Crystallization Of The CHAP Domain Of The Endolysin From Staphylococcus Aureus Bacteriophage K

CHAPK is the N-terminal cysteine, histidine-dependent amidohydrolase/peptidase domain (CHAP domain) of the Staphylococcus aureus bacteriophage K endolysin LysK. It is formed from the first 165 residues of LysK and functions by cleaving specific peptidoglycan peptide bonds, causing bacterial lysis. CHAPK can lyse S. aureus when applied exogenously, making it a good candidate for the treatment of multidrug-resistant Staphylococcus aureus infections. Here, the crystallization of CHAPK and the collection of native and derivative data to high resolution, which allowed structure solution, are reported. The structure may help to elucidate the mechanism of action and in the design of chimeric proteins or mutants with improved antibacterial activity

Evaluating an implementation programme for medication review with follow-up in community pharmacy using a hybrid effectiveness study design: translating evidence into practice.

OBJECTIVES: To evaluate an implementation programme of a community pharmacy medication review with follow-up (MRF) service using a hybrid effectiveness-implementation study design, and to compare the clinical and humanistic outcomes with those in a previously conducted cluster randomised controlled trial (cRCT). SETTING: Community pharmacies in Spain. PARTICIPANTS: 135 community pharmacies and 222 pharmacists providing MRF to polymedicated patients aged 65 or over. INTERVENTION: The intervention was an implementation programme for the MRF service. A national level group was established, mirrored with a provincial level group. A series of interventions were defined (1) to engage pharmacy owners with the implementation model and (2) to provide training to pharmacists consisting of clinical case studies, process of MRF, communication skills and data collection methods and (3) practice change facilitators. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcomes for the implementation programme were progress, reach, fidelity and integration. The secondary outcomes were number of medications, non-controlled health problems, emergency visits, hospitalisations and health-related quality of life, which were compared with a previous 6-month cluster RCT. RESULTS: 55% of pharmacies reached the implementation phase and 35.6% remained in the testing phase at 12 months. A reach of 89.3% (n=844) was achieved. Fidelity average score was 8.45 (min: 6.2, max: 9.3) out of 10. The integration mean score was 3.39 (SD: 0.72) out of 5. MRF service outcomes were similar to the cluster RCT study; however, the magnitude of the outcomes was delayed. CONCLUSIONS: The implementation of pharmacy services is a complex multifactorial process, conditioned by numerous implementation factors. In the absence of remuneration, the implementation of the MRF service is a slow process, taking at least 12 months to complete. TRIAL REGISTRATION NUMBER: CGFTRA-2017-01

Situational judgment test of basic employability competences development: validation of a psychoeducative instrument for socioeducative intervention

[ES] Las competencias básicas de empleabilidad, también denominadas competen-cias clave, son fundamentales para acceder, mantener y promocionar en el empleo, y son es-pecialmente relevantes en la promoción de la inserción laboral de los jóvenes desfavorecidos.En este estudio se describe el desarrollo de un instrumento psicoeducativo copyleft ba-sado en el modelo de Arnau et al. (2014) que permite a los profesionales de la pedagogía social evaluar las competencias básicas de empleabilidad en adolescentes y jóvenes de 12 a 18 años: El Test Situacional de Desarrollo de Competencias de Empleabilidad.Se diseñaron 29 situaciones-problema que se sucedían a lo largo de 5 historias de la vida cotidiana de cualquier adolescente. Se entrevistó a 102 adolescentes y jóvenes preguntándo-les cómo reaccionarían ante dichas situaciones-problema. El análisis de contenido de dichas respuestas permitió seleccionar las respuestas más frecuentes indicativas de diferentes nive-les de desarrollo competencial. 10 expertos asignaron las situaciones-problema a una de las 8 competencias propuestas por Arnau et al. (2014) y posteriormente asignaron puntuaciones de entre 0 a 5 a las diferentes respuestas en función del nivel de desarrollo que indicaban las respuestas, con altos niveles de acuerdo. Después de una aplicación piloto a un grupo de 47 jóvenes, que permitió comprobar la variabilidad de las respuestas, se administró el test a 1,011 jóvenes procedentes de 6 centros formativos. Del análisis factorial de las respuestas emergió una estructura unifactorial de 23 ítems, con valores elevados de ajuste del modelo y de la fiabilidad.Los resultados obtenidos avalan la validez de contenido, ecológica y de constructo del test DCBE recibiendo una buena aceptación tanto entre los alumnos como entre los profeso-res por su atractivo y utilidad. El test posibilita iniciar la preparación para la empleabilidad en etapas tempranas previas a la formación postobligatoria. Su carácter copyleft posibilita una amplia utilización por parte de los profesionales de la Pedagogía Social. [EN] Basic employability competences, also known as key competences, are essential in accessing, retaining and advancing in employment, and are especially relevant in promoting the employment of disadvantaged young people.This study describes the development of a copyleft psychoeducational instrument based on the model posited by Arnau et al. (2014) that Social Pedagogy professionals can use to evaluate the basic employability competences in adolescents and young people aged 12 to 18: The Situational Test of Basic Employability Competences Development (DCBE).A total of 29 problem situations were designed and included within five stories related to the daily life of any adolescent. A total of 102 adolescents and young people were interviewed and asked how they would react to these problem situations. The responses were subjected to a content analysis in order to select the most frequent responses indicative of different levels of competence development. Ten experts then assigned the problem situations to one of the eight competences proposed by Arnau et al. (2014), before assigning scores of 0 to 5 to the different responses based on the level of development indicated by the responses, with high levels of agreement.Following a pilot study on a group of 47 young people to verify the variability of the responses, the test was administered to 1,011 young people at six training centres. A factor analysis of the responses yielded a unifactorial structure of 23 items, with high values for model fit and reliability.The results obtained support the content, ecological and construct validity of the DCBE test, which was well accepted by both students and teachers for its attractiveness and use-fulness. The test makes it possible to begin preparing students for employment in the early stages prior to post-compulsory training. Its copyleft nature means it can be widely used by Social Pedagogy professionals

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Dermatology-oncolog

rDock: A Fast, Versatile and Open Source Program for Docking Ligands to Proteins and Nucleic Acids

Identification of chemical compounds with specific biological activities is an important step in both chemical biology and drug discovery. When the structure of the intended target is available, one approach is to use molecular docking programs to assess the chemical complementarity of small molecules with the target; such calculations provide a qualitative measure of affinity that can be used in virtual screening (VS) to rank order a list of compounds according to their potential to be active. rDock is a molecular docking program developed at Vernalis for high-throughput VS (HTVS) applications. Evolved from RiboDock, the program can be used against proteins and nucleic acids, is designed to be computationally very efficient and allows the user to incorporate additional constraints and information as a bias to guide docking. This article provides an overview of the program structure and features and compares rDock to two reference programs, AutoDock Vina (open source) and Schrodinger's Glide (commercial). In terms of computational speed for VS, rDock is faster than Vina and comparable to Glide. For binding mode prediction, rDock and Vina are superior to Glide. The VS performance of rDock is significantly better than Vina, but inferior to Glide for most systems unless pharmacophore constraints are used; in that case rDock and Glide are of equal performance. The program is released under the Lesser General Public License and is freely available for download, together with the manuals, example files and the complete test sets, at http://rdock.sourceforge.net

Cost-Utility Analysis of a Medication Adherence Management Service Alongside a Cluster Randomized Control Trial in Community Pharmacy.

Background: It is necessary to determine the cost utility of adherence interventions in chronic diseases due to humanistic and economic burden of non-adherence. Purpose: To evaluate, alongside a cluster-randomized controlled trial, the cost-utility of a pharmacist-led medication adherence management service (MAMS) compared with usual care in community pharmacies. Materials and Methods: The trial was conducted over six months. Patients with treatments for hypertension, asthma or chronic obstructive pulmonary disease (COPD) were included. Patients in the intervention group (IG) received a MAMS based on a brief complex intervention, whilst patients in the control group (CG) received usual care. The cost–utility analysis adopted a health system perspective. Costs related to medications, healthcare resources and adherence intervention were included. The effectiveness was estimated as quality-adjusted life years (QALYs), using a multiple imputation missing data model. The incremental cost–utility ratio (ICUR) was calculated on the total sample of patients. Results: A total of 1186 patients were enrolled (IG: 633; CG: 553). The total intervention cost was estimated to be € 27.33 ± 0.43 per patient for six months. There was no statistically significant difference in total cost of medications and healthcare resources per patient between IG and CG. The values of EQ-5D-5L at 6 months were significantly higher in the IG [IG: 0.881 ± 0.005 vs CG: 0.833 ± 0.006; p = 0.000]. In the base case, the service was more expensive and more effective than usual care, resulting in an ICUR of € 1,494.82/QALY. In the complete case, the service resulted in an ICUR of € 2,086.30/QALY, positioned between the north-east and south-east quadrants of the cost–utility plane. Using a threshold value of € 20,000/QALY gained, there is a 99% probability that the intervention is cost-effective. Conclusion: The medication adherence management service resulted in an improvement in the quality of life of the population with chronic disease, with similar costs compared to usual care. The service is cost-effective

Effectiveness of a medication adherence management intervention in a community pharmacy setting: a cluster randomised controlled trial

BackgroundNon-adherence to medications continues to be a burden worldwide, with significant negative consequences. Community pharmacist interventions seem to be effective at improving medication adherence. However, more evidence is needed regarding their impact on disease-specific outcomes. The aim was to evaluate the impact of a community pharmacist-led adherence management intervention on adherence and clinical outcomes in patients with hypertension, asthma and chronic obstructive pulmonary disease (COPD).MethodsA 6-month cluster randomised controlled trial was conducted in Spanish community pharmacies. Patients suffering from hypertension, asthma and COPD were recruited. Patients in the intervention group received a medication adherence management intervention and the control group received usual care. The intervention was based on theoretical frameworks for changing patient behaviour. Medication adherence, disease-specific outcomes (Asthma Control Questionnaire (ACQ) scores, Clinical COPD Questionnaire (CCQ) scores and blood pressure levels) and disease control were evaluated. A multilevel regression model was used to analyse the data.ResultsNinety-eight pharmacies and 1186 patients were recruited, with 1038 patients completing the study. Patients receiving the intervention had an OR of 5.12 (95% CI 3.20 to 8.20, pConclusionsA community pharmacist-led medication adherence intervention was effective at improving medication adherence and clinical outcomes in patients suffering from hypertension, asthma and COPD. Future research should explore the implementation of these interventions in routine practice.Trial registration numberACTRN12618000410257

Spanish Validation of the Leader Empowering Behavior Questionnaire (LEBQ)

[EN] The concept of empowering leadership (EL) has attracted widespread academic and practical interest and different questionnaires have been developed to measure it. However, there are no instruments to measure EL in the Spanish language. This article presents the translation, adaptation, and validation of a scale to measure this construct. In addition, it analyzes the relationship between managers¿ EL and employees¿ job satisfaction. In turn, the study analyzes whether employees who participate in a greater number of continuous improvement (CI) programs have supervisors who favor more empowering behaviors. A total of 739 participants with various occupations from different companies that have implemented CI processes filled out the Spanish version of the Leader Empowering Behavior Questionnaire (LEBQ-sp). Two different subsamples were used to test the relationships between the LEBQ and job satisfaction and CI, by means of Pearson¿s correlation coefficient and analysis of variance, making it possible to provide evidence about the validity of the Spanish LEBQ. The confirmatory factor analysis supported the original structure of the six-factor model. The factors show a high level of internal consistency, as well as sufficient convergent and discriminant validity. Moreover, the results show that the more companies invest in formal CI programs, the more important it is for their leaders to adapt their behavior by displaying more EL. The LEBQ-sp is a valid and reliable instrument for use in research and a useful tool for applied purposes in the context of Spanish-speaking countries.Bonavía Martín, T.; Marin-Garcia, JA. (2019). Spanish Validation of the Leader Empowering Behavior Questionnaire (LEBQ). Frontiers in Psychology. 10:1-9. https://doi.org/10.3389/fpsyg.2019.02368S191

Risk of Serious Infections in Patients with Psoriasis on Biologic Therapies: A Systematic Review and Meta-Analysis

A comprehensive evaluation of the risk of serious infections in biologic therapies for psoriasis is lacking. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) and prospective cohort studies reporting serious infections in people taking any licensed biologic therapy for psoriasis compared with those taking placebo, nonbiologic therapy, or other biologic therapies. The quality of the studies was assessed using Grading of Recommendations Assessment, Development and Evaluation criteria. No significant heterogeneity was detected in data from 32 RCTs (n = 13,359 participants) and one cohort study (n = 4,993 participants). In adults, low- to very-low-quality RCT data showed no significant difference between any biologic therapy and placebo at weeks 12–16 (overall pooled Peto odds ratio = 0.71, 95% confidence interval = 0.36–1.41) and weeks 20–30 (odds ratio = 2.27, 95% confidence interval = 0.45–11.49). No significant differences were found in any of the other comparisons in underpowered RCT data. Prospective cohort study data of low quality suggests that only adalimumab (adjusted hazard ratio [adjHR] = 2.52, 95% confidence interval = 1.47–4.32) was associated with a significantly higher risk of serious infection compared with retinoid and/or phototherapy in adults. No association between biologic therapies and serious infections in patients with psoriasis who were eligible for RCTs was detected. Further observational studies are needed to inform the uncertainty around this risk in the real world

Validation of Ti(III) as a reducing agent in the Chemiluminescent determination of nitrate and nitrite in seawater

Titanium (III) trichloride is validated here for the quantitative conversion of all nitrate plus nitrite in seawater to nitric oxide gas, thereby providing an alternative to the typically used reducing agent, ferrous ammonium sulfate plus ammonium molybdate, in the chemiluminescent detection of nitrate plus nitrite at the nanomolar level. We find that both Fe(II)+Mo(VI) and Ti(III) methods yield identical results for standards and seawater samples over a validated concentration range of 1 to 1000 nM, and are both in agreement with traditional colorimetric results. Benefits of the Ti(III) reduction chemistry are: simpler preparation, decreased ammonium contamination in a laboratory that measures low-level nutrients, 30% reduction of the sulfuric acid catalyst, and a higher sample through-put. Most importantly, though, this work can be considered the first step on a path toward a much-needed, direct measurement of dissolved organic nitrogen concentrations, as has already been achieved for dissolved organic carbon