Single-cell analysis divides bovine monocyte-derived dendritic cells into subsets expressing either high or low levels of inducible nitric oxide synthase

Dendritic cells (DC) are important cells at the interface between innate and adaptive immunity. DC have a key role in antigen processing and presentation to T cells. Effector functions of DC related to innate immunity have not been explored extensively. We show that bovine monocyte-derived DC (mDC) express inducible nitric oxide synthase (iNOS) mRNA and protein and produce NO upon triggering with interferon-gamma (IFN-gamma) and heat-killed Listeria monocytogenes (HKLM). An immunocytochemical analysis revealed that a sizeable subset (20-60%) copiously expresses iNOS (iNOShi) upon IFN-gamma/HKLM triggering, whereas the other subset expressed low levels of iNOS (iNOSlo). Monocyte-derived macrophages (mMphi) are more homogeneous with regard to iNOS expression. The number of cells within the iNOSlo mDC subset is considerably larger than the number of dead cells or cells unresponsive to IFN-gamma/HKLM. The large majority of cells translocated p65 to the nucleus upon triggering by IFN-gamma/HKLM. A contamination of mDC with iNOS-expressing mMphi was excluded as follows. (i) Cell surface marker analysis suggested that mDC were relatively homogeneous, and no evidence for a contaminating subset expressing macrophage markers (e.g. high levels of CD14) was obtained. (ii) iNOS expression was stronger in iNOShi mDC than in mMphi. The use of maturation-promoting stimuli revealed only subtle phenotypic differences between immature and mature DC in cattle. Nevertheless, these stimuli promoted development of considerably fewer iNOShi mDC upon triggering with IFN-gamma/HKLM. Immunocytochemical results showed that although a significant proportion of cells expressed iNOS only or TNF only upon triggering with IFN-gamma/HKLM, a significant number of cells expressed both iNOS and TNF, suggesting that TNF and iNOS producing (TIP) DC are present within bovine mDC populations obtained in vitro.

Activation of T cells by carbamazepine and carbamazepine metabolites

BACKGROUND: T-cell-mediated hypersensitivity is a rare but serious manifestation of drug therapy. OBJECTIVES: To explore the mechanisms of drug presentation to T cells and the possibility that generation of metabolite-specific T cells may provoke cross-sensitization between drugs. METHODS: A lymphocyte transformation test was performed on 13 hypersensitive patients with carbamazepine, oxcarbazepine, and carbamazepine metabolites. Serial dilution experiments were performed to generate drug (metabolite)-specific T-cell clones to explore the structural basis of the T-cell response and mechanisms of antigen presentation. 3-Dimensional energy-minimized structures were generated by using computer modeling. The role of drug metabolism was analyzed with 1-aminobenzotriazole. RESULTS: Lymphocytes and T-cell clones proliferated with carbamazepine, oxcarbazepine, and some (carbamazepine 10,11 epoxide, 10-hydroxy carbamazepine) but not all stable carbamazepine metabolites. Structure activity studies using 29 carbamazepine (metabolite)-specific T-cell clones revealed 4 patterns of drug recognition, which could be explained by generation of preferred 3-dimensional structural conformations. T cells were stimulated by carbamazepine (metabolites) bound directly to MHC in the absence of processing. The activation threshold for T-cell proliferation varied between 5 minutes and 4 hours. 1-Aminobenzotriazole, which inhibits cytochrome P450 activity, did not prevent carbamazepine-related T-cell proliferation. Substitution of the terminal amine residue of carbamazepine with a methyl group diminished T-cell proliferation. CONCLUSION: These data show that carbamazepine and certain stable carbamazepine metabolites stimulate T cells rapidly via a direct interaction with MHC and specific T-cell receptors. CLINICAL IMPLICATIONS: Some patients with a history of carbamazepine hypersensitivity possess T cells that cross-react with oxcarbazepine, providing a rationale for cross-sensitivity between the 2 drugs.

Meta-analysis: chondroitin for osteoarthritis of the knee or hip

BACKGROUND: Previous meta-analyses described moderate to large benefits of chondroitin in patients with osteoarthritis. However, recent large-scale trials did not find evidence of an effect. PURPOSE: To determine the effects of chondroitin on pain in patients with osteoarthritis. DATA SOURCES: The authors searched the Cochrane Central Register of Controlled Trials (1970 to 2006), MEDLINE (1966 to 2006), EMBASE (1980 to 2006), CINAHL (1970 to 2006), and conference proceedings; checked reference lists; and contacted authors. The last update of searches was performed on 30 November 2006. STUDY SELECTION: Studies were included if they were randomized or quasi-randomized, controlled trials that compared chondroitin with placebo or with no treatment in patients with osteoarthritis of the knee or hip. There were no language restrictions. DATA EXTRACTION: The authors extracted data in duplicate. Effect sizes were calculated from the differences in means of pain-related outcomes between treatment and control groups at the end of the trial, divided by the pooled SD. Trials were combined by using random-effects meta-analysis. DATA SYNTHESIS: 20 trials (3846 patients) contributed to the meta-analysis, which revealed a high degree of heterogeneity among the trials (I2 = 92%). Small trials, trials with unclear concealment of allocation, and trials that were not analyzed according to the intention-to-treat principle showed larger effects in favor of chondroitin than did the remaining trials. When the authors restricted the analysis to the 3 trials with large sample sizes and an intention-to-treat analysis, 40% of patients were included. This resulted in an effect size of -0.03 (95% CI, -0.13 to 0.07; I2 = 0%) and corresponded to a difference of 0.6 mm on a 10-cm visual analogue scale. A meta-analysis of 12 trials showed a pooled relative risk of 0.99 (CI, 0.76 to 1.31) for any adverse event. LIMITATIONS: For 9 trials, the authors had to use approximations to calculate effect sizes. Trial quality was generally low, heterogeneity among the trials made initial interpretation of results difficult, and exploring sources of heterogeneity in meta-regression and stratified analyses may be unreliable. CONCLUSIONS: Large-scale, methodologically sound trials indicate that the symptomatic benefit of chondroitin is minimal or nonexistent. Use of chondroitin in routine clinical practice should therefore be discouraged.

Cathepsin G is differentially expressed in primary human antigen-presenting cells

Cathepsins are required for the processing of antigens in order to make them suitable for loading on major histocompatibility complex (MHC) class II molecules, for subsequent presentation to CD4(+) T cells. It was shown that antigen processing in monocyte-derived dendritic cells (DC), a commonly used DC model, is different from that of primary human DC. Here, we report that the two subsets of human myeloid DC (mDC) and plasmacytoid DC (pDC) differ in their cathepsin distribution. The serine protease cathepsin G (CatG) was detected in mDC1, mDC2, pDC, cortical thymic epithelial cells (cTEC) and high levels of CatG were determined in pDC. To address the role of CatG in the processing and presentation of a Multiple Sclerosis-associated autoantigen myelin basic protein (MBP), we used a non-CatG expressing fibroblast cell line and fibroblasts, which were preloaded with purified CatG. We find that preloading fibroblasts with CatG results in a decrease of MBP84-98-specific T cell proliferation, when compared to control cells. Our data suggest a different processing signature in primary human antigen-presenting cells and CatG may be of functional importance.

[Second victim : Critical incident stress management in clinical medicine]

BACKGROUND Critical incidents in clinical medicine can have far-reaching consequences on patient health. In cases of severe medical errors they can seriously harm the patient or even lead to death. The involvement in such an event can result in a stress reaction, a so-called acute posttraumatic stress disorder in the healthcare provider, the so-called second victim of an adverse event. Psychological distress may not only have a long lasting impact on quality of life of the physician or caregiver involved but it may also affect the ability to provide safe patient care in the aftermath of adverse events. METHODS A literature review was performed to obtain information on care giver responses to medical errors and to determine possible supportive strategies to mitigate negative consequences of an adverse event on the second victim. An internet search and a search in Medline/Pubmed for scientific studies were conducted using the key words "second victim, "medical error", "critical incident stress management" (CISM) and "critical incident stress reporting system" (CIRS). Sources from academic medical societies and public institutions which offer crisis management programs where analyzed. The data were sorted by main categories and relevance for hospitals. Analysis was carried out using descriptive measures. RESULTS In disaster medicine and aviation navigation services the implementation of a CISM program is an efficient intervention to help staff to recover after a traumatic event and to return to normal functioning and behavior. Several other concepts for a clinical crisis management plan were identified. CONCLUSIONS The integration of CISM and CISM-related programs in a clinical setting may provide efficient support in an acute crisis and may help the caregiver to deal effectively with future error events and employee safety.

Iowa State Daily (April 5, 2012)

ContentsEnjoy a caveman's dietFair focuses on science, technology, math fieldsStudents present research at CapitolRacism finds its sociological roots Track and field looks to future of conference

Patient classification system: An integrated method for measuring nursing intensity and optimizing resource allocation

A patient classification system was developed integrating a patient acuity instrument with a computerized nursing distribution method based on a linear programming model. The system was designed for real-time measurement of patient acuity (workload) and allocation of nursing personnel to optimize the utilization of resources.^ The acuity instrument was a prototype tool with eight categories of patients defined by patient severity and nursing intensity parameters. From this tool, the demand for nursing care was defined in patient points with one point equal to one hour of RN time. Validity and reliability of the instrument was determined as follows: (1) Content validity by a panel of expert nurses; (2) predictive validity through a paired t-test analysis of preshift and postshift categorization of patients; (3) initial reliability by a one month pilot of the instrument in a practice setting; and (4) interrater reliability by the Kappa statistic.^ The nursing distribution system was a linear programming model using a branch and bound technique for obtaining integer solutions. The objective function was to minimize the total number of nursing personnel used by optimally assigning the staff to meet the acuity needs of the units. A penalty weight was used as a coefficient of the objective function variables to define priorities for allocation of staff.^ The demand constraints were requirements to meet the total acuity points needed for each unit and to have a minimum number of RNs on each unit. Supply constraints were: (1) total availability of each type of staff and the value of that staff member (value was determined relative to that type of staff's ability to perform the job function of an RN (i.e., value for eight hours RN = 8 points, LVN = 6 points); (2) number of personnel available for floating between units.^ The capability of the model to assign staff quantitatively and qualitatively equal to the manual method was established by a thirty day comparison. Sensitivity testing demonstrated appropriate adjustment of the optimal solution to changes in penalty coefficients in the objective function and to acuity totals in the demand constraints.^ Further investigation of the model documented: correct adjustment of assignments in response to staff value changes; and cost minimization by an addition of a dollar coefficient to the objective function. ^

Evaluation of the LBJ Hospital Ask Your Nurse Advice Line

This retrospective, case-control study investigated the effectiveness of the Houston, Texas Ask Your Nurse Advice Line (AYN) in diverting callers with non-emergent medical conditions away from the emergency department (ED). After asking callers a series of questions, AYN nurses evaluate the medical condition and make recommendations for appropriate care, e.g., home care, see a clinic physician, or visit the ED. To evaluate the AYN, the rate of caller ED visits before accessing the AYN for the first time was compared to the caller ED visit rate afterwards. The pre-post rate change was compared to that of a control group of similar caller age, race, gender, and insurance status drawn from a Harris County Hospital District HCHD database. ^ The treatment group (AYN caller) had a 66% reduction in ED visits after the first AYN call compared to an 18% drop in ED visits among control group subjects during the same time period. Study results were presented to HCHD staff on August 30th, 2007 and recommendations were made for future studies that would provide a basis for policy development. ^

Spit & lies: Does social desirability predict smoking cessation success?

This study examines the role of socially desirable responding (SDR) on smoking cessation program success. SDR is the tendency for individuals to give responses that put themselves in what they perceive to be a socially desirable light. ^ This research is a secondary analysis of data from Project Cognition, a study designed to examine the associations between performance on cognitive assessments and subsequent relapse to smoking. Adult smokers (N=183) were recruited from the greater Houston area to participate in the smoking cessation study. In this portion of the research, participants' smoking status was assessed on their quit day (QD), one week after QD, and four weeks after QD. Primary outcome measures were self-reported relapse, true cessation determined by biological measure, discrepancies between self-reported smoking status and biological assessments of smoking, and dropping out. ^ Primary predictor measures were the Balanced Inventory of Desirable Responding (BIDR) and self-reported motivation to quit smoking. The BIDR is a 40-item questionnaire that assesses Self-deceptive Enhancement (SDE; the tendency to give self-reports that are honest but positively biased) and Impression Management (IM; deliberate self-presentation to an audience). Scores were used to create a dichotomous BIDR total score group variable, a dichotomous SDE group variable, and a dichotomous IM group variable. Participants at one standard deviation above the mean were in the "high" group, and scores below one standard deviation were in the "normal" group. In addition, age, race, and gender were analyzed as covariates. ^ The overall findings of this study suggest that in the general population BIDR informs participants' self-reports and the IM and SDR subscales inform participants' behavior. BIDR predicted self-reported relapse in the general population and trended toward indicating that a participant will claim smoking cessation success when biological measures indicate otherwise. SDE interacted with motivation to predict biologically verified cessation success. There was no main effect for BIDR, IM, or SDE predicting drop out; however, IM interacted with age to predict participants' likelihood of drop out. Used in conjunction, the BIDR, IM subscale, and SDR subscale can be used to more accurately tailor smoking cessation programs to the needs of individual participants.^

Creación de la red de egresados de la Facultad de Odontología de la UNCuyo

Este trabajo tiene como objetivo realizar una propuesta personal para la universidad actual. El marco legal vigente propone y respalda importantes innovaciones que puedan ser introducidas para aportar a la subvención de las universidades. Se propone la creación de una red de graduados (RG) de una facultad. Esto puede servir de modelo para la creación de la misma red para una Universidad, y esto ampliarse periféricamente a otras universidades.

Los promotores en la metodología de intervención del programa Pro-Huerta Córdoba, Argentina

El Pro-Huerta (PPH) es un programa estatal nacional que aborda la seguridad alimentaria, dirigido a la población pobre. La zona Gran Córdoba comprende la ciudad de Córdoba y un amplio territorio que involucra los pueblos cercanos en un radio aproximado de unos 50 km de la capital, donde se trabaja con más de 120 promotores y 14.500 huerteros. Debido a que los promotores son los actores que los técnicos destacan como fundamentales en el funcionamiento del programa, las principales preguntas que este estudio se formula son: ¿quiénes son los actores que participan como promotores en el PPH de la provincia de Córdoba? y ¿cómo perciben los promotores los beneficios y limitaciones del componente de capacitación? La metodología utilizada combina procedimientos cuanti y cualitativos en el tratamiento de los datos. El universo de promotores fue clasificado contemplando las funciones que desempeñan en el programa y sus demandas de capacitación. Se observó una relación significativa entre el subtipo que cumple una función de promoción más integral y el subtipo que demanda capacitación en aspectos sociales. Asimismo es importante la relación entre el subtipo que limita su función sólo a convocar reuniones para repartir semillas con el que manifiesta una menor demanda de capacitación en general.

Some reflections on the IT challenges for a multilingual semantic web

Many attempts have been made to provide multilinguality to the Semantic Web, by means of annotation properties in Natural Language (NL), such as RDFs or SKOS labels, and other lexicon-ontology models, such as lemon, but there are still many issues to be solved if we want to have a truly accessible Multilingual Semantic Web (MSW). Reusability of monolingual resources (ontologies, lexicons, etc.), accessibility of multilingual resources hindered by many formats, reliability of ontological sources, disambiguation problems and multilingual presentation to the end user of all this information in NL can be mentioned as some of the most relevant problems. Unless this NL presentation is achieved, MSW will be restricted to the limits of IT experts, but even so, with great dissatisfaction and disenchantment

Evaluación de patrones de programación de usabilidad para tres casos de estudio

La calidad es uno de los principales retos de la construcción de software. En la Ingeniería del Software (IS) se considera a la usabilidad como un atributo de calidad. Al principio se veía a la usabilidad como un requisito no funcional.Se asumía que la usabilidad era una propiedad exclusiva de la presentación de la información.Se creía que separando la capa de presentación del resto, se podía desarrollar un producto software usable.Debido a la naturaleza del sistema y a las necesidades del usuario, a menudo se debe ir más lejos y no basta con tener en cuenta la presentación para obtener un software usable. La comunidad de la Interacción Personar Ordenador (IPO) ha propuesto recomendaciones para mejorar la usabilidad. Algunas de esas recomendaciones tienen impacto directo en la funcionalidad del producto software. En estudios recientes también se ha evaluado la relación entre la usabilidad y los requisitos funcionales. Estas investigaciones sugieren que la usabilidad debe ser tenida en cuenta desde las etapas iniciales de la construcción para evitar costosos cambios posteriores. La incorporación de las características de usabilidad agrega cierta complejidad al proceso de desarrollo. El presente trabajo evalúa la posibilidad de usar patrones para la incorporación de usabilidad en el desarrollo de un producto software. Concretamente se evalúan los siguientes patrones de programación de usabilidad (PPUs): Abort Operation,Progress Feedback y Preferences. Se utilizan unas Pautas de Desarrollo de Mecanismos de Usabilidad(PDMUs) para estos tres mecanismos de usabilidad. Estas pautas poponen patrones para la educción y posterior incorporación de la usabilidad en las distintas fases de la programación. En esta investigación se aborda el desarrollo de un producto software desde la deducción de requisitos hasta la implementación. En cada fase se incorporan los mecanismos de usabilidad de acuerdo a las recomendaciones de las PDMUs. Mediante el desarrollo de un software real se ha evaluado la factibilidad del uso de las PDMUs obteniendo como resultado propuestas de mejoras en estas pautas. Se evalúa asimismo el esfuerzo de incorporación de los mecanismos de usabilidad. Cada evaluación aporta datos que proporcionan una estimación del esfuerzo adicional requerido para incorporar cada mecanismo de usabilidad en el proceso de desarrollo del software.---ABSTRACT---Quality is a major challenge in software construction. Software engineers consider usability to be a quality attribute. Originally, usability was viewed as a nonr functional requirement. Usability was assumed to be simply an information presentation property. There was a belief that a usable software product could be developed by separating the presentation layer from the rest of the system. Depending on the system type and user needs, however, usability often runs deeper, and it is not enough to consider just presentation to build usable software. The humanrcomputer interaction (HCI) community put forward a list of recommendations to improve usability. Some such recommendations have a direct impact on software product functionality. Recent studies have also evaluated the relationship between usability and functional requirements. This research suggests that usability should be taken into account as of the early stages of software construction to prevent costly rework later on. The inclusion of usability features is an added complication to the development process. The research reported here evaluates the possibility of using patterns to incorporate usability into a software product. Specifically, it evaluates the following usability programming patterns (UPPs): Abort Operation, Progress Feedback and Preferences. Usability Mechanism Development Guides (USDG) are applied to these three usability mechanisms. These guides propose patterns for eliciting and later incorporating usability into the different software development phases, including programming. The reported research addresses the development of a software product from requirements elicitation through to implementation. Usability mechanisms are incorporated into each development phase in accordance with USDG recommendations. A real piece of software was developed to test the feasibility of using USDGs, outputting proposals for improving the guides. Each evaluation yields data providing an estimate of the additional workload required to incorporate each usability mechanism into the software development process.

Cleavage motifs of the yeast 20S proteasome β subunits deduced from digests of enolase 1

The 436-amino acid protein enolase 1 from yeast was degraded in vitro by purified wild-type and mutant yeast 20S proteasome particles. Analysis of the cleavage products at different times revealed a processive degradation mechanism and a length distribution of fragments ranging from 3 to 25 amino acids with an average length of 7 to 8 amino acids. Surprisingly, the average fragment length was very similar between wild-type and mutant 20S proteasomes with reduced numbers of active sites. This implies that the fragment length is not influenced by the distance between the active sites, as previously postulated. A detailed analysis of the cleavages also allowed the identification of certain amino acid characteristics in positions flanking the cleavage site that guide the selection of the P1 residues by the three active β subunits. Because yeast and mammalian proteasomes are highly homologous, similar cleavage motifs might be used by mammalian proteasomes. Therefore, our data provide a basis for predicting proteasomal degradation products from which peptides are sampled by major histocompatibility complex class I molecules for presentation to cytotoxic T cells.