Health Disparities in the Treatment of Supraventricular Tachycardia in Pediatric Patients.

Supraventricular tachycardia (SVT) is a common pediatric arrhythmia. The objective of this investigation was to investigate the existence and degree of the health disparities in the treatment of pediatric patients with supraventricular tachycardia based on sociodemographic factors. This was retrospective cohort study at a large academic medical center including children ages 5-18 years old diagnosed with SVT. Patients with congenital heart disease and myocarditis were excluded. Initial treatment and ultimate treatment with either medical management or ablation were determined. The odds of having an ablation procedure were determined based on patient age, sex, race, ethnicity, and insurance status. There was a larger portion of non-White patients (p = 0.033) within the cohort that did not receive an ablation during the study period. Patients that were younger, female, American Indian/Alaskan Native, unknown race, and had missing insurance information were less likely to receive ablation therapy during the study period. In this single center, regional evaluation, we demonstrated that disparities in the treatment of pediatric SVT are present based on multiple patient sociodemographic factors. This study adds evidence to the presence of inequities in health care delivery across pediatric populations.

New High-Confinement Regime with Fast Ions in the Core of Fusion Plasmas.

The key result of the present work is the theoretical prediction and observation of the formation of a new type of transport barrier in fusion plasmas, called F-ATB (fast ion-induced anomalous transport barrier). As demonstrated through state-of-the-art global electrostatic and electromagnetic simulations, the F-ATB is characterized by a full suppression of the turbulent transport-caused by strongly sheared, axisymmetric E×B flows-and an increase of the neoclassical counterpart, albeit keeping the overall fluxes at significantly reduced levels. The trigger mechanism is shown to be a mainly electrostatic resonant interaction between suprathermal particles, generated via ion-cyclotron-resonance heating, and plasma microturbulence. These findings are obtained by realistic simulations of the ASDEX Upgrade discharge No. 36637-properly designed to maximized the beneficial role of the wave-particle resonance interaction-which exhibits the expected properties of improved confinement produced by energetic particles.

[Vertigo as the first manifestation of ovarian cancer]. / Vertigo als eerste teken van een ovariumcarcinoom.

BACKGROUND: Vertigo is a common complaint and may rarely be the presenting symptom of a paraneoplastic neurological syndrome (PNS). CASE DESCRIPTION: A 76-year-old woman presented at the ER with subacute cerebellar syndrome and severe vertigo. Laboratory testing revealed mild anaemia. A cerebral CT scan showed no intracranial pathology. The patient was admitted for observation. History-taking revealed she been suffering from general malaise and had unintentionally lost 16 kg in weight over recent months. Further PET-CT investigations revealed multiple enlarged mediastinal and abdominal lymph nodes with high metabolic activity. Histopathological investigation of a lymph node biopsy showed a malignancy originating from the genital tract. Positive anti-neuronal antibodies (anti-Yo) and an elevated CA-125 concentration were found in peripheral blood. We diagnosed paraneoplastic cerebellar degeneration as the first manifestation of hitherto undiagnosed occult ovarian cancer. CONCLUSION: In a patient with subacute, cerebellar syndrome with severe vertigo, after ruling out other causes, the diagnosis of PNS should be considered. Determination of anti-neuronal antibodies can help in the diagnosis. Early recognition of PNS is important for the diagnosis and treatment of the underlying malignancy.

Pacing in Patients with Congenital Heart Disease: When Is It Helpful and When Is It Harmful?

PURPOSE OF REVIEW: Pacing in pediatric and adult patients with congenital heart disease requires careful evaluation and thoughtful planning. Review of current guidelines with assessment of risk/benefit must be performed along with planning on a case-by-case basis in order to achieve maximal success and reduce risk in this specialized population of patients that is rapidly increasing in size. RECENT FINDINGS: Guidelines for pacing in pediatric and congenital heart disease patients span many years. Most recent consensus and summary guidelines address pacing in adult patients with or without congenital heart disease. Pediatric recommendations from prior documents must be included in current decision-making. Pacing in pediatric and congenital heart disease patients is important therapy. Creation of an individualized plan of care with attention to risk/benefit decision-making regarding when and how to pace is critical in this population to maximize beneficial outcome.

Observations of core ion cyclotron emission on ASDEX Upgrade tokamak.

The B-dot probe diagnostic suite on the ASDEX Upgrade tokamak has recently been upgraded with a new 125 MHz, 14 bit resolution digitizer to study ion cyclotron emission (ICE). While classic edge emission from the low field side plasma is often observed, we also measure waves originating from the core with fast fusion protons or beam injected deuterons being a possible emission driver. Comparing the measured frequency values with ion cyclotron harmonics present in the plasma places the origin of this emission on the magnetic axis, with the fundamental hydrogen/second deuterium cyclotron harmonic matching the observed values. The actual values range from ∼27 MHz at the on-axis toroidal field BT = -1.79 T to ∼40 MHz at BT = -2.62 T. When the magnetic axis position evolves during this emission, the measured frequency values track the changes in the estimated on-axis cyclotron frequency values. Core ICE is usually a transient event lasting ∼100 ms during the neutral beam startup phase. However, in some cases, core emission occurs in steady-state plasmas and lasts for longer than 1 s. These observations suggest an attractive possibility of using a non-perturbing ICE-based diagnostic to passively monitor fusion alpha particles at the location of their birth in the plasma core, in deuterium-tritium burning devices such as ITER and DEMO.

Rapid regression of large cardiac rhabdomyomas in neonates after sirolimus therapy.

Cardiac rhabdomyomas are the most common tumours in children and are typically seen in association with the tuberous sclerosis complex. Although benign and often associated with spontaneous regression, in rare circumstances surgical resection is indicated to relieve obstruction or other mass-related effects. Recent clinical trials have demonstrated the benefits of mammalian target of rapamycin inhibitors for the treatment of other tumour sub-types associated with tuberous sclerosis. Here we report rapid regression of several massive cardiac rhadomyomas in two neonates with the use of the mammalian target of rapamycin inhibitor sirolimus.

Anaesthetics stop diverse plant organ movements, affect endocytic vesicle recycling and ROS homeostasis, and block action potentials in Venus flytraps.

Background and Aims: Anaesthesia for medical purposes was introduced in the 19th century. However, the physiological mode of anaesthetic drug actions on the nervous system remains unclear. One of the remaining questions is how these different compounds, with no structural similarities and even chemically inert elements such as the noble gas xenon, act as anaesthetic agents inducing loss of consciousness. The main goal here was to determine if anaesthetics affect the same or similar processes in plants as in animals and humans. Methods: A single-lens reflex camera was used to follow organ movements in plants before, during and after recovery from exposure to diverse anaesthetics. Confocal microscopy was used to analyse endocytic vesicle trafficking. Electrical signals were recorded using a surface AgCl electrode. Key Results: Mimosa leaves, pea tendrils, Venus flytraps and sundew traps all lost both their autonomous and touch-induced movements after exposure to anaesthetics. In Venus flytrap, this was shown to be due to the loss of action potentials under diethyl ether anaesthesia. The same concentration of diethyl ether immobilized pea tendrils. Anaesthetics also impeded seed germination and chlorophyll accumulation in cress seedlings. Endocytic vesicle recycling and reactive oxygen species (ROS) balance, as observed in intact Arabidopsis root apex cells, were also affected by all anaesthetics tested. Conclusions: Plants are sensitive to several anaesthetics that have no structural similarities. As in animals and humans, anaesthetics used at appropriate concentrations block action potentials and immobilize organs via effects on action potentials, endocytic vesicle recycling and ROS homeostasis. Plants emerge as ideal model objects to study general questions related to anaesthesia, as well as to serve as a suitable test system for human anaesthesia.

Comparing the survival rate of juvenile Chinook salmon migrating through hydropower systems using injectable and surgical acoustic transmitters.

Acoustic telemetry is one of the primary technologies for studying the behavior and survival of fishes throughout the world. The size and performance of the transmitter are key limiting factors. The newly developed injectable transmitter is the first acoustic transmitter that can be implanted via injection instead of surgery. A two-part field study was conducted to evaluate the performance of the injectable transmitter and its effect on the survival of implanted fish. The injectable transmitter performed well and similarly to the proceeding generation of commercially-available JSATS transmitters tested concurrently. Snake River subyearling Chinook salmon smolts implanted with the injectable transmitter had a higher survival probability from release to each of eleven downstream detection arrays, because reach-specific survival estimates were significantly higher for the injectable group in three of the eleven reaches examined. Overall, the injectable group had a 0.263 (SE = 0.017) survival probability over the entire 500 km study area compared to 0.199 (0.012) for the surgically implanted group. The reduction in size and ability to implant the new transmitter via injection has reduced the tag or tagging effect bias associated with studying small fishes. The information gathered with this new technology is helping to evaluate the impacts of dams on fishes.

A new compact solid-state neutral particle analyser at ASDEX Upgrade: Setup and physics modeling.

At ASDEX Upgrade (AUG), a new compact solid-state detector has been installed to measure the energy spectrum of fast neutrals based on the principle described by Shinohara et al. [Rev. Sci. Instrum. 75, 3640 (2004)]. The diagnostic relies on the usual charge exchange of supra-thermal fast-ions with neutrals in the plasma. Therefore, the measured energy spectra directly correspond to those of confined fast-ions with a pitch angle defined by the line of sight of the detector. Experiments in AUG showed the good signal to noise characteristics of the detector. It is energy calibrated and can measure energies of 40-200 keV with count rates of up to 140 kcps. The detector has an active view on one of the heating beams. The heating beam increases the neutral density locally; thereby, information about the central fast-ion velocity distribution is obtained. The measured fluxes are modeled with a newly developed module for the 3D Monte Carlo code F90FIDASIM [Geiger et al., Plasma Phys. Controlled Fusion 53, 65010 (2011)]. The modeling allows to distinguish between the active (beam) and passive contributions to the signal. Thereby, the birth profile of the measured fast neutrals can be reconstructed. This model reproduces the measured energy spectra with good accuracy when the passive contribution is taken into account.

An injectable acoustic transmitter for juvenile salmon.

Salmon recovery and the potential detrimental effects of dams on fish have been attracting national attention due to the environmental and economic implications. In recent years acoustic telemetry has been the primary method for studying salmon passage. However, the size of the existing transmitters limits the minimum size of fish that can be studied, introducing a bias to the study results. We developed the first acoustic fish transmitter that can be implanted by injection instead of surgery. The new injectable transmitter lasts four times longer and weighs 30% less than other transmitters. Because the new transmitter costs significantly less to use and may substantially reduce adverse effects of implantation and tag burden, it will allow for study of migration behavior and survival of species and sizes of fish that have never been studied before. The new technology will lead to critical information needed for salmon recovery and the development of fish-friendly hydroelectric systems.

microRNA miR-17-92 cluster is highly expressed in epidermal Langerhans cells but not required for its development.

Langerhans cells (LCs) are bone marrow-derived immature skin-residential dendritic cells (DCs) with a life cycle distinct from that of other types of DCs. The mechanisms involved in LC homeostasis and immunological functions are still not clear. MicroRNAs (miRNAs) are a class of short noncoding RNAs that regulate gene expression through either translational repression or mRNA degradation. A recent study showed that specific deletion of total miRNAs in DCs affects the homeostasis and function of only LCs, but not of other types of DCs. The roles of specific individual miRNA in LC development are still lacking. The miRNA miR-17-92 class, encoding miR-17, miR-18, miR-19a, miR-19b, miR-20 and miR-92, plays a very important role in B- and T-cell development and function. Here, we first report that epidermal LCs highly express the miR-17-92 class compared with spleen naive T cells. To further characterize the role of miR-17-92 in LC development, we generated LC-specific miR-17-92 knockout and knock-in mice. Interestingly, LC-specific gain- and loss-of-function of miR-17-92 cluster did not significantly change LC homeostasis, maturation ability, antigen capture and migration to draining lymph nodes. Thus, the miR-17-92 cluster may be functionally redundant and not critically required for LC development and function.

Multi-view fast-ion D-alpha spectroscopy diagnostic at ASDEX Upgrade.

A novel fast-ion D-alpha (FIDA) diagnostic that is based on charge exchange spectroscopy has been installed at ASDEX Upgrade. The diagnostic uses a newly developed high-photon-throughput spectrometer together with a low-noise EM-CCD camera that allow measurements with 2 ms exposure time. Absolute intensities are obtained by calibrating the system with an integrating sphere and the wavelength dependence is determined to high accuracy using a neon lamp. Additional perturbative contributions to the spectra, such as D2-molecular lines, the Stark broadened edge D-alpha emission, and passive FIDA radiation have been identified and can be subtracted or avoided experimentally. The FIDA radiation from fast deuterium ions after charge exchange reactions can therefore be analyzed continuously without superimposed line emissions at large Doppler shifts. Radial information on the fast ions is obtained from radially distributed lines of sight. The investigation of the fast-ion velocity distribution is possible due to three different viewing geometries. The independent viewing geometries access distinct parts of the fast-ion velocity space and make tomographic reconstructions possible.

Cleavage of the IPS-1/Cardif/MAVS/VISA does not inhibit T cell-mediated elimination of hepatitis C virus non-structural 3/4A-expressing hepatocytes.

BACKGROUND: Hepatitis C virus (HCV) effectively establishes persistent infection in human livers. The non-structural (NS) 3/4A complex participates in this process by cleavage of interferon beta (IFN beta) promoter stimulator-1 (IPS-1; also termed Cardif/MAVS/VISA), which inhibits responses to double stranded (ds) RNA. However, it is not known whether this effect extends beyond innate responses. AIMS: To test if HCV NS3/4A affects innate and adaptive immune responses in vivo. METHODS: NS3 levels were semi-quantified in human liver biopsies, transfected cells, and in transgenic (Tg) mouse livers by western blot. The effect of NS3/4A on dsRNA-mediated signalling and on the integrity of IPS-1 was analysed using in vitro translation, transfected cells and Tg mice. Cytotoxic T cell (CTL)-mediated clearance of transient firefly luciferase (FLuc)- and/or NS3/4A-Tg hepatocytes was determined using in vivo imaging and western blot. RESULTS: NS3 protein levels were in a comparable range (0.1-49 microg/g tissue) in infected human livers and Tg mouse livers. Importantly, these levels of NS3/4A reduced murine innate responses to synthetic dsRNA in vivo, supporting the possibility that this occurs also in infected humans. The likely explanation for this was the NS3/4A-mediated cleavage of mouse IPS-1, albeit less efficiently than human IPS-1. Despite this, FLuc- and/or NS3/4A-expressing murine hepatocytes were effectively eliminated by hepatic CTLs, utilising the classical molecules for virus-infected cell lysis, including CD8, IFN gamma, perforin and FasL. CONCLUSIONS: Although HCV NS3/4A inhibits the innate immunity, this does not prevent CTL-mediated clearance of NS3/4A-expressing hepatocytes in vivo. Thus, other HCV proteins are most likely responsible for interfering with the adaptive immunity.

The hepatitis C virus and immune evasion: non-structural 3/4A transgenic mice are resistant to lethal tumour necrosis factor alpha mediated liver disease.

BACKGROUND: The hepatitis C virus (HCV) establishes chronic infection by incompletely understood mechanisms. The non-structural (NS) 3/4A protease/helicase has been proposed as a key complex in modulating the infected hepatocyte, although nothing is known about the effects this complex exerts in vivo. AIM: To generate mice with stable and transient hepatocyte expression of the HCV NS3/4A proteins to study its effects in vivo. METHODS: NS3/4A expression was determined by western blot and immunohistochemistry. Two independent pathologists determined the liver histology. Hepatic immunity was characterised by quantifying intrahepatic immune cell subsets. Liver damage was induced using carbon tetrachloride (CCl(4)), lipopolysaccaride (LPS), tumour necrosis factor alpha (TNFalpha), and anti-Fas antibody. RESULTS: Expression of NS3/4A was restricted to the cytoplasm of hepatocytes, and did not cause liver cancer or any spontaneous liver pathology. However, the presence of NS3/4A modulated the intrahepatic immunity, as follows: first, the CD4+ T cell and type I/II dendritic cell subsets were reduced in transgenic livers; second, NS3/4A protected hepatocytes from liver damage mediated in vivo by CCl(4), LPS, TNFalpha, but not FAS; and third, both stable and transiently NS3/4A transgenic mice were resistant to lethal doses of liver targeted TNFalpha, and the resistance could be reverted by treatment with a p38 mitogen activated protein kinase inhibitor (MAPK). CONCLUSIONS: Hepatic expression of NS3/4A does not induce spontaneous liver disease. NS3/4A does, however, alter the intrahepatic immune cell subsets and protects hepatocytes against TNFalpha induced liver damage in vivo. The TNFalpha resistance can be reverted by treatment with a p38 MAPK inhibitor. This represents a new immune evasion strategy conferred by NS3/4A.

Secretory antibodies against Giardia intestinalis in lactating Nicaraguan women.

Secretory IgA (sIgA) antibodies are important in the host defence against the intestinal protozoan parasite Giardia intestinalis. However, few antigens have been identified. In this study 100 milk and saliva samples from lactating women, living in an endemic region (León, Nicaragua), were screened for the presence of antibodies against G. intestinalis. Most milk and saliva samples contained anti-Giardia antibodies (59% and 52%, respectively), with a mean sIgA content 50 times higher in milk than in saliva. The positive samples reacted with trophozoite membrane, flagella and cytoplasmic antigens. Western blot analysis showed that milk and saliva anti-Giardia sIgA recognized up to 16 different Giardia proteins in the molecular weight region 20-165 kDa. Two-dimensional Western blotting showed that the major immunoreactive proteins were the same as the immunoreactive proteins identified by serum from acute giardiasis patients in a non-endemic country. The major difference was a stronger reactivity against the variant surface proteins (VSPs) in the milk samples. Milk sIgAs also recognized recombinant Giardia proteins such as alpha-1 giardin, ornithine carbamoyl transferase, VSP-4EX, arginine deaminase and alpha-enolase. These antigens will be important targets in the development of new immunodiagnostic tools and vaccines.

Size of pancreatic islets of Langerhans: a key parameter for viability after cryopreservation.

Large amounts and excellent viabilities of pancreatic islets are prerequisites for recent advances in islet transplantation. Cryopreservation has been shown to enlarge transplanted cell mass, but has been accompanied by reduced viability. In this study rat pancreatic islets were differentiated into small (<200 micro m), medium (200-400 micrometers) and large (>400 micrometers) categories and their susceptibilities to different freezing conditions were evaluated: concentration of cryoprotectant (0.7-3.1 M), equilibration (15 vs. 45 min, 22 degrees C vs. on ice) and post-thaw removal of cryoprotectant (15 vs. 30 min, stepwise vs. one-step). The most prominent finding was a negative correlation between islet size and viability observed in non-frozen islets to a minor degree (r=-0.44) and significantly enhanced after cryopreservation (r<-0.8). The concentration of cryoprotectant showed the most significant influence on viability affecting small, medium and large islets. Different techniques of equilibration with the cryoprotectant resulted in significant changes of islet viability of medium islets, whereas small and large islets were unaffected. For different techniques of removal of the cryoprotectant, no significant influence on viabilities was found. We conclude that large islets represented a highly susceptible population concerning damage due to cryopreservation.

[3-dimensional surface measurement of spinal deformities with video rasterstereography]. / Die dreidimensionale Oberflächenvermessung von Wirbelsäulendeformitäten anhand der Videorasterstereographie.

QUESTION: Video rasterstereography is a method for back surface measurement comprising automatic back surface reconstruction and shape analysis. Aim of this prospective study was to determine the accuracy of this method in comparison to the conventional frontal and lateral standing radiographs. METHOD: 95 patients with idiopathic scoliosis or scoliotic postural abnormalities and 18 patients with thoracic hyperkyphosis and Scheuermann's disease were investigated. The Cobb angles, the sagittal profile and apical vertebral rotation as well as pelvic obliquity and trunk decompensation were measured. The analysis was carried out by two independent observers. RESULTS: The root mean square (r.m.s.) deviation of the Cobb angle in the cases of idiopathic scoliosis ranged between 7 degrees and 8 degrees. In video rasterstereography there were no false negative results and two false positive results concerning differentiation between structural scoliosis and scoliotic postural abnormality. The r.m.s. deviation of apical vertebral rotation averaged 7.9 degrees and for pelvic obliquity respectively trunk imbalance 0.65 cm respectively 1.07 cm. The thoracic hyperkyphosis in Scheuermann's disease showed a r.m.s. deviation of 5.6 degrees. CONCLUSIONS: Video rasterstereography is a reliable method in the three-dimensional evaluation of spinal deformities and constitutes a valuable additional tool to the clinical examination and can reduce the number of radiographs.