Dutch home-based pre-reading intervention with children at familial risk of dyslexia

Children (5 and 6 years old, n = 30) at familial risk of dyslexia received a home-based intervention that focused on phoneme awareness and letter knowledge in the year prior to formal reading instruction. The children were compared to a no-training at-risk control group (n = 27), which was selected a year earlier. After training, we found a small effect on a composite score of phoneme awareness (d = 0.29) and a large effect on receptive letter knowledge (d = 0.88). In first grade, however, this did not result in beneficial effects for the experimental group in word reading and spelling. Results are compared to three former intervention studies in The Netherlands and comparable studies from Denmark and Australia

A combined magnetic-acoustic device for simultaneous, co-aligned application of magnetic and ultrasonic fields

Acoustically-responsive microbubbles have been widely researched as agents for both diagnostic and therapeutic applications of ultrasound. Recently, there has also been considerable interest in magnetically functionalised microbubbles as multi-modality imaging agents and carriers for magnetically targeted drug delivery. The latter application in particular requires simultaneous application of magnetic and acoustic fields to a target region. This can present a significant practical challenge, especially in vivo where access is typically limited. In this paper, we present a design for an integrated device capable of generating co-aligned magnetic and acoustic fields in order to accumulate microbubbles at a specific location and then to activate them acoustically. For the purposes of this proof of concept study, the magnetic component of the device was designed to concentrate microbubbles at a distance of 10 mm from the probe’s surface, commensurate with relevant tissue depths in preclinical small animal models. The ultrasound transducer was designed to maximise the acoustic intensity in the same region in order to induce cavitation of the magnetically captured microbubbles. Previous studies have indicated that both microbubble concentration and duration of cavitation activity are positively correlated with therapeutic effect. The ability of the device to trap and activate microbubbles was therefore assessed by a series of in vitro tests in a tissue mimicking phantom containing a single vessel of 1.2 mm diameter. At a flow rate of 4.2 mm/s magnetic trapping produced an increase in intensity under B-mode ultrasound imaging consistent with the predicted accumulation profile. When the microbubbles were exposed to the ultrasound field from the probe, the resulting cavitation activity was sustained for a period more than 4 times longer than that achieved with an identical acoustic field but in the absence of a magnet. The feasibility of developing a larger scale device for human applications is discussed

A Combined Magnetic-Acoustic Device for Simultaneous, Coaligned Application of Magnetic and Ultrasonic Fields

Acoustically‐responsive microbubbles have been widely researched as agents for both diagnostic and therapeutic applications of ultrasound. There has also been considerable interest in magnetically‐functionalised microbubbles as multi‐modality imaging agents and carriers for targeted drug delivery. In this paper, we present a design for an integrated device capable of generating co‐aligned magnetic and acoustic fields in order to accumulate microbubbles at a specific location and to activate them acoustically. For this proof‐of‐concept study, the device was designed to concentrate microbubbles at a distance of 10 mm from the probe's surface, commensurate with relevant tissue depths in preclinical small animal models. Previous studies have indicated that both microbubble concentration and duration of cavitation activity are positively correlated with therapeutic effect. The utility of the device was assessed in vitro tests in a tissue‐mimicking phantom containing a single vessel (1.2 mm diameter). At a peak fluid velocity of 4.2 mm s−1 microbubble accumulation was observed under B‐mode ultrasound imaging and the corresponding cavitation activity was sustained for a period more than 4 times longer than that achieved with an identical acoustic field but in the absence of a magnet. The feasibility of developing a larger scale device for human applications is discussed

Sonothrombolysis with magnetically targeted microbubbles

Microbubble-enhanced sonothrombolysis is a promising approach to increase the safety and efficacy of current pharmacological treatments for ischemic stroke. Maintaining therapeutic concentrations of microbubbles and drugs at the clot site however poses a challenge. The objective of this study was to investigate the efficacy of magnetic microbubble targeting upon clot lysis rates in vitro. Retracted whole porcine blood clots were placed in a flow phantom of a partially occluded middle cerebral artery. The clots were treated with a combination of tissue plasminogen activator (0.75µg/mL), magnetic microbubbles (~107 microbubbles/mL), and ultrasound (0.5MHz, 630kPa peak rarefactional pressure, 0.2Hz pulse repetition frequency, 2% duty cycle). Magnetic targeting was achieved using a single permanent magnet element (0.08-0.38T and 12-140T/m in the region of the clot). The change in clot diameter was measured optically over the course of the experiment. Magnetic targeting produced a three-fold average increase in lysis rates and linear correlation was observed between lysis rate and total energy of acoustic emissions

Magnetic microbubble mediated chemo-sonodynamic therapy using a combined magnetic-acoustic device

Recent pre-clinical studies have demonstrated the potential of combining chemotherapy and sonodynamic therapy for the treatment of pancreatic cancer. Oxygen-loaded magnetic microbubbles have been explored as a targeted delivery vehicle for this application. Despite preliminary positive results, a previous study identified a significant practical challenge regarding the co-alignment of the magnetic and ultrasound fields. The aim of this study was to determine whether this challenge could be addressed through the use of a magnetic-acoustic device (MAD) combining a magnetic array and ultrasound transducer in a single unit, to simultaneously concentrate and activate the microbubbles at the target site. in vitro experiments were performed in tissue phantoms and followed by in vivo treatment of xenograft pancreatic cancer (BxPC-3) tumours in a murine model. In vitro, a 1.4-fold (p < .01) increase in the deposition of a model therapeutic payload within the phantom was achieved using the MAD compared to separate magnetic and ultrasound devices. In vivo, tumours treated with the MAD had a 9% smaller mean volume 8 days after treatment, while tumours treated with separate devices or microbubbles alone were respectively 45% and 112% larger. This substantial and sustained decrease in tumour volume suggests that the proposed drug delivery approach has the potential to be an effective neoadjuvant therapy for pancreatic cancer patients

Not just a fluidifying effect: omega-3 phospholipids induce formation of non-lamellar structures in biomembranes

Polyunsaturated omega-3 fatty acid docosahexaenoic acid (DHA) is found in very high concentrations in a few peculiar tissues, suggesting that it must have a specialized role. DHA was proposed to affect the function of the cell membrane and related proteins through an indirect mechanism of action, based on the DHA-phospholipid effects on the lipid bilayer structure. In this respect, most studies have focused on its influence on lipid-rafts, somehow neglecting the analysis of effects on liquid disordered phases that constitute most of the cell membranes, by reporting in these cases only a general fluidifying effect. In this study, by combining neutron reflectivity, cryo-transmission electron microscopy, small angle neutron scattering, dynamic light scattering and electron paramagnetic resonance spectroscopy, we characterize liquid disordered bilayers formed by the naturally abundant 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine and different contents of a di-DHA glycero-phosphocholine, 22:6-22:6PC, from both a molecular/microscopic and supramolecular/mesoscopic viewpoint. We show that, below a threshold concentration of about 40% molar percent, incorporation of 22:6-22:6PC in the membrane increases the lipid dynamics slightly but sufficiently to promote the membrane deformation and increase of multilamellarity. Notably, beyond this threshold, 22:6-22:6PC disfavours the formation of lamellar phases, leading to a phase separation consisting mostly of small spherical particles that coexist with a minority portion of a lipid blob with water-filled cavities. Concurrently, from a molecular viewpoint, the polyunsaturated acyl chains tend to fold and expose the termini to the aqueous medium. We propose that this peculiar tendency is a key feature of the DHA-phospholipids making them able to modulate the local morphology of biomembranes. This journal i