Accurate simulation of transcranial ultrasound propagation for ultrasonic neuromodulation and stimulation.

Non-invasive, focal neurostimulation with ultrasound is a potentially powerful neuroscientific tool that requires effective transcranial focusing of ultrasound to develop. Time-reversal (TR) focusing using numerical simulations of transcranial ultrasound propagation can correct for the effect of the skull, but relies on accurate simulations. Here, focusing requirements for ultrasonic neurostimulation are established through a review of previously employed ultrasonic parameters, and consideration of deep brain targets. The specific limitations of finite-difference time domain (FDTD) and k-space corrected pseudospectral time domain (PSTD) schemes are tested numerically to establish the spatial points per wavelength and temporal points per period needed to achieve the desired accuracy while minimizing the computational burden. These criteria are confirmed through convergence testing of a fully simulated TR protocol using a virtual skull. The k-space PSTD scheme performed as well as, or better than, the widely used FDTD scheme across all individual error tests and in the convergence of large scale models, recommending it for use in simulated TR. Staircasing was shown to be the most serious source of error. Convergence testing indicated that higher sampling is required to achieve fine control of the pressure amplitude at the target than is needed for accurate spatial targeting.

Beam distortion due to gold fiducial markers during salvage high-intensity focused ultrasound in the prostate.

PURPOSE: High intensity focused ultrasound (HIFU) provides a non-invasive salvage treatment option for patients with recurrence after external beam radiation therapy (EBRT). As part of EBRT the prostate is frequently implanted with permanent fiducial markers. To date, the impact of these markers on subsequent HIFU treatment is unknown. The objective of this work was to systematically investigate, using computational simulations, how these fiducial markers affect the delivery of HIFU treatment. METHODS: A series of simulations was performed modelling the propagation of ultrasound pressure waves in the prostate with a single spherical or cylindrical gold marker at different positions and orientations. For each marker configuration, a set of metrics (spatial-peak temporal-average intensity, focus shift, focal volume) was evaluated to quantify the distortion introduced at the focus. An analytical model was also developed describing the marker effect on the intensity at the focus. The model was used to examine the marker's impact in a clinical setting through case studies. RESULTS: The simulations show that the presence of the marker in the pre-focal region causes reflections which induce a decrease in the focal intensity and focal volume, and a shift of the maximum pressure point away from the transducer's focus. These effects depend on the shape and orientation of the marker and become more pronounced as its distance from the transducer's focus decreases, with the distortion introduced by the marker greatly increasing when placed within 5 mm of the focus. The analytical model approximates the marker's effect and can be used as an alternative method to the computationally intensive and time consuming simulations for quickly estimating the intensity at the focus. A retrospective review of a small patient cohort selected for focal HIFU after failed EBRT indicates that the presence of the marker may affect HIFU treatment delivery. CONCLUSIONS: The distortion introduced by the marker to the HIFU beam when positioned close to the focus may result in an undertreated region beyond the marker due to less energy arriving at the focus, and an overtreated region due to reflections. Further work is necessary to investigate whether the results presented here justify the revision of the patient selection criteria or the markers' placement protocol.

N-(2-hydroxypropyl) methacrylamide based cryogels--synthesis and biomimetic modification for stem cell applications.

The design of favorable mechanical properties and suitable surface modifications of hydrogels in order to stimulate specific cell response is a great challenge. N-(2-Hydroxypropyl) methacryl-amide (HPMA) was utilized to form macroporous cryogel scaffolds for stem cell applications. Furthermore, one group of scaffolds was enhanced by copolymerization of HPMA with methacryloyl-GGGRGDS-OH peptide in an effort to integrate biomimetic adhesion sites. The cryogels were characterized by stiffness and equilibrium swelling measurements as well as by scanning electron microscopy. Cell culture experiments were performed with human adipose-derived stem cells and substrates were found completely non-toxic. Moreover, RGDS-enriched cryogels supported cell attachment, spreading and proliferation, so they can be considered suitable for designed aims.

Adoptive therapy with donor lymphocyte infusion after allogenic hematopoietic SCT in pediatric patients.

The aim of this study was to analyse the experience of Polish Pediatric Group for Hematopoietic Stem Cell Transplantation in respect to donor lymphocyte infusion procedure. The study included 51 pediatric patients with malignant (45) and non-malignant (6) diseases treated with DLI in the period 1993-2012. The indications for DLI were as follows: (1) increasing recipient chimerism after non-ablative hematopoietic SCT (18 patients); (2) immunomodulation after a reduced intensity conditioning regimen (2 patients); (3) increase in minimal residual disease detection (3 patients); and (4) relapse (28 patients). DLI was carried out at a median of 6 (0.5-79) months after SCT. DLI was administered as either a single-dose (in 19 cases) or in escalating-dose regimens (in 32 cases). The median total dose of CD3-positive T cells was 28.0 (0.1-730.0) × 10(6)/kg body weight. The time for assessment of DLI efficacy ranged from 0 to 70 (median 3) months. At evaluation, 18 patients experienced CR, 3 achieved PR, 19 showed relapse and 11 rejected the graft. DLI was found to be effective in 39% of cases. Complications of the procedure occurred in 18 patients; of these, 2 died. To sum up DLI shows efficacy in a significant percentage of children. Mortality related to the therapy adverse effects is low. However, this method requires standardization.

Properties of neural crest-like cells differentiated from human embryonic stem cells.

Neural crest cells (NCCs) derive early in vertebrate ontogenesis from neural tube as a population of migratory cells with exquisite differentiation potential. Abnormalities in NCC behaviour are cause of debilitating diseases including cancers and a spectrum of neurocristopathies. Thanks to their multilineage differentiation capacity NCCs offer a cell source for regenerative medicine. Both these aspects make NCC biology an important issue to study, which can currently be addressed using methodologies based on pluripotent stem cells. Here we contributed to understanding the biology of human NCCs by refining the protocol for differentiation/propagation of NCClike cells from human embryonic stem cells and by characterizing the molecular and functional phenotype of such cells. Most importantly, we improved formulation of media for NCC culture, we found that poly-L-ornithine combined with fibronectin provide good support for NCC growth, we unravelled the tendency of cultured NCCs to maintain heterogeneity of CD271 expression, and we showed that NCCs derived here possess the capacity to react to BMP4 signals by dramatically up-regulating MSX1, which is linked to odontogenesis.

Bacterial growth on chitosan-coated polypropylene textile.

Biofouling is a problem common in all systems where microorganisms and aqueous environment meet. Prevention of biofouling is therefore important in many industrial processes. The aim of this study was to develop a method to evaluate the ability of material coating to inhibit biofilm formation. Chitosan-coated polypropylene nonwoven textile was prepared using dielectric barrier discharge plasma activation. Resistance of the textile to biofouling was then tested. First, the textile was submerged into a growth medium inoculated with green fluorescein protein labelled Pseudomonas aeruginosa. After overnight incubation at 33°C, the textile was observed using confocal laser scanning microscopy for bacterial enumeration and biofilm structure characterisation. In the second stage, the textile was used as a filter medium for prefiltered river water, and the pressure development on the in-flow side was measured to quantify the overall level of biofouling. In both cases, nontreated textile samples were used as a control. The results indicate that the chitosan coating exhibits antibacterial properties. The developed method is applicable for the evaluation of the ability to inhibit biofilm formation.

Search for a new gauge boson in electron-nucleus fixed-target scattering by the APEX experiment.

We present a search at the Jefferson Laboratory for new forces mediated by sub-GeV vector bosons with weak coupling α' to electrons. Such a particle A' can be produced in electron-nucleus fixed-target scattering and then decay to an e + e- pair, producing a narrow resonance in the QED trident spectrum. Using APEX test run data, we searched in the mass range 175-250 MeV, found no evidence for an A'→ e+ e- reaction, and set an upper limit of α'/α ~/= 10(-6). Our findings demonstrate that fixed-target searches can explore a new, wide, and important range of masses and couplings for sub-GeV forces.

[Ultrasonographic examination in the follow-up of patients after kidney transplantation]. / Prínos ultrasonografického vysetrení pro sledování nemocných po transplantaci ledviny.

The authors followed-up in 1988-1994 a total of 134 patients after renal transplantation by ultrasonographic examinations in the B mode, Doppler frequency analysis and coloured Doppler mapping. They summarize the basic sonographic pictures during a normal development after transplantation and in case of surgical and non-surgical complications. They evaluate sonography as the basic examination method which is not quite specific for different complications but makes it possible to detect them in the initial stage and to indicate in time further examinations and treatment.

[Typology characteristics of preschool-age gypsy children in the Czech Republic]. / Typologická charakteristika romských detí predskolního veku z Ceské republiky.

The study assesses the somatotype (using the method of Heath-Carter, 1967) and its changes in 439 pre-school 3-7 years old Gypsy children and compares results with the situation in 348 non-Gypsy children. A change in somatotype with age and a typical dominance of the mesomorphic component in the pre-school age in both Gypsy and non-Gypsy children has been confirmed. This is in agreement with studies on non-Gypsy children. The above findings and the fact that differences in somatotype between ethnic groups are smaller than those between sexes show that the somatotype and its developmental tendencies in pre-school age are almost identical in Gypsy and non-Gypsy children.

The concept of pain.

The experience of pain is a mysterious consequence of the human condition. In the Western world, our understanding of pain has evolved in concert with our understanding of the world around us. As attitudes toward pain have changed, methods to alleviate pain have been developed in accordance with the science and religious climate of the period.

[Pathologico-morphologic changes in the digestive system in rabid foxes]. / Patologicko-morfologické zmeny v trávicím ústrojí rabických lisek.

Pathologico-morphological changes in the digestive tract were investigated in fifty naturally infected common foxes (Vulpes vulpes crucigera). Nineteen animals were found to suffer from mild cachexia, 31 animals suffered from complete cachexia. Erosions were observed in the mucosa of oral cavities of 21 foxes. Traumatic injuries appeared in the teeth of 11 animals. One case of swollen and hyperaemic tongue was described; in three cases there occurred sialo-adenitis. A mild degree of inflammation was recorded in the gullet in three animals. Fifteen animals had empty stomachs, thirty-five animals had atypical food or foreign bodies in the stomach contents; simple hyperaemia was recorded 18 times, acute catarrhal gastritis 19 times and haemorrhagic gastritis was observed in two cases. Acute catarrhal enteritis was found in six cases, haemorrhagic enteritis in one case.

[Typing of districts for a study of the health status of the Czechoslovak population]. / Typologie okresu pro setrení zdravotního stavu obyvatel CSSR.

The Institute of Social Medicine and Organization of Health Services is conducting at present the so far most extensive survey of the health status of the population in a sample comprising almost 20,000 subjects, i.e. subjects taking advantage of health services, as well as those who do not use the health services either because they are healthy or assume that they are healthy, or possibly for other reasons. For this survey a population sample is used which was previously used by the Federal Statistical Office for a survey of the class and social structure in the CSSR in 1984. This sample which is too large for our work had to be reduced. This reduction was made by selecting from the original sample, which comprised the entire territory of Czechoslovakia, only some districts where the survey was made. In order to make the selected districts representative for the entire territory of the country, we elaborated a typology of districts which contains demographic, economic, social and oecological parameters. For elaboration of the typology cluster analysi was used.

[Survival of rabies virus under external conditions]. / Prezívání viru vztekliny ve vnejsích podmínkách.

The survival of the street rabies virus in a 10% suspension, prepared from the salivary gland of a naturally infected fox, was studied under various conditions. A bioassay and titration on mice were used for the identification of the virus in different intervals. The heat inactivation of the virus in a suspension kept in a test tube at the temperatures of 20 degrees C and 37 degrees C was performed in two stages. The rapid reduction of the titre within 24 hours was followed by a slower decrease, reaching total inactivation after 96 hours at both temperatures. When the virus was tested by means of the contamination of various substrates (glass, metal sheet, plant leaf) with 0.1 ml of infection suspension in a thin layer, the longest survival of the virus was recorded at the temperature of 5 degrees C--144 hours. At the temperature of 20 to 21 degrees C the virus kept its activity on the glass and plant leaf for 24 hours and on the metal sheet for 48 hours although the applied drops looked like having dried. The temperature of 30 degrees C combined with intensive sunshine devitalized the virus within 1.5 hours, whereas without sunshine the virus still remained active, at the temperature of 30 degrees C, after 20 hours.

Potent enhancement of [3H]nitrendipine binding in rat cerebral cortical and cardiac homogenates: a putative mechanism for the action of MDL 12,330A.

[3H]Nitrendipine [( 3H]NTD), a specific high-affinity calcium channel antagonist, was used to label dihydropyridine binding sites associated with calcium channels in rat cerebral cortical and cardiac homogenates. A novel lactamimide compound, MDL 12,330A, has been shown previously to have negative inotropic and chronotropic effects in isolated working guinea-pig hearts and these effects are reversed by the administration of calcium. MDL 12,330A is potent in enhancing [3H]NTD binding in membranes prepared from the cerebral cortex and the heart, with EC50 values of 6.1 X 10(-8) and 3.4 X 10(-8) M, respectively, at 37 degrees C. This allosteric effect by MDL 12,330A is similar to that produced by a known calcium channel antagonist, d-cis diltiazem, which has been shown previously to enhance [3H]NTD binding at 37 degrees C. The extent of enhancement by MDL 12,330A depends on incubation temperature (37 degrees C greater than 25 degrees C greater than 0 degrees C). The mechanism of this enhancement by MDL 12,330A is due to a decrease in the dissociation rate constant of the dihydropyridine-calcium channel supramolecular complex. MDL 12,330A is the most potent drug thus far examined which demonstrates the enhancement of [3H]NTD binding.

[Excretion of the rabies virus in foxes after experimental infection]. / Vylucování viru vztekliny u lisek po experimentální infekci.

Fourteen foxes (Vulpes vulpes crucigera) were experimentally infected with rabies. The excretion of the virus in saliva was subjected to qualitative study. Three different street strains isolated in the territory of the Czech Socialist Republic were used for the intramuscular infection at the doses of 50 or 5000 MICLD50. The presence of the virus in saliva was demonstrated in 12 animals (86%). Post-mortal examination revealed the virus in the salivary gland of 13 animals (93%). The virus started to be excreted in saliva maximally two days before the onset of the clinical signs of the disease and it lasted maximally six days. The affinity of the virus for the salivary gland was related to the strain used, and increased when a lower infection dose had been administered.

[The prevention and therapy of fascioloidiasis using bithionol sulfoxide]. / Prevence a terapie fascioloidózy skotu bithionolsulfoxidem.

The elimination of the sources of invasion, i. e. hay and forage coming from the infested biotopes, combined with the administration of bithionol sulphoxide, resulted in a reduction of the invasion of cattle by Fascioloides magna from 21.1 to 3.2% within two years. The Czechoslovak-produced bithionol sulphoxide, administered at a rate of 40 to 50 mg per kg body weight as medicated feed, showed 100% effectiveness. At doses higher than 30 mg per kg body weight, the protective period should be prolonged to three or four weeks.

[Effectiveness of various barbiturates in chickens of different ages]. / Ucinnost nekterých barbituranu u kurat rozdílného veku

Phenobarbital, allobarbital, and pentobarbital in the doses of 40 and 80 mg per 1 kg body mass were applied intramuscularly to groups of the cockerels of the WL breed at the age of two days, one, two, and six weeks (each group had ten birds) and to eight-week-old WL cockerels in groups of five birds. The methods of clinical observation and repeated determination of the response of the animals to sonic stimuli and contact stimuli, and the evaluation of the quality of some reflexes (particularly the spontaneous position of the body and the correction of the lateral position) were used for the study of suppression evoked by the applied barbiturates. Sleep occurred first after the application of pentobarbital (sooner in younger age groups). The latest beginning of sleep was observed after phenobarbital; in the latter case, sleep was hard to evaluate because it was not very deep. The time of sleep had the longest duration after allobarbital (only in the eight-week-old sleep was longer after pentobarbital), and the shortest after phenobarbital; there were also differences in the duration of sleep between the age groups of birds. The pentobarbital dose of 80 mg kg-1 of body mass killed birds in the three youngest age groups )in the two-day-old it killed nine of ten birds, in the one-week-old eight of ten birds, and in the two-week-old two of ten birds). The differences in the effectiveness of the applied barbiturates in two doses per unit of body mass were related to the age of the animals, even in the cases of the shortest age intervals between individual groups. Very high interspecies differences ensue from a comparison with the doses of these barbiturates usually applied to man.