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Fascial and muscular abnormalities in women with urethral hypermobility and anterior vaginal wall prolapse.

OBJECTIVE: Our purpose was to assess the structural integrity of individual elements of the urethral and anterior vaginal wall support system. STUDY DESIGN: Notes were made during retropubic operations for cystourethrocele and stress incontinence in 71 women aged 52 +/- 12.4 (SD) years. Vaginal support was assessed with the Baden-Walker system with the following average findings: urethra 1.9 +/- 0.6, bladder 1.9 +/- 1.0, apex 0.8 +/- 1.1, upper posterior wall 0.3 +/- 0.8, and rectocele 1.1 +/- 0.7. The presence of the following features was noted: paravaginal defect, integrity of the pubic and ischial attachments of the arcus tendineus fascia pelvis (ATFP), appearance of the ATFP on the sidewall, and abnormalities in the pubococcygeal muscle. RESULTS: Paravaginal defects were present in 87.3% on the left and in 88.7% on the right. Detachment of the ATFP from the pubic bone was present in 1.4% (left) and 2.8% (right). The ATFP was detached from the ischial spine in 97.6% (left) and 95.1% (right). Remnants of the ATFP were present on the sidewall in 62% (left) and 63% (right). Of these, 9% extended one fourth the distance to the spine, 21% one half the distance, 3% three fourths the distance, and 17% all the way to the spine. The pubococcygeal muscle was visibly normal in 45% (left) and 39% (right). It showed localized atrophy in 22% (left) and 30% (right) and generalized atrophy in 22.5% (left) 30.0% (right). CONCLUSION: The ATFP usually detaches from the ischial spine, but not from the pubis; slightly less than half of these women have visibly abnormal levator ani muscles.

Female↗

Integrity of Lichen Cell Membranes in Relation to Concentration of Airborne Elements

This study dealt with the impact of air pollution on the integrity of cell membranes in the lichen Ramalina duriaei. The lichen was transplanted from a relatively unpolluted site in Israel to more polluted sites, adjacent to a 40-year-old town, for a period of 10 months. The concentrations of K, B, Al, Cr, Fe, Si, Ti, Zn, P, Ba, Cu, Mg, Na, Pb, Ca, Mn, Sr, and S in lichen thalli were compared with injury caused to the cell membranes. The study indicates that electric conductivity reflects adequately cellular injury to lichen thalli transplanted to sites near a motorway, an oil-fueled power plant and a rural community (a kibbutz). The concentrations of S, B, Al, Cr, Fe, Si, Ti, and Zn correlated with injury in cell membranes of R. duriaei retrieved from the biomonitoring sites, whereas the concentration of K in the thalli correlated inversely with the electric conductivity parameter. Leakage of K from lichen thalli as a result of air pollutants is suggested. This K leakage correlates positively with concentrations of S and Cr in transplants of R. duriaei to the Ashdod region.

Journal Article↗

Tn 10 transposition in vivo: temporal separation of cleavages at the two transposon ends and roles of terminal basepairs subsequent to interaction of ends.

During Tn10 transposition, the transposon is fully excised from the donor site by double strand cleavages at the two ends of the element prior to integration at a new target site. Results presented here demonstrate that an interaction between the two transposon ends is required for double strand cleavage at either end. Furthermore, despite this essential interaction of ends, subsequent cleavages at the two ends can occur at observably distinct times prior to occurrence of strand transfer at either end. Moreover, the time between cleavages at the two ends is exaggerated by the presence of an appropriate mutation at one end of the element. Biological rationales for this constellation of mechanistic features are suggested. Additional results demonstrate that mutations at the three terminal basepairs of Tn10 confer defects subsequent to interaction of ends, in confirmation of inferences from genetic analysis. More specifically, mutations in bp 1-3 confer strong defects during conversion of the full excision intermediate to a complete strand transfer product; mutations in bp 1 and 2 also confer more subtle defects subsequent to interaction of ends but prior to full excision. Such defects might reflect roles for these basepairs in the chemical steps of transposition per se, the positioning of terminal residues for those chemical steps, and/or the coupling of cleavage(s) to subsequent conformational changes.

DNA Mutational Analysis↗

Analysis of the 5' junctions of R2 insertions with the 28S gene: implications for non-LTR retrotransposition.

R2 elements are non-long terminal repeat retrotransposable elements that insert into 28S rRNA genes of most insect species. The single open reading frame of R2 encodes a protein with both endonuclease activity, which cleaves the target site, and reverse transcriptase activity, which uses this cleavage to prime reverse transcription. This target-primed reverse transcription mechanism is also used by group II introns. Little is known of the mechanism by which the 5' end of R2 is integrated after reverse transcription. We have determined the 5' junction sequence of 94 R2 elements from 14 different species of Drosophila. Only 37% of the full-length elements contained precise 5' junctions; the remainder contained deletions of the 28S gene and/or insertions of additional sequences. Because the 5' junctions of truncated copies were similar to full-length elements, no sequences at the 5' end of R2 appear to be required for element integration. A model in which the R2 reverse transcriptase is capable of switching templates from the R2 RNA transcript to the upstream 28S gene can best explain the observed 5' junction sequences. This template jumping is analogous to the template switching of retroviral reverse transcriptases during formation of the double-stranded integration products.

Animals↗

Alternative splicing of pre-mRNA: developmental consequences and mechanisms of regulation.

Alternative splicing of pre-mRNAs is a powerful and versatile regulatory mechanism that can effect quantitative control of gene expression and functional diversification of proteins. It contributes to major developmental decisions and also to fine tuning of gene function. Genetic and biochemical approaches have identified cis-acting regulatory elements and trans-acting factors that control alternative splicing of specific pre-mRNAs. Both approaches are contributing to an understanding of their mode of action. Some alternative splicing decisions are controlled by specific factors whose expression is highly restricted during development, but others may be controlled by more modest variations in the levels of general factors acting cooperatively or antagonistically. Certain factors play active roles in both constitutive splicing and regulation of alternative splicing. Cooperative and antagonistic effects integrated at regulatory elements are likely to be important for specificity and for finely tuned differences in cell-type-specific alternative splicing patterns.

Alternative Splicing↗

Conjugative transfer of the Lactococcus lactis chromosomal sex factor promotes dissemination of the Ll.LtrB group II intron.

The Ll.LtrB group II intron from the low-G+C gram-positive bacterium Lactococcus lactis was the first bacterial group II intron shown to splice and mobilize in vivo. This retroelement interrupts the relaxase gene (ltrB) of three L. lactis conjugative elements: plasmids pRS01 and pAH90 and the chromosomal sex factor. Conjugative transfer of a plasmid harboring a segment of the pRS01 conjugative plasmid including the Ll.LtrB intron allows dissemination of Ll.LtrB among L. lactis strains and lateral transfer of this retroelement from L. lactis to Enterococcus faecalis. Here we report the dissemination of the Ll.LtrB group II intron among L. lactis strains following conjugative transfer of the native chromosomally embedded L. lactis sex factor. We demonstrated that Ll.LtrB dissemination is highly variable and often more efficient from this integrative and conjugative element than from an engineered conjugative plasmid. Cotransfer among L. lactis strains of both Ll.LtrB-containing elements, the conjugative plasmid and the sex factor, was detected and shown to be synergistic. Moreover, following their concurrent transfer, both mobilizable elements supported the spread of their respective copies of the Ll.LtrB intron. Our findings explain the unusually high efficiency of Ll.LtrB mobility observed following conjugation of intron-containing plasmids.

Chromosomes, Bacterial↗

Narrative means to humanistic ends.

BACKGROUND: Efforts to "rehumanize" medical education through curriculum reform and program development have been numerous and ongoing in recent years. One particularly intriguing contribution has come from the area of narrative studies. It is now common to use literature in general, and physician--patient narratives in particular, both to expand students' understanding of the clinical encounter and to sensitize them to the humanistic aspects of medicine. DESCRIPTION: In this article, we describe the process by which we have introduced key insights from and elements of narrative theory into our 1st-year clinical skills program. Rather than limiting our efforts to the use of literature and to the description of individual narrative encounters, however, we have framed our entire course as an exercise in narrative construction. We refer to this process as "narrative structuring." EVALUATION: A combination of short essays on topics related to the various literary materials utilized in the course, written reports on ethical aspects of the clinical cases presented in the clinical skills sessions, and student journaling are integral components of the evaluation of this course. CONCLUSION: Characterizing our course in terms of narrative structuring serves both to integrate the various elements of our complex curriculum around a common theme and to remind both students and faculty alike of the privileges and responsibilities we share as we participate in the writing of one another's stories.

Altruism↗

Rapid musculoskeletal magnetic resonance imaging using integrated parallel acquisition techniques (IPAT)--initial experiences.

PURPOSE: To investigate the feasibility of using multiple receiver coil elements for time saving integrated parallel imaging techniques (iPAT) in traumatic musculoskeletal disorders. MATERIAL AND METHODS: 6 patients with traumatic derangements of the knee, ankle and hip underwent MR imaging at 1.5 T. For signal detection of the knee and ankle, we used a 6-channel body array coil that was placed around the joints, for hip imaging two 4-channel body array coils and two elements of the spine array coil were combined for signal detection. All patients were investigated with a standard imaging protocol that mainly consisted of different turbo spin-echo sequences (PD-, T (2)-weighted TSE with and without fat suppression, STIR). All sequences were repeated with an integrated parallel acquisition technique (iPAT) using a modified sensitivity encoding (mSENSE) technique with an acceleration factor of 2. Overall image quality was subjectively assessed using a five-point scale as well as the ability for detection of pathologic findings. RESULTS: Regarding overall image quality, there were no significant differences between standard imaging and imaging using mSENSE. All pathologies (occult fracture, meniscal tear, torn and interpositioned Hoffa's cleft, cartilage damage) were detected by both techniques. iPAT led to a 48 % reduction of acquisition time compared with standard technique. Additionally, time savings with iPAT led to a decrease of pain-induced motion artifacts in two cases. CONCLUSION: In times of increasing cost pressure, iPAT using multiple coil elements seems to be an efficient and economic tool for fast musculoskeletal imaging with diagnostic performance comparable to conventional techniques.

Adolescent↗

Retron for the 67-base multicopy single-stranded DNA from Escherichia coli: a potential transposable element encoding both reverse transcriptase and Dam methylase functions.

The region (retron-Ec67) required for the biosynthesis of a branched-RNA-linked multicopy single-stranded DNA (msDNA-Ec67) from a clinical isolate of Escherichia coli was mapped at a position equivalent to 19 min on the K-12 chromosome. The element containing the retron consisted of a unique 34-kilobase sequence that was flanked by direct repeats of a 26-base-pair sequence found in the K-12 chromosomal DNA. This suggests that the 34-kilobase element was probably integrated into the E. coli genome by a mechanism related to transposition or phage integration. In the 34-kilobase sequence an open reading frame of 285 residues was found, which displays 44% sequence identity with the E. coli Dam methylase. Interestingly, there are three GATC sequences, the site of Dam methylation, in the promoter region of the gene for reverse transcriptase.

Amino Acid Sequence↗

Structural comparison of three types of staphylococcal cassette chromosome mec integrated in the chromosome in methicillin-resistant Staphylococcus aureus.

The beta-lactam resistance gene mecA of Staphylococcus aureus is carried by a novel mobile genetic element, designated staphylococcal cassette chromosome mec (SCCmec), identified in the chromosome of a Japanese methicillin-resistant S. aureus (MRSA) strain. We now report identification of two additional types of mecA-carrying genetic elements found in the MRSA strains isolated in other countries of the world. There were substantial differences in the size and nucleotide sequences between the elements and the SCCmec. However, new elements shared the chromosomal integration site with the SCCmec. Structural analysis of the new elements revealed that they possessed all of the salient features of the SCCmec: conserved terminal inverted repeats and direct repeats at the integration junction points, conserved genetic organization around the mecA gene, and the presence of cassette chromosome recombinase (ccr) genes responsible for the movements of SCCmec. The elements, therefore, were considered to comprise the SCCmec family of staphylococcal mobile genetic elements together with the previously identified SCCmec. Among 38 epidemic MRSA strains isolated in 20 countries, 34 were shown to possess one of the three typical SCCmec elements on the chromosome. Our findings indicated that there are at least three distinct MRSA clones in the world with different types of SCCmec in their chromosome.

Amino Acid Sequence↗

[Use of R plasmids for isolating Vibrio cholerae donor strains].

Vibrio cholerae and Vibrio eltor donor strains were obtained using R plasmids RP1ts, pRP19.6, pTH10 and pNS10 which carry IS or Tn elements. Resulting from integration of the plasmids into cholera vibrio chromosome, two types of donors were constructed: those resembling Escherichia coli Hfr's and the strains analogous to F+ or F' donors. The order of some chromosome markers were determined in crosses between the donors obtained and V. cholerae recipient strains.

Chromosome Mapping↗

Glycoprotein contributions to mammary gland and mammary tumor structure and function: roles of adherens junctions, ErbBs and membrane MUCs.

Mammary function is dependent on its three-dimensional organization, which is established and maintained by cell adhesive junctions linked through the membrane to the cell cytoskeleton. These junctions serve not only as structural elements, but also function as initiators and integrators of cell signals. In this review we discuss three types of glycoproteins whose interactions impinge on the function of mammary cell-cell junctions, cadherins, ErbB receptor tyrosine kinases and membrane mucins, as a microcosm of events regulating mammary cell behaviors. Actions of these components are integrated by the critical signaling element beta-catenin. When functioning properly, these glycoproteins, beta-catenin and associated signaling pathways mesh into a highly structured program for development and function of the gland. However, disruption or dysfunction of these glycoproteins or the signaling elements can lead to disorganization of the epithelia and ultimately to neoplasia.

Adherens Junctions↗

Comparing Traditional Motor Speech Practice to Contextualized Speech Practice in Preschoolers With Childhood Apraxia of Speech.

PURPOSE: The aim of this study was to compare retention of real-word targets across practice conditions (contextualized vs. motor-only) within a modified integral stimulation treatment for preschoolers with childhood apraxia of speech (CAS). METHOD: A single-subject experimental design with alternating treatments was used with matched target sets randomly assigned to contextualized practice, motor-only practice, or no treatment. Three preschoolers with CAS completed 18 therapy sessions, each consisting of two 25-min blocks: one contextualized practice and one motor-only practice. Order of practice was randomized each visit. Changes in percent phonemes correct (PPC) and lexical stress accuracy, derived from blinded transcription, were explored with visual analysis and effect sizes (standardized mean difference, d statistic). RESULTS: Meaningful improvements (d > 1) were observed in PPC across words treated in contextualized practice for all three children immediately posttreatment and for two of three children at the 1-month follow-up. Meaningful improvements in the motor-only condition were observed in two of three children immediately posttreatment and at follow-up. No meaningful changes were observed in lexical stress across any conditions in any participant. CONCLUSIONS: This study provides preliminary support for the feasibility of a modified integral stimulation therapy that incorporates elements of linguistically grounded therapies (linguistic retrieval, recasts, expansions) that may facilitate target retention in some preschoolers with CAS. However, other elements should be explored in conjunction with integral stimulation to maximize clinical outcomes. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.33228981.

Humans↗

Characterization of the class 3 integron and the site-specific recombination system it determines.

Integrons capture gene cassettes by using a site-specific recombination mechanism. As only one class of integron and integron-determined site-specific recombination system has been studied in detail, the properties of a second class, the only known class 3 integron, were examined. The configuration of the three potentially definitive features of integrons, the intI3 gene, the adjacent attI3 recombination site, and the P(c) promoter that directs transcription of the cassettes, was similar to that found in the corresponding region (5' conserved segment) of class 1 integrons. The integron features are flanked by a copy of the terminal inverted repeat, IRi, from class 1 integrons on one side and a resolvase-encoding tniR gene on the other, suggesting that they are part of a transposable element related to Tn402 but with the integron module in the opposite orientation. The IntI3 integrase was active and able to recognize and recombine both known types of IntI-specific recombination sites, the attI3 site in the integron, and different cassette-associated 59-be (59-base element) sites. Both integration of circularized cassettes into the attI3 site and excision of integrated cassettes were also catalyzed by IntI3. The attI3 site was localized to a short region adjacent to the intI3 gene. Recombination between a 59-be and secondary sites was also catalyzed by IntI3, but at frequencies significantly lower than observed with IntI1, the class 1 integron integrase.

Attachment Sites, Microbiological↗

Gene islands integrated into tRNA(Gly) genes confer genome diversity on a Pseudomonas aeruginosa clone.

Intraclonal genome diversity of Pseudomonas aeruginosa was studied in one of the most diverse mosaic regions of the P. aeruginosa chromosome. The ca. 110-kb large hypervariable region located near the lipH gene in two members of the predominant P. aeruginosa clone C, strain C and strain SG17M, was sequenced. In both strains the region consists of an individual strain-specific gene island of 111 (strain C) or 106 (SG17M) open reading frames (ORFs) and of a 7-kb stretch of clone C-specific sequence of 9 ORFs. The gene islands are integrated into conserved tRNA(Gly) genes and have a bipartite structure. The first part adjacent to the tRNA gene consists of strain-specific ORFs encoding metabolic functions and transporters, the majority of which have homologs of known function in other eubacteria, such as hemophores, cytochrome c biosynthesis, or mercury resistance. The second part is made up mostly of ORFs of yet-unknown function. Forty-seven of these ORFs are mutual homologs with a pairwise amino acid sequence identity of 35 to 88% and are arranged in the same order in the two gene islands. We hypothesize that this novel type of gene island derives from mobile elements which, upon integration, endow the recipient with strain-specific metabolic properties, thus possibly conferring on it a selective advantage in its specific habitat.

Bacterial Proteins↗

Determination of the entire sequence of turtle CR1: the first open reading frame of the turtle CR1 element encodes a protein with a novel zinc finger motif.

CR1 elements are a family of retroposons. They are classified as long interspersed elements (LINEs) or non-long-terminal-repeat (non-LTR) retrotransposons, and they have been found in the genomes of many vertebrates. However, they have been only partially characterized, and only a 2-kb region of the 3' end of chicken CR1 has been sequenced. In the present study, we determined the entire consensus sequence of CR1 elements in the turtle genome, designated PsCR1. The first open reading frame (ORF1) of PsCR1 has two unusual arrangements of Cys residues. One of them includes a zinc finger motif, CX2CX14CX2C. The putative zinc finger has cysteine residues with identical spacing and a similar amino acid composition to those found in the species-specific transcription initiation factors SL1 and TIF-IB. The 5' untranslated region (5' UTR) of PsCR1 contains a sequence similar to part of the human L1 promoter, L1 site A, and several cis elements of the type found in eukaryotic genes. Within a region of about 500 bp, there are nine "E boxes," cis elements that are recognized by the basic helix-loop-helix (bHLH) family of proteins. This observation raises the possibility that cellular transcription factors that bind to these sequences might act in concert to regulate the expression of PsCR1. The extent of the sequence divergence of the 3' UTR of CR1 between species was found to be lower than the rate of nonsynonymous substitutions per site in ORF2, suggesting that a strict functional constraint must exist for this region. This result strongly suggests that the conserved 3'-end sequence of CR1 is the recognition site for the reverse transcriptase of CR1. A discussion is presented of a possible mechanism for the integration of CR1 elements and also of the intriguing possible recruitment of the reverse transcriptase for the retroposition of SINEs.

Amino Acid Sequence↗

Twelve-month outcomes of trauma-informed interventions for women with co-occurring disorders.

OBJECTIVE: Women with co-occurring mental health and substance use disorders frequently have a history of interpersonal violence, and past research has suggested that they are not served effectively by the current service system. The goal of the Women, Co-occurring Disorders, and Violence Study was to develop and test the effectiveness of new service approaches specifically designed for these women. METHODS: A quasi-experimental treatment outcome study was conducted from 2001 to 2003 at nine sites. Although intervention specifics such as treatment length and modality varied across sites, each site used a comprehensive, integrated, trauma-informed, and consumer-involved approach to treatment. Substance use problem severity, mental health symptoms, and trauma symptoms were measured at baseline, and follow-up data were analyzed with prospective meta-analysis and hierarchical linear modeling. RESULTS: A total of 2,026 women had data at the 12-month follow-up: 1,018 in the intervention group and 1,008 in the usual-care group. For substance use outcomes, no effect was found. The meta-analysis demonstrated small but statistically significant overall improvement in women's trauma and mental health symptoms in the intervention relative to the usual-care comparison condition. Analysis of key program elements demonstrated that integrating substance abuse, mental health, and trauma-related issues into counseling yielded greater improvement, whereas the delivery of numerous core services yielded less improvement relative to the comparison group. A few person-level characteristics were associated with increases or decreases in the intervention effect. These neither moderated nor supplanted the effects of integrated counseling. CONCLUSIONS: Outcomes for women with co-occurring disorders and a history of violence and trauma may improve with integrated treatment.

Adult↗

The association between clinical integration of care and transfer of veterans with acute coronary syndromes from primary care VHA hospitals.

BACKGROUND: Few studies report on the effect of organizational factors facilitating transfer between primary and tertiary care hospitals either within an integrated health care system or outside it. In this paper, we report on the relationship between degree of clinical integration of cardiology services and transfer rates of acute coronary syndrome (ACS) patients from primary to tertiary hospitals within and outside the Veterans Health Administration (VHA) system. METHODS: Prospective cohort study. Transfer rates were obtained for all patients with ACS diagnoses admitted to 12 primary VHA hospitals between 1998 and 1999. Binary variables measuring clinical integration were constructed for each primary VHA hospital reflecting: presence of on-site VHA cardiologist; referral coordinator at the associated tertiary VHA hospital; and/or referral coordinator at the primary VHA hospital. We assessed the association between the integration variables and overall transfer from primary to tertiary hospitals, using random effects logistic regression, controlling for clustering at two levels and adjusting for patient characteristics. RESULTS: Three of twelve hospitals had a VHA cardiologist on site, six had a referral coordinator at the tertiary VHA hospital, and four had a referral coordinator at the primary hospital. Presence of a VHA staff cardiologist on site and a referral coordinator at the tertiary VHA hospital decreased the likelihood of any transfer (OR 0.45, 95% CI 0.27-0.77, and 0.46, p = 0.002, CI 0.27-0.78). Conversely, having a referral coordinator at the primary VHA hospital increased the likelihood of transfer (OR 6.28, CI 2.92-13.48). CONCLUSIONS: Elements of clinical integration are associated with transfer, an important process in the care of ACS patients. In promoting optimal patient care, clinical integration factors should be considered in addition to patient characteristics.

Acute Disease↗