Biomedical nanoparticles modulate specific CD4+ T cell stimulation by inhibition of antigen processing in dendritic cells

Understanding how nanoparticles may affect immune responses is an essential prerequisite to developing novel clinical applications. To investigate nanoparticle-dependent outcomes on immune responses, dendritic cells (DCs) were treated with model biomedical poly(vinylalcohol)-coated super-paramagnetic iron oxide nanoparticles (PVA-SPIONs). PVA-SPIONs uptake by human monocyte-derived DCs (MDDCs) was analyzed by flow cytometry (FACS) and advanced imaging techniques. Viability, activation, function, and stimulatory capacity of MDDCs were assessed by FACS and an in vitro CD4+ T cell assay. PVA-SPION uptake was dose-dependent, decreased by lipopolysaccharide (LPS)-induced MDDC maturation at higher particle concentrations, and was inhibited by cytochalasin D pre-treatment. PVA-SPIONs did not alter surface marker expression (CD80, CD83, CD86, myeloid/plasmacytoid DC markers) or antigen-uptake, but decreased the capacity of MDDCs to process antigen, stimulate CD4+ T cells, and induce cytokines. The decreased antigen processing and CD4+ T cell stimulation capability of MDDCs following PVA-SPION treatment suggests that MDDCs may revert to a more functionally immature state following particle exposure.

Novel magnetic iron oxide nanoparticles coated with poly(ethylene imine)-g-poly(ethylene glycol) for potential biomedical application: synthesis, stability, cytotoxicity and MR imaging

Magnetic iron oxide nanoparticles have found application as contrast agents for magnetic resonance imaging (MRI) and as switchable drug delivery vehicles. Their stabilization as colloidal carriers remains a challenge. The potential of poly(ethylene imine)-g-poly(ethylene glycol) (PEGPEI) as stabilizer for iron oxide (γ-Fe₂O₃) nanoparticles was studied in comparison to branched poly(ethylene imine) (PEI). Carrier systems consisting of γ-Fe₂O₃-PEI and γ-Fe₂O₃-PEGPEI were prepared and characterized regarding their physicochemical properties including magnetic resonance relaxometry. Colloidal stability of the formulations was tested in several media and cytotoxic effects in adenocarcinomic epithelial cells were investigated. Synthesized γ-Fe₂O₃ cores showed superparamagnetism and high degree of crystallinity. Diameters of polymer-coated nanoparticles γ-Fe₂O₃-PEI and γ-Fe₂O₃-PEGPEI were found to be 38.7 ± 1.0 nm and 40.4 ± 1.6 nm, respectively. No aggregation tendency was observable for γ-Fe₂O₃-PEGPEI over 12 h even in high ionic strength media. Furthermore, IC₅₀ values were significantly increased by more than 10-fold when compared to γ-Fe₂O₃-PEI. Formulations exhibited r₂ relaxivities of high numerical value, namely around 160 mM⁻¹ s⁻¹. In summary, novel carrier systems composed of γ-Fe₂O₃-PEGPEI meet key quality requirements rendering them promising for biomedical applications, e.g. as MRI contrast agents.

A novel interface for hybrid mock circulations to evaluate ventricular assist devices

This paper presents a novel mock circulation for the evaluation of ventricular assist devices (VADs), which is based on a hardware-in-the-loop concept. A numerical model of the human blood circulation runs in real time and computes instantaneous pressure, volume, and flow rate values. The VAD to be tested is connected to a numerical-hydraulic interface, which allows the interaction between the VAD and the numerical model of the circulation. The numerical-hydraulic interface consists of two pressure-controlled reservoirs, which apply the computed pressure values from the model to the VAD, and a flow probe to feed the resulting VAD flow rate back to the model. Experimental results are provided to show the proper interaction between a numerical model of the circulation and a mixed-flow blood pump.

High-accuracy patient-to-image registration for the facilitation of image-guided robotic microsurgery on the head

Image-guided microsurgery requires accuracies an order of magnitude higher than today's navigation systems provide. A critical step toward the achievement of such low-error requirements is a highly accurate and verified patient-to-image registration. With the aim of reducing target registration error to a level that would facilitate the use of image-guided robotic microsurgery on the rigid anatomy of the head, we have developed a semiautomatic fiducial detection technique. Automatic force-controlled localization of fiducials on the patient is achieved through the implementation of a robotic-controlled tactile search within the head of a standard surgical screw. Precise detection of the corresponding fiducials in the image data is realized using an automated model-based matching algorithm on high-resolution, isometric cone beam CT images. Verification of the registration technique on phantoms demonstrated that through the elimination of user variability, clinically relevant target registration errors of approximately 0.1 mm could be achieved.

Can Andean medicine coexist with biomedical healthcare? A comparison of two rural communities in Peru and Bolivia

Background It is commonly assumed that indigenous medical systems remain strong in developing countries because biomedicine is physically inaccessible or financially not affordable. This paper compares the health-seeking behavior of households from rural Andean communities at a Peruvian and a Bolivian study site. The main research question was whether the increased presence of biomedicine led to a displacement of Andean indigenous medical practices or to coexistence of the two healing traditions. Methodology Open-ended interviews and free listing exercises were conducted between June 2006 and December 2008 with 18 households at each study site. Qualitative identification of households’ therapeutic strategies and use of remedies was carried out by means of content analysis of interview transcriptions and inductive interference. Furthermore, a quantitative assessment of the incidence of culture-bound illnesses in local ethnobiological inventories was performed. Results Our findings indicate that the health-seeking behavior of the Andean households in this study is independent of the degree of availability of biomedical facilities in terms of quality of services provided, physical accessibility, and financial affordability, except for specific practices such as childbirth. Preference for natural remedies over pharmaceuticals coexists with biomedical healthcare that is both accessible and affordable. Furthermore, our results show that greater access to biomedicine does not lead to less prevalence of Andean indigenous medical knowledge, as represented by the levels of knowledge about culture-bound illnesses. Conclusions The take-home lesson for health policy-makers from this study is that the main obstacle to use of biomedicine in resource-poor rural areas might not be infrastructural or economic alone. Rather, it may lie in lack of sufficient recognition by biomedical practitioners of the value and importance of indigenous medical systems. We propose that the implementation of health care in indigenous communities be designed as a process of joint development of complementary knowledge and practices from indigenous and biomedical health traditions.

Control of muscle relaxation during anesthesia: a novel approach for clinical routine

During general anesthesia drugs are administered to provide hypnosis, ensure analgesia, and skeletal muscle relaxation. In this paper, the main components of a newly developed controller for skeletal muscle relaxation are described. Muscle relaxation is controlled by administration of neuromuscular blocking agents. The degree of relaxation is assessed by supramaximal train-of-four stimulation of the ulnar nerve and measuring the electromyogram response of the adductor pollicis muscle. For closed-loop control purposes, a physiologically based pharmacokinetic and pharmacodynamic model of the neuromuscular blocking agent mivacurium is derived. The model is used to design an observer-based state feedback controller. Contrary to similar automatic systems described in the literature this controller makes use of two different measures obtained in the train-of-four measurement to maintain the desired level of relaxation. The controller is validated in a clinical study comparing the performance of the controller to the performance of the anesthesiologist. As presented, the controller was able to maintain a preselected degree of muscle relaxation with excellent precision while minimizing drug administration. The controller performed at least equally well as the anesthesiologist.

Reporting of randomized controlled trials in Hodgkin lymphoma in biomedical journals

BACKGROUND: Randomized controlled trials (RCTs) are the best tool to evaluate the effectiveness of clinical interventions. The Consolidated Standards for Reporting Trials (CONSORT) statement was introduced in 1996 to improve reporting of RCTs. We aimed to determine the extent of ambiguity and reporting quality as assessed by adherence to the CONSORT statement in published reports of RCTs involving patients with Hodgkin lymphoma from 1966 through 2002. METHODS: We analyzed 242 published full-text reports of RCTs in patients with Hodgkin lymphoma. Quality of reporting was assessed using a 14-item questionnaire based on the CONSORT checklist. Reporting was studied in two pre-CONSORT periods (1966-1988 and 1989-1995) and one post-CONSORT period (1996-2002). RESULTS: Only six of the 14 items were addressed in 75% or more of the studies in all three time periods. Most items that are necessary to assess the methodologic quality of a study were reported by fewer than 20% of the studies. Improvements over time were seen for some items, including the description of statistics methods used, reporting of primary research outcomes, performance of power calculations, method of randomization and concealment allocation, and having performed intention-to-treat analysis. CONCLUSIONS: Despite recent improvements, reporting levels of CONSORT items in RCTs involving patients with Hodgkin lymphoma remain unsatisfactory. Further concerted action by journal editors, learned societies, and medical schools is necessary to make authors even more aware of the need to improve the reporting RCTs in medical journals to allow assessment of validity of published clinical research.

Safety of Active Implantable Devices during MRI Examinations: A Finite Element Analysis of an Implantable Pump

The goal of this study was to propose a general numerical analysis methodology to evaluate the magnetic resonance imaging (MRI)-safety of active implants. Numerical models based on the finite element (FE) technique were used to estimate if the normal operation of an active device was altered during MRI imaging. An active implanted pump was chosen to illustrate the method. A set of controlled experiments were proposed and performed to validate the numerical model. The calculated induced voltages in the important electronic components of the device showed dependence with the MRI field strength. For the MRI radiofrequency fields, significant induced voltages of up to 20 V were calculated for a 0.3T field-strength MRI. For the 1.5 and 3.0T MRIs, the calculated voltages were insignificant. On the other hand, induced voltages up to 11 V were calculated in the critical electronic components for the 3.0T MRI due to the gradient fields. Values obtained in this work reflect to the worst case situation which is virtually impossible to achieve in normal scanning situations. Since the calculated voltages may be removed by appropriate protection circuits, no critical problems affecting the normal operation of the pump were identified. This study showed that the proposed methodology helps the identification of the possible incompatibilities between active implants and MR imaging, and can be used to aid the design of critical electronic systems to ensure MRI-safety

Accurate and robust reconstruction of proximal femur from sparse intraoperative data and dense point distribution model for surgical navigation

Constructing a 3D surface model from sparse-point data is a nontrivial task. Here, we report an accurate and robust approach for reconstructing a surface model of the proximal femur from sparse-point data and a dense-point distribution model (DPDM). The problem is formulated as a three-stage optimal estimation process. The first stage, affine registration, is to iteratively estimate a scale and a rigid transformation between the mean surface model of the DPDM and the sparse input points. The estimation results of the first stage are used to establish point correspondences for the second stage, statistical instantiation, which stably instantiates a surface model from the DPDM using a statistical approach. This surface model is then fed to the third stage, kernel-based deformation, which further refines the surface model. Handling outliers is achieved by consistently employing the least trimmed squares (LTS) approach with a roughly estimated outlier rate in all three stages. If an optimal value of the outlier rate is preferred, we propose a hypothesis testing procedure to automatically estimate it. We present here our validations using four experiments, which include 1 leave-one-out experiment, 2 experiment on evaluating the present approach for handling pathology, 3 experiment on evaluating the present approach for handling outliers, and 4 experiment on reconstructing surface models of seven dry cadaver femurs using clinically relevant data without noise and with noise added. Our validation results demonstrate the robust performance of the present approach in handling outliers, pathology, and noise. An average 95-percentile error of 1.7-2.3 mm was found when the present approach was used to reconstruct surface models of the cadaver femurs from sparse-point data with noise added.