Neutral proteases of human polymorphonuclear granulocytes: putative mediators of pulmonary damage.

Tissue proteolytic enzymes are currently believed to be critical to the pathogenesis of panacinar emphysema. Polymorphonuclear leukocytes (Polys) have several enzymes including elastase and cathepsin G in their azurophil granules. They have collagenase in their specific granules. We have found that this collagenase is doubly latent. It has the lysosomal type of latency that depends on the impermeability of the unit membrane that surrounds each specific granule. In addition it has a latency that is converted to activity by proteolytic enzymes. The cathepsin G of the azurophil granule is a potent activator of this latent collagenase once the collagenase is released from its membrane dependent latency. Thus latency of enzymes, the nature of the latency and accessibility of the latent enzymes to activating mechanisms must all be taken into account in any analysis of their contribution to pathogenesis of local lung disease. Equally important is that fact that polys are not a prominent cellular component of normal lung. Polys must be attracted to the lung by chemotactic peptides. These peptides must be released by the interaction of inflammatory stimuli, such as smoke particles, with complement components or they must be provided by other sources. The hypothesis that lung damage in panacinar emphysema is mediated by polys and their proteases is attractive and suggestive evidence supporting this is available. However, more evidence that takes into full account the cell biology of the proteases any poly turnover in the lung are needed to extend the hypothesis and to form a rational basis for therapeutic and prophylactic measures

Clinical outcomes of all‐ceramic single crowns and fixed dental prostheses supported by ceramic implants: A systematic review and meta‐analyses

Objective: To analyze the clinical outcomes of all-ceramic single crowns (SCs) and fixed dental prostheses (FDPs) supported by ceramic implants. Materials and methods: Based on a focused question and customized PICO framework, electronic (Medline/EMBASE/Cochrane) and manual searches for studies reporting the clinical outcomes of all-ceramic SCs and FDPs supported by ceramic implants ≥12 months were performed. The primary outcomes were reconstruction survival and the chipping proportion. The secondary outcomes were implant survival, technical complications, and patient-related outcome measurements. Meta-analyses were performed after 1, 2, and 5 years using random-effect meta-analyses. Results: Eight of the 1,403 initially screened titles and 55 full texts were included. Five reported on monolithic lithium disilicate (LS2) SCs, one on veneered zirconia SCs, and two on veneered zirconia SCs and FDPs, which reported all on cement-retained reconstructions (mean observation: 12.0-61.0 months). Meta-analyses estimated a 5-year survival rate of 94% (95% confidence interval [CI]: 82%-100%) for overall implant survival. Reconstruction survival proportions after 5 years were: monolithic LS2, 100% (95%CI: 95%-100%); veneered zirconia SCs, 89% (95%CI: 62%-100%); and veneered zirconia FDPs 94% (95%CI: 81%-100%). The chipping proportion after 5 years was: monolithic LS2, 2% (95%CI: 0%-11%); veneered zirconia SCs, 38% (95%CI: 24%-54%); and veneered zirconia FDPs, 57% (95%CI: 38%-76%). Further outcomes were summarized descriptively. Conclusions: Due to the limited data available, only tendencies could be identified. All-ceramic reconstructions supported by ceramic implants demonstrated promising survival rates after mid-term observation. However, high chipping proportions of veneered zirconia SCs and, particularly, FDPs diminished the overall outcome. Monolithic LS2 demonstrated fewer clinical complications. Monolithic reconstructions could be a valid treatment option for ceramic implants. Keywords: ceramics; dental implants; implant-supported dental prosthesis; meta-analysis; survival analysis; systematic review; treatment outcome; zirconia

Reducing Occupational Distress in Veterinary Medicine Personnel with Acceptance and Commitment Training: A Pilot Study

Aims To determine whether an educational programme targeting the reaction of veterinary personnel to difficult client interactions reduced burden transfer, stress and burnout in veterinary staff. Methods Employees of three small-animal veterinary hospitals in the south-western United States of America were recruited and randomised to intervention (educational programme; n = 16) or control (no intervention; n = 18) groups. Participants of this randomised, parallel arms trial completed pre-programme assessment including the Burden Transfer Inventory (BTI), Perceived Stress Scale, and Copenhagen Burnout Inventory. Assessment was followed by two, group-format educational sessions, based on acceptance and commitment training, tailored to reducing reactivity to difficult veterinary client interactions (intervention group only). After training was completed, both groups were assessed using the same measures and the intervention participants provided use and acceptability ratings. Results Intervention participants rated the programme as useful and appropriate, and reported that programme techniques were used a median of 43 (min 9, max 68) times during the 2 weeks prior to retesting. Relative to pre-programme scores, median post-programme scores for reaction (subscore of BTI) to difficult client interactions decreased in the intervention group (33 vs. 54; p = 0.047), but not in the control group (51 vs. 59; p = 0.210). Changes in median scores for stress and burnout from pre- to post-programme were non-significant for both groups. Conclusions This pilot and feasibility trial showed high rates of acceptability and use by participants, as well as promising reductions in burden transfer. A larger scale clinical trial with follow-up at extended time points is needed to more fully examine the efficacy of this novel programme

Risky sexual behaviors and sexually transmitted diseases: a comparison study of cocaine-dependent individuals in treatment versus a community-matched sample

Cocaine users routinely engage in high-risk sexual behaviors that place them at an elevated risk of contracting HIV and other blood-borne infections. The purpose of the present study was to compare trading sex for drugs and/or money, having 10 or more sexual partners in 1 year, and sexually transmitted diseases (STDs) of cocaine-dependent individuals in treatment for their dependence across race and gender and against participants who live in their community. Cocaine-dependent individuals (n = 459) were identified through nine publicly and privately funded inpatient and outpatient chemical dependency treatment centers in the St. Louis area during 2001–2006. Community-based participants (n = 459) were matched to cocaine-dependent participants on age, ethnicity, gender, and zip code of residence. Mean age of the sample was 36 years old, 50% were Caucasians, 50% were African American, and 47% were male. Nearly half of cocaine-dependent participants in treatment had traded sex for drugs and/or money and over one-third had more than 10 sexual partners in 1 year with a risk concentrated among African Americans even after controlling for income and educational attainment. Participants recruited from the community with some exposure to cocaine reported similar rates of high risk sexual behaviors as the cocaine dependent subjects from treatment settings. It is important for clinicians to recognize that once released from treatment, cocaine-dependent individuals may be returning to high-risk environments where sexual risk behaviors are occurring in the context of cocaine use

Nonoxidative antimicrobial effects of human polymorphonuclear leukocyte granule proteins on Chlamydia spp. in vitro.

Proteins from isolated granules of human polymorphonuclear leukocytes were assessed for their nonoxidative microbicidal effect on chlamydiae by two different methods: a radioisotope assay for elementary body integrity and a biological assay for inclusion development. Crude granule extract, which consisted of a mixture of all granule proteins, caused a 20 to 30% decrease in infectivity and a 52% decrease in infectivity when incubated with Chlamydia psittaci CAL-10 and Chlamydia trachomatis serovar E, respectively. To define more specifically the components that were damaging to chlamydiae, crude granule extract was subjected to Sephadex G-75 column chromatography and isolated granule fractions were obtained. Only fractions containing lysozyme as the major component consistently caused reductions in infectivity of C. trachomatis elementary bodies. In contrast, fractions collected after the lysozyme fraction, containing proteins with molecular masses of 13,000 daltons or less, had detrimental effects on C. psittaci infectivity. Additional experiments using highly purified human polymorphonuclear leukocyte lysozyme confirmed its infectivity-reducing action upon C. trachomatis but not upon C. psittaci

A unifying perspective on protocol mediation: interoperability in the Future Internet

Given the highly dynamic and extremely heterogeneous software systems composing the Future Internet, automatically achieving interoperability between software components —without modifying them— is more than simply desirable, it is quickly becoming a necessity. Although much work has been carried out on interoperability, existing solutions have not fully succeeded in keeping pace with the increasing complexity and heterogeneity of modern software, and meeting the demands of runtime support. On the one hand, solutions at the application layer target higher automation and loose coupling through the synthesis of intermediary entities, mediators, to compensate for the differences between the interfaces of components and coordinate their behaviours, while assuming the use of the same middleware solution. On the other hand, solutions to interoperability across heterogeneous middleware technologies do not reconcile the differences between components at the application layer. In this paper we propose a unified approach for achieving interoperability between heterogeneous software components with compatible functionalities across the application and middleware layers. First, we provide a solution to automatically generate cross-layer parsers and composers that abstract network messages into a uniform representation independent of the middleware used. Second, these generated parsers and composers are integrated within a mediation framework to support the deployment of the mediators synthesised at the application layer. More specifically, the generated parser analyses the network messages received from one component and transforms them into a representation that can be understood by the application-level mediator. Then, the application-level mediator performs the necessary data conversion and behavioural coordination. Finally, the composer transforms the representation produced by the application-level mediator into network messages that can be sent to the other component. The resulting unified mediation framework reconciles the differences between software components from the application down to the middleware layers. We validate our approach through a case study in the area of conference management

Cytokinesis in bloodstream stage Trypanosoma brucei requires a family of katanins and spastin

Microtubule severing enzymes regulate microtubule dynamics in a wide range of organisms and are implicated in important cell cycle processes such as mitotic spindle assembly and disassembly, chromosome movement and cytokinesis. Here we explore the function of several microtubule severing enzyme homologues, the katanins (KAT80, KAT60a, KAT60b and KAT60c), spastin (SPA) and fidgetin (FID) in the bloodstream stage of the African trypanosome parasite, Trypanosoma brucei. The trypanosome cytoskeleton is microtubule based and remains assembled throughout the cell cycle, necessitating its remodelling during cytokinesis. Using RNA interference to deplete individual proteins, we show that the trypanosome katanin and spastin homologues are non-redundant and essential for bloodstream form proliferation. Further, cell cycle analysis revealed that these proteins play essential but discrete roles in cytokinesis. The KAT60 proteins each appear to be important during the early stages of cytokinesis, while downregulation of KAT80 specifically inhibited furrow ingression and SPA depletion prevented completion of abscission. In contrast, RNA interference of FID did not result in any discernible effects. We propose that the stable microtubule cytoskeleton of T. brucei necessitates the coordinated action of a family of katanins and spastin to bring about the cytoskeletal remodelling necessary to complete cell divisio

Mediating Connector Patterns for Components Interoperability

International audienceA key objective for ubiquitous environments is to enable system interoperability between system's components that are highly heterogeneous. In particular, the challenge is to embed in the system architecture the necessary support to cope with behavioral diversity in order to allow components to coordinate and communicate. In this paper we present the design building blocks for the dynamic and on-the-fly interoperability between heterogeneous components. Specifically, we describe an Architectural Pattern called Mediating Connector, that is the key enabler for communication. In addition, we present a set of Basic Mediator Patterns, that describe the basic mismatches which can occur when components try to interact, and their corresponding solution

Measurement of the quasi-elastic axial vector mass in neutrino-oxygen interactions

The weak nucleon axial-vector form factor for quasi-elastic interactions is determined using neutrino interaction data from the K2K Scintillating Fiber detector in the neutrino beam at KEK. More than 12,000 events are analyzed, of which half are charged-current quasi-elastic interactions nu-mu n to mu- p occurring primarily in oxygen nuclei. We use a relativistic Fermi gas model for oxygen and assume the form factor is approximately a dipole with one parameter, the axial vector mass M_A, and fit to the shape of the distribution of the square of the momentum transfer from the nucleon to the nucleus. Our best fit result for M_A = 1.20 \pm 0.12 GeV. Furthermore, this analysis includes updated vector form factors from recent electron scattering experiments and a discussion of the effects of the nucleon momentum on the shape of the fitted distributions.Comment: 14 pages, 10 figures, 6 table