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Maintenance of skin integrity as a clinical indicator of nursing care.

OBJECTIVE: To assess maintenance of skin integrity in hospitalized patients as a clinical indicator of quality nursing care. DESIGN: Descriptive correlational study. SETTING: 17 acute care urban and rural hospitals in Texas. PARTICIPANTS: 723 hospitalized patients from 33 medical-surgical units. MAIN OUTCOME MEASURES: Pressure ulcers since admission and nursing care practices per unit. MAIN RESULTS: Overall prevalence of pressure ulcers since admission (4.7%) was lower than previously reported for acute care settings. Prevalence of pressure ulcers in hospitalized patients (10%) was higher than found in the Texas Nurses Association feasibility study (3.7%). The skin integrity ratio was strongly correlated for several unit variables, including number of beds per unit (r = 0.623) and average daily census per unit (r = 0.909). Benchmarking data across units showed that units with subjects that maintained skin integrity had a lower percentage of patients assessed on admission and performed daily assessments less frequently than did the units with subjects that did not maintain skin integrity. In addition, the units with subjects that maintained skin integrity classified fewer patients as at risk for pressure ulcer development and did not implement a skin care protocol for these patients. CONCLUSION: Patients who developed a pressure ulcer after admission were older and had more risk for pressure ulcers than those who maintained skin integrity. Benchmarking data detected various differences in nursing care. Significant relationships between study variables demonstrate the importance of assessing clinical indicators to monitor nursing care. Outcomes such as skin integrity, pressure ulcer since admission, and nosocomial ratio represent the quality of nursing care.

Adolescent↗

Integrated backscatter for the assessment of myocardial viability.

PURPOSE OF REVIEW: Ultrasonic tissue characterization is a non-invasive diagnostic method that uses myocardial integrated backscatter analysis to determine contractile performance and myocardial viability independent of wall motion. This review discusses recent clinical findings regarding the application of ultrasonic tissue characterization for the assessment of myocardial viability. RECENT FINDINGS: As this technique is non-invasive, ultrasonic tissue characterization can be used to predict the patency of infarct-related arteries in patients in the early stage of acute myocardial infarction. Several recent studies have shown that this technique is useful in identifying myocardial contractile reserve. The accuracy of ultrasonic tissue characterization for predicting functional recovery after coronary reperfusion is comparable to dobutamine echocardiography and radionuclide methods. Several studies have suggested that the cyclic variation of myocardial integrated backscatter reflects myocardial viability rather than contractile reserve. The cyclic variation of integrated backscatter is associated with myocardial viability confirmed by the integrity of the microvasculature identified by contrast echocardiography. In addition, the cyclic variation of integrated backscatter better reflects myocardial viability confirmed by the integrity of cellar metabolism than contractile reserve. SUMMARY: Ultrasonic tissue characterization with integrated backscatter is a useful non-invasive method that can provide unique information for the assessment of myocardial viability.

Coronary Stenosis↗

Integration of viral DNA sequences in cells transformed by adenovirus 2 or SV40.

We have cloned and propagated in prokaryotic vectors the viral DNA sequences that are integrated in a variety of cells transformed by adenovirus 2 or SV40. Analysis of the clones reveals that the viral DNA sequences sometimes are arranged in a simple fashion, collinear with the viral genome; in other cell lines there are complex arrangements of viral sequences in which tracts of the viral genome are inverted with respect to each other. In several cases the nucleotide sequences at the joints between cell and viral sequences have been determined: usually there is a sharp transition between cellular and viral DNAs. The viral sequences are integrated at different locations within the genomes of different cell lines; likewise there is no specific site on the viral genomes at which integration occurs. Sometimes the viral sequences are integrated within repetitive cellular DNA, and sometimes within unique sequences. In some cases there is evidence that the viral sequences along with the flanking cell DNA have been amplified after integration. The sequences that flank the viral insertion in the line of SV40-transformed rat cells known as 14B have been used as probes to isolate, from untransformed rat cells, clones that carry the region of the chromosome in which integration occurred. Analysis of the structure of these clones by restriction endonculease digestion and heteroduplex formation shows that a rearrangement of cellular sequences has occurred, presumably as a consequence of integration.

Adenoviruses, Human↗

Simian virus 40 (SV40) large T antigen-dependent amplification of an Epstein-Barr virus-SV40 hybrid shuttle vector integrated into the human HeLa cell genome.

We analysed the DNA rearrangements that occurred during the integration and amplification of an Epstein-Barr virus (EBV)-simian virus 40 (SV40) hybrid shuttle vector in human cells. The human HeLa cell line was episomally transformed with the EBV-SV40 p205-GTI plasmid. After a 2 month culture in a selective medium, a HeLa cell-derived population (H-G1 cells) was obtained in which the p205-GTI vector was integrated as a single intact copy deleted in the EBV latent origin of replication (OriP). Sequencing data showed that the endpoints of the plasmid sequences, at the plasmid-cell DNA junctions, are located within the two essential elements of EBV OriP, which may form several secondary structures. This result suggests that a specific DNA sequence (OriP) or palindromic structures could play a role in this integration process. This represents the first fully characterized site of integration of an EBV vector in human cells. The transient expression of the SV40 large T antigen in H-G1 cells leads to the appearance of episomal molecules with an extremely heterogeneous size pattern. Individual analysis of these episomes after rescue in bacteria indicated that they retained sequences of both the p205-GTI plasmid and cellular DNA. Comparison of the structure of these circular DNAs with those of the integrated p205-GTI copy indicated that large T antigen expression in human cells leads to the amplification of the integrated shuttle vector according to the 'onion skin' model developed for transformed rodent cells. Indeed, amplified sequences were colinear with the integrated p205-GTI copy and its surrounding cellular sequences, distributed almost equally around the SV40 replication origin, and circularized by illegitimate recombination which did not involve specific nucleotide sequences. This system is of interest in that it enables easy recovery of individual recombined molecules in host bacteria. Each isolated clone contains a unique recombination junction which is easily and rapidly characterized and sequenced.

Antigens, Polyomavirus Transforming↗

Homologous integration in mammalian cells without target gene selection.

Homologous integrations into a nonselectable target locus have been highly enriched for following DNA transfections into mammalian cells. The target gene, the SV40 early region in COS1 cells, provides transcription signals to activate a defective selectable marker, the gpt gene. We find that nearly half of the selected clones have integrated the gpt gene at the homologous sequence in the COS1 genome. This is an estimated 100-fold enrichment for homologous events compared with transfections in which the gpt gene is transcriptionally active. As shown for yeast integration events, a double-strand break at a position of homology between the transfected DNA and the genomic target is necessary to achieve a high frequency of homologous integrations. Furthermore, the arrangement of sequences at the integration site includes a repair of the double-strand gap, which was present on the transfected DNA, suggesting that similarities exist between yeast and mammalian integrations. The experimental design, in which a defective marker is activated following a homologous integration, may have general applications for gene targeting in mammalian cells.

Animals↗

Synthesis and integration of avian sarcoma virus DNA.

In this paper, we have presented data regarding the integration of viral DNA and the persistence of unintegrated viral DNA. We know that integration occurs with specificity with respect to the viral genome, and yet it remains to be established which, if any, of the unintegrated DS DNA species-either the linear or the covalently closed circular forms-is the immediate precursor to the DNA that does become integrated. The results of the present studies indicate that the viral DNA species that are able to persist in an unintegrated state may be transcribed to yield new virions. Furthermore, these species may not be intermediates as far as the integration pathway, but may instead be terminal products of a synthesis reaction that has proceeded beyond the point where integration normally occurs. Varmus et al. (1977) have shown that integration occurs only into newly replicated cellular DNA. Therefore, we would speculate that integration may occur by an interaction between a replication fork of the host cell DNA and an earlier, non-double-strand form of viral DNA.

Alpharetrovirus↗

Evaluating the impact of moving from discipline-based to integrated assessment.

BACKGROUND: The move from discipline-based to problem-based learning (PBL) at Adelaide University in 2000 offered exciting opportunities to integrate the teaching and learning of the basic and clinical sciences for medical undergraduates. However, several cohorts of students still needed to progress through the first 3 years of the more traditional curriculum. Paradoxically, their readiness to function in the integrated learning and assessment environment of the last 3 years was assessed in 7 separate discipline-based examinations at the end of third year. When considerable examination-related stress was noted in the 1997 cohort and students petitioned formally for a reduced examination load, it was considered to be time for assessment to lead the way in integrating the disciplines. AIM: After introducing third year integrated written assessments in 1998, we aimed to develop an integrated practical examination (IPE) linking theory to practice, and evaluate its impact on staff and students. METHODS: After extensive staff collaboration, a structured objective multistation IPE was developed and administered in 1999 and 2000. Its utility was evaluated using a model proposed earlier. RESULTS: Assessment validity was maximised by an extensive item review process. Reliability, as measured by Cronbach's alpha, was 0.79 and 0.80 in 1999 and 2000, respectively. An independent evaluation yielded qualitative data on the examination's educational impact, cost and acceptability. CONCLUSIONS: Investing time in changing from discipline-based to integrated assessment, integrating theory and practice, resulted in gains in assessment reliability, validity and educational impact on both staff and students.

Australia↗

In vivo analysis of integration of membrane proteins in Escherichia coli.

The in vivo process of membrane protein integration was studied by pulse-labelling Escherichia coli cells, and assessing integral anchoring of labelled proteins to the lipid bilayer based on their resistance to alkali extraction. To conduct this experiment, conditions for extracting E. coli proteins with alkali were refined, and the immunoprecipitation procedures were improved to allow effective detection of integral membrane proteins. Examination of pulse-labelled, integral membrane proteins, including lactose permease (LacY), SecY, cytochrome omicron subunit II and leader peptidase revealed that all were in the alkali-insoluble fraction, indicating that membrane integration of these proteins takes place rapidly in wild-type cells. However, when LacY was synthesized in excess from a multicopy plasmid, significant proportions were found in the alkali-soluble fraction, indicating that the solubility in alkali is not an intrinsic property of the protein, and suggesting that LacY depends on some limited cellular factor for membrane integration. The unintegrated species of LacY sedimented slowly through an alkaline sucrose gradient. The secY24 mutant cells accumulated higher proportions of unintegrated LacY molecules at lower levels of overproduction than the sec+ cells. LacY overproduction in wild-type cells was found to inhibit processing (export) of beta-lactamase but not of OmpA and OmpF. These results are interpreted to mean that integration of LacY depends on multiple cellular components, one of which is also involved in export of beta-lactamase.

Cell Membrane↗

Social integration and mortality in Australia.

OBJECTIVE: To investigate the relationship between social integration and mortality at the aggregate level of analysis. METHOD: The data were compiled from several Australian Bureau of Statistics documents. The unit of analysis was State (Territory)-year. The multivariate regression analysis included data from all States and the Australian Capital Territory for 1990-96. Five indicators of social integration--percentage of people living alone; divorce rate; unemployment rate; proportion of people who are discouraged job seekers; and unionization rate--were used as predictors of nine measures of mortality. RESULTS: Higher levels of social integration, as measured by all indicators except unionization, were associated with lower mortality rates. In the case of unionization, higher levels were associated with increased mortality rates. CONCLUSION: Studies concerning the relationship between social integration and health should investigate the 'type' and 'level' of social integration that is conducive to better health. IMPLICATIONS: To help reduce disparities in health and mortality across communities, public health researchers and policy makers need to closely monitor geographic and temporal trends in social integration measures. Social policies that emphasise investment in social integration or social capital through job creation and training, provision of gainful employment and social services for discouraged and marginalized workers, improved work conditions and social support may lower mortality directly or through their beneficial effects on health-promoting behaviours such as reduced levels of smoking, drinking and physical inactivity.

Australia↗

Enhancing tissue integration in cartilage repair procedures.

Arguably, the gold standard of biological repair of articular cartilage lesions is autologous chondrocyte transplantation. Although the clinical outcomes appear to range between good and excellent in most cases, there are, nevertheless, both clinical and biological challenges that remain to improve rehabilitation and clinical outcome. One of the major biological problems relates to tissue integration of the reparative tissue into the host tissue at a predictable level. Often within a single lesion, varying degrees of integration can be observed from total integration through to non-integration as one passes through the defect. Here we briefly review some of the literature relating to this problem and include some of our own data drawn from questions we have posed about the biological nature of cartilage/cartilage integration. The nature and status of the tissue that comprises the wound lesion edge is central to tissue integration, and controlling aspects of trauma and free-radical-induced cell death together with matrix synthesis are identified as two components that require further investigation. Interestingly, there appears to be a limited ability of chondrocytes to be able to infiltrate existing cartilage matrices and even to occupy empty chondrocyte lacunae. Proliferation as a result of blunt and sharp trauma shows differential responses. As expected, blunt trauma induces a greater proliferative burst than sharp trauma and is more widespread from the lesion edge. However, in the case of sharp trauma, the basal cells enter proliferation before surface zone chondrocytes, which is not the case in blunt wounds. Regulation of these and associated processes will be necessary in order to devise strategies that can predict successful integration in biological repair procedures.

Cartilage, Articular↗

Violation of the patient's integrity, seen by staff in long-term care.

The aim of the study was to describe the views held by staff (n = 233) in long-term care on what they regard as a violation of patient's integrity and to define the concept "integrity" in simple terms. The design of the investigation was inductive. The answers were coded into 775 items. Agreement was reached between the authors on 770 of the items when sorted into 13 categories: the unique personality, autonomous self, personal opinions, secret self, personal competence, professional self, family self, cultural self, information self, personal properties, private territory, corporal self, and ridiculing. The number of categories shows a great variation in the ordinary language definitions given by staff. It was also shown in two other ways: the difference in the level of abstraction in the items, and the fact that integrity referred to the patient, directly or indirectly. Our conclusion is that integrity by the staff reflects an ethical value and not a personal trait. If the staff have to violate the patient's integrity, because other vital values are involved, it is absolutely essential that they consider the ethical aspects of the situation carefully. Such violation demands that they preserve their respect for the patient to the greatest extent possible. It seems important in the training of different staff groups to show the complexity in the concept "integrity" and the ethical dilemmas that arise, especially in the interaction with vulnerable patients who are not able to protect and maintain their own integrity.

Adult↗

High throughput gene expression profiling: a molecular approach to integrative physiology.

Integrative physiology emphasizes the importance of understanding multiple pathways with overlapping, complementary, or opposing effects and their interactions in the context of intact organisms. The DNA microarray technology, the most commonly used method for high-throughput gene expression profiling, has been touted as an integrative tool that provides insights into regulatory pathways. However, the physiology community has been slow in acceptance of these techniques because of early failure in generating useful data and the lack of a cohesive theoretical framework in which experiments can be analysed. With recent advances in both technology and analysis, we propose a concept of multidimensional integration of physiology that incorporates data generated by DNA microarray and other functional, genomic, and proteomic approaches to achieve a truly integrative understanding of physiology. Analysis of several studies performed in simpler organisms or in mammalian model animals supports the feasibility of such multidimensional integration and demonstrates the power of DNA microarray as an indispensable molecular tool for such integration. Evaluation of DNA microarray techniques indicates that these techniques, despite limitations, have advanced to a point where the question-driven profiling research has become a feasible complement to the conventional, hypothesis-driven research. With a keen sense of homeostasis, global regulation, and quantitative analysis, integrative physiologists are uniquely positioned to apply these techniques to enhance the understanding of complex physiological functions.

Animals↗

Temporal integration, frequency resolution, and off-frequency listening in normal-hearing and cochlear-impaired listeners.

Temporal integration for a 1000-Hz signal was determined for normal-hearing and cochlear hearing-impaired listeners in quiet and in masking noise of variable bandwidth. Critical ratio and 3-dB critical band measures of frequency resolution were derived from the masking data. Temporal integration for the normal-hearing listeners was markedly reduced in narrow-band noise, when contrasted with temporal integration in quiet or in wideband noise. The effect of noise bandwidth on temporal integration was smaller for the hearing-impaired group. Hearing-impaired subjects showed both reduced temporal integration and reduced frequency resolution for the 200-ms signal. However, a direct relation between temporal integration and frequency resolution was not indicated. Frequency resolution for the normal-hearing listeners did not differ from that of the hearing-impaired listeners for the 20-ms signal. It was suggested that some of the frequency resolution and temporal integration differences between normal-hearing and hearing-impaired listeners could be accounted for by off-frequency listening.

Adult↗

Spectro-temporal integration in signal detection.

This paper is concerned with aspects of temporal integration and across-frequency integration in signal detection. Previous experiments on the detection of brief broadband signals (clicks) in continuous broadband noise revealed efficient spectral integration. The extent to which this effect is restricted to a critical time window was investigated by manipulating the temporal relations among the signal components in different frequency regions. In a typical experiment, the signal consists of nine brief Gaussian-shaped tone pulses, equally distributed at 1/3-oct intervals, each with a spectral width of about 1/3 oct, and each equally detectable in white noise. In the synchronized condition (i.e. coinciding peaks of the nine Gaussian envelopes), the detection threshold is reached when the levels of the nine individual tone pulses are about 8 dB below their individual threshold levels (efficient spectral integration). When the signal is progressively desynchronized (i.e. noncoinciding peaks of the Gaussian envelopes), detection threshold is found to increase. This suggests that efficient spectral integration in signal detection is confined to a narrow time window, with a typical value of 30 ms. Similar experiments were performed with respect to the efficiency of temporal integration. For constant-duration signals (100 ms), the detection threshold is found to increase when progressively widening signal bandwidth. The data indicate that the efficient temporal integration in signal detection is confined to a narrow frequency window, which, not surprisingly, corresponds to the critical bandwidth.

Adult↗

Auditory-visual speech recognition by hearing-impaired subjects: consonant recognition, sentence recognition, and auditory-visual integration.

Factors leading to variability in auditory-visual (AV) speech recognition include the subject's ability to extract auditory (A) and visual (V) signal-related cues, the integration of A and V cues, and the use of phonological, syntactic, and semantic context. In this study, measures of A, V, and AV recognition of medial consonants in isolated nonsense syllables and of words in sentences were obtained in a group of 29 hearing-impaired subjects. The test materials were presented in a background of speech-shaped noise at 0-dB signal-to-noise ratio. Most subjects achieved substantial AV benefit for both sets of materials relative to A-alone recognition performance. However, there was considerable variability in AV speech recognition both in terms of the overall recognition score achieved and in the amount of audiovisual gain. To account for this variability, consonant confusions were analyzed in terms of phonetic features to determine the degree of redundancy between A and V sources of information. In addition, a measure of integration ability was derived for each subject using recently developed models of AV integration. The results indicated that (1) AV feature reception was determined primarily by visual place cues and auditory voicing + manner cues, (2) the ability to integrate A and V consonant cues varied significantly across subjects, with better integrators achieving more AV benefit, and (3) significant intra-modality correlations were found between consonant measures and sentence measures, with AV consonant scores accounting for approximately 54% of the variability observed for AV sentence recognition. Integration modeling results suggested that speechreading and AV integration training could be useful for some individuals, potentially providing as much as 26% improvement in AV consonant recognition.

Adult↗

Multicopy integration and expression of heterologous genes in Methylobacterium extorquens ATCC 55366.

High-level expression of chromosomally integrated genes in Methylobacterium extorquens ATCC 55366 was achieved under the control of the strong M. extorquens AM1 methanol dehydrogenase promoter (PmxaF) using the mini-Tn7 transposon system. Stable maintenance and expression of the integrated genes were obtained in the absence of antibiotic selective pressure. Furthermore, using this technology, a multicopy integration protocol for M. extorquens was also developed. Chromosomal integration of one to five copies of the gene encoding the green fluorescent protein (gfp) was achieved. The multicopy-based expression system permitted expression of a preset number of gene copies. A unique specific Tn7 integration locus in the chromosome of M. extorquens, known as the Tn7 attachment site (attTn7 site), was identified. This single attTn7 site was identified in an intergenic region between glmS, which encodes the essential enzyme glucosamine-6-phosphate synthetase, and dhaT, which encodes 1,3-propanediol dehydrogenase. The fact that the integration event is site specific and the fact that the attTn7 site is a noncoding region of the chromosome make the mini-Tn7 transposon system very useful for insertion of target genes and subsequent expression. In all transformants tested, expression and segregation of the transforming gene were stable without generation of secondary mutations in the host. In this paper, we describe single and multicopy chromosome integration and stable expression of heterologous genes (bgl [beta-galactosidase], est [esterase], and gfp [green fluorescent protein]) in M. extorquens.

Alcohol Oxidoreductases↗

Integration and excision of a newly discovered bacteroides conjugative transposon, CTnBST.

Conjugative transposons (CTns) are major contributors to the spread of antibiotic resistance genes among Bacteroides species. CTnBST, a newly discovered Bacteroides conjugative transposon, carries an erythromycin resistance gene, ermB, and previously has been estimated to be about 100 kbp in size. We report here the locations and sequencing of both of its ends. We have also located and sequenced the gene that catalyzes the integration of CTnBST, intBST. The integrase gene encodes a 377-amino-acid protein that has the C-terminal R-K-H-R-H-Y motif that is characteristic of members of the tyrosine recombinase family of integrases. DNA sequence comparisons of the ends of CTnBST, the joined ends of the circular intermediate, and the preferred site into which the circular form of CTnBST had integrated revealed that the preferred integration site (attB1) contained an 18-bp sequence of identity to the crossover region, attBST, on CTnBST. Although this site was used in about one-half of the integration events, sequence analysis of these integration events revealed that both CTnBST and a miniature form of CTnBST (miniBST) integrated into a variety of other sites in the chromosome. All of the sites had two conserved regions, AATCTG and AAAT. These two regions flanked a 2-bp sequence, bp 10 and bp 11 of the 18-bp sequence, that varied in some of the different sites and sometimes in the attBST sequences. Our results suggest that CTnBST integrates site selectively and that the crossover appears to occur within a 12-bp region that contains the two regions of conserved sequences.

Amino Acid Sequence↗

Conditional-replication, integration, excision, and retrieval plasmid-host systems for gene structure-function studies of bacteria.

We have developed a series of powerful and versatile conditional-replication, integration, and modular (CRIM) plasmids. CRIM plasmids can be replicated at medium or high copy numbers in different hosts for making gene (or mutant) libraries. They can be integrated in single copies into the chromosomes of Escherichia coli and related bacteria to study gene function under normal physiological conditions. They can be excised from the chromosome, e.g., to verify that phenotypes are caused by their presence. Furthermore, they can be retrieved singly or en masse for subsequent molecular analyses. CRIM plasmids are integrated into the chromosome by site-specific recombination at one of five different phage attachment sites. Integrants are selected as antibiotic-resistant transformations. Since CRIM plasmids encode different forms of resistance, several can be used together in the same cell for stable expression of complex metabolic or regulatory pathways from diverse sources. Following integration, integrants are stably maintained in the absence of antibiotic selection. Each CRIM plasmid has a polylinker or one of several promoters for ectopic expression of the inserted DNA. Their modular design allows easy construction of new variants with different combinations of features. We also report a series of easily curable, low-copy-number helper plasmids encoding all the requisite Int proteins alone or with the respective Xis protein. These helper plasmids facilitate integration, excision ("curing"), or retrieval of the CRIM plasmids.

Attachment Sites, Microbiological↗