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PubMed1998

Influencing physicians: the three critical elements of a successful strategy.

UNLABELLED: This activity is designed for leaders and managers of healthcare organizations, particularly those involved in the development of physician incentive and physician management programs. GOAL: To describe the challenges inherent in influencing physicians and review the essential elements of any successful strategy for achieving physician support and participation. OBJECTIVES: 1. Describe the reasons why healthcare organizations and medical groups need to influence physicians to be successful. 2. Cite the reasons why it is difficult to influence physicians. 3. Review the current strategies healthcare organizations and medical groups use to influence physicians. 4. Outline the three essential elements of any program designed to influence physicians.

Behavior↗

PubMed1999

Molecular interactions between single-stranded DNA-binding proteins associated with an essential MCAT element in the mouse smooth muscle alpha-actin promoter.

Transcriptional activity of the mouse vascular smooth muscle alpha-actin gene in fibroblasts is regulated, in part, by a 30-base pair asymmetric polypurine-polypyrimidine tract containing an essential MCAT enhancer motif. The double-stranded form of this sequence serves as a binding site for a transcription enhancer factor 1-related protein while the separated single strands interact with two distinct DNA binding activities termed VACssBF1 and 2 (Cogan, J. G., Sun, S., Stoflet, E. S., Schmidt, L. J., Getz, M. J., and Strauch, A. R. (1995) J. Biol. Chem. 270, 11310-11321; Sun, S., Stoflet, E. S., Cogan, J. G., Strauch, A. R., and Getz, M. J. (1995) Mol. Cell. Biol. 15, 2429-2936). VACssBF2 has been recently cloned and shown to consist of two closely related proteins, Puralpha and Purbeta (Kelm, R. J., Elder, P. K., Strauch, A. R., and Getz, M. J. (1997) J. Biol. Chem. 272, 26727-26733). In this study, we demonstrate that Puralpha and Purbeta interact with each other via highly specific protein-protein interactions and bind to the purine-rich strand of the MCAT enhancer in the form of both homo- and heteromeric complexes. Moreover, both Pur proteins interact with MSY1, a VACssBF1-like protein cloned by virtue of its affinity for the pyrimidine-rich strand of the enhancer. Interactions between Puralpha, Purbeta, and MSY1 do not require the participation of DNA. Combinatorial interactions between these three single-stranded DNA-binding proteins may be important in regulating activity of the smooth muscle alpha-actin MCAT enhancer in fibroblasts.

Actins↗

PubMed2005

Multielemental accumulation and its intracellular distribution in tissues of some aquatic birds.

This study was aimed at determining multielemental concentration and its intracellular distribution in selected tissues of cormorant and waterfowl species. Non-essential elements such as Hg, Tl, Cd, Pb and V in tissues were generally consistent with those in ingested items, indicating the significance of food sources of non-essential metal accumulation in great cormorants and mallards. Great cormorants and four waterfowl species examined reflected natural background levels of toxic metals such as Cd, Hg and Pb as well as some essential elements, indicating no specific metal exposure from local sources. Most of Cu, Zn, Se, Rb, Ag, Cd, Cs, and Hg contents were present in the hepatocytosolic fraction, whereas a large percentage of V and Mo were present in insoluble fraction in great cormorant, mallard, and spot-billed duck. The major role of these subcelluar fractions in elemental regulation accounts for the high percentage contribution of each cellular fraction to the total metal contents. Cadmium and Cu are chiefly sequestered through binding to metallothioneins (MTs) of hepatocytosolic fraction in these three avian species. Both MTs and high-molecular-weight substance (HMWS) for Zn and low-molecular-weight substance (LMWS) for Rb were also involved in their sequestration in cytosolic fractions. Relatively different species-specific cytosolic substances were responsible for varying degrees of Ag, Mn, and Co accumulation. It is worth noting that these intracellular metal levels in birds are closely regulated by metal-associated cellular constituents. Therefore, risk assessment studies of metal accumulation in such wild birds should take intracellular metal distribution and specific cellular constituents into account.

Animals↗

PubMed1996

[Particle Induced X-ray Emission (PIXE) for analysis of trace elements in biological materials].

Outline of Particle Induced X-ray Emission (PIXE) and its application to biomedical samples are described. Charged particles from cyclotron or van de Graaff generator bombards analytical samples and semiconductor detector measures energy and intensity of induced characteristic x-ray. Simultaneous determination for 22Na to 92U is possible by PIXE. 100 nA of 3 MeV protons bombards biomedical samples and detection limits for almost all trace essential elements are sub microgram/g. Only 1 mg of biomedical sample is necessary for determination of trace elements and no chemical procedure is necessary for preparation of analytical sample. PIXE is powerful tool for determination of essential elements and applied for diagnosis for several diseases.

Animals↗

PubMed1999

An intronic NF-kappaB element is essential for induction of the human manganese superoxide dismutase gene by tumor necrosis factor-alpha and interleukin-1beta.

Tumor necrosis factor-alpha (TNF) and interleukin-1beta (IL-1) are cytokines that induce expression of various genes through activation of the redox-sensitive transcription factor nuclear factor-kappaB (NF-kappaB). We have previously cloned the entire human MnSOD (SOD2) gene and found several NF-kappaB-binding sites in the 5' and 3' flanking and intronic regions. To test whether these putative NF-kappaB-binding sites are able to respond to TNF and IL-1, we performed induction analysis using various deletion constructs ligated to a luciferase reporter gene. We found that the 5' and 3' flanking regions containing several NF-kappaB-binding sites do not mediate MnSOD induction by TNF or IL-1. When a 342-bp intron 2 fragment containing NF-kappaB, C/EBP, and NF-1 binding sites was linked to the basal promoter of the SOD2 gene, transcriptional activities were significantly increased in response to TNF and IL-1 in an orientation- and position-independent manner. To accurately identify the element that is most critical for the enhancer activity, deletions and specific mutations of each individual site were studied. The results indicated that the NF-kappaB binding site is essential but not sufficient for TNF- or IL-1-mediated induction. Furthermore, NF-kappaB elements in the 5' and 3' flanking regions could be made to function in TNF or IL-1 induction when they were transposed to the intronic fragment. Taken together, these results suggest that an NF-kappaB element and its location in the SOD2 gene is critical for TNF/IL-1-mediated induction. However, a complex interaction between NF-kappaB and other transcription elements is needed for a high-level induction.

Base Sequence↗

PubMed1998

The proximal interferon-stimulated response elements are essential for interferon responsiveness: a promoter analysis of the antiviral MxA gene.

Interferon (IFN)-inducible human MxA protein mediates resistance against influenza and several other RNA viruses. The MxA gene is under the control of type I IFN and, in certain cell types, is also directly activated by viruses. Here we show that in human macrophages, MxA mRNA levels are upregulated by very low doses of IFN-alpha in a dose-dependent manner. A similar, albeit much weaker, dose-dependent induction was seen with IFN-gamma. The induction was rapid and independent of protein synthesis. Interleukin-6 (IL-6) or tumor necrosis factor-alpha (TNF-alpha) did not influence MxA mRNA levels alone or in combination with IFNs, in spite of the presence of putative response elements of these cytokines in the MxA promoter. We show that the promoter of the MxA gene contains two functional IFN-stimulated response elements (ISRE) near the transcription start site and one homologous ISRE-like element, which is apparently nonfunctional, further upstream. The two proximal ISRE sites are essential for IFN-alpha-induced transcription and appear to be binding sites for IFN-stimulated gene factor 3 complex. In addition, EMSA and DNAse I footprinting analysis demonstrated that Spl binds with high affinity to a region encompassing nucleotides -25 and -50 and, thus, may provide means of interaction with the basal transcriptional machinery.

Antiviral Agents↗

PubMed2000

Osteoporosis.

Osteoporosis is a disorder of decreased bone mass, microarchitectural deterioration, and fragility fractures. Osteoporosis is widespread and can affect people of all ethnic backgrounds and many older women and men. An essential element in preventing osteoporosis is the achievement of normal peak bone mass. Adequate nutrition, appropriate calcium and vitamin D intake, regular menstrual cycles and a well balanced exercise program of exercise are essential elements in achieving peak bone mass. At menopause women undergo accelerated bone loss. Thereafter, women and men gradually lose bone mass. A loss of one standard deviation give rise to an enhanced twofold risk of spine fractures or a 2.5 risk of hip fracture. Bone mass is determined by dual energy x-ray absorptiometry, quantitative computed tomography scan, and a peripheral ultrasound. Dual energy x-ray absorptiometry has outstanding precision (within 1% to 2%), and has the ability to show the efficacy of drug intervention. Peripheral measurements may identify osteoporosis but only have a 70% correlation with hip and spine bone mass. Dual energy x-ray absorptiometry determines bone mass in a patient but the bone collagen breakdown products (N-telopeptide crosslinks) establish the current rate of bone loss. Major risk factors leading to fragility fracture include low body weight, history of fracture, family history of osteoporosis, and smoking. All individuals should ingest adequate calcium and vitamin D, exercise, and prevent falls. Women with low bone mass, high urinary bone collagen breakdown products, and/or major risk factors should consider hormone replacement therapy or a selective estrogen receptor modulator (Evista), calcitonin and bisphosphonates (alendronate). These agents successfully increase bone mass and limit fracture risk. Men at risk for fragility fractures respond similarly as women to alendronate and calcitonin. Although vertebral compression fractures can occur spontaneously, hip fractures are attributable to low bone mass coupled with a fall. Hence, fall prevention programs in addition to medical treatment are critical in the prevention of fragility fractures.

Female↗

PubMed2005

Maintenance of certification for radiation oncology.

Maintenance of Certification (MOC) recognizes that in addition to medical knowledge, several essential elements involved in delivering quality care must be developed and maintained throughout one's career. The MOC process is designed to facilitate and document professional development of American Board of Radiology (ABR) diplomates in the essential elements of quality care in Radiation Oncology and Radiologic Physics. ABR MOC has been developed in accord with guidelines of the American Board of Medical Specialties. All Radiation Oncology certificates issued since 1995 are 10-year, time-limited certificates; diplomates with time-limited certificates who wish to maintain specialty certification must complete specific requirements of the American Board of Radiology MOC program. Diplomates with lifelong certificates are not required to participate but are strongly encouraged to do so. Maintenance of Certification is based on documentation of participation in the four components of MOC: (1) professional standing, (2) lifelong learning and self-assessment, (3) cognitive expertise, and (4) performance in practice. Through these components, MOC addresses six competencies-medical knowledge, patient care, interpersonal and communication skills, professionalism, practice-based learning and improvement, and systems-based practice. Details of requirements for components 1, 2, and 3 of MOC are outlined along with aspects of the fourth component currently under development.

Certification↗

PubMed2005

The cell clone ecology hypothesis and the cell fusion model of cancer progression and metastasis: history and experimental support.

The two-stage initiation-progression model of cancer is widely accepted. Although mutations explain initiation of neoplasia, the assumption that mutations are responsible for progression of neoplasia to cancer appears to have little experimental support. The "cell clone ecology hypothesis" explains why neoplasia evolve and the "cell fusion model of cancer progression and metastasis" describes how they evolve into clinically significant tumors. A brief history of important concepts and experiments is provided. Clinically significant cancers are effectively new parasite species that live, expand and evolve within the host. It is hypothesized that survival and fate of the parasite clones called "cancer" are governed by the principles of ecology. It is argued that while mutations or aneuploidy (asexual reproduction) can result in transient/self-limiting neoplasia, neither of these asexual modes of forming new karyotypes can maintain the ecologically fit parasites that develop into clinically significant cancer. Mutations and/or unstable genomes (aneuploidy) progressively degrade cell lines and if only these mechanisms were at work, neoplasia would spontaneously become extinct or benign (enfeebled) before reaching clinical significance (an example of "Muller's ratchet"). In the cell fusion model of (clinically significant) cancer progression and metastasis, cell-cell fusion is the essential element allowing normal cells or (transient) neoplasia to evolve into clinically significant cancers. Cell-cell fusion is required for producing and sustaining clinically significant cancer because it provides a sex-like mode of reproduction essential for an ecologically fit parasite organism. Cell-cell fusion provides the opportunity needed for tumors to rejuvenate cell lines containing abnormal genomes and rapidly evolve to acquire dramatically aggressive traits such as metastasis. Indeed, metastasis appears to require cell-cell fusion. Cell-cell fusion also partially overcomes erosion of teleomeres during clone expansion and allows the essential elements of a tumorigenic genome to hide from chemotherapy as recessive traits in cells with normal phenotypes and re-emerge (by cell-cell fusion) as a new cancer after the phenotypically cancerous cells have been eradicated by classical chemotherapy. Eradication of the cancer parasite cannot be routinely achieved by classical toxic chemotherapy alone or even by chemotherapy augmented with techniques needed to overcome anti-apoptotic traits of cancer cells. Direct chemical intervention against cell-cell fusion concurrent with classical toxic chemotherapy holds a promise of preventing re-lapse of the disease. Intervention against cell-cell fusion may also directly suppress metastasis based on the model presented here. The paper also summarizes work on the cell surface glycoprotein CD44 that implicates it as a key element in cell-cell fusion and hence cancer.

Cell Fusion↗

PubMed1984

Effect of metal chelators on excretion and tissue levels of essential trace elements.

The influence of one, three, and six doses of ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA), and triethylenetetramine (TETA) on the urinary excretion of Ca, Cu, Fe, and Zn, and on their levels in liver, kidneys, heart, and serum in rats, was investigated to ascertain their suitability in amelioration of metal intoxication. While excretion of all the essential trace metals examined was enhanced significantly, the tissue and serum levels of some of them either increased or decreased after administration of the chelators. The results suggest depletion of some of the endogenous trace metals from the body and their intertissue redistribution following treatment with these chelating agents.

Animals↗

PubMed1998

In vitro mineral availability from digested tea: a rich dietary source of managanese.

Tea is potentially a rich source of some dietary metals and approximately 70 l are drunk per capita per year in the UK. In particular, tea may be an important source of Mn, since leaf tea contains 350-900 micrograms g-1 of this essential element. However, the leaching and bioavailability of Mn from tea have been little studied, so a recently developed in vitro assay was applied to compare the bioavailability of Mn from tea infusions with that of other major and trace essential elements. Analysis of tea infusions before digestion showed that 1.0 l contained 115% of the average daily dietary intake of Mn but < 6% of all other minerals. Samples of these infusions were incubated with human gastric juice (37 degrees C, 1 h) and some were then adjusted to pH 6.5 to simulate intestinal pH. All were centrifuged through ultrafilters with molecular mass cut-offs of 3, 10 and 30 kDa. The percentages of ultrafilterable (< 3 kDa) elements following simulated gastrointestinal digestion were (n = 3; mean +/- s) Ca 47.7 +/- 10.7, Cu 45.3 (n = 1), Fe < 5, Mg 66.4 +/- 1.6, Mn 39.8 +/- 11.4, K 40.3 +/- 2.2, Na 100.0 +/- 5.3 and Zn 33.7 +/- 1.1. Hence the ultrafilterability of elements showed the general trend M+ > M2+ > M3+, which is probably the inverse of the order of their strengths of binding to tea polyphenols. However, Mn was the only element found in significant dietary amounts in tea, and under simulated intestinal conditions was still 40% bioavailable.

Biological Availability↗

PubMed1995

A developmentally regulated chromosomal origin of replication uses essential transcription elements.

Only one of the two chromosomes in the asymmetric Caulobacter predivisional cell initiates replication in the progeny cells. Transcription from a strong promoter within the origin occurs uniquely from the replication-competent chromosome at the stalked pole of the predivisional cell. This regulated promoter has an unusual sequence organization, and transcription from this promoter is essential for regulated (cell type-specific) replication. Our analysis defines a new class of bacterial origins and suggests a coupling between transcription and replication that is consistent with the phylogenetic relationship of Caulobacter to the ancestral mitochondrion.

Base Sequence↗

PubMed2005

The American Board of Radiology Maintenance of Certification (MOC) Program in Radiologic Physics.

Maintenance of Certification (MOC) recognizes that in addition to medical knowledge, several essential elements involved in delivering quality care must be developed and maintained throughout one's career. The MOC process is designed to facilitate and document the professional development of each diplomate of The American Board of Radiology (ABR) through its focus on the essential elements of quality care in Diagnostic Radiology and its subspecialties, and in the specialties of Radiation Oncology and Radiologic Physics. The initial elements of the ABR-MOC have been developed in accord with guidelines of The American Board of Medical Specialties. All diplomates with a ten-year, time-limited primary certificate in Diagnostic Radiologic Physics, Therapeutic Radiologic Physics, or Medical Nuclear Physics who wish to maintain certification must successfully complete the requirements of the appropriate ABR-MOC program for their specialty. Holders of multiple certificates must meet ABR-MOC requirements specific to the certificates held. Diplomates with lifelong certificates are not required to participate in the MOC, but are strongly encouraged to do so. MOC is based on documentation of individual participation in the four components of MOC: (1) professional standing, (2) lifelong learning and self-assessment, (3) cognitive expertise, and (4) performance in practice. Within these components, MOC addresses six competencies: medical knowledge, patient care, interpersonal and communication skills, professionalism, practice-based learning and improvement, and systems-based practice.

Certification↗

PubMed1995

Therapeutic communities for addictions: a theoretical framework.

Adaptation of therapeutic communities (TCs) for new clients and in different settings has resulted in a diversity of programs with unique treatment protocols and different planned duration of stays. The extent to which the various adaptations retain the essential elements of the TC model is not known, and moreover, casts questions about the general effectiveness of the therapeutic community modality. This paper outlines a theoretical framework of the addiction TC to advance research and guide training, practice, and program development. The essential elements of the TC are organized into four areas: its perspective, treatment approach, program model, and the treatment process. Some implications of a TC theory, model, and method are discussed in terms of research, treatment, and policy issues.

Goals↗

PubMed1996

[Overview--suppression effect of essential trace elements on arteriosclerotic development and it's mechanism].

It is known that the peroxidation of LDL is a trigger for developing arteriosclerosis. The oxidized LDL is produced by either oxidative stress or a few oxidant. Selenium decreased in serum and some organs of stroke-prone spontaneously hypertensive rats (SHRSP), which is a cofactor of glutamine peroxidase. Serum magnesium decreased in patients with diabetes mellitus, with ischemic heart disease, with essential hypertension and with cerebral vascular lesions. Calcium to magnesium ratio was higher in some organs of SHRSP as compared to Wistar Kyoto rats (WKY). These changes accelerated vascular lesions in SHRSP.

Animals↗

PubMed1998

Choice, isolation, and preparation of cells for bioartificial vascular grafts.

Preparation of cells and tissues for bioartificial vascular grafts is discussed from the viewpoint of tissue engineering. In general, a neointima is not formed on vascular prostheses except at the anastomotic sites. Graft surfaces do not heal and are covered with fresh thrombi for a long period of time after implantation. The delayed healing is, so to speak, an intractable ulcer of the vascular wall. To overcome this problem, we have developed a tissue fragment transplantation method. We consider that neointima formation of vascular prostheses after implantation is a product of tissue engineering in vivo. Therefore, 3 essential elements for tissue engineering, i.e., cells, extracellular matrices, and cytokines, are required for neointima formation. Synthetic vascular prostheses lack one or more of these elements. In this study we demonstrated a standard healing process of fabric vascular prostheses and an antithrombogenic polymer graft using animal models. Then we showed the tissue fragment transplantation method using venous tissues, adipose tissues, and bone marrow. This method provided the 3 essential elements to the prostheses. To allow these elements to be actively engaged in neointima formation, we treated cells and tissues as clumps without enzymatic digestion. We also took advantage of the in vivo environment. With the results we demonstrate our way of thinking in relation to bioartificial vascular grafts.

Adipose Tissue↗

PubMedDate not supplied

Major and trace elements in spruce needles by NAA.

Concentrations of 23 elements in needles of Norway spruce (P. abies) have been determined at 47 sites. It is shown that a thorough removal of the aerosols sitting on the needles surface is necessary in order to get the inherent needle concentrations. Neutron activation was used to determine concentrations from 10(-9) to 10(-2) g/g. Irradiation and counting conditions are given. The essential elements, Ca, Cl, Cu, Fe, K, Mg, Mn, P, Zn, and the nonessential elements, Al, As, Ba, Br, Co, Cs, Hg, La, Na, Rb, Sb, Sc, Sr, and V, could be determined. The concentrations of most elements are about a factor of 6 smaller than the mean concentrations in land plants. Analytical reproducibility was much better than the variation among individual trees, and the variation within sites is smaller than among sites. In general, essential elements have smaller variations than nonessential elements. For some elements, variations between sites are owing to differences in the soil pH or the emission situation.

Neutron Activation Analysis↗

PubMed1999

Concentrations of essential trace elements in maternal serum and the effect on birth weight and newborn body mass index in sub-arctic and arctic populations of Norway and Russia.

BACKGROUND: This project is part of an assessment of the impact of environmental factors on human health in the Kola Peninsula of Russia and the neighboring arctic area of Norway. Pregnant women and their newborns were studied to explore a relationship between maternal status of essential metals and birth weight. METHODS: Life-style information and serum specimens were collected from at least 50 consecutive mother-infant pairs from hospital delivery departments in three Russian and three Norwegian communities (N=151 and 167, respectively). Pregnancy outcomes were verified by consulting medical records. Copper, selenium and zinc in serum were determined by atomic absorption spectrometry and ferritin by an automated analyzer method. RESULTS: Mean birth weight and child's body mass index (BMIC) were significantly lower in the Russian group (p<0.001), with or without adjustment for gestational age. Copper, iron (as ferritin) and selenium serum concentrations were in the normal range, while zinc levels in both countries were mostly below the lower limit (10.8 micromol/L) of reported reference intervals. A positive correlation between zinc and birth weight or BMIC was only observed for concentrations exceeding 10.8 micromol/L. Analysis by quartiles showed that maternal urinary creatinine and birth weight were negatively correlated (p=0.001). The influence of the different elements on BMIC, grouped by quartiles, was significantly positive only for selenium (p=0.03) and ferritin (p=0.02), while there was no significant relationship for copper or zinc. Adjustment of birth weight and BMIC for gestational age did not alter substantially the various associations indicated. CONCLUSIONS: With the exception of zinc, the mineral status of delivering women in arctic and sub-arctic regions of Norway and western Russia appears to be adequate. The significantly lower BMIC for the Russian group suggests the likely occurrence of nutritional deficiencies during pregnancy in Russia. However, the significant contribution of a country factor in the predictive model implies that the maternal serum trace-element concentrations explored in this study are incomplete indicators of fetal undernourishment.

Adult↗