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Emerging credentialing practices, malpractice liability policies, and guidelines governing complementary and alternative medical practices and dietary supplement recommendations: a descriptive study of 19 integrative health care centers in the United States.

BACKGROUND: Little is known about policies governing the integration of complementary and alternative medical (CAM) therapies and providers. METHODS: To document emerging approaches in 19 US hospitals regarding credentialing, malpractice liability, and pharmacy policies governing integration of CAM therapies and providers into conventional medical settings, we surveyed 21 academic medical centers and 13 non-academically affiliated hospitals that are nationally visible and are integrating CAM therapies into conventional medical settings. Of the 19 respondents, 11 were tertiary care hospitals, 6 were community hospitals, 1 was a freestanding center associated with a community-based hospital, and 1 was a university-based rehabilitation hospital. RESULTS: Institutions had no consistent approach to provider mix and authority within the integrative care team, and minimum requirements for professional liability insurance, informed consent disclosure, and hiring status. Less than a third had a formal (stated) policy concerning dietary supplements; those selling supplements in their pharmacy lacked consistent, evidence-based rationales regarding which products and brands to include or exclude. Although many hospitals confiscated patient supplements on admission, institutions had inconsistent criteria regarding allowance of home supply. CONCLUSIONS: Hospitals are using heterogeneous approaches to address licensure, credentialing, scope of practice, malpractice liability, and dietary supplement use in developing models of integrative care. The environment creates significant impediments to the delivery of consistent clinical care and multisite evaluations of the safety, efficacy, and cost-effectiveness (or lack thereof) of CAM therapies (or integrative models) as applied to management of common medical conditions. Consensus policies need to be developed.

Complementary Therapies↗

Integration analysis of pSK41 in the chromosome of a methicillin-resistant Staphylococcus aureus K-1.

An integrate of pUB110 carrying aadD and blmS genes conferring resistance to 4'-OH containing aminoglycosides and bleomycin, respectively, is found in the Staphylococcal conjugative plasmid pSK41 and in the mec chromosomal region. In this study, we found an integrated copy of pSK41 in the chromosome of an arbekacin-resistant MRSA strain, K-1, clinically isolated in Japan. This is the first report of the chromosomal integration of this large plasmid in MRSA. Analysis of the nucleotide sequence and restriction map revealed a complete homology of the blmS-containing region of the integrate to wild type pSK41, except for the deletion of aadD and a part of the repU gene. In addition, we have discovered an insertion of IS1182 within the pSK41 integrate. Pulse-field gel electrophoresis-Southern analysis showed that the integration occurred outside the mec region. We also found that deletion of aadD resulted in an aberration of blmS transcription.

Acetyltransferases↗

Increased production of Bacillus keratinase by chromosomal integration of multiple copies of the kerA gene.

To increase the production of keratinase, stable strains of Bacillus licheniformis carrying multiple keratinase gene copies in the chromosome were developed. Integrative vectors carrying kerA with or without P43-promoter were constructed and subcloned into B. licheniformis T399D and Bacillus subtilis DB104. In T399D, multiple copies of kerA integration into the chromosome were identified and determined by Southern blot. The optimal integration of kerA was found in the range of 3-5 copies. Higher integration of gene copies (>5) caused reduced processing and secretion of the extracellular keratinase. In DB104, kerA was cloned in the plasmid, not integrated into the chromosome. The strong constitutive promoter P43 not only increased the keratinase production in plasmid-based expression in DB104 but also improved the enzyme yield of the integrants of T399D. New strains were able to enhance cell growth and enzyme yield at higher concentrations of medium substrate. When they were grown in either soy or feather medium, the keratinase activity was stable and improved by about 4-6 times.

Bacillus↗

Interactive multi-window integration of two-parameter flow cytometric data fields.

Integration is necessary to determine the particle content of regions of interest of flow cytometric two-parameter fields. The improved program of the Cytomic 12 analyzer (1) offers: window trace integration for relatively simple window structures. The field of interest is surrounded by an integration trace (window). Eight independent windows can be stored and successively evaluated. It also offers painted field integration for complicated window structures. The pointer or a small window is interactively moved over the structures to be integrated like the brush of a painter. The "painted field" defines the window to be integrated. Window sets and painted fields can be stored on a floppy disk. Painted fields can be added and may also serve as look up tables for sorting.

Cell Count↗

Integration and collaboration in public health--a conceptual framework.

With the increasing differentiation of organisations involved in the pursuit of public health, there is also a growing need for inter-organisational integration. Starting from the concepts of differentiation and integration, this article is attempting a theoretical reconstruction based on published research on inter-organisational integration in public health and related welfare services. Different forms of integration are defined and related to each other in a conceptual framework, which is in itself an integration of different theoretical perspectives. According to this framework, integration in the field of public health requires inter-organisational collaboration across different sectors of the society. Such intersectoral collaboration can be organised mainly in the form of multidisciplinary teams across the boundaries of different organisations and sectors. Such an organisation is fragile and volatile, however, which means that it needs a lot of management support in order to survive.

Cooperative Behavior↗

Increased plasma DNA integrity index in head and neck cancer patients.

Analysis of the length of circulating DNA in plasma has been reported as a marker for solid tumor detection. We assessed the sensitivity and specificity of increased plasma DNA length to identify patients with head and neck squamous cell carcinoma (HNSCC) and monitor posttreatment disease status. Fifty-eight HNSCC patients with paired pre- and postoperative plasma and 47 plasma samples from control subjects were analyzed using quantitative PCR to determine plasma DNA integrity index. We found that the mean DNA integrity index was significantly greater in the plasma from HNSCC patients, 0.24 (95% CI: 0.11, 0.38), when compared to plasma from the control subjects, -2.24 (95% CI: -2.92, -1.56), p < 0.0001 using multivariate analysis. The optimal sensitivity (the value for which sensitivity equals specificity) was found at a plasma DNA integrity index of 0.82: sensitivity, 84.5%; specificity, 83%. However, there was no significant difference noted between pre- and postoperative DNA integrity index in plasma samples from HNSCC patients. This study shows that DNA integrity index in the plasma of the patients with HNSCC is increased in comparison with that in the plasma from non-HNSCC control subjects. Lack of normalization of plasma DNA integrity index after surgical resection implies the persistence of a population of cells with an altered pattern of DNA degradation despite removal of malignancy.

Adult↗

The integrated conjugative plasmid pSAM2 of Streptomyces ambofaciens is related to temperate bacteriophages.

Streptomyces ambofaciens ATCC23877 and derivatives contain the 11-kb element pSAM2 present in an integrated state or as a free and integrated plasmid. This element, able to integrate site-specifically in the genome of different Streptomyces species, is conjugative and mobilizes chromosomal markers. Besides these plasmid functions, we have shown that the site-specific recombination system of pSAM2 presents strong similarities with that of several temperate phages. The integration event is promoted by a site-specific recombinase of the integrase family. The int gene encoding this integrase is closely linked to the plasmid attachment site (attP). A small open reading frame (ORF) overlaps the int gene and the predicted protein exhibits similarities with Xis proteins involved in phages excision. The integrated copy of pSAM2 in strain ATCC23877 is flanked by att sequences (attL and attR). Another att sequence (attX) is present in this strain and attX and attL are the boundaries of a 42-kb fragment (xSAM1) absent, as well as pSAM2, from S.ambofaciens DSM40697. Sequences partially similar to pSAM2 int gene are found near the chromosomal integration zone in both S.ambofaciens strains. The possible origin of pSAM2, an element carrying plasmid as well as phage features, is discussed.

Amino Acid Sequence↗

An analysis of the integration between articular cartilage and nondegradable hydrogel using magnetic resonance imaging.

A hydrogel is a highly hydrated polymer gel suitable for use as a scaffold for tissue engineering. One important application is to the repair of cartilage defects due to injury or osteoarthritis. Integration of the hydrogel with surrounding tissue is critical for the long-term functionality of the implant; however direct visualization of integration is difficult and invasive. Accordingly, we used MRI to noninvasively investigate the integration of hydrogel in cartilage. Two integration methods were assessed: (1) cartilage-initiated and (2) chemical, using chondroitin sulphate-methacrylate-aldehyde (CS-MA-ald) as an adhesive. These were compared to a control group, that is, standard, nonintegrated hydrogel photopolymerization. Spatial variation of the transverse relaxation time, T(2), across the transition region was used to determine the effectiveness of integration. In the CS-MA-ald group only, two interfaces were found. This provides evidence of an intermediate adhesive layer between hydrogel and cartilage. Second, the thickness of the transition region between hydrogel to cartilage in the CS-MA-ald group was 1.32 mm as compared to 1.20 mm and 1.17 mm in the tissue-initiated and nonintegrated groups, respectively. We interpret this as a more gradual transition region of hydrogel to cartilage and hence a greater degree of integration when an adhesive layer is present.

Animals↗

Efficiency of the algorithms for the calculation of Slater molecular integrals in polyatomic molecules.

The performances of the algorithms employed in a previously reported program for the calculation of integrals with Slater-type orbitals are examined. The integrals are classified in types and the efficiency (in terms of the ratio accuracy/cost) of the algorithm selected for each type is analyzed. These algorithms yield all the one- and two-center integrals (both one- and two-electron) with an accuracy of at least 12 decimal places and an average computational time of very few microseconds per integral. The algorithms for three- and four-center electron repulsion integrals, based on the discrete Gauss transform, have a computational cost that depends on the local symmetry of the molecule and the accuracy of the integrals, standard efficiency being in the range of eight decimal places in hundreds of microseconds.

Journal Article↗

What's an integrationist? A study of self-identified integrative and (occasionally) eclectic psychologists.

We examined the views and practices of self-identified eclectic and integrative psychologists, particularly in the context of historical changes since 1977 and 1988. Results from 187 eclectic clinical psychologists indicated that 50% previously adhered to another theoretical orientation, the majority preferred the term integrative to eclectic, and 85% conceptualized eclecticism/integration as the endorsement of a broader orientation. The most common paths toward integration were theoretical integration, common factors, and assimilative integration, as opposed to technical eclecticism. The most frequent theoretical contributor to integrative practice was cognitive therapy.

Health Personnel↗

Analysis of site-specific transgene integration following cotransduction with recombinant adeno-associated virus and a rep encodingplasmid.

BACKGROUND: Recombinant adeno-associated virus (rAAV) has many advantages for gene therapeutic applications in comparison with other vector systems. One of the most promising features is the ability of wild-type (wt) AAV to integrate site-specifically into human chromosome 19. However, this feature is lost in rAAV vectors due to the removal of the rep-coding sequences. METHODS: HeLa cells were transfected with a rep expression plasmid, infected by rAAV and grown with or without selection pressure. Single cell clones were generated and genomic DNA was analyzed for site-specific integration by Southern blotting analysis and fluorescence in situ hybridization (FISH). RESULTS: Transfection of HeLa cells with a rep expression plasmid followed by transduction with a rAAV vector resulted in site-specific integration of the transgene at AAVS1 on human chromosome 19 in 7 of 10 cell clones analyzed. In marked contrast, transduction of cells with rAAV alone did not result in any site-specific integration of the transgene. CONCLUSIONS: The high frequency with which the site-specific integration took place in the presence of Rep protein is comparable with the results observed with wtAAV. These results offer opportunities for the development of specifically integrating rAAV vectors.

Adenoviridae↗

Characterization of integration patterns and flanking cellular sequences of hepatitis B virus in childhood hepatocellular carcinomas.

Hepatitis B virus (HBV) DNA integration into host chromosomes is detected in more than 80% of HBV-related hepatocellular carcinomas (HCC), yet its significance in tumor development remains obscure. In this study, we re-examined the integration pattern of HBV in childhood HCC tissues, which has less environmental confounding factors than adult HCC. The HBV junctions and flanking cellular sequences were amplified from five childhood HCC patients by the inverse polymerase chain reaction (IPCR) method using primers located near HBV direct repeats (DR) 1 and 2. The viral junctions in nine of the ten obtained IPCR clones were demonstrated to be located near HBV DR1, and their patterns were classified to type I integrants. Southern blot analyses demonstrate that the cellular junctions derived from two of the five HCC tissues were male specific and contained sequences homologous to human long interspersed DNA elements (LINE-1). HBV integrant of one HCC tissue (1217T) was integrated into a RNA binding motif Y chromosome (RBMY) gene. The expression of RBMY, which is normally found only in male germ cells, was detected in HCC tissue 1217T by RT-PCR but not in the corresponding non-tumor liver tissue. The prevalence of RBMY expression in liver tissues from the tumor and non-tumor parts of ten other HCC children and seven biliary atresia (BA) children was studied by RT-PCR. No RBMY transcripts were detected in the non-tumor parts of HCC patients or the cirrhotic livers of BA children, whereas 30% (three of ten) of HCC tissues specifically expressed RBMY. The results indicate that HBV integration and activation of RBMY gene expression in liver cells may be associated with the development of childhood HCC.

Base Sequence↗

Occupational therapy using a sensory integrative approach for children with developmental disabilities.

This article provides an introduction and overview of sensory integration theory as it is used in occupational therapy practice for children with developmental disabilities. This review of the theoretical tenets of the theory, its historical foundations, and early research provides the reader with a basis for exploring current uses and applications. The key principles of the sensory integrative approach, including concepts such as "the just right challenge" and "the adaptive response" as conceptualized by A. Jean Ayres, the theory's founder, are presented to familiarize the reader with the approach. The state of research in this area is presented, including studies underway to further delineate the subtypes of sensory integrative dysfunction, the neurobiological mechanisms of poor sensory processing, advances in theory development, and the development of a fidelity measure for use in intervention studies. Finally, this article reviews the current state of the evidence to support this approach and suggests that consensual knowledge and empirical research are needed to further elucidate the theory and its utility for a variety of children with developmental disabilities. This is especially critical given the public pressure by parents of children with autism and other developmental disabilities to obtain services and who have anecdotally noted the utility of sensory integration therapy for helping their children function more independently. Key limiting factors to research include lack of funding, paucity of doctorate trained clinicians and researchers in occupational therapy, and the inherent heterogeneity of the population of children affected by sensory integrative dysfunction. A call to action for occupational therapy researchers, funding agencies, and other professions is made to support ongoing efforts and to develop initiatives that will lead to better diagnoses and effective intervention for sensory integrative dysfunction, which will improve the lives of children and their families.

Child↗

Cooling and freezing damage platelet membrane integrity.

Cytoskeletal rearrangements and a membrane lipid phase transition (liquid crystalline to gel) occur in platelets on cooling from 23 to 4 degrees C. A consequence of these structural alterations is irreversible cellular damage. We investigated whether platelet membrane integrity could be preserved by (a) previously studied combinations of a calcium chelator (EGTA) and microfilament stabilizer (cytochalasin B) with apparent benefit in protecting platelets from cooling injury or (b) agents of known benefit in protecting membranes and proteins from freezing injury. Platelet function and activation before and after freezing or cooling were measured by agglutination with ristocetin, aggregation with thrombin or ADP, platelet-induced clot retraction (PICR), and expression of P-selectin. Platelets were loaded with 10 nM fluorescein diacetate. After freezing or cooling, the preparations were centrifuged and the supernatant was measured for fluorescein. For cooling experiments, fresh platelets were chilled at 4 degrees C for 1 to 21 days with or without the combination of 80 microM EGTA/AM and 2 microM cytochalasin B (EGTA/AM-CytoB) and then warmed rapidly at 37 degrees C. For freezing experiments, 5% dimethyl sulfoxide (Me2SO) or 5 mM glycerol were added to fresh platelets. The preparations were then frozen at -1 degrees C/min to -70 degrees C and then thawed rapidly at 37 degrees C. Platelet membrane integrity, as measured by supernatant levels of fluorescein, correlated inversely with platelet function. Chilling platelets at 4 degrees C with EGTA/AM-CytoB showed a gradual loss of membrane integrity, with maximum loss reached on day 7. The loss of membrane integrity preceded complete loss of function as demonstrated by PICR. In contrast, platelets chilled without these agents had complete loss of membrane integrity and function after 1 day of storage. Freezing platelets in Me2SO resulted in far less release of fluorescein than did freezing with or without other cryoprotectants (P < 0.001). This result correlated with enhanced function as demonstrated by PICR and supports earlier observations that Me2SO protects platelet membranes from freezing injury. Release of fluorescein into the surrounding medium reflected loss of membrane integrity and function in both cooled and frozen platelets. Membrane cytoskeletal rearrangements are linked to membrane changes during storage. These results may be generally applicable to the study of platelet storage.

Adenosine Diphosphate↗

Iterative Solution Method for the Linearized Poisson-Boltzmann Equation: Indirect Boundary Integral Equation Approach.

An iterative solution scheme is proposed for solving the electrical double-layer interactions governed by the linearized Poisson-Boltzmann equation. The method is based on the indirect integral equation formulation with the double-layer potential kernel of the linearized Poisson-Boltzmann equation. In contrast to the conventional direct integral equation approach that yields Fredholm integral equations of the first kind, the indirect integral equation approach yields well-posed Fredholm integral equations of the second kind. The eigenvalue analysis reveals that the spectral radius of the double-layer integral operator is always less than one. Thus, iterative solution schemes can be successfully implemented for solving the electrical double-layer interactions for very large and complex systems. The utility of the iterative indirect method is demonstrated for several examples which include spherical and spheroidal particles. Copyright 2001 Academic Press.

Journal Article↗

Construction of first-generation lactococcal integrative cloning vectors.

Using a randomly-cloned, HindIII-digested, chromosomal fragment from Lactococcus lactis subsp. lactis LM0230, first-generation lactococcal integrative cloning vectors were developed. Through dideoxy DNA sequence analysis, the cloned chromosomal DNA fragment was determined to be 1026 base pairs. Southern hybridization studies demonstrated applicability of the integrative vector to other strains of L. lactis and L. lactis subsp. cremoris. Identification of a single NruI site near the middle of the chromosomal fragment allowed insertion of the erythromycin (Em)-resistance (eryr) gene obtained from L. lactis IL1837. Integration of the eryr gene into the L. lactis LM0230 chromosome was achieved by a Campbell-like recombination. The nisin (Nis)-resistance (nisr) gene from L. lactis IL1904 was inserted into the NruI site in a separate clone and integration into the L. lactis LM0230 chromosome was achieved via a replacement recombination event following electroporation of the linearized nisr fragment flanked by the cloned chromosomal DNA. Transformants grown in the absence of either Em or Nis for > 200 generations and subsequently transferred to various concentrations of the selectable agent confirmed the stability of the integrated genes. Further studies involving the Nis-resistant (NisR) transformant suggested that the integrated nisr gene may be amplifying within the host chromosome.

Base Sequence↗

Chromosomal integration sites of human papillomavirus DNA in three cervical cancer cell lines mapped by in situ hybridization.

Metaphase chromosomes of three cervical cancer cell lines (HeLa, CasKi, SiHa) were subjected to in situ hybridizations with the DNA of human papillomaviruses (HPV) types 16 and 18, respectively. Previous studies have demonstrated multiple copies of HPV 18 DNA in HeLa and of HPV 16 DNA in CasKi cells, but only 1-2 HPV 16 copies in cells of the SiHa line. The viral DNA persists in an integrated state (Schwarz et al 1985). Analysis of the integration sites revealed at least 11 chromosomal sites of HPV 16 integration in CasKi cells. SiHa cells contain integrated HPV 16 DNA in the region q21-q31 of chromosome No. 13. In HeLa cells integration of HPV 18 occurred in chromosome No. 8, band q24. Thus, no evidence was obtained for the existence of preferential chromosomal regions for HPV integration. The data indirectly support a trans-acting function of HPV-mediated cell transformation.

Cell Line↗

Fragments of plastid DNA in the nuclear genome of tomato: prevalence, chromosomal location, and possible mechanism of integration.

We have undertaken a systematic search for plastid DNA sequences integrated in the tomato nuclear genome, using heterologous probes taken from intervals of a plastid DNA region spanning 58 kb. A total of two short integrates (202 and 141 nucleotides) were isolated and mapped to chromosomes 9 and 5, respectively. The nucleotide sequence of the integrates and that of the flanking regions were determined. The integration sites contain direct repeat elements similar in position (but not in length or sequence) to the direct repeats previously observed with another plastid integrate in the tomato nuclear genome. Based on these results, a model for the process of movement and integration of plastid sequences into the nuclear genome is discussed.

Amino Acid Sequence↗