Superior venous drainage in the "LifeBox": a portable extracorporeal oxygenator with a self-expanding venous cannula.

BACKGROUND: In an experimental setting, the performance of the LifeBox, a new portable extracorporeal membrane oxygenator (ECMO) system suitable for patient transport, is presented. Standard rectilinear percutaneous cannulae are normally employed for this purpose, but have limited flow and pressure delivery due to their rigid structure. Therefore, we aimed to determine the potential for flow increase by using self-expanding venous cannulae. METHODS: Veno-arterial bypass was established in three pigs (40.6+/-5.1 kg). The venous line of the cardiopulmonary bypass was established by cannulation of the external jugular vein. The arterial side of the circulation was secured by cannulation of the common carotid artery. Two different venous cannulae (SmartCanula 18/36F 430mm and Biomedicus 19F) were examined for their functional integrity when used in conjunction with the centrifugal pump (500-3000 RPM) of the LifeBox system. RESULTS: At 1500, 2000, 2500, and 3000 RPM, the blood flow increased steadily for each cannula, but remained higher in the self-expanding cannula. That is, the 19F rectilinear cannula achieved a blood flow of 0.93+/-0.14, 1.47+/-0.37, 1.9+/-0.68, and 1.5+/-0.9 l/min, respectively, and the 18/36F self-expanding cannula achieved 1.1+/-0.1, 1.9+/-0.33, 2.8+/-0.39 and 3.66+/-0.52 l/min. However, when tested for venous line pressure, the standard venous cannula achieved -29+/-10.7mmHg while the self-expanding cannula achieved -13.6 +/-4.3mmHg at 1500 RMP. As the RPM increased from 2500 to 3000, the venous line pressure accounted for -141.9+/-20 and -98+/-7.3mmHg for the 19F rectilinear cannula and -30.6+/-6.4 and -45+/-11.6mmHg for the self-expanding cannula. CONCLUSION: The self-expanding cannula exhibited superior venous drainage ability when compared to the performance of the standard rectilinear cannula with the use of the LifeBox. The flow rate achieved was approximately 40% greater than the standard drainage device, with a maximal pump flow recorded at 4.3l/min.

Differentiation of heroin and cocaine using dual-energy CT-an experimental study.

OBJECTIVE: To evaluate if heroin and cocaine can be distinguished using dual-energy CT. MATERIALS AND METHODS: Twenty samples of heroin and cocaine at different concentrations and standardized compression (SC) were scanned in dual-energy mode on a newest generation Dual Energy 64-row MDCT scanner. CT number, spectral graphs, and dual-energy index (DEI) were evaluated. Results were prospectively tested on six original samples from a body packer. Wilcoxon's test was used for statistical evaluation. RESULTS: Values are given as median and range. Under SC, the CT number of cocaine samples (-29.87 Hounsfield unit (HU) [-125.85; 16.16 HU]) was higher than the CT number of heroin samples (-184.37 HU [-199.81; -159.25 HU]; p < 0.01). Slope of spectral curves for cocaine was -2.36 HU/keV [-7.15; -0.67 HU/keV], and for heroin, 1.75 HU/keV [1.28; 2.5 HU/keV] (p < 0.01). DEI was 0.0352 [0.0081; 0.0528] for cocaine and significantly higher than for heroin samples (-0.0127 [-0.0097; -0.0159]; p < 0.001). While CT number was inconclusive, all six original packs were correctly classified after evaluation of the spectral curve and DEI. In contrast to the CT number, slope of the spectral curve and DEI were independent of concentration and compression. CONCLUSION: The slope of the spectral curve and the DEI from dual-energy CT data can be used to distinguish heroin and cocaine in vitro; these results are independent of compression and concentration in the measured range.

Biomechanical concept and clinical outcome of dual mobility cups.

Dual mobility cup systems in total hip arthroplasty consist of a metal back with a non-constrained liner, in which a constrained standard head articulates. While superior stability of such implants in comparison with standard total hip replacements is assumed, it is the purpose of this study to outline the biomechanical concept of dual mobility cups and to describe implant survival and dislocation rate based on the series published in the English-speaking and Francophone literature. A growing body of evidence indicates reduced dislocation rates in primary and revision total hip arthroplasty and in selected tumour cases. The limited availability of studies evaluating long-term implant survival and existing concerns with regard to increased wear rates and aseptic loosening, leads to the conclusion that such implants have to be used with prudence, particularly in standard primary hip arthroplasty and in young patients.

Evolution of self-organized division of labor in a response threshold model.

Division of labor in social insects is determinant to their ecological success. Recent models emphasize that division of labor is an emergent property of the interactions among nestmates obeying to simple behavioral rules. However, the role of evolution in shaping these rules has been largely neglected. Here, we investigate a model that integrates the perspectives of self-organization and evolution. Our point of departure is the response threshold model, where we allow thresholds to evolve. We ask whether the thresholds will evolve to a state where division of labor emerges in a form that fits the needs of the colony. We find that division of labor can indeed evolve through the evolutionary branching of thresholds, leading to workers that differ in their tendency to take on a given task. However, the conditions under which division of labor evolves depend on the strength of selection on the two fitness components considered: amount of work performed and on worker distribution over tasks. When selection is strongest on the amount of work performed, division of labor evolves if switching tasks is costly. When selection is strongest on worker distribution, division of labor is less likely to evolve. Furthermore, we show that a biased distribution (like 3:1) of workers over tasks is not easily achievable by a threshold mechanism, even under strong selection. Contrary to expectation, multiple matings of colony foundresses impede the evolution of specialization. Overall, our model sheds light on the importance of considering the interaction between specific mechanisms and ecological requirements to better understand the evolutionary scenarios that lead to division of labor in complex systems. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00265-012-1343-2) contains supplementary material, which is available to authorized users.

Self-measurement of blood pressure in clinical trials and therapeutic applications

Self-measurement of blood pressure (SMBP) is increasingly used to assess blood pressure outside the medical setting. A prerequisite for the wide use of SMBP is the availability of validated devices providing reliable readings when they are handled by patients. This is the case today with a number of fully automated oscillometric apparatuses. A major advantage of SMBP is the great number of readings, which is linked with high reproducibility. Given these advantages, one of the major indications for SMBP is the need for evaluation of antihypertensive treatment, either for individual patients in everyday practice or in clinical trials intended to characterize the effects of blood-pressure-lowering medications. In fact, SMBP is particularly helpful for evaluating resistant hypertension and detecting white-coat effect in patients exhibiting high office blood pressure under antihypertensive therapy. SMBP might also motivate the patient and improve his or her adherence to long-term treatment. Moreover, SMBP can be used as a sensitive technique for evaluating the effect of antihypertensive drugs in clinical trials; it increases the power of comparative trials, allowing one to study fewer patients or to detect smaller differences in blood pressure than would be possible with the office measurement. Therefore, SMBP can be regarded as a valuable technique for the follow-up of treated patients as well as for the assessment of antihypertensive drugs in clinical trials.

A 3 years retrospective study of survival for zirconia-based single crowns fabricated from intraoral digital impressions.

OBJECTIVE: To evaluate the clinical performance of glass-ceramic/zirconia crowns fabricated using intraoral digital impressions - a retrospective study with a three-year follow-up. METHODS: 70 consecutive patients with a total of 86 glass-ceramic/zirconia crowns were treated by a single clinician using standardized clinical and laboratory protocols. A complete digital workflow was adopted for the purpose except for the veneering procedure for the glass-ceramic crowns. Occlusal adjustments were made before the ceramic glazing procedure. Before cementation, all abutments where carefully cleaned with a 70% alcoholic solution and air dried. Cementation was performed using dual-curing, self-adhesive resin cement. Patients were re-examined after 12, 24 and 36 months, to assess crown chipping/fractures. RESULTS: After the three-year follow-up, none of the zirconia-based restoration was lost ("apparent" survival rate 100%) otherwise, the chipping rate of the veneering material increased from 9.3% after 12 months, to 14% after 24 months to 30.2% after 36 months. As a consequence, the "real" success rate after 3 years was 69.8%. CONCLUSIONS: After 3 years the success rate of zirconia-based crowns was 69.8%, while the incidence of the chipping was 30.2%. Assuming an exponential increase in chipping rate between 12 and 36 months it can be argued that, among others, the fatigue-mechanism could be advocated as the main factor for the failure of glass-ceramic veneered zirconia especially after 24 months.

The C-terminal domain of Plasmodium falciparum merozoite surface protein 3 self-assembles into alpha-helical coiled coil tetramer.

Proteins located on the surface of the pathogenic malaria parasite Plasmodium falciparum are objects of intensive studies due to their important role in the invasion of human cells and the accessibility to host antibodies thus making these proteins attractive vaccine candidates. One of these proteins, merozoite surface protein 3 (MSP3) represents a leading component among vaccine candidates; however, little is known about its structure and function. Our biophysical studies suggest that the 40 residue C-terminal domain of MSP3 protein self-assembles into a four-stranded alpha-helical coiled coil structure where alpha-helices are packed "side-by-side". A bioinformatics analysis provides an extended list of known and putative proteins from different species of Plasmodium which have such MSP3-like C-terminal domains. This finding allowed us to extend some conclusions of our studies to a larger group of the malaria surface proteins. Possible structural and functional roles of these highly conserved oligomerization domains in the intact merozoite surface proteins are discussed.

Phase-sensitive dual-inversion recovery for accelerated carotid vessel wall imaging.

OBJECTIVES: Dual-inversion recovery (DIR) is widely used for magnetic resonance vessel wall imaging. However, optimal contrast may be difficult to obtain and is subject to RR variability. Furthermore, DIR imaging is time-inefficient and multislice acquisitions may lead to prolonged scanning times. Therefore, an extension of phase-sensitive (PS) DIR is proposed for carotid vessel wall imaging. METHODS: The statistical distribution of the phase signal after DIR is probed to segment carotid lumens and suppress their residual blood signal. The proposed PS-DIR technique was characterized over a broad range of inversion times. Multislice imaging was then implemented by interleaving the acquisition of 3 slices after DIR. Quantitative evaluation was then performed in healthy adult subjects and compared with conventional DIR imaging. RESULTS: Single-slice PS-DIR provided effective blood-signal suppression over a wide range of inversion times, enhancing wall-lumen contrast and vessel wall conspicuity for carotid arteries. Multislice PS-DIR imaging with effective blood-signal suppression is enabled. CONCLUSIONS: A variant of the PS-DIR method has successfully been implemented and tested for carotid vessel wall imaging. This technique removes timing constraints related to inversion recovery, enhances wall-lumen contrast, and enables a 3-fold increase in volumetric coverage at no extra cost in scanning time.

Thrombin-sensitive dual fluorescence imaging and therapeutic agent for detection and treatment of synovial inflammation in murine rheumatoid arthritis.

We have developed a thrombin-sensitive polymeric photosensitizer prodrug (T-PS) to selectively image and eradicate inflammatory lesions in rheumatoid arthritis (RA). Thrombin is a serine protease up-regulated in synovial tissues of rheumatoid arthritis (RA) patients. T-PS consists of a polymeric backbone, to which multiple photosensitizer (PS) units are tethered via short thrombin-cleavable peptide linkers. Fluorescence emission and phototoxicity of the prodrug are efficiently quenched due to the interaction of neighboring photosensitizer units. The prodrug is passively delivered to the inflammation site via the enhanced permeability and retention (EPR) effect. Subsequent site-selective proteolytic cleavage of the peptide linkers restores its photoactivity by increasing the mutual distance between PS. Whole animal imaging in murine collagen-induced arthritis, an experimental model of RA revealed a dose-dependent fluorescence increase in arthritic paws after systemic prodrug injection. In addition, administration of T-PS resulted in much higher fluorescence selectivity for arthritic joints as compared to the free PS. Irradiation of the arthritic joints induced light dose dependent phototoxic effects such as apoptosis, vascular damage and local hemorrhage. Long-term observations showed complete regression of the latter. Irradiated non-arthritic tissues or non-irradiated arthritic tissues showed no histological effects after photodynamic therapy with T-PS. This illustrates that T-PS can localize inflammatory lesions with excellent selectivity and induce apoptosis and vascular shut down after irradiation.

Association of working conditions with self-reported work-related symptoms: results from the Swiss dataset of the European Working Conditions Survey

Working conditions are important determinants of health. The aims of this article are to 1) identify working conditions and work characteristics that are associated with workers' perceptions that their work is harmful to their health and 2) identify with what symptoms these working conditions are associated.We used the Swiss dataset from the 2005 edition of the European Working Conditions Survey. The dependent variable was based on the question "Does your work affect your health?". Logistic regression was used to identify a set of variables collectively associated with self-reported work-related adverse health effects.A total of 330 (32%) participants reported having their health affected by work. The most frequent symptoms included backache (17.1%), muscular pains (13.1%), stress (18.3%) and overall fatigue (11.7%). Scores for self-reported exposure to physicochemical risks, postural and physical risks, high work demand, and low social support were all significantly associated with workers' perceptions that their work is harmful to their health, regardless of gender or age. A high level of education was associated with stress symptoms, and reports that health was affected by work was associated with low job satisfaction.Many workers believe that their work affects their health. Health specialists should pay attention to the potential association between work and their patients' health complaints. This is particularly relevant when patients mention symptoms such as muscular pains, backache, overall fatigue, and stress. Specific attention should be given to complaints of stress in highly educated workers.

Detecting and measuring deprivation in primary care: development, validity and reliability of a self-reported questionnaire - the DiPCare-Q

Background: General practitioners play a central role in taking deprivation into consideration when caring for patients in primary care. Validated questions to identify deprivation in primary-care practices are still lacking. For both clinical and research purposes, this study therefore aims to develop and validate a standardized instrument measuring both material and social deprivation at an individual level. Methods: The Deprivation in Primary Care Questionnaire (DiPCare-Q) was developed using qualitative and quantitative approaches between 2008 and 2011. A systematic review identified 199 questions related to deprivation. Using judgmental item quality, these were reduced to 38 questions. Two focus groups (primary-care physicians, and primary-care researchers), structured interviews (10 laymen), and think aloud interviews (eight cleaning staff) assured face validity. Item response theory analysis was then used to derive the DiPCare-Q index using data obtained from a random sample of 200 patients who were to complete the questionnaire a second time over the phone. For construct and criterion validity, the final 16 questions were administered to a random sample of 1,898 patients attending one of 47 different private primary-care practices in western Switzerland (validation set) along with questions on subjective social status (subjective SES ladder), education, source of income, welfare status, and subjective poverty. Results: Deprivation was defined in three distinct dimensions (table); material deprivation (eight items), social deprivation (five items) and health deprivation (three items). Item consistency was high in both the derivation (KR20 = 0.827) and the validation set (KR20 = 0.778). The DiPCare-Q index was reliable (ICC = 0.847). For construct validity, we showed the DiPCare-Q index to be correlated to patients' estimation of their position on the subjective SES ladder (rs = 0.539). This position was correlated to both material and social deprivation independently suggesting two separate mechanisms enhancing the feeling of deprivation. Conclusion: The DiPCare-Q is a rapid, reliable and validated instrument useful for measuring both material and social deprivation in primary care. Questions from the DiPCare-Q are easy to use when investigating patients' social history and could improve clinicians' ability to detect underlying social distress related to deprivation.

Jagged1-dependent Notch signaling is dispensable for hematopoietic stem cell self-renewal and differentiation.

Jagged1-mediated Notch signaling has been suggested to be critically involved in hematopoietic stem cell (HSC) self-renewal. Unexpectedly, we report here that inducible Cre-loxP-mediated inactivation of the Jagged1 gene in bone marrow progenitors and/or bone marrow (BM) stromal cells does not impair HSC self-renewal or differentiation in all blood lineages. Mice with simultaneous inactivation of Jagged1 and Notch1 in the BM compartment survived normally following a 5FU-based in vivo challenge. In addition, Notch1-deficient HSCs were able to reconstitute mice with inactivated Jagged1 in the BM stroma even under competitive conditions. In contrast to earlier reports, these data exclude an essential role for Jagged1-mediated Notch signaling during hematopoiesis.