Previous studies using echocardiography in healthy subjects have reported conflicting data regarding the percentage of the stroke volume (SV) of the left ventricle (LV) resulting from longitudinal and radial function, respectively. Therefore, the aim was to quantify the percentage of SV explained by longitudinal atrioventricular plane displacement (AVPD) in controls, athletes, and patients with decreased LV function due to dilated cardiomyopathy (DCM). Twelve healthy subjects, 12 elite triathletes, and 12 patients with DCM and ejection fraction below 30% were examined by cine magnetic resonance imaging. AVPD and SV were measured in long- and short-axis images, respectively. The percentage of the SV explained by longitudinal function (SVAVPD%) was calculated as the mean epicardial area of the largest short-axis slices in end diastole multiplied by the AVPD and divided by the SV. SV was higher in athletes [140 ± 4 ml (mean ± SE), P = 0.009] and lower in patients (72 ± 7 ml, P < 0.001) when compared with controls (116 ± 6 ml). AVPD was similar in athletes (17 ± 1 mm, P = 0.45) and lower in patients (7 ± 1 mm, P < 0.001) when compared with controls (16 ± 0 mm). SVAVPD% was similar both in athletes (57 ± 2%, P = 0.51) and in patients (67 ± 4%, P = 0.24) when compared with controls (60 ± 2%). In conclusion, longitudinal AVPD is the primary contributor to LV pumping and accounts for ~60% of the SV. Although AVPD is less than half in patients with DCM when compared with controls and athletes, the contribution of AVPD to LV function is maintained, which can be explained by the larger short-axis area in DCM.

In this paper we present improvements to our Bayesian approach for describing the position distribution of the endocardium in cardiac ultrasound image sequences. The problem is represented as a latent variable model, which represents the inside and outside of the endocardium, for which the posterior density is estimated. We start our construction by assuming a three-component Rayleigh mixture model: for blood, echocardiographic artifacts, and tissue. The Rayleigh distribution has been previously shown to be a suitable model for blood and tissue in cardiac ultrasound images. From the mixture model parameters we build a latent variable model, with two realizations: tissue and endocardium. The model is refined by incorporating priors for spatial and temporal smoothness, in the form of total variation, connectivity, preferred shapes and position, by using the principal components and location distribution of manually segmented training shapes. The posterior density is sampled by a Gibbs method to estimate the expected latent variable image which we call the Bayesian ProbabilityMap, since it describes the probability of pixels being classified as either heart tissue or within the endocardium. By sampling the translation distribution of the latent variables, we improve the convergence rate of the algorithm. Our experiments show promising results indicating the usefulness of the Bayesian Probability Maps for the clinician since, instead of producing a single segmenting curve, it highlights the uncertain areas and suggests possible segmentations.

Mesoporous silica particles (MSPs) have great potential to be used as drug carriers for inhalable treatments based on their physiochemical composition. MSPs are biocompatible microparticles that break down into nanoparticles when solved in biological fluids. The small size raises concerns about translocation from lung tissue into the bloodstream. The interaction of MSPs with erythrocytes is a critical point to be addressed, and the hemolytic assay is a classical test used to evaluate particle toxicity. This project used naked MSPs and MSPs loaded with an antibiotic and degraded MSPs to determine their influence on hemolytic activity. Scanning electron microscopy (SEM) was performed on erythrocytes to observe if the interaction caused changes to the cell morphology. The percentage of induced hemolysis was calculated and evaluated according to standard practice. The results showed that only the highest concentration of naked and loaded MSPs, at 25 mg/L, caused enough hemolysis to be considered slightly hemolytic but no replicate induced hemolysis above 5%. Hemolysis was not affected by using naked MSPs compared to loaded MSPs. Degraded MSPs were identified as significantly more compatible than intact MSPs and didn’t induce >2% hemolysis. There were no noticeable cell morphology changes observed through the SEM. The experiment concluded that intact MSP is not considered hemolytic under static conditions at 12.5 mg/L or lower. However, hemolytic assays using moving and dynamic flow models should be performed before a complete assessment of MSPs hemolytic activity can be made. Future studies on interactions between MSPs and various human cells and tissues will determine the medical applicability of MSPs as drug carriers for inhalable therapy. 

There is a clinical need for conceptually new treatments that target the excessive activation of inflammatory pathways during systemic infection. Thrombin-derived C-terminal peptides (TCPs) are endogenous anti-infective immunomodulators interfering with CD14-mediated TLR-dependent immune responses. Here we describe the development of a peptide-based compound for systemic use, sHVF18, expressing the evolutionarily conserved innate structural fold of natural TCPs. Using a combination of structure- and in silico-based design, nuclear magnetic resonance spectroscopy, biophysics, mass spectrometry, cellular, and in vivo studies, we here elucidate the structure, CD14 interactions, protease stability, transcriptome profiling, and therapeutic efficacy of sHVF18. The designed peptide displays a conformationally stabilized, protease resistant active innate fold and targets the LPS-binding groove of CD14. In vivo, it shows therapeutic efficacy in experimental models of endotoxin shock in mice and pigs and increases survival in mouse models of systemic polymicrobial infection. The results provide a drug class based on Nature´s own anti-infective principles.

Peptide imprinted polymers were developed for detection of progastrin releasing peptide (ProGRP); a low abundant blood based biomarker for small cell lung cancer. The polymers targeted the proteotypic nona-peptide sequence NLLGLIEAK and were used for selective enrichment of the proteotypic peptide prior to LCMS based quantification. Peptide imprinted polymers with the best affinity characteristics were first identified from a 96-polymer combinatorial library. The effects of functional monomers, crosslinker, porogen, and template on adsorption capacity and selectivity for NLLGLIEAK were investigated and optimized. Ultimately, a solid phase extraction method was developed for highly selective enrichment of the target peptide from tryptic digests.

Pulmonary delivery and formulation of biologics are among the more complex and growing scientific topics in drug delivery. We herein developed a dry powder formulation using disordered mesoporous silica particles (MSP) as the sole excipient and lysozyme, the most abundant antimicrobial proteins in the airways, as model protein. The MSP had the optimal size for lung deposition (2.43 ± 0.13 µm). A maximum lysozyme loading capacity (0.35 mg/mg) was achieved in 150 mM PBS, which was seven times greater than that in water. After washing and freeze-drying, we obtained a dry powder consisting of spherical, non-aggregated particles, free from residual buffer, or unabsorbed lysozyme. The presence of lysozyme was confirmed by TGA and FT-IR, while N₂ adsorption/desorption and SAXS analysis indicate that the protein is confined within the internal mesoporous structure. The dry powder exhibited excellent aerodynamic performance (fine particle fraction <5 µm of 70.32%). Lysozyme was released in simulated lung fluid in a sustained kinetics and maintaining high enzymatic activity (71–91%), whereas LYS-MSP were shown to degrade into aggregated nanoparticulate microstructures, reaching almost complete dissolution (93%) within 24 h. MSPs were nontoxic to in vitro lung epithelium. The study demonstrates disordered MSP as viable carriers to successfully deliver protein to the lungs, with high deposition and retained activity.

Background: In general, it is known that continuity of care can contribute to an increase inpatient satisfaction, reduce health care costs, and improve patient outcomes. A guarantee of continuityin pharmacotherapy is a big challenge facing Japanese health care as a system that encouragescooperation/collaboration for pharmacists with other health care professions is currently lacking.Method: This is a narrative review. Results: The Lund Integrated Medicine Management (LIMM)model describes a systematic approach to individuals and was developed in Sweden to optimizepharmacotherapy among elderly inpatients. The aim of the LIMM model is to provide patientswith continuous pharmacotherapy at different levels of care. The LIMM model, in which a clinicalpharmacist is the catalyst and leads other health care professions in completing the process, has thepotential to reduce potentially inappropriate prescriptions, reduce rehospitalization risk, unscheduledhospital revisits due to problems related to medications, reduce total medical expenditure, andprovide a comprehensive understanding of patients’ conditions of taking medicine. Conclusions:Introducing a framework such as Sweden’s LIMM model, anchored by clinical pharmacists, couldprovide a good opportunity to promote collaborations among different health care professionals andimprove continuity in pharmacotherapy.

Background: Visual assessment of left ventricular ejection fraction (LVEF) is often used in clinical routine despite general recommendations to use quantitative biplane Simpsons (BPS) measurements. Even thou quantitative methods are well validated and from many reasons preferable, the feasibility of visual assessment (eyeballing) is superior. There is to date only sparse data comparing visual EF assessment in comparison to quantitative methods available. The aim of this study was to compare visual EF assessment by two-dimensional echocardiography (2DE) and triplane echocardiography (TPE) using quantitative real-time three-dimensional echocardiography (RT3DE) as the reference method. Methods: Thirty patients were enrolled in the study. Eyeballing EF was assessed using apical 4-and 2 chamber views and TP mode by two experienced readers blinded to all clinical data. The measurements were compared to quantitative RT3DE. Results: There were an excellent correlation between eyeballing EF by 2D and TP vs 3DE (r = 0.91 and 0.95 respectively) without any significant bias (-0.5 ± 3.7% and -0.2 ± 2.9% respectively). Intraobserver variability was 3.8% for eyeballing 2DE, 3.2% for eyeballing TP and 2.3% for quantitative 3D-EF. Interobserver variability was 7.5% for eyeballing 2D and 8.4% for eyeballing TP. Conclusion: Visual estimation of LVEF both using 2D and TP by an experienced reader correlates well with quantitative EF determined by RT3DE. There is an apparent trend towards a smaller variability using TP in comparison to 2D, this was however not statistically significant.

BACKGROUND: This study explores the feasibility of non-invasive evaluation of left ventricular (LV) flow-volume dynamics using 3-dimensional (3D) echocardiography, and the capacity of such an approach to identify altered LV hemodynamic states caused by valvular abnormalities. METHODS: Thirty-one patients with moderate-severe aortic (AS) and mitral (MS) stenoses (21 and 10 patients, respectively) and 10 healthy volunteers underwent 3D echocardiography with full volume acquisition using Philips Sonos 7500 equipment. The digital 3D data were post- processed using TomTec software. LV flow-volume loops were subsequently constructed for each subject by plotting instantaneous LV volume data sampled throughout the cardiac cycle vs. their first derivative representing LV flow. After correction for body surface area, an average flow-volume loop was calculated for each subject group. RESULTS: Flow-volume loops were obtainable in all subjects, except 3 patients with AS. The flow-volume diagrams displayed clear differences in the form and position of the loops between normal individuals and the respective patient groups. In patients with AS, an "obstructive" pattern was observed, with lower flow values during early systole and larger end-systolic volume. On the other hand, patients with MS displayed a "restrictive" flow-volume pattern, with reduced diastolic filling and smaller end-diastolic volume. CONCLUSION: Non-invasive evaluation of LV flow-volume dynamics using 3D-echocardiographic data is technically possible and the approach has a capacity to identify certain specific types of alteration of LV flow-volume pattern caused by valvular abnormalities, thus reflecting underlying hemodynamic states specific for these abnormalities.

Cubosome particles were produced by fragmenting a cubic crystalline phase of glycerol monooleate and water in the presence of a stabilizing poly(ethylene oxide)-based polymer. The aim of our investigation was to study the interaction between these particles and mucin to gain information on how they would perform as a vehicle for mucosal drug delivery. Particle electrophoresis was used to investigate the interactions between particles and mucin in solution, and ellipsometry was utilized to study the interactions between particles and mucin-coated silica surfaces. The interaction studies were performed at relevant physiological conditions, and the pH and ionic strength were varied to gain more information about the driving forces for the interaction. The results from electrophoretic measurements showed that mucin in solution adsorbed to the particles at pH 4, whereas at pH 6 no clear interaction was detected. From ellipsometric measurements it was evident that the particles adsorb reversibly to a mucin-coated silica surface at pH 4, while no adsorption of particles could be detected at pH 6. The overall conclusion is that the interaction between these particles and mucin is weak and pH-dependent. These findings are in agreement with other investigations of the interactions between mucin and poly(ethylene oxide) chains.

BACKGROUND: Relatively limited and conflicting data are available on the effects of cardiac resynchronization therapy (CRT) on coronary blood flow (CBF). AIMS: To investigate changes in the left anterior descending coronary artery (LAD) flow under different CRT pacing modes by means of transthoracic Doppler echocardiography (TTE). METHODS: Twenty-two responders to CRT (67+/-11 years) with idiopathic dilated cardiomyopathy underwent TTE assessment of LAD flow and Tissue Velocity Imaging during 4 programming modes: intrinsic conduction (IC), right ventricular pacing (RV), simultaneous biventricular pacing (BVP), BVP with left ventricular (LV) pre-activation. RESULTS: Mean coronary flow velocity (CFV) was increased by simultaneous BVP (p=0.0063 vs. IC) and BVP with LV pre-activation (p<0.0001 vs. IC; p=0.027 vs. simultaneous BVP). Peak CFV and LAD flow velocity/time integral were highest during BVP with LV pre-activation. A reduction in septal-to-lateral delay and an increase in peak systolic velocity in the basal septum were observed during simultaneous BVP and BVP with LV pre-activation. CONCLUSIONS: In CRT responders with idiopathic dilated cardiomyopathy, an increase in LAD flow, assessed by TTE, was observed during simultaneous BVP and BVP with LV pre-activation. This was associated with an improvement in regional myocardial contraction and a decrease in intraventricular dyssynchrony.