Role of retinal pigment epithelium permeability in drug transfer between posterior eye segment and systemic blood circulation

Retinal pigment epithelium (RPE) is a major part of blood-retinal barrier that affects drug elimination from the vitreous to the blood and drug distribution from blood circulation into the eye. Even though drug clearance from the vitreous has been well studied, the role of RPE in the process has not been quantified. The aim of this work was to study the role of RPE clearance (CLRpE) as part of drug elimination from the vitreous and ocular drug distribution from the systemic blood circulation. We determined the bidirectional permeability of eight small molecular weight drugs and bevacizumab antibody across isolated bovine RPE-choroid. Permeability of small molecules was 10(-6) -10(-5)cm/s showing 13-15 fold range of outward and inward permeation, while permeability of bevacizumab was lower by 2-3 orders of magnitude. Most small molecular weight drugs showed comparable outward (vitreous-to-choroid) and inward (choroid-to-vitreous) permeability across the RPEchoroid, except ciprofloxacin and ketorolac that had an over 6 and 14-fold higher outward than inward permeability, respectively, possibly indicating active transport, Six of seven tested small molecular weight drugs had outward CLRPE values that were comparable with their intravitreal clearance (CLIvr) values (0.84-2.6 fold difference). On the contrary, bevacizumab had an outward CLRPE that was only 3.5% of the CLIvt, proving that its main route of elimination (after intravitreal injection) is not RPE permeation. Experimental values were used in pharmacokinetic simulations to assess the role of the RPE in drug transfer from the systemic blood circulation to the vitreous (CLBv). We conclude that for small molecular weight drugs the RPE is an important route in drug transfer between the vitreal cavity and blood, whereas it effectively hinders the movement of bevacizumab from the vitreous to the systemic circulation.Peer reviewe

Communication as a mechanism for culture integration

Autonomy of employees is one way to ensure the flexibility, adaptability and innovation competence needed in organisations working on a global market. This has to be dynamically balanced on a system level by integration of the employees into the organisation. Formulation and communication of an organisational culture is one way to integrate employees to an understanding of the work that increases the chances of co-ordinated behaviour towards the goal of the organisation. The aim of this article is to increase the knowledge about processes leading to integration of employees into the organizational culture. The hypothesis is that culture emerges in the interaction between members of a social group. Thus, the article is studying the importance of communication, the research questions are: What makes the culture of a work group similar to the organizational culture?, How is a work group culture constructed? and How is it possible that some members of the workgroup are integrated in the organizational culture while others are not? Theories used are about culture as an organizing structure emerging in interaction between actors, about organizational culture as a way for management to exert control, and about social networks as a way to describe the interaction processes is. The empirical data comes from a merchant bank in Sweden famous for: long term competitiveness, a decentralized organisation and the use of organizational culture. 105 respondents from ten work groups of this bank have answered questions about their communication and their integration into the organisational culture. The results show that communication between members of a group is a mechanism behind the development of the sub-culture of the group and the integration of each individual member into this subculture. There seems to be a self-reinforcing spiral between collegial talk, especially about goals, plans and changes at the work place, and culture integration. To build a strong subculture it is important to have all members of a group included in this communication, since persons in the periphery of the talk pattern tends to be less integrated. The value system of the group’s supervisor is strongly influencing the sub-culture of the work group. Thus, to hire supervisors with the correct values and giving resources to employees for communication is central for an organisation using organisational culture as a tool for control

Swedish school nurses' experience of identifying students who are exposed to violence – a qualitative study

Aim: This study aims to describe how school nurses identify students who are being exposed to violence. Design: The study has a qualitative design focusing on illuminating the meanings embodied in lived experiences Method: Fourteen qualitative interviews with school nurses were conducted and a descriptive qualitative meaning analysis was used to cast light on the phenomenon. The COREQ checklist was used to ensure trustworthiness. Results: Four themes were highlighted: opportunity in the health dialogue, necessity to create and prove trustworthiness, cooperation with other professionals, and awareness of factors that could complicate reporting exposure to violence. The study provided new insights such as the school nurse having an important role in the identification of students exposed to violence. It is important that school nurses have an open approach and are systematic in the health dialogue, using questions about violence to create opportunities for students to talk about their living conditions.CC BY-NC 4.0Funding: Financial support for the manuscript preparation was provided by University of Skövde, Institution for Health Sciences research milieu DHEAR and research group FamCeH.</p

Measurement of bacterial size via image analysis of epifluorescence preparations: description of an inexpensive system and solutions to some of the most common problems

11 páginas, 9 figuras, 3 tables[EN] Computerized image-analysis of epifluorescence preparations is the most accurate and simple method for the estimation of bacterial size. We present a simple and inexpensive image-analysis system used to measure and count planktonic bacteria and presently in operation in our laboratory. We show that there is a wide range of image exposures (brightness) over which the system performs correctly. Even though the procedure involves some steps that depend upon operator intervention, the results obtained are highly reproducible and we have estimated the among-operator variability at 5%. We then discuss the advantages and disadvantages of different algorithms used for the estimation of volume from two-dimensional images and we identify those that perform better for curved and unusual cells. We finally estimate that 4 to 6 images and 200 - 250 cells are the optimal number of images to be processed and cells to be measured to obtain accurate estimates of population values with the minimum effort. These calibrations should be useful to all those laboratories that are implementing image-analysis systems[ES] El análisis de imágenes obtenidas a partir de preparaciones de epifluorescencia es el método más sencillo y preciso para medir el tamaño bacteriano. En este trabajo se presenta un sistema de análisis de imágenes sencillo y asequible, actualmente en funcionamiento en nuestro laboratorio, desarrollado para medir y contar bacterias planctónicas. Se demuestra que el sistema funciona correctamente dentro de un rango amplio de brillo de imagen. Aunque algunos pasos del proceso dependen del operador, los resultados obtenidos fueron altamente reproducibles, y se estimó una variabilidad entre operadores del 5%. Se discuten las ventajas de los diferentes algoritmos usados para calcular el biovolumen a partir de imágenes de dos dimensiones, e identificamos el algoritmo que funciona mejor en células curvados o de formas inusuales. Finalmente, se estimó que para obtener medidas precisas del tamaño medio de la población con el mínimo esfuerzo se debían procesar entre 4 y 6 imágenes y contar entre 200 y 250 células. La información presentada en este trabajo puede ser útil para aquellos laboratorios que deseen desarrollar sistemas de análisis de imágenes parecidosThis paper was developed while working for the EU MAS2-CT93-0077, EU MAS3-CT95-0016 (MEDEA) projects and partially financed by project DGICYT PB91-075Peer reviewe

Falling outside the system : Occupational safety and health inspectors’ experiences of micro-enterprises in Sweden

In this study, 11Swedish occupational safety and health (OSH)i nspectors were interviewed about their views of and experiences interacting with micro-enterprises (1-9 employees). The qualitative content analysis found one  theme, “Falling outside thes ystem”, and three subthemes, “The inspector—shaped by specific standards”, “The bureaucrat and the micro-entrepreneur—two separate worlds”, and “System faults and system changes”. According to the inspectors, the Swedish OSH regulatory system, with inspectors on the frontline, neglects the specific needs, circumstance and characteristics of micro-enterprises.Therefore,we suggest revising the OSH regulatory system and following inspection methods and enforcement styles to better address the needs of micro enterprises.Ingår i projekt finansierat av Arbetsmiljöverket (The Swedish Work Environment Authority). (Grant No. 2015/033753-31). </p

EUCAST rapid antimicrobial susceptibility testing (RAST) in blood cultures: Validation in 55 european laboratories

© The Author(s) 2020.Objectives: When bloodstream infections are caused by resistant bacteria, rapid antimicrobial susceptibility testing (RAST) is important for adjustment of therapy. The EUCAST RAST method, directly from positive blood cultures, was validated in a multi-laboratory study in Europe. Methods: RAST was performed in 40 laboratories in northern Europe (NE) and 15 in southern Europe (SE) from clinical blood cultures positive for Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus or Streptococcus pneumoniae. Categorical results at 4, 6 and 8 h of incubation were compared with results for EUCAST standard 16–20 h disc diffusion. The method, preliminary breakpoints and the performance of the laboratories were evaluated. Results: The total number of isolates was 833/318 in NE/SE. The number of zone diameters that could be read (88%, 96% and 99%) and interpreted (70%, 81% and 85%) increased with incubation time (4, 6 and 8 h). The categorical agreement was acceptable, with total error rates in NE/SE of 2.4%/4.9% at 4 h, 1.1%/3.5% at 6 h and 1.1%/3.3% at 8 h. False susceptibility at 4, 6 and 8 h of incubation was below 0.3% and 1.1% in NE and SE, respectively, and the corresponding percentages for false resistance were below 1.9% and 2.8%. After fine-tuning breakpoints, more zones could be interpreted (73%, 89% and 93%), with only marginally affected error rates. Conclusions: The EUCAST RAST method can be implemented in routine laboratories without major investments. It provides reliable antimicrobial susceptibility testing results for relevant bloodstream infection pathogens after 4–6 h of incubation