed

Luciani, G B; Santini, F; Auriemma, S; Barozzi, L; Bertolini, P; Mazzucco, A

2001-05-01

This study seeks to define the long-term results after Biocor PSB stentless aortic valve replacement (AVR) in elderly patients, including the effects of No-React treatment. We reviewed the outcomes of 106 consecutive patients, aged 70+/-6 years, having Biocor PSB (93 standard, 13 No-React) AVR between October 1992 and October 1996. There were three early deaths (3%) and 15 late deaths (15%), during a mean follow-up of 5.8+/-1.6 years. At 8 years, survival was 82%+/-4% and freedom from cardiac death was 94%+/-3%. Freedom from valve failure was 92%+/-4% at 8 years (No-React: 92%+/-8% at 4 years). Replacement of the xenograft was required in 5 patients. Freedom from reoperation was 91%+/-4% at 8 years (No-React: 92%+/-8% at 4 years). Four bleeding and two embolic events were recorded: overall valve-related event-free survival was 81%+/-7% at 8 years (No-React: 76%+/-12% at 4 years). Age of long-term survivors averaged 77+/-5 years and their New York Heart Association status was 1.3+/-0.6 (versus 2.9+/-0.6 preoperatively, p = 0.01). Satisfactory freedom from cardiac events and from valve deterioration added to uniform improvement in functional status despite advanced age and high prevalence of comorbid conditions make AVR with the Biocor PSB xenograft a valid long-term therapy for the elderly. No-React treatment does not influence xenograft durability.

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

PubMed

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

2015-01-01

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.

Enzyme replacement therapy in classical infantile pompe disease: results of a ten-month follow-up study.

PubMed

Klinge, L; Straub, V; Neudorf, U; Voit, T

2005-02-01

Infantile Pompe disease (IPD) is a fatal, autosomal recessive muscle-wasting disorder. Due to a deficiency of the lysosomal enzyme acid alpha-glucosidase patients develop a generalized myopathy, diaphragmatic weakness, and cardiomyopathy leading to death usually within the first year of life. So far there is no therapy available. We report on the safety and efficacy of transgenically derived recombinant human precursor acid alpha-glucosidase (rhGAA) in a 10-month follow-up study in two children with IPD who previously completed a 48-week course of enzyme replacement therapy (ERT) with the same medication at the same dose in a phase II clinical trial. Under this therapy cardiac status and muscle strength had improved, leading to survival beyond the age of one year. These results, together with data from two other phase II clinical trials encouraged further evaluation of the long-term safety and efficacy of enzyme replacement therapy in patients with infantile-onset Pompe disease. During the 10-month follow-up period, ERT was well-tolerated and neither patient experienced a single infusion-associated reaction. The initial improvements in cardiac size and function, as measured by left ventricular mass index and the fractional shortening, were maintained in both patients, and a continued improvement of motor function, as measured by the Alberta infant motor scale, was observed.

Enzyme Replacement Therapy for Murine Hypophosphatasia*

PubMed Central

Millán, José Luis; Narisawa, Sonoko; Lemire, Isabelle; Loisel, Thomas P; Boileau, Guy; Leonard, Pierre; Gramatikova, Svetlana; Terkeltaub, Robert; Camacho, Nancy Pleshko; McKee, Marc D; Crine, Philippe; Whyte, Michael P

2008-01-01

Introduction Hypophosphatasia (HPP) is the inborn error of metabolism that features rickets or osteomalacia caused by loss-of-function mutation(s) within the gene that encodes the tissue-nonspecific isozyme of alkaline phosphatase (TNALP). Consequently, natural substrates for this ectoenzyme accumulate extracellulary including inorganic pyrophosphate (PPi), an inhibitor of mineralization, and pyridoxal 5`-phosphate (PLP), a co-factor form of vitamin B6. Babies with the infantile form of HPP often die with severe rickets and sometimes hypercalcemia and vitamin B6-dependent seizures. There is no established medical treatment. Materials and Methods Human TNALP was bioengineered with the C terminus extended by the Fc region of human IgG for one-step purification and a deca-aspartate sequence (D10) for targeting to mineralizing tissue (sALP-FcD10). TNALP-null mice (Akp2−/−), an excellent model for infantile HPP, were treated from birth using sALP-FcD10. Short-term and long-term efficacy studies consisted of once daily subcutaneous injections of 1, 2, or 8.2 mg/kg sALP-FcD10 for 15, 19, and 15 or 52 days, respectively. We assessed survival and growth rates, circulating levels of sALP-FcD10 activity, calcium, PPi, and pyridoxal, as well as skeletal and dental manifestations using radiography, μCT, and histomorphometry. Results Akp2−/− mice receiving high-dose sALP-FcD10 grew normally and appeared well without skeletal or dental disease or epilepsy. Plasma calcium, PPi, and pyridoxal concentrations remained in their normal ranges. We found no evidence of significant skeletal or dental disease. Conclusions Enzyme replacement using a bone-targeted, recombinant form of human TNALP prevents infantile HPP in Akp2−/− mice. PMID:18086009

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

PubMed

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

2015-12-01

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.

Long-term follow-up of the experimental replacement of the esophagus with a collagen-silicone composite tube.

PubMed

Takimoto, Y; Okumura, N; Nakamura, T; Natsume, T; Shimizu, Y

1993-01-01

This study investigated ways of preventing late stenosis after replacing the esophagus with a prosthetic device and increasing survival time in an animal model. In a previous study, the authors induced neoesophageal formation and re-epithelialization at an early stage, although stenosis in the chronic stage remained a problem, and long-term survival was prevented. The authors developed an artificial esophagus made from a collagen-silicone composite tube. The silicone tube (25 mm in diameter, 50 mm long, and 1 mm thick) was covered with collagen sponge (5 mm thick). The collagen sponge was intended to be replaced by host tissue, leading to neoesophageal regeneration. The authors thought stenosis was caused primarily by poor regeneration of submucosal tissue, rather than reepithelialization. Thus, they examined the grade of stenosis relative to the time the stent became dislodged. They concluded that the occurrence of stenosis after anastomosis depends upon the duration of stenting and that stenosis did not develop when the portion replaced by the artificial esophagus was stented for at least 4 weeks.

Enzyme replacement therapy in patients with Fabry disease: state of the art and review of the literature.

PubMed

Pisani, Antonio; Visciano, Bianca; Roux, Graciana Diez; Sabbatini, Massimo; Porto, Caterina; Parenti, Giancarlo; Imbriaco, Massimo

2012-11-01

Anderson-Fabry disease is an X-linked lysosomal storage disorder resulting from the deficiency of the hydrolytic enzyme alpha galactosidase A, with consequent accumulation of globotrioasoyl ceramide in cells and tissues of the body, resulting in a multi-system pathology including end organ failure. In the classical phenotype, cardiac failure, renal failure and stroke result in a reduced median life expectancy. The current causal treatment for Fabry disease is the enzyme replacement therapy (ERT): two different products, Replagal (agalsidase alfa) and Fabrazyme (agalsidase beta), have been commercially available in Europe for almost 10 years and they are both indicated for long-term treatment. In fact, clinical trials, observational studies and registry data have provided many evidences for safety and efficacy of ERT in improving symptoms of pain, gastrointestinal disturbances, hypohidrosis, left ventricular mass index, glomerular filtration rate and quality of life. Few data are available on comparison of the two treatments and on the clinical course of the disease. This article reviews the published evidence for clinical efficacy of the two available enzyme preparations. Copyright © 2012 Elsevier Inc. All rights reserved.

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

ERIC Educational Resources Information Center

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

2013-01-01

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…

Diagnosis, Treatment and Long-Term Follow Up of Patients with ADA Deficiency: a Single-Center Experience.

PubMed

Baffelli, Renata; Notarangelo, Lucia D; Imberti, Luisa; Hershfield, Michael S; Serana, Federico; Santisteban, Ines; Bolda, Federica; Porta, Fulvio; Lanfranchi, Arnalda

2015-10-01

We carried out a retrospective analysis of 27 patients with Adenosine Deaminase (ADA) deficiency diagnosed in a single center from 1997 to the 2013, for evaluating whether data regarding types of disease-inducing mutations, biochemical and immunological features as well as clinical outcomes of patients treated with enzyme replacement or transplantation, were comparable to those obtained in multicenter studies. The ADA deficiency diagnosis was performed with biochemical, immunological and molecular techniques. Ten patients treated with hematopoietic stem cell transplantation and three in treatment with enzyme replacement were followed up in our center. Twenty-four different mutations were identified and five were not previously reported. Identical mutations were found among patients from the same Romani ethnic group or from the same geographical region. A more rapid recovery was observed in enzyme replacement treated patients in comparison with those transplanted that, however, showed a continuous and long-lasting improvement both in terms of immune and metabolic recovery. The data obtained in our single center are comparable with those that have been reported in multicenter surveys.

Replacement of the ureter by an ileal loop. Quantitative aspects of long-term morphological alterations in minipigs.

PubMed

Pabst, R; Kamran, D

1983-06-01

In minipigs 1 ureter was replaced by a loop of the terminal ileum and the contralateral kidney removed. After 2.5 to 3 years the morphology of the replaced ureter was compared with the normal ileum. Independent of the 3 different operative techniques used, in about half of the pigs there was loss or flattening of the villi. In the other pigs the morphometrically determined number of intraepithelial lymphocytes, the cell density in the lamina propria and the length of the villi did not differ significantly compared with the normal ileum. There was no increase in goblet cells in the crypts. The transitional epithelium covered only a short distance at the anastomotic junctions. Peyer's patches of normal age-related size were found in the replaced ureter. Despite the long-term contact with urine instead of gut contents, in many pigs a normal amount of lymphocytes remained in the "ileal ureter".

Long-term treatment patterns of testosterone replacement medications.

PubMed

Donatucci, Craig; Cui, Zhanglin; Fang, Yun; Muram, David

2014-08-01

Testosterone replacement therapy (TRT) is prescribed to men diagnosed with hypogonadism to alleviate symptoms, improve quality of life, and improve overall health. However, most men use TRT for only a short duration. To evaluate the long-term treatment patterns in hypogonadal men using topical TRT or short-lasting TRT injections. Using the Truven MarketScan(®) Database, 15,435 men who received their first (index) topical TRT prescription and 517 men who received their short-lasting TRT injection index prescription in 2009 were followed from 12 to 30 months after treatment initiation. Treatment interruption was defined as a medication gap of >30 days. Patients who remained off treatment were classified as having discontinued treatment. Patients who restarted therapy after 30 days were classified as cyclic users. Patients were required to have continuous insurance coverage during 1 year prior to treatment initiation and at least 1 year afterward. Main outcome measures were length of therapy, discontinuation, and restarts of topical TRT or short-lasting TRT injections. The patient characteristics were similar for patients who received topical TRT or short-lasting TRT injections. Of the patients who discontinued therapy during the follow-up period, the percentages of patients who were still on therapy after 3 months were 52% and 31% for topical TRT and short-lasting TRT users, respectively. For cyclic users, there was an attrition rate of approximately 40% to 50% of patients in each cycle. For both topical TRT and short-lasting TRT injections, the gap between stopping and restarting therapy tended to decrease over time. In this analysis, high discontinuation rates were observed. The treatment pattern of TRT may be related to the disease state rather than dosing, daily use, or mode of administration. © 2014 International Society for Sexual Medicine.

78 FR 36449 - State Long-Term Care Ombudsman Program

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-18

... 0985-AA08 State Long-Term Care Ombudsman Program AGENCY: Administration on Aging, Administration for... Act, the State Long-Term Care Ombudsman program. This proposed rule replaces AoA's 1994 Notice of... highlighted the difficulty of determining State compliance in carrying out the Long-Term Care Ombudsman...

Enzyme replacement therapy on hypophosphatasia mouse model

PubMed Central

Montaño, Adriana M.; Shimada, Tsutomu; Sly, William S.

2013-01-01

Hypophosphatasia (HPP) is an inborn error of metabolism caused by deficiency of the tissue-nonspecific alkaline phosphatase (TNSALP), resulting in a defect of bone mineralization. Natural substrates for this ectoenzyme accumulate extracellulary including inorganic pyrophosphate (PPi), an inhibitor of mineralization, and pyridoxal 5-phosphate (PLP), a co-factor form of vitamin B6. Enzyme replacement therapy (ERT) for HPP by functional TNSALP is one of the therapeutic options. The C-terminal-anchorless human recombinant TNSALP derived from Chinese hamster ovary cell lines was purified. TNSALP-null mice (Akp2−/−), an infantile model of HPP, were treated from birth using TNSALP and vitamin B6 diet. Long-term efficacy studies of ERT consisted of every 3 days subcutaneous or intravenous injections till 28 days old (dose 20 U/g) and subsequently every 3 days intravenous injections for 6 months (dose 10 U/g). We assessed therapeutic effect by growth and survival rates, fertility, skeletal manifestations, and radiographic and pathological finding. Treated Akp2−/− mice grew normally till 4 weeks and appeared well with a minimum skeletal abnormality as well as absence of epilepsy, compared with untreated mice which died by 3 weeks old. The prognosis of TNSALP-treated Akp2−/− mice was improved substantially: 1) prolonged life span over 6 months, 2) improvement of the growth, and 3) normal fertility. After 6 months of treatment, we found moderate hypomineralization with abnormal proliferative chondrocytes in growth plate and articular cartilage. In conclusion, ERT with human native TNSALP improves substantial clinical manifestations in Akp2−/− mice, suggesting that ERT with anchorless TNSALP is also a potential therapy for HPP. PMID:23978959

Medium- to Long-Term Results of the Nexgen Legacy Posterior Stabilized Fixed-Bearing Knee Replacement.

PubMed

Arikupurathu, Oommen Mathew; Johnston, Linda; MacInnes, Alasdair; Nicol, Graeme; Nassif, Manhal

2018-06-20

The NexGen legacy posterior stabilized (LPS) prosthesis was introduced in 1997 after many design changes to its predecessor, the Insall-Burstein II prosthesis. However, there have been no reported long-term studies on the performance of this implant. Prospectively, collected data from a local database comprising primary total knee replacements (TKRs) with LPS between 1997 and 2002 was analyzed. All implants were fixed with cement. Patients were followed up at 1, 3, 5, 7, and 10 years, with patient satisfaction, range of movement, and Knee Society score (KSS) assessed. A total of 621 primary TKRs were analyzed with an average follow-up of 11.25 years (9.15-14.55). The mean age was 69.53 years. The mean KSS was 88.97 and mean flexion increased from 88.3 to 103.5 degrees at 10 years. Kaplan-Meier's analysis revealed a survivorship of 96.5% with revision for any reason as the end point and 98.9% if aseptic loosening was the reason for revision at 14 years. This study revealed excellent mid- to long-term results with the NexGen LPS prosthesis. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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

PubMed Central

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

2014-01-01

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 250 units/g body weight was administered intravenously in MPS IVA mice at day 2 or 3. The infused enzyme was primarily recovered in liver and spleen, with detectable activity in bone and brain. Second, newborn ERT was conducted after 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 week were intravenous into the tail vein. MPS IVA mice treated with GALNS showed clearance of lysosomal storage in liver, spleen, and sinus lining cells in bone marrow. The column structure of the growth plate was organized better than adult mice treated with ERT; however, hyaline and fibrous cartilage cells in 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 mouse. PMID:24953405

Highly phosphomannosylated enzyme replacement therapy for GM2 gangliosidosis.

PubMed

Tsuji, Daisuke; Akeboshi, Hiromi; Matsuoka, Kazuhiko; Yasuoka, Hiroko; Miyasaki, Eri; Kasahara, Yoshiko; Kawashima, Ikuo; Chiba, Yasunori; Jigami, Yoshifumi; Taki, Takao; Sakuraba, Hitoshi; Itoh, Kohji

2011-04-01

Novel recombinant human lysosomal β-hexosaminidase A (HexA) was developed for enzyme replacement therapy (ERT) for Tay-Sachs and Sandhoff diseases, ie, autosomal recessive GM2 gangliosidoses, caused by HexA deficiency. A recombinant human HexA (Om4HexA) with a high mannose 6-phosphate (M6P)-type-N-glycan content, which was produced by a methylotrophic yeast strain, Ogataea minuta, overexpressing the OmMNN4 gene, was intracerebroventricularly (ICV) administered to Sandhoff disease model mice (Hexb⁻/⁻ mice) at different doses (0.5-2.5 mg/kg), and then the replacement and therapeutic effects were examined. The Om4HexA was widely distributed across the ependymal cell layer, dose-dependently restored the enzyme activity due to uptake via cell surface cation-independent M6P receptor (CI-M6PR) on neural cells, and reduced substrates, including GM2 ganglioside (GM2), asialo GM2 (GA2), and oligosaccharides with terminal N-acetylglucosamine residues (GlcNAc-oligosaccharides), accumulated in brain parenchyma. A significant inhibition of chemokine macrophage inflammatory protein-1 α (MIP-1α) induction was also revealed, especially in the hindbrain (< 63%). The decrease in central neural storage correlated with an improvement of motor dysfunction as well as prolongation of the lifespan. This lysosome-directed recombinant human enzyme drug derived from methylotrophic yeast has the high therapeutic potential to improve the motor dysfunction and quality of life of the lysosomal storage diseases (LSDs) patients with neurological manifestations. We emphasize the importance of neural cell surface M6P receptor as a delivery target of neural cell-directed enzyme replacement therapy (NCDERT) for neurodegenerative metabolic diseases. Copyright © 2010 American Neurological Association.

Aortic cusp extension valvuloplasty with or without tricuspidization in children and adolescents: long-term results and freedom from aortic valve replacement.

PubMed

Polimenakos, Anastasios C; Sathanandam, Shyam; Elzein, Chawki; Barth, Mary J; Higgins, Robert S D; Ilbawi, Michel N

2010-04-01

Aortic cusp extension valvuloplasty is increasingly used in the management of children and adolescents with aortic stenosis or regurgitation. The durability of this approach and the freedom from valve replacement are not well defined. A study was undertaken to investigate outcomes. From July 1987 to November 2008, 142 patients aged less than 19 years underwent aortic cusp extension valvuloplasty in the form of pericardial cusp extension and tricuspidization (when needed). Three patients with truncus arteriosus and severe truncal valve insufficiency were excluded. From the available follow-up data of 139 patients, 50 had bicuspid aortic valves, 40 had congenital aortic valve stenosis, 41 had combined congenital aortic valve stenosis/insufficiency, and 8 had other diagnoses. Median follow-up was 14.4 years (0.1-21.4). Long-term mortality and freedom from aortic valve replacement were studied. There were no early, intermediate, or late deaths. Z-values of left ventricular end-diastolic dimension, aortic annulus, aortic sinus diameter, and sinotubular junction diameter before aortic valve replacement were 4.2 +/- 3.11, 2.3 +/- 1.25, 4.4 +/- 1.23, and 1.84 +/- 1.28, respectively. During the follow-up period, 64 patients underwent aortic valve reinterventions. The Ross procedure was performed in 32 of 139 patients (23%) undergoing aortic cusp extension valvuloplasty. Other aortic valve replacements were undertaken after 16 aortic cusp extension valvuloplasties (11.5%). Freedom from a second aortic cusp extension valvuloplasty or aortic valve replacement at 18 years was 82.1% +/- 4.2% and 60.0% +/- 7.2%, respectively. Aortic cusp extension valvuloplasty is a safe and effective surgical option with excellent survival and good long-term outcomes in children and adolescents. The procedure provides acceptable durability and satisfactory freedom from aortic valve replacement. Copyright 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights

Nicotine, Carcinogen, and Toxin Exposure in Long-Term E-Cigarette and Nicotine Replacement Therapy Users: A Cross-sectional Study.

PubMed

Shahab, Lion; Goniewicz, Maciej L; Blount, Benjamin C; Brown, Jamie; McNeill, Ann; Alwis, K Udeni; Feng, June; Wang, Lanqing; West, Robert

2017-03-21

Given the rapid increase in the popularity of e-cigarettes and the paucity of associated longitudinal health-related data, the need to assess the potential risks of long-term use is essential. To compare exposure to nicotine, tobacco-related carcinogens, and toxins among smokers of combustible cigarettes only, former smokers with long-term e-cigarette use only, former smokers with long-term nicotine replacement therapy (NRT) use only, long-term dual users of both combustible cigarettes and e-cigarettes, and long-term users of both combustible cigarettes and NRT. Cross-sectional study. United Kingdom. The following 5 groups were purposively recruited: combustible cigarette-only users, former smokers with long-term (≥6 months) e-cigarette-only or NRT-only use, and long-term dual combustible cigarette-e-cigarette or combustible cigarette-NRT users (n = 36 to 37 per group; total n = 181). Sociodemographic and smoking characteristics were assessed. Participants provided urine and saliva samples and were analyzed for biomarkers of nicotine, tobacco-specific N-nitrosamines (TSNAs), and volatile organic compounds (VOCs). After confounders were controlled for, no clear between-group differences in salivary or urinary biomarkers of nicotine intake were found. The e-cigarette-only and NRT-only users had significantly lower metabolite levels for TSNAs (including the carcinogenic metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol [NNAL]) and VOCs (including metabolites of the toxins acrolein; acrylamide; acrylonitrile; 1,3-butadiene; and ethylene oxide) than combustible cigarette-only, dual combustible cigarette-e-cigarette, or dual combustible cigarette-NRT users. The e-cigarette-only users had significantly lower NNAL levels than all other groups. Combustible cigarette-only, dual combustible cigarette-NRT, and dual combustible cigarette-e-cigarette users had largely similar levels of TSNA and VOC metabolites. Cross-sectional design with self-selected sample. Former

Comparison of short- and long-term exposure effects of cruciferous and apiaceous vegetables on carcinogen metabolizing enzymes in Wistar rats.

PubMed

Kim, Jae Kyeom; Strapazzon, Noemia; Gallaher, Cynthia M; Stoll, Dwight R; Thomas, William; Gallaher, Daniel D; Trudo, Sabrina P

2017-10-01

Cruciferous and apiaceous vegetables may be chemopreventive due to their ability to modulate carcinogen-metabolizing enzymes but whether the effects on such enzymes are sustained over time is unknown. To examine the short- and long-term effects of the vegetables, rats were fed one of four diets for 7, 30, or 60 d: AIN-93G, CRU (21% cruciferous vegetables-fresh broccoli, green cabbage, watercress), API (9% apiaceous vegetables - fresh parsnips, celery), or API + CRU (10.5% CRU + 4.5% API). Although CRU increased activity and protein expression of cytochrome P450 (CYP) 1A1 and CYP1A2 after 7 d, only activity was sustained after 30 and 60 d. There was a trend towards an interaction between the length of feeding period and CRU for CYP1A1 activity; activity increased with greater time of feeding. API increased CYP1A2 activity but decreased sulfotransferase 1A1 activity after 7 d, although not at later times. Altogether, increased CYP1A activity by CRU was maintained with long term feeding while protein amount decreased, suggesting influence by mechanisms other than, or in addition to, transcriptional regulation. Thus, response patterns and interactions with length of feeding may differ, depending upon the types of vegetables and enzymes, requiring caution when interpreting the results of short-term feeding studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

The dead seed coat functions as a long-term storage for active hydrolytic enzymes

PubMed Central

Raviv, Buzi; Aghajanyan, Lusine; Granot, Gila; Makover, Vardit; Frenkel, Omer; Gutterman, Yitzchak

2017-01-01

Seed development culminates in programmed cell death (PCD) and hardening of organs enclosing the embryo (e.g., pericarp, seed coat) providing essentially a physical shield for protection during storage in the soil. We examined the proposal that dead organs enclosing embryos are unique entities that store and release upon hydration active proteins that might increase seed persistence in soil, germination and seedling establishment. Proteome analyses of dead seed coats of Brassicaceae species revealed hundreds of proteins being stored in the seed coat and released upon hydration, many are stress-associated proteins such as nucleases, proteases and chitinases. Functional analysis revealed that dead seed coats function as long-term storage for multiple active hydrolytic enzymes (e.g., nucleases) that can persist in active forms for decades. Substances released from the dead seed coat of the annual desert plant Anastatica hierochuntica displayed strong antimicrobial activity. Our data highlighted a previously unrecognized feature of dead organs enclosing embryos (e.g., seed coat) functioning not only as a physical shield for embryo protection but also as a long-term storage for active proteins and other substances that are released upon hydration to the “seedsphere” and could contribute to seed persistence in the soil, germination and seedling establishment. PMID:28700755

The dead seed coat functions as a long-term storage for active hydrolytic enzymes.

PubMed

Raviv, Buzi; Aghajanyan, Lusine; Granot, Gila; Makover, Vardit; Frenkel, Omer; Gutterman, Yitzchak; Grafi, Gideon

2017-01-01

Seed development culminates in programmed cell death (PCD) and hardening of organs enclosing the embryo (e.g., pericarp, seed coat) providing essentially a physical shield for protection during storage in the soil. We examined the proposal that dead organs enclosing embryos are unique entities that store and release upon hydration active proteins that might increase seed persistence in soil, germination and seedling establishment. Proteome analyses of dead seed coats of Brassicaceae species revealed hundreds of proteins being stored in the seed coat and released upon hydration, many are stress-associated proteins such as nucleases, proteases and chitinases. Functional analysis revealed that dead seed coats function as long-term storage for multiple active hydrolytic enzymes (e.g., nucleases) that can persist in active forms for decades. Substances released from the dead seed coat of the annual desert plant Anastatica hierochuntica displayed strong antimicrobial activity. Our data highlighted a previously unrecognized feature of dead organs enclosing embryos (e.g., seed coat) functioning not only as a physical shield for embryo protection but also as a long-term storage for active proteins and other substances that are released upon hydration to the "seedsphere" and could contribute to seed persistence in the soil, germination and seedling establishment.

Response of soil physicochemical properties and enzyme activities to long-term reclamation of coastal saline soil, Eastern China.

PubMed

Xie, Xuefeng; Pu, Lijie; Wang, Qiqi; Zhu, Ming; Xu, Yan; Zhang, Meng

2017-12-31

Soil enzyme activity during different years of reclamation and land use patterns could indicate changes in soil quality. The objective of this research is to explore the dynamics of 5 soil enzyme activities (dehydrogenase, amylase, urease, acid phosphatase and alkaline phosphatase) involved in C, N, and P cycling and their responses to changes in soil physicochemical properties resulting from long-term reclamation of coastal saline soil. Soil samples from a total of 55 sites were collected from a coastal reclamation area with different years of reclamation (0, 7, 32, 40, 63a) in this study. The results showed that both long-term reclamation and land use patterns have significant effects on soil physicochemical properties and enzyme activities. Compared with the bare flat, soil water content, soil bulk density, pH and electrical conductivity showed a decreasing trend after reclamation, whereas soil organic carbon, total nitrogen and total phosphorus tended to increase. Dehydrogenase, amylase and acid phosphatase activities initially increased and then decreased with increasing years of reclamation, whereas urease and alkaline phosphatase activities were characterized by an increase-decrease-increase trend. Moreover, urease, acid phosphatase and alkaline phosphatase activities exhibited significant differences between coastal saline soil with 63years of reclamation and bare flat, whereas dehydrogenase and amylase activities remained unchanged. Aquaculture ponds showed higher soil water content, pH and EC but lower soil organic carbon, total nitrogen and total phosphorus than rapeseed, broad bean and wheat fields. Rapeseed, broad bean and wheat fields displayed higher urease and alkaline phosphatase activities and lower dehydrogenase, amylase and acid phosphatase activities compared with aquaculture ponds. Redundancy analysis revealed that the soil physicochemical properties explained 74.5% of the variation in soil enzyme activities and that an obvious relationship

A meta-analysis and meta-regression of long-term outcomes of transcatheter versus surgical aortic valve replacement for severe aortic stenosis.

PubMed

Villablanca, Pedro A; Mathew, Verghese; Thourani, Vinod H; Rodés-Cabau, Josep; Bangalore, Sripal; Makkiya, Mohammed; Vlismas, Peter; Briceno, David F; Slovut, David P; Taub, Cynthia C; McCarthy, Patrick M; Augoustides, John G; Ramakrishna, Harish

2016-12-15

Transcatheter aortic valve replacement (TAVR) has emerged as an alternative to surgical aortic-valve replacement (SAVR) for patients with severe symptomatic aortic stenosis (AS) who are at high operative risk. We sought to determine the long-term (≥1year follow-up) safety and efficacy TAVR compared with SAVR in patients with severe AS. A comprehensive search of PubMed, EMBASE, Cochrane Central Register of Controlled Trials, conference proceedings, and relevant Web sites from inception through 10 April 2016. Fifty studies enrolling 44,247 patients met the inclusion criteria. The mean duration follow-up was 21.4months. No difference was found in long-term all-cause mortality (risk ratios (RR), 1.06; 95% confidence interval (CI) 0.91-1.22). There was a significant difference favoring TAVR in the incidence of stroke (RR, 0.82; 95% CI 0.71-0.94), atrial fibrillation (RR, 0.43; 95% CI 0.33-0.54), acute kidney injury (RR, 0.70; 95% CI 0.53-0.92), and major bleeding (RR, 0.57; 95% CI 0.40-0.81). TAVR had significant higher incidence of vascular complications (RR, 2.90; 95% CI 1.87-4.49), aortic regurgitation (RR, 7.00; 95% CI 5.27-9.30), and pacemaker implantation (PPM) (RR, 2.02; 95% CI 1.51-2.68). TAVR demonstrated significantly lower stroke risk compared to SAVR in high-risk patients (RR, 1.49; 95% CI 1.06-2.10); no differences in PPM implantation were observed in intermediate-risk patients (RR, 1.68; 95% CI 0.94-3.00). In a meta-regression analysis, the effect of TAVR baseline clinical features did not affect the long-term all-cause mortality outcome. TAVR and SAVR showed similar long-term survival in patients with severe AS; with important differences in treatment-associated morbidity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Long-term results with the Atlas IIIp elastic cementless acetabular component in total hip replacement.

PubMed

Lee, Paul Yuh Feng; Rachala, Madhu; Teoh, Kar Ho; Woodnutt, David John

2016-09-01

Modular cementless elastic acetabular systems have advantages over cemented and hard shell cementless acetabular systems. There are few reports on the medium-term and long-term follow up of this particular type of implant. This study describes our experience with the Atlas IIIp modular acetabular system, which is a thin shell cementless elastic acetabular implant for total hip replacement commercialized under this name in many countries. We prospectively followed 244 patients treated with Atlas IIIp acetabular system between 2001 and 2004. Minimum ten year follow up was available for 148 hips (139 patients) from the original cohort of 263 hips (244 patients). One hundred five patients had died from unrelated causes and were excluded from the results. Post-operative and follow up radiographs of patients were assessed; and Harris hip scores were used as clinical outcome. Revision for any reason was defined as the end point for survivorship analysis. The mean pre-operative Harris hip score was 48 (S.D. 16) and the average post-operative score was 82 (S.D. 12). The mean follow up in our series was 11.5 years, ranging from ten to 13.5 years. Thirteen hips required further surgery in our cohort; of which ten cases required cup revision. The 13-years cumulative implant survival was 91.2 % and the risk of implant revision was 8.8 % at 13 years in 148 hips (139 patients). Kaplan-Meier analysis showed the implant survival rate of 95.2 % at ten years for revision for any reason and 99.4 % for aseptic loosening. Our clinical experience with this acetabular cup suggests good long-term survival rates that are similar to other cups on the market. The clinical experience in this study shows long-term survival rates that are consistent, acceptable and good results achieved with a low revision rate. Therapeutic III; therapeutic study.

The Status of Long-Term Disability Plans in Higher Education.

ERIC Educational Resources Information Center

Cook, Thomas J.

1981-01-01

Long-term disability income coverage is seen as the most rapidly growing staff benefit in recent years. A Teachers Insurance and Annuity Association's survey of existing long-term disability plans, which provide adequate income replacement, is discussed. (MLW)

Long-term results of aortic valve replacement with Edwards Prima Plus stentless bioprosthesis: eleven years' follow up.

PubMed

Auriemma, Stefano; D'Onofrio, Augusto; Brunelli, Massimo; Magagna, Paolo; Paccanaro, Mariemma; Rulfo, Fanny; Fabbri, Alessandro

2006-09-01

The Edwards Lifesciences Prima Plus stentless valve (ELSV) is a bioprosthesis manufactured from a porcine aortic root. The study aim was to evaluate late clinical outcomes after aortic valve replacement (AVR) with ELSV implanted as a miniroot in patients with aortic valve disease. Between 1993 and 2004, 318 patients (232 males, 86 females; mean age 69 +/- 9 years; range: 37-83 years) underwent AVR with the ELSV. Preoperatively, 102 patients (32%), 162 (51%) and 54 (17%) were in NYHA classes I/II, III and IV, respectively. Aortic stenosis, aortic regurgitation and combined lesions were present in 124 patients (39%), 114 (36%) and 41 (13%), respectively. Twenty patients (6%) were referred for an acute aortic dissection, 20 (6%) for an aortic root aneurysm, and 139 (44%) had an associated aneurysmal dilatation of the ascending aorta. The ascending aorta was replaced in 159 patients (50%); aortic arch replacement was required in 10 (3%). Coronary artery bypass graft was performed in 86 patients (27%). The follow up was based on clinical data. Operative mortality was 5% (n = 17). There were 49 late deaths (5.2%/pt-yr). Valve-related mortality occurred in 10 patients (1%/pt-yr). Actuarial survival at five and 10 years was 78% and 33%, respectively. Actuarial freedom from valve reoperation and structural valve deterioration at 10 years were 100% and 64%. Actuarial freedom from embolic events and endocarditis at 10 years were 84% and 81%, respectively. The ELSV, when implanted as a miniroot, provided good early and long-term results in terms of survival and freedom from major complications.

Impact of enzyme replacement therapy on cardiac morphology and function and late enhancement in Fabry's cardiomyopathy.

PubMed

Beer, Meinrad; Weidemann, Frank; Breunig, Frank; Knoll, Anita; Koeppe, Sabrina; Machann, Wolfram; Hahn, Dietbert; Wanner, Christoph; Strotmann, Jörg; Sandstede, Jörn

2006-05-15

The present study evaluated the evolution of cardiac morphology, function, and late enhancement as a noninvasive marker of myocardial fibrosis, and their inter-relation during enzyme replacement therapy in patients with Fabry's disease using magnetic resonance imaging and color Doppler myocardial imaging. Late enhancement, which was present in up to 50% of patients, was associated with increased left ventricular mass, the failure of a significant regression of hypertrophy during enzyme replacement therapy, and worse segmental myocardial function. Late enhancement may predict the effect of enzyme replacement therapy on left ventricular mass and cardiac function.

A Chaperone Enhances Blood α-Glucosidase Activity in Pompe Disease Patients Treated With Enzyme Replacement Therapy

PubMed Central

Parenti, Giancarlo; Fecarotta, Simona; la Marca, Giancarlo; Rossi, Barbara; Ascione, Serena; Donati, Maria Alice; Morandi, Lucia Ovidia; Ravaglia, Sabrina; Pichiecchio, Anna; Ombrone, Daniela; Sacchini, Michele; Pasanisi, Maria Barbara; De Filippi, Paola; Danesino, Cesare; Della Casa, Roberto; Romano, Alfonso; Mollica, Carmine; Rosa, Margherita; Agovino, Teresa; Nusco, Edoardo; Porto, Caterina; Andria, Generoso

2014-01-01

Enzyme replacement therapy is currently the only approved treatment for Pompe disease, due to acid α-glucosidase deficiency. Clinical efficacy of this approach is variable, and more effective therapies are needed. We showed in preclinical studies that chaperones stabilize the recombinant enzyme used for enzyme replacement therapy. Here, we evaluated the effects of a combination of enzyme therapy and a chaperone on α-glucosidase activity in Pompe disease patients. α-Glucosidase activity was analyzed by tandem-mass spectrometry in dried blood spots from patients treated with enzyme replacement therapy, either alone or in combination with the chaperone N-butyldeoxynojirimycin given at the time of the enzyme infusion. Thirteen patients with different presentations (3 infantile-onset, 10 late-onset) were enrolled. In 11 patients, the combination treatment resulted in α-glucosidase activities greater than 1.85-fold the activities with enzyme replacement therapy alone. In the whole patient population, α-glucosidase activity was significantly increased at 12 hours (2.19-fold, P = 0.002), 24 hours (6.07-fold, P = 0.001), and 36 hours (3.95-fold, P = 0.003). The areas under the curve were also significantly increased (6.78-fold, P = 0.002). These results suggest improved stability of recombinant α-glucosidase in blood in the presence of the chaperone. PMID:25052852

Human β-glucuronidase: structure, function, and application in enzyme replacement therapy.

PubMed

Naz, Huma; Islam, Asimul; Waheed, Abdul; Sly, William S; Ahmad, Faizan; Hassan, Imtaiyaz

2013-10-01

Lysosomal storage diseases occur due to incomplete metabolic degradation of macromolecules by various hydrolytic enzymes in the lysosome. Despite structural differences, most of the lysosomal enzymes share many common features including a lysosomal targeting motif and phosphotransferase recognition sites. β-Glucuronidase (GUSB) is an important lysosomal enzyme involved in the degradation of glucuronate-containing glycosaminoglycan. The deficiency of GUSB causes mucopolysaccharidosis type VII (MPSVII), leading to lysosomal storage in the brain. GUSB is a well-studied protein for its expression, sequence, structure, and function. The purpose of this review is to summarize our current understanding of sequence, structure, function, and evolution of GUSB and its lysosomal enzyme targeting. Enzyme replacement therapy reported for this protein is also discussed.

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

NASA Astrophysics Data System (ADS)

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

2014-12-01

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

Safety and efficacy of enzyme replacement therapy in the nephropathy of Fabry disease

PubMed Central

Fervenza, Fernando C; Torra, Roser; Warnock, David G

2008-01-01

Kidney involvement with progressive loss of kidney function (Fabry nephropathy) is an important complication of Fabry disease, an X-linked lysosomal storage disorder arising from deficiency of α-galactosidase activity. Clinical trials have shown that enzyme replacement therapy (ERT) with recombinant human α-galactosidase clears globotriaosylceramide from kidney cells, and can stabilize kidney function in patients with mild to moderate Fabry nephropathy. Recent trials show that patients with more advanced Fabry nephropathy and overt proteinuria do not respond as well to ERT alone, but can benefit from anti-proteinuric therapy given in conjunction with ERT. This review focuses on the use of enzyme replacement therapy with agalsidase-alfa and agalsidase-beta in adults with Fabry nephropathy. The current results are reviewed and evaluated. The issues of dosing of enzyme replacement therapy, the use of adjunctive agents to control urinary protein excretion, and the individual factors that affect disease severity are reviewed. PMID:19707461

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

PubMed

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

2016-12-01

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. © The Author(s) 2016.

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

PubMed

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

2008-05-01

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.

Engineering of GlcNAc-1-Phosphotransferase for Production of Highly Phosphorylated Lysosomal Enzymes for Enzyme Replacement Therapy.

PubMed

Liu, Lin; Lee, Wang-Sik; Doray, Balraj; Kornfeld, Stuart

2017-06-16

Several lysosomal enzymes currently used for enzyme replacement therapy in patients with lysosomal storage diseases contain very low levels of mannose 6-phosphate, limiting their uptake via mannose 6-phosphate receptors on the surface of the deficient cells. These enzymes are produced at high levels by mammalian cells and depend on endogenous GlcNAc-1-phosphotransferase α/β precursor to phosphorylate the mannose residues on their glycan chains. We show that co-expression of an engineered truncated GlcNAc-1-phosphotransferase α/β precursor and the lysosomal enzyme of interest in the producing cells resulted in markedly increased phosphorylation and cellular uptake of the secreted lysosomal enzyme. This method also results in the production of highly phosphorylated acid β-glucocerebrosidase, a lysosomal enzyme that normally has just trace amounts of this modification.

Hormone replacement therapy: short-term versus long-term use.

PubMed

Rousseau, Mary Ellen

2002-01-01

Midwives manage health care of women throughout the life cycle including prescribing hormone replacement therapy (HRT). This article presents a history of research on the use of HRT, as well as risks and benefits. Older research on the effects of HRT on heart disease, osteoporosis, and breast cancer is included. The results and recommendations of the Women's Health Initiative are examined.

The emerging phenotype of long-term survivors with infantile Pompe disease

PubMed Central

Prater, Sean N.; Banugaria, Suhrad G.; DeArmey, Stephanie M.; Botha, Eleanor G.; Stege, Erin M.; Case, Laura E.; Jones, Harrison N.; Phornphutkul, Chanika; Wang, Raymond Y.; Young, Sarah P.; Kishnani, Priya S.

2013-01-01

Purpose Enzyme replacement therapy with alglucosidase alfa for infantile Pompe disease has improved survival creating new management challenges. We describe an emerging phenotype in a retrospective review of long-term survivors. Methods Inclusion criteria included ventilator-free status and age ≤6 months at treatment initiation, and survival to age ≥5 years. Clinical outcome measures included invasive ventilator-free survival and parameters for cardiac, pulmonary, musculoskeletal, gross motor and ambulatory status; growth; speech, hearing, and swallowing; and gastrointestinal and nutritional status. Results Eleven of 17 patients met study criteria. All were cross-reactive immunologic material-positive, alive, and invasive ventilator-free at most recent assessment, with a median age of 8.0 years (range: 5.4 to 12.0 years). All had marked improvements in cardiac parameters. Commonly present were gross motor weakness, motor speech deficits, sensorineural and/or conductive hearing loss, osteopenia, gastroesophageal reflux disease, and dysphagia with aspiration risk. Seven of 11 patients were independently ambulatory and four required the use of assistive ambulatory devices. All long-term survivors had low or undetectable anti-alglucosidase alfa antibody titers. Conclusions Long-term survivors exhibited sustained improvements in cardiac parameters and gross motor function. Residual muscle weakness, hearing loss, risk for arrhythmias, hypernasal speech, dysphagia with risk for aspiration, and osteopenia were commonly observed findings. PMID:22538254

Hip joint replacement

MedlinePlus

... Total hip replacement; Hip hemiarthroplasty; Arthritis - hip replacement; Osteoarthritis - hip replacement ... total hip replacement surgery in patients with hip osteoarthritis: a long-term follow-up of a randomised ...

Efficacy of pancreatic enzyme replacement therapy in chronic pancreatitis: systematic review and meta-analysis

PubMed Central

de la Iglesia-García, Daniel; Huang, Wei; Szatmary, Peter; Baston-Rey, Iria; Gonzalez-Lopez, Jaime; Prada-Ramallal, Guillermo; Mukherjee, Rajarshi; Nunes, Quentin M; Domínguez-Muñoz, J Enrique

2017-01-01

Objective The benefits of pancreatic enzyme replacement therapy (PERT) in chronic pancreatitis (CP) are inadequately defined. We have undertaken a systematic review and meta-analysis of randomised controlled trials of PERT to determine the efficacy of PERT in exocrine pancreatic insufficiency (EPI) from CP. Design Major databases were searched from 1966 to 2015 inclusive. The primary outcome was coefficient of fat absorption (CFA). Effects of PERT versus baseline and versus placebo, and of different doses, formulations and schedules were determined. Results A total of 17 studies (511 patients with CP) were included and assessed qualitatively (Jadad score). Quantitative data were synthesised from 14 studies. PERT improved CFA compared with baseline (83.7±6.0 vs 63.1±15.0, p<0.00001; I2=89%) and placebo (83.2±5.5 vs 67.4±7.0, p=0.0001; I2=86%). PERT improved coefficient of nitrogen absorption, reduced faecal fat excretion, faecal nitrogen excretion, faecal weight and abdominal pain, without significant adverse events. Follow-up studies demonstrated that PERT increased serum nutritional parameters, improved GI symptoms and quality of life without significant adverse events. High-dose or enteric-coated enzymes showed a trend to greater effectiveness than low-dose or non-coated comparisons, respectively. Subgroup, sensitive and meta-regression analyses revealed that sample size, CP diagnostic criteria, study design and enzyme dose contributed to heterogeneity; data on health inequalities were lacking. Conclusions PERT is indicated to correct EPI and malnutrition in CP and may be improved by higher doses, enteric coating, administration during food and acid suppression. Further studies are required to determine optimal regimens, the impact of health inequalities and long-term effects on nutrition. PMID:27941156

Efficacy of pancreatic enzyme replacement therapy in chronic pancreatitis: systematic review and meta-analysis.

PubMed

de la Iglesia-García, Daniel; Huang, Wei; Szatmary, Peter; Baston-Rey, Iria; Gonzalez-Lopez, Jaime; Prada-Ramallal, Guillermo; Mukherjee, Rajarshi; Nunes, Quentin M; Domínguez-Muñoz, J Enrique; Sutton, Robert

2017-08-01

The benefits of pancreatic enzyme replacement therapy (PERT) in chronic pancreatitis (CP) are inadequately defined. We have undertaken a systematic review and meta-analysis of randomised controlled trials of PERT to determine the efficacy of PERT in exocrine pancreatic insufficiency (EPI) from CP. Major databases were searched from 1966 to 2015 inclusive. The primary outcome was coefficient of fat absorption (CFA). Effects of PERT versus baseline and versus placebo, and of different doses, formulations and schedules were determined. A total of 17 studies (511 patients with CP) were included and assessed qualitatively (Jadad score). Quantitative data were synthesised from 14 studies. PERT improved CFA compared with baseline (83.7±6.0 vs 63.1±15.0, p<0.00001; I 2 =89%) and placebo (83.2±5.5 vs 67.4±7.0, p=0.0001; I 2 =86%). PERT improved coefficient of nitrogen absorption, reduced faecal fat excretion, faecal nitrogen excretion, faecal weight and abdominal pain, without significant adverse events. Follow-up studies demonstrated that PERT increased serum nutritional parameters, improved GI symptoms and quality of life without significant adverse events. High-dose or enteric-coated enzymes showed a trend to greater effectiveness than low-dose or non-coated comparisons, respectively. Subgroup, sensitive and meta-regression analyses revealed that sample size, CP diagnostic criteria, study design and enzyme dose contributed to heterogeneity; data on health inequalities were lacking. PERT is indicated to correct EPI and malnutrition in CP and may be improved by higher doses, enteric coating, administration during food and acid suppression. Further studies are required to determine optimal regimens, the impact of health inequalities and long-term effects on nutrition. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Rapid Immunochromatographic Detection of Serum Anti-α-Galactosidase A Antibodies in Fabry Patients after Enzyme Replacement Therapy.

PubMed

Nakano, Sachie; Tsukimura, Takahiro; Togawa, Tadayasu; Ohashi, Toya; Kobayashi, Masahisa; Takayama, Katsuyoshi; Kobayashi, Yukuharu; Abiko, Hiroshi; Satou, Masatsugu; Nakahata, Tohru; Warnock, David G; Sakuraba, Hitoshi; Shibasaki, Futoshi

2015-01-01

We developed an immunochromatography-based assay for detecting antibodies against recombinant α-galactosidase A proteins in serum. The evaluation of 29 serum samples from Fabry patients, who had received enzyme replacement therapy with agalsidase alpha and/or agalsidase beta, was performed by means of this assay method, and the results clearly revealed that the patients exhibited the same level of antibodies against both agalsidase alpha and agalsidase beta, regardless of the species of recombinant α-galactosidase A used for enzyme replacement therapy. A conventional enzyme-linked immunosorbent assay supported the results. Considering these, enzyme replacement therapy with agalsidase alpha or agalsidase beta would generate antibodies against the common epitopes in both agalsidase alpha and agalsidase beta. Most of the patients who showed immunopositive reaction exhibited classic Fabry phenotype and harbored gene mutations affecting biosynthesis of α-galactosidase A. As immunochromatography is a handy and simple assay system which can be available at bedside, this assay method would be extremely useful for quick evaluation or first screening of serum antibodies against agalsidase alpha or agalsidase beta in Fabry disease with enzyme replacement therapy.

Bile salt kinetics in cystic fibrosis: influence of pancreatic enzyme replacement

DOE Office of Scientific and Technical Information (OSTI.GOV)

Watkins, J.B.; Tercyak, A.M.; Szczepanik, P.

1977-01-01

Bile acid kinetics was investigated by stable isotope dilution technique in 6 children (ages 3/sup 1///sub 2/ months to 4/sup 1///sub 2/ years) with previously untreated cystic fibrosis. All of the patients had clinical and laboratory evidence of malabsorption, normal intestinal mucosal function, as judged by glucose absorption, intestinal histology, disaccharidase levels, and normally functioning gallbladders. The children were maintained on a constant diet throughout the study period; fat intake averaged 4.2 g per kg per day. Before administration of pancreatic enzyme replacement, fat excretion equalled 50 +- 4% (mean +- SE) of intake and was reduced to 20 +-more » 1.0% of intake after therapy. Total bile acid pool size nearly doubled during enzyme replacement from 379 +- 32 ..mu..moles per kg to 620 +- 36 ..mu..moles per kg with secondary bile acids comprising 57% of the total pool before therapy and 40% after therapy. The data indicate that both primary and secondary bile acids are conserved within the enterohepatic circulation during enzyme therapy, and that the mechanism for the regulation of hepatic bile acid synthesis is intact in cystic fibrosis. However, the demonstration that large amounts of bile acid continue to be excreted during therapy suggests that interruption of the enterohepatic circulation continues and that deficiencies of the intraluminal phase may persist during enzyme therapy in this disease.« less

Interactions among plants, bacteria, and fungi reduce extracellular enzyme activities under long-term N fertilization.

PubMed

Carrara, Joseph E; Walter, Christopher A; Hawkins, Jennifer S; Peterjohn, William T; Averill, Colin; Brzostek, Edward R

2018-06-01

Atmospheric nitrogen (N) deposition has enhanced soil carbon (C) stocks in temperate forests. Most research has posited that these soil C gains are driven primarily by shifts in fungal community composition with elevated N leading to declines in lignin degrading Basidiomycetes. Recent research, however, suggests that plants and soil microbes are dynamically intertwined, whereby plants send C subsidies to rhizosphere microbes to enhance enzyme production and the mobilization of N. Thus, under elevated N, trees may reduce belowground C allocation leading to cascading impacts on the ability of microbes to degrade soil organic matter through a shift in microbial species and/or a change in plant-microbe interactions. The objective of this study was to determine the extent to which couplings among plant, fungal, and bacterial responses to N fertilization alter the activity of enzymes that are the primary agents of soil decomposition. We measured fungal and bacterial community composition, root-microbial interactions, and extracellular enzyme activity in the rhizosphere, bulk, and organic horizon of soils sampled from a long-term (>25 years), whole-watershed, N fertilization experiment at the Fernow Experimental Forest in West Virginia, USA. We observed significant declines in plant C investment to fine root biomass (24.7%), root morphology, and arbuscular mycorrhizal (AM) colonization (55.9%). Moreover, we found that declines in extracellular enzyme activity were significantly correlated with a shift in bacterial community composition, but not fungal community composition. This bacterial community shift was also correlated with reduced AM fungal colonization indicating that declines in plant investment belowground drive the response of bacterial community structure and function to N fertilization. Collectively, we find that enzyme activity responses to N fertilization are not solely driven by fungi, but instead reflect a whole ecosystem response, whereby declines in the

Rapid Immunochromatographic Detection of Serum Anti-α-Galactosidase A Antibodies in Fabry Patients after Enzyme Replacement Therapy

PubMed Central

Nakano, Sachie; Tsukimura, Takahiro; Togawa, Tadayasu; Ohashi, Toya; Kobayashi, Masahisa; Takayama, Katsuyoshi; Kobayashi, Yukuharu; Abiko, Hiroshi; Satou, Masatsugu; Nakahata, Tohru; Warnock, David G.; Sakuraba, Hitoshi; Shibasaki, Futoshi

2015-01-01

We developed an immunochromatography-based assay for detecting antibodies against recombinant α-galactosidase A proteins in serum. The evaluation of 29 serum samples from Fabry patients, who had received enzyme replacement therapy with agalsidase alpha and/or agalsidase beta, was performed by means of this assay method, and the results clearly revealed that the patients exhibited the same level of antibodies against both agalsidase alpha and agalsidase beta, regardless of the species of recombinant α-galactosidase A used for enzyme replacement therapy. A conventional enzyme-linked immunosorbent assay supported the results. Considering these, enzyme replacement therapy with agalsidase alpha or agalsidase beta would generate antibodies against the common epitopes in both agalsidase alpha and agalsidase beta. Most of the patients who showed immunopositive reaction exhibited classic Fabry phenotype and harbored gene mutations affecting biosynthesis of α-galactosidase A. As immunochromatography is a handy and simple assay system which can be available at bedside, this assay method would be extremely useful for quick evaluation or first screening of serum antibodies against agalsidase alpha or agalsidase beta in Fabry disease with enzyme replacement therapy. PMID:26083343

Tricuspid valve replacement: postoperative and long-term results.

PubMed

Van Nooten, G J; Caes, F; Taeymans, Y; Van Belleghem, Y; François, K; De Bacquer, D; Deuvaert, F E; Wellens, F; Primo, G

1995-09-01

mechanical prostheses (Smeloff-Cutter and Kay-Shiley) (p = 0.04) but not between the bioprostheses and the bileaflet valves (p = 0.15). When the follow-up period was stratified according to less than 7 years and more than 7 years of follow-up, no difference was observed for the first period, but for the late follow-up the new mechanical prostheses did better than the bioprostheses (p = 0.05), suggesting a degradation of the bioprostheses after 7 years and favoring mechanical prostheses for those patients with a good long-term prognosis.

Effects of information framing on the intentions of family physicians to prescribe long-term hormone replacement therapy.

PubMed

Nikolajevic-Sarunac, J; Henry, D A; O'Connell, D L; Robertson, J

1999-10-01

To determine whether the way in which information on benefits and harms of long-term hormone replacement therapy (HRT) is presented influences family physicians' intentions to prescribe this treatment. Family physicians were randomized to receive information on treatment outcomes expressed in relative terms, or as the number needing to be treated (NNT) with HRT to prevent or cause an event. A control group received no information. Primary care. Family physicians practicing in the Hunter Valley, New South Wales, Australia. Estimates of the impact of long-term HRT on risk of coronary events, hip fractures, and breast cancer were summarized as relative (proportional) decreases or increases in risk, or as NNT. Intention to prescribe HRT for seven hypothetical patients was measured on Likert scales. Of 389 family physicians working in the Hunter Valley, 243 completed the baseline survey and 215 participated in the randomized trial. Baseline intention to prescribe varied across patients-it was highest in the presence of risk factors for hip fracture, but coexisting risk factors for breast cancer had a strong negative influence. Overall, a larger proportion of subjects receiving information expressed as NNT had reduced intentions, and a smaller proportion had increased intentions to prescribe HRT than those receiving the information expressed in relative terms, or the control group. However, the differences were small and only reached statistical significance for three hypothetical patients. Framing effects were minimal when the hypothetical patient had coexisting risk factors for breast cancer. Information framing had some effect on family physicians' intentions to prescribe HRT, but the effects were smaller than those previously reported, and they were modified by the presence of serious potential adverse treatment effects.

Long-Term Health Benefit of Transcatheter Aortic Valve Replacement in Patients With Chronic Lung Disease.

PubMed

Crestanello, Juan A; Popma, Jeffrey J; Adams, David H; Deeb, G Michael; Mumtaz, Mubashir; George, Barry; Huang, Jian; Reardon, Michael J

2017-11-27

This study sought to characterize the long-term effect of chronic lung disease (CLD) on mortality, clinical outcomes, quality of life, and health benefits after transcatheter aortic valve replacement (TAVR) with a self-expanding bioprosthesis. The long-term effect of CLD after TAVR is unknown. Prevalence and severity of CLD was determined at baseline in high- and extreme-risk patients with aortic stenosis from the CoreValve US Pivotal Trial. Clinical outcomes and health status were assessed using the Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OS). A favorable health benefit was defined as alive with a KCCQ-OS ≥60 and stability (<10-point decrease) or improvement in the KCCQ-OS from baseline. CLD was present in 55% (20% mild, 13% moderate, 22% severe) of the 1,030 patients studied. All-cause mortality was higher in patients with moderate and severe CLD at 1 year (19.6% mild, 28.1% moderate, 26.9% severe CLD vs. 19.2% non-CLD; p = 0.030) and 3 years (44.8% mild, 53.0% moderate, 51.9% severe vs. 37.7% non-CLD; p < 0.001). New York Heart Association functional class improved in more than 80% of patients with CLD at 1 and 3 years. All patients had a nearly 20-point improvement in KCCQ-OS at 1 and 3 years. However, only 43.3% of patients with CLD had a favorable health benefit at 1 year and 22.5% at 3 years. Moderate and severe CLD increases 1- and 3-year mortality after TAVR. Although functional status and quality of life were improved in CLD at 1 and 3 years after TAVR, a favorable health benefit was only achieved in selected patients. (Safety and Efficacy Study of the Medtronic CoreValve System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement; NCT01240902). Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Long-Term Risk for Aortic Complications After Aortic Valve Replacement in Patients With Bicuspid Aortic Valve Versus Marfan Syndrome.

PubMed

Itagaki, Shinobu; Chikwe, Joanna P; Chiang, Yuting P; Egorova, Natalia N; Adams, David H

2015-06-09

Bicuspid aortic valves are associated with valve dysfunction, ascending aortic aneurysm and dissection. Management of the ascending aorta at the time of aortic valve replacement (AVR) in these patients is controversial and has been extrapolated from experience with Marfan syndrome, despite the absence of comparative long-term outcome data. This study sought to assess whether the natural history of thoracic aortopathy after AVR in patients with bicuspid aortic valve disease is substantially different from that seen in patients with Marfan syndrome. In this retrospective comparison, outcomes of 13,205 adults (2,079 with bicuspid aortic valves, 73 with Marfan syndrome, and 11,053 control patients with acquired aortic valve disease) who underwent primary AVR without replacement of the ascending aorta in New York State between 1995 and 2010 were compared. The median follow-up time was 6.6 years. The long-term incidence of thoracic aortic dissection was significantly higher in patients with Marfan syndrome (5.5 ± 2.7%) compared with those with bicuspid valves (0.55 ± 0.21%) and control group patients (0.41 ± 0.08%, p < 0.001). Thoracic aortic aneurysms were significantly more likely to be diagnosed in late follow-up in patients with Marfan syndrome (10.8 ± 4.4%) compared with those with bicuspid valves (4.8 ± 0.8%) and control group patients (1.4 ± 0.2%) (p < 0.001). Patients with Marfan syndrome were significantly more likely to undergo thoracic aortic surgery in late follow-up (10.4 ± 4.3%) compared with those with bicuspid valves (2.5 ± 0.6%) and control group patients (0.50 ± 0.09%) (p < 0.001). The much higher long-term rates of aortic complications after AVR observed in patients with Marfan syndrome compared with those with bicuspid aortic valves confirm that operative management of patients with bicuspid aortic valves should not be extrapolated from Marfan syndrome and support discrete treatment algorithms for these different clinical entities

Does early use of enzyme replacement therapy alter the natural history of mucopolysaccharidosis I? Experience in three siblings.

PubMed

Laraway, Sarah; Breen, Catherine; Mercer, Jean; Jones, Simon; Wraith, James E

2013-07-01

Enzyme replacement therapy is widely used as treatment for mucopolysaccharidosis I (MPS I), and there is evidence that this produces improvement in certain clinical domains. There does appear to be variation in the response of clinical features to treatment once these are established. In a reported sibling pair, when enzyme replacement therapy was commenced pre-symptomatically in the younger child, the natural history of the condition appeared to be affected. We present data from three siblings treated with enzyme replacement therapy at different ages which supports this finding. Copyright © 2013 Elsevier Inc. All rights reserved.

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

PubMed Central

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

2015-01-01

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. PMID:25706998

[Short and long term results of aortic valve replacement in patients 80 years of age and older].

PubMed

Mortasawi, A; Gehle, S; Yaghmaie, M; Schröder, T; Ennker, I C; Rosendahl, U; Albert, A; Ennker, J

2001-03-01

Due to demographic changes in average life expectancy the age of patients undergoing cardiac surgery is increasing as well. We have reviewed the short- and long-term outcome in patients over 80 years of age after aortic valve replacement with or without concomitant coronary grafting. From 1.1.1995 until 31.12.1999, 126 patients (93 women, 33 men between 80 and 89 years, 82.8 +/- 2.4) underwent aortic valve replacement. 64 patients (group A) received isolated valve replacement, 62 (group B) underwent myocardial revascularization as well. The 30-day hospital mortality rate was 6.3% for group A and 14.5% for group B. The follow-up time ranged between 3 and 63 months (32 +/- 16). None of the patients had to be reoperated for prosthetic valve dysfunction or endocarditis. Bleeding complications due to anticoagulation therapy were observed by one patient from group A 3 years after the operation. Of the 15 deaths during the follow-up period seven (47%) were cardiac in nature and two (13%) related to stroke. Acturial survival rates for group A were 89%, 85% and 77% at 1, 2 and 3 years, and for group B 76%, 72% and 70%. Permanent nursing care was not required 1 year after the operation by 100% of patients in group A (2 years: 98%, 3 years 95%) and by 100% of patients in group B (2 years: 93%, 3 years: 90%). At an interval of 1 year after the operation 96% of patients in group A had not been hospitalized as a result of cardiac disorders (2 years: 96%, 3 years: 94%). The rates for group B were 88%, 81% and 75%. Compared with younger age groups, aortic valve replacement in patients 80 years of age and older is associated with a distinctly increased mortality and morbidity. However, our data suggest that considering the poor prognosis of conservative therapy of symptomatic aortic valve disease, functional status as well as life expectancy in this age group seem to be positively influenced by aortic valve replacement.

Long-term survival, valve durability, and reoperation for 4 aortic root procedures combined with ascending aorta replacement.

PubMed

Svensson, Lars G; Pillai, Saila T; Rajeswaran, Jeevanantham; Desai, Milind Y; Griffin, Brian; Grimm, Richard; Hammer, Donald F; Thamilarasan, Maran; Roselli, Eric E; Pettersson, Gösta B; Gillinov, A Marc; Navia, Jose L; Smedira, Nicholas G; Sabik, Joseph F; Lytle, Bruce W; Blackstone, Eugene H

2016-03-01

To evaluate long-term results of aortic root procedures combined with ascending aorta replacement for aneurysms, using 4 surgical strategies. From January 1995 to January 2011, 957 patients underwent 1 of 4 aortic root procedures: valve preservation (remodeling or modified reimplantation, n = 261); composite biologic graft (n = 297); composite mechanical graft (n = 156); or allograft root (n = 243). Seven deaths occurred (0.73%), none after valve-preserving procedures, and 13 strokes (1.4%). Composite grafts exhibited higher gradients than allografts or valve preservation, but the latter 2 exhibited more aortic regurgitation (2.7% biologic and 0% mechanical composite grafts vs 24% valve-preserving and 19% allografts at 10 years). Within 2 to 5 years, valve preservation exhibited the least left ventricular hypertrophy, allograft replacement the greatest; however, valve preservation had the highest early risk of reoperation, allograft replacement the lowest. Patients receiving allografts had the highest risk of late reoperation (P < .05), and those receiving composite mechanical grafts and valve preservation had the lowest. Composite bioprosthesis patients had the highest risk of late death (57% at 15 years vs 14%-26% for the remaining procedures, P < .0001), because they were substantially older and had more comorbidities (P < .0001). These 4 aortic root procedures, combined with ascending aorta replacement, provide excellent survival and good durability. Valve-preserving and allograft procedures have the lowest gradients and best ventricular remodeling, but they have more late regurgitation, and likely, less risk of valve-related complications, such as bleeding, hemorrhage, and endocarditis. Despite the early risk of reoperation, we recommend valve-preserving procedures for young patients when possible. Composite bioprostheses are preferable for the elderly. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights

Long Term Survivorship of a Severely Notched Femoral Stem after Replacing the Fractured Ceramic head with a Cobalt-Chromium Head

PubMed Central

Panagopoulos, Andreas; Tatani, Irini; Megas, Panagiotis

2016-01-01

Background: Although ceramic head fracture occurs infrequently today, in the event of a fracture, the resulting revision surgery can prove very challenging, since the ceramic particles lodge into the surrounding soft tissue and can cause rapid implant failure Case Presentation: A case of long term survivorship of a severed notched femoral stem after replacing the fractured femoral head with a cobalt-chromium one is reported in a 40-year old woman with hip dysplasia who underwent an uncomplicated total hip arthroplasty. The incident of ceramic femoral head fracture occurred 14 months postoperatively without reporting any significant trauma. Intraoperative findings at revision were a multifragmented femoral head and a damaged polyethylene insert along with diffuse metallosis and excessive wear of the cone of the stem. Both the stem and the acetabular component were stable. After removal of ceramic fragments, metallotic tissue excision and careful lavage of the joint, the inlay was replaced by a similar one and a cobalt-chromium femoral head was placed to the existing notched taper of the firmly incorporated stem. At the 13th year follow up examination, the patient had no pain, used no walking aids, and had normal activity with no signs of wearing or loosening in the plain x-rays. Conclusion: Despite current recommendations of using ceramic femoral heads in cases of fracture or to revise the severely damaged stems we were able to provide a long term survivorship up to 13 years postoperatively of a cobalt-chromium femoral head applied to a severe damaged stem. PMID:28217203

Long Term Survivorship of a Severely Notched Femoral Stem after Replacing the Fractured Ceramic head with a Cobalt-Chromium Head.

PubMed

Panagopoulos, Andreas; Tatani, Irini; Megas, Panagiotis

2016-01-01

Although ceramic head fracture occurs infrequently today, in the event of a fracture, the resulting revision surgery can prove very challenging, since the ceramic particles lodge into the surrounding soft tissue and can cause rapid implant failure. A case of long term survivorship of a severed notched femoral stem after replacing the fractured femoral head with a cobalt-chromium one is reported in a 40-year old woman with hip dysplasia who underwent an uncomplicated total hip arthroplasty. The incident of ceramic femoral head fracture occurred 14 months postoperatively without reporting any significant trauma. Intraoperative findings at revision were a multifragmented femoral head and a damaged polyethylene insert along with diffuse metallosis and excessive wear of the cone of the stem. Both the stem and the acetabular component were stable. After removal of ceramic fragments, metallotic tissue excision and careful lavage of the joint, the inlay was replaced by a similar one and a cobalt-chromium femoral head was placed to the existing notched taper of the firmly incorporated stem. At the 13 th year follow up examination, the patient had no pain, used no walking aids, and had normal activity with no signs of wearing or loosening in the plain x-rays. Despite current recommendations of using ceramic femoral heads in cases of fracture or to revise the severely damaged stems we were able to provide a long term survivorship up to 13 years postoperatively of a cobalt-chromium femoral head applied to a severe damaged stem.

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.

PubMed

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

2016-03-01

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

Effects of Information Framing on the Intentions of Family Physicians to Prescribe Long-Term Hormone Replacement Therapy

PubMed Central

Nikolajevic-Sarunac, Jasminka; Henry, David A; Henry, David A; O'Connell, Dianne L; Robertson, Jane; Robertson, Jane

1999-01-01

OBJECTIVE To determine whether the way in which information on benefits and harms of long-term hormone replacement therapy (HRT) is presented influences family physicians' intentions to prescribe this treatment. DESIGN Family physicians were randomized to receive information on treatment outcomes expressed in relative terms, or as the number needing to be treated (NNT) with HRT to prevent or cause an event. A control group received no information. SETTING Primary care. PARTICIPANTS Family physicians practicing in the Hunter Valley, New South Wales, Australia. INTERVENTION Estimates of the impact of long-term HRT on risk of coronary events, hip fractures, and breast cancer were summarized as relative (proportional) decreases or increases in risk, or as NNT. MEASUREMENTS AND MAIN RESULTS Intention to prescribe HRT for seven hypothetical patients was measured on Likert scales. Of 389 family physicians working in the Hunter Valley, 243 completed the baseline survey and 215 participated in the randomized trial. Baseline intention to prescribe varied across patients—it was highest in the presence of risk factors for hip fracture, but coexisting risk factors for breast cancer had a strong negative influence. Overall, a larger proportion of subjects receiving information expressed as NNT had reduced intentions, and a smaller proportion had increased intentions to prescribe HRT than those receiving the information expressed in relative terms, or the control group. However, the differences were small and only reached statistical significance for three hypothetical patients. Framing effects were minimal when the hypothetical patient had coexisting risk factors for breast cancer. CONCLUSIONS Information framing had some effect on family physicians' intentions to prescribe HRT, but the effects were smaller than those previously reported, and they were modified by the presence of serious potential adverse treatment effects. PMID:10571703

COMPARING THE ENZYME REPLACEMENT THERAPY COST IN POST PANCREATECTOMY PATIENTS DUE TO PANCREATIC TUMOR AND CHRONIC PANCREATITIS.

PubMed

Fragoso, Anna Victoria; Pedroso, Martha Regina; Herman, Paulo; Montagnini, André Luis

2016-01-01

Among late postoperative complications of pancreatectomy are the exocrine and endocrine pancreatic insufficiencies. The presence of exocrine pancreatic insufficiency imposes, as standard treatment, pancreatic enzyme replacement. Patients with chronic pancreatitis, with intractable pain or any complications with surgical treatment, are likely to present exocrine pancreatic insufficiency or have this condition worsened requiring adequate dose of pancreatic enzymes. The aim of this study is to compare the required dose of pancreatic enzyme and the enzyme replacement cost in post pancreatectomy patients with and without chronic pancreatitis. Observational cross-sectional study. In the first half of 2015 patients treated at the clinic of the Department of Gastrointestinal Surgery at Hospital das Clínicas, Universidade de São Paulo, Brazil, who underwent pancreatectomy for at least 6 months and in use of enzyme replacement therapy were included in this series. The study was approved by the Research Ethics Committee. The patients were divided into two groups according to the presence or absence of chronic pancreatitis prior to pancreatic surgery. For this study, P<0.05 was considered statistically significant. The annual cost of the treatment was R$ 2150.5 ± 729.39; R$ 2118.18 ± 731.02 in patients without pancreatitis and R$ 2217.74 ± 736.30 in patients with pancreatitis. There was no statistically significant difference in the cost of treatment of enzyme replacement post pancreatectomy in patients with or without chronic pancreatitis prior to surgical indication.

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

PubMed

Petit-Eisenmann, Hélène; Epailly, Eric; Velten, Michel; Radojevic, Jelena; Eisenmann, Bernard; Kremer, Hélène; Kindo, Michel

2016-12-01

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 (VO 2max ). The study included 75 patients who had undergone isolated mechanical AVR for aortic stenosis with normal left ventricular (LV) function between 1994 and 2012. Their functional capacity was evaluated on average 4.6 years after AVR by exercise testing, including measurement of their VO 2max , and by determining their New York Heart Association functional class and Short Form-36 score. Two groups were defined by measuring the patients' indexed effective orifice area (iEOA) by transthoracic echocardiography: a PPM group (iEOA < 0.85 cm 2 /m 2 ) and a no-PPM group (iEOA ≥ 0.85 cm 2 /m 2 ). PPM was present in 37.0% of the patients. The percentage of the predicted VO 2max achieved was significantly lower in the PPM group (86.7 ± 19.5% vs 97.5 ± 23.0% in the no-PPM group; P = 0.04). Compared with the no-PPM group, the PPM group contained fewer patients in New York Heart Association functional class I and their mean Short Form-36 physical component summary score was significantly lower. The mean transvalvular gradient was significantly higher in the PPM group than in the no-PPM group (P < 0.001). Systolic and diastolic function and LV mass had normalized in both groups. PPM is associated in the long term with moderate but significant impairment of functional capacity, despite optimal LV reverse remodelling and normalization of LV systolic and diastolic function. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Gastrointestinal manifestations of Fabry disease: clinical response to enzyme replacement therapy.

PubMed

Banikazemi, Maryam; Ullman, Thomas; Desnick, Robert J

2005-08-01

Gastrointestinal symptoms are often an early and prominent manifestation of Fabry disease, an X-linked inborn error of metabolism caused by the deficient activity of the lysosomal enzyme, alpha-galactosidase A. This enzyme deficiency results in the progressive accumulation of globotriaosylceramide and other glycosphingolipids in tissue lysosomes throughout the body. In classically affected patients, glycosphingolipid accumulation in the vascular endothelium eventually culminates in life-threatening renal, cardiac, and cerebrovascular disease. In addition, over 50% of patients experience post-prandial abdominal pain and diarrhea that interferes with the ability to work and quality of life. Here, we describe four males aged 17-40 years with classic Fabry disease and severe gastrointestinal symptoms who participated in clinical trials of enzyme replacement therapy with agalsidase beta (Fabrazyme, 1 mg/kg every 2 weeks). Before therapy, the three adult patients experienced post-prandial abdominal pain, bloating, and severe diarrhea with 7-10 bowel movements per day every day and the 17-year-old had weekly episodes of diarrhea with six bowel movements per day. Other symptoms included vomiting, food intolerance, and poor weight gain. All patients took medications for these symptoms (diphenoxylate-atropine [Lomotil], ranitidine hydrochloride [Zantac], or sulfasalazine). After 6-7 months of agalsidase beta therapy, all patients reported "no or only occasional" abdominal pain or diarrhea, had discontinued their gastrointestinal medications, and had gained 3-8 kg. These marked improvements in gastrointestinal symptoms have persisted for over 3 years of treatment. In such patients, enzyme replacement at 1 mg/kg effects an early and significant clinical improvement in the gastrointestinal manifestations of Fabry disease.

Immune tolerance improves the efficacy of enzyme replacement therapy in canine mucopolysaccharidosis I

PubMed Central

Dickson, Patricia; Peinovich, Maryn; McEntee, Michael; Lester, Thomas; Le, Steven; Krieger, Aimee; Manuel, Hayden; Jabagat, Catherine; Passage, Merry; Kakkis, Emil D.

2008-01-01

Mucopolysaccharidoses (MPSs) are lysosomal storage diseases caused by a deficit in the enzymes needed for glycosaminoglycan (GAG) degradation. Enzyme replacement therapy with recombinant human α-l-iduronidase successfully reduces lysosomal storage in canines and humans with iduronidase-deficient MPS I, but therapy usually also induces antibodies specific for the recombinant enzyme that could reduce its efficacy. To understand the potential impact of α-l-iduronidase–specific antibodies, we studied whether inducing antigen-specific immune tolerance to iduronidase could improve the effectiveness of recombinant iduronidase treatment in canines. A total of 24 canines with MPS I were either tolerized to iduronidase or left nontolerant. All canines received i.v. recombinant iduronidase at the FDA-approved human dose or a higher dose for 9–44 weeks. Nontolerized canines developed iduronidase-specific antibodies that proportionally reduced in vitro iduronidase uptake. Immune-tolerized canines achieved increased tissue enzyme levels at either dose in most nonreticular tissues and a greater reduction in tissue GAG levels, lysosomal pathology, and urinary GAG excretion. Tolerized MPS I dogs treated with the higher dose received some further benefit in the reduction of GAGs in tissues, urine, and the heart valve. Therefore, immune tolerance to iduronidase improved the efficacy of enzyme replacement therapy with recombinant iduronidase in canine MPS I and could potentially improve outcomes in patients with MPS I and other lysosomal storage diseases. PMID:18654665

Gene therapy/bone marrow transplantation in ADA-deficient mice: roles of enzyme-replacement therapy and cytoreduction.

PubMed

Carbonaro, Denise A; Jin, Xiangyang; Wang, Xingchao; Yu, Xiao-Jin; Rozengurt, Nora; Kaufman, Michael L; Wang, Xiaoyan; Gjertson, David; Zhou, Yang; Blackburn, Michael R; Kohn, Donald B

2012-11-01

Gene therapy (GT) for adenosine deaminase-deficient severe combined immune deficiency (ADA-SCID) can provide significant long-term benefit when patients are given nonmyeloablative conditioning and ADA enzyme-replacement therapy (ERT) is withheld before autologous transplantation of γ-retroviral vector-transduced BM CD34+ cells. To determine the contributions of conditioning and discontinuation of ERT to the therapeutic effects, we analyzed these factors in Ada gene knockout mice (Ada(-/-)). Mice were transplanted with ADA-deficient marrow transduced with an ADA-expressing γ-retroviral vector without preconditioning or after 200 cGy or 900 cGy total-body irradiation and evaluated after 4 months. In all tissues analyzed, vector copy numbers (VCNs) were 100- to 1000-fold greater in mice receiving 900 cGy compared with 200 cGy (P < .05). In mice receiving 200 cGy, VCN was similar whether ERT was stopped or given for 1 or 4 months after GT. In unconditioned mice, there was decreased survival with and without ERT, and VCN was very low to undetectable. When recipients were conditioned with 200 cGy and received transduced lineage-depleted marrow, only recipients receiving ERT (1 or 4 months) had detectable vector sequences in thymocytes. In conclusion, cytoreduction is important for the engraftment of gene-transduced HSC, and short-term ERT after GT did not diminish the capacity of gene-corrected cells to engraft and persist.

Globotriaosylsphingosine (lyso-Gb3) might not be a reliable marker for monitoring the long-term therapeutic outcomes of enzyme replacement therapy for late-onset Fabry patients with the Chinese hotspot mutation (IVS4+919G>A)

PubMed Central

2014-01-01

Background In Taiwan, DNA-based newborn screening showed a surprisingly high incidence (1/875 in males and 1/399 in females) of a cardiac Fabry mutation (IVS4 + 919G > A). However, the natural course, long-term treatment outcomes and suitable biomarkers for monitoring the therapeutic outcomes of these patients are largely unknown. Methods Fabry disease (FD) patients who had received enzyme replacement therapy (ERT) for more than 1 year were enrolled in this study from December 2008 to April 2013. Periodic echocardiography and serum globotriaosylsphingosine (lyso-Gb3) analysis were carried out. Before and after ERT, left ventricular mass index (LVMI) and serum lyso-Gb3 level were compared and the correlation between the change of LVMI and the change of serum lyso-Gb3 were also analyzed. Results Thirty-six patients, in four patient groups, were enrolled: (1) 16 males with IVS4 + 919G > A mutation; (2) 7 females with IVS4 + 919G > A mutation; (3) 2 males with classical mutations; and (4) 11 females with classical mutations. The follow-up period was 13–46 months. There were significant LVMI reductions after ERT in all four groups after excluding confounding factors. However, interestingly, serum lyso-Gb3 decreased significantly in the early period after ERT in all groups, but increased gradually after an average of 11.1 months after ERT in late-onset male and female Fabry groups, even when their LVMI still decreased or remained stable. Furthermore, there was no correlation between the change of serum lyso-Gb3 and the change of LVMI in both classical and IVS4 + 919G > A FD patients. Conclusion Although lyso-Gb3 has a high diagnostic sensitivity in late-onset Fabry patients and has a good response to ERT during the early stages, it might not be a reliable marker for monitoring the long-term therapeutic outcomes of ERT for late-onset Fabry patients with the Chinese hotspot mutation (IVS4 + 919G > A). PMID:25047006

Thyroiditis de Quervain. Are there predictive factors for long-term hormone-replacement?

PubMed

Schenke, S; Klett, R; Braun, S; Zimny, M

2013-01-01

Subacute thyroiditis is a usually self-limiting disease of the thyroid. However, approximately 0.5-15% of the patients require permanent thyroxine substitution. Aim was to determine predictive factors for the necessity of long-term hormone-replacement (LTH). We retrospectively reviewed the records of 72 patients with subacute thyroiditis. Morphological and serological parameters as well as type of therapy were tested as predictive factors of consecutive hypothyroidism. Mean age was 49 ± 11 years, f/m-ratio was 4.5 : 1. Thyroid pain and signs of hyperthyroidism were leading symptoms. Initial subclinical or overt hyperthyroidism was found in 20% and 37%, respectively. Within six months after onset 15% and 1.3% of the patients developed subclinical or overt hypothyroidism, respectively. At latest follow-up 26% were classified as liable to LTH. At onset the thyroid was enlarged in 64%, and at latest follow-up in 8.3%, with a significant reduction of the thyroid volume after three months. At the endpoint the thyroid volume was less in patients in the LTH group compared with the non-LTH group (41.7% vs. 57.2% of sex-adjusted upper norm, p = 0.041). Characteristic ultrasonographic features occurred in 74% of the patients in both lobes. Serological and morphological parameters as well as type of therapy were not related with the need of LTH. In this study the proportion of patients who received LTH was 26%. At the endpoint these patients had a lower thyroid volume compared with euthyroid patients. No predictive factors for LTH were found.

Computerized cognitive testing in patients with type I Gaucher disease: effects of enzyme replacement and substrate reduction.

PubMed

Elstein, Deborah; Guedalia, Judith; Doniger, Glen M; Simon, Ely S; Antebi, Vered; Arnon, Yael; Zimran, Ari

2005-02-01

Because of concern for drug-induced cognitive dysfunction during clinical trials using substrate reduction therapy (miglustat) in type 1 Gaucher disease and because it has been suggested that some patients with type 1 Gaucher disease may develop neurocognitive impairment as part of the natural history, two different batteries of neuropsychological tests were devised to examine these issues. Using these tests, cognitive function was assessed in patients treated with miglustat, in patients receiving enzyme replacement (standard care for symptomatic patients), and in untreated (milder) patients. For this study, 55/60 patients exposed to miglustat in Israel participated in psychologist-administered testing; 36/55 participated in computerized testing. Of these, 31 enzyme-treated patients and 22 untreated patients participated in the psychologist-administered testing, and 15 enzyme-treated patients and 18 untreated patients participated in computerized testing. The psychologist-administered battery consisted of 18 standard neuropsychological subtests specific to executive and visuospatial functioning. The computerized battery (Mindstreams, NeuroTrax Corp., New York, NY) consisted of 10 subtests tapping multiple cognitive domains. Between-group analyses for each modality compared cognitive performance. In the psychologist-administered testing, patients exposed to miglustat performed significantly less well than the other groups in 5/18 subtests. On the computerized tests, all patients performed comparably to normal controls. Scores in patients exposed to miglustat were higher than in untreated patients, particularly in visuospatial function, whereas enzyme-treated patients performed less well. However, with the exception of visuospatial function, these results were not statistically significant. It is unclear why different testing methods yielded discordant results. Any dysfunction suggested by the current study is apparently subtle and of doubtful clinical relevance

Neuraxial anesthesia improves long-term survival after total joint replacement: a retrospective nationwide population-based study in Taiwan.

PubMed

Chen, Wei-Hung; Hung, Kuo-Chuan; Tan, Ping-Heng; Shi, Hon-Yi

2015-04-01

This study explored the effects of general (GA) and neuraxial (NA) anesthesia on the outcomes of primary total joint replacement (TJR) in terms of postoperative mortality, length of stay (LOS), and hospital treatment costs. From 1997 to 2010, this nationwide population-based study retrospectively evaluated 7,977 patients in Taiwan who underwent primary total hip or knee replacement. We generated two propensity-score-matched subgroups, each containing an equal number of patients who underwent TJR with either GA or NA. Of the 7,977 patients, 2,990 (37.5%) underwent GA and 4,987 (62.5%) underwent NA. Propensity-score matching was used to create comparable GA and NA groups adjusted for age, sex, comorbidities, surgery type, hospital volume, and surgeon volume. Survival over the first three years following surgery was similar. The proportion of patients alive up to 14 years postoperatively for those undergoing NA was 58.2% (95% confidence interval [CI] 50.4 to 66.0), and for those undergoing GA it was 57.3% (95% CI 51.4 to 63.2). Neuraxial anesthesia was associated with lower median [interquartile range; IQR] hospital treatment cost ($4,079 [3,805-4,444] vs $4,113 [3,812-4,568]; P < 0.001) and shorter median [IQR] LOS (8 [7-10] days vs 8 [6-10] days, respectively; P = 0.024). Our results support the use of NA for primary TJR. The improvements in hospital costs persist even when anesthesia costs are removed. The mechanism underlying the association between NA and long-term survival is unknown.

Fabry disease, enzyme replacement therapy and the significance of antibody responses.

PubMed

Deegan, Patrick B

2012-03-01

Fabry disease is an X-linked disorder caused by a deficiency of α-galactosidase A. This leads to a progressive accumulation of globotriaosylceramide in tissues throughout the body. Cardiac, renal and neurological manifestations are common and life expectancy is significantly reduced relative to the general population. Management of Fabry disease involves the administration of intravenous enzyme replacement therapy (ERT). Two forms - agalsidase alfa and agalsidase beta - have been licensed in certain jurisdictions and are generally well tolerated; however, some patients develop antibodies to the infused enzyme, which may impair the efficacy and safety of treatment. Agalsidase alfa and agalsidase beta are produced in different systems; this leads to certain differences in post-translational modification that may affect immunogenicity. Immunoglobulin (Ig) G antibodies have frequently been reported in patients with Fabry disease receiving ERT; IgG responses are reported in a greater proportion of patients receiving agalsidase beta than in patients receiving agalsidase alfa. IgE antibodies are less common than IgG antibodies, and have not been observed in patients receiving agalsidase alfa. However, these data are difficult to interpret due to methodological differences in the assessment of seropositivity, and in the doses of enzyme used. The clinical impact of the development of IgG antibodies to ERT in patients with Fabry disease remains unclear, due to lack of data and to the marked heterogeneity of patients both in terms of disease manifestations and response to therapy. Further studies that examine the development of antibodies in patients with Fabry disease and the potential impact of such antibodies on the outcome of ERT are necessary.

Reduction of healthcare-associated infections in a long-term care brain injury ward by replacing regular linens with biocidal copper oxide impregnated linens.

PubMed

Lazary, A; Weinberg, I; Vatine, J-J; Jefidoff, A; Bardenstein, R; Borkow, G; Ohana, N

2014-07-01

Contaminated textiles in hospitals contribute to endogenous, indirect-contact, and aerosol transmission of nosocomial related pathogens. Copper oxide impregnated linens have wide-spectrum antimicrobial, antifungal, and antiviral properties. Our aim was to determine if replacing non-biocidal linens with biocidal copper oxide impregnated linens would reduce the rates of healthcare-associated infections (HAI) in a long-term care ward. We compared the rates of HAI in two analogous patient cohorts in a head injury care ward over two 6-month parallel periods before (period A) and after (period B) replacing all the regular non-biocidal linens and personnel uniforms with copper oxide impregnated biocidal products. During period B, in comparison to period A, there was a 24% reduction in the HAI per 1000 hospitalization-days (p<0.05), a 47% reduction in the number of fever days (>38.5°C) per 1000 hospitalization-days (p<0.01), and a 32.8% reduction in total number of days of antibiotic administration per 1000 hospitalization-days (p<0.0001). Accordingly there was saving of approximately 27% in costs of antibiotics, HAI-related treatments, X-rays, disposables, labor, and laundry, expenses during period B. The use of biocidal copper oxide impregnated textiles in a long-term care ward may significantly reduce HAI, fever, antibiotic consumption, and related treatment costs. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Expensive drugs for rare disorders: to treat or not to treat? The case of enzyme replacement therapy for mucopolysaccharidosis VI.

PubMed

Schlander, M; Beck, M

2009-05-01

Mucopolysaccharidosis VI (MPS VI) is a very rare, chronically debilitating lysosomal storage disorder that develops in people with an enzyme deficiency. Clinical characteristics and progression rates vary widely between patients. The recent introduction of enzyme replacement therapy (ERT) has improved considerably the lives of patients with MPS VI, at an annual cost of treatment between euro 150,000 and euro 450,000 per patient. This Commentary article addresses the controversial topic of granting reimbursement for expensive treatment options for orphan diseases, such as MPS VI. The discussion reflects clinical, economic and ethical aspects and incorporates insights from the relevant literature (based on a Medline search to September 2008) on MPS VI, efficacy of ERT, orphan drugs, and the economics and ethics of health-care prioritisation. Although ERT for MPS VI received marketing authorisation in the European Union in January 2006, patients' access to this therapy varies geographically due to differences between national reimbursement schemes for orphan drugs. Some inclusion and exclusion criteria for treatment of MPS VI patients with ERT appear arbitrary and may contribute to the exclusion from treatment of patients who could benefit in the long term. Reimbursement schemes which rely on proof of short-term treatment effectiveness may discriminate against slowly progressive patients, as health gain can often not be confirmed over a short period of time in these patients. Conventional cost-effectiveness analysis remains silent on crucial issues related to budgetary impact, i.e. opportunity cost from a system perspective, and fair access to treatment. To prevent patients from being deprived of effective treatment, it is suggested that inclusion and exclusion criteria for treatment should be primarily based on a careful individual assessment of expected long-term clinical benefits. Once treatment has been agreed to as the correct option on clinical grounds, it is

HDAC inhibition modulates hippocampus-dependent long-term memory for object location in a CBP-dependent manner

PubMed Central

Haettig, Jakob; Stefanko, Daniel P.; Multani, Monica L.; Figueroa, Dario X.; McQuown, Susan C.; Wood, Marcelo A.

2011-01-01

Transcription of genes required for long-term memory not only involves transcription factors, but also enzymatic protein complexes that modify chromatin structure. Chromatin-modifying enzymes, such as the histone acetyltransferase (HAT) CREB (cyclic-AMP response element binding) binding protein (CBP), are pivotal for the transcriptional regulation required for long-term memory. Several studies have shown that CBP and histone acetylation are necessary for hippocampus-dependent long-term memory and hippocampal long-term potentiation (LTP). Importantly, every genetically modified Cbp mutant mouse exhibits long-term memory impairments in object recognition. However, the role of the hippocampus in object recognition is controversial. To better understand how chromatin-modifying enzymes modulate long-term memory for object recognition, we first examined the role of the hippocampus in retrieval of long-term memory for object recognition or object location. Muscimol inactivation of the dorsal hippocampus prior to retrieval had no effect on long-term memory for object recognition, but completely blocked long-term memory for object location. This was consistent with experiments showing that muscimol inactivation of the hippocampus had no effect on long-term memory for the object itself, supporting the idea that the hippocampus encodes spatial information about an object (such as location or context), whereas cortical areas (such as the perirhinal or insular cortex) encode information about the object itself. Using location-dependent object recognition tasks that engage the hippocampus, we demonstrate that CBP is essential for the modulation of long-term memory via HDAC inhibition. Together, these results indicate that HDAC inhibition modulates memory in the hippocampus via CBP and that different brain regions utilize different chromatin-modifying enzymes to regulate learning and memory. PMID:21224411

Resolution of Hydronephrosis in a Patient With Mucopolysaccharidosis Type II With Enzyme Replacement Therapy.

PubMed

Nishiyama, Kei; Imai, Takashi; Ohkubo, Kazuhiro; Sanefuji, Masafumi; Takada, Hidetoshi

2017-03-01

Mucopolysaccharidosis type II (MPS II) is caused by deficiency of lysosomal enzyme iduronate-2-sulfatase. Insufficient activity of the enzyme results in accumulation of glycosaminoglycans leading to progressive multisystem pathologies. MPS II is less likely to be complicated by kidney and urinary tract problems. We report a boy with MPS II, who developed left hydronephrosis. His hydronephrosis improved after starting enzyme replacement therapy. It was suggested that MPS II was closely associated with the pathogenesis of hydronephrosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Long-Term Dose-Dependent Agalsidase Effects on Kidney Histology in Fabry Disease.

PubMed

Skrunes, Rannveig; Tøndel, Camilla; Leh, Sabine; Larsen, Kristin Kampevold; Houge, Gunnar; Davidsen, Einar Skulstad; Hollak, Carla; van Kuilenburg, André B P; Vaz, Frédéric M; Svarstad, Einar

2017-09-07

Dose-dependent clearing of podocyte globotriaosylceramide has previously been shown in patients with classic Fabry disease treated with enzyme replacement. Our study evaluates the dose-dependent effects of agalsidase therapy in serial kidney biopsies of patients treated for up to 14 years. Twenty patients with classic Fabry disease (12 men) started enzyme replacement therapy at a median age of 21 (range =7-62) years old. Agalsidase- α or - β was prescribed for a median of 9.4 (range =5-14) years. The lower fixed dose group received agalsidase 0.2 mg/kg every other week throughout the follow-up period. The higher dose group received a range of agalsidase doses (0.2-1.0 mg/kg every other week). Dose changes were made due to disease progression, suboptimal effect, or agalsidase- β shortage. Serial kidney biopsies were performed along with clinical assessment and biomarkers and scored according to recommendations from the International Study Group of Fabry Nephropathy. No statistical differences were found in baseline or final GFR or albuminuria. Kidney biopsies showed significant reduction of podocyte globotriaosylceramide in both the lower fixed dose group (-1.39 [SD=1.04]; P =0.004) and the higher dose group (-3.16 [SD=2.39]; P =0.002). Podocyte globotriaosylceramide (Gb3) reduction correlated with cumulative agalsidase dose ( r =0.69; P =0.001). Arterial/arteriolar intima Gb3 cleared significantly in the higher dose group, all seven patients with baseline intimal Gb3 cleared the intima, one patient gained intimal Gb3 inclusions ( P =0.03), and medial Gb3 did not change statistically in either group. Residual plasma globotriaosylsphingosine levels remained higher in the lower fixed dose group (20.1 nmol/L [SD=11.9]) compared with the higher dose group (10.4 nmol/L [SD=8.4]) and correlated with cumulative agalsidase dose in men ( r =0.71; P =0.01). Reduction of podocyte globotriaosylceramide was found in patients with classic Fabry disease treated with long-term

Lazy workers are necessary for long-term sustainability in insect societies

PubMed Central

Hasegawa, Eisuke; Ishii, Yasunori; Tada, Koichiro; Kobayashi, Kazuya; Yoshimura, Jin

2016-01-01

Optimality theory predicts the maximization of productivity in social insect colonies, but many inactive workers are found in ant colonies. Indeed, the low short-term productivity of ant colonies is often the consequence of high variation among workers in the threshold to respond to task-related stimuli. Why is such an inefficient strategy among colonies maintained by natural selection? Here, we show that inactive workers are necessary for the long-term sustainability of a colony. Our simulation shows that colonies with variable thresholds persist longer than those with invariable thresholds because inactive workers perform the critical function of replacing active workers when they become fatigued. Evidence of the replacement of active workers by inactive workers has been found in ant colonies. Thus, the presence of inactive workers increases the long-term persistence of the colony at the expense of decreasing short-term productivity. Inactive workers may represent a bet-hedging strategy in response to environmental stochasticity. PMID:26880339

Gene therapy/bone marrow transplantation in ADA-deficient mice: roles of enzyme-replacement therapy and cytoreduction

PubMed Central

Jin, Xiangyang; Wang, Xingchao; Yu, Xiao-Jin; Rozengurt, Nora; Kaufman, Michael L.; Wang, Xiaoyan; Gjertson, David; Zhou, Yang; Blackburn, Michael R.; Kohn, Donald B.

2012-01-01

Gene therapy (GT) for adenosine deaminase–deficient severe combined immune deficiency (ADA-SCID) can provide significant long-term benefit when patients are given nonmyeloablative conditioning and ADA enzyme-replacement therapy (ERT) is withheld before autologous transplantation of γ-retroviral vector-transduced BM CD34+ cells. To determine the contributions of conditioning and discontinuation of ERT to the therapeutic effects, we analyzed these factors in Ada gene knockout mice (Ada−/−). Mice were transplanted with ADA-deficient marrow transduced with an ADA-expressing γ-retroviral vector without preconditioning or after 200 cGy or 900 cGy total-body irradiation and evaluated after 4 months. In all tissues analyzed, vector copy numbers (VCNs) were 100- to 1000-fold greater in mice receiving 900 cGy compared with 200 cGy (P < .05). In mice receiving 200 cGy, VCN was similar whether ERT was stopped or given for 1 or 4 months after GT. In unconditioned mice, there was decreased survival with and without ERT, and VCN was very low to undetectable. When recipients were conditioned with 200 cGy and received transduced lineage-depleted marrow, only recipients receiving ERT (1 or 4 months) had detectable vector sequences in thymocytes. In conclusion, cytoreduction is important for the engraftment of gene-transduced HSC, and short-term ERT after GT did not diminish the capacity of gene-corrected cells to engraft and persist. PMID:22833548

Long-term outcome on renal replacement therapy in patients who previously received a keto acid-supplemented very-low-protein diet.

PubMed

Chauveau, Philippe; Couzi, Lionel; Vendrely, Benoit; de Précigout, Valérie; Combe, Christian; Fouque, Denis; Aparicio, Michel

2009-10-01

The consequences of a supplemented very-low-protein diet remain a matter of debate with regard to patient outcome before or after the onset of renal replacement therapy. We evaluated the long-term clinical outcome during maintenance dialysis and/or transplantation in patients who previously received a supplemented very-low-protein diet. We assessed the outcome of 203 patients who received a supplemented very-low-protein diet for >3 mo (inclusion period: 1985-2000) and started dialysis after a mean diet duration of 33.1 mo (4-230 mo). The survival rate in the whole cohort was 79% and 63% at 5 and 10 y, respectively. One hundred two patients continued with chronic dialysis during the entire follow-up, and 101 patients were grafted at least once. Patient outcomes were similar to those of the French Dialysis Registry patients for the dialysis group and similar to the 865 patients who were transplanted in Bordeaux during the same period for the transplant group. There was no correlation between death rate and duration of diet. The lack of correlation between death rate and duration of diet and the moderate mortality rate observed during the first 10 y of renal replacement therapy confirm that a supplemented very-low-protein diet has no detrimental effect on the outcome of patients with chronic kidney disease who receive renal replacement therapy.

The impact of the immune system on the safety and efficiency of enzyme replacement therapy in lysosomal storage disorders.

PubMed

Broomfield, A; Jones, S A; Hughes, S M; Bigger, B W

2016-07-01

In the light of clinical experience in infantile onset Pompe patients, the immunological impact on the tolerability and long-term efficacy of enzyme replacement therapy (ERT) for lysosomal storage disorders has come under renewed scrutiny. This article details the currently proposed immunological mechanisms involved in the development of anti-drug antibodies and the current therapies used in their treatment. Given the current understanding of the adaptive immune response, it focuses particularly on T cell dependent mechanisms and the paradigm of using lymphocytic negative selection as a predictor of antibody formation. This concept originally postulated in the 1970s, stipulated that the genotypically determined lack of production or production of a variant protein determines an individual's lymphocytic repertoire. This in turn is the key factor in determining the potential severity of an individual's immunological response to ERT. It also highlights the need for immunological assay standardization particularly those looking at describing the degree of functional impact, robust biochemical or clinical endpoints and detailed patient subgroup identification if the true evaluations of impact are to be realised.

The association between renal recovery after acute kidney injury and long-term mortality after transcatheter aortic valve replacement.

PubMed

Thongprayoon, Charat; Cheungpasitporn, Wisit; Srivali, Narat; Kittanamongkolchai, Wonngarm; Sakhuja, Ankit; Greason, Kevin L; Kashani, Kianoush B

2017-01-01

This study aimed to examine the association between renal recovery status at hospital discharge after acute kidney injury (AKI) and long-term mortality following transcatheter aortic valve replacement (TAVR). We screened all adult patients who survived to hospital discharge after TAVR for aortic stenosis at a quaternary referral medical center from January 1, 2008, through June 30, 2014. An AKI was defined as an increase in serum creatinine level of 0.3 mg/dL or a relative increase of 50% from baseline. Renal outcome at the time of discharge was evaluated by comparing the discharge serum creatinine level to the baseline level. Complete renal recovery was defined as no AKI at discharge, whereas partial renal recovery was defined as AKI without a need for renal replacement therapy at discharge. No renal recovery was defined as a need for renal replacement therapy at discharge. The study included 374 patients. Ninty-eight (26%) patients developed AKI during hospitalization: 55 (56%) had complete recovery; 39 (40%), partial recovery; and 4 (4%), no recovery. AKI development was significantly associated with increased risk of 2-year mortality (hazard ratio [HR], 2.20 [95% CI, 1.37-3.49]). For patients with AKI, the 2-year mortality rate for complete recovery was 34%; for partial recovery, 43%; and for no recovery, 75%; compared with 20% for patients without AKI (P < .001). In adjusted analysis, complete recovery (HR, 1.87 [95% CI, 1.03-3.23]); partial recovery (HR, 2.65 [95% CI, 1.40-4.71]) and no recovery (HR, 10.95 [95% CI, 2.59-31.49]) after AKI vs no AKI were significantly associated with increased risk of 2-year mortality. The mortality rate increased for all patients with AKI undergoing TAVR. A reverse correlation existed for progressively higher risk of death and the extent of AKI recovery.

Transmission of the PabI family of restriction DNA glycosylase genes: mobility and long-term inheritance.

PubMed

Kojima, Kenji K; Kobayashi, Ichizo

2015-10-19

R.PabI is an exceptional restriction enzyme that functions as a DNA glycosylase. The enzyme excises an unmethylated base from its recognition sequence to generate apurinic/apyrimidinic (AP) sites, and also displays AP lyase activity, cleaving the DNA backbone at the AP site to generate the 3'-phospho alpha, beta-unsaturated aldehyde end in addition to the 5'-phosphate end. The resulting ends are difficult to religate with DNA ligase. The enzyme was originally isolated in Pyrococcus, a hyperthermophilic archaeon, and additional homologs subsequently identified in the epsilon class of the Gram-negative bacterial phylum Proteobacteria, such as Helicobacter pylori. Systematic analysis of R.PabI homologs and their neighboring genes in sequenced genomes revealed co-occurrence of R.PabI with M.PabI homolog methyltransferase genes. R.PabI and M.PabI homolog genes are occasionally found at corresponding (orthologous) loci in different species, such as Helicobacter pylori, Helicobacter acinonychis and Helicobacter cetorum, indicating long-term maintenance of the gene pair. One R.PabI and M.PabI homolog gene pair is observed immediately after the GMP synthase gene in both Campylobacter and Helicobacter, representing orthologs beyond genera. The mobility of the PabI family of restriction-modification (RM) system between genomes is evident upon comparison of genomes of sibling strains/species. Analysis of R.PabI and M.PabI homologs in H. pylori revealed an insertion of integrative and conjugative elements (ICE), and replacement with a gene of unknown function that may specify a membrane-associated toxin (hrgC). In view of the similarity of HrgC with toxins in type I toxin-antitoxin systems, we addressed the biological significance of this substitution. Our data indicate that replacement with hrgC occurred in the common ancestor of hspAmerind and hspEAsia. Subsequently, H. pylori with and without hrgC were intermixed at this locus, leading to complex distribution of hrgC in East

Enzyme replacement therapy with velmanase alfa (human recombinant alpha-mannosidase): Novel global treatment response model and outcomes in patients with alpha-mannosidosis.

PubMed

Harmatz, Paul; Cattaneo, Federica; Ardigò, Diego; Geraci, Silvia; Hennermann, Julia B; Guffon, Nathalie; Lund, Allan; Hendriksz, Christian J; Borgwardt, Line

2018-06-01

Alpha-mannosidosis is an ultra-rare monogenic disorder resulting from a deficiency in the lysosomal enzyme alpha-mannosidase, with a prevalence estimated to be as low as 1:1,000,000 live births. The resulting accumulation of mannose-rich oligosaccharides in all tissues leads to a very heterogeneous disorder with a continuum of clinical manifestations with no distinctive phenotypes. Long-term enzyme replacement therapy (ERT) with velmanase alfa is approved in Europe for the treatment of non-neurological manifestations in patients with mild to moderate alpha-mannosidosis. The clinical heterogeneity and rarity of the disease limit the sensitivity of single parameters to detect clinically relevant treatment effects. Thus, we propose a novel multiple variable responder analysis to evaluate the efficacy of ERT for alpha-mannosidosis and present efficacy analyses for velmanase alfa using this method. Global treatment response to velmanase alfa (defined by response to ≥2 domains comprising pharmacodynamic, functional, and quality of life outcomes) was applied post hoc to data from the pivotal placebo-controlled rhLAMAN-05 study and to the longer-term integrated data from all patients in the clinical development program (rhLAMAN-10). After 12 months of treatment, a global treatment response was achieved by 87% of patients receiving velmanase alfa (n = 15) compared with 30% of patients receiving placebo (n = 10). Longer-term data from all patients in the clinical program (n = 33) showed 88% of patients were global responders, including all (100%) pediatric patients (n = 19) and the majority (71%) of adult patients (n = 14). The responder analysis model demonstrates a clinically meaningful treatment effect with velmanase alfa and supports the early initiation and continued benefit of longer-term treatment of all patients with alpha-mannosidosis with this ERT. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Effects of long-term estrogen replacement therapy on bone turnover in periarticular tibial osteophytes in surgically postmenopausal cynomolgus monkeys

PubMed Central

Olson, Erik J.; Lindgren, Bruce R.; Carlson, Cathy S.

2008-01-01

The aims of the present study were to assess the effects of long-term estrogen replacement therapy (ERT) on size and indices of bone turnover in periarticular osteophytes in ovariectomized cynomolgus monkeys and to compare dynamic indices of bone turnover in osteophyte bone with those of subchondral bone (SCB) and epiphyseal/metaphyseal cancellous (EMC) bone. One hundred sixty-five adult female cynomolgus macaques were bilaterally ovariectomized and randomly divided into three age- and weight-matched treatment groups for a 36-month treatment period. Group 1 (OVX control) received no treatment, Group 2 (SPE) received soy phytoestrogens, and Group 3 (ERT) received conjugated equine estrogens in the diet; all monkeys were labeled with calcein before necropsy. A midcoronal, plastic-embedded section of the right proximal tibia from 20 randomly selected animals per treatment group was examined histologically. Forty-nine of the sections (OVX control, n=16; SPE, n=16; ERT, n=17) contained lateral abaxial osteophytes, and static and dynamic histomorphometry measurements were taken from osteophyte bone, SCB from the lateral tibial plateau, and EMC bone. Data were analyzed using the ANOVA and Kruskal-Wallis test, correlation and regression methods, and the Friedman and Wilcoxon signed rank test. There was no significant effect of long-term ERT on osteophyte area or on any static or dynamic histomorphometry parameters. The bone volume, trabecular number, and trabecular thickness in osteophyte bone were considerably higher than in EMC bone; whereas, trabecular separation was considerably lower in osteophyte bone. In all three treatment groups, BS/BV was significantly lower in osteophyte bone vs. EMC bone and significantly higher in osteophyte bone vs. lateral SCB. We conclude that osteophyte area and static and dynamic histomorphometry parameters within periarticular tibial osteophytes in ovariectomized cynomolgus monkeys are not significantly influenced by long-term ERT, but

Effects of long-term estrogen replacement therapy on bone turnover in periarticular tibial osteophytes in surgically postmenopausal cynomolgus monkeys.

PubMed

Olson, Erik J; Lindgren, Bruce R; Carlson, Cathy S

2008-05-01

The aims of the present study were to assess the effects of long-term estrogen replacement therapy (ERT) on size and indices of bone turnover in periarticular osteophytes in ovariectomized cynomolgus monkeys and to compare dynamic indices of bone turnover in osteophyte bone with those of subchondral bone (SCB) and epiphyseal/metaphyseal cancellous (EMC) bone. One hundred sixty-five adult female cynomolgus macaques were bilaterally ovariectomized and randomly divided into three age- and weight-matched treatment groups for a 36-month treatment period. Group 1 (OVX control) received no treatment, Group 2 (SPE) received soy phytoestrogens, and Group 3 (ERT) received conjugated equine estrogens in the diet; all monkeys were labeled with calcein before necropsy. A midcoronal, plastic-embedded section of the right proximal tibia from 20 randomly selected animals per treatment group was examined histologically. Forty-nine of the sections (OVX control, n=16; SPE, n=16; ERT, n=17) contained lateral abaxial osteophytes, and static and dynamic histomorphometry measurements were taken from osteophyte bone, SCB from the lateral tibial plateau, and EMC bone. Data were analyzed using the ANOVA and Kruskal-Wallis test, correlation and regression methods, and the Friedman and Wilcoxon signed rank test. There was no significant effect of long-term ERT on osteophyte area or on any static or dynamic histomorphometry parameters. The bone volume, trabecular number, and trabecular thickness in osteophyte bone were considerably higher than in EMC bone; whereas, trabecular separation was considerably lower in osteophyte bone. In all three treatment groups, BS/BV was significantly lower in osteophyte bone vs. EMC bone and significantly higher in osteophyte bone vs. lateral SCB. We conclude that osteophyte area and static and dynamic histomorphometry parameters within periarticular tibial osteophytes in ovariectomized cynomolgus monkeys are not significantly influenced by long-term ERT, but

Long-term effectiveness of mailed nicotine replacement therapy: study protocol of a randomized controlled trial 5-year follow-up.

PubMed

Kushnir, Vladyslav; Selby, Peter; Zawertailo, Laurie; Tyndale, Rachel F; Leatherdale, Scott T; Cunningham, John A

2017-07-18

Our group recently completed a randomized controlled trial, evaluating the efficacy of providing 5 weeks of free nicotine replacement therapy (NRT; in the form of the nicotine patch) by expedited postal mail without behavioral assistance to regular adult smokers interested in receiving it. The findings revealed that mailed provision of nicotine patches resulted in more than a doubling of quit rates at a six-month follow-up compared to a no intervention control group. While this trial provided evidence for the effectiveness of mailed nicotine patches in promoting cessation, the findings speak only to the short term effectiveness of this approach. As relapse to smoking is known to occur beyond the 6 month period, it is important to evaluate whether the net benefit of NRT in naturalistic settings can be maintained long-term. The present study aims to perform a 5-year follow-up survey of participants in the original trial to evaluate the long-term effectiveness of mailed NRT. Trained interviewers will contact participants in the randomized controlled trial 5 years post-enrollment. A total of 924 participants will be eligible to be contacted. Interviewers will first assess participants' smoking status and their level of nicotine dependence. Participants reporting not currently smoking will be asked whether they have smoked tobacco, even a puff, in the last 30 days (primary outcome measure: 30-day point prevalence abstinence), past 6 months (secondary outcome measure: prolonged 6-month abstinence), and since the 8-week follow-up survey (secondary outcome measure: > 4 year continuous abstinence). Interviewers will be blind to experimental condition at the time the primary outcome measure will be assessed. It is hypothesized that participants who received nicotine patches at baseline will display significantly higher quit rates at the 5-year follow-up as compared to participants who did not receive nicotine patches at baseline. If the study finds that the mailed

Testosterone Replacement Therapy: Long-Term Safety and Efficacy

PubMed Central

Corona, Giovanni; Sforza, Alessandra

2017-01-01

Recent position statements and guidelines have raised the distinction between a true and false, age-related hypogonadism (HG) or late-onset hypogonadism (LOH). The former is the consequence of congenital or acquired “organic” damage of the brain centers or of the testis. The latter is mainly secondary to age-related comorbidities and does not require testosterone (T) therapy (TTh). In addition, concerns related to cardiovascular (CV) safety have further increased the scepticism related to TTh. In this paper, we reviewed the available evidence supporting the efficacy of TTh in non-organic HG and its long term safety. A large amount of evidence has documented that sexual symptoms are the most specific correlates of T deficiency. TTh is able to improve all aspects of sexual function independent of the pathogenetic origin of the disease supporting the scientific demonstration that LOH does exist according to an “ex-juvantibus” criterion. Although the presence of metabolic derangements could mitigate the efficacy of TTh on erectile dysfunction, the positive effect of TTh on body composition and insulin sensitivity might counterbalance the lower efficacy. CV safety concerns related to TTh are essentially based on a limited number of observational and randomized controlled trials which present important methodological flaws. When HG is properly diagnosed and TTh correctly performed no CV and prostate risk have been documented. PMID:28497912

Testosterone Replacement Therapy: Long-Term Safety and Efficacy.

PubMed

Corona, Giovanni; Sforza, Alessandra; Maggi, Mario

2017-08-01

Recent position statements and guidelines have raised the distinction between a true and false, age-related hypogonadism (HG) or late-onset hypogonadism (LOH). The former is the consequence of congenital or acquired "organic" damage of the brain centers or of the testis. The latter is mainly secondary to age-related comorbidities and does not require testosterone (T) therapy (TTh). In addition, concerns related to cardiovascular (CV) safety have further increased the scepticism related to TTh. In this paper, we reviewed the available evidence supporting the efficacy of TTh in non-organic HG and its long term safety. A large amount of evidence has documented that sexual symptoms are the most specific correlates of T deficiency. TTh is able to improve all aspects of sexual function independent of the pathogenetic origin of the disease supporting the scientific demonstration that LOH does exist according to an "ex-juvantibus" criterion. Although the presence of metabolic derangements could mitigate the efficacy of TTh on erectile dysfunction, the positive effect of TTh on body composition and insulin sensitivity might counterbalance the lower efficacy. CV safety concerns related to TTh are essentially based on a limited number of observational and randomized controlled trials which present important methodological flaws. When HG is properly diagnosed and TTh correctly performed no CV and prostate risk have been documented. Copyright © 2017 Korean Society for Sexual Medicine and Andrology.

Vesico-ureteric reflux: occurrence and long-term risks.

PubMed

Jacobson, S H; Hansson, S; Jakobsson, B

1999-11-01

The prevalence of vesico-ureteric reflux in the general population is unknown, but it is increased in risk groups, such as children with symptomatic urinary tract infection, schoolgirls with asymptomatic bacteriuria, first-degree relatives of patients with reflux and children with prenatal dilatation of their upper urinary tract. Children and adults with pyelonephritic renal scarring are at risk of serious long-term complications, e.g. hypertension and renal failure. Modern paediatric care, with early detection and treatment of urinary tract infections and reflux during childhood and adolescence, may improve long-term prognosis. In the adult patient with established pyelonephritic renal scarring, careful control of hypertension may retard the rate of progression, and angiotensin converting enzyme inhibitors may have renal protective properties.

Long-term hearing result using Kurz titanium ossicular implants.

PubMed

Hess-Erga, Jeanette; Møller, Per; Vassbotn, Flemming Slinning

2013-05-01

Titanium implants in middle ear surgery were introduced in the late 90s and are now frequently used in middle ear surgery. However, long-term studies of patient outcome are few and have only been published in subgroups of patients. We report the long-term effect of titanium middle ear implants for ossicular reconstruction in chronic ear disease investigated in a Norwegian tertiary otological referral centre. Retrospective chart reviews were performed for procedures involving 76 titanium implants between 2000 and 2007. All patients who underwent surgery using the Kurz Vario titanium implant were included in the study. Audiological parameters using four frequencies, 0.5, 1, 2, and 3 kHz, according to AAO-HNS guidelines, was assessed pre and postoperatively. Otosurgical procedures, complications, revisions, and extrusion rates were analyzed. The study had no dropouts. The partial ossicular replacement prosthesis (PORP) was used in 44 procedures and the total ossicular replacement prosthesis (TORP) in 32 procedures, respectively. Mean follow-up was 5.2 years (62 months). The ossiculoplasties were performed as staging procedures or in combination with other chronic ear surgery. The same surgeon performed all the procedures. A postoperative air-bone gap of ≤ 20 dB was obtained in 74 % of the patients, 82 % for the Bell (PORP) prosthesis, and 63 % for the Arial (TORP) prosthesis. The extrusion rate was 5 %. We conclude that titanium ossicular implants give stable and excellent long-term hearing results.

[Risk for hyperkalemia during long-term treatment with angiotensin-converting enzyme inhibitors in insulin-dependent type 2 diabetics in relation to the glomerular filtration rate].

PubMed

Raml, A; Schmekal, B; Grafinger, P; Biesenbach, G

2001-11-23

The risk for hyperkalaemia during therapy with angiotensin-converting enzyme inhibitors is especially increased in the elderly diabetic because of a decrease in glomerular filtration rate (GFR), as well as the occurrence of hyporeninaemic hypoaldosteronism. We evaluated the risk for hyperkalaemia under long-term angiotensin-converting enyzme inhibition in 86 insulin-dependent type 2 diabetic patients in relation to their GFR. We compared the influence of a 3 to 6 months long treatment with angiotensin-converting enzyme inhibitors on the serum potassium levels, the creatinine clearance and the urinary albumin excretion in insulin-dependent type 2 diabetic patients with an initial creatinine clearance < 50 ml/min/1.73m(2) (n = 15, age 66 +/- 6 years) and >/= 50 ml/min/1.73m(2) respectively (n = 71, age 61 +/- 10 years). In addition, we also investigated the influence on the metabolic control and the blood pressure values in both groups of patients. In the patients with creatinine clearance >/= 50 ml/min/1,73m(2) the mean potassium level increased from 4.3 +/- 0.2 to 4.6 +/- 0.4 mmol/l (P < 0,01), while the incidence of a potassium level > 5 mmol/l was 17 %. In the group with a creatinine clearance < 50 ml/min/1.73m(2) the potassium level rose from 4.5 +/- 0.2 to 5.0 +/- 0.4 mmol/l (P < 0.01). The incidence of potassium levels > 5 mmol/l was 66 % (P < 0,01). In both patient groups the creatinine clearances did not change significantly during angiotensin-converting enzyme inhibition, and the urinary albumin excretion as well as the HbA(1c) values and blood pressure showed only a tendency towards a decrease. Long-term treatment with angiotensin-converting enzyme inhibitors in insulin-dependent type 2 diabetic patients leads to a significant increase in serum potassium. The incidence of hyperkalaemia with potassium levels > 5 mmol/l is significantly higher in the patients with initial creatinine clearance < 50 ml/min/1.73m(2). Severe hyperkalaemia with potassium levels

Hypomagnesaemia associated with long-term use of proton pump inhibitors

PubMed Central

Toh, James Wei Tatt; Ong, Evonne; Wilson, Robert

2015-01-01

Hypomagnesaemia and associated hypocalcaemia and hypoparathyroidism have been increasingly recognised as rare long-term side-effects of proton pump inhibitors (PPIs). The PPIs may inhibit active magnesium (Mg) absorption by interfering with transcellular transient receptor potential melastatin-6 and -7 (TRPM 6 and 7) channels. More recent cell culture studies have suggested concomitant inhibition of passive Mg absorption by omeprazole. After being treated with a range of PPIs, the four patients in our case series developed hypomagnesaemia, which responded to withdrawal of therapy and initiation of Mg replacement. Their clinical course and management demonstrate key aspects of hypomagnesaemia associated with long-term use of PPIs. PMID:25138239

Replacement of long segments of the esophagus with a collagen-silicone composite tube.

PubMed

Takimoto, Y; Nakamura, T; Teramachi, M; Kiyotani, T; Shimizu, Y

1995-01-01

Artificial esophagi designed thus far can be classified into three types in terms of the materials used: natural, artificial, and composite. In conventional models, even when artificial esophagi were made of ideal materials with high tissue affinity, they remained in the tissue as a foreign body, and therefore were not free of the complications caused by implanted material. The authors have designed a new type of artificial esophagus composed of a Silicone tube covered with nonantigenic collagen. The novel feature of this artificial esophagus is that the prosthesis does not remain in the implanted site, but is replaced by regenerated host tissue. Using this artificial esophagus, the authors have already succeeded in replacing a 5 cm gap in the esophagus. In this study, replacement of longer portions of the esophagus was assessed in seven dogs using a 10 cm long artificial esophagus. Stenosis did not occur in five of the seven dogs and, consequently, these dogs survived by oral feeding alone for more than 6 months without dry weight loss. The other two animals died of anesthetic accidents at the time of stent removal 6 weeks after surgery. In both cases, the internal surface of the neoesophagus was covered with a polylayer of squamous epithelium. Regenerated esophagi had normal esophageal glands and immature muscle tissue. It is therefore concluded that this new artificial esophagus is also applicable for replacement of long segments of esophagus.

Guanidinylated Neomycin Conjugation Enhances Intranasal Enzyme Replacement in the Brain.

PubMed

Tong, Wenyong; Dwyer, Chrissa A; Thacker, Bryan E; Glass, Charles A; Brown, Jillian R; Hamill, Kristina; Moremen, Kelley W; Sarrazin, Stéphane; Gordts, Philip L S M; Dozier, Lara E; Patrick, Gentry N; Tor, Yitzhak; Esko, Jeffrey D

2017-12-06

Iduronidase (IDUA)-deficient mice accumulate glycosaminoglycans in cells and tissues and exhibit many of the same neuropathological symptoms of patients suffering from Mucopolysaccharidosis I. Intravenous enzyme-replacement therapy for Mucopolysaccharidosis I ameliorates glycosaminoglycan storage and many of the somatic aspects of the disease but fails to treat neurological symptoms due to poor transport across the blood-brain barrier. In this study, we examined the delivery of IDUA conjugated to guanidinoneomycin (GNeo), a molecular transporter. GNeo-IDUA and IDUA injected intravenously resulted in reduced hepatic glycosaminoglycan accumulation but had no effect in the brain due to fast clearance from the circulation. In contrast, intranasally administered GNeo-IDUA entered the brain rapidly. Repetitive intranasal treatment with GNeo-IDUA reduced glycosaminoglycan storage, lysosome size and number, and neurodegenerative astrogliosis in the olfactory bulb and primary somatosensory cortex, whereas IDUA was less effective. The enhanced efficacy of GNeo-IDUA was not the result of increased nose-to-brain delivery or enzyme stability, but rather due to more efficient uptake into neurons and astrocytes. GNeo conjugation also enhanced glycosaminoglycan clearance by intranasally delivered sulfamidase to the brain of sulfamidase-deficient mice, a model of Mucopolysaccharidosis IIIA. These findings suggest the general utility of the guanidinoglycoside-based delivery system for restoring missing lysosomal enzymes in the brain. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Long-term stability of GOES-8 and -9 attitude control

NASA Astrophysics Data System (ADS)

Carr, James L.

1996-10-01

An independent audit of the in-orbit behavior of the GOES-8 and GOES-9 satellites has been conducted for the NASA/GSFC. This audit utilized star and landmark observations from the GOES imager to determine long-term histories for spacecraft attitude, orbital position, and instrument internal misalignments. The paper presents results from this audit. Long-term drifts are found in the attitude histories, whereas the misalignment histories are shown to be diurnally stable. The GOES image navigation and registration system is designed to compensate for instrument internal misalignments, and both the diurnally repeatable and drift components of the attitude. Correlations between GOES-8 and GOES-9 long-term roll and pitch drifts implicate the Earth sensor as the origin of these observed drifts. This results clearly demonstrates the enhanced registration stability to be obtained with stellar inertial attitude determination replacing or supplementing Earth sensor control on future GOES missions.

Efficacy of lifestyle modification for long-term weight control.

PubMed

Wadden, Thomas A; Butryn, Meghan L; Byrne, Kirstin J

2004-12-01

A comprehensive program of lifestyle modification induces loss of approximately 10% of initial weight in 16 to 26 weeks, as revealed by a review of recent randomized controlled trials, including the Diabetes Prevention Program. Long-term weight control is facilitated by continued patient-therapist contact, whether provided in person or by telephone, mail, or e-mail. High levels of physical activity and the consumption of low-calorie, portion-controlled meals, including liquid meal replacements, can also help maintain weight loss. Additional studies are needed of the effects of macronutrient content (e.g., low-fat vs. low-carbohydrate diets) on long-term changes in weight and health. Research also is needed on effective methods of providing comprehensive weight loss control to the millions of Americans who need it.

Hair cortisol content in patients with adrenal insufficiency on hydrocortisone replacement therapy.

PubMed

Gow, Rachel; Koren, Gideon; Rieder, Michael; Van Uum, Stan

2011-06-01

Patients with adrenal insufficiency (AI) require life-long replacement therapy with exogenous glucocorticoids. Several studies have shown impaired subjective health status in these patients as well as increased morbidity and mortality risk, which may be caused by glucocorticoid over-replacement. As a measure of long-term cortisol exposure, the usefulness of hair cortisol analysis in patients receiving glucocorticoid replacement therapy was investigated. Hair samples, demographics, medical history and perceived stress scale questionnaires were collected from 93 patients across North America diagnosed with primary or secondary AI. Sixty-two household partners served as a control group. Cortisol was measured in the proximal 2 cm of hair, representing the most recent 2 months of exposure. A modified enzyme immunoassay was used for the measurement of cortisol. The male patients had significantly higher hair cortisol levels than the male controls (P < 0·05), while there was no significant difference among females. Hair cortisol content correlated significantly with glucocorticoid dose (r = 0·3, P < 0·01). Patients with AI had significantly higher subjective stress scores than control subjects. Hair cortisol content correlates with hydrocortisone (HC) dose in patients with AI. Our results suggest that some AI patients may be over-treated and hence may be at risk for the adverse effects of cortisol. Measurement of HC in hair may become a useful monitoring tool for long-term cortisol exposure in patients treated with glucocorticoids. © 2011 Blackwell Publishing Ltd.

Progressive renal failure despite long-term biweekly enzyme replacement therapy in a patient with Fabry disease secondary to a new α-galactosidase mutation of Leu311Arg (L311R).

PubMed

Suzuki, Keisuke; Miura, Naoto; Kitagawa, Wataru; Suzuki, Shinkichi; Komatsuda, Atsushi; Nishikawa, Kazuhiro; Watanabe, Daisuke; Imai, Hirokazu

2011-12-01

A 37-year-old Japanese man affected by Fabry disease secondary to a novel mutation of Leu311Arg (L311R) in α-galactosidase demonstrated progressive renal failure despite biweekly enzyme replacement therapy (ERT) for approximately 10 years. Kidney biopsy revealed foamy glomerular epithelial cells, compatible with the typical pathologic features of Fabry disease. The patient entered a phase III study of Replagal (agalsidase alfa) in 2001, allowing him to continue ERT with biweekly dosing for almost 10 years. During 2 years of that period, he was continued on Fabrazyme (agalsidase beta) biweekly dosing. His estimated GFR was calculated to decrease by 9.9 mL/min/1.73 m(2) per year. Patients with Fabry disease have been reported to have a mean decrease in GFR of 12.2 ± 8.1 mL/min/1.73 m(2) per year. This result suggests that biweekly ERT is only mildly effective at preventing loss of kidney function.

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

PubMed Central

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

2015-01-01

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

Bioprosthetic mitral valve replacement in patients aged 65 years or younger: long-term outcomes with the Carpentier-Edwards PERIMOUNT pericardial valve.

PubMed

Bourguignon, Thierry; Espitalier, Fabien; Pantaleon, Clémence; Vermes, Emmanuelle; El-Arid, Jean Marc; Loardi, Claudia; Karam, Elias; Candolfi, Pascal; Ivanes, Fabrice; Aupart, Michel

2018-02-12

Mitral valve replacement using a bioprosthesis remains controversial in young patients because data on long-term outcomes are missing. This study evaluated the long-term results of the PERIMOUNT pericardial mitral bioprosthesis in patients aged 65 years or younger. From 1984 to 2010, 148 Carpentier-Edwards PERIMOUNT mitral bioprostheses were implanted in 148 patients aged 65 years or younger. Baseline clinical, perioperative and follow-up data were recorded prospectively. Structural valve deterioration (SVD) was defined by strict echocardiographic assessment. The mean follow-up period was 8.6 ± 5.5 years, for a total of 1269 valve-years. Operative mortality rate was 2.0%. Fifty-one late deaths occurred (linearized rate 4.0% per valve-year). Actuarial survival rates averaged 70 ± 4%, 53 ± 6% and 31 ± 7% after 10, 15 and 20 years of follow-up, respectively. Actuarial freedom from SVD at 10, 15 and 20 years was 78 ± 5%, 47 ± 7% and 19 ± 7%, respectively. Reoperation was associated with no operative mortality. Actuarial freedom from reoperation due to SVD at 10, 15 and 20 years was 82 ± 4%, 50 ± 6% and 25 ± 8%, respectively. Competing risk analysis demonstrated an actual risk of explantation secondary to SVD at 20 years of 44 ± 5%. Expected valve durability was 14.2 years for this age group. In the selected patients aged 65 years or younger undergoing mitral valve replacement with a pericardial bioprosthesis, the expected valve durability was 14.2 years. Reoperation for SVD was associated with a low risk of mortality. © The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Mobile dental operations: capital budgeting and long-term viability.

PubMed

Arevalo, Oscar; Chattopadhyay, Amit; Lester, Harold; Skelton, Judy

2010-01-01

The University of Kentucky College of Dentistry (UKCD) runs a large mobile dental operation. Economic conditions dictate that as the mobile units age it will be harder to find donors willing or able to provide the financial resources for asset replacement. In order to maintain current levels of access for the underserved, consideration of replacement is paramount. A financial analysis for a new mobile unit was conducted to determine self-sustainability, return on investment (ROI), and feasibility of generating a cash reserve for its replacement in 12 years. Information on clinical income, operational and replacement costs, and capital costs was collected. A capital budgeting analysis (CBA) was conducted using the Net Present Value (NPV) methodology in four different scenarios. Depreciation funding was calculated by transferring funds from cash inflows and reinvested to offset depreciation at fixed compound interest. A positive ROI was obtained for two scenarios. He depreciation fund did not generate a cash reserve sufficient to replace the mobile unit. Mobile dental programs can play a vital role in providing access to care to underserved populations and ensuring their mission requires long-term planning. Careful financial viability and CBA based on sound assumptions are excellent decision-making tools.

'Enzyme Test Bench': A biochemical application of the multi-rate modeling

NASA Astrophysics Data System (ADS)

Rachinskiy, K.; Schultze, H.; Boy, M.; Büchs, J.

2008-11-01

In the expanding field of 'white biotechnology' enzymes are frequently applied to catalyze the biochemical reaction from a resource material to a valuable product. Evolutionary designed to catalyze the metabolism in any life form, they selectively accelerate complex reactions under physiological conditions. Modern techniques, such as directed evolution, have been developed to satisfy the increasing demand on enzymes. Applying these techniques together with rational protein design, we aim at improving of enzymes' activity, selectivity and stability. To tap the full potential of these techniques, it is essential to combine them with adequate screening methods. Nowadays a great number of high throughput colorimetric and fluorescent enzyme assays are applied to measure the initial enzyme activity with high throughput. However, the prediction of enzyme long term stability within short experiments is still a challenge. 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 conducted 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 optimum 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 results of the characterization, based on micro liter format experiments of hours, are in good agreement with the results of long term experiments in 1L format. Thus, the new technique allows for both

A replaceable dual-enzyme capillary microreactor using magnetic beads and its application for simultaneous detection of acetaldehyde and pyruvate.

PubMed

Shi, Jing; Zhao, Wenwen; Chen, Yuanfang; Guo, Liping; Yang, Li

2012-07-01

A novel replaceable dual-enzyme capillary microreactor was developed and evaluated using magnetic fields to immobilize the alcohol dehydrogenase (ADH)- and lactate dehydrogenase (LDH)-coated magnetic beads at desired positions in the capillary. The dual-enzyme assay was achieved by measuring the two consumption peaks of the coenzyme β-nicotinamide adenine dinucleotide (NADH), which were related to the ADH reaction and LDH reaction. The dual-enzyme capillary microreactor was constructed using magnetic beads without any modification of the inner surface of the capillary, and showed great stability and reproducibility. The electrophoretic resolution for different analytes can be easily controlled by altering the relative distance of different enzyme-coated magnetic beads. The apparent K(m) values for acetaldehyde with ADH-catalyzed reaction and for pyruvate with LDH-catalyzed reaction were determined. The detection limits for acetaldehyde and pyruvate determination are 0.01 and 0.016 mM (S/N = 3), respectively. The proposed method was successfully applied to simultaneously determine the acetaldehyde and pyruvate contents in beer samples. The results indicated that combing magnetic beads with CE is of great value to perform replaceable and controllable multienzyme capillary microreactor for investigation of a series of enzyme reactions and determination of multisubstrates. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Long-Term Monitoring Research Needs: A DOE Perspective

NASA Astrophysics Data System (ADS)

Moore, B.; Davis, C. B.

2002-05-01

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

A biochemical and pharmacological comparison of enzyme replacement therapies for the glycolipid storage disorder Fabry disease.

PubMed

Lee, Karen; Jin, Xiaoying; Zhang, Kate; Copertino, Lorraine; Andrews, Laura; Baker-Malcolm, Jennifer; Geagan, Laura; Qiu, Huawei; Seiger, Keirsten; Barngrover, Debra; McPherson, John M; Edmunds, Tim

2003-04-01

Fabry disease is a lysosomal storage disease arising from deficiency of the enzyme alpha-galactosidase A. Two recombinant protein therapeutics, Fabrazyme (agalsidase beta) and Replagal (agalsidase alfa), have been approved in Europe as enzyme replacement therapies for Fabry disease. Both contain the same human enzyme, alpha-galactosidase A, but they are produced using different protein expression systems and have been approved for administration at different doses. To determine if there is recognizable biochemical basis for the different doses, we performed a comparison of the two drugs, focusing on factors that are likely to influence biological activity and availability. The two drugs have similar glycosylation, both in the type and location of the oligosaccharide structures present. Differences in glycosylation were mainly limited to the levels of sialic acid and mannose-6-phosphate present, with Fabrazyme having a higher percentage of fully sialylated oligosaccharides and a higher level of phosphorylation. The higher levels of phosphorylated oligomannose residues correlated with increased binding to mannose-6-phosphate receptors and uptake into Fabry fibroblasts in vitro. Biodistribution studies in a mouse model of Fabry disease showed similar organ uptake. Likewise, antigenicity studies using antisera from Fabry patients demonstrated that both drugs were indistinguishable in terms of antibody cross-reactivity. Based on these studies and present knowledge regarding the influence of glycosylation on protein biodistribution and cellular uptake, the two protein preparations appear to be functionally indistinguishable. Therefore, the data from these studies provide no rationale for the use of these proteins at different therapeutic doses.

Effect of long-term treatment with urocortin on the activity of somatic angiotensin-converting enzyme in spontaneously hypertensive rats.

PubMed

Yang, Cui; Liu, Xiuxia; Li, Shengnan

2010-02-01

Our previous acute study on urocortin (Ucn) demonstrated that Ucn altered serum and tissue angiotensin-converting enzyme (ACE) activity in rats. Therefore, the present investigation was designed to explore the effect of long-term treatment with Ucn on somatic ACE (sACE) and other components of the renin-angiotensin system (RAS). After 8 weeks of intravenous administration of Ucn in spontaneously hypertensive rats (SHR), serum and tissue sACE, angiotensin II (Ang II), nitric oxide (NO), Ang-(1-7), and tissue chymase activities were evaluated. RT-PCR analysis was performed to determine the quantity of tissue sACE mRNA. Serum sACE activity was reduced by Ucn, although tissue sACE activity and tissue sACE mRNA were elevated. Chymase activity was observed to be enhanced by Ucn, whereas the ACE inhibitor enalapril failed to influence chymase. Serum and tissue Ang II activity was reduced, but NO and Ang-(1-7) production was increased in a concentration-dependent manner after Ucn treatment. Meanwhile, a significant decrease of the systolic blood pressure (SBP) was observed after the long-term Ucn administration, and there was a significant positive correlation (r2 = 0.6993) between serum ACE activity and SBP. Pretreatment with the corticotropin-releasing factor (CRF) blocker astressin and the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway blocker PD98059 abolished these effects of Ucn. Our findings further support the hypothesis that the changes of sACE activity and the production of other RAS components may play roles in the vasodilatory property of Ucn via the activation of the ERK1/2 pathway.

Medium-term outcome of Toronto aortic valve replacement: single center experience.

PubMed

Li, Wei; Price, Susanna; O'Sullivan, Christine A; Kumar, Pankaj; Jin, Xu Y; Henein, Michael Y; Pepper, John R

2008-09-26

Long-term competence of any aortic prosthesis is critical to its clinical durability. Bioprosthetic valves, and in particular the stentless type have been proposed to offer superior haemodynamic profiles with consequent potential for superior left-ventricular mass regression. These benefits however are balanced by the potential longevity of the implanted valve. The aims of this study were to assess medium-term Toronto aortic valve function and its effect on left-ventricular function. Between 1992 and 1996 86 patients underwent Toronto aortic valve replacement for aortic valve disease and were followed up annually. Prospectively collected data was analyzed for all patients where detailed echocardiographic follow-up was available. Echocardiographic studies were analyzed at 2+/-0.6 and 6+/-1.4 years after valve replacement. Data collected included left-ventricular systolic and diastolic dimensions, fractional shortening and left-ventricular mass. In addition, data on aortic valve and root morphology, peak aortic velocities, time velocity integral, stroke volume and the mechanism of valve failure where relevant, were also collected. Complete echocardiographic data were available for eighty-four patients, age 69+/-9 years, 62 male. Additional coronary artery bypass grafting was performed in 38% of patients. Twelve (14%) valves had failed during follow-up, 7 (8%) requiring re-operation. Valve failure was associated with morphologically bicuspid native aortic valve (9/12), and progressive dilatation of the aortic sinuses, sino-tubular junction and ascending aorta (11/12). Left-ventricular mass index remained high (184+/-75 g/m(2)) and did not continue to regress between early and medium-term follow-up (175.8+/-77 g/m(2)). Although more than 90% of implanted Toronto aortic valves remained haemodynamically stable with low gradient at medium-term follow-up, young age and larger aortic dimensions in patients with valve failure suggest better outcome if used in the elderly

Long-Term Outcomes in Idiopathic Membranous Nephropathy Using a Restrictive Treatment Strategy

PubMed Central

van Dijk, Peter R.; Hofstra, Julia M.; Wetzels, Jack F.M.

2014-01-01

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. PMID:24029426

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

Treesearch

M. R. Bayan; F. Eivazi

1993-01-01

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...

Drosophila Neprilysins Are Involved in Middle-Term and Long-Term Memory.

PubMed

Turrel, Oriane; Lampin-Saint-Amaux, Aurélie; Préat, Thomas; Goguel, Valérie

2016-09-14

Neprilysins are type II metalloproteinases known to degrade and inactivate a number of small peptides. Neprilysins in particular are the major amyloid-β peptide-degrading enzymes. In mouse models of Alzheimer's disease, neprilysin overexpression improves learning and memory deficits, whereas neprilysin deficiency aggravates the behavioral phenotypes. However, whether these enzymes are involved in memory in nonpathological conditions is an open question. Drosophila melanogaster is a well suited model system with which to address this issue. Several memory phases have been characterized in this organism and the neuronal circuits involved are well described. The fly genome contains five neprilysin-encoding genes, four of which are expressed in the adult. Using conditional RNA interference, we show here that all four neprilysins are involved in middle-term and long-term memory. Strikingly, all four are required in a single pair of neurons, the dorsal paired medial (DPM) neurons that broadly innervate the mushroom bodies (MBs), the center of olfactory memory. Neprilysins are also required in the MB, reflecting the functional relationship between the DPM neurons and the MB, a circuit believed to stabilize memories. Together, our data establish a role for neprilysins in two specific memory phases and further show that DPM neurons play a critical role in the proper targeting of neuropeptides involved in these processes. Neprilysins are endopeptidases known to degrade a number of small peptides. Neprilysin research has essentially focused on their role in Alzheimer's disease and heart failure. Here, we use Drosophila melanogaster to study whether neprilysins are involved in memory. Drosophila can form several types of olfactory memory and the neuronal structures involved are well described. Four neprilysin genes are expressed in adult Drosophila Using conditional RNA interference, we show that all four are specifically involved in middle-term memory (MTM) and long-term

First long-term evidence supporting endovascular repair of abdominal aortic aneurysms.

PubMed

Indes, Jeffrey E; Muhs, Bart E; Dardik, Alan

2013-04-01

The traditional method of treating abdominal aortic aneurysms with open surgical repair has been steadily replaced by endovascular repair, thought to be a more minimally invasive approach. It is not known, however, whether the endovascular approach is truly less invasive for operative physiology; in addition, this approach has a different spectrum of complications. As such, it is uncertain whether elective endovascular repair of nonruptured aortic aneurysms reduces long-term morbidity and mortality compared with traditional open approaches. In this article, the authors evaluate a recent publication investigating long-term outcomes of a prospective randomized multicenter trial evaluating patients with asymptomatic abdominal aortic aneurysms treated with either endovascular or open repair, and discuss the results in the context of current evidence.

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

PubMed

Alfadhel, Majid; Sirrs, Sandra

2011-01-01

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.

Effects of Short-Term Set-Aside Management Practices on Soil Microorganism and Enzyme Activity in China.

PubMed

Li, Guangyu; Wu, Cifang

2017-08-14

Set-aside farmland can effectively improve the self-rehabilitation of arable soil. Long-term set-asides however cannot satisfy provisionment, therefore the use of short-term set-asides to restore cultivated soil is a better option. Few studies have compared short-term set-aside patterns, and the effects of set-asides on soil microbial community and enzyme enzymes. We analyzed the bacterial structure, microbial biomass carbon/nitrogen and enzyme activity of farmland soil under different set-aside regimes in the Yellow River Delta of China. Bacterial alpha diversity was relatively lower under only irrigation, and farmyard manure applications showed clear advantages. Set-asides should consider their influence on soil organic carbon and nitrogen, which were correlated with microbial community structure. Nitrospira (0.47-1.67%), Acidobacteria Gp6 (8.26-15.91%) and unclassified Burkholderiales (1.50-2.81%) were significantly altered ( p < 0.01). Based on functions of these genera, some set-aside patterns led to a relative balance in nitrogen and carbon turnover. Partial treatments showed a deficiency in organic matter. In addition, farmyard manure may lead to the increased consumption of organic matter, with the exception of native plants set-asides. Conventional farming (control group) displayed a significant enzyme activity advantage. Set-aside management practices guided soil microbial communities to different states. Integrated soil microbiota and the content of carbon and nitrogen, native plants with farmyard manure showed an equilibrium state relatively, which would be helpful to improve land quality in the short-term.

Enzyme replacement therapy for Fabry disease: lessons from two alpha-galactosidase A orphan products and one FDA approval.

PubMed

Desnick, Robert J

2004-07-01

Two virtually identical products have been developed for enzyme replacement therapy for the treatment of Fabry disease, which is a rare and debilitating genetic disease caused by decreased activity of the lysosomal enzyme alpha-galactosidase A. Lack of this enzyme results in progressive tissue accumulation of globotriaosylceramide (GL-3), resulting in life-threatening renal, cardiac and cerebrovascular complications. Both enzyme replacement products, agalsidase alfa (Replagal; Transkaryotic Therapies, Cambridge, MA, USA) and agalsidase beta (Fabrazyme; Genzyme Corporation, Cambridge, MA, USA), were approved by the European Agency for the Evaluation of Medicinal Products in 2001; agalsidase alfa at a recommended dose of 0.2 mg/kg and agalsidase beta at a recommended dose of 1 mg/kg. In the US, however, orphan drug laws dictated that only one of these products could be approved. In April 2003, after a rigorous evaluation of both products by the US FDA, this approval was granted to agalsidase beta. This decision reflected clinical trial design, how dosages were determined, antibody effects and the ability of each product to demonstrate either clinical efficacy or reduction of tissue storage of GL-3 in major organs of pathology when administered at the recommended dosage. The process also highlighted important issues in the evaluation of drugs to treat life-threatening genetic diseases for which the pathological basis is well-defined.

Biochemical Changes in Erythrocytes as a Molecular Marker of Cell Damage during Long-Term Simvastatin Treatment.

PubMed

Mikashinovich, Z I; Belousova, E S

2016-08-01

Long-term administration of simvastatin to rats, irrespective of the baseline cholesterol levels, induced biochemical changes in erythrocytes attesting to hypoxic damage (accumulation of lactate and 2,3-diphosphoglycerate), disturbances in ATP-dependent mechanisms of ion homeostasis regulation (decrease in total ATPase and Ca(2+)-ATPase activities), and antioxidant enzymes system imbalance. These changes can be considered as a sensitive indicator and molecular basis of cell damage during long-term administration of statins.

Comprehensive long-term efficacy and safety of recombinant human alpha-mannosidase (velmanase alfa) treatment in patients with alpha-mannosidosis.

PubMed

Lund, Allan M; Borgwardt, Line; Cattaneo, Federica; Ardigò, Diego; Geraci, Silvia; Gil-Campos, Mercedes; De Meirleir, Linda; Laroche, Cécile; Dolhem, Philippe; Cole, Duncan; Tylki-Szymanska, Anna; Lopez-Rodriguez, Monica; Guillén-Navarro, Encarna; Dali, Christine I; Héron, Bénédicte; Fogh, Jens; Muschol, Nicole; Phillips, Dawn; Van den Hout, J M Hannerieke; Jones, Simon A; Amraoui, Yasmina; Harmatz, Paul; Guffon, Nathalie

2018-05-03

Long-term outcome data provide important insights into the clinical utility of enzyme replacement therapies. Such data are presented for velmanase alfa in the treatment of alpha-mannosidosis (AM). Patient data (n = 33; 14 adults, 19 paediatric) from the clinical development programme for velmanase alfa were integrated in this prospectively-designed analysis of long-term efficacy and safety. Patients who participated in the phase I/II or phase III trials and were continuing to receive treatment after completion of the trials were invited to participate in a comprehensive evaluation visit to assess long-term outcomes. Primary endpoints were changes in serum oligosaccharide and the 3-minute stair climb test (3MSCT). Mean (SD) treatment exposure was 29.3 (15.2) months. Serum oligosaccharide levels were significantly reduced in the overall population at 12 months (mean change: -72.7%, P < 0.001) and remained statistically significant at last observation (-62.8%, P < 0.001). A mean improvement of +9.3% in 3MSCT was observed at 12 months (P = 0.013), which also remained statistically significant at last observation (+13.8%, P = 0.004), with a more pronounced improvement detected in the paediatric subgroup. No treatment-emergent adverse events were reported leading to permanent treatment discontinuation. Patients treated with velmanase alfa experienced improvements in biochemical and functional measures that were maintained for up to 4 years. Long term follow-up is important and further supports the use of velmanase alfa as an effective and well-tolerated treatment for AM. Based on the currently available data set, no baseline characteristic can be predictive of treatment outcome. Early treatment during paediatric age showed better outcome in functional endpoints.

Health reform: setting the agenda for long term care.

PubMed

Hatch, O G; Wofford, H; Willging, P R; Pomeroy, E

1993-06-01

The White House Task Force on National Health Care Reform, headed by First Lady Hillary Rodham Clinton, is expected to release its prescription for health care reform this month. From the outset, Clinton's mandate was clear: to provide universal coverage while reining in costs for delivering quality health care. Before President Clinton was even sworn into office, he had outlined the major principles that would shape the health reform debate. Global budgeting would establish limits on all health care expenditures, thereby containing health costs. Under a system of managed competition, employers would form health alliances for consumers to negotiate for cost-effective health care at the community level. So far, a basic approach to health care reform has emerged. A key element is universal coverage--with an emphasis on acute, preventive, and mental health care. Other likely pieces are employer-employee contributions to health care plans, laws that guarantee continued coverage if an individual changes jobs or becomes ill, and health insurance alliances that would help assure individual access to low-cost health care. What still is not clear is the extent to which long term care will be included in the basic benefits package. A confidential report circulated by the task force last month includes four options for long term care: incremental Medicaid reform; a new federal/state program to replace Medicaid; a social insurance program for home and community-based services; or full social insurance for long term care. Some work group members have identified an additional option: prefunded long term care insurance.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term assessment of financial maturity, diameter-limit selection in the central Appalachians

Treesearch

Thomas M. Schuler; David W. McGill

2007-01-01

Financial maturity, diameter-limit (FMDL) selection was proposed more than three decades ago as a replacement for diameter-limit cutting. FMDL incorporates financial maturity guidelines for individual trees, high-priority removal of poorquality trees, and guidelines for residual basal area. We provide the first long-term assessment of this practice after more than...

Long-Term Experience with First-Generation Implantable Neurostimulation Device in Central Sleep Apnea Treatment.

PubMed

Fox, Henrik; Bitter, Thomas; Horstkotte, Dieter; Oldenburg, Olaf; Gutleben, Klaus-Jürgen

2017-05-01

Sleep-disordered breathing (SDB) and Cheyne-Stokes respiration (CSR) are associated with shorter survival in patients with heart failure. A novel treatment method for this patient group is unilateral phrenic nerve stimulation by the remedē® system (Respicardia Inc., Minnetonka, MN, USA), a transvenously implantable neurostimulation device, which has recently been studied in a large randomized, controlled trial. Previous literature has shown efficacy and safety of the treatment with this first-generation device, but hardly any data are available on long-term clinical parameters, the remedē® device's battery lifetime, device exchangeability, lead position stability, surgical accessibility, and manageability. We performed remedē® device replacements in consecutive patients for battery depletion, and documented clinical parameters, longevity, operation procedure, complications, and difficulties. All patients were on neurostimulation treatment by phrenic nerve neurostimulation when device replacement became necessary. Apnea-hypopnea index (from 45 ± 4/h to 9 ± 4/h), oxygen-desaturation index (from 35 ± 7/h to 7 ± 6/h), and time spent with oxygen saturation of <90% (T < 90% from 5 ± 7% to 0 ± 0%) were improved and improvements remained constant throughout the 4-year follow-up. Mean battery life was 4.2 ± 0.2 years and mean replacement procedure time was 25 ± 5.1 minutes. Apart from conventional X-ray documentation of stable lead positions in a long-term setting, no radiation or contrast dye usage was needed and no major complications occurred. In addition, clinical exercise capacity and sleepiness symptoms improved. Novel remedē® device shows sustained therapy efficacy and safety in terms of stable lead positions over 4 years. Long-term phrenic nerve neurostimulation therapy for central SDB/CSR appears feasible in a clinical routine setting. © 2017 Wiley Periodicals, Inc.

Effect of enzyme replacement therapy with alglucosidase alfa (Myozyme®) in 12 patients with advanced late-onset Pompe disease.

PubMed

Papadopoulos, Constantinos; Orlikowski, David; Prigent, Hélène; Lacour, Arnaud; Tard, Céline; Furby, Alain; Praline, Julien; Solé, Guilhem; Hogrel, Jean-Yves; De Antonio, Marie; Semplicini, Claudio; Deibener-Kaminsky, Joelle; Kaminsky, Pierre; Eymard, Bruno; Taouagh, Nadjib; Perniconi, Barbara; Hamroun, Dalil; Laforêt, Pascal

2017-09-01

The efficacy of enzyme replacement therapy (ERT) in patients at an advanced stage of Pompe disease has only been addressed in a few studies. Our objective was to assess the long term effects of ERT in a cohort of patients with severe Pompe disease. We identified patients from the French Pompe Registry with severe respiratory failure and permanent wheelchair use (assisted walk for a few meters was allowed) when starting ERT. Patients' medical records were collected and reviewed and respiratory and motor functions, before ERT initiation and upon last evaluation were compared. Twelve patients (7 males) were identified. Median age at symptom onset was 24years [IQR=15.5; 36.0]. At baseline ventilation was invasive in 11 patients and noninvasive in one, with a median ventilation time of 24h [IQR=21.88; 24.00] (min 20; max 24). ERT was initiated at a median age of 52.5years [IQR=35.75; 66.50]. Median treatment duration was 55months [IQR=39.5; 81.0]. During observational period no adverse reaction to ERT was recorded, five patients (41.67%) died, three decreased their ventilation time by 30, 60 and 90min and two increased their assisted walking distance, by 80 and 20m. Some patients at a very advanced stage of Pompe disease may show a mild benefit from ERT, in terms of increased time of autonomous ventilation and of enlarged distance in assisted walk. ERT can be initiated in these patients in order to retain their current level of independence and ability to perform daily life activities. Copyright © 2017 Elsevier Inc. All rights reserved.

Functional Sites Induce Long-Range Evolutionary Constraints in Enzymes

PubMed Central

Jack, Benjamin R.; Meyer, Austin G.; Echave, Julian; Wilke, Claus O.

2016-01-01

Functional residues in proteins tend to be highly conserved over evolutionary time. However, to what extent functional sites impose evolutionary constraints on nearby or even more distant residues is not known. Here, we report pervasive conservation gradients toward catalytic residues in a dataset of 524 distinct enzymes: evolutionary conservation decreases approximately linearly with increasing distance to the nearest catalytic residue in the protein structure. This trend encompasses, on average, 80% of the residues in any enzyme, and it is independent of known structural constraints on protein evolution such as residue packing or solvent accessibility. Further, the trend exists in both monomeric and multimeric enzymes and irrespective of enzyme size and/or location of the active site in the enzyme structure. By contrast, sites in protein–protein interfaces, unlike catalytic residues, are only weakly conserved and induce only minor rate gradients. In aggregate, these observations show that functional sites, and in particular catalytic residues, induce long-range evolutionary constraints in enzymes. PMID:27138088

[Long-term psychiatric hospitalizations].

PubMed

Plancke, L; Amariei, A

2017-02-01

Long-term hospitalizations in psychiatry raise the question of desocialisation of the patients and the inherent costs. Individual indicators were extracted from a medical administrative database containing full-time psychiatric hospitalizations for the period 2011-2013 of people over 16 years old living in the French region of Nord-Pas-de-Calais. We calculated the proportion of people who had experienced a hospitalization with a duration of 292 days or more during the study period. A bivariate analysis was conducted, then ecological data (level of health-care offer, the deprivation index and the size of the municipalities of residence) were included into a multilevel regression model in order to identify the factors significantly related to variability of long-term hospitalization rates. Among hospitalized individuals in psychiatry, 2.6% had had at least one hospitalization of 292 days or more during the observation period; the number of days in long-term hospitalization represented 22.5% of the total of days of full-time hospitalization in psychiatry. The bivariate analysis revealed that seniority in the psychiatric system was strongly correlated with long hospitalization rates. In the multivariate analysis, the individual indicators the most related to an increased risk of long-term hospitalization were: total lack of autonomy (OR=9.0; 95% CI: 6.7-12.2; P<001); diagnoses of psychological development disorders (OR=9.7; CI95%: 4.5-20.6; P<.001); mental retardation (OR=4.5; CI95%: 2.5-8.2; P<.001): schizophrenia (OR=3.0; CI95%: 1.7-5.2; P<.001); compulsory hospitalization (OR=1.7; CI95%: 1.4-2.1; P<.001); having experienced therapeutic isolation (OR=1.8; CI95%: 1.5-2.1; P<.001). Variations of long-term hospitalization rates depending on the type of establishment were very high, but the density of hospital beds or intensity of ambulatory activity services were not significantly linked to long-term hospitalization. The inhabitants of small urban units had

Mineralogical impact on long-term patterns of soil nitrogen and phosphorus enzyme activities

NASA Astrophysics Data System (ADS)

Mikutta, Robert; Turner, Stephanie; Meyer-Stüve, Sandra; Guggenberger, Georg; Dohrmann, Reiner; Schippers, Axel

2014-05-01

Soil chronosequences provide a unique opportunity to study microbial activity over time in mineralogical diverse soils of different ages. The main objective of this study was to test the effect of mineralogical properties, nutrient and organic matter availability over whole soil pro-files on the abundance and activity of the microbial communities. We focused on microbio-logical processes involved in nitrogen and phosphorus cycling at the 120,000-year Franz Josef soil chronosequence. Microbial abundances (microbial biomass and total cell counts) and enzyme activities (protease, urease, aminopeptidase, and phosphatase) were determined and related to nutrient contents and mineralogical soil properties. Both, microbial abundances and enzyme activities decreased with soil depth at all sites. In the organic layers, microbial biomass and the activities of N-hydrolyzing enzymes showed their maximum at the intermediate-aged sites, corresponding to a high aboveground biomass. In contrast, the phosphatase activity increased with site age. The activities of N-hydrolyzing enzymes were positively correlated with total carbon and nitrogen contents, whereas the phosphatase activity was negatively correlated with the phosphorus content. In the mineral soil, the enzyme activities were generally low, thus reflecting the presence of strongly sorbing minerals. Sub-strate-normalized enzyme activities correlated negatively to clay content as well as poorly crystalline Al and Fe oxyhydroxides, supporting the view that the evolution of reactive sec-ondary mineral phases alters the activity of the microbial communities by constraining sub-strate availability. Our data suggest a strong mineralogical influence on nutrient cycling par-ticularly in subsoil environments.

Short- and long-term responses to molybdenum-99 shortages in nuclear medicine.

PubMed

Ballinger, J R

2010-11-01

Most nuclear medicine studies use (99)Tc(m), which is the decay product of (99)Mo. The world supply of (99)Mo comes from only five nuclear research reactors and availability has been much reduced in recent times owing to problems at the largest reactors. In the short-term there are limited actions that can be taken owing to capacity issues on alternative imaging modalities. In the long-term, stability of (99)Mo supply will rely on a combination of replacing conventional reactors and developing new technologies.

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

PubMed Central

Bliss, Timothy V.P.; Cooke, Sam F

2011-01-01

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. PMID:21779718

Long-term outcomes and social independence level after arterial switch operation.

PubMed

Yamazaki, Akira; Yamamoto, Noboru; Sakamoto, Takahiko; Ishihara, Kazuaki; Iwata, Yusuke; Matsumura, Goki; Kurosawa, Hiromi

2008-02-01

Various issues regarding the long-term survivors of arterial switch operation (ASO) have been clarified according to the improvement of surgical mortality. We reviewed the long-term results and social independence level after ASO. Two hundred and four (204) patients who had undergone ASO more than 15 years ago were studied retrospectively. ASO was performed as a primary operation (group I, n=99) or as a secondary operation (group II, n=105). Lecompte procedure was performed in 197 patients, modified Aubert procedure in 5, and original Jatene procedure in 2. There were 11 late deaths. Kaplan-Meier survival rate (not including operative deaths) was 94.9% at 10 years and 94.9% at 15 years in group I, and 96.9% at 10 years and 94.4% at 15 years in group II. Forty-eight reoperations were performed (aortic valve replacement in 6, aortic valvoplasty in 2, Konno procedure in 1, double valve replacement in 1, right ventricular outflow tract reconstruction in 35). The reoperation-free rate including late death was 82.2% at 10 years and 75.7% at 15 years in group I, and 88.2% at 10 years and 78.1% at 15 years in group II. One hundred and seventy-eight patients were classified as NYHA class I and 7 patients as class II. All the patients except those with mental disorder (1) or neurodevelopmental impairment (3) were attending school or working. There was no significant difference in left ventricular function between group I and II, both showing values within the normal range. The long-term (>15 years) outcome of ASO survivors was satisfactory. Most patients showed excellent cardiac function and were socially independent.

Comparison of the characteristics of long-term users of electronic cigarettes versus nicotine replacement therapy: A cross-sectional survey of English ex-smokers and current smokers.

PubMed

Nelson, Victoria A; Goniewicz, Maciej L; Beard, Emma; Brown, Jamie; Sheals, Kate; West, Robert; Shahab, Lion

2015-08-01

Electronic cigarettes (ECs) and nicotine replacement therapy (NRT) are non-combustible nicotine delivery devices being widely used as a partial or a complete long-term substitute for smoking. Little is known about the characteristics of long-term users, their smoking behaviour, attachment to smoking, experience of nicotine withdrawal symptoms, or their views on these devices. This study aimed to provide preliminary evidence on this and compare users of the different products. UK participants were recruited from four naturally occurring groups of long-term (≥6 months) users of either EC or NRT who had stopped or continued to smoke (N=36 per group, total N=144). Participants completed a questionnaire assessing socio-demographic and smoking characteristics, nicotine withdrawal symptoms, smoker identity and attitudes towards the products they were using. Adjusting for relevant confounders, EC use was associated with a stronger smoker identity (Wald X(2)(1)=3.9, p=0.048) and greater product endorsement (Wald X(2)(1)=4.6, p=0.024) than NRT use, irrespective of smoking status. Among ex-smokers, EC users reported less severe mood and physical symptoms (Wald X(2)(1)=6.1, p=0.014) and cravings (Wald X(2)(1)=8.5, p=0.003), higher perceived helpfulness of the product (Wald X(2)(1)=4.8, p=0.028) and lower intentions to stop using the product (Wald X(2)(1)=17.6, p<0.001) than NRT users. Compared with people who use NRT for at least 6 months, those who use EC over that time period appear to have a stronger smoker identity and like their products more. Among long-term users who have stopped smoking, ECs are perceived as more helpful than NRT, appear more effective in controlling withdrawal symptoms and continued use may be more likely. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

The operation of the century: total hip replacement.

PubMed

Learmonth, Ian D; Young, Claire; Rorabeck, Cecil

2007-10-27

In the 1960s, total hip replacement revolutionised management of elderly patients crippled with arthritis, with very good long-term results. Today, young patients present for hip-replacement surgery hoping to restore their quality of life, which typically includes physically demanding activities. Advances in bioengineering technology have driven development of hip prostheses. Both cemented and uncemented hips can provide durable fixation. Better materials and design have allowed use of large-bore bearings, which provide an increased range of motion with enhanced stability and very low wear. Minimally invasive surgery limits soft-tissue damage and facilitates accelerated discharge and rehabilitation. Short-term objectives must not compromise long-term performance. Computer-assisted surgery will contribute to reproducible and accurate placement of implants. Universal economic constraints in healthcare services dictate that further developments in total hip replacement will be governed by their cost-effectiveness.

Dose response of bone-targeted enzyme replacement for murine hypophosphatasia.

PubMed

Yadav, Manisha C; Lemire, Isabelle; Leonard, Pierre; Boileau, Guy; Blond, Laurent; Beliveau, Martin; Cory, Esther; Sah, Robert L; Whyte, Michael P; Crine, Philippe; Millán, José Luis

2011-08-01

Hypophosphatasia (HPP) features rickets or osteomalacia from tissue-nonspecific alkaline phosphatase (TNSALP) deficiency due to deactivating mutations within the ALPL gene. Enzyme replacement therapy with a bone-targeted, recombinant TNSALP (sALP-FcD(10), renamed ENB-0040) prevents manifestations of HPP when initiated at birth in TNSALP knockout (Akp2(-/-)) mice. Here, we evaluated the dose-response relationship of ENB-0040 to various phenotypic traits of Akp2(-/-) mice receiving daily subcutaneous (SC) injections of ENB-0040 from birth at 0.5, 2.0, or 8.2mg/kg for 43days. Radiographs, μCT, and histomorphometric analyses documented better bone mineralization with increasing doses of ENB-0040. We found a clear, positive correlation between ENB-0040 dose and prevention of mineralization defects of the feet, rib cage, lower limbs, and jaw bones. According to a dose-response model, the ED(80) (the dose that prevents bone defects in 80% of mice) was 3.2, 2.8 and 2.9mg/kg/day for these sites, respectively. Long bones seemed to respond to lower daily doses of ENB-0040. There was also a positive relationship between ENB-0040 dose and survival. Median survival, body weight, and bone length all improved with increasing doses of ENB-0040. Urinary PP(i) concentrations remained elevated in all treatment groups, indicating that while this parameter is a good biochemical marker for diagnosing HPP in patients, it may not be a good follow up marker for evaluating response to treatment when administering bone-targeted TNSALP to mice. These dose-response relationships strongly support the pharmacological efficacy of ENB-0040 for HPP, and provide the experimental basis for the therapeutic range of ENB-0040 chosen for clinical trials. Copyright © 2011 Elsevier Inc. All rights reserved.

Dose response of bone-targeted enzyme replacement for murine hypophosphatasia

PubMed Central

Yadav, Manisha C.; Lemire, Isabelle; Leonard, Pierre; Boileau, Guy; Blond, Laurent; Beliveau, Martin; Cory, Esther; Sah, Robert L.; Whyte, Michael P.; Crine, Philippe; Millán, José Luis

2011-01-01

Hypophosphatasia (HPP) features rickets or osteomalacia from tissue-nonspecific alkaline phosphatase (TNSALP) deficiency due to deactivating mutations within the ALPL gene. Enzyme replacement therapy with a bone-targeted, recombinant TNSALP (sALP-FcD10, renamed ENB-0040) prevents manifestations of HPP when initiated at birth in TNSALP knockout (Akp2−/−) mice. Here, we evaluated the dose-response relationship of ENB-0040 to various phenotypic traits of Akp2−/− mice receiving daily subcutaneous (SC) injections of ENB-0040 from birth at 0.5, 2.0, or 8.2 mg/kg for 43 days. Radiographs, μCT, and histomorphometric analyses documented better bone mineralization with increasing doses of ENB-0040. We found a clear, positive correlation between ENB-0040 dose and prevention of mineralization defects of the feet, rib cage, lower limbs, and jaw bones. According to a dose-response model, the ED80 (the dose prevents the bone defects in 80% of mice) was 3.2, 2.8 and 2.9 mg/kg/day for these sites, respectively. Long bones seemed to respond to lower daily doses of ENB-0040. There was also a positive relationship between ENB-0040 dose and survival. Median survival, body weight, and bone length all improved with increasing doses of ENB-0040. Urinary PPi concentrations remained elevated in all treatment groups, indicating that while this parameter is a good biochemical marker for diagnosing HPP, it may not be a good follow up marker for evaluating response to treatment when administering bone-targeted TNSALP. These dose-response relationships strongly support the pharmacological efficacy of ENB-0040 for HPP, and provide the experimental basis for the therapeutic range of ENB-0040 chosen for clinical trials. PMID:21458605

Effects of Short-Term Set-Aside Management Practices on Soil Microorganism and Enzyme Activity in China

PubMed Central

Wu, Cifang

2017-01-01

Set-aside farmland can effectively improve the self-rehabilitation of arable soil. Long-term set-asides however cannot satisfy provisionment, therefore the use of short-term set-asides to restore cultivated soil is a better option. Few studies have compared short-term set-aside patterns, and the effects of set-asides on soil microbial community and enzyme enzymes. We analyzed the bacterial structure, microbial biomass carbon/nitrogen and enzyme activity of farmland soil under different set-aside regimes in the Yellow River Delta of China. Bacterial alpha diversity was relatively lower under only irrigation, and farmyard manure applications showed clear advantages. Set-asides should consider their influence on soil organic carbon and nitrogen, which were correlated with microbial community structure. Nitrospira (0.47–1.67%), Acidobacteria Gp6 (8.26–15.91%) and unclassified Burkholderiales (1.50–2.81%) were significantly altered (p < 0.01). Based on functions of these genera, some set-aside patterns led to a relative balance in nitrogen and carbon turnover. Partial treatments showed a deficiency in organic matter. In addition, farmyard manure may lead to the increased consumption of organic matter, with the exception of native plants set-asides. Conventional farming (control group) displayed a significant enzyme activity advantage. Set-aside management practices guided soil microbial communities to different states. Integrated soil microbiota and the content of carbon and nitrogen, native plants with farmyard manure showed an equilibrium state relatively, which would be helpful to improve land quality in the short-term. PMID:28805737

The Place of Assisted Living in Long-Term Care and Related Service Systems

ERIC Educational Resources Information Center

Stone, Robyn I.; Reinhard, Susan C.

2007-01-01

Purpose: The purpose of this article is to describe how assisted living (AL) fits with other long-term-care services. Design and Methods: We analyzed the evolution of AL, including the populations served, the services offered, and federal and state policies that create various incentives or disincentives for using AL to replace other forms of care…

Angiotensin-converting enzyme inhibitors in patients with coronary artery disease and absence of heart failure or left ventricular systolic dysfunction: an overview of long-term randomized controlled trials.

PubMed

Danchin, Nicolas; Cucherat, Michel; Thuillez, Christian; Durand, Eric; Kadri, Zena; Steg, Philippe G

2006-04-10

Results of randomized trials of angiotensin-converting enzyme inhibitors in patients with coronary artery disease (CAD) and preserved left ventricular function are conflicting. We undertook this study to determine whether long-term prescription of angiotensin-converting enzyme inhibitors decreases major cardiovascular events and mortality in patients who have CAD and no evidence of left ventricular systolic dysfunction. We searched MEDLINE, EMBASE, and IPA databases, the Cochrane Controlled Trials Register (1990-2004), and reports from scientific meetings (2003-2004), and we reviewed secondary sources. Search terms included angiotensin-converting enzyme inhibitors, coronary artery disease, randomi(s)zed controlled trials, clinical trials, and myocardial infarction. Eligible studies included randomized controlled trials in patients who had CAD and no heart failure or left ventricular dysfunction, with follow-up omicronf 2 years or longer. Of 1146 publications screened, 7 met our selection criteria and included a total of 33 960 patients followed up for a mean of 4.4 years. Five trials included only patients with documented CAD. One trial included patients with documented CAD (80%) or patients who had diabetes mellitus and 1 or more additional risk factors, and another trial included patients who had CAD, a history of transient ischemic attack, or intermittent claudication. Treatment with angiotensin-converting enzyme inhibitors decreased overall mortality (odds ratio, 0.86; 95% confidence interval, 0.79-0.93), cardiovascular mortality (odds ratio, 0.81; 95% confidence interval, 0.73-0.90), myocardial infarction (odds ratio, 0.82; 95% confidence interval, 0.75-0.89), and stroke (odds ratio, 0.77; 95% confidence interval, 0.66-0.88). Other end points, including resuscitation after cardiac arrest, myocardial revascularization, and hospitalization because of heart failure, were also reduced. Angiotensin-converting enzyme inhibitors reduce total mortality and major

Short- and long-term responses to molybdenum-99 shortages in nuclear medicine

PubMed Central

Ballinger, J R

2010-01-01

Most nuclear medicine studies use 99Tcm, which is the decay product of 99Mo. The world supply of 99Mo comes from only five nuclear research reactors and availability has been much reduced in recent times owing to problems at the largest reactors. In the short-term there are limited actions that can be taken owing to capacity issues on alternative imaging modalities. In the long-term, stability of 99Mo supply will rely on a combination of replacing conventional reactors and developing new technologies. PMID:20965898

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

PubMed

Yue, Yun; Hu, Ling; Tian, Qin-jie; Jiang, Jing-mei; Dong, Yi-long; Jin, Zheng-yu; Cheng, Yu-hang; Hong, Xia; Ge, Qin-sheng; Zuo, Ping-ping

2007-08-01

To study the effects of long-term, low-dose sex hormone replacement therapy (HRT) on the volume and biochemical changes of the hippocampus in postmenopausal women carrying apolipoprotein E (apoE) gene epsilon3 or epsilon4. 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 epsilon4 and epsilon3 carriers. Six common cognitive tests were used to make an overall evaluation of cognitive function. Analysis with the apoE epsilon4 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 epsilon4 carriers in the HRT group, compared with the control group. For the apoE epsilon3 carriers, the least squares means (LSMEAN) of the HRT group was higher than that of the control group. 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 epsilon3 carriers.

ALTERATIONS IN BRAIN CREATINE CONCENTRATIONS UNDER LONG-TERM SOCIAL ISOLATION (EXPERIMENTAL STUDY).

PubMed

Koshoridze, N; Kuchukashvili, Z; Menabde, K; Lekiashvili, Sh; Koshoridze, M

2016-02-01

Stress represents one of the main problems of modern humanity. This study was done for understanding more clearly alterations in creatine content of the brain under psycho-emotional stress induced by long-term social isolation. It was shown that under 30 days social isolation creatine amount in the brain was arisen, while decreasing concentrations of synthesizing enzymes (AGAT, GAMT) and creatine transporter protein (CrT). Another important point was that such changes were accompanied by down-regulation of creatine kinase (CK), therefore the enzyme's concentration was lowered. In addition, it was observed that content of phosphocreatine (PCr) and ATP were also reduced, thus indicating down-regulation of energy metabolism of brain that is really a crucial point for its normal functioning. To sum up the results it can be underlined that long-term social isolation has negative influence on energy metabolism of brain; and as a result reduce ATP content, while increase of free creatine concentration, supposedly maintaining maximal balance for ATP amount, but here must be also noted that up-regulated oxidative pathways might have impact on blood brain barrier, resulting on its permeability.

Iron Deficiency in Long-Term Parenteral Nutrition Therapy.

PubMed

Hwa, Yi L; Rashtak, Shahrooz; Kelly, Darlene G; Murray, Joseph A

2016-08-01

Iron is not routinely added to parenteral nutrition (PN) formulations in the United States because of the risk of anaphylaxis and concerns about incompatibilities. Studies have shown that iron dextran in non-lipid-containing PN solutions is safe. Data are limited on iron status, prevalence of iron deficiency anemia (IDA), and efficacy of intravenous iron infusion in long-term home PN (HPN). We aimed to determine the incidence of IDA and to examine the effectiveness of parenteral iron replacement in patients receiving HPN. Medical records of patients receiving HPN at the Mayo Clinic from 1977 to 2010 were reviewed. Diagnoses, time to IDA development, and hemoglobin, ferritin, and mean corpuscular volume (MCV) values were extracted. Response of iron indices to intravenous iron replacement was investigated. Of 185 patients (122 women), 60 (32.4%) were iron deficient. Five patients were iron deficient, and 18 had unknown iron status before HPN. Of 93 patients who had sufficient iron storage, 37 had IDA development after a mean of 27.2 months (range, 2-149 months) of therapy. Iron was replaced by adding maintenance iron dextran to PN or by therapeutic iron infusion. Patients with both replacement methods had significant improvement in iron status. With intravenous iron replacement, mean ferritin increased from 10.9 to 107.6 mcg/L (P < .0001); mean hemoglobin increased from 11.0 to 12.5 g/dL (P = .0001); and mean MCV increased from 84.5 to 89.0 fL (P = .007). Patients receiving HPN are susceptible to IDA. Iron supplementation should be addressed for patients who rely on PN. © 2015 American Society for Parenteral and Enteral Nutrition.

Substitution of sugar-sweetened beverages with other beverage alternatives: a review of long-term health outcomes.

PubMed

Zheng, Miaobing; Allman-Farinelli, Margaret; Heitmann, Berit Lilienthal; Rangan, Anna

2015-05-01

Excessive consumption of sugar-sweetened beverages (SSBs) has become an intractable public health concern worldwide, making investigation of healthy beverage alternatives for SSBs imperative. To summarize the available evidence on the effects of replacing SSBs with beverage alternatives on long-term health outcomes. We systematically retrieved studies from six electronic databases from inception to November 2013. Prospective cohort studies and randomized controlled trials (RCTs) examining the effects of substituting beverage alternatives for SSBs on long-term health outcomes in both children and adults were included. The quality of included studies was assessed using the Scottish Intercollegiate Guidelines Network 50 methodology checklists. Six cohort studies and four RCTs were included in the systematic review with the quality rating ranging from acceptable to high. Evidence from both cohort studies and RCTs showed substitution of SSBs by various beverage alternatives was associated with long-term lower energy intake and lower weight gain. However, evidence was insufficient to draw conclusions regarding the effect of beverage substitution on other health outcomes, and which beverage alternative is the best choice. Although studies on this topic are sparse, the available evidence suggests a potential beneficial effect on body weight outcomes when SSBs are replaced by water or low-calorie beverages. Further studies in this area are warranted to fully understand the long-term health implications of beverage substitutions. Copyright © 2015 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

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.

PubMed

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

2016-01-01

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.

Long-term follow-up in Bietti crystalline dystrophy

PubMed Central

MANSOUR, A.M.; UWAYDAT, S.H.; CHAN, C.-C.

2008-01-01

Purpose To present a long-term follow-up of Bietti crystalline dystrophy. Methods Two brothers are presented including the clinical findings, fluorescein angiography, electrophysiology (electroretinography [ERG], electrooculography [EOG], adaptometry), optical coherence tomography (OCT), and transmission electron microscopy of bulbar conjunctiva and peripheral blood lymphocytes. The clinical findings were documented over a period of 25 years in one brother and 5 years in the other. Results The most striking features were deposits in the retina that were formed de novo with old ones replaced by choroidal atrophy in advanced stage of the disease. The light rise (EOG), rod- and cone-driven responses (ERG), and visual fields were affected progressively during the course. These changes of the retinal pigment epithelium and choriocapillaris were observed in the second decade and worsened gradually. OCT demonstrated preferential crystal accumulation in the inner retina. Cytoplasmic lipid crystalline inclusions were found in lymphocytes and conjunctival fibroblasts by transmission electron microscopy. Conclusions Bietti crystalline retinopathy is a progressive retinal disease characterized by retinal crystals gradually replaced by atrophy of the retinal pigment epithelium and gradual constriction of visual fields. PMID:17671952

Digestive Enzyme Supplementation in Gastrointestinal Diseases.

PubMed

Ianiro, Gianluca; Pecere, Silvia; Giorgio, Valentina; Gasbarrini, Antonio; Cammarota, Giovanni

2016-01-01

Digestive enzymes are able to break down proteins and carbohydrates and lipids, and their supplementation may play a role in the management of digestive disorders, from lactose intolerance to cystic fibrosis. To date, several formulations of digestive enzymes are available on the market, being different each other in terms of enzyme type, source and origin, and dosage. This review, performed through a non-systematic search of the available literature, will provide an overview of the current knowledge of digestive enzyme supplementation in gastrointestinal disorders, discussion of the use of pancreatic enzymes, lactase (β-galactosidase) and conjugated bile acids, and also exploring the future perspective of digestive enzyme supplementation. Currently, the animal-derived enzymes represent an established standard of care, however the growing study of plant-based and microbe-derived enzymes offers great promise in the advancement of digestive enzyme therapy. New frontiers of enzyme replacement are being evaluated also in the treatment of diseases not specifically related to enzyme deficiency, whereas the combination of different enzymes might constitute an intriguing therapeutic option in the future.

Nicotine Uses Neuron-Glia Communication to Enhance Hippocampal Synaptic Transmission and Long-term Memory

PubMed Central

López-Hidalgo, Mónica; Salgado-Puga, Karla; Alvarado-Martínez, Reynaldo; Medina, Andrea Cristina; Prado-Alcalá, Roberto A.; García-Colunga, Jesús

2012-01-01

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. PMID:23185511

Near-Term Actions to Address Long-Term Climate Risk

NASA Astrophysics Data System (ADS)

Lempert, R. J.

2014-12-01

Addressing climate change requires effective long-term policy making, which occurs when reflecting on potential events decades or more in the future causes policy makers to choose near-term actions different than those they would otherwise pursue. Contrary to some expectations, policy makers do sometimes make such long-term decisions, but not as commonly and successfully as climate change may require. In recent years however, the new capabilities of analytic decision support tools, combined with improved understanding of cognitive and organizational behaviors, has significantly improved the methods available for organizations to manage longer-term climate risks. In particular, these tools allow decision makers to understand what near-term actions consistently contribute to achieving both short- and long-term societal goals, even in the face of deep uncertainty regarding the long-term future. This talk will describe applications of these approaches for infrastructure, water, and flood risk management planning, as well as studies of how near-term choices about policy architectures can affect long-term greenhouse gas emission reduction pathways.

Concomitant tricuspid valve repair or replacement during left ventricular assist device implant demonstrates comparable outcomes in the long term.

PubMed

Deo, Salil V; Hasin, Tal; Altarabsheh, Salah E; McKellar, Stephen H; Shah, Ishan K; Durham, Lucian; Stulak, John M; Daly, Richard C; Park, Soon J; Joyce, Lyle D

2012-11-01

Severe tricuspid regurgitation (TR) is present in nearly half the patients undergoing implant of a left ventricular assist device (LVAD) and its correction confers better long-term outcome. To compare the early and late results of tricuspid valve repair (TVrpr) or replacement (TVR) with LVAD implant. Sixty-four from a cohort of 126 patients had a concomitant tricuspid valve procedure; 48 (75%) underwent a TVrpr whereas 16 (25%) had TVR. All preoperative hemodynamic parameters including the mean TR grade (TVrpr; 3.6 vs. TVR; 3.7) were comparable (p = 0.7). The mean TR grade was 1.6 ± 1.5 for the remaining 62 patients who did not have a concomitant tricuspid valve procedure, with 4/62 (6%) having severe TR (p < 0.0001). Cardiopulmonary bypass time was longer for patients undergoing TVR (p = 0.01). There was a significant reduction in right atrial pressure for the entire cohort (p < 0.01) and the postoperative right atrial pressure was not statistically different between TVrpr (13.6 ± 4.6) and TVR (11.6 ± 4.3; p = 0.6. Postoperative intensive care unit stay was comparable as was the duration of inotropic support (p = 0.5) or need for temporary right ventricular mechanical support. In-hospital mortality (12%) was not different between groups. The mean time for LVAD support was 12.3 ± 9.71 months and the last transthoracic echocardiographic examination was performed at mean intervals of 13.8 ± 10.8 months (TVrpr) and 11.8 ± 7.6 months (TVR; p = 0.47). Reduction in TR grade was similar between groups (p = 0.27). Late mortality (p = 1.00) was comparable in both groups. Using log-rank analysis, there was no significant difference in the estimated survival between TVrpr and TVR (p = 0.88). TVrpr repair at the time of LVAD implant is effective in correcting TR even at the end of one year of follow-up. The choice to repair or replace does not affect the clinical outcome. © 2012 Wiley Periodicals, Inc.

Long-Term Evolution of Email Networks: Statistical Regularities, Predictability and Stability of Social Behaviors.

PubMed

Godoy-Lorite, Antonia; Guimerà, Roger; Sales-Pardo, Marta

2016-01-01

In social networks, individuals constantly drop ties and replace them by new ones in a highly unpredictable fashion. This highly dynamical nature of social ties has important implications for processes such as the spread of information or of epidemics. Several studies have demonstrated the influence of a number of factors on the intricate microscopic process of tie replacement, but the macroscopic long-term effects of such changes remain largely unexplored. Here we investigate whether, despite the inherent randomness at the microscopic level, there are macroscopic statistical regularities in the long-term evolution of social networks. In particular, we analyze the email network of a large organization with over 1,000 individuals throughout four consecutive years. We find that, although the evolution of individual ties is highly unpredictable, the macro-evolution of social communication networks follows well-defined statistical patterns, characterized by exponentially decaying log-variations of the weight of social ties and of individuals' social strength. At the same time, we find that individuals have social signatures and communication strategies that are remarkably stable over the scale of several years.

3D printed cellular solid outperforms traditional stochastic foam in long-term mechanical response

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maiti, A.; Small, W.; Lewicki, J.

3D printing of polymeric foams by direct-ink-write is a recent technological breakthrough that enables the creation of versatile compressible solids with programmable microstructure, customizable shapes, and tunable mechanical response including negative elastic modulus. However, in many applications the success of these 3D printed materials as a viable replacement for traditional stochastic foams critically depends on their mechanical performance and micro-architectural stability while deployed under long-term mechanical strain. To predict the long-term performance of the two types of foams we employed multi-year-long accelerated aging studies under compressive strain followed by a time-temperature-superposition analysis using a minimum-arc-length-based algorithm. The resulting master curvesmore » predict superior long-term performance of the 3D printed foam in terms of two different metrics, i.e., compression set and load retention. To gain deeper understanding, we imaged the microstructure of both foams using X-ray computed tomography, and performed finite-element analysis of the mechanical response within these microstructures. As a result, this indicates a wider stress variation in the stochastic foam with points of more extreme local stress as compared to the 3D printed material, which might explain the latter’s improved long-term stability and mechanical performance.« less

3D printed cellular solid outperforms traditional stochastic foam in long-term mechanical response

DOE PAGES

Maiti, A.; Small, W.; Lewicki, J.; ...

2016-04-27

3D printing of polymeric foams by direct-ink-write is a recent technological breakthrough that enables the creation of versatile compressible solids with programmable microstructure, customizable shapes, and tunable mechanical response including negative elastic modulus. However, in many applications the success of these 3D printed materials as a viable replacement for traditional stochastic foams critically depends on their mechanical performance and micro-architectural stability while deployed under long-term mechanical strain. To predict the long-term performance of the two types of foams we employed multi-year-long accelerated aging studies under compressive strain followed by a time-temperature-superposition analysis using a minimum-arc-length-based algorithm. The resulting master curvesmore » predict superior long-term performance of the 3D printed foam in terms of two different metrics, i.e., compression set and load retention. To gain deeper understanding, we imaged the microstructure of both foams using X-ray computed tomography, and performed finite-element analysis of the mechanical response within these microstructures. As a result, this indicates a wider stress variation in the stochastic foam with points of more extreme local stress as compared to the 3D printed material, which might explain the latter’s improved long-term stability and mechanical performance.« less

3D printed cellular solid outperforms traditional stochastic foam in long-term mechanical response

NASA Astrophysics Data System (ADS)

Maiti, A.; Small, W.; Lewicki, J. P.; Weisgraber, T. H.; Duoss, E. B.; Chinn, S. C.; Pearson, M. A.; Spadaccini, C. M.; Maxwell, R. S.; Wilson, T. S.

2016-04-01

3D printing of polymeric foams by direct-ink-write is a recent technological breakthrough that enables the creation of versatile compressible solids with programmable microstructure, customizable shapes, and tunable mechanical response including negative elastic modulus. However, in many applications the success of these 3D printed materials as a viable replacement for traditional stochastic foams critically depends on their mechanical performance and micro-architectural stability while deployed under long-term mechanical strain. To predict the long-term performance of the two types of foams we employed multi-year-long accelerated aging studies under compressive strain followed by a time-temperature-superposition analysis using a minimum-arc-length-based algorithm. The resulting master curves predict superior long-term performance of the 3D printed foam in terms of two different metrics, i.e., compression set and load retention. To gain deeper understanding, we imaged the microstructure of both foams using X-ray computed tomography, and performed finite-element analysis of the mechanical response within these microstructures. This indicates a wider stress variation in the stochastic foam with points of more extreme local stress as compared to the 3D printed material, which might explain the latter’s improved long-term stability and mechanical performance.

3D printed cellular solid outperforms traditional stochastic foam in long-term mechanical response

PubMed Central

Maiti, A.; Small, W.; Lewicki, J. P.; Weisgraber, T. H.; Duoss, E. B.; Chinn, S. C.; Pearson, M. A.; Spadaccini, C. M.; Maxwell, R. S.; Wilson, T. S.

2016-01-01

3D printing of polymeric foams by direct-ink-write is a recent technological breakthrough that enables the creation of versatile compressible solids with programmable microstructure, customizable shapes, and tunable mechanical response including negative elastic modulus. However, in many applications the success of these 3D printed materials as a viable replacement for traditional stochastic foams critically depends on their mechanical performance and micro-architectural stability while deployed under long-term mechanical strain. To predict the long-term performance of the two types of foams we employed multi-year-long accelerated aging studies under compressive strain followed by a time-temperature-superposition analysis using a minimum-arc-length-based algorithm. The resulting master curves predict superior long-term performance of the 3D printed foam in terms of two different metrics, i.e., compression set and load retention. To gain deeper understanding, we imaged the microstructure of both foams using X-ray computed tomography, and performed finite-element analysis of the mechanical response within these microstructures. This indicates a wider stress variation in the stochastic foam with points of more extreme local stress as compared to the 3D printed material, which might explain the latter’s improved long-term stability and mechanical performance. PMID:27117858

Dietary long-chain unsaturated fatty acids acutely and differently reduce the activities of lipogenic enzymes and of citrate carrier in rat liver.

PubMed

Gnoni, Antonio; Giudetti, Anna M

2016-09-01

The activities of lipogenic enzymes appear to fluctuate with changes in the level and type of dietary fats. Polyunsaturated fatty acids (PUFAs) are known to induce on hepatic de novo lipogenesis (DNL) the highest inhibitory effect, which occurs through a long-term adaptation. Data on the acute effects of dietary fatty acids on DNL are lacking. In this study with rats, the acute 1-day effect of high-fat (15 % w/w) diets (HFDs) enriched in saturated fatty acids (SFAs) or unsaturated fatty acids (UFAs), i.e., monounsaturated (MUFA) and PUFA, of the ω-6 and ω-3 series on DNL and plasma lipid level was investigated; a comparison with a longer time feeding (21 days) was routinely carried out. After 1-day HFD administration UFA, when compared to SFA, reduced plasma triacylglycerol (TAG) level and the activities of the lipogenic enzymes acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), a decreased activity of the citrate carrier (CIC), a mitochondrial protein linked to lipogenesis, was also detected. In this respect, ω-3 PUFA was the most effective. On the other hand, PUFA maintained the effects at longer times, and the acute inhibition induced by MUFA feeding on DNL enzyme and CIC activities was almost nullified at 21 days. Mitochondrial fatty acid composition was slightly but significantly changed both at short- and long-term treatment, whereas the early changes in mitochondrial phospholipid composition vanished in long-term experiments. Our results suggest that in the early phase of administration, UFA coordinately reduced both the activities of de novo lipogenic enzymes and of CIC. ω-3 PUFA showed the greatest effect.

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

PubMed

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

2017-03-01

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 (HbA 1C ), 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.

Long-life slab replacement concrete.

DOT National Transportation Integrated Search

2015-03-01

This research was initiated following reports of high incidence of cracking on FDOT concrete pavement replacement : slab projects. Field slabs were instrumented for data acquisition from high-early-strength concrete pavement : replacement slabs place...

Local anaesthetic infiltration for peri-operative pain control in total hip and knee replacement: systematic review and meta-analyses of short- and long-term effectiveness

PubMed Central

2014-01-01

mobilisation, and lower incidence of vomiting. Few studies reported long-term outcomes. Conclusions Local anaesthetic infiltration is effective in reducing short-term pain and hospital stay in patients receiving THR and TKR. Studies should assess whether local anaesthetic infiltration can prevent long-term pain. Enhanced pain control with additional analgesia through a catheter should be weighed against a possible infection risk. PMID:24996539

Local anaesthetic infiltration for peri-operative pain control in total hip and knee replacement: systematic review and meta-analyses of short- and long-term effectiveness.

PubMed

Marques, Elsa M R; Jones, Hayley E; Elvers, Karen T; Pyke, Mark; Blom, Ashley W; Beswick, Andrew D

2014-07-05

long-term outcomes. Local anaesthetic infiltration is effective in reducing short-term pain and hospital stay in patients receiving THR and TKR. Studies should assess whether local anaesthetic infiltration can prevent long-term pain. Enhanced pain control with additional analgesia through a catheter should be weighed against a possible infection risk.

Long-term follow-up of a female with congenital adrenal hyperplasia due to P450-oxidoreductase deficiency.

PubMed

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

2016-10-01

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.

Long-term ecosystem nitrogen storage and soil nitrogen availability in post-fire lodgepole pine ecosystems

Treesearch

Erica A. H. Smithwick; Daniel M. Kashian; Michael G. Ryan; Monica G.  Turner

2009-01-01

Long-term, landscape patterns in inorganic nitrogen (N) availability and N stocks following infrequent, stand-replacing fire are unknown but are important for interpreting the effect of disturbances on ecosystem function. Here, we present results from a replicated chronosequence study in the Greater Yellowstone Ecosystem (Wyoming, USA) directed at measuring inorganic N...

Replacement Planning: A Starting Point for Succession Planning and Talent Management

ERIC Educational Resources Information Center

Rothwell, William J.

2011-01-01

Replacement planning is a process of identifying short-term or long-term backups so that organizations have people who can assume responsibility for critical positions during emergencies. Individuals identified as "replacements" are not promised promotions; rather, they are prepared to the point where they can assume a critical position long…

[The switch of enzyme therapy in Fabry disease].

PubMed

Riccio, Eleonora; Pisani, Antonio

2014-01-01

Fabry disease (FD) is a multiorgan X-linked lysosomal storage disorder resulted from the deficiency of the lysosomal enzyme alpha galactosidase A. It particularly affects the heart, kidneys and cerebrovascular system. The treatment options for FD patients include long-term enzyme replacement therapy (ERT). Two recombinant enzyme formulations for the ERT of FD are available on European market: agalsidase alfa and agalsidase beta. Numerous evidences in the literature have confirmed the safety and efficacy of ERT. However, to date, there have been limited comparisons between the two agents, and no firm conclusion can be drawn regarding their specific efficacy and safety. In June 2009, a viral contamination in the manufacturing process of Fabrazyme led to a global shortage of agalsidase beta. Recommendations to shift patients to the recommended dose of Replagal were published by the European Medicines Agency (EMA) for all patients receiving Fabrazyme. This offered the unique opportunity to compare, although indirectly, the two drugs evaluating any clinical modification or adverse events that occurred after the switch. Moreover, with the increased availability of agalsidase beta in the last 3 months of 2012, some of the patients who previously switched to agalsidase alfa, were switched-back and returned to full-dose agalsidase beta. This article reviews the published evidence for the clinical efficacy of the two available enzyme preparations and compare it with the experience of our center.

Long-term outcome of large artificial patch aortic repair for diffuse stenosis in Williams syndrome.

PubMed

Sughimoto, Koichi; Takahara, Yoshiharu; Mogi, Kenji; Sakurai, Manabu; Aoki, Chikashi

2010-10-01

There have been only a few reports concerning the long-term results of a surgical procedure using a large artificial patch for patients with Williams syndrome. Twelve years have passed since a patient with William's syndrome underwent a surgery with a patch angioplasty for the diffuse supravalvular aortic stenosis and deformities of the neck branch arteries. The patient had a well-balanced aortic growth without stenotic or aneurysmal changes, which was confirmed during the time of the second surgery when replacing the mitral valve. This technique of using a large patch has proven to be safe for Williams syndrome patients with diffuse supravalvular aortic stenosis in the long term.

Textile for heart valve prostheses: fabric long-term durability testing.

PubMed

Heim, Frederic; Durand, Bernard; Chakfe, Nabil

2010-01-01

The rapid developments and success in percutaneous vascular surgery over the last two decades with the now common stent grafts implantation, make the noninvasive surgery technique today attractive even for heart valve replacement. Less traumatic for the patient and also less time consuming, percutaneous heart valve replacement is however at its beginning and restricted to end of life patients. The noninvasive procedure expects from the heart valve prosthesis material to be resistant and adapted to folding requirements of the implantation process (catheter). Polyester fabric could be a suited material for heart valve implanted percutaneously. Highly flexible and resistant, polyester fabric proved to be well adapted to the dynamic behavior of a valve and polyester (Dacron) is also widely used for vascular grafts implantation and shows good biocompatibility and durability. However, today there's no data available on long-term durability of fabric used as heart valve material. The purpose of this work is to study the long term behavior of a microdenier polyester fabric construction under combined in vitro flexure and tension fatigue stress. In the novel in vitro testing technique presented, a fabric specimen was subjected to combined flexural and tensile fatigue generated by fluid flow under physiological pressure conditions. The results obtained show how flexural properties change with fatigue time, which reflects directly on the suitability of a fabric in such devices. It was also observed that these fabric structural changes directly influence the in vitro behavior of the textile heart valve prosthesis. (c) 2009 Wiley Periodicals, Inc.

Long-term urethral catheterisation.

PubMed

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.

Long-term solar-terrestrial observations

NASA Technical Reports Server (NTRS)

1988-01-01

The results of an 18-month study of the requirements for long-term monitoring and archiving of solar-terrestrial data is presented. The value of long-term solar-terrestrial observations is discussed together with parameters, associated measurements, and observational problem areas in each of the solar-terrestrial links (the sun, the interplanetary medium, the magnetosphere, and the thermosphere-ionosphere). Some recommendations are offered for coordinated planning for long-term solar-terrestrial observations.

HDAC Inhibition Modulates Hippocampus-Dependent Long-Term Memory for Object Location in a CBP-Dependent Manner

ERIC Educational Resources Information Center

Haettig, Jakob; Stefanko, Daniel P.; Multani, Monica L.; Figueroa, Dario X.; McQuown, Susan C.; Wood, Marcelo A.

2011-01-01

Transcription of genes required for long-term memory not only involves transcription factors, but also enzymatic protein complexes that modify chromatin structure. Chromatin-modifying enzymes, such as the histone acetyltransferase (HAT) CREB (cyclic-AMP response element binding) binding protein (CBP), are pivotal for the transcriptional regulation…

Long-term results of heart valve replacement with the Edwards Duromedics bileaflet prosthesis: a prospective ten-year clinical follow-up.

PubMed

Podesser, B K; Khuenl-Brady, G; Eigenbauer, E; Roedler, S; Schmiedberger, A; Wolner, E; Moritz, A

1998-05-01

The Edwards Duromedics valve (Baxter Healthcare Corp., Edwards Division, Santa Ana, Calif.) was designed with a self-irrigating hinge mechanism to reduce thromboembolic complications. After good initial clinical results, distribution was suspended in 1988 after reports of valve fracture after 20,000 valves had been implanted. The manufacturer conducted extensive studies to improve the Edwards Duromedics and reintroduced a modified version, which is available as Edwards Tekna. The purpose of the study was the evaluation of long-term results of the original Edwards Duromedics that might be important for the current version, the Edwards Tekna valve. A prospective clinical 10-year follow-up was performed of 508 patients who underwent valve replacement with the Edwards Duromedics valve in the aortic (n = 268), mitral (n = 183), and aortic and mitral (n = 56) position. The perioperative mortality rate was 6.9%; follow-up was 98% complete, comprising 3648 patient-years for a mean follow-up of 86 months (range: 33 to 144 months). The actuarial freedom from complications at the 10-year follow-up and the incidence rate (percent per patient-year) were as follows: late mortality rate, 69.2% +/- 2.4% (3.5% per patient-year); thromboembolism, 90.7% +/- 1.6% (0.96% per patient-year); anticoagulation-related hemorrhage, 87.7% +/- 1.7% (1.34% per patient-year); prosthetic valve endocarditis, 96.7% +/- 0.09% (0.38% per patient-year); valve-related mortality rate, 89.3% +/- 1.6% (1.21% per patient-year); valve failure, 86.2% +/- 1.85% (1.54% per patient-year); and valve-related morbidity and mortality rate, 71.1% +/- 2.3% (3.2% per patient-year). Three leaflet escapes were observed (one lethal, two successful reoperations; 99.1% +/- 0.05% freedom, 0.08% per patient-year). All patients functionally improved (86% in New York Heart Association classes I and II), and incidence of anemia was insignificant. These results confirm that the Edwards Duromedics valve shows excellent performance

Effects of short-term and long-term treatment with medium- and long-chain triglycerides ketogenic diet on cortical spreading depression in young rats.

PubMed

de Almeida Rabello Oliveira, Marcela; da Rocha Ataíde, Terezinha; de Oliveira, Suzana Lima; de Melo Lucena, Ana Luíza; de Lira, Carla Emmanuela Pereira Rodrigues; Soares, Anderson Acioli; de Almeida, Clarissa Beatriz Santos; Ximenes-da-Silva, Adriana

2008-03-21

The ketogenic diet (KD) is a high fat and low carbohydrate and protein diet. It is used in the clinical treatment of epilepsy, in order to decrease cerebral excitability. KD is usually composed by long-chain triglycerides (LCT) while medium-chain triglycerides (MCT) diet is beginning to be used in some clinical treatment of disorders of pyruvate carboxylase enzyme and long-chain fatty acid oxidation. Our study aimed to analyze the effects of medium- and long-chain KD on cerebral electrical activity, analyzing the propagation of the phenomenon of cortical spreading depression (CSD). Three groups of weaned rats (21 days old) received, for 7 weeks, either a control (AIN-93G diet), or a MCT-KD (rich in triheptanoin oil), or a LCT-KD (rich in soybean oil). They were compared to another three groups (21 days old) receiving the same diets for just 10 days. CSD propagation was evaluated just after ending the dietary treatments. Results showed that short-term KD treatment resulted in a significant reduction of the CSD velocity of propagation (control group: 4.02+/-1.04mm/min; MCT-KD: 0.81+/-1.46mm/min and LCT-KD: 2.26+/-0.41mm/min) compared to the control group. However, long-term treatment with both KDs had no effect on the CSD velocity (control group: 3.10+/-0.41mm/min, MCT-KD: 2.91+/-1.62mm/min, LCT-KD: 3.02+/-2.26mm/min) suggesting that both short-term KDs have a positive effect in decreasing brain cerebral excitability in young animals. These data show for the first time that triheptanoin has an effect on central nervous system.

Long-term care: long-term care insurance--2005. End of Year Issue Brief.

PubMed

Tanner, Rachel; Bercaw, Lawren

2005-12-31

As the "Baby Boom" generation approaches retirement, state and federal lawmakers are struggling to ensure that the nation's long-term care system will provide adequate services for the growing number of senior citizens. A 2003 Administration on Aging report predicted that the elderly population will double by 2030. Accordingly, policymakers must prepare for the impending squeeze on public health and Medicaid resources. Many consumers are exploring private long-term care insurance options as a means of preparing for the cost of eldercare. Yet, a lack of market uniformity has rendered the long-term care insurance industry somewhat difficult for consumers to decipher. In addition, senior care insurance is often costly, particularly for those over age 50.

Enzyme replacement prevents enamel defects in hypophosphatasia mice

PubMed Central

Yadav, Manisha C.; de Oliveira, Rodrigo Cardoso; Foster, Brian L.; Fong, Hanson; Cory, Esther; Narisawa, Sonoko; Sah, Robert L.; Somerman, Martha; Whyte, Michael P.; Millán, José Luis

2012-01-01

Hypophosphatasia (HPP) is the inborn error of metabolism characterized by deficiency of alkaline phosphatase activity leading to rickets or osteomalacia and to dental defects. HPP occurs from loss-of-function mutations within the gene that encodes the tissue-nonspecific isozyme of alkaline phosphatase (TNAP). TNAP knockout (Alpl−/−, a.k.a. Akp2−/−) mice closely phenocopy infantile HPP, including the rickets, vitamin B6-responsive seizures, improper dentin mineralization, and lack of acellular cementum. Here, we report that lack of TNAP in Alpl−/− mice also causes severe enamel defects, which are preventable by enzyme replacement with mineral-targeted TNAP (ENB-0040). Immunohistochemistry was used to map the spatiotemporal expression of TNAP in the tissues of the developing enamel organ of healthy mouse molars and incisors. We found strong, stage-specific expression of TNAP in ameloblasts. In the Alpl−/− mice, histological, μCT, and scanning electron microscopy analysis showed reduced mineralization and disrupted organization of the rods and inter-rod structures in enamel of both the molars and incisors. All of these abnormalities were prevented in mice receiving from birth daily subcutaneous injections of mineral-targeting, human TNAP (sALP-FcD10, a.k.a. ENB-0040) at 8.2 mg/kg/day for up to 44 days. These data reveal an important role for TNAP in enamel mineralization, and demonstrate the efficacy of mineral-targeted TNAP to prevent enamel defects in HPP. PMID:22461224

Fabry disease in children: agalsidase-beta enzyme replacement therapy.

PubMed

Borgwardt, L; Feldt-Rasmussen, U; Rasmussen, A K; Ballegaard, M; Meldgaard Lund, A

2013-05-01

Fabry disease is a rare, multiorgan disease. The most serious complications involve the kidney, brain and heart. This study aims to assess the effect of enzyme replacement therapy (ERT) using agalsidase-beta in children with Fabry disease. We carried out a nationwide, descriptive and observational retrospective cohort study of 10 children (9-16 years at baseline), who underwent regular systematic investigations for 1-8 years after initiation of ERT with agalsidase-beta (Fabryzyme®, Genzyme). Ophthalmological, echocardiographic abnormalities and hypohidrosis were found at baseline and during the follow-up period. Serious kidney, heart or brain involvement had not developed at the last follow-up examination. For the majority of the patients improvements were found concerning headache, acroparaesthesias and gastrointestinal pain during the follow-up period. The level of energy and physical activity also increased. Treatment with agalsidase-beta was associated with a reduction of neuropathic and abdominal pain and headache. Although all aspects of the Fabry pain phenotype cannot be treated with ERT, the observed effects were clinically significant in the lives of the majority of Fabry children and together with the absence of serious Fabry manifestations at last follow-up, we argue that early initiation of ERT may be considered. © 2012 John Wiley & Sons A/S.

Long-term associative learning predicts verbal short-term memory performance.

PubMed

Jones, Gary; Macken, Bill

2018-02-01

Studies using tests such as digit span and nonword repetition have implicated short-term memory across a range of developmental domains. Such tests ostensibly assess specialized processes for the short-term manipulation and maintenance of information that are often argued to enable long-term learning. However, there is considerable evidence for an influence of long-term linguistic learning on performance in short-term memory tasks that brings into question the role of a specialized short-term memory system separate from long-term knowledge. Using natural language corpora, we show experimentally and computationally that performance on three widely used measures of short-term memory (digit span, nonword repetition, and sentence recall) can be predicted from simple associative learning operating on the linguistic environment to which a typical child may have been exposed. The findings support the broad view that short-term verbal memory performance reflects the application of long-term language knowledge to the experimental setting.

Organomatics and organometrics: Novel platforms for long-term whole-organ culture

PubMed Central

Bruinsma, Bote G.; Yarmush, Martin L.; Uygun, Korkut

2014-01-01

Organ culture systems are instrumental as experimental whole-organ models of physiology and disease, as well as preservation modalities facilitating organ replacement therapies such as transplantation. Nevertheless, a coordinated system of machine perfusion components and integrated regulatory control has yet to be fully developed to achieve long-term maintenance of organ function ex vivo. Here we outline current strategies for organ culture, or organomatics, and how these systems can be regulated by means of computational algorithms, or organometrics, to achieve the organ culture platforms anticipated in modern-day biomedicine. PMID:25035864

Asthma Medicines: Long-Term Control

MedlinePlus

... 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. ...

Association of Patient-Reported Health Status with Long-Term Mortality after Transcatheter Aortic Valve Replacement: A Report from the STS/ACC TVT Registry™

PubMed Central

Arnold, Suzanne V.; Spertus, John A.; Vemulapalli, Sreekanth; Dai, Dadi; O’Brien, Sean M.; Baron, Suzanne J.; Kirtane, Ajay J.; Mack, Michael J.; Green, Philip; Reynolds, Matthew R.; Rumsfeld, John S.; Cohen, David J.

2015-01-01

Background Although transcatheter aortic valve replacement (TAVR) is an effective treatment for aortic stenosis, long-term mortality after TAVR remains high and challenging to predict. The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a health status measure, assessed directly from patients, that integrates two clinically relevant factors (symptoms and functional status) that may predict TAVR outcomes. Methods and Results Among 7769 patients from 286 sites in the STS-ACC TVT Registry, we examined the association between pre-procedure (baseline) patient health status, as assessed by the KCCQ, and 1-year mortality after TAVR. The KCCQ Overall Summary Score was categorized as very poor: <25, poor: 25–49, fair: 50–74, or good: ≥75. Prior to TAVR, health status was rated as very poor in 28%, poor in 38%, fair in 24%, and good in 10%. Patients with worse health status were more likely to be female and had more comorbidities and higher STS mortality risk scores. Compared with those with good health status prior to TAVR, and after adjusting for a broad range of baseline covariates, patients with very poor health status had a 2-fold increased hazard of death over the first year after TAVR (adjusted HR 2.00, 95% CI 1.58–2.54), while those with poor and fair health status had intermediate outcomes (adjusted HRs 1.54, 95% CI 1.22–1.95 and 1.20, 95% CI 0.94–1.55, respectively). Conclusions In a national, contemporary practice cohort, worse pre-procedure patient health status, as assessed by the KCCQ, was associated with greater long-term mortality after TAVR. These results support the measurement and integration of the KCCQ into mortality risk assessments for patients considering TAVR. PMID:26643740

Determination of Monoamine Oxidase A and B Activity in Long-Term Treated Patients With Parkinson Disease.

PubMed

Müller, Thomas; Riederer, Peter; Grünblatt, Edna

Biogenic amines and monoamine oxidase inhibitors influence peripheral monoamine oxidase enzyme activity in chronic levodopa/dopa decarboxylase inhibitor-treated patients with Parkinson disease. Rasagiline is an irreversible inhibitor of monoamine oxidase B. Safinamide blocks this isoenzyme in a reversible fashion. The aim of this study was to determine monoamine oxidase A (plasma) and B (platelets) enzyme activity in long-term levodopa-treated patients without and with additional oral intake of 50- or 100-mg safinamide or 1-mg rasagiline or first-time intake of rasagiline. Monoamine oxidase A enzyme activity did not differ between all groups. Patients on rasagiline or safinamide showed lower monoamine oxidase-B enzyme activity compared with patients without monoamine oxidase B inhibitor intake. No impact of the number of previous oral levodopa intakes was found. Rasagiline and safinamide did not essentially differ in terms of inhibition of monoamine oxidase B despite their different pharmacology regarding reversibility of monoamine oxidase B inhibition. In view of the observed, considerable heterogeneity of enzyme activities, we suggest to determine activities of monoamine oxidase A and B to reduce the risk for tyramine-induced hypertension and the serotonergic syndrome during chronic therapy with rasagiline or safinamide.

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

PubMed

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

2016-04-01

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.

Physiological performance of the intertidal Manila clam (Ruditapes philippinarum) to long-term daily rhythms of air exposure

PubMed Central

Yin, Xuwang; Chen, Peng; Chen, Hai; Jin, Wen; Yan, Xiwu

2017-01-01

Intertidal organisms, especially the sessile species, often experience long-term periodic air exposure during their lives. Learning the biochemical and physiological responses of intertidal organisms to long-term periodic air exposure and the relationship to duration of air exposure provides insight into adaptation to this variably stressful environment. We studied the Manila clam, Ruditapes philippinarum, an important species in world aquaculture, as a model to evaluate survival, growth, lipid composition, oxygen consumption, oxidative damage, and antioxidant enzyme activity in relation to the duration of air exposure in a long-term (60 days) laboratory study of varying durations of periodic emersion and re-immersion. Our results show: (1) clams undergoing a longer period of air exposure had lower survival and growth compared to those given a shorter exposure, (2) levels of oxidative damage and activities of antioxidant enzymes were higher in all air exposure treatments, but did not increase with duration of air exposure, and (3) the content of docosahexaenoic acid increased with duration of air exposure. Our results can largely be interpreted in the context of the energy expenditure by the clams caused by aerobic metabolism during the daily cycle of emersion and re-immersion and the roles of docosahexaenoic acid against oxidative stress. PMID:28128354

Reforming long-term care financing through insurance

PubMed Central

Meiners, Mark R.

1988-01-01

Until recently, insurance for long-term care was not viewed as feasible. This perception has changed dramatically in the past few years. Several models of long-term care insurance have begun to be tested. Although the application of insurance principles to long-term care is still new, the emergence of private market interest in developing long-term care insurance has been a catalyst to renewed public-policy support for reforming the way we pay for long-term care. States, in particular, have become interested in developing public-private partnerships to support the emergence of long-term care insurance that could help relieve the mounting pressure on Medicaid budgets. PMID:10312962

Management training in long-term care.

PubMed

Evashwick, Connie

2002-01-01

The education of health care administrators faces its most dramatic change since the inception of the field. Recent discussions at the national level call for major overhaul of curricula and teaching modalities, including moving education to position students for evidence-based practice. This paper presents recommendations for incorporating training about chronic and long-term care into health care management curricula. It asserts that all health care management students should have a basic knowledge of the fundamental policy, operating, and financing principles of long-term care. The majority of people using the health care delivery system today, and increasingly in the future, suffer from chronic conditions. Long-term care services, although less expansive in structure, far outnumber acute care services and health plans. They will grow in the future to meet the portending demand. To maximize job opportunities and to optimize performance in any job, health care administrators need to know about the long-term care delivery system. This paper delineates critical topics pertaining to long-term care, organized according to 11 fundamental management areas in which the field is developing core competencies. The contents were derived from a year-long process of asking stakeholders in the various facets of long-term care what topics they thought were essential for administrators to know. The topics delineated in this document represent the consensus about essential knowledge that all health care administrators should have about long-term care, whether specializing in long-term care or following a more general management career. The education of health care administrators faces its most dramatic change since the inception ofthe field. Recent discussions at the national level call for major overhaul of curricula and teaching modalities, including moving education to position students to perform according to evidence-based practice. It is thus timely to consider content, as

Recent Patents and Designs on Hip Replacement Prostheses

PubMed Central

Derar, H; Shahinpoor, M

2015-01-01

Hip replacement surgery has gone through tremendous evolution since the first procedure in 1840. In the past five decades the advances that have been made in technology, advanced and smart materials innovations, surgical techniques, robotic surgery and methods of fixations and sterilization, facilitated hip implants that undergo multiple design revolutions seeking the least problematic implants and a longer survivorship. Hip surgery has become a solution for many in need of hip joint remedy and replacement across the globe. Nevertheless, there are still long-term problems that are essential to search and resolve to find the optimum implant. This paper reviews several recent patents on hip replacement surgery. The patents present various designs of prostheses, different materials as well as methods of fixation. Each of the patents presents a new design as a solution to different issues ranging from the longevity of the hip prostheses to discomfort and inconvenience experienced by patients in the long-term. PMID:25893020

Placenta previa and long-term morbidity of the term offspring.

PubMed

Walfisch, Asnat; Beharier, Ofer; Shoham-Vardi, Ilana; Sergienko, Ruslan; Landau, Daniella; Sheiner, Eyal

2016-08-01

The long-term impact of placenta previa on term infants is unknown. We aimed to investigate whether abnormal placentation increases the risk for long-term morbidity of the term offspring. A population-based cohort study compared the incidence of long-term hospitalizations up to the age of 18 due to cardiovascular, endocrine, neurological, hematological, respiratory and urinary morbidity of children born at term in pregnancies diagnosed with placenta previa and those without. Deliveries occurred between the years 1991-2013 in a tertiary medical center. Multiple pregnancies, and fetal congenital malformations were excluded. Kaplan-Meier survival curves were used to compare cumulative morbidity incidence over time. A multivariable generalized estimating equation (GEE) logistic regression model analysis was used to control for confounders and for maternal clusters. During the study period 233,123 term deliveries met the inclusion criteria; 0.2% (n=502) of the children were born to mothers with placenta previa. During the follow-up period, children born to mothers with placenta previa did not have an increased risk for long-term cardiovascular, endocrine, hematological, neurological, respiratory, and urinary morbidity. Term offsprings of mothers diagnosed with placenta previa do not appear to be at an increased risk for long-term morbidity up to the age of 18. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Consider long-term care as service alternative.

PubMed

Loria, L S

1987-04-01

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.

Long-term data archiving

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moore, David Steven

2009-01-01

Long term data archiving has much value for chemists, not only to retain access to research and product development records, but also to enable new developments and new discoveries. There are some recent regulatory requirements (e.g., FDA 21 CFR Part 11), but good science and good business both benefit regardless. A particular example of the benefits of and need for long term data archiving is the management of data from spectroscopic laboratory instruments. The sheer amount of spectroscopic data is increasing at a scary rate, and the pressures to archive come from the expense to create the data (or recreatemore » it if it is lost) as well as its high information content. The goal of long-term data archiving is to save and organize instrument data files as well as any needed meta data (such as sample ID, LIMS information, operator, date, time, instrument conditions, sample type, excitation details, environmental parameters, etc.). This editorial explores the issues involved in long-term data archiving using the example of Raman spectral databases. There are at present several such databases, including common data format libraries and proprietary libraries. However, such databases and libraries should ultimately satisfy stringent criteria for long term data archiving, including readability for long times into the future, robustness to changes in computer hardware and operating systems, and use of public domain data formats. The latter criterion implies the data format should be platform independent and the tools to create the data format should be easily and publicly obtainable or developable. Several examples of attempts at spectral libraries exist, such as the ASTM ANDI format, and the JCAMP-DX format. On the other hand, proprietary library spectra can be exchanged and manipulated using proprietary tools. As the above examples have deficiencies according to the three long term data archiving criteria, Extensible Markup Language (XML; a product of the World Wide

Long-Term Control Medications for Lung Diseases

MedlinePlus

... Asthma Medications Long-Term Control Medications Long-Term Control Medications Make an Appointment Ask a Question Refer Patient Long-term control medications are taken daily to control and prevent ...

Reforming Long-Term Care Funding in Alberta.

PubMed

Crump, R Trafford; Repin, Nadya; Sutherland, Jason M

2015-01-01

Like many provinces across Canada, Alberta is facing growing demand for long-term care. Issues with the mixed funding model used to pay long-term care providers had Alberta Health Services concerned that it was not efficiently meeting the demand for long-term care. Consequently, in 2010, Alberta Health Services introduced the patient/care-based funding (PCBF) model. PCBF is similar to activity-based funding in that it directly ties the complexity and care needs of long-term care residents to the payment received by long-term care providers. This review describes PCBF and discusses some of its strengths and weaknesses. In doing so, this review is intended to inform other provinces faced with similar long-term care challenges and contemplating their own funding reforms.

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

PubMed Central

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

2003-01-01

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

Long-term health of dopaminergic neuron transplants in Parkinson's disease patients.

PubMed

Hallett, Penelope J; Cooper, Oliver; Sadi, Damaso; Robertson, Harold; Mendez, Ivar; Isacson, Ole

2014-06-26

To determine the long-term health and function of transplanted dopamine neurons in Parkinson's disease (PD) patients, the expression of dopamine transporters (DATs) and mitochondrial morphology were examined in human fetal midbrain cellular transplants. DAT was robustly expressed in transplanted dopamine neuron terminals in the reinnervated host putamen and caudate for at least 14 years after transplantation. The transplanted dopamine neurons showed a healthy and nonatrophied morphology at all time points. Labeling of the mitochondrial outer membrane protein Tom20 and α-synuclein showed a typical cellular pathology in the patients' own substantia nigra, which was not observed in transplanted dopamine neurons. These results show that the vast majority of transplanted neurons remain healthy for the long term in PD patients, consistent with clinical findings that fetal dopamine neuron transplants maintain function for up to 15-18 years in patients. These findings are critically important for the rational development of stem-cell-based dopamine neuronal replacement therapies for PD. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Mitral valve replacement with preservation of the subvalvular apparatus.

PubMed

Reardon, M J; David, T E

1999-03-01

The introduction of the Starr-Edwards valve allowed complete replacement of diseased left-sided heart valves. With improved cardiopulmonary bypass, myocardial protection, and surgical techniques the mortality rate from aortic valve replacement decreased substantially, whereas the mortality rate from mitral valve replacement remained high, largely because of low cardiac output syndrome. Increasing use of mitral valve repair techniques resulted in a marked decrease in short-term and long-term morbidity and mortality when treating patients with mitral regurgitation. Some believed that this resulted from maintenance of the mitral annular papillary muscle continuity during mitral valve repair. Subsequent experimental and clinical studies have validated the positive short-term and long-term effects of maintaining the integrity of the mitral valve subvalvular apparatus. This article considers the history of the clinical use of preservation of the subvalvular apparatus, the physiologic studies examining this concept, and the clinical data available on its use. It also examines the following: 1) mitral stenosis versus mitral regurgitation and the preservation of the subvalvular apparatus; 2) whether the anterior, posterior, or both areas of the subvalvular apparatus should be preserved; and 3) the surgical techniques for the preservation of the subvalvular apparatus and valve implantation.

Hormonal development therapy (HDT) in hypogonadism in long-term view.

PubMed

Heinz, Marlene

2010-04-01

Since the 1960s, oestrogen deficiency in hypogonadism in girls has been successfully treated by a sort of analogous application of the menopausal hormone replacement therapy (HRT) scheme, here however, to induce and support sexual development in puberty and adolescence. The essential distinction between goals, ways and means of the two distinct hormonal treatments caused by menopause and by hypogonadism in puberty also suggests that the latter treatment is more characteristic of defining hormonal development therapy (HDT). Moreover, specific HDT in hypogonadism is essential for longitudinal growth of girls, functions of female reproductive system, bone and lipid metabolism and the immune, central nervous and cardiovascular systems. By contrast, the aim of menopausal replacement therapy in elderly women is treating negative effects of physiological loss of oestrogens as hot flush, lacks of female well-being and osteoporosis, while in hypogonadal girls there is of course nothing that might be replaced eventually. Especially in cases of absolute oestrogen deficiency, as in Turner syndrome and in other cases of premature ovarian failure, HDT has to be started at the age of expected puberty. An international consensus suggests possibly lifelong HDT for the lasting support of female development and functions. However, neither reliable studies about possible risks and side effects of continuous hormonal therapy in adult women with hypogonadismus nor a more precise consensus have emerged yet. Emphasising the term HDT particularly aims at putting more effort in getting over these paucities simultaneously. Indications, hormonal therapy, dosage, application and timing in puberty are described in this article. Aspects of long-term hormonal treatment are critically discussed. Copyright 2010 Elsevier Ltd. All rights reserved.

The outcome of clinical parameters in adults with severe Type I Gaucher disease using very low dose enzyme replacement therapy.

PubMed

Wilson, Callum; Spearing, Ruth; Teague, Lochie; Robertson, Patsy; Blacklock, Hilary

2007-01-01

Enzyme replacement therapy is now well established as the treatment of choice in Type I Gaucher disease. Historically higher dosage regimens have been used in preference to lower doses despite the little clinical evidence in the way of large controlled clinical trials to support this. Moreover, the extraordinary cost of therapy means that not all eligible patients are able to be treated at the higher dose. Twelve type I adult patients with relatively severe disease were commenced on a very low dose of 7.5U of alglucerase/imiglucerase per kg every two weeks (initially given thrice weekly and later weekly). Follow-up 5 year data reveal a good visceral and haematological response with outcomes consistent with recently published treatment guidelines. Satisfactory clinical and radiological skeletal improvement was also demonstrated in most patients. Three patients had an inadequate overall skeletal response to therapy. Biomarkers also steadily improved although perhaps not quite at the same rate as that seen in higher doses. Very low dose enzyme replacement therapy may be appropriate for adult type I Gaucher patients with mild-moderate skeletal disease.

Cardiomyopathy and response to enzyme replacement therapy in a male mouse model for Fabry disease.

PubMed

Nguyen Dinh Cat, Aurelie; Escoubet, Brigitte; Agrapart, Vincent; Griol-Charhbili, Violaine; Schoeb, Trenton; Feng, Wenguang; Jaimes, Edgar; Warnock, David G; Jaisser, Frederic

2012-01-01

Fabry disease is an X-linked disorder of glycosphingolipid metabolism that results in progressive accumulation of neutral glycosphingolipids, (predominately globotriaosylceramide; GL-3) in lysosomes, as well as other cellular compartments and the extracellular space. Our aim was to characterize the cardiac phenotype of male knock-out mice that are deficient in alpha-galactosidase A activity, as a model for Fabry disease and test the efficacy of Enzyme Replacement Therapy with agalsidase-beta. Male mice (3-4 months of age) were characterized with awake blood pressure and heart rate measurements, cardiac echocardiography and electrocardiography measurements under light anesthesia, histological studies and molecular studies with real-time polymerase chain reaction. The Fabry knock-out mouse has bradycardia and lower blood pressure than control wild type (CB7BL/6J) mice. In Fabry knock-out mice, the cardiomyopathy associated mild hypertrophy at echography with normal systolic LV function and mild diastolic dysfunction. Premature atrial contractions were more frequent in without conduction defect. Heart weight normalized to tibial length was increased in Fabry knock-out mice. Ascending aorta dilatation was observed. Molecular studies were consistent with early stages of cardiac remodeling. A single dose of agalsidase-beta (3 mg/kg) did not affect the LV hypertrophy, function or heart rate, but did improve the mRNA signals of early cardiac remodeling. In conclusion, the alpha-galactosidase A deficient mice at 3 to 4 months of age have cardiac and vascular alterations similar to that described in early clinical stage of Fabry disease in children and adolescents. Enzyme replacement therapy affects cardiac molecular remodeling after a single dose.

Cardiomyopathy and Response to Enzyme Replacement Therapy in a Male Mouse Model for Fabry Disease

PubMed Central

Nguyen Dinh Cat, Aurelie; Escoubet, Brigitte; Agrapart, Vincent; Griol-Charhbili, Violaine; Schoeb, Trenton; Feng, Wenguang; Jaimes, Edgar; Warnock, David G.; Jaisser, Frederic

2012-01-01

Fabry disease is an X-linked disorder of glycosphingolipid metabolism that results in progressive accumulation of neutral glycosphingolipids, (predominately globotriaosylceramide; GL-3) in lysosomes, as well as other cellular compartments and the extracellular space. Our aim was to characterize the cardiac phenotype of male knock-out mice that are deficient in alpha-galactosidase A activity, as a model for Fabry disease and test the efficacy of Enzyme Replacement Therapy with agalsidase-beta. Male mice (3–4 months of age) were characterized with awake blood pressure and heart rate measurements, cardiac echocardiography and electrocardiography measurements under light anesthesia, histological studies and molecular studies with real-time polymerase chain reaction. The Fabry knock-out mouse has bradycardia and lower blood pressure than control wild type (CB7BL/6J) mice. In Fabry knock-out mice, the cardiomyopathy associated mild hypertrophy at echography with normal systolic LV function and mild diastolic dysfunction. Premature atrial contractions were more frequent in without conduction defect. Heart weight normalized to tibial length was increased in Fabry knock-out mice. Ascending aorta dilatation was observed. Molecular studies were consistent with early stages of cardiac remodeling. A single dose of agalsidase-beta (3 mg/kg) did not affect the LV hypertrophy, function or heart rate, but did improve the mRNA signals of early cardiac remodeling. In conclusion, the alpha-galactosidase A deficient mice at 3 to 4 months of age have cardiac and vascular alterations similar to that described in early clinical stage of Fabry disease in children and adolescents. Enzyme replacement therapy affects cardiac molecular remodeling after a single dose. PMID:22574107

Long-life slab replacement concrete : [summary].

DOT National Transportation Integrated Search

2015-04-01

Concrete slab replacement projects in Florida have demonstrated a high incidence of : replacement slab cracking. Causes of cracking have not been reliably determined. University of South Florida researchers : sought to identify the factors or : param...

Meal replacement reduces insulin requirement, HbA1c and weight long-term in type 2 diabetes patients with >100 U insulin per day.

PubMed

Kempf, K; Schloot, N C; Gärtner, B; Keil, R; Schadewaldt, P; Martin, S

2014-04-01

Despite high insulin doses, good glycaemic control is often lacking in type 2 diabetes patients and new therapeutic options are needed. In a proof of principle study, an energy-restricted, protein-rich meal replacement (PRMR) was examined as a means of reducing insulin requirement, HbA1C and body weight. Obese type 2 diabetes patients (n = 22) with >100 U insulin per day replaced, in week 1, the three main meals with 50 g of PRMR (Almased-Vitalkost) each (= 4903 kJ day(-1) ). In weeks 2-4, breakfast and dinner were replaced, and, in weeks 5-12, only dinner was replaced. Clinical parameters were determined at baseline, and after 4, 8 and 12 weeks, as well as after 1.5 years of follow-up. The Wilcoxon signed-rank test was used for the intention-to-treat analysis and the Mann-Whitney U-test for subgroup analyses. The 12-week-programme was completed by 15 participants (68%). After 1 week, the mean insulin dose was reduced from 147 (75) U to 91 (55) U day(-1) (P = 0.0001), and to 65 (32) U (P < 0.0001) after 12 weeks of study. Over a period of 12 weeks, HbA1c decreased from 8.8% (1.4%) to 8.1% (1.6%) (P = 0.048) and weight decreased from 118.0 (19.7) kg to 107.4 (19.2) kg (P < 0.0001). Moreover, body mass index, waist and hip circumference, fasting blood glucose, triglycerides and high-density lipoprotein cholesterol improved significantly. After 1.5 years, insulin requirement and weight remained significantly lower than baseline. Participants who continued PRMR further reduced their HbA1c, weight and insulin dose. Two patients were able to stop insulin therapy altogether. Energy-restricted PRMR was effective in reducing insulin requirement of type 2 diabetes patients with intensified insulin therapy accompanied by a reduction of HbA1c, weight and other cardiometabolic risk factors. With the continuous use of PRMR, glycaemic control might be improved in the long term. © 2013 The British Dietetic Association Ltd.

Catalyzed enzyme electrodes

DOEpatents

Zawodzinski, Thomas A.; Wilson, Mahlon S.; Rishpon, Judith; Gottesfeld, Shimshon

1993-01-01

An enzyme electrode is prepared with a composite coating on an electrical conductor. The composite coating is formed from a casting solution of a perfluorosulfonic acid polymer, an enzyme, and a carbon supported catalyst. The solution may be cast directly on the conductor surface or may be formed as a membrane and applied to the surface. The perfluorosulfonic acid ionomer formed from the casting solution provides an insoluble biocompatible protective matrix for the enzyme and acts to retain the enzyme for long term availability in the electrode structure. The carbon supported catalyst provides catalytic sites throughout the layer for the oxidation of hydrogen peroxide from the enzyme reactions. The carbon support then provides a conductive path for establishing an electrical signal to the electrical conductor. In one embodiment, the electrical conductor is a carbon cloth that permits oxygen or other gas to be introduced to the perfluorosulfonic polymer to promote the enzyme reaction independent of oxygen in the solution being tested.

Cerebellar Alterations and Gait Defects as Therapeutic Outcome Measures for Enzyme Replacement Therapy in α-Mannosidosis

PubMed Central

Damme, Markus; Stroobants, Stijn; Walkley, Steven U.; Lüllmann-Rauch, Renate; D`Hooge, Rudi; Fogh, Jens; Saftig, Paul; Lübke, Torben; Blanz, Judith

2011-01-01

α-Mannosidosis is a rare lysosomal storage disease with accumulation of undegraded mannosyl-linked oligosaccharides in cells throughout the body, most notably in the CNS. This leads to a broad spectrum of neurological manifestations, including progressive intellectual impairment, disturbed motor functions and cerebellar atrophy. To develop therapeutic outcome measures for enzyme replacement therapy (ERT) that could be used for human patients, a gene knockout model of α-mannosidosis in mice was analyzed for CNS pathology and motor deficits. In the cerebellar molecular layer, α-mannosidosis mice display clusters of activated Bergman glia, infiltration of phagocytic macrophages and accumulation of free cholesterol and gangliosides (GM1), notably in regions lacking Purkinje cells. α-mannosidosis brain lysates also displayed increased expression of Lamp1 and hyperglycosylation of the cholesterol binding protein NPC2. Detailed assessment of motor function revealed age-dependent gait defects in the mice that resemble the disturbed motor function in human patients. Short-term ERT partially reversed the observed cerebellar pathology with fewer activated macrophages and astrocytes but unchanged levels of hyperglycosylated NPC2, gangliosides and cholesterol. The present study demonstrates cerebellar alterations in α-mannosidosis mice that relate to the motor deficits and pathological changes seen in human patients and can be used as therapeutic outcome measures. PMID:21157375

The Long-Term Budget Outlook

DTIC Science & Technology

2005-12-01

Revenues Under CBO’s Long-Term Budget Scenarios 56A-8. Real Gross Domestic Product Under CBO’s Long-Term Budget Scenarios 57A-9. Total Surplus or...scenarios suggest that total federal spending for Medicare and Medicaid in 2050 could range anywhere from 7 percent of gross domestic product (GDP)—a...see the Congressional Budget Office’s glossary of budgetary and economic terms, available at www.cbo.gov. 2. The future path of productivity growth

Long-term associations of nut consumption with body weight and obesity1234

PubMed Central

Jackson, Chandra L

2014-01-01

There is some concern that the high-fat, energy-dense content of nuts may promote weight gain. Nuts, however, are rich in protein and dietary fiber, which are associated with increased satiety. They also contain high amounts of vitamins, minerals, antioxidants, and phytoesterols that may confer health benefits for cardiovascular disease and type 2 diabetes delay and prevention. Therefore, it is important to determine the association between nut consumption and long-term weight change and disease risk to reach scientific consensus and to make evidence-based public health recommendations. Several cross-sectional analyses have shown an inverse association between higher nut consumption and lower body weight. In addition, several independent prospective studies found that increasing nut consumption was associated with lower weight gain over relatively long periods of time. Moreover, high consumption of nuts (especially walnuts) has been associated with lower diabetes risk. Therefore, regular consumption (approximately one handful daily) of nuts over the long term, as a replacement to less healthful foods, can be incorporated as a component of a healthy diet for the prevention of obesity and type 2 diabetes. PMID:24898229

Long-term outcomes after severe shock.

PubMed

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

2015-02-01

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 < 0.001), whereas mental health scores were similar to population norms. Nineteen percent of the patients had symptoms of depression, 39% had symptoms of anxiety, and 8% had symptoms of posttraumatic stress disorder. Thirty-six percent were disabled, and 17% were working full-time. Early survivors of severe 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

Short-term Action Intentions Overrule Long-Term Semantic Knowledge

ERIC Educational Resources Information Center

van Elk, M.; van Schie, H.T.; Bekkering, H.

2009-01-01

In the present study, we investigated whether the preparation of an unusual action with an object (e.g. bringing a cup towards the eye) could selectively overrule long-term semantic representations. In the first experiment it was found that unusual action intentions activated short-term semantic goal representations, rather than long-term…

Compensation for PKMζ in long-term potentiation and spatial long-term memory in mutant mice.

PubMed

Tsokas, Panayiotis; Hsieh, Changchi; Yao, Yudong; Lesburguères, Edith; Wallace, Emma Jane Claire; Tcherepanov, Andrew; Jothianandan, Desingarao; Hartley, Benjamin Rush; Pan, Ling; Rivard, Bruno; Farese, Robert V; Sajan, Mini P; Bergold, Peter John; Hernández, Alejandro Iván; Cottrell, James E; Shouval, Harel Z; Fenton, André Antonio; Sacktor, Todd Charlton

2016-05-17

PKMζ is a persistently active PKC isoform proposed to maintain late-LTP and long-term memory. But late-LTP and memory are maintained without PKMζ in PKMζ-null mice. Two hypotheses can account for these findings. First, PKMζ is unimportant for LTP or memory. Second, PKMζ is essential for late-LTP and long-term memory in wild-type mice, and PKMζ-null mice recruit compensatory mechanisms. We find that whereas PKMζ persistently increases in LTP maintenance in wild-type mice, PKCι/λ, a gene-product closely related to PKMζ, persistently increases in LTP maintenance in PKMζ-null mice. Using a pharmacogenetic approach, we find PKMζ-antisense in hippocampus blocks late-LTP and spatial long-term memory in wild-type mice, but not in PKMζ-null mice without the target mRNA. Conversely, a PKCι/λ-antagonist disrupts late-LTP and spatial memory in PKMζ-null mice but not in wild-type mice. Thus, whereas PKMζ is essential for wild-type LTP and long-term memory, persistent PKCι/λ activation compensates for PKMζ loss in PKMζ-null mice.

Private capital investments in health care provision through mergers and acquisitions: from long-term to acute care.

PubMed

Angeli, Federica; Maarse, Hans

2016-10-01

This work aims to test whether different segments of healthcare provision differentially attract private capital and thus offer heterogeneous opportunities for private investors' diversification strategies. Thomson Reuter's SDC Platinum database provided data on 2563 merger and acquisition (M&A) deals targeting healthcare providers in Western Europe between 1990 and 2010. Longitudinal trends of industrial and geographical characteristics of M&As' targets and acquirers are examined. Our analyses highlight: (i) a relative decrease of long-term care facilities as targets of M&As, replaced by an increasing prominence of general hospitals, (ii) a shrinking share of long-term care facilities as targets of financial service organizations' acquisitions, in favor of general hospitals, and (iii) an absolute and relative decrease of long-term care facilities' role as target of cross-border M&As. We explain the decreasing interest of private investors towards long-term care facilities along three lines of reasoning, which take into account the saturation of the long-term care market and the liberalization of acute care provision across Western European countries, regulatory interventions aimed at reducing private ownership to ensure resident outcomes and new cultural developments in favor of small-sized facilities, which strengthen the fragmentation of the sector. These findings advance the literature investigating the effect of private ownership on health outcomes in long-term facilities. Market, policy and cultural forces have emerged over two decades to jointly regulate the presence of privately owned, large-sized long-term care providers, seemingly contributing to safeguard residents' well-being. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

[Long-term results of the surgical treatment of chronic pancreatitis].

PubMed

Padillo Ruiz, F J; Rufián, S; Varo, E; Solorzano, G; Miño, G; Pera Madrazo, C

1994-08-01

We analized the long-term results after surgical treatment in 41 patients with chronic pancreatitis. Twenty one of them underwent resection: 19 pancreaticoduodenectomy (11 Whipple procedure and 8 Traverso Longmire); total pancreatectomy (1) and near-total pancreatectomy (1). In the remaining 20 patients a drainage procedure was carried out: Puestow-Duval (5); Partington (7); double derivation: pancreatic and biliar (5); triple derivation: pancreatic, biliar, gastric (2) and Nardi procedure+quisteduodenostomy in one patient. The following were evaluated: persistent pain; chronic alcoholism; nutrition status; exocrine function (syntomatic steatorrea, use of pancreatic enzyme preparation and fecal determination of glucide, protids and lipids) and endocrine function (glucose and insulin levels and glucose oral test). Surgery failed to relieve pain in 15.6% of the patients; failures were associated chronic alcoholism (p < 0.05); 18 patients (44%) required oral pancreatic enzymes. There weren't significant differences between resection and drainage procedures regarding the exocrine function. However, endocrine function was significantly worse (p < 0.05) after pancreaticoduodenectomy than after drainages procedures. Among the late, the endocrine function was better after Partington operation than after the Puestow-Duval.

Estimating long-term multivariate progression from short-term data.

PubMed

Donohue, Michael C; Jacqmin-Gadda, Hélène; Le Goff, Mélanie; Thomas, Ronald G; Raman, Rema; Gamst, Anthony C; Beckett, Laurel A; Jack, Clifford R; Weiner, Michael W; Dartigues, Jean-François; Aisen, Paul S

2014-10-01

Diseases that progress slowly are often studied by observing cohorts at different stages of disease for short periods of time. The Alzheimer's Disease Neuroimaging Initiative (ADNI) follows elders with various degrees of cognitive impairment, from normal to impaired. The study includes a rich panel of novel cognitive tests, biomarkers, and brain images collected every 6 months for as long as 6 years. The relative timing of the observations with respect to disease pathology is unknown. We propose a general semiparametric model and iterative estimation procedure to estimate simultaneously the pathological timing and long-term growth curves. The resulting estimates of long-term progression are fine-tuned using cognitive trajectories derived from the long-term "Personnes Agées Quid" study. We demonstrate with simulations that the method can recover long-term disease trends from short-term observations. The method also estimates temporal ordering of individuals with respect to disease pathology, providing subject-specific prognostic estimates of the time until onset of symptoms. When the method is applied to ADNI data, the estimated growth curves are in general agreement with prevailing theories of the Alzheimer's disease cascade. Other data sets with common outcome measures can be combined using the proposed algorithm. Software to fit the model and reproduce results with the statistical software R is available as the grace package. ADNI data can be downloaded from the Laboratory of NeuroImaging. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

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

NASA Astrophysics Data System (ADS)

Gosz, J.

2001-12-01

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

Long-Term Opioid Therapy Reconsidered

PubMed Central

Von Korff, Michael; Kolodny, Andrew; Deyo, Richard A.; Chou, Roger

2012-01-01

In the past 20 years, primary care physicians have greatly increased prescribing of long-term opioid therapy. However, the rise in opioid prescribing has outpaced the evidence regarding this practice. Increased opioid availability has been accompanied by an epidemic of opioid abuse and overdose. The rate of opioid addiction among patients receiving long-term opioid therapy remains unclear, but research suggests that opioid misuse is not rare. Recent studies report increased risks for serious adverse events, including fractures, cardiovascular events, and bowel obstruction, although further research on medical risks is needed. New data indicate that opioid-related risks may increase with dose. From a societal perspective, higher-dose regimens account for the majority of opioids dispensed, so cautious dosing may reduce both diversion potential and patient risks for adverse effects. Limiting long-term opioid therapy to patients for whom it provides decisive benefits could also reduce risks. Given the warning signs and knowledge gaps, greater caution and selectivity are needed in prescribing long-term opioid therapy. Until stronger evidence becomes available, clinicians should err on the side of caution when considering this treatment. PMID:21893626

Very long-term sequelae of craniopharyngioma.

PubMed

Wijnen, Mark; van den Heuvel-Eibrink, Marry M; Janssen, Joseph A M J L; Catsman-Berrevoets, Coriene E; Michiels, Erna M C; van Veelen-Vincent, Marie-Lise C; Dallenga, Alof H G; van den Berge, J Herbert; van Rij, Carolien M; van der Lely, Aart-Jan; Neggers, Sebastian J C M M

2017-06-01

Studies investigating long-term health conditions in patients with craniopharyngioma are limited by short follow-up durations and generally do not compare long-term health effects according to initial craniopharyngioma treatment approach. In addition, studies comparing long-term health conditions between patients with childhood- and adult-onset craniopharyngioma report conflicting results. The objective of this study was to analyse a full spectrum of long-term health effects in patients with craniopharyngioma according to initial treatment approach and age group at craniopharyngioma presentation. Cross-sectional study based on retrospective data. We studied a single-centre cohort of 128 patients with craniopharyngioma treated from 1980 onwards (63 patients with childhood-onset disease). Median follow-up since craniopharyngioma presentation was 13 years (interquartile range: 5-23 years). Initial craniopharyngioma treatment approaches included gross total resection ( n  = 25), subtotal resection without radiotherapy ( n  = 44), subtotal resection with radiotherapy ( n  = 25), cyst aspiration without radiotherapy ( n  = 8), and 90 Yttrium brachytherapy ( n  = 21). Pituitary hormone deficiencies (98%), visual disturbances (75%) and obesity (56%) were the most common long-term health conditions observed. Different initial craniopharyngioma treatment approaches resulted in similar long-term health effects. Patients with childhood-onset craniopharyngioma experienced significantly more growth hormone deficiency, diabetes insipidus, panhypopituitarism, morbid obesity, epilepsy and psychiatric conditions compared with patients with adult-onset disease. Recurrence-/progression-free survival was significantly lower after initial craniopharyngioma treatment with cyst aspiration compared with other therapeutic approaches. Survival was similar between patients with childhood- and adult-onset craniopharyngioma. Long-term health conditions were comparable after

Enzyme replacement therapy with galsulfase in 34 children younger than five years of age with MPS VI.

PubMed

Horovitz, Dafne D G; Magalhães, Tatiana S P C; Acosta, Angelina; Ribeiro, Erlane M; Giuliani, Liane R; Palhares, Durval B; Kim, Chong A; de Paula, Ana Carolina; Kerstenestzy, Marcelo; Pianovski, Mara A D; Costa, Maria Ione F; Santos, Francisca C; Martins, Ana Maria; Aranda, Carolina S; Correa Neto, Jordão; Holanda, Gervina Brady Moreira; Cardoso, Laércio; da Silva, Carlos A B; Bonatti, Renata C F; Ribeiro, Bethania F R; Rodrigues, Maria do Carmo S; Llerena, Juan C

2013-05-01

Mucopolysaccharidosis type VI (MPS VI) is a progressive, chronic and multisystem lysosomal storage disease with a wide disease spectrum. Clinical and biochemical improvements have been reported for MPS VI patients on enzyme replacement therapy (ERT) with rhASB (recombinant human arylsulfatase B; galsulfase, Naglazyme®, BioMarin Pharmaceutical Inc.), making early diagnosis and intervention imperative for optimal patient outcomes. Few studies have included children younger than five years of age. This report describes 34 MPS VI patients that started treatment with galsulfase before five years of age. Data from patients who initiated treatment at <5 years of age were collected from patients' medical records. Baseline and follow-up assessments of common symptoms that led to diagnosis and that were used to evaluate disease progression and treatment efficacy were evaluated. A significant negative correlation was seen with treatment with ERT and urinary GAG levels. Of those with baseline and follow-up growth data, 47% remained on their pre-treatment growth curve or moved to a higher percentile after treatment. Of the 9 patients with baseline and follow-up sleep studies, 5 remained unaffected and 1 patient initially with mild sleep apnea showed improvement. Data regarding cardiac, ophthalmic, central nervous system, hearing, surgical interventions and development are also reported. No patient discontinued treatment due to an adverse event and all that were treatment-emergent resolved. The prescribed dosage of 1mg/kg IV weekly with galsulfase ERT is shown to be safe and effective in slowing and/or improving certain aspects of the disease, although patients should be closely monitored for complications associated with the natural history of the disease, especially cardiac valve involvement and spinal cord compression. A long-term follow-up investigation of this group of children will provide further information on the benefits of early treatment as well as disease

Long-term care in international perspective.

PubMed

Doty, P

1988-12-01

The findings of a study of long-term care policies in 18 countries are reported in this article. Initial data were collected by a questionnaire survey under the auspices of the International Social Security Association. These data were supplemented by published documents and government statistics obtained while researching long-term care for the International Social Security Association and, subsequently, for the Organization for Economic Cooperation and Development. The principal focus is a cross-national comparison of institutionalization rates for the elderly. Differences in use rates for medically oriented facilities are less than those for nonmedical residential long-term care facilities. Only a small amount of variation is related to demographic differences, such as older or more female elderly populations in those countries with higher institutionalization rates. Included also is a description of the modes of financing long-term care.

Compensation for PKMζ in long-term potentiation and spatial long-term memory in mutant mice

PubMed Central

Tsokas, Panayiotis; Hsieh, Changchi; Yao, Yudong; Lesburguères, Edith; Wallace, Emma Jane Claire; Tcherepanov, Andrew; Jothianandan, Desingarao; Hartley, Benjamin Rush; Pan, Ling; Rivard, Bruno; Farese, Robert V; Sajan, Mini P; Bergold, Peter John; Hernández, Alejandro Iván; Cottrell, James E; Shouval, Harel Z; Fenton, André Antonio; Sacktor, Todd Charlton

2016-01-01

PKMζ is a persistently active PKC isoform proposed to maintain late-LTP and long-term memory. But late-LTP and memory are maintained without PKMζ in PKMζ-null mice. Two hypotheses can account for these findings. First, PKMζ is unimportant for LTP or memory. Second, PKMζ is essential for late-LTP and long-term memory in wild-type mice, and PKMζ-null mice recruit compensatory mechanisms. We find that whereas PKMζ persistently increases in LTP maintenance in wild-type mice, PKCι/λ, a gene-product closely related to PKMζ, persistently increases in LTP maintenance in PKMζ-null mice. Using a pharmacogenetic approach, we find PKMζ-antisense in hippocampus blocks late-LTP and spatial long-term memory in wild-type mice, but not in PKMζ-null mice without the target mRNA. Conversely, a PKCι/λ-antagonist disrupts late-LTP and spatial memory in PKMζ-null mice but not in wild-type mice. Thus, whereas PKMζ is essential for wild-type LTP and long-term memory, persistent PKCι/λ activation compensates for PKMζ loss in PKMζ-null mice. DOI: http://dx.doi.org/10.7554/eLife.14846.001 PMID:27187150

Competitive short-term and long-term memory processes in spatial habituation.

PubMed

Sanderson, David J; Bannerman, David M

2011-04-01

Exposure to a spatial location leads to habituation of exploration such that, in a novelty preference test, rodents subsequently prefer exploring a novel location to the familiar location. According to Wagner's (1981) theory of memory, short-term and long-term habituation are caused by separate and sometimes opponent processes. In the present study, this dual-process account of memory was tested. Mice received a series of exposure training trials to a location before receiving a novelty preference test. The novelty preference was greater when tested after a short, rather than a long, interval. In contrast, the novelty preference was weaker when exposure training trials were separated by a short, rather than a long interval. Furthermore, it was found that long-term habituation was determined by the independent effects of the amount of exposure training and the number of exposure training trials when factors such as the intertrial interval and the cumulative intertrial interval were controlled. A final experiment demonstrated that a long-term reduction of exploration could be caused by a negative priming effect due to associations formed during exploration. These results provide evidence against a single-process account of habituation and suggest that spatial habituation is determined by both short-term, recency-based memory and long-term, incrementally strengthened memory.

Long and short term effects of plasma treatment on meristematic plant cells

NASA Astrophysics Data System (ADS)

Puač, N.; Živković, S.; Selaković, N.; Milutinović, M.; Boljević, J.; Malović, G.; Petrović, Z. Lj.

2014-05-01

In this paper, we will present results of plasma treatments of meristematic cells of Daucus carota. Plasma needle was used as an atmospheric pressure/gas composition source of non-equilibrium plasma in all treatments. Activity of antioxidant enzymes superoxide dismutase and catalase was measured immediately after plasma treatment and after two weeks following the treatment. Superoxide dismutase activity was increased in samples immediately after the plasma treatment. On the other hand, catalase activity was much higher in treated samples when measured two weeks after plasma treatment. These results show that there is a direct proof of the triggering of signal transduction in the cells by two reactive oxygen species H2O2 and O2-, causing enzyme activity and short and long term effects even during the growth of calli, where the information is passed to newborn cells over the period of two weeks.

Novel functional Renilla luciferase mutant provides long-term serum stability and high luminescence activity.

PubMed

Song, Woo Chul; Sung, Hye-Jin; Park, Kyung Soo; Choi, Jeong-Woo; Cho, Je-Yeol; Um, Soong Ho

2013-10-01

Fluorescent and luminescent chemical probes are essential in recent medical diagnostics. However, the use of these probes in vivo has raised concerns due to their low sensitivity, background signal interference, and non-biocompatibility. Therefore, biological chromophores have received much attention as new alternatives. In particular, luciferase, a class of oxidative enzyme with bioluminescence, has emerged as a promising fluorophore due to its improved biocompatibility. However, the enzyme usually possesses weaker luminescence and stability relative to its chemically-based competitors. Here, we report a novel functional mutant luciferase with both enhanced luminescence and long-term serum stability. For the preparation of the modified Renilla luciferase, a new bacterial subcloning design was established. The luciferase coding DNA sequence was redesigned so that mutant luciferase could be easily expressed in an Escherichia coli system. The mutant Renilla luciferase, which we called "m-Rluc," demonstrated characteristic enzymatic functions and showed a 5.6-fold increase in luminescence activity. In addition, the enzyme's physiological stability remained >80% for more than 5days, in contrast to conventional luciferase, termed "hrluc," which disappeared within a few hours. We suggest that this novel biological luciferase probe may be a great tool for both in vitro and in vivo medical diagnostics. Copyright © 2013 Elsevier Inc. All rights reserved.

Severe infusion reactions to fabry enzyme replacement therapy: rechallenge after tracheostomy.

PubMed

Nicholls, K; Bleasel, K; Becker, G

2012-01-01

A 34-year-old male patient with Fabry disease (OMIM 301500) commenced enzyme replacement therapy (ERT) with Agalsidase alfa, with positive clinical response. Infusion reactions, initially mild and easily managed, commenced during his 13th infusion, and continued over the next 3 years. Severity of reactions subsequently increased despite very slow infusion, extended prophylactic medication and attempted desensitisation, requiring regular intensive care unit (ICU) admissions. Facial oedema and flushing, throat tightness, headache and joint pain typically occurred 4-36 h after completion of most infusions, responding rapidly to subcutaneous adrenaline. Low titre specific IgG seroconversion was noted at 12 months, with subsequent reversion to negative after 5 years, despite persistence of infusion reactions. Specific IgE and skin testing was negative. Trial of ERT product switch to Agalsidase-beta resulted in no improvement in reactions. At 5 years, ERT was ceased in the face of recurrent ICU readmissions. In the face of progressive clinical deterioration, he underwent tracheostomy to allow recommencement of ERT. Two years later, he has clinically improved on regular attenuated dose Agalsidase-beta, administered by slow infusion in a local hospital setting.

Intravenous lipid emulsions in term infants: impact on laboratory and clinical outcomes and long-term consequences.

PubMed

Hartman, Corina; Shamir, Raanan

2015-01-01

Parenteral nutrition (PN) in term newborns and older infants is often required for nutritional support for temporary or permanent intestinal failure from any reason. Lipid emulsions (LEs) are an essential source of high-density energy, essential fatty acids, and fat-soluble vitamins. Depending on the fatty acid type, LEs may also have significant immunomodulatory effects. All LEs, starting with soybean oil-based LE and subsequently with medium-chain triglycerides-, olive oil- and fish oil-based LEs, have been investigated in newborns and infants. Laboratory data (mainly liver enzymes, plasma lipid profiles and some metabolic markers) have been investigated for some LEs. The outcome of intestinal failure-associated liver disease after switching to new fish oil-based LEs has been sporadically reported. Long-term outcome data have only looked at the relationship between PN and mortality/morbidity, especially liver disease, and a few studies have looked at growth. There are no controlled studies in this age group that investigated the relationship between different types of LEs and long-term outcomes. In spite of their contribution to understanding the use and indications of various LEs as well as their advantages and adverse effects, most studies in newborns and infants have been observational or retrospective, and the investigated population has been heterogeneous, either in terms of the degree of maturation, age or diagnoses. High-quality studies, preferably randomized and controlled, in this particular population are needed, especially with the widespread use of PN and the emergence of new LEs. © 2015 S. Karger AG, Basel.

Long-term toxic effects of deltamethrin and fenvalerante in soil.

PubMed

Song, Yufang; Kai, Jianrong; Song, Xueying; Zhang, Wei; Li, Lingling

2015-05-30

In this study, the long-term toxic effects of pyrethroids on the earthworm Eisenia fetida were evaluated. Earthworms were exposed to moist filter paper and soil for 14 days to evaluate the survival, exposed to soil for 56 days to assess the reproductive success and for 28 days to identify the cytotoxicity. Results showed that the earthworm survival rate decreased with increasing the concentration of either deltamethrin or fenvalerate in both filter paper test and soil test. No worms survived at 602.15 μg cm(-2) of deltamethrin and 0.86 μg cm(-2) of fenvalerate in the filter paper test, however 100-125 mg kg(-1) of both chemicals resulted in the maximum mortality of 90% in the soil test. The CYP3A4 enzyme activity responded significantly to deltamethrin and fenvalerante in soil at low concentration levels, however, the toxicity response of worms under the long-term exposure conflicted with the degradation of deltamethrin and fenvalerate in soil, indicating the possible formation of more toxic pyrethroid metabolites. This study gave an insight into the toxicological effects profile of pyrethroids for a better risk assessment of pyrethroids deltamethrin and fenvalerante in soil. Copyright © 2015 Elsevier B.V. All rights reserved.

[Enzyme replacement therapy in patients with Fabry disease: state of the art and review of the literature].

PubMed

Riccio, Eleonora; Capuano, Ivana; Visciano, Bianca; Marchetiello, Cristina; Petrillo, Fortunato; Pisani, Antonio

2013-01-01

Anderson-Fabry disease is a hereditary X-linked lysosomal storage disorder caused by a deficiency of the lysosomal enzyme alpha galactosidase A. It results in the accumulation of the glycosphingolypid globotrioasoyl ceramide (Gb3 in different cells and organs, resulting in a multi-system pathology including end organ failure. Patients with Fabry disease present clinically with cardiac, renal and neurological involvement; both life expectancy and quality of life are severely compromised. The current causal treatment for Fabry disease is enzyme replacement therapy (ERT), available since 2001. The two recombinant preparations available for ERT are agalsidase alfa (Replagal) and agalsidase beta (Fabrazyme). They have both been showed to have positive effect on kidney and heart, on the symptoms of pain and quality of life. Few data to date are available on comparison of the two preparations of ERT. This article reviews evidence of the literature and shows our personal experience about the safety and efficacy of ERT.

Long-term outcomes of children treated for Cushing's disease: a single center experience.

PubMed

Yordanova, Galina; Martin, Lee; Afshar, Farhad; Sabin, Ian; Alusi, Ghassan; Plowman, Nicholas P; Riddoch, Fiona; Evanson, Jane; Matson, Matthew; Grossman, Ashley B; Akker, Scott A; Monson, John P; Drake, William M; Savage, Martin O; Storr, Helen L

2016-12-01

Pediatric Cushing's disease (CD) is rare and there are limited data on the long-term outcomes. We assessed CD recurrence, body composition, pituitary function and psychiatric comorbidity in a cohort of pediatric CD patients. Retrospective review of 21 CD patients, mean age at diagnosis 12.1 years (5.7-17.8), managed in our center between 1986 and 2010. Mean follow-up from definitive treatment was 10.6 years (2.9-27.2). Fifteen patients were in remission following transsphenoidal surgery (TSS) and 5 were in remission following TSS + external pituitary radiotherapy (RT). One patient underwent bilateral adrenalectomy (BA). CD recurrence occurred in 3 (14.3 %) patients: 2 at 2 and 6 years after TSS and 1 7.6 years post-RT. The BA patient developed Nelson's syndrome requiring pituitary RT 0.6 years post-surgery. Short-term growth hormone deficiency (GHD) was present in 14 patients (81 % patients tested) (11 following TSS and 3 after RT) and 4 (44 % of tested) had long-term GHD. Gonadotropin deficiency caused impaired pubertal development in 9 patients (43 %), 4 requiring sex steroid replacement post-puberty. Four patients (19 %) had more than one pituitary hormone deficiency, 3 after TSS and 1 post-RT. Five patients (24 %) had long-term psychiatric co-morbidities (cognitive dysfunction or mood disturbance). There were significant long-term improvements in growth, weight and bone density but not complete reversal to normal in all patients. The long-term consequences of the diagnosis and treatment of CD in children is broadly similar to that seen in adults, with recurrence of CD after successful treatment uncommon but still seen. Pituitary hormone deficiencies occurred in the majority of patients after remission, and assessment and appropriate treatment of GHD is essential. However, while many parameters improve, some children may still have mild but persistent defects.

A time-course study of long term over-expression of ARR19 in mice

PubMed Central

Qamar, Imteyaz; Ahmad, Mohammad Faiz; Narayanasamy, Arul

2015-01-01

A leucine-rich protein, ARR19 (androgen receptor corepressor-19 kDa), is highly expressed in male reproductive organs and moderately in others. Previously, we have reported that ARR19 is differentially expressed in adult Leydig cells during the testis development and inhibits steroidogenesis by reducing the expression of steroidogenic enzymes. Whereas in prostate, ARR19 represses the transcriptional activity of AR (androgen receptor), it is important for male sexual differentiation and maturation in prostate and epididymis, through the recruitment of HDAC4. In this study we show that long term adenovirus mediated overexpression of ARR19 in mice testis has the potential of inhibiting the differentiation of testicular and prostatic cells by reducing the size of testis and prostate but has no effect on the growth of seminal vesicles. Further, it reduces the level of progesterone and testosterone by reducing the steroidogenic enzymes such as 3HSD, P450c17 and StAR. This is the first study reporting a time-course analysis of the implications of long term overexpression of ARR19 in mice testis and its effect on other organs such as prostate and seminal vesicles. Taken together, these results suggest that ARR19 may play an important role in the differentiation of male reproductive organs such as testis and prostate. PMID:26260329

Toward reducing immunogenicity of enzyme replacement therapy: altering the specificity of human β-glucuronidase to compensate for α-iduronidase deficiency.

PubMed

Chuang, Huai-Yao; Suen, Ching-Shu; Hwang, Ming-Jing; Roffler, Steve R

2015-11-01

Enzyme replacement therapy (ERT) is an effective treatment for many patients with lysosomal storage disorders caused by deficiency in enzymes involved in cell metabolism. However, immune responses that develop against the administered enzyme in some patients can hinder therapeutic efficacy and cause serious side effects. Here we investigated the feasibility of a general approach to decrease ERT immunogenicity by altering the specificity of a normal endogenous enzyme to compensate for a defective enzyme. We sought to identify human β-glucuronidase variants that display α-iduronidase activity, which is defective in mucopolysaccharidosis (MPS) type I patients. A human β-glucuronidase library was screened by the Enzyme Cleavable Surface-Tethered All-purpose Screen sYstem to isolate variants that exhibited 100-290-fold greater activity against the α-iduronidase substrate 4-methylumbelliferyl α-l-iduronide and 7900-24 500-fold enzymatic specificity shift when compared with wild-type β-glucuronidase. In vitro treatment of MPS I cells with the β-glucuronidase variants significantly restored lysosome appearance similar to treatment with α-iduronidase. Our study suggests that β-glucuronidase variants can be isolated to display α-iduronidase activity and produce significant phenotype improvement of MPS I cells. This strategy may represent a possible approach to produce enzymes that display therapeutic benefits with potentially less immunogenicity. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Long Periodic Terms in the Solar System

NASA Technical Reports Server (NTRS)

Bretagnon, P.

1982-01-01

The long period variations of the first eight planets in the solar system are studied. First, the Lagrangian solution is calculated and then the long period terms with fourth order eccentricities and inclinations are introduced into the perturbation function. A second approximation was made taking into account the short period terms' contribution, namely the perturbations of first order with respect to the masses. Special attention was paid to the determination of the integration constants. The relative importance of the different contributions is shown. It is useless, for example, to introduce the long period terms of fifth order if no account has been taken of the short period terms. Meanwhile, the terms that have been neglected would not introduce large changes in the integration constants. Even so, the calculation should be repeated with higher order short period terms and fifth order long periods.

Long-Term Hearing Results After Ossiculoplasty.

PubMed

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

2017-04-01

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 < 0.001; 2-tailed), as well as average long-term PTA-ABG (ρ = 0.950, p < 0.001; 2-tailed). The OOPS index makes it possible to accurately prognosticate hearing outcomes in adult and pediatric patients undergoing ossiculoplasty in both the short term and the long term.

Short-term memory and long-term memory are still different.

PubMed

Norris, Dennis

2017-09-01

A commonly expressed view is that short-term memory (STM) is nothing more than activated long-term memory. If true, this would overturn a central tenet of cognitive psychology-the idea that there are functionally and neurobiologically distinct short- and long-term stores. Here I present an updated case for a separation between short- and long-term stores, focusing on the computational demands placed on any STM system. STM must support memory for previously unencountered information, the storage of multiple tokens of the same type, and variable binding. None of these can be achieved simply by activating long-term memory. For example, even a simple sequence of digits such as "1, 3, 1" where there are 2 tokens of the digit "1" cannot be stored in the correct order simply by activating the representations of the digits "1" and "3" in LTM. I also review recent neuroimaging data that has been presented as evidence that STM is activated LTM and show that these data are exactly what one would expect to see based on a conventional 2-store view. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Short-Term Memory and Long-Term Memory are Still Different

PubMed Central

2017-01-01

A commonly expressed view is that short-term memory (STM) is nothing more than activated long-term memory. If true, this would overturn a central tenet of cognitive psychology—the idea that there are functionally and neurobiologically distinct short- and long-term stores. Here I present an updated case for a separation between short- and long-term stores, focusing on the computational demands placed on any STM system. STM must support memory for previously unencountered information, the storage of multiple tokens of the same type, and variable binding. None of these can be achieved simply by activating long-term memory. For example, even a simple sequence of digits such as “1, 3, 1” where there are 2 tokens of the digit “1” cannot be stored in the correct order simply by activating the representations of the digits “1” and “3” in LTM. I also review recent neuroimaging data that has been presented as evidence that STM is activated LTM and show that these data are exactly what one would expect to see based on a conventional 2-store view. PMID:28530428

Triheptanoin: long-term effects in the very long-chain acyl-CoA dehydrogenase-deficient mouse[S

PubMed Central

Tucci, Sara; Floegel, Ulrich; Beermann, Frauke; Behringer, Sidney; Spiekerkoetter, Ute

2017-01-01

A rather new approach in the treatment of long-chain fatty acid oxidation disorders is represented by triheptanoin, a triglyceride with three medium-odd-chain heptanoic acids (C7), due to its anaplerotic potential. We here investigate the effects of a 1-year triheptanoin-based diet on the clinical phenotype of very long-chain-acyl-CoA-dehydrogenase-deficient (VLCAD−/−) mice. The cardiac function was assessed in VLCAD−/− mice by in vivo MRI. Metabolic adaptations were identified by the expression of genes regulating energy metabolism and anaplerotic processes using real-time PCR, and the results were correlated with the measurement of the glycolytic enzymes pyruvate dehydrogenase and pyruvate kinase. Finally, the intrahepatic lipid accumulation and oxidative stress in response to the long-term triheptanoin diet were assessed. Triheptanoin was not able to prevent the development of systolic dysfunction in VLCAD−/− mice despite an upregulation of cardiac glucose oxidation. Strikingly, the anaplerotic effects of triheptanoin were restricted to the liver. Despite this, the hepatic lipic content was increased upon triheptanoin supplementation. Our data demonstrate that the concept of anaplerosis does not apply to all tissues equally. PMID:27884962

Thermophilic Enzyme or Mesophilic Enzyme with Enhanced Thermostability: Can We Draw a Line?

PubMed

Jing, Xiaomin; Evangelista Falcon, Wilfredo; Baudry, Jerome; Serpersu, Engin H

2017-07-27

Aminoglycoside nucleotidyltransferase 4' (ANT) is a homodimeric enzyme that modifies the C4'-OH site of aminoglycoside antibiotics by nucleotidylation. A few single- and double-residue mutants of this enzyme (T130K, D80Y, and D80Y/T130K) from Bacillus stearothermophilus show increased thermostability. This article investigates how such residue replacements, which are distant from the active site and monomer-monomer interface, result in various changes of the thermostability of the enzyme. In this work, we show that the thermodynamic properties of enzyme-ligand complexes and protein dynamics may be indicators of a thermophilic behavior. Our data suggests that one of the single-site mutants of ANT, D80Y, may be a thermophilic protein and the other thermostable mutant, T130K, is actually a more heat-stable variant of the mesophilic wild type (WT) with a higher T m . Our data also suggest that T130K and D80Y adopt different global dynamics strategies to achieve different levels of thermostability enhancement and that the differences between the properties of the species can be described in terms of global dynamics rather than in terms of specific structural features. Thermophilicity of the D80Y comes at the cost of less favorable thermodynamic parameters for ligand binding relative to WT. On the other hand, the T130K species exhibits the same affinity to ligands and the same thermodynamic parameters of complex formation as the WT enzyme. These observations suggest that a quantitative characterization of ligand binding and protein dynamics can be used to differentiate thermophilic proteins from their simply more heat-stable mesophilic counterparts.

Hypersurface Insertion Window for Long Term Orbital Stability of Artificial Satellites About the Planet Venus

DTIC Science & Technology

1988-12-01

Conversion of the Geopotential into the Modified Orbital Elements 83 Appendix C: Useful Derivatives for the Geopotential Calculations 87 Appendix D...replaced by two equinoctial elements , h and k (from a coordinate system with singularities at i = x and for rectilinear orbits ). Also, for long term 3...0. 10 and 0.55 i 15.5) a more well behaved set of variables will be used: two of the equinoctial elements , h and k. These elements eliminate the

In vivo genome editing of the albumin locus as a platform for protein replacement therapy

PubMed Central

Sharma, Rajiv; Anguela, Xavier M.; Doyon, Yannick; Wechsler, Thomas; DeKelver, Russell C.; Sproul, Scott; Paschon, David E.; Miller, Jeffrey C.; Davidson, Robert J.; Shivak, David; Zhou, Shangzhen; Rieders, Julianne; Gregory, Philip D.; Holmes, Michael C.; Rebar, Edward J.

2015-01-01

Site-specific genome editing provides a promising approach for achieving long-term, stable therapeutic gene expression. Genome editing has been successfully applied in a variety of preclinical models, generally focused on targeting the diseased locus itself; however, limited targeting efficiency or insufficient expression from the endogenous promoter may impede the translation of these approaches, particularly if the desired editing event does not confer a selective growth advantage. Here we report a general strategy for liver-directed protein replacement therapies that addresses these issues: zinc finger nuclease (ZFN) –mediated site-specific integration of therapeutic transgenes within the albumin gene. By using adeno-associated viral (AAV) vector delivery in vivo, we achieved long-term expression of human factors VIII and IX (hFVIII and hFIX) in mouse models of hemophilia A and B at therapeutic levels. By using the same targeting reagents in wild-type mice, lysosomal enzymes were expressed that are deficient in Fabry and Gaucher diseases and in Hurler and Hunter syndromes. The establishment of a universal nuclease-based platform for secreted protein production would represent a critical advance in the development of safe, permanent, and functional cures for diverse genetic and nongenetic diseases. PMID:26297739

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)

PubMed Central

Konaka, Hiroyuki; Sugimoto, Kazuhiro; Orikasa, Hideki; Iwamoto, Teruaki; Takamura, Toshinari; Takeda, Yoshiyu; Shigehara, Kazuyoshi; Iijima, Masashi; Koh, Eitetsu; Namiki, Mikio

2016-01-01

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. PMID:25761833

Long-Term Memory Performance in Adult ADHD.

PubMed

Skodzik, Timo; Holling, Heinz; Pedersen, Anya

2017-02-01

Memory problems are a frequently reported symptom in adult ADHD, and it is well-documented that adults with ADHD perform poorly on long-term memory tests. However, the cause of this effect is still controversial. The present meta-analysis examined underlying mechanisms that may lead to long-term memory impairments in adult ADHD. We performed separate meta-analyses of measures of memory acquisition and long-term memory using both verbal and visual memory tests. In addition, the influence of potential moderator variables was examined. Adults with ADHD performed significantly worse than controls on verbal but not on visual long-term memory and memory acquisition subtests. The long-term memory deficit was strongly statistically related to the memory acquisition deficit. In contrast, no retrieval problems were observable. Our results suggest that memory deficits in adult ADHD reflect a learning deficit induced at the stage of encoding. Implications for clinical and research settings are presented.

Is physiological glucocorticoid replacement important in children?

PubMed Central

Porter, John; Blair, Joanne; Ross, Richard J

2017-01-01

Cortisol has a distinct circadian rhythm with low concentrations at night, rising in the early hours of the morning, peaking on waking and declining over the day to low concentrations in the evening. Loss of this circadian rhythm, as seen in jetlag and shift work, is associated with fatigue in the short term and diabetes and obesity in the medium to long term. Patients with adrenal insufficiency on current glucocorticoid replacement with hydrocortisone have unphysiological cortisol concentrations being low on waking and high after each dose of hydrocortisone. Patients with adrenal insufficiency complain of fatigue, a poor quality of life and there is evidence of poor health outcomes including obesity potentially related to glucocorticoid replacement. New technologies are being developed that deliver more physiological glucocorticoid replacement including hydrocortisone by subcutaneous pump, Plenadren, a once-daily modified-release hydrocortisone and Chronocort, a delayed and sustained absorption hydrocortisone formulation that replicates the overnight profile of cortisol. In this review, we summarise the evidence regarding physiological glucocorticoid replacement with a focus on relevance to paediatrics. PMID:27582458

Reliability of Modern Scores to Predict Long-Term Mortality After Isolated Aortic Valve Operations.

PubMed

Barili, Fabio; Pacini, Davide; D'Ovidio, Mariangela; Ventura, Martina; Alamanni, Francesco; Di Bartolomeo, Roberto; Grossi, Claudio; Davoli, Marina; Fusco, Danilo; Perucci, Carlo; Parolari, Alessandro

2016-02-01

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

Amperometric biosensor based on glassy carbon electrode modified with long-length carbon nanotube and enzyme

NASA Astrophysics Data System (ADS)

Furutaka, Hajime; Nemoto, Kentaro; Inoue, Yuki; Hidaka, Hiroki; Muguruma, Hitoshi; Inoue, Hitoshi; Ohsawa, Tatsuya

2016-05-01

An amperometric biosensor based on a glassy carbon electrode modified with long-length multiwalled carbon nanotubes (MWCNTs) and enzyme nicotinamide-adenine-dinucleotide-dependent glucose dehydrogenase (GDH) is presented. We demonstrate the effect of the MWCNT length on the amperometric response of the enzyme biosensor. The long length of MWCNT is 200 µm (average), whereas the normal length of MWCNT is 1 µm (average). The response of the long MWCNT-GDH electrode is 2 times more sensitive than that of the normal-length MWCNT-GDH electrode in the concentration range from 0.25-35 mM. The result of electrochemical impedance spectroscopy measurements suggest that the long-length MWCNT-GDH electrode formed a better electron transfer network than the normal-length one.

Antibody production in rats after long-term exposure to formaldehyde

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holmstroem, M.R.; Rynnel-Dagoeoe, B.Wi.; Wilhelmsson, B.

1989-09-01

Sprague-Dawley rats were vaccinated with pneumococcal polysaccharide antigens and tetanus toxoid to evaluate the immunologic effects of long-term formaldehyde exposure. The antibody response to vaccination was measured 3 to 4 weeks later by enzyme-linked immunosorbent assay. An IgG response to pneumococcal polysaccharides and to tetanus toxoid was found in both the formaldehyde-exposed group and a control group of rats not exposed to formaldehyde. The IgM response to tetanus toxoid was significant in both groups but neither group showed a significant IgM response to pneumococcal polysaccharides. There were thus no signs of impaired B-cell function in rats exposed to a highmore » concentration (12.6 ppm) of formaldehyde for nearly 2 years.« less

Virtual Models of Long-Term Care

ERIC Educational Resources Information Center

Phenice, Lillian A.; Griffore, Robert J.

2012-01-01

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…

Legacy effects overwhelm the short-term effects of exotic plant invasion and restoration on soil microbial community structure, enzyme activities, and nitrogen cycling.

PubMed

Elgersma, Kenneth J; Ehrenfeld, Joan G; Yu, Shen; Vor, Torsten

2011-11-01

Plant invasions can have substantial consequences for the soil ecosystem, altering microbial community structure and nutrient cycling. However, relatively little is known about what drives these changes, making it difficult to predict the effects of future invasions. In addition, because most studies compare soils from uninvaded areas to long-established dense invasions, little is known about the temporal dependence of invasion impacts. We experimentally manipulated forest understory vegetation in replicated sites dominated either by exotic Japanese barberry (Berberis thunbergii), native Viburnums, or native Vacciniums, so that each vegetation type was present in each site-type. We compared the short-term effect of vegetation changes to the lingering legacy effects of the previous vegetation type by measuring soil microbial community structure (phospholipid fatty acids) and function (extracellular enzymes and nitrogen mineralization). We also replaced the aboveground litter in half of each plot with an inert substitute to determine if changes in the soil microbial community were driven by aboveground or belowground plant inputs. We found that after 2 years, the microbial community structure and function was largely determined by the legacy effect of the previous vegetation type, and was not affected by the current vegetation. Aboveground litter removal had only weak effects, suggesting that changes in the soil microbial community and nutrient cycling were driven largely by belowground processes. These results suggest that changes in the soil following either invasion or restoration do not occur quickly, but rather exhibit long-lasting legacy effects from previous belowground plant inputs.

Enzyme replacement therapy for mucopolysaccharidosis VI: Growth and pubertal development in patients treated with recombinant human N-acetylgalactosamine 4-sulfatase

PubMed Central

Decker, Celeste; Yu, Zi-Fan; Giugliani, Roberto; Schwartz, Ida Vanessa D.; Guffon, Nathalie; Teles, Elisa Leão; Miranda, M. Clara Sá; Wraith, J. Edmond; Beck, Michael; Arash, Laila; Scarpa, Maurizio; Ketteridge, David; Hopwood, John J.; Plecko, Barbara; Steiner, Robert; Whitley, Chester B.; Kaplan, Paige; Swiedler, Stuart J.; Conrad, Susan; Harmatz, Paul

2010-01-01

Background and Methods Growth failure is characteristic of untreated mucopolysaccharidosis type VI (MPS VI: Maroteaux-Lamy syndrome). Growth was studied in fifty-six MPS VI patients (5 to 29 years old) prior to and for up to 240 weeks of weekly infusions of recombinant human arylsulfatase B (rhASB) at 1 mg/kg during Phase 1/2, Phase 2, Phase 3 or Phase 3 Extension clinical trials. Height, weight, and Tanner stage data were collected. Pooled data were analyzed to determine mean height increase by treatment week, growth impacts of pubertal status, baseline urinary GAG, and age at treatment initiation. Growth rate for approximately 2 years prior to and following treatment initiation was analyzed using longitudinal modeling. Results Mean height increased by 2.9 cm after 48 weeks and 4.3 cm after 96 weeks on enzyme replacement therapy (ERT). Growth on ERT was not correlated with baseline urinary GAG. Patients under 16 years of age showed greatest increases in height on treatment. Model results based on pooled data showed significant improvement in growth rate during 96 weeks of ERT when compared to the equivalent pretreatment time period. Delayed pubertal onset or progression was noted in 10 patients entering the clinical trials; all of whom showed progression of at least one Tanner stage during 2 years on ERT, and 6 of whom (60%) completed puberty. Conclusion Analysis of mean height by treatment week and longitudinal modeling demonstrate significant increase in height and growth rate in MPS VI patients receiving long-term ERT. This impact was greatest in patients aged below 16 years. Height increase may result from bone growth and/or reduction in joint contractures. Bone growth and resolution of delayed puberty may be related to improvements in general health, bone cell health, nutrition, endocrine gland function and reduced inflammation. PMID:20634905

Prevalence of Long-Term Opioid Use in Long-Stay Nursing Home Residents.

PubMed

Hunnicutt, Jacob N; Chrysanthopoulou, Stavroula A; Ulbricht, Christine M; Hume, Anne L; Tjia, Jennifer; Lapane, Kate L

2018-01-01

Overall and long-term opioid use among older adults have increased since 1999. Less is known about opioid use in older adults in nursing homes (NHs). Cross-sectional. U.S. NHs (N = 13,522). Long-stay NH resident Medicare beneficiaries with a Minimum Data Set 3.0 (MDS) assessment between April 1, 2012, and June 30, 2012, and 120 days of follow-up (N = 315,949). We used Medicare Part D claims to measure length of opioid use in the 120 days from the index assessment (short-term: ≤30 days, medium-term: >30-89 days, long-term: ≥90 days), adjuvants (e.g., anticonvulsants), and other pain medications (e.g., corticosteroids). MDS assessments in the follow-up period were used to measure nonpharmacological pain management use. Modified Poisson models were used to estimate adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) for age, gender, race and ethnicity, cognitive and physical impairment, and long-term opioid use. Of all long-stay residents, 32.4% were prescribed any opioid, and 15.5% were prescribed opioids long-term. Opioid users (versus nonusers) were more commonly prescribed pain adjuvants (32.9% vs 14.9%), other pain medications (25.5% vs 11.0%), and nonpharmacological pain management (24.5% vs 9.3%). Long-term opioid use was higher in women (aPR = 1.21, 95% CI = 1.18-1.23) and lower in racial and ethnic minorities (non-Hispanic blacks vs whites: APR = 0.93, 95% CI = 0.90-0.94) and those with severe cognitive impairment (vs no or mild impairment, aPR = 0.82, 95% CI = 0.79-0.83). One in seven NH residents was prescribed opioids long-term. Recent guidelines on opioid prescribing for pain recommend reducing long-term opioid use, but this is challenging in NHs because residents may not benefit from nonpharmacological and nonopioid interventions. Studies to address concerns about opioid safety and effectiveness (e.g., on pain and functional status) in NHs are needed. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics

Herbivory and drought generate short-term stochasticity and long-term stability in a savanna understory community.

PubMed

Riginos, Corinna; Porensky, Lauren M; Veblen, Kari E; Young, Truman P

2018-03-01

Rainfall and herbivory are fundamental drivers of grassland plant dynamics, yet few studies have examined long-term interactions between these factors in an experimental setting. Understanding such interactions is important, as rainfall is becoming increasingly erratic and native wild herbivores are being replaced by livestock. Livestock grazing and episodic low rainfall are thought to interact, leading to greater community change than either factor alone. We examined patterns of change and stability in herbaceous community composition through four dry periods, or droughts, over 15 years of the Kenya Long-term Exclosure Experiment (KLEE), which consists of six different combinations of cattle, native wild herbivores (e.g., zebras, gazelles), and mega-herbivores (giraffes, elephants). We used principal response curves to analyze the trajectory of change in each herbivore treatment relative to a common initial community and asked how droughts contributed to community change in these treatments. We examined three measures of stability (resistance, variability, and turnover) that correspond to different temporal scales and found that each had a different response to grazing. Treatments that included both cattle and wild herbivores had higher resistance (less net change over 15 years) but were more variable on shorter time scales; in contrast, the more lightly grazed treatments (no herbivores or wild herbivores only) showed lower resistance due to the accumulation of consistent, linear, short-term change. Community change was greatest during and immediately after droughts in all herbivore treatments. But, while drought contributed to directional change in the less grazed treatments, it contributed to both higher variability and resistance in the more heavily grazed treatments. Much of the community change in lightly grazed treatments (especially after droughts) was due to substantial increases in cover of the palatable grass Brachiaria lachnantha. These results

Effect of long-term actual spaceflight on the expression of key genes encoding serotonin and dopamine system

NASA Astrophysics Data System (ADS)

Popova, Nina; Shenkman, Boris; Naumenko, Vladimir; Kulikov, Alexander; Kondaurova, Elena; Tsybko, Anton; Kulikova, Elisabeth; Krasnov, I. B.; Bazhenova, Ekaterina; Sinyakova, Nadezhda

The effect of long-term spaceflight on the central nervous system represents important but yet undeveloped problem. The aim of our work was to study the effect of 30-days spaceflight of mice on Russian biosatellite BION-M1 on the expression in the brain regions of key genes of a) serotonin (5-HT) system (main enzymes in 5-HT metabolism - tryptophan hydroxylase-2 (TPH-2), monoamine oxydase A (MAO A), 5-HT1A, 5-HT2A and 5-HT3 receptors); b) pivotal enzymes in DA metabolism (tyrosine hydroxylase, COMT, MAO A, MAO B) and D1, D2 receptors. Decreased expression of genes encoding the 5-HT catabolism (MAO A) and 5-HT2A receptor in some brain regions was shown. There were no differences between “spaceflight” and control mice in the expression of TPH-2 and 5-HT1A, 5-HT3 receptor genes. Significant changes were found in genetic control of DA system. Long-term spaceflight decreased the expression of genes encoding the enzyme in DA synthesis (tyrosine hydroxylase in s.nigra), DA metabolism (MAO B in the midbrain and COMT in the striatum), and D1 receptor in hypothalamus. These data suggested that 1) microgravity affected genetic control of 5-HT and especially the nigrostriatal DA system implicated in the central regulation of muscular tonus and movement, 2) the decrease in the expression of genes encoding key enzyme in DA synthesis, DA degradation and D1 receptor contributes to the movement impairment and dyskinesia produced by the spaceflight. The study was supported by Russian Foundation for Basic Research grant No. 14-04-00173.

Complex network structure influences processing in long-term and short-term memory.

PubMed

Vitevitch, Michael S; Chan, Kit Ying; Roodenrys, Steven

2012-07-01

Complex networks describe how entities in systems interact; the structure of such networks is argued to influence processing. One measure of network structure, clustering coefficient, C, measures the extent to which neighbors of a node are also neighbors of each other. Previous psycholinguistic experiments found that the C of phonological word-forms influenced retrieval from the mental lexicon (that portion of long-term memory dedicated to language) during the on-line recognition and production of spoken words. In the present study we examined how network structure influences other retrieval processes in long- and short-term memory. In a false-memory task-examining long-term memory-participants falsely recognized more words with low- than high-C. In a recognition memory task-examining veridical memories in long-term memory-participants correctly recognized more words with low- than high-C. However, participants in a serial recall task-examining redintegration in short-term memory-recalled lists comprised of high-C words more accurately than lists comprised of low-C words. These results demonstrate that network structure influences cognitive processes associated with several forms of memory including lexical, long-term, and short-term.

LONG TERM OPERATION ISSUES FOR ELECTRICAL CABLE SYSTEMS IN NUCLEAR POWER PLANTS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fifield, Dr Leonard S; Duckworth, Robert C; Glass III, Dr. Samuel W.

Nuclear power plants contain hundreds of kilometers of electrical cables including cables used for power, for instrumentation, and for control. It is essential that safety-related cable systems continue to perform following a design-basis event. Wholesale replacement of electrical cables in existing plants facing licensing period renewal is both impractical and cost-prohibitive. It is therefore important to understand the long term aging of cable materials to have confidence that aged cables will perform when needed. It is equally important in support of cable aging management to develop methods to evaluate the health of installed cables and inform selective cable replacement decisions.more » The most common insulation materials for electrical cables in nuclear power plants are cross-linked polyethylene and ethylene-propylene rubber. The mechanical properties of these materials degrade over time in the presence of environmental stresses including heat, gamma irradiation, and moisture. Mechanical degradation of cable insulation beyond a certain threshold is unacceptable because it can lead to insulation cracking, exposure of energized conductors, arcing and burning or loss of the ability of the cable system to function during a design-basis accident. While thermal-, radiation-, and moisture-related degradation of polymer insulation materials has been extensively studied over the last few decades, questions remain regarding the long-term performance of cable materials in nuclear plant-specific environments. Identified knowledge gaps include an understanding of the temperature-dependence of activation energies for thermal damage and an understanding of the synergistic effects of radiation and thermal stress on polymer degradation. Many of the outstanding questions in the aging behavior of cable materials relate to the necessity of predicting long-term field degradation using accelerated aging results from the laboratory. Materials degrade faster under more extreme

Long-term outcomes of acute kidney injury.

PubMed

Coca, Steven G

2010-05-01

The goal of this review is to summarize the recent plethora of data that relate to long-term outcomes after acute kidney injury (AKI). Surviving patients with AKI are still at high risk for long-term adverse outcomes, even if serum creatinine returns to normal. After adjusting for potential confounders, many recent studies have demonstrated that AKI is independently associated with chronic kidney disease, end-stage renal disease, and premature death. Unfortunately, definitive evidence from randomized controlled trials demonstrating that prevention or treatment of AKI prevents long-term adverse outcomes is not yet available. AKI is clearly a prognostic marker for poor long-term outcomes, but more studies will be needed to determine whether AKI is truly causal and whether or not the risk is modifiable.

Long-term results of percutaneous balloon valvuloplasty in pulmonary valve stenosis in the pediatric population.

PubMed

Merino-Ingelmo, Raquel; Santos-de Soto, José; Coserria-Sánchez, Félix; Descalzo-Señoran, Alfonso; Valverde-Pérez, Israel

2014-05-01

Percutaneous pulmonary valvuloplasty is the preferred interventional procedure for pulmonary valve stenosis. The aim of this study was to evaluate the effectiveness of this technique, assess the factors leading to its success, and determine the long-term results in the pediatric population. The study included 53 patients with pulmonary valve stenosis undergoing percutaneous balloon valvuloplasty between December 1985 and December 2000. Right ventricular size and functional echocardiographic parameters, such as pulmonary regurgitation and residual transvalvular gradient, were assessed during long-term follow-up. Peak-to-peak transvalvular gradient decreased from 74 mmHg [interquartile range, 65-100 mmHg] to 20 mmHg [interquartile range, 14-34 mmHg]. The procedure was unsuccessful in 2 patients (3.77%). The immediate success rate was 73.58%. Follow-up ranged from 10 years to 24 years (median, 15 years). During follow-up, all patients developed late pulmonary regurgitation which was assessed as grade II in 58.4% and grade III in 31.2%. There was only 1 case of long-term restenosis (2.1%). Severe right ventricular dilatation was observed in 27.1% of the patients. None of the patients developed significant right ventricular dysfunction. Pulmonary valve replacement was not required in any of the patients. Percutaneous balloon valvuloplasty is an effective technique in the treatment of pulmonary valve stenosis with good long-term results. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

Long-term follow-up of stentless prosthesis.

PubMed

Sansone, Fabrizio; Dato, Guglielmo Mario Actis; Zingarelli, Edoardo; Ferrero, Emanuele; Prot, Sara; Ceresa, Fabrizio; Patanè, Francesco; Casabona, Riccardo

2014-05-01

Stentless prostheses have an interesting hemodynamic performance when compared to stented prostheses and are recommended in cases of small aortic annulus. From January 1996 to January 2004, 138 patients suffering from aortic disease, underwent aortic valve replacement. • Group A: 93 patients underwent stentless aortic valve implantation [stentless Biocor (Biocor Industria e Pesguisa Ltda, Belo Horizonte, Brazil) and stentless Sorin (Sorin Group, Saluggia, Italy)]. • Group B: 45 patients underwent stented aortic valve implantation (stented Biocor). Patients were assessed by clinical evaluation and echocardiography after a mean follow up of 124.5 ± 58.2 months. There was a significant difference in terms of time of extracorporeal circulation and aortic cross clamp. The actuarial survival at 4, 8, 12, and 15 years is 77%, 50%, 21%, and 18%, respectively. Freedom from reoperation at 4, 8, 12, and 14 years was 92%, 83%, 73%, and 63%, respectively. Freedom from all events, death, and reoperation at 4, 8, 12, and 14 years was 70%, 39%, 13%, and 8%, respectively. There is no statistical difference among the two groups in terms of actuarial survival, freedom from reoperation, and freedom from re-hospitalization for prosthesis-related causes. There was a significantly higher incidence of pacemaker implantation in Group A and the causes are not known. The rate of freedom from reoperation is high in both groups for the patients who remained alive. There was no statistical difference about prosthesis dysfunction between the two groups. The higher incidence of death in Group A cannot be explained by causes related to the prosthesis because there is no difference in terms of causes of death. Rates of reoperation did not differ between the two groups. The results obtained with stentless prostheses are encouraging even in long-term follow-up. Copyright © 2013 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

[Directions for reoperation of patients with Björk-Shiley convexo-concave valve prosthesis, based on long-term experience].

PubMed

Yamaki, F; Nakano, K; Endo, M; Hashimoto, A; Koyanagi, H

1994-02-01

Although a high incidence of strut fracture of the Björk-Shiley convexo-concave (C-C) valve prosthesis has been reported, it is still controversial whether the prosthesis functioning normally should be replaced electively. To clarify our policy for this issue, we reviewed 28 patients who had undergone mitral valve replacement with a C-C valve prosthesis, and evaluated long-term results according to STS guidelines. The incidence of valve-related complications expressed as % patient-year were; structural deterioration 0.30, nonstructural dysfunction 0.30, thromboembolism 1.20. There were no thrombosed valves, anticoagulant-related hemorrhage or prosthetic valve endocarditis. The actuarial free rate after valve replacement with the C-C at 10 years, constructed by the Kaplan-Meier method, were compared with those with St. Jude Medical (SJM) valve prosthesis. (1) Actuarial survival: 77.9 vs 87.3 (NS), (2) Reoperation-free: 91.6 vs 98.0 (p < 0.05), (3) thromboembolism-free: 83.7 vs 83.9 (NS), (4) Event-free (hospital death+reoperation+valve-related complications: 71.2 vs 77.7 (NS). The long-term results with the C-C were compatible to those with a SJM valve prosthesis. However, if a strut fracture occurs, it is very difficult to save the patient's life. The hospital mortality of re-replacement of valve prosthesis during the last 10 years, at our institute, was 2.6%, which is almost equal to the cumulative risk of strut fracture of the C-C valve after 10 years (3.0%).(ABSTRACT TRUNCATED AT 250 WORDS)

GnRH neurons of young and aged female rhesus monkeys co-express GPER but are unaffected by long-term hormone replacement

PubMed Central

Naugle, Michelle M.; Gore, Andrea C.

2014-01-01

Menopause is caused by changes in the function of the hypothalamic-pituitary-gonadal (HPG) axis that controls reproduction. Hypophysiotropic gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus orchestrate the activity of this axis and are regulated by hormonal feedback loops. The mechanisms by which GnRH responses to the primary regulatory sex-steroid hormone, estradiol (E2) are still poorly understood in the context of menopause. Our goal was to determine whether the G protein-coupled estrogen receptor (GPER) is co-expressed in adult primate GnRH neurons, and whether this changes with aging and/or E2 treatment. We used immunofluorescence double labeling to characterize the co-expression of GPER in GnRH perikarya and terminals in the hypothalamus. Young and aged rhesus macaques were ovariectomized and given long-term (~2 year) hormone treatments (E2, E2 + progesterone, or vehicle) selected to mimic currently prescribed hormone replacement therapies used for the alleviation of menopausal symptoms in women. We found that about half of GnRH perikarya co-expressed GPER, while only about 12% of GnRH processes and terminals in the median eminence (ME) were double labeled. Additionally, many GPER labeled processes were in direct contact with GnRH neurons, often wrapped around the perikarya and processes and in close proximity in the ME. These results extend prior work by showing robust colocalization of GPER in GnRH in a clinically relevant model, and support the possibility that GPER-mediated E2 regulation of GnRH occurs both in the soma and terminals in nonhuman primates. PMID:25428637

Long-term metapopulation study of the Glanville fritillary butterfly (Melitaea cinxia): survey methods, data management, and long-term population trends.

PubMed

Ojanen, Sami P; Nieminen, Marko; Meyke, Evgeniy; Pöyry, Juha; Hanski, Ilkka

2013-10-01

Long-term observational studies conducted at large (regional) spatial scales contribute to better understanding of landscape effects on population and evolutionary dynamics, including the conditions that affect long-term viability of species, but large-scale studies are expensive and logistically challenging to keep running for a long time. Here, we describe the long-term metapopulation study of the Glanville fritillary butterfly (Melitaea cinxia) that has been conducted since 1991 in a large network of 4000 habitat patches (dry meadows) within a study area of 50 by 70 km in the Åland Islands in Finland. We explain how the landscape structure has been described, including definition, delimitation, and mapping of the habitat patches; methods of field survey, including the logistics, cost, and reliability of the survey; and data management using the EarthCape biodiversity platform. We describe the long-term metapopulation dynamics of the Glanville fritillary based on the survey. There has been no long-term change in the overall size of the metapopulation, but the level of spatial synchrony and hence the amplitude of fluctuations in year-to-year metapopulation dynamics have increased over the years, possibly due to increasing frequency of exceptional weather conditions. We discuss the added value of large-scale and long-term population studies, but also emphasize the need to integrate more targeted experimental studies in the context of long-term observational studies. For instance, in the case of the Glanville fritillary project, the long-term study has produced an opportunity to sample individuals for experiments from local populations with a known demographic history. These studies have demonstrated striking differences in dispersal rate and other life-history traits of individuals from newly established local populations (the offspring of colonizers) versus individuals from old, established local populations. The long-term observational study has stimulated the

Long-term metapopulation study of the Glanville fritillary butterfly (Melitaea cinxia): survey methods, data management, and long-term population trends

PubMed Central

Ojanen, Sami P; Nieminen, Marko; Meyke, Evgeniy; Pöyry, Juha; Hanski, Ilkka

2013-01-01

Long-term observational studies conducted at large (regional) spatial scales contribute to better understanding of landscape effects on population and evolutionary dynamics, including the conditions that affect long-term viability of species, but large-scale studies are expensive and logistically challenging to keep running for a long time. Here, we describe the long-term metapopulation study of the Glanville fritillary butterfly (Melitaea cinxia) that has been conducted since 1991 in a large network of 4000 habitat patches (dry meadows) within a study area of 50 by 70 km in the Åland Islands in Finland. We explain how the landscape structure has been described, including definition, delimitation, and mapping of the habitat patches; methods of field survey, including the logistics, cost, and reliability of the survey; and data management using the EarthCape biodiversity platform. We describe the long-term metapopulation dynamics of the Glanville fritillary based on the survey. There has been no long-term change in the overall size of the metapopulation, but the level of spatial synchrony and hence the amplitude of fluctuations in year-to-year metapopulation dynamics have increased over the years, possibly due to increasing frequency of exceptional weather conditions. We discuss the added value of large-scale and long-term population studies, but also emphasize the need to integrate more targeted experimental studies in the context of long-term observational studies. For instance, in the case of the Glanville fritillary project, the long-term study has produced an opportunity to sample individuals for experiments from local populations with a known demographic history. These studies have demonstrated striking differences in dispersal rate and other life-history traits of individuals from newly established local populations (the offspring of colonizers) versus individuals from old, established local populations. The long-term observational study has stimulated the

Long-Term Dynamics of Autonomous Fractional Differential Equations

NASA Astrophysics Data System (ADS)

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.

Gill Na+,K+-ATPase of Atlantic salmon smolts in freshwater is not a predictor of long-term growth in seawater

USGS Publications Warehouse

Zydlewski, Gayle B.; Zydlewski, Joseph D.

2012-01-01

Gill Na+,K+-ATPase activity is a widely used measure of osmoregulatory preparedness in salmonid smolts. The degree to which this measure may predict long term performance is uncertain. In order to assess the relationship of this enzyme to long term growth and ion homeostasis, a cohort of Atlantic salmon hatchery smolts was used in a controlled environment with no salinity perturbations. In May 2006, gill Na+,K+-ATPase activity from 940 individually PIT tagged, Penobscot River smolts (USFWS, Green Lake National Fish Hatchery, Maine, United States) was measured immediately prior to isothermal transfer from freshwater to 32 ppt seawater. From the observed range of activities, individuals were classified as having “low”, “middle”, or “high” enzyme activity levels. Individual size (fork length and mass) was recorded on days 0, 1, 3, and 14 and monthly for four months. Growth rates over four time periods were calculated for individual fish maintained until the end of the experiment. Gill Na+,K+-ATPase activities were also measured from a subset of sampled fish. All groups effectively osmoregulated as evidenced by minor perturbations in plasma osmolyte levels. Apart from initial weight loss on transfer, fish grew throughout the experiment, however, there were no differences (fish size, growth rate, and gill Na+,K+-ATPase activity in seawater) among groups with initially different gill Na+,K+-ATPase activities (prior to seawater entry). While gill Na+,K+-ATPase activity may be predictive of performance during the acute phase of acclimation (first few days), typical variation in this enzyme, expressed in freshwater at the peak of smolting, does not appear to be predictive of long-term growth in seawater.

The Womanly World of Long Term Care: The Plight of the Long Term Care Worker. Gray Paper.

ERIC Educational Resources Information Center

Older Women's League, Washington, DC.

Long-term care workers (those who are paid to provide custodial care for long-term patients in nursing homes or at home) must care for a growing number of increasingly disabled or dependent persons. They are working for agencies and institutions under growing pressure to increase productivity. They face new training and competency requirements,…

Meal Replacement Mass Reduction and Integration Acceptability Study

NASA Technical Reports Server (NTRS)

Sirmons, T.; Barrett, A.; Richardson, M.; Arias, D.; Schneiderman, J.; Slack, K.; Williams, T.; Douglas, G.

2017-01-01

NASA, in planning for long-duration missions, has an imperative to provide a food system with the necessary nutrition, acceptability, and safety to ensure sustainment of crew health and performance. The Orion Multi-Purpose Crew Vehicle (MPCV) and future exploration missions are mass constrained; therefore the team is challenged to reduce the mass of the food system by 10% while maintaining product safety, nutrition, and acceptability. Commercially available products do not meet the nutritional requirements for a full meal replacement in the spaceflight food system, and it is currently unknown if daily meal replacements will impact crew food intake and psychosocial health over time. The purpose of this study was to develop a variety of nutritionally balanced breakfast replacement bars that meet spaceflight nutritional, microbiological, sensorial, and shelf-life requirements, while enabling a 10% savings in food mass. To date, six nutrient-dense meal replacement bars (approximately 700 calories per bar) have been developed, using traditional methods of compression as well as novel ultrasonic compression technologies developed by Creative Resonance Inc. (Phoenix, AZ). The four highest rated bars were evaluated in the Human Exploration Research Analog (HERA) to assess the frequency with which actual meal replacement options may be implemented. Specifically, overall impact of bars on mood, satiety, digestive discomfort, and satisfaction with food. These factors are currently being analyzed to inform successful implementation strategies where crew maintain adequate food intake. In addition, these bars are currently undergoing shelf-life testing to determine long-term sensory acceptability, nutritional stability, qualitative stability of analytical measurements (i.e. water activity and texture), and microbiological compliance over two years of storage at room temperature and potential temperature abuse conditions to predict long-term acceptability. It is expected that

Long-term studies of dopamine agonists.

PubMed

Hubble, Jean P

2002-02-26

Dopamine agonists have long been used as adjunctive therapy for the treatment of Parkinson's disease (PD). In more recent years these drugs have also been proved safe and effective as initial therapy in lieu of levodopa in the treatment of PD. Long-term levodopa therapy is associated with motor complications, including fluctuating response patterns and dyskinesia. By initially introducing a dopamine agonist as symptomatic drug therapy, it may be possible to postpone the use of levodopa and delay or prevent the development of motor complications. Recently, four clinical trials have explored this hypothesis by comparing the long-term response and side effects of levodopa with dopamine agonist therapy. The drugs studied have included ropinirole, pramipexole, cabergoline, and pergolide. In each of these projects, the occurrence of motor complications, such as wearing off and dyskinesia, was significantly less in the subjects assigned to initiation of therapy with a dopamine agonist. The addition of levodopa could be postponed by many months or even several years. Therefore, these long-term studies of dopamine agonists support the initiation of a dopamine agonist instead of levodopa in an effort to postpone levodopa-related motor complications. This therapeutic approach may be particularly appropriate in PD patients with a long treatment horizon on the basis of age and general good health. The extension phase of the long-term study comparing pramipexole with levodopa is ongoing, and follow-up information may help to establish the value of this treatment strategy.

Enzyme replacement therapy and fatigue in adults with Pompe disease.

PubMed

Güngör, Deniz; de Vries, Juna M; Brusse, Esther; Kruijshaar, Michelle E; Hop, Wim C J; Murawska, Magda; van den Berg, Linda E M; Reuser, Arnold J J; van Doorn, Pieter A; Hagemans, Marloes L C; Plug, Iris; van der Ploeg, Ans T

2013-06-01

Pompe disease is a hereditary metabolic myopathy, for which enzyme replacement therapy (ERT) has been available since 2006. We investigated whether ERT reduces fatigue in adult patients with Pompe disease. In this prospective international observational survey, we used the Fatigue Severity Scale (FSS) to measure fatigue. Repeated measures ANOVA was used to analyze the data over time. In a subgroup of patients, we also evaluated muscle strength using the Medical Research Council Scale, measured pulmonary function as Forced Vital Capacity, and assessed depression using the Hospital Anxiety and Depression Scale. We followed 163 patients for a median period of 4 years before ERT and for 3 years during ERT. Before ERT, the mean FSS score remained stable at around 5.3 score points; during ERT, scores improved significantly by 0.13 score points per year (p < 0.001). Fatigue decreased mainly in women, in older patients and in those with shorter disease duration. Patients' improvements in fatigue were moderately correlated with the effect of ERT on depression (r 0.55; CI 95% 0.07 to 0.70) but not with the effect of ERT on muscle strength or pulmonary function. Fatigue is a common and disabling problem in patients with early and advanced stages of Pompe disease. Our finding that ERT helps to reduce fatigue is therefore important for this patient population, irrespective of the mechanisms underlying this effect. Copyright © 2013 Elsevier Inc. All rights reserved.

Long-Term Outcomes in Critically Ill Septic Patients Who Survived Cardiopulmonary Resuscitation.

PubMed

Chao, Pei-Wen; Chu, Hsi; Chen, Yung-Tai; Shih, Yu-Ning; Kuo, Shu-Chen; Li, Szu-Yuan; Ou, Shuo-Ming; Shih, Chia-Jen

2016-06-01

To evaluate the long-term survival rate of critically ill sepsis survivors following cardiopulmonary resuscitation on a national scale. Retrospective and observational cohort study. Data were extracted from Taiwan's National Health Insurance Research Database. A total of 272,897 ICU patients with sepsis were identified during 2000-2010. Patients who survived to hospital discharge were enrolled. Post-discharge survival outcomes of ICU sepsis survivors who received cardiopulmonary resuscitation were compared with those of patients who did not experience cardiopulmonary arrest using propensity score matching with a 1:1 ratio. None. Only 7% (n = 3,207) of sepsis patients who received cardiopulmonary resuscitation survived to discharge. The overall 1-, 2-, and 5-year postdischarge survival rates following cardiopulmonary resuscitation were 28%, 23%, and 14%, respectively. Compared with sepsis survivors without cardiopulmonary arrest, sepsis survivors who received cardiopulmonary resuscitation had a greater risk of all-cause mortality after discharge (hazard ratio, 1.38; 95% CI, 1.34-1.46). This difference in mortality risk diminished after 2 years (hazard ratio, 1.11; 95% CI, 0.96-1.28). Multivariable analysis showed that independent risk factors for long-term mortality following cardiopulmonary resuscitation were male sex, older age, receipt of care in a nonmedical center, higher Charlson Comorbidity Index score, chronic kidney disease, cancer, respiratory infection, vasoactive agent use, and receipt of renal replacement therapy during ICU stay. The long-term outcome was worse in ICU survivors of sepsis who received in-hospital cardiopulmonary resuscitation than in those who did not, but this increased risk of mortality diminished at 2 years after discharge.

Sebelipase alfa: first global approval.

PubMed

Shirley, Matt

2015-11-01

Sebelipase alfa (Kanuma™) is a recombinant human lysosomal acid lipase (LAL) developed by Synageva BioPharma Corp. (now Alexion Pharmaceuticals, Inc.) for long-term enzyme replacement therapy in patients with LAL deficiency. The agent, administered by intravenous infusion once weekly or once every other week, acts to replace the deficient enzyme activity in patients with LAL deficiency, reducing lysosomal lipid accumulation, and thereby improving disease-related abnormalities such as dyslipidaemia and liver abnormalities. Sebelipase alfa received its first global approval, in the EU, in August 2015 for long-term enzyme replacement therapy in patients of all ages with LAL deficiency. Regulatory submissions have also been filed in the USA, Mexico and Japan for use in this indication. This article summarizes the milestones in the development of sebelipase alfa leading to this first approval for the treatment of LAL deficiency.

Effect of the cellular structure on thermal conductivity of rigid closed-cell foam polymers during long-term aging

NASA Astrophysics Data System (ADS)

Dementyev, A. G.; Dementyev, M. A.; Zinger, P. A.; Metlyakova, I. R.

1999-03-01

The thermal conductivity of rigid closed-cell polyurethane foams during long-term aging has been studied. The similarity between the kinetics of changes in the physical and mechanical characteristics of PU foams on progressive aging is established, which is attributed to the effect of matrix destruction. It is found that rigid foams have cell walls of various strength, whose impact on the kinetics of changes in the physical characteristics of the foams during long-term aging is ascertained. The results of predicting the thermal conductivity of PU foams by the method of temperature-time analogy and establishing the limits of its application are discussed. The research presented is of interest both in determining the foam durability and in replacing freons by alternative, ecologically less harmful blowing agents.

Changes observed in urine microbiology following replacement of long-term urinary catheters: need to modify UTI guidelines in the UK?

PubMed

Batura, Deepak; Gopal Rao, G; Foran, Marion; Brempong, Fatmata

2018-01-01

Bacteria adherent to long-term urinary catheters (LTUC) may give misleading urine culture results. Guidelines in the USA recommend changing LTUC before urine collection to diagnose UTI and before commencing appropriate antimicrobial treatment. However, in the UK there is no such guidance. In this study, we evaluated differences in urine cultures before and after changing LTUC. In a prospective study in a UK urology department, we made a quantitative and qualitative comparison between paired urines collected before and after catheter change in patients with LTUC. We measured culture growth on a four-point ordinal scale as nil, scanty (< 10 7  cfu/L), moderate (10 7 -10 8  cfu/L) or heavy (> 10 8  cfu/L) and recorded the range of bacterial species isolated. Statistical analysis was by Wilcoxon matched-pairs test. Sixty-six patients (55 males, 11 females) took part in the study. Urines with no growth increased from 7/66 (11%) before change of catheter to 21/66(32%) after change of catheter. Cultures reported as heavy growth (> 10 8  cfu/L) reduced from 48/66 (73%) to 25/66 (38%) after catheter change (p < 0.001). Except for Pseudomonas spp., other organisms were isolated less frequently after catheter change. No Proteus spp. was isolated after catheter change. This study confirms that failure to change long-term catheters before collecting urine for culture may give misleading results. In the interest of accurate diagnosis and antimicrobial stewardship, UK guidelines should recommend changing long-term urinary catheters before collection of urine for culture.

A prospective 10-year study of individualized, intensified enzyme replacement therapy in advanced Fabry disease.

PubMed

Schiffmann, Raphael; Swift, Caren; Wang, Xuan; Blankenship, Derek; Ries, Markus

2015-11-01

To test the hypothesis that more frequent enzyme replacement therapy (ERT) slows the decline in kidney function in adult patients with Fabry disease. A single center open label 10-year prospective clinical trial of 12 patients with advanced Fabry disease who, after having experienced an ongoing decline in renal function after 2-4 years of receiving ERT at the approved dose of 0.2 mg/kg agalsidase alfa every other week (EOW), were switched to weekly (EW) ERT at the same dose. We used linear regression to fit each individual patient's longitudinal estimated glomerular filtration rate (eGFR) record in order to compare the deterioration rates between EOW and EW ERT. For the entire group, mean slope on agalsidase alfa every 2 weeks was -7.92 ± 2.88 ml/min/1.73 m(2)/year and 3.84 ± 4.08 ml/min/1.73 m(2)/year on weekly enzyme infusions (p = 0.01, two-tailed paired t test). Three patients (25 %) completed the entire study with relatively preserved renal function while 50 % of patients reached end-stage renal disease (ESRD) during the 10 years of this study. The estimated average delay to ESRD was 13.8 years [n = 11; 95 % CI 0.66, 27]. One patient had a positive eGFR slope on weekly infusions while the patient with the highest antibody titer had a steeper slope after switching. Mean globotriaosylceramide concentrations in urine and plasma as well as urine protein excretion remained unchanged. Weekly enzyme infusions slow the decline of renal function in a subgroup of more severe patients thus showing that existing ERT can be further optimized.

Long term performance of membranes in an anaerobic membrane bioreactor treating municipal wastewater.

PubMed

Dong, Qirong; Parker, Wayne; Dagnew, Martha

2016-02-01

The long term impact of SRT (100-40 days) and recovery cleaning on membrane performance of an AnMBR treating authentic municipal wastewater in a large pilot plant was assessed. Successful operation of the pilot plant at a flux of 17 LMH was maintained for a period of 536 days during which the longest period of operation without recovery cleaning or membrane replacement was 178 days. Lower SRT (40 days) reduced the fouling propensity of the mixed liquor in terms of TSS concentration and the dewaterability indicators including colloidal COD (cCOD) concentration and capillary suction time (CST). Critical fluxes ranged from 21 to 23 LMH to 25-27 LMH for SRTs of 70 and 40 days respectively and this was consistent with the reduced concentrations of TSS and improved dewaterability under the latter conditions. Recovery cleaning was found to result in substantial reduction of resistance as indicated by both pilot plant operation and clean water flux tests. The long-term fouling rate was observed to be higher with cleaned membranes as compared to virgin membranes. The lower membrane fouling with virgin membranes suggested that accumulation of foulants, which were resistant to cleaning, caused the higher fouling rates for the cleaned membranes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Long Term TOA - M Data and Information

Atmospheric Science Data Center

2017-09-06

... A Long-Term TOA and Constrained Surface Radiation Budget Project A Long-Term TOA and Constrained Surface Readiation ... Budget Experiment (ERBE) and Clouds and the Earth's Radiant Energy System (CERES), that span nearly 30 years to date.   The ...

Long-term biological investigations in space.

PubMed

Lotz, R G; Fuchs, H; Bertsche, U

1975-01-01

Missions in space within the next two decades will be of longer duration than those carried out up to the present time, and the effects of such long-term flights on biological organisms are unknown. Results of biological experiments that have been performed to date cannot be extrapolated to results in future flights because of the unknown influence of adaptation over a long period of time. Prior experiments with Axolotl, fishes, and vertebrates by our research team (in part with sounding rockets) showed that these specimens did not appear to be suitable for long-term missions on which minimization of expense, technique, and energy is required. Subsequent investigations have shown the suitability of the leech (Hirudo medicinalis), which consumes blood of mammals up to ten times its own weight (1 g) and can live more than 2 years without further food supply. Emphasis in the experiments with Hirudo medicinalis is placed on metabolic rhythm and motility. Resorption and diffusion in tissue, development, and growth under long-term effects of cosmic proton radiation and zero-gravity are other focal points. The constancy of cellular life in the mature animals is a point in favor of these specimens. We have also taken into account the synergistic effects of the space environment on the problems just mentioned. The life-support system constructed for the leech has been tested successfully in four sounding rocket flights and, on that basis, has been prepared for a long-term mission. Long-term investigations out of the terrestrial biosphere will provide us with information concerning the degree of adaptation of certain physiological and biochemical functions and as to what extent biological readjustment or repair processes can occur under the specific stress conditions of space flight.

Antiproteinuric therapy and fabry nephropathy: sustained reduction of proteinuria in patients receiving enzyme replacement therapy with agalsidase-beta.

PubMed

Tahir, Hindia; Jackson, Leslie L; Warnock, David G

2007-09-01

This report describes an open-label, nonrandomized, prospective evaluation of the effects of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy on patients who have Fabry disease and also received enzyme replacement therapy with agalsidase-beta, given at 1 mg/kg body wt every 2 wk. Previous placebo-controlled phase III and phase IV trials with agalsidase-beta demonstrated clearing of globotriaosylceramide from vascular endothelia but little effect on proteinuria or progressive loss of kidney function in patients with Fabry disease and severe chronic kidney disease marked by overt proteinuria and/or estimated GFR <60 ml/min per 1.73 m2. Angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker therapy is the standard of care for patients with proteinuric kidney diseases, but their use is challenging in patients with Fabry disease and low or low-normal baseline systemic BP. A group of patients with Fabry disease were treated with antiproteinuric therapy, in conjunction with agalsidase-beta; sustained reductions in proteinuria with stabilization of kidney function were achieved in a group of six patients who had severe Fabry nephropathy; the progression rate was -0.23 +/- 1.12 ml/min per 1.73 m2 per yr with 30 mo of follow-up.

Embolization of renal angiomyolipomas: short-term and long-term outcomes, complications, and tumor shrinkage.

PubMed

Lee, Shen-Yang; Hsu, Hsiang-Hao; Chen, Yung-Chang; Huang, Chen-Chih; Wong, Yon-Cheong; Wang, Li-Jen; Chuang, Cheng-Keng; Yang, Chih-Wei

2009-11-01

This study retrospectively evaluated outcomes, complications, and tumor shrinkage in renal angiomyolipomas after transcatheter arterial embolization (TAE). All renal angiomyolipoma patients who underwent TAE between August 2000 and December 2008 and had short-term (long-term (>6 months) follow-up images were evaluated. Complications and tumor relapse after TAE were reviewed. The sizes of embolized tumors were measured to calculate size reductions and reduction rates after TAE. Differences in tumor size, size reduction, and reduction rate between different time points (pre-TAE, short-term follow-up, and long-term follow-up) and groups (completely and incompletely embolized) were determined. Eleven renal angiomyolipoma patients who had undergone TAE were included. Seven (63.6%) patients had postembolization syndrome and one had abscess formation following TAE. Two patients had a tumor relapse (18.2%). The mean tumor size was 8.57+/-2.66 cm on pre-TAE images. The mean size reduction was 3.1 cm (33.3%) and 3.8 cm (43.0%) at short-term and long-term follow-up. Tumor sizes differed significantly between pre-TAE and short-term (p=0.004) or long-term images (p=0.022) but not between short-term and long-term images (p=0.059). Results stratified by the completeness of embolization indicate that only the short-term size reduction rate differed significantly (p=0.025), while the long-term reduction rate and short- and long-term follow-up tumor size and size reduction were comparable between the two groups. In conclusion, selective TAE is effective for tumor shrinkage in most renal angiomyolipomas, with acceptable complication and relapse rates. Tumor shrinkage occurring within 6 months after TAE may reflect the long-term effect of TAE.

Effects of replacing groundnut cake with rumen content supplemented with or without enzyme in the diet of weaner rabbits.

PubMed

Adeniji, A A; Rumak, S; Oluwafemi, R A

2015-12-18

Rabbits are also herbivores which efficiently convert fodder to food. They are prolific and converter of plant proteins of little or no use to people as food into high-value animal protein. Rabbit meat is high in protein, low in calories and low in fat and cholesterol contents, being considered as a delicacy and a healthy food product. Feeding rabbits with concentrates is expensive and therefore in order to reduce cost of production, hence the use of rumen content in this study as alternative feedstuff without competition. A total of thirty six (36) weaner rabbits (oryctalagus cuniculus) of different body weight and age where use in this experiment to determine the effects of replacing rumen content with or without enzyme supplementation for groundnut cake. This feeding trial which lasted for 8 weeks was carried out in order to determine the replacement value of groundnut cake with rumen content with or without enzyme in the diet of weaner rabbit. A 3x2 factorial experiment was adopted such that there where three (3) replacement level of rumen content (0, 25 and 50 %) for groundnut cake by two supplemental level (no enzyme and enzyme supplement). The results showed that increased inclusion level of rumen content has significant effects (p < 0.05) on daily feed intake, rate of weight gain, feed to gain ratio, nitrogen retention, faecal nitrogen, total nitrogen output and nitrogen digestibility. The weight gained by rabbits fed on 0, 25 and 50 % were all comparable (p > 0.05) with weight gained value of 7.62,7.44 and 7.36 g respectively. Similarly there was a significant (p < 0.05) effect of supplement added on the body weight gain of the experimental animals. There was significant effect (p < 0.05) of the diet on the obtained feed to gain ratio. However, there was no significant effect (p > 0.05) of the treatment on urinary nitrogen. Significant (p < 0.05) effects of supplementation was observed on the feed intake, weight gain, feed to gain

Short-term outcome of 1,465 computer-navigated primary total knee replacements 2005-2008.

PubMed

Gøthesen, Oystein; Espehaug, Birgitte; Havelin, Leif; Petursson, Gunnar; Furnes, Ove

2011-06-01

and purpose Improvement of positioning and alignment by the use of computer-assisted surgery (CAS) might improve longevity and function in total knee replacements, but there is little evidence. In this study, we evaluated the short-term results of computer-navigated knee replacements based on data from the Norwegian Arthroplasty Register. Primary total knee replacements without patella resurfacing, reported to the Norwegian Arthroplasty Register during the years 2005-2008, were evaluated. The 5 most common implants and the 3 most common navigation systems were selected. Cemented, uncemented, and hybrid knees were included. With the risk of revision for any cause as the primary endpoint and intraoperative complications and operating time as secondary outcomes, 1,465 computer-navigated knee replacements (CAS) and 8,214 conventionally operated knee replacements (CON) were compared. Kaplan-Meier survival analysis and Cox regression analysis with adjustment for age, sex, prosthesis brand, fixation method, previous knee surgery, preoperative diagnosis, and ASA category were used. Kaplan-Meier estimated survival at 2 years was 98% (95% CI: 97.5-98.3) in the CON group and 96% (95% CI: 95.0-97.8) in the CAS group. The adjusted Cox regression analysis showed a higher risk of revision in the CAS group (RR = 1.7, 95% CI: 1.1-2.5; p = 0.02). The LCS Complete knee had a higher risk of revision with CAS than with CON (RR = 2.1, 95% CI: 1.3-3.4; p = 0.004)). The differences were not statistically significant for the other prosthesis brands. Mean operating time was 15 min longer in the CAS group. With the introduction of computer-navigated knee replacement surgery in Norway, the short-term risk of revision has increased for computer-navigated replacement with the LCS Complete. The mechanisms of failure of these implantations should be explored in greater depth, and in this study we have not been able to draw conclusions regarding causation.

Long-term clinical study and multiscale analysis of in vivo biodegradation mechanism of Mg alloy

PubMed Central

Lee, Jee-Wook; Han, Hyung-Seop; Han, Kyeong-Jin; Park, Jimin; Jeon, Hojeong; Ok, Myoung-Ryul; Seok, Hyun-Kwang; Ahn, Jae-Pyoung; Lee, Kyung Eun; Lee, Dong-Ho; Yang, Seok-Jo; Cho, Sung-Youn; Cha, Pil-Ryung; Kwon, Hoon; Nam, Tae-Hyun; Han, Jee Hye Lo; Rho, Hyoung-Jin; Lee, Kang-Sik; Kim, Yu-Chan; Mantovani, Diego

2016-01-01

There has been a tremendous amount of research in the past decade to optimize the mechanical properties and degradation behavior of the biodegradable Mg alloy for orthopedic implant. Despite the feasibility of degrading implant, the lack of fundamental understanding about biocompatibility and underlying bone formation mechanism is currently limiting the use in clinical applications. Herein, we report the result of long-term clinical study and systematic investigation of bone formation mechanism of the biodegradable Mg-5wt%Ca-1wt%Zn alloy implant through simultaneous observation of changes in element composition and crystallinity within degrading interface at hierarchical levels. Controlled degradation of Mg-5wt%Ca-1wt%Zn alloy results in the formation of biomimicking calcification matrix at the degrading interface to initiate the bone formation process. This process facilitates early bone healing and allows the complete replacement of biodegradable Mg implant by the new bone within 1 y of implantation, as demonstrated in 53 cases of successful long-term clinical study. PMID:26729859

CD77 levels over enzyme replacement treatment in Fabry Disease Family (V269M).

PubMed

Pereira, Ester Miranda; Silva, Adalberto Socorro da; Silva, Raimundo Nonato da; Monte Neto, José Tiburcio; Nascimento, Fernando F do; Sousa, Jackeline L M; Costa Filho, Henrique César Saraiva de Arêa Leão; Sales Filho, Herton Luiz Alves; Labilloy, Anatalia; Monte, Semiramis Jamil Hadad do

2018-06-04

Fabry disease (FD) is a disorder caused by mutations in the gene encoding for lysosomal enzyme α-galactosidase A (α-GAL). Reduced α-GAL activity leads to progressive accumulation of globotriaosylceramide (Gb3), also known as CD77. The recent report of increased expression of CD77 in blood cells of patients with FD indicated that this molecule can be used as a potential marker for monitoring enzyme replacement therapy (ERT). The purpose of this study was to evaluate the CD77 levels throughout ERT in FD patients (V269M mutation). We evaluated the fluctuations in PBMC (peripheral blood mononuclear cell) membrane CD77 expression in FD patients undergoing ERT and correlated these levels with those observed in different cell types. A greater CD77 expression was found in phagocytes of patients compared to controls at baseline. Interestingly, the variability in CD77 levels is larger in patients at baseline (340 - 1619 MIF) and after 12 months of ERT (240 - 530 MIF) compared with the control group (131 - 331 MFI). Furthermore, by analyzing the levels of CD77 in phagocytes from patients throughout ERT, we found a constant decrease in CD77 levels. The increased CD77 levels in the phagocytes of Fabry carriers together with the decrease in CD77 levels throughout ERT suggest that measuring CD77 levels in phagocytes is a promising tool for monitoring the response to ERT in FD.

Divergent clinical outcomes of alpha-glucosidase enzyme replacement therapy in two siblings with infantile-onset Pompe disease treated in the symptomatic or pre-symptomatic state.

PubMed

Matsuoka, Takashi; Miwa, Yoshiyuki; Tajika, Makiko; Sawada, Madoka; Fujimaki, Koichiro; Soga, Takashi; Tomita, Hideshi; Uemura, Shigeru; Nishino, Ichizo; Fukuda, Tokiko; Sugie, Hideo; Kosuga, Motomichi; Okuyama, Torayuki; Umeda, Yoh

2016-12-01

Pompe disease is an autosomal recessive, lysosomal glycogen storage disease caused by acid α-glucosidase deficiency. Infantile-onset Pompe disease (IOPD) is the most severe form and is characterized by cardiomyopathy, respiratory distress, hepatomegaly, and skeletal muscle weakness. Untreated, IOPD generally results in death within the first year of life. Enzyme replacement therapy (ERT) with recombinant human acid alpha glucosidase (rhGAA) has been shown to markedly improve the life expectancy of patients with IOPD. However, the efficacy of ERT in patients with IOPD is affected by the presence of symptoms and cross-reactive immunologic material (CRIM) status. We have treated two siblings with IOPD with ERT at different ages: the first was symptomatic and the second was asymptomatic. The female proband (Patient 1) was diagnosed with IOPD and initiated ERT at 4 months of age. Her younger sister (Patient 2) was diagnosed with IOPD at 10 days of age and initiated ERT at Day 12. Patient 1, now 6 years old, is alive but bedridden, and requires 24-hour invasive ventilation due to gradually progressive muscle weakness. In Patient 2, typical symptoms of IOPD, including cardiac failure, respiratory distress, progressive muscle weakness, hepatomegaly and myopathic facial features were largely absent during the first 12 months of ERT. Her cardiac function and mobility were well-maintained for the first 3 years, and she had normal motor development. However, she developed progressive hearing impairment and muscle weakness after 3 years of ERT. Both siblings have had low anti-rhGAA immunoglobulin G (IgG) antibody titers during ERT and have tolerated the treatment well. These results suggest that initiation of ERT during the pre-symptomatic period can prevent and/or attenuate the progression of IOPD, including cardiomyopathy, respiratory distress, and muscle weakness for first several years of ERT. However, to improve the long-term efficacy of ERT for IOPD, new strategies

Measure Guideline: Window Repair, Rehabilitation, and Replacement

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baker, P.

2012-12-01

This measure guideline provides information and guidance on rehabilitating, retrofitting, and replacing existing window assemblies in residential construction. The intent is to provide information regarding means and methods to improve the energy and comfort performance of existing wood window assemblies in a way that takes into consideration component durability, in-service operation, and long term performance of the strategies.

Periodontal and periimplant maintenance: a critical factor in long-term treatment success.

PubMed

Shumaker, Nicholas D; Metcalf, Brett T; Toscano, Nicholas T; Holtzclaw, Dan J

2009-09-01

Periodontal maintenance (PM) is a critical factor in the long-term success of both periodontal and dental implant therapy. Studies have shown both modern periodontal and dental implant therapies are effective in maintaining natural teeth and replacing lost teeth, respectively. However, without a regular program of clinical reevaluation, plaque control, oral hygiene instruction, and reassessment of biomechanical factors, the benefits of treatment often are lost and inflammatory disease in the form of recurrent periodontitis or periimplantitis may result. This article reviews the goals, types, and appropriate frequency of PM in periodontal and dental implant therapy, as well as the incidence and etiology of periimplant disease and strategies for management when recurrent disease develops during the maintenance phase of treatment.

Transforaminal Endoscopic Decompression for Foot Drop Twelve Years After Lumbar Total Disc Replacment: Technical Note.

PubMed

Telfeian, Albert E; Oyelese, Adetokunbo; Fridley, Jared; Gokaslan, Ziya L

2018-05-19

Lumbar total disc replacement (LTDR) is considered for the treatment of lumbar degenerative disc disease with the hope that by preserving motion the long-term fusion complication of adjacent segment disease can be avoided. The complications of LTDR can be divided into approach-related and long-term complications. Very little has been described about the complications and treatment for complications more than 10 years after the device has been implanted. Here we describe a tranforaminal endoscopic discectomy procedure for a patient presenting with foot drop twelve years after a L5-S1 total disc replacement. Copyright © 2018. Published by Elsevier Inc.

Effects of long- and short-term management on the functional structure of meadows through species turnover and intraspecific trait variability.

PubMed

Volf, Martin; Redmond, Conor; Albert, Ágnes J; Le Bagousse-Pinguet, Yoann; Biella, Paolo; Götzenberger, Lars; Hrázský, Záboj; Janeček, Štěpán; Klimešová, Jitka; Lepš, Jan; Šebelíková, Lenka; Vlasatá, Tereza; de Bello, Francesco

2016-04-01

The functional structures of communities respond to environmental changes by both species replacement (turnover) and within-species variation (intraspecific trait variability; ITV). Evidence is lacking on the relative importance of these two components, particularly in response to both short- and long-term environmental disturbance. We hypothesized that such short- and long-term perturbations would induce changes in community functional structure primarily via ITV and turnover, respectively. To test this we applied an experimental design across long-term mown and abandoned meadows, with each plot containing a further level of short-term management treatments: mowing, grazing and abandonment. Within each plot, species composition and trait values [height, shoot biomass, and specific leaf area (SLA)] were recorded on up to five individuals per species. Positive covariations between the contribution of species turnover and ITV occurred for height and shoot biomass in response to both short- and long-term management, indicating that species turnover and intraspecific adjustments selected for similar trait values. Positive covariations also occurred for SLA, but only in response to long-term management. The contributions of turnover and ITV changed depending on both the trait and management trajectory. As expected, communities responded to short-term disturbances mostly through changes in intraspecific trait variability, particularly for height and biomass. Interestingly, for SLA they responded to long-term disturbances by both species turnover and intraspecific adjustments. These findings highlight the importance of both ITV and species turnover in adjusting grassland functional trait response to environmental perturbation, and show that the response is trait specific and affected by disturbance regime history.

42 CFR 412.536 - Special payment provisions for long-term care hospitals and satellites of long-term care...

Code of Federal Regulations, 2010 CFR

2010-10-01

... December 29, 2007, was co-located with an entity that is a provider-based, off-campus location of a... hospital or the satellite facility from any individual hospital not co-located with the long-term care... from any individual hospital not co-located with the long-term care hospital or with the satellite of a...

Dynamics of plasma proteome during leptin-replacement therapy in genetically based leptin deficiency.

PubMed

Andreev, V P; Dwivedi, R C; Paz-Filho, G; Krokhin, O V; Wong, M-L; Wilkins, J A; Licinio, J

2011-06-01

The effects of leptin-replacement therapy on the plasma proteome of three unique adults with genetically based leptin deficiency were studied longitudinally during the course of recombinant human leptin-replacement treatment. Quantitative proteomics analysis was performed in plasma samples collected during four stages: before leptin treatment was initiated, after 1.5 and 6 years of leptin-replacement treatment, and after 7 weeks of temporary interruption of leptin-replacement therapy. Of 500 proteins reliably identified and quantitated in those four stages, about 100 were differentially abundant twofold or more in one or more stages. Synchronous dynamics of abundances of about 90 proteins was observed reflecting both short- and long-term effects of leptin-replacement therapy. Pathways and processes enriched with overabundant synchronous proteins were cell adhesion, cytoskeleton remodeling, cell cycle, blood coagulation, glycolysis, and gluconeogenesis. Plausible common regulators of the above synchronous proteins were identified using transcription regulation network analysis. The generated network included two transcription factors (c-Myc and androgen receptor) that are known to activate each other through a double-positive feedback loop, which may represent a potential molecular mechanism for the long-term effects of leptin-replacement therapy. Our findings may help to elucidate the effects of leptin on insulin resistance.

Density-dependent microbial turnover improves soil carbon model predictions of long-term litter manipulations

NASA Astrophysics Data System (ADS)

Georgiou, Katerina; Abramoff, Rose; Harte, John; Riley, William; Torn, Margaret

2017-04-01

Climatic, atmospheric, and land-use changes all have the potential to alter soil microbial activity via abiotic effects on soil or mediated by changes in plant inputs. Recently, many promising microbial models of soil organic carbon (SOC) decomposition have been proposed to advance understanding and prediction of climate and carbon (C) feedbacks. Most of these models, however, exhibit unrealistic oscillatory behavior and SOC insensitivity to long-term changes in C inputs. Here we diagnose the sources of instability in four models that span the range of complexity of these recent microbial models, by sequentially adding complexity to a simple model to include microbial physiology, a mineral sorption isotherm, and enzyme dynamics. We propose a formulation that introduces density-dependence of microbial turnover, which acts to limit population sizes and reduce oscillations. We compare these models to results from 24 long-term C-input field manipulations, including the Detritus Input and Removal Treatment (DIRT) experiments, to show that there are clear metrics that can be used to distinguish and validate the inherent dynamics of each model structure. We find that widely used first-order models and microbial models without density-dependence cannot readily capture the range of long-term responses observed across the DIRT experiments as a direct consequence of their model structures. The proposed formulation improves predictions of long-term C-input changes, and implies greater SOC storage associated with CO2-fertilization-driven increases in C inputs over the coming century compared to common microbial models. Finally, we discuss our findings in the context of improving microbial model behavior for inclusion in Earth System Models.

Long-term disease management of patients with coronary disease by cardiac rehabilitation program staff.

PubMed

Squires, Ray W; Montero-Gomez, Aura; Allison, Thomas G; Thomas, Randal J

2008-01-01

Randomized-clinical trials have demonstrated the benefits of disease management for patients with coronary disease. It is not known if long-term disease management in routine clinical practice provided by cardiac rehabilitation (CR) program staff is possible. The goal of this study was to evaluate the feasibility and clinical benefits of a 3-year disease-management program in the setting of an outpatient CR facility. Consecutive patients (n = 503) referred to CR and who were available for long-term follow-up served as subjects. After a phase II CR program, disease managers assessed secondary-prevention goals every 3 to 6 months via face-to-face meetings with each patient. Outcome measures included use of cardioprotective medications, coronary risk factors, amount of habitual exercise training, and all-cause mortality. At 3 years, aspirin usage was 91%, statin usage 91%, beta-blocker usage 78%, and angiotensin-converting enzyme inhibitor usage 76%. Low-density lipoprotein cholesterol was 90 +/- 23 mg/dL, systolic blood pressure was 126 +/- 19 mm Hg, and body mass index was 29.0 +/- 5.1 kg/m2. Exercise training averaged 139 +/- 123 minutes per week. Annual mortality was 1.9%. There were no differences (P > .05) in medication usage or low-density lipoprotein cholesterol for men versus women, or for age below 65 years versus age 65 years or greater. Long-term disease management of patients with coronary disease in routine clinical practice by CR program staff is feasible and effective in achieving and maintaining secondary-prevention goals. Overweight remains a prevalent and persistent risk factor. We advocate expansion of CR programs into long-term coronary disease-management programs.

Hippocampal Focal Knockout of CBP Affects Specific Histone Modifications, Long-Term Potentiation, and Long-Term Memory

PubMed Central

Barrett, Ruth M; Malvaez, Melissa; Kramar, Eniko; Matheos, Dina P; Arrizon, Abraham; Cabrera, Sara M; Lynch, Gary; Greene, Robert W; Wood, Marcelo A

2011-01-01

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

Short-term and long-term treatment outcomes with Class III activator

PubMed Central

Ryu, Hyo-kyung; Chong, Hyun-Jeong; An, Ki-Yong

2015-01-01

Objective The purpose of this retrospective study was to investigate short-term and long-term skeletodental outcomes of Class III activator treatment. Methods A Class III activator treatment group (AG) comprised of 22 patients (9 boys, 13 girls) was compared with a Class III control group (CG) comprised of 17 patients (6 boys, 11 girls). The total treatment period was divided into three stages; the initial stage (T1), the post-activator treatment or post-mandibular growth peak stage (T2), and the long-term follow-up stage (T3). Cephalometric changes were evaluated statistically via the Mann-Whitney U-test and the Friedman test. Results The AG exhibited significant increases in the SNA angle, ANB angle, Wits appraisal, A point-N perpendicular, Convexity of A point, and proclination of the maxillary incisors, from T1 to T2. In the long-term follow-up (T1-T3), the AG exhibited significantly greater increases in the ANB angle, Wits appraisal, and Convexity of A point than the CG. Conclusions Favorable skeletal outcomes induced during the Class III activator treatment period were generally maintained until the long-term follow-up period of the post-mandibular growth peak stage. PMID:26445717

Enzyme Replacement Therapy Prevents Dental Defects in a Model of Hypophosphatasia

PubMed Central

McKee, M.D.; Nakano, Y.; Masica, D.L.; Gray, J.J.; Lemire, I.; Heft, R.; Whyte, M.P.; Crine, P.; Millán, J.L.

2011-01-01

Hypophosphatasia (HPP) occurs from loss-of-function mutation in the tissue-non-specific alkaline phosphatase (TNALP) gene, resulting in extracellular pyrophosphate accumulation that inhibits skeletal and dental mineralization. TNALP-null mice (Akp2-/-) phenocopy human infantile hypophosphatasia; they develop rickets at 1 week of age, and die before being weaned, having severe skeletal and dental hypomineralization and episodes of apnea and vitamin B6-responsive seizures. Delay and defects in dentin mineralization, together with a deficiency in acellular cementum, are characteristic. We report the prevention of these dental abnormalities in Akp2-/- mice receiving treatment from birth with daily injections of a mineral-targeting, human TNALP (sALP-FcD10). sALP-FcD10 prevented hypomineralization of alveolar bone, dentin, and cementum as assessed by micro-computed tomography and histology. Osteopontin – a marker of acellular cementum – was immuno-localized along root surfaces, confirming that acellular cementum, typically missing or reduced in Akp2-/- mice, formed normally. Our findings provide insight concerning how acellular cementum is formed on tooth surfaces to effect periodontal ligament attachment to retain teeth in their osseous alveolar sockets. Furthermore, they provide evidence that this enzyme-replacement therapy, applied early in post-natal life – where the majority of tooth root development occurs, including acellular cementum formation – could prevent the accelerated tooth loss seen in individuals with HPP. PMID:21212313

Enzyme replacement therapy prevents dental defects in a model of hypophosphatasia.

PubMed

McKee, M D; Nakano, Y; Masica, D L; Gray, J J; Lemire, I; Heft, R; Whyte, M P; Crine, P; Millán, J L

2011-04-01

Hypophosphatasia (HPP) occurs from loss-of-function mutation in the tissue-non-specific alkaline phosphatase (TNALP) gene, resulting in extracellular pyrophosphate accumulation that inhibits skeletal and dental mineralization. TNALP-null mice (Akp2(-/-)) phenocopy human infantile hypophosphatasia; they develop rickets at 1 week of age, and die before being weaned, having severe skeletal and dental hypomineralization and episodes of apnea and vitamin B(6)-responsive seizures. Delay and defects in dentin mineralization, together with a deficiency in acellular cementum, are characteristic. We report the prevention of these dental abnormalities in Akp2(-/-) mice receiving treatment from birth with daily injections of a mineral-targeting, human TNALP (sALP-FcD(10)). sALP-FcD(10) prevented hypomineralization of alveolar bone, dentin, and cementum as assessed by micro-computed tomography and histology. Osteopontin--a marker of acellular cementum--was immuno-localized along root surfaces, confirming that acellular cementum, typically missing or reduced in Akp2(-/-) mice, formed normally. Our findings provide insight concerning how acellular cementum is formed on tooth surfaces to effect periodontal ligament attachment to retain teeth in their osseous alveolar sockets. Furthermore, they provide evidence that this enzyme-replacement therapy, applied early in post-natal life--where the majority of tooth root development occurs, including acellular cementum formation--could prevent the accelerated tooth loss seen in individuals with HPP.

[Psychosocial issues of long-term cancer survivors].

PubMed

Weis, J; Faller, H

2012-04-01

Although cancer incidence rates are increasing, recent statistical studies suggest that cancer patients are showing higher cure rates as well as improved overall survival rates for most cancer locations. These advances are explained by improved strategies in early diagnoses as well as improved cancer therapies. Therefore, the number of long-term cancer survivors has also increased, but only few studies, especially within the last years, have focused on psychosocial issues of this subgroup. Some studies show that overall quality of life of long-term cancer survivors is quite high and comparable to that of the normal population. Nevertheless, a substantial percentage of former patients shows reduced quality of life and suffers from various sequelae of cancer and its treatment. This review focuses on the most common psychosocial issue of long-term survivors such as reduced psychological wellbeing, neuropsychological deficits and cancer-related fatigue syndrome. Finally, recommendations for problem-oriented interventions as well as improvement of psychosocial care of long-term survivors are given.

A security/safety survey of long term care facilities.

PubMed

Acorn, Jonathan R

2010-01-01

What are the major security/safety problems of long term care facilities? What steps are being taken by some facilities to mitigate such problems? Answers to these questions can be found in a survey of IAHSS members involved in long term care security conducted for the IAHSS Long Term Care Security Task Force. The survey, the author points out, focuses primarily on long term care facilities operated by hospitals and health systems. However, he believes, it does accurately reflect the security problems most long term facilities face, and presents valuable information on security systems and practices which should be also considered by independent and chain operated facilities.

Depletion of perineuronal nets enhances recognition memory and long-term depression in the perirhinal cortex

PubMed Central

Romberg, Carola; Yang, Sujeong; Melani, Riccardo; Andrews, Melissa R.; Horner, Alexa E.; Spillantini, Maria G.; Bussey, Timothy J.; Fawcett, James W.; Pizzorusso, Tommaso; Saksida, Lisa M.

2013-01-01

Perineuronal nets are extracellular matrix structures surrounding cortical neuronal cell bodies and proximal dendrites, and are involved in the control of brain plasticity and the closure of critical periods. Expression of the link protein Crtl1/Hapln1 in neurons has recently been identified as the key event triggering the formation of perineuronal nets. Here we show that the genetic attenuation of perineuronal nets in adult brain Crtl1 knockout mice enhances long term object recognition memory and facilitates long-term depression in the perirhinal cortex, a neural correlate of object recognition memory. Identical prolongation of memory follows localised digestion of perineuronal nets with chondroitinase ABC, an enzyme that degrades the chondroitin sulphate proteoglycans (CSPGs) components of PNNs. The memory-enhancing effect of chondroitinase ABC treatment attenuated over time, suggesting that regeneration of PNNs gradually restored control plasticity levels. Our findings indicate that perineuronal nets regulate both memory and experience-driven synaptic plasticity in adulthood. PMID:23595763

Long-Term Care Financing: Lessons From France

PubMed Central

Doty, Pamela; Nadash, Pamela; Racco, Nathalie

2015-01-01

Context An aging population leads to a growing demand for long-term services and supports (LTSS). In 2002, France introduced universal, income-adjusted, public long-term care coverage for adults 60 and older, whereas the United States funds means-tested benefits only. Both countries have private long-term care insurance (LTCI) markets: American policies create alternatives to out-of-pocket spending and protect purchasers from relying on Medicaid. Sales, however, have stagnated, and the market's viability is uncertain. In France, private LTCI supplements public coverage, and sales are growing, although its potential to alleviate the long-term care financing problem is unclear. We explore whether France's very different approach to structuring public and private financing for long-term care could inform the United States’ long-term care financing reform efforts. Methods We consulted insurance experts and conducted a detailed review of public reports, academic studies, and other documents to understand the public and private LTCI systems in France, their advantages and disadvantages, and the factors affecting their development. Findings France provides universal public coverage for paid assistance with functional dependency for people 60 and older. Benefits are steeply income adjusted and amounts are low. Nevertheless, expenditures have exceeded projections, burdening local governments. Private supplemental insurance covers 11% of French, mostly middle-income adults (versus 3% of Americans 18 and older). Whether policyholders will maintain employer-sponsored coverage after retirement is not known. The government's interest in pursuing an explicit public/private partnership has waned under President François Hollande, a centrist socialist, in contrast to the previous center-right leader, President Nicolas Sarkozy, thereby reducing the prospects of a coordinated public/private strategy. Conclusions American private insurers are showing increasing interest in long-term

Reduction of elevated plasma globotriaosylsphingosine in patients with classic Fabry disease following enzyme replacement therapy.

PubMed

van Breemen, Mariëlle J; Rombach, Saskia M; Dekker, Nick; Poorthuis, Ben J; Linthorst, Gabor E; Zwinderman, Aeilko H; Breunig, Frank; Wanner, Christoph; Aerts, Johannes M; Hollak, Carla E

2011-01-01

Fabry disease is treated by two-weekly infusions with α-galactosidase A, which is deficient in this X-linked globotriaosylceramide (Gb3) storage disorder. Elevated plasma globotriaosylsphingosine (lysoGb3) is a hallmark of classical Fabry disease. We investigated effects of enzyme replacement therapy (ERT) on plasma levels of lysoGb3 and Gb3 in patients with classical Fabry disease treated with agalsidase alfa at 0.2mg/kg, agalsidase beta at 0.2mg/kg or at 1.0mg/kg bodyweight. Each treatment regimen led to prominent reductions of plasma lysoGb3 in Fabry males within 3 months (P=0.0313), followed by relative stability later on. Many males developed antibodies against α-galactosidase A, particularly those treated with agalsidase beta. Patients with antibodies tended towards smaller correction in plasma lysoGb3 concentration, whereas treatment with high dose agalsidase beta allowed a reduction comparable to patients without antibodies. Pre-treatment plasma lysoGb3 concentrations of Fabry females were relatively low. In all females and with each treatment regimen, ERT gave reduction or stabilisation of plasma lysoGb3. Our investigation revealed that ERT of Fabry patients reduces plasma lysoGb3, regardless of the recombinant enzyme used. This finding shows that ERT can correct a characteristic biochemical abnormality in Fabry patients. Copyright © 2010 Elsevier B.V. All rights reserved.

Long-term care financing: options for the future.

PubMed

Mulvey, Janemarie; Li, Annelise

2002-01-01

The aging of the baby boomers will have an enormous impact on the future of long-term care costs. This article projects the magnitude of that impact, discusses sources of financing, and considers the cost and feasibility of three options for financing future long-term care services. The authors investigate the alternatives of increasing personal savings, raising payroll taxes and expanding employer-sponsored private long-term care insurance coverage, respectively.

A retrospective analysis of the potential impact of IgG antibodies to agalsidase beta on efficacy during enzyme replacement therapy for Fabry disease.

PubMed

Bénichou, Bernard; Goyal, Sunita; Sung, Crystal; Norfleet, Andrea M; O'Brien, Fanny

2009-01-01

Fabry disease results from a genetic deficiency of alpha-galactosidase A (alpha GAL) and the impaired catabolism of globotriasoylceramide (GL-3) and other glycosphingolipid substrates, which then accumulate pathogenically within most cells. Enzyme replacement therapy (ERT) with agalsidase beta (Fabrazyme), one of two available forms of recombinant human alpha GAL, involves regular intravenous infusions of the therapeutic protein. Immunoglobulin G (IgG) antibodies to recombinant alpha GAL develop in the majority of patients upon repeated infusion. To explore whether anti-alpha GAL IgG interferes with therapeutic efficacy, retrospective analyses were conducted using data obtained from a total of 134 adult male and female patients with Fabry disease who were treated with agalsidase beta at 1mg/kg every 2 weeks for up to 5 years during placebo-controlled trials and the corresponding open-label extension studies. The analyses did not reveal a correlation between anti-alpha GAL IgG titers and the onset of clinical events or the rate of change in estimated GFR during treatment, and no statistically significant association was found between anti-alpha GAL IgG titers and abnormal elevations in plasma GL-3 during treatment. However, a statistically significant association was found between anti-alpha GAL IgG titers and observation of some GL-3 deposition in the dermal capillary endothelial cells of skin during treatment, suggesting that GL-3 clearance may be partially impaired in some patients with high antibody titers. Determination of the long-term impact of circulating anti-alpha GAL IgG antibodies on clinical outcomes will require continued monitoring, and serology testing is recommended as part of the routine care of Fabry disease patients during ERT.

Long-Term Memory and Learning

ERIC Educational Resources Information Center

Crossland, John

2011-01-01

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…

Long-term performance of the Hancock bioprosthetic valved conduit in the aortic root position.

PubMed

Badiu, Catalin C; Bleiziffer, Sabine; Eichinger, Walter B; Hettich, Ina; Krane, Markus; Bauernschmitt, Robert; Lange, Rüdiger

2011-03-01

The study aim was to assess long-term morbidity and mortality with special regard to prosthesis durability after aortic root replacement with the Hancock bioprosthetic porcine conduit. Between 1975 and 2004, a total of 81 patients (55 males, 26 females; mean age 58 +/- 18 years) underwent aortic root replacement with the Hancock conduit for aortic dissection (n = 22; 27%), ascending aortic aneurysm (n = 57; 70%), or porcelain aorta (n = 2; 3%). Twenty-five patients (31%) underwent an emergency operation, 12 (15%) presented with Marfan syndrome, and eight (10%) had undergone previous cardiac surgery. Concomitant procedures were performed in 26 cases (32%). The follow up was 98% complete; the mean follow up was 4.8 +/- 4.0 years (range: 1 day to 16.7 years), and the cumulative follow up was 403 patient-years. Actuarial event-free rates were calculated, and valve-related complications classified according to guidelines for reporting morbidity and mortality after cardiac valvular operations. There were seven (9%) operative deaths and four (5%) in-hospital deaths. Actuarial survival rates at five and 10 years (excluding operative deaths) were 77.0 +/- 5.3% and 54.0 +/- 7.5%, respectively. Actuarial freedom from aortic valve reoperation at five and 10 years was 98 +/- 1.6% and 64 +/- 10.2%, from structural valve deterioration 88.1 +/- 4.7% and 49.9 +/- 9.6%, from thromboembolic events 87.4 +/- 4.6% and 75.1 +/- 9.5%, and from major bleeding events 90.2 +/- 3.9% and 75.4 +/- 8.1%, respectively. Among redo procedures, the stentless Hancock valve could be excised without separating the synthetic graft from the left ventricular outflow tract, and a stented valve prosthesis thus implanted. Hence, it was possible to avoid a second Bentall operation. The long-term survival rates after aortic root replacement with the bioprosthetic Hancock conduit were reasonable for this demanding patient cohort. However, the durability of the prosthesis was inferior to that reported for the

Role of calcitonin gene-related peptide in cardioprotection of short-term and long-term exercise preconditioning.

PubMed

Sun, Xiao-Juan; Pan, Shan-Shan

2014-07-01

To examine the role of calcitonin gene-related peptide (CGRP) in cardioprotection of short-term and long-term exercise preconditioning (EP). Male Sprague-Dawley rats were, respectively, subjected to continuous intermittent treadmill training 3 days or 3 weeks as short-term or long-term EP protocols. The myocardial injury induced by isoproterenol (ISO) was performed 24 hours after short-term and long-term EP. The myocardial injury was evaluated in terms of the serum cardiac troponin levels and the hematoxylin-basic fuchsin-picric acid staining. Additionally, serum CGRP levels, CGRP expression in the dorsal root ganglion (DRG), and heart were analyzed as possible mechanisms to explain short-term and long-term EP-induced cardioprotection. Both short-term and long-term EP markedly attenuated the isoproterenol-induced myocardial ischemia with lower serum cardiac troponin levels. Short-term EP does not alter serum CGRP levels and CGRP expression in the DRG and heart. Long-term EP significantly increases serum CGRP levels and CGRP expression in the DRG and heart. The results indicate that short-term EP does not increase the synthesis and release of CGRP. Therefore, the cardioprotective effect of short-term EP does not involve CGRP adaptation. Furthermore, long-term EP increases CGRP synthesis in the DRG and promotes CGRP release in the blood and heart. Hence, CGRP may play an important role in the cardioprotective effect of long-term EP.

In vivo genome editing of the albumin locus as a platform for protein replacement therapy.

PubMed

Sharma, Rajiv; Anguela, Xavier M; Doyon, Yannick; Wechsler, Thomas; DeKelver, Russell C; Sproul, Scott; Paschon, David E; Miller, Jeffrey C; Davidson, Robert J; Shivak, David; Zhou, Shangzhen; Rieders, Julianne; Gregory, Philip D; Holmes, Michael C; Rebar, Edward J; High, Katherine A

2015-10-08

Site-specific genome editing provides a promising approach for achieving long-term, stable therapeutic gene expression. Genome editing has been successfully applied in a variety of preclinical models, generally focused on targeting the diseased locus itself; however, limited targeting efficiency or insufficient expression from the endogenous promoter may impede the translation of these approaches, particularly if the desired editing event does not confer a selective growth advantage. Here we report a general strategy for liver-directed protein replacement therapies that addresses these issues: zinc finger nuclease (ZFN) -mediated site-specific integration of therapeutic transgenes within the albumin gene. By using adeno-associated viral (AAV) vector delivery in vivo, we achieved long-term expression of human factors VIII and IX (hFVIII and hFIX) in mouse models of hemophilia A and B at therapeutic levels. By using the same targeting reagents in wild-type mice, lysosomal enzymes were expressed that are deficient in Fabry and Gaucher diseases and in Hurler and Hunter syndromes. The establishment of a universal nuclease-based platform for secreted protein production would represent a critical advance in the development of safe, permanent, and functional cures for diverse genetic and nongenetic diseases. © 2015 by The American Society of Hematology.

Planning long-term vegetation studies at landscape scales

USGS Publications Warehouse

Stohlgren, Thomas J.

1995-01-01

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.

Zeitgeists and development trends in long-term care facility design.

PubMed

Wang, Chia-Hui; Kuo, Nai-Wen

2006-06-01

Through literature analysis, in-depth interviews, and the application of the Delphi survey, this study explored long-term care resident priorities with regard to long-term care facility design in terms of both physical and psychological needs. This study further clarified changing trends in long-term care concepts; illustrated the impact that such changes are having on long-term care facility design; and summarized zeitgeists related to the architectural design of long-term care facilities. Results of our Delphi survey indicated the following top five priorities in long-term care facility design: (1) creating a home-like feeling; (2) adhering to Universal Design concepts; (3) providing well-defined private sleeping areas; (4) providing adequate social space; and (5) decentralizing residents' rooms into clusters. The three major zeitgeists related to long-term care facility design include: (1) modern long-term care facilities should abandon their traditional "hospital" image and gradually reposition facilities into homelike settings; (2) institution-based care for the elderly should be de-institutionalized under the concept of aging-in-place; and (3) living clusters, rather than traditional hospital-like wards, should be designed into long-term care facilities.

Long-term cryopreservation of decellularised oesophagi for tissue engineering clinical application.

PubMed

Urbani, Luca; Maghsoudlou, Panagiotis; Milan, Anna; Menikou, Maria; Hagen, Charlotte Klara; Totonelli, Giorgia; Camilli, Carlotta; Eaton, Simon; Burns, Alan; Olivo, Alessandro; De Coppi, Paolo

2017-01-01

Oesophageal tissue engineering is a therapeutic alternative when oesophageal replacement is required. Decellularised scaffolds are ideal as they are derived from tissue-specific extracellular matrix and are non-immunogenic. However, appropriate preservation may significantly affect scaffold behaviour. Here we aim to prove that an effective method for short- and long-term preservation can be applied to tissue engineered products allowing their translation to clinical application. Rabbit oesophagi were decellularised using the detergent-enzymatic treatment (DET), a combination of deionised water, sodium deoxycholate and DNase-I. Samples were stored in phosphate-buffered saline solution at 4°C (4°C) or slow cooled in medium with 10% Me2SO at -1°C/min followed by storage in liquid nitrogen (SCM). Structural and functional analyses were performed prior to and after 2 and 4 weeks and 3 and 6 months of storage under each condition. Efficient decellularisation was achieved after 2 cycles of DET as determined with histology and DNA quantification, with preservation of the ECM. Only the SCM method, commonly used for cell storage, maintained the architecture and biomechanical properties of the scaffold up to 6 months. On the contrary, 4°C method was effective for short-term storage but led to a progressive distortion and degradation of the tissue architecture at the following time points. Efficient storage allows a timely use of decellularised oesophagi, essential for clinical translation. Here we describe that slow cooling with cryoprotectant solution in liquid nitrogen vapour leads to reliable long-term storage of decellularised oesophageal scaffolds for tissue engineering purposes.

Disability in long-term care residents explained by prevalent geriatric syndromes, not long-term care home characteristics: a cross-sectional study.

PubMed

Lane, Natasha E; Wodchis, Walter P; Boyd, Cynthia M; Stukel, Thérèse A

2017-02-10

Self-care disability is dependence on others to conduct activities of daily living, such as bathing, eating and dressing. Among long-term care residents, self-care disability lowers quality of life and increases health care costs. Understanding the correlates of self-care disability in this population is critical to guide clinical care and ongoing research in Geriatrics. This study examines which resident geriatric syndromes and chronic conditions are associated with residents' self-care disability and whether these relationships vary across strata of age, sex and cognitive status. It also describes the proportion of variance in residents' self-care disability that is explained by residents' geriatric syndromes versus long-term care home characteristics. We conducted a cross-sectional study using a health administrative cohort of 77,165 long-term care home residents residing in 614 Ontario long-term care homes. Eligible residents had their self-care disability assessed using the RAI-MDS 2.0 activities of daily living long-form score (range: 0-28) within 90 days of April 1st, 2011. Hierarchical multivariable regression models with random effects for long-term care homes were used to estimate the association between self-care disability and resident geriatric syndromes, chronic conditions and long-term care home characteristics. Differences in findings across strata of sex, age and cognitive status (cognitively intact versus cognitively impaired) were examined. Geriatric syndromes were much more strongly associated with self-care disability than chronic conditions in multivariable models. The direction and size of some of these effects were different for cognitively impaired versus cognitively intact residents. Residents' geriatric syndromes explained 50% of the variation in their self-care disability scores, while characteristics of long-term care homes explained an additional 2% of variation. Differences in long-term care residents' self-care disability are

Fabry disease and enzyme replacement therapy in classic patients with same mutation: different formulations--different outcome?

PubMed

Politei, J; Schenone, A B; Cabrera, G; Heguilen, R; Szlago, M

2016-01-01

We describe the results of the multidisciplinary evaluation in patients with Fabry disease and the same genetic mutation and their outcomes using different approved enzyme replacement therapy (ERT). We measured baseline data and serial results of neuropathic pain assessment and renal, cardiac and cerebrovascular functioning. Pain scale showed improvement in all male cases treated with agalsidasa beta. A mild improvement was detected in agalsidasa alfa-treated patients after 1 year with posterior increase. During the agalsidase beta shortage, two male patients were switched to agalsidasa alfa, after 1 year both cases presented an increase in scale values. Renal evolution showed a tendency toward a decrease in proteinuria in patients using agalsidase beta and worsening with agalsidase alfa. We found improvement in two females using agalsidase beta and no changes in the other cases regarding cardiac functioning. Brain magnetic resonance imaging (MRI) showed increase of white matter lesions in four patients. Improvement and stabilization in neuropathic pain, renal and cardiac functioning and brain MRI were found mainly in patients treated with agalsidase beta. Following the reported recommendations on reintroduction of agalsidase beta after the enzyme shortage, we decided to switch all patients to agalsidase beta. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Enhanced Polyhydroxybutyrate Production for Long-Term Spaceflight Applications

NASA Technical Reports Server (NTRS)

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

2015-01-01

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.

Long-Term Monitoring of Global Climate Forcings and Feedbacks

NASA Technical Reports Server (NTRS)

Hansen, J. (Editor); Rossow, W. (Editor); Fung, I. (Editor)

1993-01-01

A workshop on Long-Term Monitoring of Global Climate Forcings and Feedbacks was held February 3-4, 1992, at NASA's Goddard Institute for Space Studies to discuss the measurements required to interpret long-term global temperature changes, to critique the proposed contributions of a series of small satellites (Climsat), and to identify needed complementary monitoring. The workshop concluded that long-term (several decades) of continuous monitoring of the major climate forcings and feedbacks is essential for understanding long-term climate change.

Long Term Care Aide/Homemaker. Resource Handbook.

ERIC Educational Resources Information Center

Illerbrun, Marley

This handbook provides basic information for preparing individuals to work as long-term care aides and homemakers. It is written both for college students in long-term care aide/homemaker programs and for individuals already employed in these occupations. Health care agencies giving orientation training for new employees and inservice training for…

Developmental Dyslexia and Explicit Long-Term Memory

ERIC Educational Resources Information Center

Menghini, Deny; Carlesimo, Giovanni Augusto; Marotta, Luigi; Finzi, Alessandra; Vicari, Stefano

2010-01-01

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…

Positively selected amino acid replacements within the RuBisCO enzyme of oak trees are associated with ecological adaptations.

PubMed

Hermida-Carrera, Carmen; Fares, Mario A; Fernández, Ángel; Gil-Pelegrín, Eustaquio; Kapralov, Maxim V; Mir, Arnau; Molins, Arántzazu; Peguero-Pina, José Javier; Rocha, Jairo; Sancho-Knapik, Domingo; Galmés, Jeroni

2017-01-01

Phylogenetic analysis by maximum likelihood (PAML) has become the standard approach to study positive selection at the molecular level, but other methods may provide complementary ways to identify amino acid replacements associated with particular conditions. Here, we compare results of the decision tree (DT) model method with ones of PAML using the key photosynthetic enzyme RuBisCO as a model system to study molecular adaptation to particular ecological conditions in oaks (Quercus). We sequenced the chloroplast rbcL gene encoding RuBisCO large subunit in 158 Quercus species, covering about a third of the global genus diversity. It has been hypothesized that RuBisCO has evolved differentially depending on the environmental conditions and leaf traits governing internal gas diffusion patterns. Here, we show, using PAML, that amino acid replacements at the residue positions 95, 145, 251, 262 and 328 of the RuBisCO large subunit have been the subject of positive selection along particular Quercus lineages associated with the leaf traits and climate characteristics. In parallel, the DT model identified amino acid replacements at sites 95, 219, 262 and 328 being associated with the leaf traits and climate characteristics, exhibiting partial overlap with the results obtained using PAML.

Positively selected amino acid replacements within the RuBisCO enzyme of oak trees are associated with ecological adaptations

PubMed Central

Hermida-Carrera, Carmen; Fares, Mario A.; Fernández, Ángel; Gil-Pelegrín, Eustaquio; Kapralov, Maxim V.; Mir, Arnau; Molins, Arántzazu; Peguero-Pina, José Javier; Rocha, Jairo; Sancho-Knapik, Domingo

2017-01-01

Phylogenetic analysis by maximum likelihood (PAML) has become the standard approach to study positive selection at the molecular level, but other methods may provide complementary ways to identify amino acid replacements associated with particular conditions. Here, we compare results of the decision tree (DT) model method with ones of PAML using the key photosynthetic enzyme RuBisCO as a model system to study molecular adaptation to particular ecological conditions in oaks (Quercus). We sequenced the chloroplast rbcL gene encoding RuBisCO large subunit in 158 Quercus species, covering about a third of the global genus diversity. It has been hypothesized that RuBisCO has evolved differentially depending on the environmental conditions and leaf traits governing internal gas diffusion patterns. Here, we show, using PAML, that amino acid replacements at the residue positions 95, 145, 251, 262 and 328 of the RuBisCO large subunit have been the subject of positive selection along particular Quercus lineages associated with the leaf traits and climate characteristics. In parallel, the DT model identified amino acid replacements at sites 95, 219, 262 and 328 being associated with the leaf traits and climate characteristics, exhibiting partial overlap with the results obtained using PAML. PMID:28859145

Design of Composite Hip Prostheses Considering the Long-Term Behavior of the Femur

NASA Astrophysics Data System (ADS)

Lim, Jong Wan; Jeong, Jae Youn; Ha, Sung Kyu

A design method for the hip prosthesis is proposed which can alleviate problems associated with stress shielding, proximal loosening and the high stress of bone-implant interfaces after total hip replacement. The stress shielding which may lead to bone resorption, can cause a loosening of the stem and a fracture of femoral bone. Generally the composites were more suitable for hip prosthesis material in the long-term stability than metallic alloy because design cases of composite materials produced less stress shielding than titanium alloy. A bone remodeling algorithm was implemented in a nonlinear finite element program to predict the long-term performance of the hip prosthesis. The three neck shapes and three cross sections of composite hip were examined. It was found that the stress concentration in the distal region of the titanium stem which may cause the patient's thigh pains was reduced using composite material. The head neck shape was closely related with the cortical bone resorption and the cancellous bone apposition at proximal region whereas the cross-section was closely related with the relative micromotion between interfaces. The convex head neck type with the quadrangle cross-section produced less subsidence at proximal region on the medial side than the others. For all composite material cases, the cancellous bone apposition occurred at partial interfaces, which may result in a stable bio-fixation. The design performances of the convex neck head type with the hexagonal cross-section designed to insure the long-term stability were found to be more suitable than the others.

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

PubMed Central

2014-01-01

Background Infantile Pompe disease is a rare metabolic disease. Patients generally do not survive the first year of life. Enzyme replacement therapy (ERT) has proven to have substantial effects on survival in infantile Pompe disease. However, the costs of therapy are very high. In this paper, we assess the cost-effectiveness of enzyme replacement therapy in infantile Pompe disease. Methods A patient simulation model was used to compare costs and effects of ERT with costs of effects of supportive therapy (ST). The model was filled with data on survival, quality of life and costs. For both arms of the model, data on survival were obtained from international literature. In addition, survival as observed among 20 classic-infantile Dutch patients, who all received ERT, was used. Quality of life was measured using the EQ-5D and assumed to be the same in both treatment groups. Costs included the costs of ERT (which depend on a child’s weight), infusions, costs of other health care utilization, and informal care. A lifetime time horizon was used, with 6-month time cycles. Results Life expectancy was significantly longer in the ERT group than in the ST group. On average, ST receiving patients were modelled not to survive the first half year of life; whereas the life expectancy in the ERT patients was modelled to be almost 14 years. Lifetime incremental QALYs were 6.8. Incremental costs were estimated to be € 7.0 million, which primarily consisted of treatment costs (95%). The incremental costs per QALY were estimated to be € 1.0 million (range sensitivity analyses: € 0.3 million - € 1.3 million). The incremental cost per life year gained was estimated to be € 0.5 million. Conclusions The incremental costs per QALY ratio is far above the conventional threshold values. Results from univariate and probabilistic sensitivity analyses showed the robustness of the results. PMID:24884717

Advancing an ethical framework for long-term care.

PubMed

Carter, Mary Whelan

2002-02-01

This article represents an effort to formulate an ethical framework for long-term care with the explicit purpose of providing a catalyst to promote further discourse and expand consideration of what an ethic of long-term care might entail. Grounding the discussion, an introduction to traditional ethical philosophy is presented, focusing mainly on the fundamentals of deontological and teleological ethical theories. Attention then shifts to a review of the more frequently cited principles found in the long-term care ethics literature, followed by a critique of the current reliance upon principlism to resolve ethical dilemmas in long-term care. In response to this criticism, an agent-driven ethical framework stressing dignity and respect for personhood, drawn from the philosophy of Immanuel Kant, is advanced.

Long-term memory, sleep, and the spacing effect.

PubMed

Bell, Matthew C; Kawadri, Nader; Simone, Patricia M; Wiseheart, Melody

2014-01-01

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.

Short- and Long-Term Lead Release after Partial Lead Service Line Replacements in a Metropolitan Water Distribution System.

PubMed

Deshommes, Elise; Laroche, Laurent; Deveau, Dominique; Nour, Shokoufeh; Prévost, Michèle

2017-09-05

Thirty-three households were monitored in a full-scale water distribution system, to investigate the impact of recent (<2 yr) or old partial lead service line replacements (PLSLRs). Total and particulate lead concentrations were measured using repeat sampling over a period of 1-20 months. Point-of-entry filters were installed to capture sporadic release of particulate lead from the lead service lines (LSLs). Mean concentrations increased immediately after PLSLRs and erratic particulate lead spikes were observed over the 18 month post-PLSLR monitoring period. The mass of lead released during this time frame indicates the occurrence of galvanic corrosion and scale destabilization. System-wide, lead concentrations were however lower in households with PLSLRs as compared to those with no replacement, especially for old PLSLRs. Nonetheless, 61% of PLSLR samples still exceeded 10 μg/L, reflecting the importance of implementing full LSL replacement and efficient risk communication. Acute concentrations measured immediately after PLSLRs demonstrate the need for appropriate flushing procedures to prevent lead poisoning.

Uneventful pregnancy outcome after enzyme replacement therapy with agalsidase beta in a heterozygous female with Fabry disease: A case report.

PubMed

Germain, Dominique P; Bruneval, Patrick; Tran, Thi-Chien; Balouet, Pierre; Richalet, Bernard; Benistan, Karelle

2010-01-01

No reproductive studies have been performed with enzyme replacement therapy (ERT) for Fabry disease (FD, OMIM 301500), a lysosomal storage disorder. Therefore, use during pregnancy is theoretically contraindicated. We report the first case of agalsidase beta treatment throughout pregnancy. High-range proteinuria remained stable and the patient gave birth to a healthy boy after an uncomplicated pregnancy. The decision to administer ERT during pregnancy should be made on an individual basis, considering the FD status and possible risks. Copyright 2009 Elsevier Masson SAS. All rights reserved.

Long-term course of opioid addiction.

PubMed

Hser, Yih-Ing; Evans, Elizabeth; Grella, Christine; Ling, Walter; Anglin, Douglas

2015-01-01

Opioid addiction is associated with excess mortality, morbidities, and other adverse conditions. Guided by a life-course framework, we review the literature on the long-term course of opioid addiction in terms of use trajectories, transitions, and turning points, as well as other factors that facilitate recovery from addiction. Most long-term follow-up studies are based on heroin addicts recruited from treatment settings (mostly methadone maintenance treatment), many of whom are referred by the criminal justice system. Cumulative evidence indicates that opioid addiction is a chronic disorder with frequent relapses. Longer treatment retention is associated with a greater likelihood of abstinence, whereas incarceration is negatively related to subsequent abstinence. Over the long term, the mortality rate of opioid addicts (overdose being the most common cause) is about 6 to 20 times greater than that of the general population; among those who remain alive, the prevalence of stable abstinence from opioid use is low (less than 30% after 10-30 years of observation), and many continue to use alcohol and other drugs after ceasing to use opioids. Histories of sexual or physical abuse and comorbid mental disorders are associated with the persistence of opioid use, whereas family and social support, as well as employment, facilitates recovery. Maintaining opioid abstinence for at least five years substantially increases the likelihood of future stable abstinence. Recent advances in pharmacological treatment options (buprenorphine and naltrexone) include depot formulations offering longer duration of medication; their impact on the long-term course of opioid addiction remains to be assessed.

Long term outcomes of transcatheter aortic valve implantation (TAVI): a systematic review of 5-year survival and beyond.

PubMed

Chakos, Adam; Wilson-Smith, Ashley; Arora, Sameer; Nguyen, Tom C; Dhoble, Abhijeet; Tarantini, Giuseppe; Thielmann, Matthias; Vavalle, John P; Wendt, Daniel; Yan, Tristan D; Tian, David H

2017-09-01

Transcatheter aortic valve implantation/replacement (TAVI/TAVR) is becoming more frequently used to treat aortic stenosis (AS), with increasing push for the procedure in lower risk patients. Numerous randomized controlled trials have demonstrated that TAVI offers a suitable alternative to the current gold standard of surgical aortic valve replacement (SAVR) in terms of short-term outcomes. The present review evaluates long-term outcomes following TAVI procedures. Literature search using three electronic databases was performed up to June 2017. Studies which included 20 or more patients undergoing TAVI procedures, either as a stand-alone or concomitant procedure and with a follow-up of at least 5 years, were included in the present review. Literature search and data extraction were performed by two independent researchers. Digitized survival data were extracted from Kaplan-Meier curves in order to re-create the original patient data using an iterative algorithm and subsequently aggregated for analysis. Thirty-one studies were included in the present analysis, with a total of 13,857 patients. Two studies were national registries, eight were multi-institutional collaborations and the remainder were institutional series. Overall, 45.7% of patients were male, with mean age of 81.5±7.0 years. Where reported, the mean Logistic EuroSCORE (LES) was 22.1±13.7 and the mean Society of Thoracic Surgeons (STS) score was 9.2±6.6. The pooled analysis found 30-day mortality, cerebrovascular accidents, acute kidney injury (AKI) and requirement for permanent pacemaker (PPM) implantation to be 8.4%, 2.8%, 14.4%, and 13.4%, respectively. Aggregated survival at 1-, 2-, 3-, 5- and 7-year were 83%, 75%, 65%, 48% and 28%, respectively. The present systematic review identified acceptable long-term survival results for TAVI procedures in an elderly population. Extended follow-up is required to assess long-term outcomes following TAVI, particularly before its application is extended into

Beyond the short term : transportation asset management for long-term sustainability, accountability and performance

DOT National Transportation Integrated Search

2010-01-01

Transportation Asset Management (TAM) has long been recognized as a sound, long-term approach to managing infrastructure. It provides decision makers with a rational, long-term systematic process for making difficult and complex decisions about how t...

Rural long-term care work, gender, and restructuring.

PubMed

Leach, Belinda; Joseph, Gillian

2011-06-01

Restructuring--the introduction of changes that alter the way health care is delivered for maximum efficiency and least cost--layered with rurality and with rural gender ideologies and practices, results in rural long-term care settings that have particular consequences for the women working in them, and for the residents and communities that they serve. This research investigated how rurality affects the implementation of patient classification in Ontario long-term care homes. Methods involved interviews and focus groups with front-line long-term care workers, administrators, and key participants. The findings revealed that rural long-term care delivery takes place when a restructured work environment intersects with gender ideologies and practices that take on particular characteristics when developed and sustained in a rural context. These factors shape the labor market and working conditions for rural women. We argue that this produces a uniquely rural experience for long-term care workers and conclude that those implementing classification systems must consider contextual factors as well as practical and financial exigencies.

Pancreatic Enzyme Replacement Therapy in Children with Severe Acute Malnutrition: A Randomized Controlled Trial.

PubMed

Bartels, Rosalie H; Bourdon, Céline; Potani, Isabel; Mhango, Brian; van den Brink, Deborah A; Mponda, John S; Muller Kobold, Anneke C; Bandsma, Robert H; Boele van Hensbroek, Michael; Voskuijl, Wieger P

2017-11-01

To assess the benefits of pancreatic enzyme replacement therapy (PERT) in children with complicated severe acute malnutrition. We conducted a randomized, controlled trial in 90 children aged 6-60 months with complicated severe acute malnutrition at the Queen Elizabeth Central Hospital in Malawi. All children received standard care; the intervention group also received PERT for 28 days. Children treated with PERT for 28 days did not gain more weight than controls (13.7 ± 9.0% in controls vs 15.3 ± 11.3% in PERT; P = .56). Exocrine pancreatic insufficiency was present in 83.1% of patients on admission and fecal elastase-1 levels increased during hospitalization mostly seen in children with nonedematous severe acute malnutrition (P <.01). Although the study was not powered to detect differences in mortality, mortality was significantly lower in the intervention group treated with pancreatic enzymes (18.6% vs 37.8%; P < .05). Children who died had low fecal fatty acid split ratios at admission. Exocrine pancreatic insufficiency was not improved by PERT, but children receiving PERT were more likely to be discharged with every passing day (P = .02) compared with controls. PERT does not improve weight gain in severely malnourished children but does increase the rate of hospital discharge. Mortality was lower in patients on PERT, a finding that needs to be investigated in a larger cohort with stratification for edematous and nonedematous malnutrition. Mortality in severe acute malnutrition is associated with markers of poor digestive function. ISRCTN.com: 57423639. Copyright © 2017 Elsevier Inc. All rights reserved.

Digestibility, productive performance, and egg quality of laying hens as affected by dried cassava pulp replacement with corn and enzyme supplementation.

PubMed

Khempaka, Sutisa; Maliwan, Prapot; Okrathok, Supattra; Molee, Wittawat

2018-02-24

Two experiments were conducted to investigate the potential use of dried cassava pulp (DCP) supplemented with enzymes as an alternative feed ingredient in laying hen diets. In experiment 1, 45 laying hens (Isa Brown) aged 45 weeks were placed in individual cages to measure nutrient digestibility for 10 days. Nine dietary treatments were control and DCP as a replacement for corn at 20, 25, 30, and 35% supplemented with mixed enzymes (cellulase, glucanase, and xylanase) at 0.10 and 0.15%. Results showed that the use of DCP at 20-35% added with mixed enzymes had no negative effects on dry matter digestibility, while organic matter digestibility and nitrogen retention decreased with increased DCP up to 30-35% in diets. Both enzyme levels (0.10 and 0.15%) showed similar results on nutrient digestibility and retention. In experiment 2, a total of 336 laying hens aged 32 weeks were randomly allocated to seven dietary treatments (control and DCP-substituted diets at 20, 25, and 30%) supplemented with mixed enzymes (0.10 and 0.15%). Diets incorporated with 20-30% of DCP and supplemented with mixed enzymes at both levels had no significant effects on egg production, egg weight, feed intake, egg mass, feed conversion ratio, protein efficiency ratio, or egg quality, except for egg yolk color being decreased with an increase of DCP in diets (P < 0.05). In conclusion, it is suggested that DCP supplemented with enzymes can be used as an energy source in laying hen diets up to 30% without showing negative effects on nutrient digestibility, productive performance, or egg quality.

[Long-term memory, neurogenesis and novelty signal].

PubMed

Sokolova, E N; Nezlina, N I

2003-01-01

In accordance with the advanced hypothesis the long-term memory is a collection of "gnostic units" selectively tuned to experienced events. The long-term memory is continuously supplemented by new neurons differentiated from stem cells during neurogenesis (particularly, in adults). The transformation of neuronal progenitors into event-selective gnostic units is accomplished with participation of hippocampal "novelty neurons" emphasizing information inputs to be stored in the long-term memory. The formation of the gnostic units is preceded by informational processes occurring in the ventral ("what?") and dorsal ("where?") systems. The formation of a new gnostic unit selectively tuned to a particular event is a result of combination of feature-detector excitation and novelty signal generated by hippocampal novelty neurons.

Space ventures and society long-term perspectives

NASA Technical Reports Server (NTRS)

Brown, W. M.

1985-01-01

A futuristic evaluation of mankind's potential long term future in space is presented. Progress in space will not be inhibited by shortages of the Earth's physical resources, since long term economic growth will be focused on ways to constrain industrial productivity by changing social values, management styles, or government competence. Future technological progress is likely to accelerate with an emphasis on international cooperation, making possible such large joint projects as lunar colonies or space stations on Mars. The long term future in space looks exceedingly bright even in relatively pessimistic scenarios. The principal driving forces will be technological progress, commercial and public-oriented satellites, space industrialization, space travel, and eventually space colonization.

Hip Replacement Surgery

MedlinePlus

... Download Download EPUB Download PDF What is it? Points To Remember About Hip Replacement Surgery Hip replacement ... This leaves your hands and arms free for balance or to use crutches. Use a long-handled " ...

Legislation on Long-Term Care Insurance. Report No. 11.

ERIC Educational Resources Information Center

Wisconsin State Legislative Council, Madison.

This report presents Wisconsin state legislation on long-term care insurance. Part I summarizes key provisions of six 1987 assembly bills concerned with long-term care insurance. Part II describes activities of the Wisconsin State Legislative Council's Special Committee on Long-Term Health Care Insurance. Part III provides background information…

Long-term results after the Rastelli repair for transposition of the great arteries.

PubMed

Hörer, Jürgen; Schreiber, Christian; Dworak, Eva; Cleuziou, Julie; Prodan, Zsolt; Vogt, Manfred; Holper, Klaus; Lange, Rüdiger

2007-06-01

This study sought to assess risk factors for late mortality after the Rastelli operation for patients with transposition of the great arteries, ventricular septal defect, and left ventricular outflow tract obstruction. Records of 39 patients who underwent the Rastelli operation between 1977 and 2004 were reviewed. Median age at the time of operation was 5.1 years (2.2 years within the last 5 years). There were no early deaths. During a median follow-up of 8.9 years (range, 0 to 25 years), 2 patients died of sudden death, 1 of pneumonia, 1 during reoperation, and 2 received heart transplantation. Freedom from death or transplantation was 93.8% +/- 4.3% and 57.5% +/- 15.1% at 10 and 20 years, respectively. Freedom from conduit replacement was 48.8% +/- 10.3% and 32.5% +/- 10.3% at 10 and 20 years, respectively. Subvalvular and valvular left ventricular outflow tract obstruction (p = 0.012), stenosis of the peripheral pulmonary arteries (p < 0.001), enlargement of the ventricular septal defect (p = 0.030), and longer ischemic time (p = 0.015) were predictive for death or transplantation. Patients younger than 4 years at the time of the Rastelli operation showed a trend toward a better freedom from death or transplantation (p = 0.068), but needed significantly more conduit replacements (p = 0.038) compared with patients 4 years or older. The Rastelli operation is a low-risk procedure with regard to early mortality. The status of the pulmonary arteries and ventricular septal defect enlargement are predictive for long-term survival. Patients 4 years of age or older at the time of the Rastelli operation require fewer reoperations for conduit exchange. Nevertheless, early Rastelli repair is recommended because patients 4 years or older are at risk for a higher long-term mortality.

Metabolic adaptations to short-term every-other-day feeding in long-living Ames dwarf mice.

PubMed

Brown-Borg, Holly M; Rakoczy, Sharlene

2013-09-01

Restrictive dietary interventions exert significant beneficial physiological effects in terms of aging and age-related disease in many species. Every other day feeding (EOD) has been utilized in aging research and shown to mimic many of the positive outcomes consequent with dietary restriction. This study employed long living Ames dwarf mice subjected to EOD feeding to examine the adaptations of the oxidative phosphorylation and antioxidative defense systems to this feeding regimen. Every other day feeding lowered liver glutathione (GSH) concentrations in dwarf and wild type (WT) mice but altered GSH biosynthesis and degradation in WT mice only. The activities of liver OXPHOS enzymes and corresponding proteins declined in WT mice fed EOD while in dwarf animals, the levels were maintained or increased with this feeding regimen. Antioxidative enzymes were differentially affected depending on the tissue, whether proliferative or post-mitotic. Gene expression of components of liver methionine metabolism remained elevated in dwarf mice when compared to WT mice as previously reported however, enzymes responsible for recycling homocysteine to methionine were elevated in both genotypes in response to EOD feeding. The data suggest that the differences in anabolic hormone levels likely affect the sensitivity of long living and control mice to this dietary regimen, with dwarf mice exhibiting fewer responses in comparison to WT mice. These results provide further evidence that dwarf mice may be better protected against metabolic and environmental perturbations which may in turn, contribute to their extended longevity. © 2013.

Long-term chemiluminescence signal is produced in the course of luminol oxidation catalyzed by enhancer-independent peroxidase purified from Jatropha curcas leaves.

PubMed

Duan, Peipei; Cai, Feng; Luo, Yongting; Chen, Yangxi; Zou, Shujuan

2015-09-01

Isoenzyme c of horseradish peroxidase (HRP-C) is widely used in enzyme immunoassay combined with chemiluminescence (CL) detection. For this application, HRP-C activity measurement is usually based on luminol oxidation in the presence of hydrogen peroxide (H2O2). However, this catalysis reaction was enhancer dependent. In this study, we demonstrated that Jatropha curcas peroxidase (JcGP1) showed high efficiency in catalyzing luminol oxidation in the presence of H2O2. Compared with HRP-C, the JcGP1-induced reaction was enhancer independent, which made the enzyme-linked immunosorbent assay (ELISA) simpler. In addition, the JcGP1 catalyzed reaction showed a long-term stable CL signal. We optimized the conditions for JcGP1 catalysis and determined the favorable conditions as follows: 50 mM Tris buffer (pH 8.2) containing 10 mM H2 O2, 14 mM luminol and 0.75 M NaCl. The optimum catalysis temperature was 30°C. The detection limit of JcGP1 under optimum condition was 0.2 pM. Long-term stable CL signal combined with enhancer-independent property indicated that JcGP1 might be a valuable candidate peroxidase for clinical diagnosis and enzyme immunoassay with CL detection. Copyright © 2014 John Wiley & Sons, Ltd.

Valuing a long-term care facility.

PubMed

Mellen, C M

1992-10-01

The business valuation industry generally uses at least one of three basic approaches to value a long-term care facility: the cost approach, sales comparison approach, or income approach. The approach that is chosen and the resulting weight that is applied to it depend largely on the circumstances involved. Because a long-term care facility is a business enterprise, more weight usually is given to the income approach which factors into the estimate of value both the tangible and intangible assets of the facility.

Measure Guideline. Wood Window Repair, Rehabilitation, and Replacement

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baker, P.; Eng, P.

2012-12-01

This measure guideline provides information and guidance on rehabilitating, retrofitting, and replacing existing window assemblies in residential construction. The intent is to provide information regarding means and methods to improve the energy and comfort performance of existing wood window assemblies in a way that takes into consideration component durability, in-service operation, and long term performance of the strategies.

Long-Term Administration of Conjugated Estrogen and Bazedoxifene Decreased Murine Fecal β-Glucuronidase Activity Without Impacting Overall Microbiome Community.

PubMed

Chen, Karen Lee Ann; Liu, Xiaoji; Zhao, Yiru Chen; Hieronymi, Kadriye; Rossi, Gianluigi; Auvil, Loretta Sue; Welge, Michael; Bushell, Colleen; Smith, Rebecca Lee; Carlson, Kathryn E; Kim, Sung Hoon; Katzenellenbogen, John A; Miller, Michael Joseph; Madak-Erdogan, Zeynep

2018-05-25

Conjugated estrogens (CE) and Bazedoxifene (BZA) combination is used to alleviate menopause-associated symptoms in women. CE+BZA undergo first-pass-metabolism in the liver and deconjugation by gut microbiome via β-glucuronidase (GUS) enzyme inside the distal gut. To date, the impact of long-term exposure to CE+BZA on the gut microbiome or GUS activity has not been examined. Our study using an ovariectomized mouse model showed that CE+BZA administration did not affect the overall cecal or fecal microbiome community except that it decreased the abundance of Akkermansia, which was identified as a fecal biomarker correlated with weight gain. The fecal GUS activity was reduced significantly and was positively correlated with the abundance of Lactobacillaceae in the fecal microbiome. We further confirmed in Escherichia coli K12 and Lactobacillus gasseri ADH that Tamoxifen-, 4-hydroxy-Tamoxifen- and Estradiol-Glucuronides competed for GUS activity. Our study for the first time demonstrated that long-term estrogen supplementation directly modulated gut microbial GUS activity. Our findings implicate that long-term estrogen supplementation impacts composition of gut microbiota and microbial activity, which affects estrogen metabolism in the gut. Thus, it is possible to manipulate such activity to improve the efficacy and safety of long-term administered estrogens for postmenopausal women or breast cancer patients.

Long-term forest ecosystem research: a programmatic view

Treesearch

Wayne Swank; James Vose

2010-01-01

Long-term research provides the building blocks of knowledge needed to address natural resource and environmental issues. "Long-term" has frequently been considered to span decades with a time frame that usually encompasses at least one generation of scientists and frequently two or more generations. In the rich history of forest science, the origin of long-...

Short- and Long-Term Consequences of Adolescent Work.

ERIC Educational Resources Information Center

Mihalic, Sharon Wofford; Elliott, Delbert

1997-01-01

Examines the short- and long-term consequences of working during adolescence. Responses from 1,725 adolescents reveal that the negative short-term effects are in the domains of school, family and friend bonding, beliefs, and substance use. The long-term beneficial effect is that the duration of early work helps employability in adulthood. (GR)

The interaction of short-term and long-term memory in phonetic category formation

NASA Astrophysics Data System (ADS)

Harnsberger, James D.

2002-05-01

This study examined the role that short-term memory capacity plays in the relationship between novel stimuli (e.g., non-native speech sounds, native nonsense words) and phonetic categories in long-term memory. Thirty native speakers of American English were administered five tests: categorial AXB discrimination using nasal consonants from Malayalam; categorial identification, also using Malayalam nasals, which measured the influence of phonetic categories in long-term memory; digit span; nonword span, a short-term memory measure mediated by phonetic categories in long-term memory; and paired-associate word learning (word-word and word-nonword pairs). The results showed that almost all measures were significantly correlated with one another. The strongest predictor for the discrimination and word-nonword learning results was nonword (r=+0.62) and digit span (r=+0.51), respectively. When the identification test results were partialed out, only nonword span significantly correlated with discrimination. The results show a strong influence of short-term memory capacity on the encoding of phonetic detail within phonetic categories and suggest that long-term memory representations regulate the capacity of short-term memory to preserve information for subsequent encoding. The results of this study will also be discussed with regards to resolving the tension between episodic and abstract models of phonetic category structure.

Short-term outcome of 1,465 computer-navigated primary total knee replacements 2005–2008

PubMed Central

2011-01-01

Background and purpose Improvement of positioning and alignment by the use of computer-assisted surgery (CAS) might improve longevity and function in total knee replacements, but there is little evidence. In this study, we evaluated the short-term results of computer-navigated knee replacements based on data from the Norwegian Arthroplasty Register. Patients and methods Primary total knee replacements without patella resurfacing, reported to the Norwegian Arthroplasty Register during the years 2005–2008, were evaluated. The 5 most common implants and the 3 most common navigation systems were selected. Cemented, uncemented, and hybrid knees were included. With the risk of revision for any cause as the primary endpoint and intraoperative complications and operating time as secondary outcomes, 1,465 computer-navigated knee replacements (CAS) and 8,214 conventionally operated knee replacements (CON) were compared. Kaplan-Meier survival analysis and Cox regression analysis with adjustment for age, sex, prosthesis brand, fixation method, previous knee surgery, preoperative diagnosis, and ASA category were used. Results Kaplan-Meier estimated survival at 2 years was 98% (95% CI: 97.5–98.3) in the CON group and 96% (95% CI: 95.0–97.8) in the CAS group. The adjusted Cox regression analysis showed a higher risk of revision in the CAS group (RR = 1.7, 95% CI: 1.1–2.5; p = 0.02). The LCS Complete knee had a higher risk of revision with CAS than with CON (RR = 2.1, 95% CI: 1.3–3.4; p = 0.004)). The differences were not statistically significant for the other prosthesis brands. Mean operating time was 15 min longer in the CAS group. Interpretation With the introduction of computer-navigated knee replacement surgery in Norway, the short-term risk of revision has increased for computer-navigated replacement with the LCS Complete. The mechanisms of failure of these implantations should be explored in greater depth, and in this study we have not been able to draw

Abstracts 1987. New Horizons in Long Term Care: A Report on the Long Term Care Research and Demonstration Projects.

ERIC Educational Resources Information Center

Illinois State Dept. of Public Aid, Springfield.

This booklet provides a description of 14 projects which were awarded funds during fiscal year 1987 for collaborative research in long-term care to find new ways to treat long-term care patients in Illinois nursing homes. It includes the organization or institution receiving the award, an abstract of the research proposal, and the name of the…

Aggression in Replacement Grower and Finisher Gilts fed a High-Tryptophan Diet and the Effect of Long-term Human-Animal Interaction

USDA-ARS?s Scientific Manuscript database

Aggression is a major problem for swine production as it negatively impacts the pigs’ health and welfare. Dietary approaches such as increasing tryptophan (TRP) ingestion to raise cerebral serotonin (5-HT) – a key neurotransmitter for aggression control, and long-term positive social handling have b...

[Participation as Target of Social Medicine and Nursing Care: - Legal Definition of Long-Term Care Dependency - Strategies to Prevent Long-Term Care Dependency].

PubMed

Nüchtern, Elisabeth; Gansweid, Barbara; Gerber, Hans; von Mittelstaedt, Gert

2017-01-01

Objective: By the "Second Bill to Strengthen Long-Term Care", a new concept of long-term care dependency will be introduced, valid from 2017. Long-term care dependency according to Social Code XI will be defined covering more aspects than today. Therefore, the working group "Nursing Care" of the division "Social Medicine in Practice and Rehabilitation" in the German Society for Social Medicine and Prevention presents their results after working on the social medicine perspective of the definition and prevention of long-term care dependency. Methods: Both the definition and strategies to prevent long-term care dependency are systematically taken into consideration from the point of view of social medicine on the basis of the International Classification of Functioning, Disability and Health (ICF), as long-term care dependency means a defined condition of disability. Results: Both the current and the new concept of long-term care dependency focus activity limitations. The perspective of social medicine considers the interactions of health condition, its effects on daily activities and personal as well as environmental factors. From this point of view approaches for social benefits concerning prevention and rehabilitation can be identified systematically so as to work against the development and progression of long-term care dependency. The reference to the ICF can facilitate the communication between different professions. The new "graduation" of long-term care dependency would allow an international "translation" referring to the ICF. Conclusion: Experts from the field of social medicine as well as those of nursing care, care-givers and nursing researchers have in common the objective that persons in need of nursing care can participate in as many aspects of life of importance to them in an autonomous and self-determined way. The point of view of social medicine on long-term care dependency is fundamental for all occupational groups that are involved and for their

A new image for long-term care.

PubMed

Wager, Richard; Creelman, William

2004-04-01

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.

Long-term characteristics of nuclear emulsion

NASA Astrophysics Data System (ADS)

Naganawa, N.; Kuwabara, K.

2010-02-01

Long-term characteristics of the nuclear emulsion so called ``OPERA film'' used in the neutrino oscillation experiment, OPERA, has been studied for 8 years since its production or refreshing after it. In the results, it turned out to be excellent in sensitivity, amount of random noise, and refreshing characteristics. The retention capacity of latent image of tracks was also studied. The result will open the way to the recycling of 7,000,000 emulsion films which will remain not developed after 5 years of OPERA's run, and other long-term experiments with emulsion.

Very-long-term and short-term chromatic adaptation: are their influences cumulative?

PubMed

Belmore, Suzanne C; Shevell, Steven K

2011-02-09

Very-long-term (VLT) chromatic adaptation results from exposure to an altered chromatic environment for days or weeks. Color shifts from VLT adaptation are observed hours or days after leaving the altered environment. Short-term chromatic adaptation, on the other hand, results from exposure for a few minutes or less, with color shifts measured within seconds or a few minutes after the adapting light is extinguished; recovery to the pre-adapted state is complete in less than an hour. Here, both types of adaptation were combined. All adaptation was to reddish-appearing long-wavelength light. Shifts in unique yellow were measured following adaptation. Previous studies demonstrate shifts in unique yellow due to VLT chromatic adaptation, but shifts from short-term chromatic adaptation to comparable adapting light can be far greater than from VLT adaptation. The question considered here is whether the color shifts from VLT adaptation are cumulative with large shifts from short-term adaptation or, alternatively, does simultaneous short-term adaptation eliminate color shifts caused by VLT adaptation. The results show the color shifts from VLT and short-term adaptation together are cumulative, which indicates that both short-term and very-long-term chromatic adaptation affect color perception during natural viewing. Copyright © 2010 Elsevier Ltd. All rights reserved.

Weight Changes in Patients with Differentiated Thyroid Carcinoma during Postoperative Long-Term Follow-up under Thyroid Stimulating Hormone Suppression

PubMed Central

Sohn, Seo Young; Joung, Ji Young; Cho, Yoon Young; Park, Sun Mi; Jin, Sang Man; Chung, Jae Hoon

2015-01-01

Background There are limited data about whether patients who receive initial treatment for differentiated thyroid cancer (DTC) gain or lose weight during long-term follow-up under thyroid stimulating hormone (TSH) suppression. This study was aimed to evaluate whether DTC patients under TSH suppression experience long-term weight gain after initial treatment. We also examined the impact of the radioactive iodine ablation therapy (RAIT) preparation method on changes of weight, comparing thyroid hormone withdrawal (THW) and recombinant human TSH (rhTSH). Methods We retrospectively reviewed 700 DTC patients who underwent a total thyroidectomy followed by either RAIT and levothyroxine (T4) replacement or T4 replacement alone. The control group included 350 age-matched patients with benign thyroid nodules followed during same period. Anthropometric data were measured at baseline, 1 to 2 years, and 3 to 4 years after thyroidectomy. Comparisons were made between weight and body mass index (BMI) at baseline and follow-up. Results Significant gains in weight and BMI were observed 3 to 4 years after initial treatment for female DTC but not in male patients. These gains among female DTC patients were also significant compared to age-matched control. Women in the THW group gained a significant amount of weight and BMI compared to baseline, while there was no increase in weight or BMI in the rhTSH group. There were no changes in weight and BMI in men according to RAIT preparation methods. Conclusion Female DTC patients showed significant gains in weight and BMI during long-term follow-up after initial treatment. These changes were seen only in patients who underwent THW for RAIT. PMID:26248858

Marketing in the long-term care continuum.

PubMed

Laurence, J Nathan; Kash, Bita A

2010-04-01

Today, long-term care facilities are composed of independent, assisted living, and skilled nursing facilities along with many variations of those themes in between. The clientele for these various types of facilities differ because of the level of care the facility provides as well as the amenities long-term care consumers are looking for. However, there many similarities and common approaches to how reaching the target audience through effective marketing activities. Knowing who the target audience is, how to reach them, and how to communicate with them will serve any facility well in this competitive market. Developing marketing strategies for long-term care settings is as important as understanding what elements of care can be marketed individually as a niche market. Determining the market base for a facility is equally crucial since the target populations differ among the three types of facilities. By reviewing current marketing articles and applying marketing practices, we have crafted some general principles for which each facility type can learn from. Finally, we will discuss the types of marketing and how they related to the spectrum of long-term care facilities.

Short-term meal replacements followed by dietary macronutrient restriction enhance weight loss in polycystic ovary syndrome.

PubMed

Moran, Lisa J; Noakes, Manny; Clifton, Peter M; Wittert, Gary A; Williams, Gemma; Norman, Robert J

2006-07-01

Polycystic ovary syndrome (PCOS), a common condition in women, improves with weight loss. Meal replacements in short-term weight loss and strategies for weight maintenance have not been investigated in PCOS. We compared in overweight women with PCOS the effects of meal replacements in short-term weight-loss and longer-term carbohydrate- or fat-restriction strategies on weight maintenance and improvements in reproductive and metabolic variables. Overweight women with PCOS (n = 43; x +/- SD age: 32.1 +/- 5.2 y; weight: 96.1 +/- 18.4 kg) followed an 8-wk weight-loss regimen (2 meal replacements/d, 4904.4 +/- 127 kJ; phase 1) and then a 6-mo weight-maintenance carbohydrate- (<120 g/d) or fat- (<50 g/d) restriction regimen (phase 2). Thirty-four women completed phase 1, and 23 women completed phase 2; the proportion of dropouts was similar in the 2 groups. During phase 1, significant (P < 0.05) reductions in weight (5.6 +/- 2.4 kg), waist circumference (6.1 +/- 2.5 cm), body fat (4.1 +/- 2.2 kg), insulin (2.8 +/- 1.1 mU/L), total testosterone (0.3 +/- 0.7 nmol/L), and free androgen index (3.1 +/- 4.6) occurred; these changes were sustained during phase 2. No significant differences between diet groups were seen for any variables. At 6 mo, both approaches resulted in a net weight loss of 4.7 +/- 4.6 kg. Improvements in menstrual cyclicity occurred for 16 (57.1%) of 28 subjects. Meal replacements are an effective strategy for the short-term management of PCOS. Advice on moderate fat or carbohydrate restriction was equally effective in maintaining weight reduction and improving reproductive and metabolic variables.

Long-term results of a smoking reduction program.

PubMed

Glasgow, Russell E; Gaglio, Bridget; Estabrooks, Paul A; Marcus, Alfred C; Ritzwoller, Debra P; Smith, Tammy L; Levinson, Arnold H; Sukhanova, Anna; O'Donnell, Colin; Ferro, Erica F; France, Eric K

2009-01-01

There have been few comprehensive evaluations of smoking reduction, especially in health care delivery systems, and little is known about its cost, maintenance of reduced smoking, or robustness across patient subgroups. A generally representative sample of 320 adult smokers from an HMO scheduled for outpatient surgery or a diagnostic procedure was randomized to enhanced usual care or a theory-based smoking reduction intervention that combined telephone counseling and tailored newsletters. Outcomes included cigarettes smoked, carbon monoxide levels, and costs. Both intervention and control conditions continued to improve from 3- to 12-month assessments. Between-condition differences using intent-to-treat analyses on both self-report and carbon monoxide measures were nonsignificant by the 12-month follow-up (25% vs. 19% achieved 50% or greater reductions in cigarettes smoked). The intervention was implemented consistently despite logistical constraints and was generally robust across patient characteristics (eg, education, ethnicity, health literacy, dependence). In the absence of nicotine replacement therapy, the long-term effects of this smoking reduction intervention seem modest and nonsignificant. Future research is indicated to enhance intervention effects and conduct more comprehensive economic analyses of program variations.

Comparative study on short- and long-term behavioral consequences of organophosphate exposure: relationship to AChE mRNA expression.

PubMed

López-Granero, Caridad; Cardona, Diana; Giménez, Estela; Lozano, Rafael; Barril, José; Aschner, Michael; Sánchez-Santed, Fernando; Cañadas, Fernando

2014-01-01

Organophosphates (OPs) affect behavior by inhibiting acetylcholinesterase (AChE). While the cognitive short-term effects may be directly attributed to this inhibition, the mechanisms that underlie OP's long-term cognitive effects remain controversial and poorly understood. Accordingly, two experiments were designed to assess the effects of OPs on cognition, and to ascertain whether both the short- and long-term effects of are AChE-dependent. A single subcutaneous dose of 250 mg/kg chlorpyrifos (CPF), 1.5mg/kg diisopropylphosphorofluoridate (DFP) or 15 mg/kg parathion (PTN) was administered to male Wistar rats. Spatial learning was evaluated 72 h or 23 weeks after exposure, and impulsive choice was tested at 10 and 30 weeks following OPs administration (experiment 1 and 2, respectively). Brain soluble and membrane-bound AChE activity, synaptic AChE-S mRNA, read-through AChE-R mRNA and brain acylpeptide hydrolase (APH) activity (as alternative non-cholinergic target) were analyzed upon completion of the behavioral testing (17 and 37 weeks after OPs exposure). Both short- and long-term CPF treatment caused statistically significant effects on spatial learning, while PTN treatment led only to statistically significant short-term effects. Neither CPF, DFP nor PTN affected the long-term impulsivity response. Long-term exposure to CPF and DFP significantly decreased AChE-S and AChE-R mRNA, while in the PTN treated group only AChE-S mRNA levels were decreased. However, after long-term OP exposure, soluble and membrane-bound AChE activity was indistinguishable from controls. Finally, no changes were noted in brain APH activity in response to OP treatment. Taken together, this study demonstrates long-term effects of OPs on AChE-S and AChE-R mRNA in the absence of changes in AChE soluble and membrane-bound activity. Thus, changes in AChE mRNA expression imply non-catalytic properties of the AChE enzyme. Copyright © 2013 Elsevier Inc. All rights reserved.

Long-term survival with modern therapeutic agents against metastatic melanoma-vemurafenib and ipilimumab in a daily life setting.

PubMed

Lang, B M; Peveling-Oberhag, A; Faidt, D; Hötker, A M; Weyer-Elberich, V; Grabbe, S; Loquai, C

2018-01-31

Despite new therapeutic options, metastatic melanoma remains to be one of the most fatal tumors. With the development of BRAF inhibitors and immune checkpoint inhibitors, overall survival could be prolonged significantly for the first time. Clinical studies implied that even long-term survival is possible with both types of drugs, but predictive markers are so far missing. In this study, we analyzed survival data from patients that received the first-in-class substances vemurafenib and ipilimumab, respectively, during the time period from registration of the drugs until availability of combination treatments. We aimed to evaluate the possibility of long-term survival in a daily life setting and to characterize patients that benefit from these drugs in order to gain insight into predictive attributes. Eighty patients were evaluated who were treated with either vemurafenib (n = 40) or ipilimumab (n = 40), and overall survival was analyzed. Subgroup analysis was performed for patients who were still alive 24 months after induction of therapy (long-term survival). Median overall survival (OS) was 8.0 months for patients treated with vemurafenib and 10.0 months for patients treated with ipilimumab (log-rank P value = 0.689). Long-term survival was achieved in 32.5% of patients (42.3% vemurafenib, 57.7% ipilimumab). Negative predictors of long-term survival in the vemurafenib group were brain and liver metastases, as well as elevated LDH, S100ß and liver enzymes. For ipilimumab, an increase in lymphocytes and eosinophils during course of treatment correlated with long-term survival. Our real-life experience shows that long-term survival is possible with using both therapeutic agents, vemurafenib and ipilimumab. Pattern of metastases and laboratory values might be of interest in decision making for a specific therapeutic approach. Combination of drugs and observational studies in larger patient cohorts are necessary to further validate our findings.

Long term stability following genioplasty: a cephalometric study.

PubMed

Kumar, B Lakshman; Raju, G Kranthi Praveen; Kumar, N Dilip; Reddy, G Vivek; Naik, B Ravindra; Achary, C Ravindranath

2015-04-01

A receding chin associated with an orthognathic mandible is a common situation and surgical changes in chin position are often required to improve the overall harmony of the face. Genioplasty is one such procedure. Stability of hard and soft tissue changes following genioplasty on a long term basis needs to be assessed. Studies on the stability of hard and soft tissue changes following genioplasty on a short term basis have revealed it as a procedure with good stability. This study is done to assess the stability of hard and soft tissue changes following genioplasty on a long term basis. Pre-surgical, postsurgical and long term post-surgical cephalograms of 15 cases treated by vertical reduction augmentation genioplasty were obtained. Paired t-test was used to compare the changes between pre-surgical, postsurgical and long term postsurgical cephalograms. Findings of this study demonstrated that genioplasty is a stable procedure. After long term follow-up period, there was a relapse of 1.5 mm at the pogonion accounting for 24% of the surgical advancement. This is attributed to the remodeling that occurs at the surgical site, but not the instability due to the surgical procedure. With the present study, it can be concluded that vertical reduction and advancement genioplasty can be considered as an adjunctive procedure that produces predictable results and the bony and soft tissue stability were generally very good.

Long-term memory, neurogenesis, and signal novelty.

PubMed

Sokolov, E N; Nezlina, N I

2004-10-01

According to our suggested hypothesis, long-term memory is a collection of "gnostic units," selectively tuned to past events. The formation of long-term memory occurs with the involvement of constantly appearing new neurons which differentiate from stem cells during the process of neurogenesis, in particular in adults. Conversion of precursor neurons into "gnostic units" selective in relation to ongoing events, supplemented by the involvement of hippocampal "novelty neurons," which increase the flow of information needing to be fixed in long-term memory. "Gnostic units" form before the informational processes occurring in the ventral ("what?") and dorsal ("where?") systems. Formation of new "gnostic units" selectively tuned to a particular event results from the combination of excitation of the detector for stimulus characteristics and the novelty signal generated by "novelty neurons" in the hippocampus.

Long-term care financing: lessons from France.

PubMed

Doty, Pamela; Nadash, Pamela; Racco, Nathalie

2015-06-01

POLICY POINTS: France's model of third-party coverage for long-term services and supports (LTSS) combines a steeply income-adjusted universal public program for people 60 or older with voluntary supplemental private insurance. French and US policies differ: the former pay cash; premiums are lower; and take-up rates are higher, in part because employer sponsorship, with and without subsidization, is more common-but also because coverage targets higher levels of need and pays a smaller proportion of costs. Such inexpensive, bare-bones private coverage, especially if marketed as a supplement to a limited public benefit, would be more affordable to those Americans currently most at risk of "spending down" to Medicaid. An aging population leads to a growing demand for long-term services and supports (LTSS). In 2002, France introduced universal, income-adjusted, public long-term care coverage for adults 60 and older, whereas the United States funds means-tested benefits only. Both countries have private long-term care insurance (LTCI) markets: American policies create alternatives to out-of-pocket spending and protect purchasers from relying on Medicaid. Sales, however, have stagnated, and the market's viability is uncertain. In France, private LTCI supplements public coverage, and sales are growing, although its potential to alleviate the long-term care financing problem is unclear. We explore whether France's very different approach to structuring public and private financing for long-term care could inform the United States' long-term care financing reform efforts. We consulted insurance experts and conducted a detailed review of public reports, academic studies, and other documents to understand the public and private LTCI systems in France, their advantages and disadvantages, and the factors affecting their development. France provides universal public coverage for paid assistance with functional dependency for people 60 and older. Benefits are steeply income

What Legislators Need to Know about Long-Term Care Insurance.

ERIC Educational Resources Information Center

Landes, David

This booklet discusses the potential importance to states of long-term care insurance, describes general policy characteristics, and summarizes state actions to both regulate and promote long-term care insurance. It is intended as a resource for legislators and others involved in long-term care financing and public policy formulation. Long-term…

Private long-term care insurance and state tax incentives.

PubMed

Stevenson, David G; Frank, Richard G; Tau, Jocelyn

2009-01-01

To increase the role of private insurance in financing long-term care, tax incentives for long-term care insurance have been implemented at both the federal and state levels. To date, there has been surprisingly little study of these initiatives. Using a panel of national data, we find that market take-up for long-term care insurance increased over the last decade, but state tax incentives were responsible for only a small portion of this growth. Ultimately, the modest ability of state tax incentives to lower premiums implies that they should be viewed as a small piece of the long-term care financing puzzle.

Cost-effectiveness of enzyme replacement therapy for Fabry disease.

PubMed

Rombach, Saskia M; Hollak, Carla E M; Linthorst, Gabor E; Dijkgraaf, Marcel G W

2013-02-19

The cost-effectiveness of enzyme replacement therapy (ERT) compared to standard medical care was evaluated in the Dutch cohort of patients with Fabry disease. Cost-effectiveness analysis was performed using a life-time state-transition model. Transition probabilities, effectiveness data and costs were derived from retrospective data and prospective follow-up of the Dutch study cohort consisting of males and females aged 5-78 years. Intervention with ERT (either agalsidase alfa or agalsidase beta) was compared to the standard medical care. The main outcome measures were years without end organ damage (renal, cardiac en cerebrovascular complications), quality adjusted life years (QALYs), and costs. Over a 70 year lifetime, an untreated Fabry patient will generate 55.0 years free of end-organ damage (53.5 years in males, 56.9 years in females) and 48.6 QALYs (47.8 in males, 49.7 in females). Starting ERT in a symptomatic patient increases the number of years free of end-organ damage by 1.5 year (1.6 in males, 1.3 in females), while the number of QALYs gained increases by a similar amount (1.7 in males, 1.4 in females). The costs of ERT starting in the symptomatic stage are between €9 - €10 million (£ 7.9 - £ 8.8 million, $13.0- $14.5 million) during a patient's lifetime. Consequently, the extra costs per additional year free of end-organ damage and the extra costs per additional QALY range from €5.5 - €7.5 million (£ 4.8 - £ 6.6 million, $ 8.0 - $ 10.8 million), undiscounted. In symptomatic patients with Fabry disease, ERT has limited effect on quality of life and progression to end organ damage. The pharmaco-economic evaluation shows that this modest effectiveness drives the costs per QALY and the costs per year free of end-organ damage to millions of euros. Differentiation of patients who may benefit from ERT should be improved to enhance cost-effectiveness.

Long-term durability of sacral nerve stimulation therapy for chronic fecal incontinence.

PubMed

Hull, Tracy; Giese, Chad; Wexner, Steven D; Mellgren, Anders; Devroede, Ghislain; Madoff, Robert D; Stromberg, Katherine; Coller, John A

2013-02-01

Limited data have been published regarding the long-term results of sacral nerve stimulation, or sacral neuromodulation, for severe fecal incontinence. The aim was to assess the outcome of sacral nerve stimulation with the use of precise tools and data collection, focusing on the long-term durability of the therapy. Five-year data were analyzed. Patients entered in a multicenter, prospective study for fecal incontinence were followed at 3, 6, and 12 months and annually after device implantation. Patients with chronic fecal incontinence in whom conservative treatments had failed or who were not candidates for more conservative treatments were selected. Patients with ≥ 50% improvement over baseline in fecal incontinence episodes per week during a 14-day test stimulation period received sacral nerve stimulation therapy. Patients were assessed with a 14-day bowel diary and Fecal Incontinence Quality of Life and Fecal Incontinence Severity Index questionnaires. Therapeutic success was defined as ≥ 50% improvement over baseline in fecal incontinence episodes per week. All adverse events were collected. A total of 120 patients (110 women; mean age, 60.5 years) underwent implantation. Seventy-six of these patients (63%) were followed a minimum of 5 years (maximum, longer than 8 years) and are the basis for this report. Fecal incontinence episodes per week decreased from a mean of 9.1 at baseline to 1.7 at 5 years, with 89% (n = 64/72) having ≥ 50% improvement (p < 0.0001) and 36% (n = 26/72) having complete continence. Fecal Incontinence Quality of Life scores also significantly improved for all 4 scales between baseline and 5 years (n = 70; p < 0.0001). Twenty-seven of the 76 (35.5%) patients required a device revision, replacement, or explant. The therapeutic effect and improved quality of life for fecal incontinence is maintained 5 years after sacral nerve stimulation implantation and beyond. Device revision, replacement, or explant rate was acceptable, but future

VALIDATION OF A METHOD FOR ESTIMATING LONG-TERM EXPOSURES BASED ON SHORT-TERM MEASUREMENTS

EPA Science Inventory

A method for estimating long-term exposures from short-term measurements is validated using data from a recent EPA study of exposure to fine particles. The method was developed a decade ago but long-term exposure data to validate it did not exist until recently. In this paper, ...

The Long-Term Conditions Questionnaire: conceptual framework and item development.

PubMed

Peters, Michele; Potter, Caroline M; Kelly, Laura; Hunter, Cheryl; Gibbons, Elizabeth; Jenkinson, Crispin; Coulter, Angela; Forder, Julien; Towers, Ann-Marie; A'Court, Christine; Fitzpatrick, Ray

2016-01-01

To identify the main issues of importance when living with long-term conditions to refine a conceptual framework for informing the item development of a patient-reported outcome measure for long-term conditions. Semi-structured qualitative interviews (n=48) were conducted with people living with at least one long-term condition. Participants were recruited through primary care. The interviews were transcribed verbatim and analyzed by thematic analysis. The analysis served to refine the conceptual framework, based on reviews of the literature and stakeholder consultations, for developing candidate items for a new measure for long-term conditions. Three main organizing concepts were identified: impact of long-term conditions, experience of services and support, and self-care. The findings helped to refine a conceptual framework, leading to the development of 23 items that represent issues of importance in long-term conditions. The 23 candidate items formed the first draft of the measure, currently named the Long-Term Conditions Questionnaire. The aim of this study was to refine the conceptual framework and develop items for a patient-reported outcome measure for long-term conditions, including single and multiple morbidities and physical and mental health conditions. Qualitative interviews identified the key themes for assessing outcomes in long-term conditions, and these underpinned the development of the initial draft of the measure. These initial items will undergo cognitive testing to refine the items prior to further validation in a survey.

The Long-Term Conditions Questionnaire: conceptual framework and item development

PubMed Central

Peters, Michele; Potter, Caroline M; Kelly, Laura; Hunter, Cheryl; Gibbons, Elizabeth; Jenkinson, Crispin; Coulter, Angela; Forder, Julien; Towers, Ann-Marie; A’Court, Christine; Fitzpatrick, Ray

2016-01-01

Purpose To identify the main issues of importance when living with long-term conditions to refine a conceptual framework for informing the item development of a patient-reported outcome measure for long-term conditions. Materials and methods Semi-structured qualitative interviews (n=48) were conducted with people living with at least one long-term condition. Participants were recruited through primary care. The interviews were transcribed verbatim and analyzed by thematic analysis. The analysis served to refine the conceptual framework, based on reviews of the literature and stakeholder consultations, for developing candidate items for a new measure for long-term conditions. Results Three main organizing concepts were identified: impact of long-term conditions, experience of services and support, and self-care. The findings helped to refine a conceptual framework, leading to the development of 23 items that represent issues of importance in long-term conditions. The 23 candidate items formed the first draft of the measure, currently named the Long-Term Conditions Questionnaire. Conclusion The aim of this study was to refine the conceptual framework and develop items for a patient-reported outcome measure for long-term conditions, including single and multiple morbidities and physical and mental health conditions. Qualitative interviews identified the key themes for assessing outcomes in long-term conditions, and these underpinned the development of the initial draft of the measure. These initial items will undergo cognitive testing to refine the items prior to further validation in a survey. PMID:27621678

Aortic expansion rate in patients with dilated post-stenotic ascending aorta submitted only to aortic valve replacement long-term follow-up.

PubMed

Gaudino, Mario; Anselmi, Amedeo; Morelli, Mauro; Pragliola, Claudio; Tsiopoulos, Vasileios; Glieca, Franco; Possati, Gianfederico

2011-08-02

This study was conceived to describe the evolution of aortic dimensions in patients with moderate post-stenotic ascending aorta dilation (50 to 59 mm) submitted to aortic valve replacement (AVR) alone. The appropriate treatment of post-stenotic ascending aorta dilation has been poorly investigated. Ninety-three patients affected by severe isolated calcific aortic valve stenosis in the tricuspid aortic valve accompanied by moderate dilation of the ascending aorta (50 to 59 mm) were submitted to AVR only. All patients were followed for a mean of 14.7 ± 4.8 years by means of periodic clinical evaluations and echocardiography and tomography scans of the thorax. Operative mortality was 1.0% (1 patient). During the follow-up, 16 patients died and 2 had to be reoperated for valve dysfunction. No patients experienced acute aortic events (rupture, dissection, pseudoaneurysm), and no patient had to be reoperated on the aorta. There was not a substantial increase in aortic dimensions: mean aortic diameter was 57 ± 11 mm at the end of the follow-up versus 56 ± 02 mm pre-operatively (p = NS). The mean ascending aorta expansion rate was 0.3 ± 0.2 mm/year. In the absence of connective tissue disorders, AVR alone is sufficient to prevent further aortic expansion in patients with moderate post-stenotic dilation of the ascending aorta. Aortic replacement can probably be reserved for patients with a long life expectancy. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Short-term and long-term attentional biases to frequently encountered target features.

PubMed

Sha, Li Z; Remington, Roger W; Jiang, Yuhong V

2017-07-01

It has long been known that frequently occurring targets are attended better than infrequent ones in visual search. But does this frequency-based attentional prioritization reflect momentary or durable changes in attention? Here we observed both short-term and long-term attentional biases for visual features as a function of different types of statistical associations between the targets, distractors, and features. Participants searched for a target, a line oriented horizontally or vertically among diagonal distractors, and reported its length. In one set of experiments we manipulated the target's color probability: Targets were more often in Color 1 than in Color 2. The distractors were in other colors. Participants found Color 1 targets more quickly than Color 2 targets, but this preference disappeared immediately when the target's color became random in the subsequent testing phase. In the other set of experiments, we manipulated the diagnostic values of the two colors: Color 1 was more often a target than a distractor; Color 2 was more often a distractor than a target. Participants found Color 1 targets more quickly than Color 2 targets. Importantly, and in contrast to the first set of experiments, the featural preference was sustained in the testing phase. These results suggest that short-term and long-term attentional biases are products of different statistical information. Finding a target momentarily activates its features, inducing short-term repetition priming. Long-term changes in attention, on the other hand, may rely on learning diagnostic features of the targets.

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

PubMed

Teo, Koon K; Yusuf, Salim; Pfeffer, Marc; Torp-Pedersen, Christian; Kober, Lars; Hall, Alistair; Pogue, Janice; Latini, Roberto; Collins, Rory

2002-10-05

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. We used the Peto-Yusuf method to undertake a systematic overview of data for 22060 patients from six long-term randomised trials of ACE inhibitors to assess whether aspirin altered the effects of ACE inhibitor therapy on major clinical outcomes (composite of death, myocardial infarction, stroke, hospital admission for congestive heart failure, or revascularisation). Baseline characteristics, and prognosis in patients allocated placebo, differed strikingly between those who were and were not taking aspirin at baseline. Results from analyses of all trials, except SOLVD, did not suggest any significant differences between the proportional reductions in risk with ACE inhibitor therapy in the presence or absence of aspirin for the major clinical outcomes (p=0.15), or in any of its individual components, except myocardial infarction (interaction p=0.01). Overall, ACE inhibitor therapy significantly reduced the risk of the major clinical outcomes by 22% (p<0.0001), with clear reductions in risk both among those receiving aspirin at baseline (odds ratio 0.80, [99% CI 0.73-0.88]) and those who were not (0.71 [99% CI 0.62-0.81], interaction p=0.07). Considering the totality of evidence on all major vascular outcomes in these trials, there is only weak evidence of any reduction in the benefit of ACE-inhibitor therapy when added to aspirin. However, there is definite evidence of clinically important benefits with respect to these major clinical outcomes with ACE-inhibitor therapy, irrespective of whether concomitant aspirin is used.

Long-term care financing through Federal tax incentives.

PubMed

Moran, D W; Weingart, J M

1988-12-01

Congress and the Administration are currently exploring various methods of promoting access to long-term care. In this article, an inventory of recent legislative proposals for using the Federal tax code to expand access to long-term care services is provided. Proposals are arrayed along a functional typology that includes tax mechanisms to encourage accumulation of funds, promote purchase of long-term care insurance, or induce the diversion of funds accumulated for another purpose (such as individual retirement accounts). The proposals are evaluated against the public policy objective of encouraging risk pooling to minimize social cost.

Long-term care financing through Federal tax incentives

PubMed Central

Moran, Donald W.; Weingart, Janet M.

1988-01-01

Congress and the Administration are currently exploring various methods of promoting access to long-term care. In this article, an inventory of recent legislative proposals for using the Federal tax code to expand access to long-term care services is provided. Proposals are arrayed along a functional typology that includes tax mechanisms to encourage accumulation of funds, promote purchase of long-term care insurance, or induce the diversion of funds accumulated for another purpose (such as individual retirement accounts). The proposals are evaluated against the public policy objective of encouraging risk pooling to minimize social cost. PMID:10312964

Long-term psychosocial consequences of surgical congenital malformations.

PubMed

Diseth, Trond H; Emblem, Ragnhild

2017-10-01

Surgical congenital malformations often represent years of treatment, large number of hospital stays, treatment procedures, and long-term functional sequels affecting patients' psychosocial functioning. Both functional defects and psychosocial difficulties that occur commonly in childhood may pass through adolescence on to adulthood. This overview presents reports published over the past 3 decades to elucidate the long-term psychosocial consequences of surgical congenital malformations. Literature searches conducted on PubMed database revealed that less than 1% of all the records of surgical congenital malformations described long-term psychosocial consequences, but with diverse findings. This inconsistency may be due to methodological differences or deficiencies; especially in study design, patient sampling, and methods. Most of the studies revealed that the functional deficits may have great impact on patients' mental health, psychosocial functioning, and QoL; both short- and long-term negative consequences. Factors other than functional problems, e.g., repeated anesthesia, multiple hospitalization, traumatic treatment procedures, and parental dysfunctioning, may also predict long-term mental health and psychosocial functioning. Through multidisciplinary approach, pediatric surgeons should also be aware of deficits in emotional and psychosocial functioning. To achieve overall optimal psychosocial functioning, the challenge is to find a compromise between physically optimal treatment procedures and procedures that are not psychologically detrimental. Copyright © 2017. Published by Elsevier Inc.

Cardiac energy metabolism is disturbed in Fabry disease and improves with enzyme replacement therapy using recombinant human galactosidase A.

PubMed

Machann, Wolfram; Breunig, Frank; Weidemann, Frank; Sandstede, Jörn; Hahn, Dietbert; Köstler, Herbert; Neubauer, Stefan; Wanner, Christoph; Beer, Meinrad

2011-03-01

In vitro studies have shown impairment of energy metabolism in cardiac fibroblasts from Fabry patients. A recent in vivo study reported an association between cardiac energy metabolism and increased myocardial mass in Fabry patients. We therefore assessed possible disturbances of cardiac energy metabolism in Fabry patients by in vivo (31)P-MR-spectroscopy. Additionally, the effect of enzyme replacement therapy (ERT) on cardiac energetics was tested. Twenty-three patients (41 ± 9 years; 10 females) with genetically proven Fabry disease were examined with a 1.5 T Scanner, and compared with an age-matched healthy control group. Eight patients underwent ERT and had follow-up examinations after 3 and 14 months. The high-energy phosphate molecules phosphocreatine (PCr) and adenosine triphosphate (ATP) were quantified in localized 31P-spectra by SLOOP (spectral localization with optimum point spread function). Cine- and late gadolinium enhancement (LGE) studies were also performed. When compared with healthy controls, Fabry patients demonstrated reduced PCr- (6.1 ± 1.9 vs. 8.8 ± 2.6 mmol/kg; P = 0.003) and ATP concentrations (3.9 ± 1.5 vs. 4.6 ± 1.0 mmol/kg; P = 0.048). During ERT, PCr concentrations increased (7.1 ± 1.5 mmol/kg vs. 6.1 ± 1.9; P < 0.05) and left ventricular mass decreased (215 ± 55 vs. 185 ± 45 g; P = 0.012). Disturbances in cardiac energetics were not correlated to the presence or absence of cardiac fibrosis on LGE. Cardiac energy metabolism is disturbed in Fabry disease; this may play an important role in the pathogenesis of Fabry cardiomyopathy. Enzyme replacement therapy ameliorates energetic depression.

Hyperfunction of muscarinic receptor maintains long-term memory in 5-HT4 receptor knock-out mice.

PubMed

Segu, Luis; Lecomte, Marie-José; Wolff, Mathieu; Santamaria, Julie; Hen, René; Dumuis, Aline; Berrard, Sylvie; Bockaert, Joël; Buhot, Marie-Christine; Compan, Valérie

2010-03-04

Patients suffering from dementia of Alzheimer's type express less serotonin 4 receptors (5-HTR(4)), but whether an absence of these receptors modifies learning and memory is unexplored. In the spatial version of the Morris water maze, we show that 5-HTR(4) knock-out (KO) and wild-type (WT) mice performed similarly for spatial learning, short- and long-term retention. Since 5-HTR(4) control mnesic abilities, we tested whether cholinergic system had circumvented the absence of 5-HTR(4). Inactivating muscarinic receptor with scopolamine, at an ineffective dose (0.8 mg/kg) to alter memory in WT mice, decreased long-term but not short-term memory of 5-HTR(4) KO mice. Other changes included decreases in the activity of choline acetyltransferase (ChAT), the required enzyme for acetylcholine synthesis, in the septum and the dorsal hippocampus in 5-HTR(4) KO under baseline conditions. Training- and scopolamine-induced increase and decrease, respectively in ChAT activity in the septum in WT mice were not detected in the 5-HTR(4) KO animals. Findings suggest that adaptive changes in cholinergic systems may circumvent the absence of 5-HTR(4) to maintain long-term memory under baseline conditions. In contrast, despite adaptive mechanisms, the absence of 5-HTR(4) aggravates scopolamine-induced memory impairments. The mechanisms whereby 5-HTR(4) mediate a tonic influence on ChAT activity and muscarinic receptors remain to be determined.

Perioperative morbidity and mortality of total hip replacement in liver transplant recipients: a 7-year single-center experience.

PubMed

Aminata, Iman; Lee, Soo-Ho; Chang, Jae-Suk; Lee, Choon-Sung; Chun, Jae-Myeung; Park, Jin-Woong; Pawaskar, Aditya; Jeon, In-Ho

2012-12-15

This study aims to evaluate perioperative mortality and morbidity after total hip replacement in liver transplant recipients and suggesting safety guidelines. Hip replacement surgery is one of the most common elective surgeries even for organ transplant recipients. However, there is a paucity of literature addressing the morbidity and complications of hip replacement surgery for liver transplant recipients. We analyzed retrospectively 33 arthroplasty cases in 20 liver transplant recipients carried out in a single center from 2005 to 2011. All perioperative clinical and laboratory data were evaluated together with early and late morbidity and mortality. Of 2253 liver transplant recipients, 20 (0.9%) patients underwent 33 total hip arthroplasties. Thirty-two arthroplasties were performed for avascular necrosis of the femoral head, whereas only one was performed for osteoarthritis. There was no death, liver failure, or infection within 30 days after surgery. Three patients showed elevated liver enzyme more than 5 times the normal value, but it eventually decreased to normal within 1 week. Of 33 cases of arthroplasty, postoperative blood transfusion was needed in 14 cases with 1 case receiving more than 4 U. On long-term follow-up, no patients have developed periprosthetic fracture, implant loosening, or liver failure. All patients showed good to excellent postoperative Harris hip score. In this series, we can infer that hip replacement surgery in liver transplantation patients is safe and gives a reliably good result. Some preoperative conditions should be obtained to reduce postoperative morbidity.

The relationship between interannual and long-term cloud feedbacks

DOE PAGES

Zhou, Chen; Zelinka, Mark D.; Dessler, Andrew E.; ...

2015-12-11

The analyses of Coupled Model Intercomparison Project phase 5 simulations suggest that climate models with more positive cloud feedback in response to interannual climate fluctuations also have more positive cloud feedback in response to long-term global warming. Ensemble mean vertical profiles of cloud change in response to interannual and long-term surface warming are similar, and the ensemble mean cloud feedback is positive on both timescales. However, the average long-term cloud feedback is smaller than the interannual cloud feedback, likely due to differences in surface warming pattern on the two timescales. Low cloud cover (LCC) change in response to interannual andmore » long-term global surface warming is found to be well correlated across models and explains over half of the covariance between interannual and long-term cloud feedback. In conclusion, the intermodel correlation of LCC across timescales likely results from model-specific sensitivities of LCC to sea surface warming.« less

L'archivage a long terme de la maquette numerique trois-dimensionnelle annotee

NASA Astrophysics Data System (ADS)

Kheddouci, Fawzi

The use of engineering drawings in the development of mechanical products, including the exchange of engineering data as well as for archiving, is common industry practice. Traditionally, paper has been the mean to deliver those needs. However, these practices have evolved in favour of computerized tools and methods for the creation, diffusion and preservation of data involved in the process of developing aeronautical products characterized by life cycles that can exceed 70 years. Therefore, it is necessary to redefine how to maintain this data in a context whereby engineering drawings are being replaced by the 3D annotated digital mock-up. This thesis addresses the issue of long-term archiving of 3D annotated digital mock-ups, which includes geometric and dimensional tolerances, as well as other notes and specifications, in compliance with the requirements formulated by the aviation industry including regulatory and legal requirements. First, we review the requirements imposed by the aviation industry in the context of long-term archiving of 3D annotated digital mock-ups. We then consider alternative solutions. We begin by identifying the theoretical approach behind the choice of a conceptual model for digital long-term archiving. Then we evaluate, among the proposed alternatives, an archiving format that will guarantee the preservation of the integrity of the 3D annotated model (geometry, tolerances and other metadata) and its sustainability. The evaluation of 3D PDF PRC as a potential archiving format is carried out on a sample of 185 3D CATIA V5 models (parts and assemblies) provided by industrial partners. This evaluation is guided by a set of criteria including the transfer of geometry, 3D annotations, views, captures and parts positioning in assembly. The results indicate that maintaining the exact geometry is done successfully when transferring CATIA V5 models to 3D PDF PRC. Concerning the transfer of 3D annotations, we observed degradation associated with

Antibody-mediated enzyme replacement therapy targeting both lysosomal and cytoplasmic glycogen in Pompe disease.

PubMed

Yi, Haiqing; Sun, Tao; Armstrong, Dustin; Borneman, Scott; Yang, Chunyu; Austin, Stephanie; Kishnani, Priya S; Sun, Baodong

2017-05-01

Pompe disease is characterized by accumulation of both lysosomal and cytoplasmic glycogen primarily in skeletal and cardiac muscles. Mannose-6-phosphate receptor-mediated enzyme replacement therapy (ERT) with recombinant human acid α-glucosidase (rhGAA) targets the enzyme to lysosomes and thus is unable to digest cytoplasmic glycogen. Studies have shown that anti-DNA antibody 3E10 penetrates living cells and delivers "cargo" proteins to the cytosol or nucleus via equilibrative nucleoside transporter ENT2. We speculate that 3E10-mediated ERT with GAA will target both lysosomal and cytoplasmic glycogen in Pompe disease. A fusion protein (FabGAA) containing a humanized Fab fragment derived from the murine 3E10 antibody and the 110 kDa human GAA precursor was constructed and produced in CHO cells. Immunostaining with an anti-Fab antibody revealed that the Fab signals did not co-localize with the lysosomal marker LAMP2 in cultured L6 myoblasts or Pompe patient fibroblasts after incubation with FabGAA. Western blot with an anti-GAA antibody showed presence of the 150 kDa full-length FabGAA in the cell lysates, in addition to the 95- and 76 kDa processed forms of GAA that were also seen in the rhGAA-treated cells. Blocking of mannose-6-phosphate receptor with mannose-6-phosphate markedly reduced the 95- and the 76 kDa forms but not the 150 kDa form. In GAA-KO mice, FabGAA achieved similar treatment efficacy as rhGAA at an equal molar dose in reducing tissue glycogen contents. Our data suggest that FabGAA retains the ability of rhGAA to treat lysosomal glycogen accumulation and has the beneficial potential over rhGAA to reduce cytoplasmic glycogen storage in Pompe disease. FabGAA can be delivered to both the cytoplasm and lysosomes in cultured cells. FabGAA equally reduced lysosomal glycogen accumulation as rhGAA in GAA-KO mice. FabGAA has the beneficial potential over rhGAA to clear cytoplasmic glycogen. This study suggests a novel antibody-enzyme fusion protein therapy

Group long-term care insurance: decision-making factors and implications for financing long-term care.

PubMed

Stum, Marlene S

2008-01-01

This study proposes and tests a systemic family decision-making framework to understand group long-term care insurance (LTCI) enrollment decisions. A random sample of public employees who were offered group LTCI as a workplace benefit were examined. Findings reveal very good predictive efficacy for the overall conceptual framework with a pseudo R2 value of .687, and reinforced the contributions of factors within the family system. Enrollees were more likely to have discussed the decision with others, used information sources, and had prior experience when compared to non-enrollees. Perceived health status, financial knowledge, attitudes regarding the role of private insurance, risk taking, and coverage features were additional factors related to enrollment decisions. The findings help to inform policymakers about the potential of LTCI as one strategy for financing long-term care.

Informed Consent to Research in Long-Term Care Settings

PubMed Central

Jablonski, Rita A.; Bourbonniere, Meg; Kolanowski, Ann

2010-01-01

Informed consent to nursing home research is a two-tiered process that begins with obtaining the consent of a long-term care community at the institutional level and progresses to the engagement of individuals in the consent process. Drawing on a review of the literature and the authors’ research experiences and institutional review board service, this paper describes the practical implications of nurse investigators’ obligation to ensure informed consent among participants in long-term care research. Recommendations focus on applying a community consent model to long-term care research, promoting an evidence-based approach to the protection of residents with decisional impairment, and increasing investigators’ attention to ethical issues involving long-term care staff. PMID:20078005

Stability of selected serum proteins after long-term storage in the Janus Serum Bank.

PubMed

Gislefoss, Randi E; Grimsrud, Tom K; Mørkrid, Lars

2009-01-01

Human serum from biobanks is frequently used in prospective epidemiological studies. Long-term storage may modify its composition. A better understanding of the stability of the serum components may improve the interpretation of future studies. The concentrations of selected proteins; immunoglobulins, carrier proteins and enzymes in samples stored at -25 degrees C for 25 years and 2 years were compared with 1-month-old samples. For each length of storage time, 130 specimens were randomly selected from apparently healthy male blood donors aged 40-49 years. We examined the distribution of values, compared dispersion and localization of central tendency, and established reference intervals for each component. The study demonstrated non-significant or numerically small group differences in the concentrations of albumin, aspartate amino transferase, cystatin C, immunoglobulin E, immunoglobulin G, and sex hormone binding globulin. Mean values between fresh and 25-year-old samples suggested larger differences during storage for alanine amino transferase (-73.4%), creatinine kinase (-96.1%), insulin C-peptide (-98.7%), ferritin (-18.5%) and transferrin (+8.2%). The findings showed that long-term storage can introduce a considerable bias for vulnerable components.

Calcium/Calmodulin-dependent Protein Kinase II is a Ubiquitous Molecule in Human Long-term Memory Synaptic Plasticity: A Systematic Review

PubMed Central

Ataei, Negar; Sabzghabaee, Ali Mohammad; Movahedian, Ahmad

2015-01-01

Background: Long-term memory is based on synaptic plasticity, a series of biochemical mechanisms include changes in structure and proteins of brain's neurons. In this article, we systematically reviewed the studies that indicate calcium/calmodulin kinase II (CaMKII) is a ubiquitous molecule among different enzymes involved in human long-term memory and the main downstream signaling pathway of long-term memory. Methods: All of the observational, case–control and review studies were considered and evaluated by the search engines PubMed, Cochrane Central Register of Controlled Trials and ScienceDirect Scopus between 1990 and February 2015. We did not carry out meta-analysis. Results: At the first search, it was fined 1015 articles which included “synaptic plasticity” OR “neuronal plasticity” OR “synaptic density” AND memory AND “molecular mechanism” AND “calcium/calmodulin-dependent protein kinase II” OR CaMKII as the keywords. A total of 335 articles were duplicates in the databases and eliminated. A total of 680 title articles were evaluated. Finally, 40 articles were selected as reference. Conclusions: The studies have shown the most important intracellular signal of long-term memory is calcium-dependent signals. Calcium linked calmodulin can activate CaMKII. After receiving information for learning and memory, CaMKII is activated by Glutamate, the most important neurotransmitter for memory-related plasticity. Glutamate activates CaMKII and it plays some important roles in synaptic plasticity modification and long-term memory. PMID:26445635

Japanese public long-term care insured: preferences for future long-term care facilities, including relocation, waiting times, and individualized care.

PubMed

Sawamura, Kanae; Sano, Hiroshi; Nakanishi, Miharu

2015-04-01

Expenditures on long-term care insurance (LTCI) in Japan have been increasing with the aging of the population, which has led to an increase in premiums. To optimize resource allocation, we aim to clarify the priorities of the functions of long-term care facilities from the viewpoint of future beneficiaries. The present study was conducted using a cross-sectional study design. We conducted a mail-in survey targeting 2400 adults aged 50-65 in 8 cities in Japan, and 371 persons responded. Conjoint analysis was applied to measure participants' preferences for long-term care facility services. Participants read 1 of 2 vignettes of an 80-year-old person with either dementia or a fracture, and were asked to envision it as a possible future scenario for themselves. Participants then completed 8 or 9 tasks to select suitable long-term care facilities for the person described. The questionnaire also contained common questions on participants' personal profiles: age, gender, family situation, education, approximate yearly family income, experience as a family caregiver, dwelling status, present health status, and possibility of requiring long-term care services in the future. The results focused mainly on (1) possibilities of individual choice for daily schedules/meals; (2) availability of regular care staff; (3) room; (4) main daily interactions; (5) necessity of relocation associated with medical deterioration; 6) Waiting time; 7) distance from present residence; and (8) monthly fees. Necessity of relocation associated with medical deterioration was consistently given the greatest importance. Participants with experience as a family caregiver showed significantly greater preference for individualized care and communication. The option of avoiding relocation was highly valued by participants compared with private rooms and individualized care. The present situation of high demand for intensive care homes for the elderly, provoked by anxiety about future residence, will not

Adverse event reporting in Czech long-term care facilities.

PubMed

Hěib, Zdenřk; Vychytil, Pavel; Marx, David

2013-04-01

To describe adverse event reporting processes in long-term care facilities in the Czech Republic. Prospective cohort study involving a written questionnaire followed by in-person structured interviews with selected respondents. Long-term care facilities located in the Czech Republic. Staff of 111 long-term care facilities (87% of long-term care facilities in the Czech Republic). None. Sixty-three percent of long-term health-care facilities in the Czech Republic have adverse event-reporting processes already established, but these were frequently very immature programs sometimes consisting only of paper recording of incidents. Compared to questionnaire responses, in-person interview responses only partially tended to confirm the results of the written survey. Twenty-one facilities (33%) had at most 1 unconfirmed response, 31 facilities (49%) had 2 or 3 unconfirmed responses and the remaining 11 facilities (17%) had 4 or more unconfirmed responses. In-person interviews suggest that use of a written questionnaire to assess the adverse event-reporting process may have limited validity. Staff of the facilities we studied expressed an understanding of the importance of adverse event reporting and prevention, but interviews also suggested a lack of knowledge necessary for establishing a good institutional reporting system in long-term care.

Long-term outcomes of children undergoing video-assisted gastrostomy.

PubMed

Salö, Martin; Santimano, Ana; Helmroth, Sofia; Stenström, Pernilla; Arnbjornsson, Einar Ólafur

2017-01-01

The aims of this study were to assess the short- and long-term complication rates after video-assisted gastrostomy (VAG), the effects of age and gender on long-term complications and the effect of duration of gastrostomy tube retention on the need for gastroraphy when the gastrostomy device was removed. This was a retrospective study of children undergoing VAG at a single institution. Children who died or moved from the area were excluded. The rates of short- and long-term complications developing at 3-6 months or 2 or more years, respectively, were compared. A total of 170 children were studied, out of a cohort of 303 children. The median age at surgery was 2 years. The median duration of postoperative long-term follow-up was 5 years (2-9 years). The complications at the respective short and long-term follow-ups were as follows: granulation tissue, leakage, infection and vomiting. There were no differences in the short- versus long-term complication rates for gender and age. Children needing gastroraphy had used a gastrostomy device significantly longer compared with children with spontaneous closure. Complications after VAG decrease over time. A longer duration of gastrostomy device retention leads to increased need for gastroraphy.

Long Term Stability Following Genioplasty: A Cephalometric Study

PubMed Central

Kumar, B Lakshman; Raju, G Kranthi Praveen; Kumar, N Dilip; Reddy, G Vivek; Naik, B Ravindra; Achary, C Ravindranath

2015-01-01

Background: A receding chin associated with an orthognathic mandible is a common situation and surgical changes in chin position are often required to improve the overall harmony of the face. Genioplasty is one such procedure. Stability of hard and soft tissue changes following genioplasty on a long term basis needs to be assessed. Studies on the stability of hard and soft tissue changes following genioplasty on a short term basis have revealed it as a procedure with good stability. This study is done to assess the stability of hard and soft tissue changes following genioplasty on a long term basis. Materials and Methods: Pre-surgical, postsurgical and long term post-surgical cephalograms of 15 cases treated by vertical reduction augmentation genioplasty were obtained. Paired t-test was used to compare the changes between pre-surgical, postsurgical and long term postsurgical cephalograms. Results: Findings of this study demonstrated that genioplasty is a stable procedure. After long term follow-up period, there was a relapse of 1.5 mm at the pogonion accounting for 24% of the surgical advancement. This is attributed to the remodeling that occurs at the surgical site, but not the instability due to the surgical procedure. Conclusion: With the present study, it can be concluded that vertical reduction and advancement genioplasty can be considered as an adjunctive procedure that produces predictable results and the bony and soft tissue stability were generally very good. PMID:25954070

Long-term EEG in children.

PubMed

Montavont, A; Kaminska, A; Soufflet, C; Taussig, D

2015-03-01

Long-term video-EEG corresponds to a recording ranging from 1 to 24 h or even longer. It is indicated in the following situations: diagnosis of epileptic syndromes or unclassified epilepsy, pre-surgical evaluation for drug-resistant epilepsy, follow-up of epilepsy or in cases of paroxysmal symptoms whose etiology remains uncertain. There are some specificities related to paediatric care: a dedicated pediatric unit; continuous monitoring covering at least a full 24-hour period, especially in the context of pre-surgical evaluation; the requirement of presence by the parents, technician or nurse; and stronger attachment of electrodes (cup electrodes), the number of which is adapted to the age of the child. The chosen duration of the monitoring also depends on the frequency of seizures or paroxysmal events. The polygraphy must be adapted to the type and topography of movements. It is essential to have at least an electrocardiography (ECG) channel, respiratory sensor and electromyography (EMG) on both deltoids. There is no age limit for performing long-term video-EEG even in newborns and infants; nevertheless because of scalp fragility, strict surveillance of the baby's skin condition is required. In the specific context of pre-surgical evaluation, long-term video-EEG must record all types of seizures observed in the child. This monitoring is essential in order to develop hypotheses regarding the seizure onset zone, based on electroclinical correlations, which should be adapted to the child's age and the psychomotor development. Copyright © 2015. Published by Elsevier SAS.

The need for the vegetarian crew for long-term LSS

NASA Astrophysics Data System (ADS)

Gorgolewski, S.

The long-term space missions pose very stringent demands on the high degree of closure levels. One obvious requirements is to assure the human crew a steady state self-supporting and self-regenerating LSS environment. The strictly vegetarian crew is the primary requirement to minimize the cost and weight of the spacecraft. This ensures the minimal matter circulation problems, because we can also use for food as many as possible fuly edible plants with nex to none, non digestable plant tissues. One important task is to select a range of plants which should satisfy the nutritional needs of the crew for a long-term, in the range of several years. Preliminary fitotron experiments with lettuce, demonstrated that one can achieve this goal, with a plant which is wholy edible even with the roots. This has been achieved with the use of several teens times stronger electrical field, than the 130 V/m fair weather global atmospheric electrical field. More experiments are in progress for the extension of the list of such vegetarian food. The selection of suitable plants which meet these highly demanding selection criteria, has to be done and can be done in ground based experiments. Plants ensure one important requirements of a closed loop CO2 and O2 circulation with the vegetarian crew in the loop. Extensive research programs are needed for this purpose using large ground based instalations like the Biosphere 2. The success of the use of electrical fields as replacement of gravitational field in the fitotron which proved the dominating role over gravity, of several kV/m electical field intensities. It also proves the feasibility of improving the crop productivity in ground based greenhouses, provided that we do restore inside the missing in "normal" designs our global electrical field. The fair weather electrical field (not to mention the enhanced field) is the missing vital environmental factor which has been systematically "overlooked" in practically all greenhouses. It is

Assessing the market for long-term care services.

PubMed

Rice, J A; Taylor, S

1984-02-01

Traditionally, long-term care services have been used by a diverse marketplace. The chronically ill, developmentally disabled, mentally ill and aging population has looked to long-term care support services as a means of physical and emotional support. Much of the time these services were housed together for the sake of efficiency. The enormous burden these services are creating on the economy, and the growing aging population, have forced the recognition that long-term care service delivery systems must change. Alternate programming for long-term care services that reach out into the community and into individual homes is becoming an attractive approach to meeting the growing demands of the marketplace. Home health, specialized housing and creative funding mechanisms such as HMOs, are examples of initiatives undertaken by healthcare organizations that view diversification as a vehicle for survival. Market research techniques that have been used in other industries are being adapted to the healthcare industry to ensure the proper mix of services that are demanded by older, more knowledgeable consumers. The programs of the future will be market driven, with the ability of the individual to pay for such services playing a significant role. The healthcare provider of today is in a position to serve the community in new ways. By becoming an integral link in the long-term care system and by developing new programs, the organization can serve as a catalyst for change. It is up to the governing bodies and managers of these facilities to become visionaries and to accept responsibility for assessing the market for long-term care services and to guide their organization into the future.

The effectiveness of dietary sunflower meal and exogenous enzyme on growth, digestive enzymes, carcass traits, and blood chemistry of broilers.

PubMed

Alagawany, Mahmoud; Attia, Adel I; Ibrahim, Zenat A; Mahmoud, Reda A; El-Sayed, Sabry A

2017-05-01

High costs of conventional protein feed sources including soybean meal (SBM) generated the need for finding other alternatives. Thus, the present study was designed to evaluate the impact of graded replacements of SBM by sunflower seed meal (SFM) with or without enzyme supplementation on growth performance, digestive enzymes, carcass traits, and blood profile of broiler chickens. A total of 240 unsexed 1-week-old broiler chicks (Hubbard) were randomly divided into eight treatment groups of 30 chicks each in five replicates each of six chicks in a factorial design (4 × 2) arrangement, including four levels of SFM (0, 25, 50, and 75% replacing SBM) and two levels of enzyme (0- or 0.1-g/kg diet) supplementation. Performance traits including feed conversion ratio, body weight, and weight gain were significantly (P < 0.01) improved with increasing SFM up to 50% substitution for SBM or with enzyme supplementation in broiler diet during the experiment. However, feed intake of broiler chicks was decreased with enzyme supplementation (P < 0.05). The activities of digestive enzymes (protease and amylase) were significantly (P < 0.05) influenced and enhanced by SFM and enzyme inclusion in diets, respectively. The activities of protease and amylase were improved with SFM diet supplemented with 0.1 g/kg enzyme in comparison with those with the un-supplemented diet. The evaluated carcass traits were not statistically (P > 0.05) influenced by feeding SFM meal or enzyme addition. Biochemical blood parameters were significantly (P < 0.01) affected by SFM, enzyme, or their interaction in broiler diets, except for globulin that was not affected by dietary enzyme. It is concluded that increasing SFM level in the diet up to 50% replacing SBM with the supplementation of enzyme improved the growth performance and enhanced positively carcass traits as well as the activity of digestive enzymes in broiler chickens.

Short-Term Plasticity and Long-Term Potentiation in Magnetic Tunnel Junctions: Towards Volatile Synapses

NASA Astrophysics Data System (ADS)

Sengupta, Abhronil; Roy, Kaushik

2016-02-01

Synaptic memory is considered to be the main element responsible for learning and cognition in humans. Although traditionally nonvolatile long-term plasticity changes are implemented in nanoelectronic synapses for neuromorphic applications, recent studies in neuroscience reveal that biological synapses undergo metastable volatile strengthening followed by a long-term strengthening provided that the frequency of the input stimulus is sufficiently high. Such "memory strengthening" and "memory decay" functionalities can potentially lead to adaptive neuromorphic architectures. In this paper, we demonstrate the close resemblance of the magnetization dynamics of a magnetic tunnel junction (MTJ) to short-term plasticity and long-term potentiation observed in biological synapses. We illustrate that, in addition to the magnitude and duration of the input stimulus, the frequency of the stimulus plays a critical role in determining long-term potentiation of the MTJ. Such MTJ synaptic memory arrays can be utilized to create compact, ultrafast, and low-power intelligent neural systems.

Long-term abstinent alcoholics have normal memory.

PubMed

Reed, R J; Grant, I; Rourke, S B

1992-08-01

It is generally believed that many non-Korsakoff alcoholics have subtle defects in memory. To determine whether such defects vary as a function of length of abstinence (LOA), we performed extensive memory testing with: (1) recently detoxified (n = 31; LOA-29 days); (2) intermediate-term abstinent (n = 28; LOA = 1.9 years); (3) long-term abstinent (n = 32; LOA-7.0 years) alcoholics; and (4) nonalcoholic controls (n = 37). All subjects were matched on age and education. Alcoholics were matched on years of alcoholic drinking. Memory measures were divided into the following domains: verbal learning, verbal recall, visual learning, visual recall, and paired associate learning. A series of MANOVAs were conducted that revealed a significant relationship between visual learning and length of abstinence, and a significant interaction between age and length of abstinence on visual recall. Long-term abstinent subjects were not significantly different from controls on any test. We conclude that memory disturbance demonstrable among recently detoxified alcoholics in the early weeks of their abstinence is not evident in demographically matched long-term abstinent alcoholics with similar drinking histories.

Long-term efficiency of mesenchymal stromal cell-mediated CD-MSC/5FC therapy in human melanoma xenograft model.

PubMed

Kucerova, L; Skolekova, S; Demkova, L; Bohovic, R; Matuskova, M

2014-10-01

Mesenchymal stromal cells (MSC) can be exploited as cellular delivery vehicles for the enzymes converting non-toxic prodrugs to toxic substances. Because of their inherent chemoresistance, they exert potent bystander and antitumor effect. Here we show that the human adipose tissue-derived MSC expressing fusion yeast cytosine deaminase::uracil phosphoribosyltransferase (CD-MSC) in combination with 5-fluorocytosine (5FC) mediated a long-term tumor-free survival in the 83.3% of tumor-bearing animals. CD-MSC/5FC treatment induced cytotoxicity against model human melanoma cells EGFP-A375. Only 4% of the therapeutic CD-MSC cells eliminated >98.5% of the tumor cells in vitro. Long-term tumor-free survival was confirmed in 15 out of the 18 animals. However, repeatedly used CD-MSC/5FC therapeutic regimen generated more aggressive and metastatic variant of the melanoma cells EGFP-A375/Rel3. These cells derived from the refractory xenotransplants exhibited increased resistance to the CD-MSC/5FC treatment, altered cell adhesion, migration, tumorigenic and metastatic properties. However, long-term curative effect was achieved by the augmentation of the CD-MSC/5FC regimen along with the inhibition of c-Met/hepatocyte growth factor signaling axis in this aggressive melanoma derivative. In summary, the CD-MSC/5FC regimen can be regarded as a very effective antitumor approach to achieve long-term tumor-free survival as demonstrated on a mouse model of aggressive human melanoma xenografts.

Predicting isoproturon long-term mineralization from short-term experiment: Can this be a suitable approach?

PubMed

Wang, Fang; Dörfler, Ulrike; Jiang, Xin; Schroll, Reiner

2016-02-01

A worldwide used pesticide - isoproturon (IPU) - was selected to test whether short-term experiments can be used to predict long-term mineralization of IPU in soil. IPU-mineralization was measured for 39 and 265 days in four different agricultural soils with a low mineralization dynamic. Additionally, in one soil IPU dissipation, formation and dissipation of metabolites, formation of non-extractable residues (NER) and (14)C-microbial biomass from (14)C-IPU were monitored for 39 and 265 days. The data from short-term and long-term experiments were used for model fitting. The long-term dynamics of IPU mineralization were considerably overestimated by the short-term experiments in two soils with neutral pH, while in two other soils with low pH and lower mineralization, the long-term mineralization of IPU could be sufficiently predicted. Additional investigations in one of the soils with neutral pH showed that dissipation of IPU and metabolites could be correctly predicted by the short-term experiment. However, the formation of NER and (14)C-microbial biomass were remarkably overestimated by the short-term experiment. Further, it could be shown that the released NER and (14)C-microbial biomass were the main contributors of (14)CO2 formation at later incubation stages. Taken together, our results indicate that in soils with neutral pH short-term experiments were inadequate to predict the long-term mineralization of IPU. Copyright © 2015 Elsevier Ltd. All rights reserved.

Focusing on Short-Term Achievement Gains Fails to Produce Long-Term Gains

ERIC Educational Resources Information Center

Grissmer, David W.; Ober, David R.; Beekman, John A.

2014-01-01

The short-term emphasis engendered by No Child Left Behind (NCLB) has focused research predominantly on unraveling the complexities and uncertainties in assessing short-term results, rather than developing methods and assessing results over the longer term. In this paper we focus on estimating long-term gains and address questions important to…

Measuring short-term and long-term physiological stress effects by cortisol reactivity in saliva and hair.

PubMed

van Holland, Berry J; Frings-Dresen, Monique H W; Sluiter, Judith K

2012-11-01

The aims of this study were to investigate (1) the concurrent relationship between short-term and long-term stress reactivity measured by cortisol excretion and (2) the relationship of these physiological stress effects with self-reported stress and need for recovery after work (NFR). Participants were production workers in the meat-processing industry. Short-term cortisol excretion was calculated by summing 18 saliva samples, sampled over a 3-day period. Samples were delivered by 37 participants. Twenty-nine of them also supplied one hair sample of at least 3 cm in length for an analysis of long-term (3 months) cortisol excretion. All of them filled in a short questionnaire on self-reported stress and NFR. Self-reported stress was assessed by a three-item stress screener; NFR was assessed by an 11-item scale. Short-term and long-term cortisol excretion are significantly, but moderately, associated (r = 0.41, P = 0.03). Short-term and long-term cortisol excretion correlated weakly to self-reported stress and NFR (correlations varied from -0.04 to 0.21). Short-term and long-term physiological stress excretion levels are moderately associated. Physiological stress effects assessed from saliva and hair cannot be used interchangeably with self-reported stress because they only correlate weakly. To better predict long-term cortisol excretion in workers, the predictive value of short-term cortisol excretion must be evaluated in a prognostic longitudinal study in a working population.

Long-Term Economic and Labor Forecast Trends for Washington. 1996.

ERIC Educational Resources Information Center

Lefberg, Irv; And Others

This publication provides actual historical and long-term forecast data on labor force, total wage and salary employment, industry employment, and personal income for the state of Washington. The data are based upon the Washington Office of Financial Management long-term population forecast. Chapter 1 presents long-term forecasts of Washington…

Long-term academic stress enhances early processing of facial expressions.

PubMed

Zhang, Liang; Qin, Shaozheng; Yao, Zhuxi; Zhang, Kan; Wu, Jianhui

2016-11-01

Exposure to long-term stress can lead to a variety of emotional and behavioral problems. Although widely investigated, the neural basis of how long-term stress impacts emotional processing in humans remains largely elusive. Using event-related brain potentials (ERPs), we investigated the effects of long-term stress on the neural dynamics of emotionally facial expression processing. Thirty-nine male college students undergoing preparation for a major examination and twenty-one matched controls performed a gender discrimination task for faces displaying angry, happy, and neutral expressions. The results of the Perceived Stress Scale showed that participants in the stress group perceived higher levels of long-term stress relative to the control group. ERP analyses revealed differential effects of long-term stress on two early stages of facial expression processing: 1) long-term stress generally augmented posterior P1 amplitudes to facial stimuli irrespective of expression valence, suggesting that stress can increase sensitization to visual inputs in general, and 2) long-term stress selectively augmented fronto-central P2 amplitudes for angry but not for neutral or positive facial expressions, suggesting that stress may lead to increased attentional prioritization to processing negative emotional stimuli. Together, our findings suggest that long-term stress has profound impacts on the early stages of facial expression processing, with an increase at the very early stage of general information inputs and a subsequent attentional bias toward processing emotionally negative stimuli. Copyright © 2016 Elsevier B.V. All rights reserved.

Economic efficiency of short-term versus long-term water rights buyouts

USDA-ARS?s Scientific Manuscript database

Because of the decline of the Ogallala Aquifer, water districts, regional water managers, and state water officers are becoming increasingly interested in conservation policies. This study evaluates both short-term and long-term water rights buyout policies. This research develops dynamic production...

[The long term (15 years) evolution after valvular replacement with mechanical prosthesis or bioprosthesis between the age of 60 and 70 years].

PubMed

Hanania, G; Michel, P L; Montély, J M; Warembourg, H; Nardi, O; Leguerrier, A; Agnino, A; Despins, P; Legault, B; Petit, H; Bouraindeloup, M

2004-01-01

the aim of this study was to document the choice between prosthesis and bioprosthesis in cases of valvular replacement during the seventh decade of life. a retrospective and cooperative study linking eleven cardiac surgical teams and five medical cardiology teams combined 497 subjects born between 1915 and 1925 (average age 64.4 years) who underwent aortic (313 cases) or mitral (184 cases) valvular replacement with mechanical prosthesis (259 cases) or bioprosthesis (238 cases). Information was collected at each centre during the year 2000 on the long term evolution (going back 15 years), in particular on the mortality, non-fatal complications linked to the valve, cardiac complications and extra-cardiac events. These results were subjected to statistical analysis. the operative mortality of this group was 4.8%. The 15 year survival was 46% for the aortic mechanical prostheses, 32% for the aortic bioprostheses (p=0.04). 34% for the mitral bioprostheses and 33% for the mitral mechanical prostheses. Events linked to the valve were more frequent for the mitral valvulopathies than for the aortic valves (49% vs 26%, p<0.001). The absence of events linked to the valve at 15 years was 69% for the aortic mechanical prostheses and 68% for the aortic bioprostheses. This was the case in only 57% of mitral mechanical prostheses and 36% of the mitral bioprostheses (p=0.11). Thromboembolic accidents were three times more frequent in the mitrals than in the aortics (11.5 vs 3.8%, p=0.002). Haemorrhage was four times more frequent for the mechanical prostheses than for the bioprostheses (7.7 vs 2%, p=0.01). The risk of degeneration for the aortic bioprostheses was 20% at 15 years, three times less so after 65 years of age (p=0.03). At 48% it was much higher in the mitral valves at 15 years with no significant difference before and after 65 years of age (p=0.3). the current life expectancy of subjects in their seventh decade is important. The greatly elevated risk of bioprosthesis

Issues in the Development of Long Term Care Gerontology Centers: The Centers Concept. Selected Topics in Long Term Care. Volume 6.

ERIC Educational Resources Information Center

Mortenson, Lee E.; Berdes, Celia M.

This document, one in a series developed to provide technical assistance to 22 Long-Term Care Gerontology Centers, describes the current administrative and structural phenomenon of these centers. Precedents useful in assessing both the current climate and actual prospects for development of long term care centers are cited. The first section…

Sleep Quality, Short-Term and Long-Term CPAP Adherence

PubMed Central

Somiah, Manya; Taxin, Zachary; Keating, Joseph; Mooney, Anne M.; Norman, Robert G.; Rapoport, David M.; Ayappa, Indu

2012-01-01

Study Objectives: Adherence to CPAP therapy is low in patients with obstructive sleep apnea/hypopnea syndrome (OSAHS). The purpose of the present study was to evaluate the utility of measures of sleep architecture and sleep continuity on the CPAP titration study as predictors of both short- and long-term CPAP adherence. Methods: 93 patients with OSAHS (RDI 42.8 ± 34.3/h) underwent in-laboratory diagnostic polysomnography, CPAP titration, and follow-up polysomnography (NPSG) on CPAP. Adherence to CPAP was objectively monitored. Short-term (ST) CPAP adherence was averaged over 14 days immediately following the titration study. Long-term (LT) CPAP adherence was obtained in 56/93 patients after approximately 2 months of CPAP use. Patients were grouped into CPAP adherence groups for ST (< 2 h, 2-4 h, and > 4 h) and LT adherence (< 4 h, > 4 h). Sleep architecture, sleep disordered breathing (SDB) indices, and daytime outcome variables from the diagnostic and titration NPSGs were compared between CPAP adherence groups. Results: There was a significant relationship between ST and LT CPAP adherence (r = 0.81, p < 0.001). Neither ST nor LT adherence were related to demographic variables, baseline severity of untreated SDB, sleep architecture, or measures of daytime impairment. Good CPAP adherence groups had significantly lower %N2 and greater %REM on the titration NPSG. A model combining change in sleep efficiency and change in sleep continuity between the diagnostic and titration NPSGs predicted 17% of the variance in LT adherence (p = 0.006). Conclusions: These findings demonstrate that characteristics of sleep architecture, even on the titration NPSG, may predict some of the variance in CPAP adherence. Better sleep quality on the titration night was related to better CPAP adherence, suggesting that interventions to improve sleep on/prior to the CPAP titration study might be used as a therapeutic intervention to improve CPAP adherence. Citation: Somiah M; Taxin Z; Keating

Long-term memory and volatility clustering in high-frequency price changes

NASA Astrophysics Data System (ADS)

oh, Gabjin; Kim, Seunghwan; Eom, Cheoljun

2008-02-01

We studied the long-term memory in diverse stock market indices and foreign exchange rates using Detrended Fluctuation Analysis (DFA). For all high-frequency market data studied, no significant long-term memory property was detected in the return series, while a strong long-term memory property was found in the volatility time series. The possible causes of the long-term memory property were investigated using the return data filtered by the AR(1) model, reflecting the short-term memory property, the GARCH(1,1) model, reflecting the volatility clustering property, and the FIGARCH model, reflecting the long-term memory property of the volatility time series. The memory effect in the AR(1) filtered return and volatility time series remained unchanged, while the long-term memory property diminished significantly in the volatility series of the GARCH(1,1) filtered data. Notably, there is no long-term memory property, when we eliminate the long-term memory property of volatility by the FIGARCH model. For all data used, although the Hurst exponents of the volatility time series changed considerably over time, those of the time series with the volatility clustering effect removed diminish significantly. Our results imply that the long-term memory property of the volatility time series can be attributed to the volatility clustering observed in the financial time series.

Long-term complications in Hodgkin's lymphoma survivors.

PubMed

Kilickap, Saadettin; Barista, Ibrahim; Ulger, Sukran; Celik, Ismail; Selek, Ugur; Güllü, Ibrahim; Yildiz, Ferah; Kars, Ayse; Ozisik, Yavuz; Tekuzman, Gülten

2012-01-01

Background. Although patients with Hodgkin's lymphoma (HL) achieve prolonged survival, long-term complications are a major cause of morbidity and mortality among long-term survivors of HL. Methods. We retrospectively evaluated long-term complications in 336 HL survivors treated between January 1990 and January 2006 at the Department of Medical Oncology of the Hacettepe University Institute of Oncology who were >16 years old at presentation. All patients were regularly followed up every 3 months for the first 2 years after complete response, biannually for 3 years, and annually after 5 years. Results. Median follow-up was 8.5 years. The mean age (±SD) of the patients at the time of diagnosis was 35.7 ± 13.1 years. The male to female ratio was 61%/39%. During follow-up, 29 second malignancies (8.6%) were diagnosed in 28 patients with HL; 22 were solid tumors and 7 were hematological malignancies. Forty-seven (14.0%) of all patients with HL were found to have thyroid abnormalities. During follow-up, 54 (16.1%) patients developed cardiovascular complications. Overall, 29 (8.6%) patients developed late pulmonary toxicities. The cumulative number of chronic viral infections was 13 (3.9%). Conclusions. Long-term survivors of HL need to be properly followed up not only for disease control but also for evaluation of possible late morbidities to minimize the consequences.

Dynamical model of long-term synaptic plasticity

PubMed Central

Abarbanel, Henry D. I.; Huerta, R.; Rabinovich, M. I.

2002-01-01

Long-term synaptic plasticity leading to enhancement in synaptic efficacy (long-term potentiation, LTP) or decrease in synaptic efficacy (long-term depression, LTD) is widely regarded as underlying learning and memory in nervous systems. LTP and LTD at excitatory neuronal synapses are observed to be induced by precise timing of pre- and postsynaptic events. Modification of synaptic transmission in long-term plasticity is a complex process involving many pathways; for example, it is also known that both forms of synaptic plasticity can be induced by various time courses of Ca2+ introduction into the postsynaptic cell. We present a phenomenological description of a two-component process for synaptic plasticity. Our dynamical model reproduces the spike time-dependent plasticity of excitatory synapses as a function of relative timing between pre- and postsynaptic events, as observed in recent experiments. The model accounts for LTP and LTD when the postsynaptic cell is voltage clamped and depolarized (LTP) or hyperpolarized (LTD) and no postsynaptic action potentials are evoked. We are also able to connect our model with the Bienenstock, Cooper, and Munro rule. We give model predictions for changes in synaptic strength when periodic spike trains of varying frequency and Poisson distributed spike trains with varying average frequency are presented pre- and postsynaptically. When the frequency of spike presentation exceeds ≈30–40 Hz, only LTP is induced. PMID:12114531

Initiating Long-Term Soil Productivity Research in Missouri

Treesearch

Felix Ponder

1997-01-01

Management practices necessary for sustaining long-term soil productivity (LTSP) afforest lands are being defined from a network of coordinated, long-term experiments established in vartous ecosystems across the United States and British Columbia according to the same basic study plan. The study was established in the Ozark Region of southeastem Missouri in Shannon...

Long-term maintenance needs planning.

DOT National Transportation Integrated Search

2005-09-01

This research contributes to Kentucky's knowledge base of long-term maintenance needs in two parts. Part I presents an estimate of the average revenue needed to maintain four categories of highway in the first fifteen years after each is built or res...

Long-term use of short- and long-acting nitrates in stable angina pectoris.

PubMed

Kosmicki, Marek Antoni

2009-05-01

Long-acting nitrates are effective antianginal drugs during initial treatment. However, their therapeutic value is compromised by the rapid development of tolerance during sustained therapy, which means that their clinical efficacy is decreased during long-term use. Sublingual nitroglycerin (NTG), a short-acting nitrate, is suitable for the immediate relief of angina. In patients with stable angina treated with oral long-acting nitrates, NTG maintains its full anti-ischemic effect both after initial oral ingestion and after intermittent long-term oral administration. However, NTG attenuates this effect during continuous treatment, when tolerance to oral nitrates occurs, and this is called cross-tolerance. In stable angina long-acting nitrates are considered third-line therapy because a nitrate-free interval is required to avoid the development of tolerance. Nitrates vary in their potential to induce the development of tolerance. During long-lasting nitrate therapy, except pentaerythritol tetranitrate (PETN), one can observe the development of reactive oxygen species (ROS) inside the muscular cell of a vessel wall, and these bind with nitric oxide (NO). This leads to decreased NO activity, thus, nitrate tolerance. PETN has no tendency to form ROS, and therefore during long-term PETN therapy, there is probably no tolerance or cross-tolerance, as during treatment with other nitrates.

What are the differences between long-term, short-term, and working memory?

PubMed

Cowan, Nelson

2008-01-01

In the recent literature there has been considerable confusion about the three types of memory: long-term, short-term, and working memory. This chapter strives to reduce that confusion and makes up-to-date assessments of these types of memory. Long- and short-term memory could differ in two fundamental ways, with only short-term memory demonstrating (1) temporal decay and (2) chunk capacity limits. Both properties of short-term memory are still controversial but the current literature is rather encouraging regarding the existence of both decay and capacity limits. Working memory has been conceived and defined in three different, slightly discrepant ways: as short-term memory applied to cognitive tasks, as a multi-component system that holds and manipulates information in short-term memory, and as the use of attention to manage short-term memory. Regardless of the definition, there are some measures of memory in the short term that seem routine and do not correlate well with cognitive aptitudes and other measures (those usually identified with the term "working memory") that seem more attention demanding and do correlate well with these aptitudes. The evidence is evaluated and placed within a theoretical framework depicted in Fig. 1.

Stirling engine - Approach for long-term durability assessment

NASA Technical Reports Server (NTRS)

Tong, Michael T.; Bartolotta, Paul A.; Halford, Gary R.; Freed, Alan D.

1992-01-01

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.

Medium-term outcomes and complications after total replacement of the temporomandibular joint. Prospective outcome analysis after 3 and 5 years.

PubMed

Gruber, E A; McCullough, J; Sidebottom, A J

2015-05-01

In this prospective analysis, we assess the medium-term benefits, efficacy, and safety of the TMJ Concepts joint replacement system in the United Kingdom. Outcome measures of pain, maximum mouth opening, and diet were recorded preoperatively and at intervals up to 3 and 5 years. All patients who had replacement temporomandibular joints (TMJ) within a 6-year period were included. A total of 58 patients (84 joints) were followed up for 3 years (mean age 47, range 19-72) and 26 (42 joints) for 5 years (mean age 46, range 27-70). The female to male ratio was 52:6 at 3 years and 23:3 at 5 years. The most common diagnosis was degenerative disease, and the mean number of previous TMJ procedures was 2.4 (range 0-14). There were significant improvements in pain scores (7.4 reduced to 0.6 at 3 years and 0.8 at 5 years), maximum mouth opening (21.0-35.5mm at 3 years and 23.8-33.7mm at 5 years), and dietary scores (4.1-9.7 at 3 years and 3.7-9.6 at 5 years). Revision operations were required in 2 patients (not included in the outcome data) for biofilm infection of the prosthesis secondary to local infection in the head and neck. One patient had weakness of the temporal branch of the facial nerve that needed correction. TMJ replacement is an effective form of management for an irreparably damaged joint, particularly in cases of ankylosis. It lessens pain and improves function with minimal long-term morbidity. Copyright © 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Finance issue brief: long-term care insurance: year end report-2003.

PubMed

Tanner, Rachel C

2003-12-31

A 1996 federal law made it more attractive for states to consider long-term care insurance, and states have responded by implementing policies to make the purchase of these long-term care coverage more affordable and consumer-friendly. At present, policymakers continue to debate the future role of private long-term care insurance in subsidizing the increasing demand for long-term care services.

Long-term Immunogenicity of Elosulfase Alfa in the Treatment of Morquio A Syndrome: Results From MOR-005, a Phase III Extension Study.

PubMed

Long, Brian; Tompkins, Troy; Decker, Celeste; Jesaitis, Lynne; Khan, Shahid; Slasor, Peter; Harmatz, Paul; O'Neill, Charles A; Schweighardt, Becky

2017-01-01

Elosulfase alfa is an enzyme replacement therapy for the treatment of Morquio A syndrome (mucopolysaccharidosis IVA), a lysosomal storage disorder caused by a deficiency of the enzyme N-acetylgalactose-amine-6-sulfatase. We previously reported immunogenicity data from our 24-week placebo-controlled Phase III study, MOR-004. Here, we report the long-term immunogenicity profile of elosulfase alfa from MOR-005, the Phase III extension trial to assess potential correlations between antidrug antibodies and efficacy and safety profile outcomes throughout 120 weeks of treatment. The long-term immunogenicity of elosulfase alfa was evaluated in patients with Morquio A syndrome in an open-label extension study for a total of 120 weeks. All patients received 2.0 mg/kg elosulfase alfa either weekly or every other week before establishment of 2.0 mg/kg/wk as the recommended dose, at which time all patients received weekly treatment. Efficacy measures were compared with those from the MOR-004 baseline, enabling analysis of changes over 120 weeks. The primary efficacy measure was the change from baseline in 6-minute walk test. Secondary measures included changes from baseline in 3-minute stair climb test and normalized urine keratan sulfate, a pharmacodynamic metric. All patients treated with elosulfase alfa developed antidrug total antibodies (TAb) by week 24 of MOR-004. In the extension study, all patients, including those who had previously received placebo, were TAb positive by study week 36 (MOR-005 week 12). All patients remained TAb positive throughout the study, and TAb titers were similar across treatment groups at week 120. Nearly all patients tested positive for neutralizing antibodies (NAb) at least once, with incidence of NAb positivity peaking at 85.9% at study week 36, then steadily declining to 66.0% at study week 120. In all treatment groups, mean urine keratan sulfate remained below treatment-naive baseline despite the presence of antidrug antibodies. No

Optimal Surgical Management of Severe Ischemic Mitral Regurgitation: To Repair or to Replace?

PubMed Central

Perrault, Louis P.; Moskowitz, Alan J.; Kron, Irving L.; Acker, Michael A.; Miller, Marissa A.; Horvath, Keith A.; Thourani, Vinod H.; Argenziano, Michael; D'Alessandro, David A.; Blackstone, Eugene H.; Moy, Claudia S.; Mathew, Joseph P.; Hung, Judy; Gardner, Timothy J.; Parides, Michael K.

2013-01-01

Background Ischemic mitral regurgitation (MR), a complication of myocardial infarction and coronary artery disease more generally, is associated with a high mortality rate and estimated to affect 2.8 million Americans. With 1-year mortality rates as high as 40%, recent practice guidelines of professional societies recommend repair or replacement, but there remains a lack of conclusive evidence supporting either intervention. The choice between therapeutic options is characterized by the trade-off between reduced operative morbidity and mortality with repair versus a better long-term correction of mitral insufficiency with replacement. The long-term benefits of repair versus replacement remain unknown, which has led to significant variation in surgical practice. Methods and Results This paper describes the design of a prospective randomized clinical trial to evaluate the safety and effectiveness of mitral valve repair and replacement in patients with severe ischemic mitral regurgitation. This trial is being conducted as part of the Cardiothoracic (CT) Surgical Trials Network. This paper addresses challenges in selecting a feasible primary endpoint, characterizing the target population (including the degree of MR), and analytical challenges in this high mortality disease. Conclusions The paper concludes by discussing the importance of information on functional status, survival, neurocognition, quality of life and cardiac physiology in therapeutic decision-making. PMID:22054660

Factors Affecting Long-Term Abstinence from Substances Use

ERIC Educational Resources Information Center

Elsheikh, Salah Elgaily

2008-01-01

Objective: The purpose of this study is to explore the attitudes of abstainers from drug use that relate to the factors leading to long-term abstinence. Materials and Methods: Cross-sectional study was carried out in Al-Amal Hospital to examine, which attitudes of abstainers related to long-term abstinence. A random survey was conducted on 62…

Long-term consequences of anorexia nervosa.

PubMed

Meczekalski, Blazej; Podfigurna-Stopa, Agnieszka; Katulski, Krzysztof

2013-07-01

Anorexia nervosa (AN) is a psychiatric disorder that occurs mainly in female adolescents and young women. The obsessive fear of weight gain, critically limited food intake and neuroendocrine aberrations characteristic of AN have both short- and long-term consequences for the reproductive, cardiovascular, gastrointestinal and skeletal systems. Neuroendocrine changes include impairment of gonadotropin releasing-hormone (GnRH) pulsatile secretion and changes in neuropeptide activity at the hypothalamic level, which cause profound hypoestrogenism. AN is related to a decrease in bone mass density, which can lead to osteopenia and osteoporosis and a significant increase in fracture risk in later life. Rates of birth complications and low birth weight may be higher in women with previous AN. The condition is associated with fertility problems, unplanned pregnancies and generally negative attitudes to pregnancy. During pregnancy, women with the condition have higher rates of hyperemesis gravidarum, anaemia and obstetric complications, as well as impaired weight gain and compromised intrauterine foetal growth. It is reported that 80% of AN patients are affected by a cardiac complications such as sinus bradycardia, a prolonged QT interval on electrocardiography, arrythmias, myocardial mass modification and hypotension. A decrease in bone mineral density (BMD) is one of the most important medical consequences of AN. Reduced BMD may subsequently lead to a three- to seven-fold increased risk of spontaneous fractures. Untreated AN is associated with a significant increase in the risk of death. Better detection and sophisticated therapy should prevent the long-term consequences of this disorder. The aims of treatment are not only recovery but also prophylaxis and relief of the long-term effects of this disorder. Further investigations of the long-term disease risk are needed. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Reconciling long-term cultural diversity and short-term collective social behavior.

PubMed

Valori, Luca; Picciolo, Francesco; Allansdottir, Agnes; Garlaschelli, Diego

2012-01-24

An outstanding open problem is whether collective social phenomena occurring over short timescales can systematically reduce cultural heterogeneity in the long run, and whether offline and online human interactions contribute differently to the process. Theoretical models suggest that short-term collective behavior and long-term cultural diversity are mutually excluding, since they require very different levels of social influence. The latter jointly depends on two factors: the topology of the underlying social network and the overlap between individuals in multidimensional cultural space. However, while the empirical properties of social networks are intensively studied, little is known about the large-scale organization of real societies in cultural space, so that random input specifications are necessarily used in models. Here we use a large dataset to perform a high-dimensional analysis of the scientific beliefs of thousands of Europeans. We find that interopinion correlations determine a nontrivial ultrametric hierarchy of individuals in cultural space. When empirical data are used as inputs in models, ultrametricity has strong and counterintuitive effects. On short timescales, it facilitates a symmetry-breaking phase transition triggering coordinated social behavior. On long timescales, it suppresses cultural convergence by restricting it within disjoint groups. Moreover, ultrametricity implies that these results are surprisingly robust to modifications of the dynamical rules considered. Thus the empirical distribution of individuals in cultural space appears to systematically optimize the coexistence of short-term collective behavior and long-term cultural diversity, which can be realized simultaneously for the same moderate level of mutual influence in a diverse range of online and offline settings.

Long-term effects of interference on short-term memory performance in the rat.

PubMed

Missaire, Mégane; Fraize, Nicolas; Joseph, Mickaël Antoine; Hamieh, Al Mahdy; Parmentier, Régis; Marighetto, Aline; Salin, Paul Antoine; Malleret, Gaël

2017-01-01

A distinction has always been made between long-term and short-term memory (also now called working memory, WM). The obvious difference between these two kinds of memory concerns the duration of information storage: information is supposedly transiently stored in WM while it is considered durably consolidated into long-term memory. It is well acknowledged that the content of WM is erased and reset after a short time, to prevent irrelevant information from proactively interfering with newly stored information. In the present study, we used typical WM radial maze tasks to question the brief lifespan of spatial WM content in rodents. Groups of rats were submitted to one of two different WM tasks in a radial maze: a WM task involving the repetitive presentation of a same pair of arms expected to induce a high level of proactive interference (PI) (HIWM task), or a task using a different pair in each trial expected to induce a low level of PI (LIWM task). Performance was effectively lower in the HIWM group than in LIWM in the final trial of each training session, indicative of a "within-session/short-term" PI effect. However, we also observed a different "between-session/long-term" PI effect between the two groups: while performance of LIWM trained rats remained stable over days, the performance of HIWM rats dropped after 10 days of training, and this impairment was visible from the very first trial of the day, hence not attributable to within-session PI. We also showed that a 24 hour-gap across training sessions known to allow consolidation processes to unfold, was a necessary and sufficient condition for the long-term PI effect to occur. These findings suggest that in the HIWM task, WM content was not entirely reset between training sessions and that, in specific conditions, WM content can outlast its purpose by being stored more permanently, generating a long-term deleterious effect of PI. The alternative explanation is that WM content could be transferred and stored

Long-term repetitive sodium lauryl sulfate-induced irritation of the skin: an in vivo study.

PubMed

Branco, Nara; Lee, Ivy; Zhai, Hongbo; Maibach, Howard I

2005-11-01

Skin may adapt to topical irritants through accommodation. This study focuses on long-term exposure to irritants and attempts to demonstrate accommodation. Sodium lauryl sulfate (SLS) induced irritant contact dermatitis at 3 concentrations (0.025% to 0.075%). Distilled water, acetone and an empty chamber served as controls. Experimental compounds were applied to forearms of 7 healthy volunteers for 24 hr before replacing by a fresh chamber for 6 non-consecutive weeks over 103 days. Possible accommodation was quantified by visual scoring (erythema and dryness) and by bioengineering parameters: transepidermal water loss (TEWL), capacitance, chromametry and laser Doppler flowmetry (LDF). Significant erythema, dryness, elevated TEWL, skin colour reflectance and LDF values occurred during the exposure periods. Upon repeat exposure, an immediate and augmented response in erythema, TEWL, skin colour reflectance and LDF developed. However, irritant skin changes were not sustained. Irritation parameters return to baseline after cessation of exposure. There was no evidence of sustained irritation or accommodation after the last exposure. Study findings do not document sustained accommodation or adaptive hyposensitivity after long-term repetitive irritant exposure under these test conditions. Alternative models should be developed to prove or disprove the accommodation hypothesis.

Long-term follow-up on Cushing disease patient after transsphenoidal surgery.

PubMed

Jeong, Insook; Oh, Moonyeon; Kim, Ja Hye; Cho, Ja Hyang; Choi, Jin-Ho; Yoo, Han-Wook

2014-09-01

Cushing disease is caused by excessive adrenocorticotropic hormone (ACTH) production by the pituitary adenoma. Transsphenoidal surgery is its first-line treatment. The incidence of Cushing disease in children and adolescents is so rare that long-term prognoses have yet to be made in most cases. We followed-up on a 16-year-old male Cushing disease patient who presented with rapid weight gain and growth retardation. The laboratory findings showed increased 24-hour urine free cortisol and lack of overnight cortisol suppression by low-dose dexamethasone test. The serum cortisol and 24-hour urine free cortisol, by high-dose dexamethasone test, also showed a lack of suppression, and a bilateral inferior petrosal sinus sampling suggested lateralization of ACTH secretion from the right-side pituitary gland. However, after a right hemihypophysectomy by the transsphenoidal approach, the 24-hour urine free cortisol levels were persistently high. Thus the patient underwent a total hypophysectomy, since which time he has been treated with hydrocortisone, levothyroxine, recombinant human growth hormone, and testosterone enanthate. Intravenous bisphosphonate for osteoporosis had been administered for three years. At his current age of 26 years, his final height had attained the target level range; his bone mineral density was normal, and his pubic hair was Tanner stage 4. This report describes the long-term treatment course of a Cushing disease patient according to growth profile, pubertal status, and responses to hormone replacement therapy. The clinical results serve to emphasize the importance of growth optimization, puberty, and bone health in the treatment management of Cushing disease patients who have undergone transsphenoidal surgery.

Enhancing Long-Term Retention of New Vocabulary Using Visual Images.

ERIC Educational Resources Information Center

Igelsrud, Karen

A practicum used a new learning tool to enhance long-term retention of new vocabulary. Sixteen seventh-graders in Language Arts, who had a long-term retention mean score of approximately 40% of newly learned vocabulary, increased their long-term retention of new vocabulary by 25% (a new mean of 65% of new vocabulary). Additional objectives…

Long-term nitrogen regulation of forest carbon sequestration

NASA Astrophysics Data System (ADS)

Yang, Y.; Luo, Y.

2009-12-01

It is well established that nitrogen (N) limits plant production but unclear how N regulates long-term terrestrial carbon (C) sequestration in response to rising atmospheric C dioxide (CO2)(Luo et al., 2004). Most experimental evidence on C-N interactions is primarily derived from short-term CO2 manipulative studies (e.g. Oren et al., 2001; Reich et al., 2006a), which abruptly increase C inputs into ecosystems and N demand from soil while atmospheric CO2 concentration in the real world is gradually increasing over time (Luo & Reynolds, 1999). It is essential to examine long-term N regulations of C sequestration in natural ecosystems. Here we present results of a synthesis of more than 100 studies on long-term C-N interactions during secondary succession. C significantly accumulates in plant, litter and forest floor in most studies, and in mineral soil in one-third studies during stand development. Substantial increases in C stock are tightly coupled with N accretion. The C: N ratio in plant increases with stand age in most cases, but remains relatively constant in litter, forest floor and mineral soil. Our results suggest that natural ecosystems could have the intrinsic capacity to maintain long-term C sequestration through external N accrual, high N use efficiency, and efficient internal N cycling.

Finance issue brief: long-term care insurance: year end report-2002.

PubMed

Tanner, Rachel

2002-12-31

A 1996 federal law made it more attractive for states to consider long-term care insurance, and states have responded by implementing policies to make the purchase of these long-term care coverage more affordable and consumer-friendly. At present, policy makers continue to debate the future role of private long-term care insurance in subsidizing the increasing demand for long-term care services.

[Prevalence of hypertension in elderly long-term care residents in Spain. The Geriatric HTA study].

PubMed

Martín-Baranera, Montserrat; Sánchez Ferrín, Pau; Armario, Pedro

2006-11-11

This study aimed to estimate the prevalence of hypertension in elderly long-term care residents in Spain and to describe such population in terms of comorbidity and hypertension treatment and control. A countrywide cross-sectional study was conducted in May 2003 among long-term care residents aged 65 or more. Patients in palliative care units were excluded. Hypertension was defined in patients who fulfilled at least one of the following criteria: diagnosis of hypertension on the medical record, antihypertensive medication and/or highest blood pressure values during the previous year > or = 140/90 mmHg. Overall, 13,272 subjects - mean age (standard deviation) 82.9 (7.5) years (range: 65-106 years) - were included from 223 centres; 70.6% were women. Almost 2 thirds of patients met at least one hypertension criterion (8,242 patients, 62.1%; 95% confidence interval, 61.3-62.9%). In those patients, other frequent cardiovascular risk factors were obesity (26.3%), diabetes (25.7%) and dislipemia (23.8%). A concomitant diagnosis of dementia, peripheral vascular disease, stroke or congestive heart failure was present in 37.1%, 28.3%, 26.0% and 25.1%, respectively. The proportion of hypertensive patients receiving at least one antihypertensive drug was 69.7%. Diuretics were the most commonly used agents (46.3%), followed by angiotensine converting enzyme inhibitors (34.6%). The latest blood pressure measurement was < 140/90 mmHg in 60.4% of the hypertensive patients. Elderly long-term care residents in Spain showed a high prevalence of hypertension and other cardiovascular risk factors, and a substantial degree of associated clinical conditions. The proportion of antihypertensive drug therapy was comparable to those reported in similar studies.

The long term agroecosystem research network - shared research strategy

Treesearch

Jean L. Steiner; Timothy Strickland; Peter J.A. Kleinman; Kris Havstad; Thomas B. Moorman; M.Susan Moran; Phil Hellman; Ray B. Bryant; David Huggins; Greg McCarty

2016-01-01

While current weather patterns and rapidly accelerated changes in technology often focus attention on short-term trends in agriculture, the fundamental demands on modern agriculture to meet society food, feed, fuel and fiber production while providing the foundation for a healthy environment requires long-term perspective. The Long- Term Agroecoystem Research Network...

Stand-replacing wildfires increase nitrification for decades in southwestern ponderosa pine forests.

PubMed

Kurth, Valerie J; Hart, Stephen C; Ross, Christopher S; Kaye, Jason P; Fulé, Peter Z

2014-05-01

Stand-replacing wildfires are a novel disturbance within ponderosa pine (Pinus ponderosa) forests of the southwestern United States, and they can convert forests to grasslands or shrublands for decades. While most research shows that soil inorganic N pools and fluxes return to pre-fire levels within a few years, we wondered if vegetation conversion (ponderosa pine to bunchgrass) following stand-replacing fires might be accompanied by a long-term shift in N cycling processes. Using a 34-year stand-replacing wildfire chronosequence with paired, adjacent unburned patches, we examined the long-term dynamics of net and gross nitrogen (N) transformations. We hypothesized that N availability in burned patches would become more similar to those in unburned patches over time after fire as these areas become re-vegetated. Burned patches had higher net and gross nitrification rates than unburned patches (P < 0.01 for both), and nitrification accounted for a greater proportion of N mineralization in burned patches for both net (P < 0.01) and gross (P < 0.04) N transformation measurements. However, trends with time-after-fire were not observed for any other variables. Our findings contrast with previous work, which suggested that high nitrification rates are a short-term response to disturbance. Furthermore, high nitrification rates at our site were not simply correlated with the presence of herbaceous vegetation. Instead, we suggest that stand-replacing wildfire triggers a shift in N cycling that is maintained for at least three decades by various factors, including a shift from a woody to an herbaceous ecosystem and the presence of fire-deposited charcoal.

The Effect on Long-Term Survivorship of Surgeon Preference for Posterior-Stabilized or Minimally Stabilized Total Knee Replacement: An Analysis of 63,416 Prostheses from the Australian Orthopaedic Association National Joint Replacement Registry.

PubMed

Vertullo, Christopher J; Lewis, Peter L; Lorimer, Michelle; Graves, Stephen E

2017-07-05

Controversy still exists as to the optimum management of the posterior cruciate ligament (PCL) in total knee arthroplasty. Surgeons can choose to kinematically substitute the PCL with a posterior-stabilized total knee replacement or alternatively to utilize a cruciate-retaining, also known as minimally stabilized, total knee replacement. Proponents of posterior-stabilized total knee replacement propose that the reported lower survivorship in registries when directly compared with minimally stabilized total knee replacement is due to confounders such as selection bias because of the preferential usage of posterior-stabilized total knee replacement in more complex or severe cases. In this study, we aimed to eliminate these possible confounders by performing an instrumental variable analysis based on surgeon preference to choose either posterior-stabilized or minimally stabilized total knee replacement, rather than the actual prosthesis received. Cumulative percent revision, hazard ratio (HR), and revision diagnosis data were obtained from the Australian Orthopaedic Association National Joint Replacement Registry from September 1, 1999, to December 31, 2014, for 2 cohorts of patients, those treated by high-volume surgeons who preferred minimally stabilized replacements and those treated by high-volume surgeons who preferred posterior-stabilized replacements. All patients had a diagnosis of osteoarthritis and underwent fixed-bearing total knee replacement with patellar resurfacing. At 13 years, the cumulative percent revision was 5.0% (95% confidence interval [CI], 4.0% to 6.2%) for the surgeons who preferred the minimally stabilized replacements compared with 6.0% (95% CI, 4.2% to 8.5%) for the surgeons who preferred the posterior-stabilized replacements. The revision risk for the surgeons who preferred posterior-stabilized replacements was significantly higher for all causes (HR = 1.45 [95% CI, 1.30 to 1.63]; p < 0.001), for loosening or lysis (HR = 1.93 [95% CI, 1

Analysis of short- and long-term metabolic effects of growth hormone replacement therapy in adult patients with craniopharyngioma and non-functioning pituitary adenoma.

PubMed

Profka, E; Giavoli, C; Bergamaschi, S; Ferrante, E; Malchiodi, E; Sala, E; Verrua, E; Rodari, G; Filopanti, M; Beck-Peccoz, P; Spada, A

2015-04-01

Adult patients operated for craniopharyngioma develop more frequently GH deficiency (GHD) than patients operated for non-functioning pituitary adenoma (NFPA). The aim of the study was to compare both short- (1 year) and long-term (5 years) effects of rhGH in 38 GHD adult patients (19 operated for Craniopharyngioma (CP) and 19 for NFPA). IGF-I levels, body composition (BF%), BMI, lipid profile and glucose homeostasis were evaluated in all patients. Pituitary MRI was performed at baseline and during follow-up, as needed. At baseline no difference between the two groups was observed, apart from a higher prevalence of diabetes insipidus in CP patients (79 vs 21%). After 12 months, IGF-I SDS normalized and BF% significantly decreased only in the NFPA group. During long-term treatment, decrease in BF% and improvement in lipid profile shown by reduction in total- and LDL-cholesterol were present in NFPA group only, while increase in insulin levels and HbA1c and decrease of QUICKI were observed in CP patients only. Accordingly, after long-term therapy, the prevalence of metabolic syndrome (MS) was significantly higher in CP than in NFPA group (37% in CP and in 5% in NFPA group; p < 0.05). The present data suggest that CP patients are less sensitive to the positive rhGH effects on lipid profile and BF% and more prone to insulin sensitivity worsening than NFPA patients, resulting in increased prevalence of MS in CP only.

Curious Cases of the Enzymes.

PubMed

Ulusu, Nuriye Nuray

2015-07-01

Life as we know it heavily relies on biological catalysis, in fact, in a very nonromantic version of it, life could be considered as a series of chemical reactions, regulated by the guarding principles of thermodynamics. In ancient times, a beating heart was a good sign of vitality, however, to me, it is actually the presence of active enzymes that counts… Though we do not usually pay attention, the history of enzymology is as old as humanity itself, and dates back to the ancient times. This paper is dedicated to these early moments of this remarkable science that touched our lives in the past and will make life a lot more efficient for humanity in the future. There was almost always a delicate, fundamentally essential relationship between mankind and the enzymes. Challenged by a very alien and hostile Nature full of predators, prehistoric men soon discovered the medicinal properties of the plants, through trial and error. In fact, they accidently discovered the enzyme inhibitors and thus, in crude terms, kindled a sparkling area of research. These plant-derivatives that acted as enzyme inhibitors helped prehistoric men in their pursuit of survival and protection from predators; in hunting and fishing… Later in history, while the underlying purposes of survival and increasing the quality of life stayed intact, the ways and means of enzymology experienced a massive transformation, as the 'trial and error' methodology of the ancients is now replaced with rational scientific theories.

Long-term deconditioning of gas-filled surge arresters

NASA Astrophysics Data System (ADS)

Stanković, Koviljka; Brajović, Dragan; Alimpijević, Mališa; Lončar, Boris

2016-07-01

The aim of this paper is to identify parameters that influence the long-term deconditioning effect of gas-filled surge arrester (GFSA) and to provide practical recommendations for mitigating this effect. Namely, after some period of time, on order of hours or days, during which there is no activation due to overvoltage, the deconditioning of GFSA occurs. This effect was observed experimentally within the paper. The observed parameters that could influence the long-term deconditioning effect were the following: shape of voltage load, gas type, gas pressure, interelectrode distance, electrode material, electrode surface topography as well as GFSA design such as two- or three-electrode configuration. According to the results obtained, it has been shown that the occurrence of long-term deconditioning in an insulating system, insulated by a noble gas at a subpressure and with small interelectrode distances, is a phenomenon that always occurs when the insulating system is at rest for about an hour. It has been found that the type of noble gas does not influence the long-term deconditioning. Analysis of such insulating systems' parameters, with a prospect of being used as GFSAs, has demonstrated that this phenomenon is less pronounced at higher pressures (for the same value of the pressure (p) and interelectrode distance (d) product) and for electrodes with microscopically embossed surfaces. According to the results that were obtained by noble gases and their mixtures, as well as the results that were obtained by mixtures of SF6 gas with noble gasses, it can be claimed with confidence that the effect of the long-term deconditioning is an electrode effect. It has also been established that the deconditioning effect does not depend on the electrode material except in the case of electrodes made out of noble metals, which reduce the effect. Based on these results, it can be recommended that the working point of GFSAs be set (according to the DC breakdown voltage value) at a

Material Science in Cervical Total Disc Replacement.

PubMed

Pham, Martin H; Mehta, Vivek A; Tuchman, Alexander; Hsieh, Patrick C

2015-01-01

Current cervical total disc replacement (TDR) designs incorporate a variety of different biomaterials including polyethylene, stainless steel, titanium (Ti), and cobalt-chrome (CoCr). These materials are most important in their utilization as bearing surfaces which allow for articular motion at the disc space. Long-term biological effects of implanted materials include wear debris, host inflammatory immune reactions, and osteolysis resulting in implant failure. We review here the most common materials used in cervical TDR prosthetic devices, examine their bearing surfaces, describe the construction of the seven current cervical TDR devices that are approved for use in the United States, and discuss known adverse biological effects associated with long-term implantation of these materials. It is important to appreciate and understand the variety of biomaterials available in the design and construction of these prosthetics and the considerations which guide their implementation.

Material Science in Cervical Total Disc Replacement

PubMed Central

Pham, Martin H.; Mehta, Vivek A.; Tuchman, Alexander; Hsieh, Patrick C.

2015-01-01

Current cervical total disc replacement (TDR) designs incorporate a variety of different biomaterials including polyethylene, stainless steel, titanium (Ti), and cobalt-chrome (CoCr). These materials are most important in their utilization as bearing surfaces which allow for articular motion at the disc space. Long-term biological effects of implanted materials include wear debris, host inflammatory immune reactions, and osteolysis resulting in implant failure. We review here the most common materials used in cervical TDR prosthetic devices, examine their bearing surfaces, describe the construction of the seven current cervical TDR devices that are approved for use in the United States, and discuss known adverse biological effects associated with long-term implantation of these materials. It is important to appreciate and understand the variety of biomaterials available in the design and construction of these prosthetics and the considerations which guide their implementation. PMID:26523281

Long-term outcomes after primary failures of artificial urinary sphincter implantation.