62 research outputs found

    Behavioral Problems In The Utilization Of New Technology To Control Caries: Patients And Provider Readiness And Motivation

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    New research developments frequently are neither adopted by providers nor utilized by patients. This dual problem of impacting the behaviors of providers and patients presents a challenge. This paper will present behavioral theories and technologies that can be utilized to impact both provider and patient behaviors

    Protein-Protein Fusion Catalyzed by Sortase A

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    Chimeric proteins boast widespread use in areas ranging from cell biology to drug delivery. Post-translational protein fusion using the bacterial transpeptidase sortase A provides an attractive alternative when traditional gene fusion fails. We describe use of this enzyme for in vitro protein ligation and report the successful fusion of 10 pairs of protein domains with preserved functionality β€” demonstrating the robust and facile nature of this reaction

    Direct Heme Transfer Reactions in the Group A Streptococcus Heme Acquisition Pathway

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    The heme acquisition machinery in Group A Streptococcus (GAS) consists of the surface proteins Shr and Shp and ATP-binding cassette transporter HtsABC. Shp cannot directly acquire heme from methemoglobin (metHb) but directly transfers its heme to HtsA. It has not been previously determined whether Shr directly relays heme from metHb to Shp. Thus, the complete pathway for heme acquisition from metHb by the GAS heme acquisition machinery has remained unclear. In this study, the metHb-to-Shr and Shr-to-Shp heme transfer reactions were characterized by spectroscopy, kinetics and protein-protein interaction analyses. Heme is efficiently transferred from the Ξ² and Ξ± subunits of metHb to Shr with rates that are 7 and 60 times greater than those of the passive heme release from metHb, indicating that Shr directly acquires heme from metHb. The rapid heme transfer from Shr to Shp involves an initial heme donor/acceptor complex and a spectrally and kinetically detectable transfer intermediate, implying that heme is directly channeled from Shr to Shp. The present results show that Shr speeds up heme transfer from metHb to Shp, whereas Shp speeds up heme transfer from Shr to HtsA. Furthermore, the findings demonstrate that Shr can interact with metHb and Shp but not HtsA. Taken together with our published results on the Shp/HtsA reaction, these findings establish a model of the heme acquisition pathway in GAS in which Shr directly extracts heme from metHb and Shp relays it from Shr to HtsA

    Systematic Evaluation of the Teaching Qualities of Obstetrics and Gynecology Faculty: Reliability and Validity of the SETQ Tools

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    BACKGROUND: The importance of effective clinical teaching for the quality of future patient care is globally understood. Due to recent changes in graduate medical education, new tools are needed to provide faculty with reliable and individualized feedback on their teaching qualities. This study validates two instruments underlying the System for Evaluation of Teaching Qualities (SETQ) aimed at measuring and improving the teaching qualities of obstetrics and gynecology faculty. METHODS AND FINDINGS: This cross-sectional multi-center questionnaire study was set in seven general teaching hospitals and two academic medical centers in the Netherlands. Seventy-seven residents and 114 faculty were invited to complete the SETQ instruments in the duration of one month from September 2008 to September 2009. To assess reliability and validity of the instruments, we used exploratory factor analysis, inter-item correlation, reliability coefficient alpha and inter-scale correlations. We also compared composite scales from factor analysis to global ratings. Finally, the number of residents' evaluations needed per faculty for reliable assessments was calculated. A total of 613 evaluations were completed by 66 residents (85.7% response rate). 99 faculty (86.8% response rate) participated in self-evaluation. Factor analysis yielded five scales with high reliability (Cronbach's alpha for residents' and faculty): learning climate (0.86 and 0.75), professional attitude (0.89 and 0.81), communication of learning goals (0.89 and 0.82), evaluation of residents (0.87 and 0.79) and feedback (0.87 and 0.86). Item-total, inter-scale and scale-global rating correlation coefficients were significant (P<0.01). Four to six residents' evaluations are needed per faculty (reliability coefficient 0.60-0.80). CONCLUSIONS: Both SETQ instruments were found reliable and valid for evaluating teaching qualities of obstetrics and gynecology faculty. Future research should examine improvement of teaching qualities when using SETQ

    Differential Function of Lip Residues in the Mechanism and Biology of an Anthrax Hemophore

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    To replicate in mammalian hosts, bacterial pathogens must acquire iron. The majority of iron is coordinated to the protoporphyrin ring of heme, which is further bound to hemoglobin. Pathogenic bacteria utilize secreted hemophores to acquire heme from heme sources such as hemoglobin. Bacillus anthracis, the causative agent of anthrax disease, secretes two hemophores, IsdX1 and IsdX2, to acquire heme from host hemoglobin and enhance bacterial replication in iron-starved environments. Both proteins contain NEAr-iron Transporter (NEAT) domains, a conserved protein module that functions in heme acquisition in Gram-positive pathogens. Here, we report the structure of IsdX1, the first of a Gram-positive hemophore, with and without bound heme. Overall, IsdX1 forms an immunoglobin-like fold that contains, similar to other NEAT proteins, a 310-helix near the heme-binding site. Because the mechanistic function of this helix in NEAT proteins is not yet defined, we focused on the contribution of this region to hemophore and NEAT protein activity, both biochemically and biologically in cultured cells. Site-directed mutagenesis of amino acids in and adjacent to the helix identified residues important for heme and hemoglobin association, with some mutations affecting both properties and other mutations affecting only heme stabilization. IsdX1 with mutations that reduced the ability to associate with hemoglobin and bind heme failed to restore the growth of a hemophore-deficient strain of B. anthracis on hemoglobin as the sole iron source. These data indicate that not only is the 310-helix important for NEAT protein biology, but also that the processes of hemoglobin and heme binding can be both separate as well as coupled, the latter function being necessary for maximal heme-scavenging activity. These studies enhance our understanding of NEAT domain and hemophore function and set the stage for structure-based inhibitor design to block NEAT domain interaction with upstream ligands

    Effectiveness of Motivational Interviewing in improving lipid level in patients with dyslipidemia assisted by general practitioners: Dislip-EM study protocol

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    <p>Abstract</p> <p>Background</p> <p>The non-pharmacological approach to cholesterol control in patients with hyperlipidemia is based on the promotion of a healthy diet and physical activity. Thus, to help patients change their habits, it is essential to identify the most effective approach. Many efforts have been devoted to explain changes in or adherence to specific health behaviors. Such efforts have resulted in the development of theories that have been applied in prevention campaigns, and that include brief advice and counseling services. Within this context, Motivational Interviewing has proven to be effective in changing health behaviors in specific cases. However, more robust evidence is needed on the effectiveness of Motivational Interviewing in treating chronic pathologies -such as dyslipidemia- in patients assisted by general practitioners. This article describes a protocol to assess the effectiveness of MI as compared with general practice (brief advice), with the aim of improving lipid level control in patients with dyslipidemia assisted by a general practitioner.</p> <p>Methods/Design</p> <p>An open, two-arm parallel, multicentre, cluster, controlled, randomized, clinical trial will be performed. A total of 48-50 general practitioners from 35 public primary care centers in Spain will be randomized and will recruit 436 patients with dyslipidemia. They will perform an intervention based either on Motivational Interviewing or on the usual brief advice. After an initial assessment, follow-ups will be performed at 2, 4, 8 and 12 months. Primary outcomes are lipid levels (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides) and cardiovascular risk. The study will assess the degree of dietary and physical activity improvement, weight loss in overweight patients, and adherence to treatment guidelines.</p> <p>Discussion</p> <p>Motivational interview skills constitute the primary strategies GPs use to treat their patients. Having economical, simple, effective and applicable techniques is essential for primary care professionals to help their patients change their lifestyle and improve their health. This study will provide scientific evidence on the effectiveness of Motivational interviewing, and will be performed under strict control over the data collected, ensuring the maintenance of therapeutic integrity.</p> <p>Trials Registration</p> <p>ClinicalTrials.gov (<a href="http://www.clinicaltrials.gov/ct2/show/NCT01282190">NCT01282190</a>).</p

    Does accreditation stimulate change? A study of the impact of the accreditation process on Canadian healthcare organizations

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    <p>Abstract</p> <p>Background</p> <p>One way to improve quality and safety in healthcare organizations (HCOs) is through accreditation. Accreditation is a rigorous external evaluation process that comprises self-assessment against a given set of standards, an on-site survey followed by a report with or without recommendations, and the award or refusal of accreditation status. This study evaluates how the accreditation process helps introduce organizational changes that enhance the quality and safety of care.</p> <p>Methods</p> <p>We used an embedded multiple case study design to explore organizational characteristics and identify changes linked to the accreditation process. We employed a theoretical framework to analyze various elements and for each case, we interviewed top managers, conducted focus groups with staff directly involved in the accreditation process, and analyzed self-assessment reports, accreditation reports and other case-related documents.</p> <p>Results</p> <p>The context in which accreditation took place, including the organizational context, influenced the type of change dynamics that occurred in HCOs. Furthermore, while accreditation itself was not necessarily the element that initiated change, the accreditation process was a highly effective tool for (i) accelerating integration and stimulating a spirit of cooperation in newly merged HCOs; (ii) helping to introduce continuous quality improvement programs to newly accredited or not-yet-accredited organizations; (iii) creating new leadership for quality improvement initiatives; (iv) increasing social capital by giving staff the opportunity to develop relationships; and (v) fostering links between HCOs and other stakeholders. The study also found that HCOs' motivation to introduce accreditation-related changes dwindled over time.</p> <p>Conclusions</p> <p>We conclude that the accreditation process is an effective leitmotiv for the introduction of change but is nonetheless subject to a learning cycle and a learning curve. Institutions invest greatly to conform to the first accreditation visit and reap the greatest benefits in the next three accreditation cycles (3 to 10 years after initial accreditation). After 10 years, however, institutions begin to find accreditation less challenging. To maximize the benefits of the accreditation process, HCOs and accrediting bodies must seek ways to take full advantage of each stage of the accreditation process over time.</p

    Gut Microbiota, Probiotics and Diabetes

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    Diabetes is a condition of multifactorial origin, involving several molecular mechanisms related to the intestinal microbiota for its development. In type 2 diabetes, receptor activation and recognition by microorganisms from the intestinal lumen may trigger inflammatory responses, inducing the phosphorylation of serine residues in insulin receptor substrate-1, reducing insulin sensitivity. In type 1 diabetes, the lowered expression of adhesion proteins within the intestinal epithelium favours a greater immune response that may result in destruction of pancreatic Ξ² cells by CD8+ T-lymphocytes, and increased expression of interleukin-17, related to autoimmunity. Research in animal models and humans has hypothesized whether the administration of probiotics may improve the prognosis of diabetes through modulation of gut microbiota. We have shown in this review that a large body of evidence suggests probiotics reduce the inflammatory response and oxidative stress, as well as increase the expression of adhesion proteins within the intestinal epithelium, reducing intestinal permeability. Such effects increase insulin sensitivity and reduce autoimmune response. However, further investigations are required to clarify whether the administration of probiotics can be efficiently used for the prevention and management of diabetes

    Sequencing and Comparative Genome Analysis of Two Pathogenic Streptococcus gallolyticus Subspecies: Genome Plasticity, Adaptation and Virulence

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    Streptococcus gallolyticus infections in humans are often associated with bacteremia, infective endocarditis and colon cancers. The disease manifestations are different depending on the subspecies of S. gallolyticus causing the infection. Here, we present the complete genomes of S. gallolyticus ATCC 43143 (biotype I) and S. pasteurianus ATCC 43144 (biotype II.2). The genomic differences between the two biotypes were characterized with comparative genomic analyses. The chromosome of ATCC 43143 and ATCC 43144 are 2,36 and 2,10 Mb in length and encode 2246 and 1869 CDS respectively. The organization and genomic contents of both genomes were most similar to the recently published S. gallolyticus UCN34, where 2073 (92%) and 1607 (86%) of the ATCC 43143 and ATCC 43144 CDS were conserved in UCN34 respectively. There are around 600 CDS conserved in all Streptococcus genomes, indicating the Streptococcus genus has a small core-genome (constitute around 30% of total CDS) and substantial evolutionary plasticity. We identified eight and five regions of genome plasticity in ATCC 43143 and ATCC 43144 respectively. Within these regions, several proteins were recognized to contribute to the fitness and virulence of each of the two subspecies. We have also predicted putative cell-surface associated proteins that could play a role in adherence to host tissues, leading to persistent infections causing sub-acute and chronic diseases in humans. This study showed evidence that the S. gallolyticus still possesses genes making it suitable in a rumen environment, whereas the ability for S. pasteurianus to live in rumen is reduced. The genome heterogeneity and genetic diversity among the two biotypes, especially membrane and lipoproteins, most likely contribute to the differences in the pathogenesis of the two S. gallolyticus biotypes and the type of disease an infected patient eventually develops
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