Effects of artepillin C on model membranes displaying liquid immiscibility.

It has been hypothesized that the therapeutic effects of artepillin C, a natural compound derived from Brazilian green propolis, are likely related to its partition in the lipid bilayer component of biological membranes. To test this hypothesis, we investigated the effects of the major compound of green propolis, artepillin C, on model membranes (small and giant unilamelar vesicles) composed of ternary lipid mixtures containing cholesterol, which display liquid-ordered (lo) and liquid-disordered (ld) phase coexistence. Specifically, we explored potential changes in relevant membrane parameters upon addition of artepillin C presenting both neutral and deprotonated states by means of small angle X-ray scattering (SAXS), differential scanning calorimetry (DSC), and confocal and multiphoton excitation fluorescence microscopy. Thermotropic analysis obtained from DSC experiments indicated a loss in the lipid cooperativity of lo phase at equilibrium conditions, while at similar conditions spontaneous formation of unilamellar vesicles from SAXS experiments showed that deprotonated artepillin C preferentially located at the surface of the membrane. Time-resolved experiments using fluorescence microscopy showed that at doses above 100 µM, artepillin C in its neutral state interacted with both liquid-ordered and liquid-disordered phases, inducing curvature stress and promoting dehydration at the membrane interface.

Super-resolution microscopy on single particles at fluid interfaces reveals their wetting properties and interfacial deformations.

Solid particles adsorbed at fluid interfaces are crucial for the mechanical stability of Pickering emulsions. The key parameter which determines the kinetic and thermodynamic properties of these colloids is the particle contact angle, θ. Several methods have recently been developed to measure the contact angle of individual particles adsorbed at liquid-liquid interfaces, as morphological and chemical heterogeneities at the particle surface can significantly affect θ. However, none of these techniques enables the simultaneous visualization of the nanoparticles and the reconstruction of the fluid interface to which they are adsorbed, in situ. To tackle this challenge, we utilize a newly developed super-resolution microscopy method, called iPAINT, which exploits non-covalent and continuous labelling of interfaces with photo-activatable fluorescent probes. Herewith, we resolve with nanometer accuracy both the position of individual nanoparticles at a water-octanol interface and the location of the interface itself. First, we determine single particle contact angles for both hydrophobic and hydrophilic spherical colloids. These experiments reveal a non-negligible dependence of θ on particle size, from which we infer an effective line tension, τ. Next, we image elliptical particles at a water-decane interface, showing that the corresponding interfacial deformations can be clearly captured by iPAINT microscopy.

Effects of artepillin C on model membranes displaying liquid immiscibility

It has been hypothesized that the therapeutic effects of artepillin C, a natural compound derived from Brazilian green propolis, are likely related to its partition in the lipid bilayer component of biological membranes. To test this hypothesis, we investigated the effects of the major compound of green propolis, artepillin C, on model membranes (small and giant unilamelar vesicles) composed of ternary lipid mixtures containing cholesterol, which display liquid-ordered (lo) and liquid-disordered (ld) phase coexistence. Specifically, we explored potential changes in relevant membrane parameters upon addition of artepillin C presenting both neutral and deprotonated states by means of small angle X-ray scattering (SAXS), differential scanning calorimetry (DSC), and confocal and multiphoton excitation fluorescence microscopy. Thermotropic analysis obtained from DSC experiments indicated a loss in the lipid cooperativity of lo phase at equilibrium conditions, while at similar conditions spontaneous formation of unilamellar vesicles from SAXS experiments showed that deprotonated artepillin C preferentially located at the surface of the membrane. Time-resolved experiments using fluorescence microscopy showed that at doses above 100 µM, artepillin C in its neutral state interacted with both liquid-ordered and liquid-disordered phases, inducing curvature stress and promoting dehydration at the membrane interface.

Impact of Region-of-Interest Delineation Methods, Reconstruction Algorithms, and Intra- and Inter-Operator Variability on Internal Dosimetry Estimates Using PET.

PURPOSE: Human dosimetry studies play a central role in radioligand development for positron emission tomography (PET). Drawing regions of interest (ROIs) on the PET images is used to measure the dose in each organ. In the study aspects related to ROI delineation methods were evaluated for two radioligands of different biodistribution (intestinal vs urinary). PROCEDURES: PET images were simulated from a human voxel-based phantom. Several ROI delineation methods were tested: antero-posterior projections (AP), 3D sub-samples of the organs (S), and a 3D volume covering the whole-organ (W). Inter- and intra-operator variability ROI drawing was evaluated by using human data. RESULTS: The effective dose estimates using S and W methods were comparable to the true values. AP methods overestimated (49 %) the dose for the radioligand with intestinal biodistribution. Moreover, the AP method showed the highest inter-operator variability: 11 ± 1 %. CONCLUSIONS: The sub-sampled organ method showed the best balance between quantitative accuracy and inter- and intra-operator variability.

iPAINT: a general approach tailored to image the topology of interfaces with nanometer resolution.

Understanding interfacial phenomena in soft materials such as wetting, colloidal stability, coalescence, and friction warrants non-invasive imaging with nanometer resolution. Super-resolution microscopy has emerged as an attractive method to visualize nanostructures labeled covalently with fluorescent tags, but this is not amenable to all interfaces. Inspired by PAINT we developed a simple and general strategy to overcome this limitation, which we coin 'iPAINT: interface Point Accumulation for Imaging in Nanoscale Topography'. It enables three-dimensional, sub-diffraction imaging of interfaces irrespective of their nature via reversible adsorption of polymer chains end-functionalized with photo-activatable moieties. We visualized model dispersions, emulsions, and foams with ∼20 nm and ∼3° accuracy demonstrating the general applicability of iPAINT to study solid/liquid, liquid/liquid and liquid/air interfaces. iPAINT thus broadens the scope of super-resolution microscopy paving the way for non-invasive, high-resolution imaging of complex soft materials.

[Encephalitis associated to anti-NMDA receptor antibodies: a description of two cases in the child/youth population]. / Encefalitis asociada a anticuerpos antirreceptor de NMDA: descripcion de dos casos en poblacion infantojuvenil.

INTRODUCTION: The clinical diagnosis of encephalitis due to anti-glutamate receptor N-methyl D-aspartate (NMDA) antibodies (anti-NMDA encephalitis) is made more complex by the fact that psychiatric clinical features are usually predominant in the early stages. This can lead to a delay in the diagnosis, treatment and prognosis of the disease. CASE REPORTS: We report on two clinical cases attended by the Child/Youth Psychiatry Section of our hospital, in collaboration with the Paediatric and Neurology services. Case 1: a 4-year-old male who was referred owing to behavioural alterations and the regression of previously acquired skills. Case 2: a 13-year-old female who was admitted due to a behavioural disorder within the context of a possible initial psychotic episode. In both cases appropriate complementary tests were performed, including lumbar puncture and anti-NMDA antibodies, which were positive. Once the diagnosis of anti-NMDA encephalitis had been reached, treatment was started: in the first case, with intravenous perfusion of corticoids and immunoglobulins, while in the second rituximab had to be associated. Both patients progressed towards clinical improvement. CONCLUSIONS: Over the last two years there has been an increase in the number of cases of anti-NMDA encephalitis diagnosed in the child/youth population. It is a neuropsychiatric, autoimmune condition, which can correspond to a paraneoplastic syndrome. Follow-up and transvaginal ultrasonography as well as thoracoabdominal computerised axial tomography scans are recommended for at least two years after diagnosis. Early diagnosis and treatment are important, which means that a multi- and interdisciplinary approach is required.

SU-E-T-290: Dosimetric Verification of Helical Tomotherapy against Experimental Measurements for Head and Neck Treatments.

PURPOSE: To verify a Tomotherapy plan for a typical head and neck treatment against experimental measurements. METHODS: The treatment plan for a head and neck case was generated by the Tomotherapy treatment planning system (TPS) to deliver ∼70 Gy in 33 sessions to the contoured PTV. The plan was calculated on a CIRS ATOM anthropomorphic phantom that provides a grid spacing of 3×3 cm2 holes to accommodate thermoluminescent detectors (TLD). The plan was verified against experimental measurements carried out by 7 LiF:Mg,Ti (TLD-700) TLD. Up to 20 locations were selected within the irradiated region and three detectors were used simultaneously at each point to decrease the statistical uncertainty. TLD locations were labeled in the planning system and dose comparisons between TPS prediction and experimental measurements were performed in terms of absolute dose to water for a single fraction. We examined the dose from (i) the corresponding 3.5MV Tomo-scan alone and (ii) the complete treatment. TLD-700 were found to fulfill the requirements of reproducibility, linearity and flat energy response in a previous study. In particular, TLD energy response was previously checked for 6 MV flattening filter free and conventional radiation beams under reference conditions. RESULTS: Doses derived from the TPS were in most cases in good agreement (4% on average) with TLD dose measurements within TLD statistical uncertainties (about 3%). Larger discrepancies up to 7% were found for points close to complex tissue inhomogeneities, such as bony structures. Dose from the scanning procedure alone is about 1 % of the dose per fraction. CONCLUSIONS: This work indicates that dose delivery plans created with Tomotherapy TPS are accurate for head and neck tumor localizations.

Current-voltage characteristic of electrospray processes in microfluidics.

We use a glass-based microfluidic device to study the electric current behavior of an electrospray process in the presence of a coflowing liquid. The current shows strong voltage dependence and weak flow rate dependence, in stark contrast to classical electrospray. By considering that the current is dominated by convection near the apex of the conical meniscus and driven by tangential electric stresses, we quantitatively capture the voltage and flow rate dependence of the current. Our results elucidate the influence of external field strength and open the way to achieve robust electric control of the current and of the drop size in microfluidics.