Intensive care 1980-1995: change in patient characteristics, nursing workload and outcome

Objective: To assess temporal changes in patient characteristics, nursing workload and outcome of the patients and to compare the actual amount of available nursing staff with the estimated needs in a medical-surgical ICU. Design: Retrospective analysis of prospectively collected data. Setting: A medical-surgical adult intensive care unit (ICU) in a Swiss university hospital. Patients: Data of all patients staying in the ICU between January 1980 and December 1995 were included. Interventions: None. Measurements and results: The estimated number of nurses needed was defined according to the Swiss Society of Intensive Care Medicine (SGI) grading system: category I=one nurse/patient/shift (=8 h), category II=one nurse/two patients/shift, category III=one nurse/three patients/shift. An intervention score (IS) was obtained, based on a number of specific activities in the ICU. There was a total of 35,327 patients (32 % medical and 68 % postoperative/trauma patients). Over time, the number of patients per year increased (1980/1995:1,825/2,305, p70 years (19 %/28 %,p<0.001), and a decrease in the number of patients<60 years (58 % /41 %, p<0.001). During the same time period, the IS increased two-fold. Measurement of nursing workload showed an increase over time. The number of nursing days per year increased (1980/1995: 7454/8681, p<0.019), as did the relative amount of patients in category I (49 %/71 %, p<0.001), whereas the portion of patients in category II (41 %/28 %,p< 0.019) and category III (10 %/0 %) decreased. During the same time period, mortality at ICU discharge decreased (9.0 %/ 7.0 %,p< 0.002). Conclusions: During the last 16 years, there has been a marked increase in workload at this medical-surgical ICU. Despite an increase in the number of severely sick patients (as defined by the nursing grading system) and patient age, ICU mortality and LOS declined from 1980 to 1995. This may be ascribed to improved patient treatment or care. Whether an increasingly liberal discharge policy (transfer to newly opened intermediate care units, transfer of patients expected to die to the ward) or a more rigorous triage (denying admission to patients with a very poor prognosis) are confounding factors cannot be answered by this investigation. The present data provide support for the tenet that there is a trend toward more complex therapies in increasingly older patients in tertiary care ICUs. Calculations for the number or nurses needed in an ICU should take into account the increased turnover of patients and the changing patient characteristic

Biological response of an in vitro human 3D lung cell model exposed to brake wear debris varies based on brake pad formulation

Wear particles from automotive friction brake pads of various sizes, morphology, and chemical composition are significant contributors towards particulate matter. Knowledge concerning the potential adverse effects following inhalation exposure to brake wear debris is limited. Our aim was, therefore, to generate brake wear particles released from commercial low-metallic and non-asbestos organic automotive brake pads used in mid-size passenger cars by a full-scale brake dynamometer with an environmental chamber simulating urban driving and to deduce their potential hazard in vitro. The collected fractions were analysed using scanning electron microscopy via energy-dispersive X-ray spectroscopy (SEM-EDS) and Raman microspectroscopy. The biological impact of the samples was investigated using a human 3D multicellular model consisting of human epithelial cells (A549) and human primary immune cells (macrophages and dendritic cells) mimicking the human epithelial tissue barrier. The viability, morphology, oxidative stress, and (pro-)inflammatory response of the cells were assessed following 24 h exposure to similar to 12, similar to 24, and similar to 48 A mu g/cm(2) of non-airborne samples and to similar to 3.7 A mu g/cm(2) of different brake wear size fractions (2-4, 1-2, and 0.25-1 A mu m) applying a pseudo-air-liquid interface approach. Brake wear debris with low-metallic formula does not induce any adverse biological effects to the in vitro lung multicellular model. Brake wear particles from non-asbestos organic formulated pads, however, induced increased (pro-)inflammatory mediator release from the same in vitro system. The latter finding can be attributed to the different particle compositions, specifically the presence of anatase.Web of Science9272351233

State-of-the-art of 3D cultures (organs-on-a-chip) in safety testing and pathophysiology.

Integrated approaches using different in vitro methods in combination with bioinformatics can (i) increase the success rate and speed of drug development; (ii) improve the accuracy of toxicological risk assessment; and (iii) increase our understanding of disease. Three-dimensional (3D) cell culture models are important building blocks of this strategy which has emerged during the last years. The majority of these models are organotypic, i.e., they aim to reproduce major functions of an organ or organ system. This implies in many cases that more than one cell type forms the 3D structure, and often matrix elements play an important role. This review summarizes the state of the art concerning commonalities of the different models. For instance, the theory of mass transport/metabolite exchange in 3D systems and the special analytical requirements for test endpoints in organotypic cultures are discussed in detail. In the next part, 3D model systems for selected organs--liver, lung, skin, brain--are presented and characterized in dedicated chapters. Also, 3D approaches to the modeling of tumors are presented and discussed. All chapters give a historical background, illustrate the large variety of approaches, and highlight up- and downsides as well as specific requirements. Moreover, they refer to the application in disease modeling, drug discovery and safety assessment. Finally, consensus recommendations indicate a roadmap for the successful implementation of 3D models in routine screening. It is expected that the use of such models will accelerate progress by reducing error rates and wrong predictions from compound testing

Macrophages Are Required for Dendritic Cell Uptake of Respiratory Syncytial Virus from an Infected Epithelium

We have previously shown that the respiratory syncytial virus [RSV] can productively infect monocyte derived dendritic cells [MoDC] and remain dormant within the same cells for prolonged periods. It is therefore possible that infected dendritic cells act as a reservoir within the airways of individuals between annual epidemics. In the present study we explored the possibility that sub-epithelial DCs can be infected with RSV from differentiated bronchial epithelium and that in turn RSV from DCs can infect the epithelium. A dual co-culture model was established in which a differentiated primary airway epithelium on an Air Liquid Interface (ALI) was cultured on a transwell insert and MoDCs were subsequently added to the basolateral membrane of the insert. Further experiments were undertaken using a triple co-culture model in which in which macrophages were added to the apical surface of the differentiated epithelium. A modified RSV [rr-RSV] expressing a red fluorescent protein marker of replication was used to infect either the MoDCs or the differentiated epithelium and infection of the reciprocal cell type was assessed using confocal microscopy. Our data shows that primary epithelium became infected when rr-RSV infected MoDCs were introduced onto the basal surface of the transwell insert. MoDCs located beneath the epithelium did not become infected with virus from infected epithelial cells in the dual co-culture model. However when macrophages were present on the apical surface of the primary epithelium infection of the basal MoDCs occurred. Our data suggests that RSV infected dendritic cells readily transmit infection to epithelial cells even when they are located beneath the basal layer. However macrophages appear to be necessary for the transmission of infection from epithelial cells to basal dendritic cells

Engineered nanomaterials: toward effective safety management in research laboratories

It is still unknown which types of nanomaterials and associated doses represent an actual danger to humans and environment. Meanwhile, there is consensus on applying the precautionary principle to these novel materials until more information is available. To deal with the rapid evolution of research, including the fast turnover of collaborators, a user-friendly and easy-to-apply risk assessment tool offering adequate preventive and protective measures has to be provided.Results: Based on new information concerning the hazards of engineered nanomaterials, we improved a previously developed risk assessment tool by following a simple scheme to gain in efficiency. In the first step, using a logical decision tree, one of the three hazard levels, from H1 to H3, is assigned to the nanomaterial. Using a combination of decision trees and matrices, the second step links the hazard with the emission and exposure potential to assign one of the three nanorisk levels (Nano 3 highest risk; Nano 1 lowest risk) to the activity. These operations are repeated at each process step, leading to the laboratory classification. The third step provides detailed preventive and protective measures for the determined level of nanorisk.Conclusions: We developed an adapted simple and intuitive method for nanomaterial risk management in research laboratories. It allows classifying the nanoactivities into three levels, additionally proposing concrete preventive and protective measures and associated actions. This method is a valuable tool for all the participants in nanomaterial safety. The users experience an essential learning opportunity and increase their safety awareness. Laboratory managers have a reliable tool to obtain an overview of the operations involving nanomaterials in their laboratories; this is essential, as they are responsible for the employee safety, but are sometimes unaware of the works performed. Bringing this risk to a three-band scale (like other types of risks such as biological, radiation, chemical, etc.) facilitates the management for occupational health and safety specialists. Institutes and school managers can obtain the necessary information to implement an adequate safety management system. Having an easy-to-use tool enables a dialog between all these partners, whose semantic and priorities in terms of safety are often different

The emergence of synaesthesia in a Neuronal Network Model via changes in perceptual sensitivity and plasticity

Synaesthesia is an unusual perceptual experience in which an inducer stimulus triggers a percept in a different domain in addition to its own. To explore the conditions under which synaesthesia evolves, we studied a neuronal network model that represents two recurrently connected neural systems. The interactions in the network evolve according to learning rules that optimize sensory sensitivity. We demonstrate several scenarios, such as sensory deprivation or heightened plasticity, under which synaesthesia can evolve even though the inputs to the two systems are statistically independent and the initial cross-talk interactions are zero. Sensory deprivation is the known causal mechanism for acquired synaesthesia and increased plasticity is implicated in developmental synaesthesia. The model unifies different causes of synaesthesia within a single theoretical framework and repositions synaesthesia not as some quirk of aberrant connectivity, but rather as a functional brain state that can emerge as a consequence of optimising sensory information processing

Ultrasensitive gold micro-structured electrodes enabling the detection of extra-cellular long-lasting potentials in astrocytes populations

Ultra-sensitive electrodes for extracellular recordings were fabricated and electrically characterized. A signal detection limit defined by a noise level of 0.3-0.4 mu V for a bandwidth of 12.5 Hz was achieved. To obtain this high sensitivity, large area (4 mm(2)) electrodes were used. The electrode surface is also micro-structured with an array of gold mushroom-like shapes to further enhance the active area. In comparison with a flat gold surface, the micro-structured surface increases the capacitance of the electrode/electrolyte interface by 54%. The electrode low impedance and low noise enable the detection of weak and low frequency quasi-periodic signals produced by astrocytes populations that thus far had remained inaccessible using conventional extracellular electrodes. Signals with 5 mu V in amplitude and lasting for 5-10 s were measured, with a peak-to-peak signal-to-noise ratio of 16. The electrodes and the methodology developed here can be used as an ultrasensitive electrophysiological tool to reveal the synchronization dynamics of ultra-slow ionic signalling between non-electrogenic cells.Portuguese Foundation for Science and Technology (FCT), through the project "Implantable organic devices for advanced therapies" (INNOVATE) [PTDC/EEI-AUT/5442/2014]; Instituto de Telecomunicacoes [UID/Multi/04326/2013]; Associated Laboratory - Institute of Nanoscience and Nanotechnology [POCI-01-0145-FEDER-016623]; [PTDC/CTM-NAN/3146/2014