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PubMed2005

A method of mapping protein sumoylation sites by mass spectrometry using a modified small ubiquitin-like modifier 1 (SUMO-1) and a computational program.

Post-translational modification by small ubiquitin-like modifier 1 (SUMO-1) is a highly conserved process from yeast to humans and plays important regulatory roles in many cellular processes. Sumoylation occurs at certain internal lysine residues of target proteins via an isopeptide bond linkage. Unlike ubiquitin whose carboxyl-terminal sequence is RGG, the tripeptide at the carboxyl terminus of SUMO is TGG. The presence of the arginine residue at the carboxyl terminus of ubiquitin allows tryptic digestion of ubiquitin conjugates to yield a signature peptide containing a diglycine remnant attached to the target lysine residue and rapid identification of the ubiquitination site by mass spectrometry. The absence of lysine or arginine residues in the carboxyl terminus of mammalian SUMO makes it difficult to apply this approach to mapping sumoylation sites. We performed Arg scanning mutagenesis by systematically substituting amino acid residues surrounding the diglycine motif and found that a SUMO variant terminated with RGG can be conjugated efficiently to its target protein under normal sumoylation conditions. We developed a Programmed Data Acquisition (PDA) mass spectrometric approach to map target sumoylation sites using this SUMO variant. A web-based computational program designed for efficient identification of the modified peptides is described.

Amino Acid Sequence↗

PubMed2006

Adaptive response of a gene network to environmental changes by fitness-induced attractor selection.

Cells switch between various stable genetic programs (attractors) to accommodate environmental conditions. Signal transduction machineries efficiently convey environmental changes to the gene regulation apparatus in order to express the appropriate genetic program. However, since the number of environmental conditions is much larger than that of available genetic programs so that the cell may utilize the same genetic program for a large set of conditions, it may not have evolved a signaling pathway for every environmental condition, notably those that are rarely encountered. Here we show that in the absence of signal transduction, switching to the appropriate attractor state expressing the genes that afford adaptation to the external condition can occur. In a synthetic bistable gene switch in Escherichia coli in which mutually inhibitory operons govern the expression of two genes required in two alternative nutritional environments, cells reliably selected the "adaptive attractor" driven by gene expression noise. A mathematical model suggests that the "non-adaptive attractor" is avoided because in unfavorable conditions, cellular activity is lower, which suppresses mRNA metabolism, leading to larger fluctuations in gene expression. This, in turn, renders the non-adaptive state less stable. Although attractor selection is not as efficient as signal transduction via a dedicated cascade, it is simple and robust, and may represent a primordial mechanism for adaptive responses that preceded the evolution of signaling cascades for the frequently encountered environmental changes.

Adaptation, Biological↗

PubMed2003

[Cardiac rehabilitation in Austria. A need to treat analysis].

The aim of this analysis is to survey the general demand and current supply of cardiac rehabilitation in Austria on the basis of best evidence practice and to produce recommendations for a cost-effective structure of the entire cardiac rehabilitation system. Following the standards of indication of the Austrian Society of Cardiology an analysis of demand of cardiac rehabilitation has been carried out and juxtaposed with the current supply of facilities for cardiac rehabilitation. According to hospitalizations in the year 2000, 11,630 patients per annum would require inpatient phase II rehabilitation, 6,270 patients institutional based outpatient phase II rehabilitation and 14,319 patients institutional based phase III rehabilitation. In the year 2000, 14,746 patients received treatment in the 9 Austrian inpatient cardiac rehabilitation centres. This number is compared with an annual demand of 11,630 admissions for phase-II treatment. It follows that an equilibrium can be argued for the supply of and demand for inpatient cardiac rehabilitation in Austria. At present, 10 approved institutions in Austria offer outpatient cardiac rehabilitation services. The maximum number of positions for treatment per institution is currently 200-250. Consequently, maximally 2,000-2,500 patients per annum can be treated. In comparison, there exists a calculated demand for 6,270 patients in institutional based outpatient phase II rehabilitation and 14,319 patients in institutional based phase III rehabilitation. Altogether this amounts to a demand for 20,588 positions for treatment per annum. In Austria, the expenditures for inpatient phase II rehabilitation of a patient given an average duration of stay of 28 days, are [symbol: see text] 4,774.-. Presuming 100% compliance, the institutional based outpatient phase II rehabilitation program costs [symbol: see text] 2,760.- per patient. The costs for institutional based phase III rehabilitation services are [symbol: see text] 2,990.- per patient. This number is accompanied by a potential effective reduction of risks for the patients and a potential effective reduction of costs for the carrier as the number of rehospitalizations and recurrent procedures would decrease significantly. At present, the supply of cardiac rehabilitation in Austria is sufficient for inpatient phase II, but insufficient for the institutional based outpatient phase II and mainly phase III. Thus, a striking asymmetry exists between supply and demand. In view of the enduring effects of institutional based phase III rehabilitation, the individual and social use and finally the expected efficiency in terms of costs, this program should at least be offered without limits to all eligible patients.

Aged↗

PubMed2006

Handmade somatic cell cloning in cattle.

Apart from the biological and ethical problems, technical difficulties also hamper the improvement and widespread application of somatic cell nuclear transfer (NT). Recently introduced zona-free procedures may offer a solution for the latter problem. The most radical approach of these techniques is the so-called handmade cloning (HMC). It does not require micromanipulators because the manipulations required for both enucleation and nucleus transfer are performed by hand. The HMC technique includes manual bisection of zona-free oocytes, selection of cytoplasts by staining, and the simultaneous fusion of the somatic cell with two cytoplasts to produce a cloned embryo. HMC is a rapid and efficient technique that suits large-scale NT programs. It requires less expertise and time than traditional NT methods and the cost of equipment is significantly less. Production efficiency is high and embryo quality, in terms of pregnancy rates and live births, is not compromised. Although HMC has been developed particularly for bovine NT, the technique is applicable to other species. The method may become a useful tool for both experimental and commercial somatic cell cloning because it allows for standardization of procedures and provides the possibility of automation.

Animals↗

PubMed2005

TRICARE; sub-acute care program; uniform skilled nursing facility benefit; home health care benefit; adopting Medicare payment methods for skilled nursing facilities and home health care providers. Final rule.

This rule partially implements the TRICARE "sub-acute and long-term care program reform" enacted by Congress in the National Defense Authorization Act for Fiscal Year 2002, specifically: Establishment of "an effective, efficient, and integrated sub-acute care benefits program," with skilled nursing facility (SNF) and home health care benefits modeled after those of the Medicare program; adoption of Medicare payment methods for skilled nursing facility, home health care, and certain other institutional health care providers; adoption of Medicare rules on balance billing of beneficiaries, prohibiting it by institutional providers and limiting it by non-institutional providers; and change in the statutory exclusion of coverage for custodial and domiciliary care.

Ambulatory Care↗

PubMed1998

Commun-I-Care: experience in the first four years.

The medically uninsured ("working poor") comprise roughly 10 percent of the citizens in South Carolina. These individuals are more likely than the insured to have chronic health conditions including hypertension, diabetes, and respiratory diseases. They appear to have poorer outcomes as as result of misallocation of health care resources from prevention to acute intervention. CIC is a novel program which represents an effort to coordinate the efficient utilization of existing resources to meet the non-emergent health care needs of the medically uninsured. The CIC program has enjoyed a successful beginning and, with the continued strong support of providers and sponsors, looks forward to exciting progress in the future.

Adolescent↗

PubMed1989

Efficacy of exercise for end-stage renal disease patients immediately following high-efficiency hemodialysis: a pilot study.

Nine patients receiving maintenance high-efficiency hemodialysis were studied before and after a 12-week conditioning program to determine the efficacy of exercise immediately following hemodialysis. Each patient performed a combination of bicycle ergometry on the Schwinn Air-Dyne ergometer (SAE) and treadmill walking three times a week for a total exercise time of 15-35 min per session. A low-level Bruce treadmill test and an exercise test on the SAE were administered before and after training. Hematological, serum electrolyte, and serum lipid profiles were also determined before and after training. Following training, there were improvements in exercise capacities for both treadmill walking and ergometry on the SAE. Although a significant increase in serum apolipoprotein A1 was seen following exercise, no significant changes were observed for total cholesterol, low-density-lipoprotein cholesterol, high-density-lipoprotein cholesterol or apolipoprotein B. Additionally, no significant changes were seen in hematological parameters and serum electrolyte profiles following the exercise program. The 9 patients demonstrated an average compliance record of 74%. This study demonstrated that patients on high-efficiency hemodialysis can safely engage in an exercise program immediately following dialysis at intensities and frequencies that can improve their physical work capacities.

Aged↗

PubMed1990

Assistant programming software: a new tool for an improved programming of pacemakers.

Programming the new DDD pacemakers is becoming increasingly difficult. One must take into account the pacemaker's complexity, the fact that some parameters are linked to others, and the clinical profile of the patient. This difficult problem will lead to the design of software to assist programming, which will help the implanting physicians in choosing adequate programmed settings adapted to the functioning of the device and to the physiology and pathology of the patient. These programming aides should meet certain basic requirements to make them safe, efficient, and easy to use. One such system designed by ELA Médical, "Programming Assistant" is herein described. The preliminary results of an initial study on the acceptance of this programming aide among physicians involved in cardiac pacing are given and discussed.

Adult↗

PubMed1999

A record-retention program can protect group practices.

Group practices can benefit from having a systematic record-retention program that includes a formal record-retention policy. While state and Federal laws require the retention of some types of business records, many other records should be retained in the event of an audit or litigation. Having a record-retention program in place can help group practices respond cost-effectively and efficiently when called upon to produce documentation. The record-retention program should include a policy that stipulates not only which records should be kept but also for how long. Group practices should retain records relating to patient care, taxes, payroll, and contracts.

Cost-Benefit Analysis↗

PubMed2002

[Progress on gene targeting].

Gene targeting is a rising technology in molecular biology,which is defined as the introduction of exogeneous DNA to specific site in genome by homologous recombination,and consequently change the hereditary character of the cell. This technology provides a new and powerful means for research in developmental biology,molecular genetics,immunology and medicine. Progresses have been made in exploring gene structure and function,gene expression and regulation,transgene and gene therapy with the application of gene targeting. But there are some problems in gene targeting,especially for the low efficiency. This article just provided a review of the principle and program of gene targeting,and discussed the possible approaches to increase the efficiency of gene targeting.

English Abstract↗

PubMed2006

The Kentucky medical curriculum: continuing innovations in educating physicians.

The University of Kentucky College of Medicine (UKCOM) retains a long history of educational commitment, quality, and innovation. Since undergoing a major curricular revision in the early 1990s, the evolving UKCOM curriculum has continued to incorporate advances in biomedical knowledge and pedagogy while meeting changing societal needs and expectations for physicians in practice. Building upon its established record of excellence in medical education, a curricular quality assurance (QA) program has been initiated to more efficiently guide improvement and innovation by providing faculty with key resources to identify and disseminate local best practices in teaching, learning, and evaluation. Through such efforts, the University of Kentucky College of Medicine is committed to providing a rich educational experience that will meet the needs of students, physicians, and patients well into the 21st century.

Area Health Education Centers↗

PubMedDate not supplied

Criteria for organized cervical screening programs. Special emphasis on The Netherlands program.

Based on the criteria of Wilson and Jungner and experiences in the population-based organized cervical screening program in the Netherlands, conditions for efficient and effective population screening for cervical cancer are described. The purpose of this paper is to determine if these criteria are met for cervical cancer screening and to give recommendations for improvement. Cervical cancer is still an important health problem; the present incidence reflects both background risk and screening activity during previous decades. A positive effect of screening is reached because of the long development time of the disease and the ability of the Pap smear test to detect precancer and early, symptomatic disease. Considerable reduction in the incidence and mortality of cervical cancers can be reached if all women attend and all detected lesions are adequately followed up. Common terminology and classification criteria for histology and cytology should be used. Whether newly developed techniques that may improve or replace cytology can be used in screening programs should be a multidisciplinary decision after clinical trials have given evidence-based information on the performance, cost-effectiveness and need of these techniques. When cervical cancer screening is undertaken, it should be offered in organized programs at the medical level closest to the patients, the general practitioner. High compliance is the most important factor in reducing cervical cancer incidence. Quality control and assurance must be performed at all levels. In the case of limited resources, the program should use a five-year interval and concentrate on the age range 25-60 years, with special attention to women who have never been screened or were screened > 10 years previously. Evaluation of medical and organizational aspects is mandatory. Cooperation between all involved parties is a prerequisite of creating a successful screening program.

Cost-Benefit Analysis↗

PubMed2004

Costs, commitment and locality: a comparison of for-profit and not-for-profit health plans.

Following on the heels of the first national study demonstrating differences in the community benefits provided by not-for-profit and for-profit health maintenance organizations (HMOs) (Schlesinger, Mitchell, and Gray 2003), this study of the New York state market shows significant differences in premiums, administrative overhead and commitment to safety net coverage between nonprofit and for-profit health plans. This study shows that for-profit health plans do act differently than not-for-profit plans in terms of performance, efficiency, and contribution to safety net programs. Moreover, it suggests that not-for-profit health insurers operating in a predominantly for-profit market act in many ways like for-profits. The New York state insurance market provides an ideal study environment because one can compare a large number of policyholders and plans in both business models (for-profit and not-for-profit) that share an identical legislative and regulatory environment. New York has large populations being provided coverage under both models and no allowances had to be made for state-to-state political and/or legal differences. Specifically, this study shows that: The downstate insurance market is predominantly for-profit, while the upstate market is almost entirely not-for-profit. The recent conversion of Empire Blue Cross Blue Shield to a for-profit model moves the downstate market further into the for-profit column, while the upstate region remains not-for-profit. Insurers in the upstate not-for-profit market are more administratively efficient than insurers in the downstate region. Compared to the downstate region, insurers in upstate New York spent 1.5% less of their operating revenues on administrative expenses. The additional 1.5% of spending on administrative expenses downstate totals dollars 137,000,000. Upstate insurers spend significantly more of the revenues received on payments for medical care. Downstate insurers spent 80.4% of operating revenues on medical care. Upstate insurers spent 87.7% of operating revenue on medical care. If health care spending patterns downstate were similar to upstate, the additional 7.3% allocated to medical care would total dollars 678,000,000. A lower level of investment in medical care in the downstate region translated into higher underwriting gains, which totaled 8.1% of operating revenue. Plans in the upstate region reported underwriting gains of only 2.3%. Not-for-profit insurers offer more cost effective (i.e., lower) premium options for consumers. In 2002, the upstate market had the lowest operating revenues (premiums) statewide, averaging dollars 184 per member per month (pmpm); the not-for-profit plans downstate averaged dollars 203 pmpm. Premiums in the for-profit segment of the downstate market averaged dollars 221 pmpm in 2002. The not-for-profit upstate market has proved its viability, while maintaining commitments to New York safety net and Medicare programs. The not-for-profit upstate market experienced a dollars 12 million loss in New York safety net programs in 2002, but generated dollars 131 million in underwriting gains for all product lines combined. Furthermore, upstate revenue gains in 2002 exceeded 2001 results by dollars 45 million. Not-for-profit HMOs, both upstate and downstate, participate in state-sponsored safety net programs to a far greater degree than the downstate for-profit managed care organizations. Within the plan group selected for this study, the not-for-profit plans supported 88% of the enrollment in New York state-sponsored programs, compared with for-profit plans' support of only 12% of safety net membership. Not-for-profit plans have also demonstrated a higher level of dedication to the Medicare Plus Choice product line than for-profit insurers downstate. In 2002, not-for-profit plans enrolled 73% of this population of 385,000 elderly statewide. Despite the favorable financial returns in the product line, for-profit insurers downstate enrolled only 105,000 Medicare risk members in 2002, or 27% of the statewide total. The emergence in New York of health care insurance markets that are predominantly for-profit raises significant public policy issues, especially with reference to community benefits and services. Should the upstate health insurance environment change with the entrance of for-profit plans or conversion of existing plans to for-profit status, the upstate market is likely to look very similar to the downstate in that there will be diminished access to care for the at-risk population; premium costs will be higher and administrative costs will be higher. The health care insurance market upstate would become less attentive to the provision of public goods as insurers strive to maximize their economic advantages.

Blue Cross Blue Shield Insurance Plans↗

PubMed1998

When science and politics listen to each other: good prospects from a new school breakfast program in Peru.

This article provides an overview of a school breakfast program implemented in 1993 in the Peruvian Andes. The program, designed by the Instituto de Investigación Nutricional in Lima and supported by the government of Peru, constitutes a clear departure from previous school feeding programs, which were heavily politicized and poorly documented. From the program's inception, nutritionists, managers, and social scientists have collaborated to produce a sound nutritional design, efficient distribution mechanisms, and effective evaluation methods. During the program's first year, controlled evaluations conducted in several Andean regions documented improved dietary intake and a significant decline in the prevalence of anemia. An educational evaluation also found improved verbal skills, higher school attendance, and lower dropout rates among recipients of the school breakfast. The results have prompted the Peruvian government to continue supporting the program, thus setting a new standard for the effective management of social expenditure in the context of economic adjustment.

Anemia↗

PubMed2006

Evidence-based health benefits management: strategies to optimize antiretroviral medication adherence and outcomes in HIV/AIDS.

OBJECTIVE: To review how evidence-based principles can be applied to benefit design, specialty network management, and medication therapy management to successfully manage pharmaceutical benefits for patients infected with human immunodeficiency virus (HIV). SUMMARY: The most critical barrier to successfully managing HIV disease is suboptimal patient adherence to antiretroviral therapy. Managing HIV infection is unique in that the risk of treatment failure increases remarkably with even relatively minor lapses in patient adherence. The incremental cost of HIV treatment failure has been approximated at $26,000 per patient per year. Treatment failure, of course, also drives mortality related to HIV and acquired immunodeficiency syndrome (AIDS). Benefit design, specialty medication management strategies, and care management programs can be integrated to deliver high-quality, efficient care that optimizes clinical outcomes for populations of HIV-infected individuals. CONCLUSION: Managed care programs can be structured to provide HIV care that allows optimal patient adherence and clinical outcomes.

Antiretroviral Therapy, Highly Active↗

PubMed2003

A humanized aldolase antibody for selective chemotherapy and adaptor immunotherapy.

Mouse monoclonal antibody 38C2 is the prototype of a new class of catalytic antibodies that were generated by reactive immunization. Through a reactive lysine, 38C2 catalyzes aldol and retro-aldol reactions using the enamine mechanism of natural aldolases. In addition to its remarkable versatility and efficacy in synthetic organic chemistry, 38C2 has been used for the selective activation of prodrugs in vitro and in vivo and thereby emerged as a promising tool for selective chemotherapy. Adding another application with relevance for cancer therapy, designated adaptor immunotherapy, we have recently shown that 38C2 can be chemically programmed to target tumors by formation of a covalent bond of defined stoichiometry with a beta-diketone derivative of an integrin alpha(v)beta(3) targeting RGD peptidomimetic. However, a major limitation for the transition from preclinical to clinical evaluation is the human anti-mouse antibody immune response that mouse 38C2 is likely to elicit in a majority of patients after single administration. Here, we report the humanization of mouse 38C2 based on rational design guided by molecular modeling. In essence, the catalytic center of mouse 38C2, which encompasses a deep hydrophobic pocket with a reactive lysine residue at the bottom, was grafted into a human antibody framework. Humanized 38C2 IgG1 was found to bind to beta-diketone haptens with conserved affinities and revealed strong catalytic activity with identical k(cat) and slightly higher K(M) values compared to the parental mouse antibody. Furthermore, humanized 38C2 IgG1 revealed efficiency in prodrug activation and chemical programming comparable to the parental mouse antibody.

Amino Acid Sequence↗

PubMedDate not supplied

Software for efficient visualization and analysis of multiple, large, multi-dimensional data sets from magnetic resonance imaging.

Comprehensive magnetic resonance imaging (MRI) protocols create multiple, large, multi-dimensional data sets that are challenging to review and interpret in an efficient manner. We report on a program called CliniViewer that uses a common data file format to display all files originating from the scanner and other post-processing programs in an integrated display matrix. The five rows of images and maps have general themes of Anatomic Images, Echo-Planar Images, Parametric Maps (derived from echo-planar images), Metabolic Images, and Non-Image Data, respectively. Each row of the matrix contains related image windows of individual MR acquisitions or maps derived from such acquisitions.An interpreter can quickly screen all images and then select any image from the display to create a separate daughter window incorporating a set of analysis tools for in-depth examination. Given that the images can be acquired in the same co-registered planes without moving the subject, regional analysis can be performed simultaneously across multiple MR image types and the corresponding maps, thereby integrating anatomic features with parametric properties. Color can be used to highlight parametric values that fall outside normal ranges to quickly identify abnormalities on each map. CliniViewer is an efficient environment for analyzing multiple images and maps from comprehensive clinical imaging protocols, aiding the neuroradiologist in providing an integrated interpretation of all available MR data for efficient clinical decision making. CliniViewer is compared to AnalyzeAVW and NIH Image, two popular MR image analysis tools. CliniViewer allows efficient clinical analysis of multiple images and maps from comprehensive clinical imaging protocols.

Brain↗

PubMed2005

Evolving binary classifiers through parallel computation of multiple fitness cases.

This paper describes two versions of a novel approach to developing binary classifiers, based on two evolutionary computation paradigms: cellular programming and genetic programming. Such an approach achieves high computation efficiency both during evolution and at runtime. Evolution speed is optimized by allowing multiple solutions to be computed in parallel. Runtime performance is optimized explicitly using parallel computation in the case of cellular programming or implicitly taking advantage of the intrinsic parallelism of bitwise operators on standard sequential architectures in the case of genetic programming. The approach was tested on a digit recognition problem and compared with a reference classifier.

Algorithms↗