Genetic therapeutic advancements for Dravet Syndrome

Dravet Syndrome is a genetic epileptic syndrome characterized by severe and intractable seizures associated with cognitive, motor, and behavioral impairments. The disease is also linked with increased mortality mainly due to sudden unexpected death in epilepsy. Over 80% of cases are due to a de novo mutation in one allele of the SCN1A gene, which encodes the α-subunit of the voltage-gated ion channel NaV1.1. Dravet Syndrome is usually refractory to antiepileptic drugs, which only alleviate seizures to a small extent. Viral, non-viral genetic therapy, and gene editing tools are rapidly enhancing and providing new platforms for more effective, alternative medicinal treatments for Dravet syndrome. These strategies include gene supplementation, CRISPR-mediated transcriptional activation, and the use of antisense oligonucleotides. In this review, we summarize our current knowledge of novel genetic therapies that are currently under development for Dravet syndrome

Exercise partially reverses the inhibitory effect of caffeine on liver gluconeogenesis in type 1 diabetic rats with hypoglycemia

The purpose was to determine the possible effects of exercise and/or caffeine on hypoglycemia and liver gluconeogenesis in diabetic rats. These were divided into four subgroups: (a) intraperitoneal insulin only, (b) exercise bout before insulin, (c) caffeine after insulin, and (d) exercise bout before and caffeine after insulin. The marked glycemic drop 45 min after insulin (0 min = 229.00, 45 min = 75.75) was considerably reduced (p  0.05) when they were combined (45 min: exercise + caffeine = 65.44) (Mean, in mg·dL−1). Caffeine alone strongly inhibited liver glucose production from 2 mM lactate 45 min after insulin (without caffeine = 3.05, with caffeine = 0.27; p −1). The improved hypoglycemia with caffeine or exercise cannot be explained by their actions on liver gluconeogenesis. As their beneficial effect disappeared when they were combined, such association in diabetic patients should be avoided during the period of hyperinsulinemia due to the risk of severe hypoglycemia

Radiation from a D-dimensional collision of shock waves: first order perturbation theory

We study the spacetime obtained by superimposing two equal Aichelburg-Sexl shock waves in D dimensions traveling, head-on, in opposite directions. Considering the collision in a boosted frame, one shock becomes stronger than the other, and a perturbative framework to compute the metric in the future of the collision is setup. The geometry is given, in first order perturbation theory, as an integral solution, in terms of initial data on the null surface where the strong shock has support. We then extract the radiation emitted in the collision by using a D-dimensional generalisation of the Landau-Lifschitz pseudo-tensor and compute the percentage of the initial centre of mass energy epsilon emitted as gravitational waves. In D=4 we find epsilon=25.0%, in agreement with the result of D'Eath and Payne. As D increases, this percentage increases monotonically, reaching 40.0% in D=10. Our result is always within the bound obtained from apparent horizons by Penrose, in D=4, yielding 29.3%, and Eardley and Giddings, in D> 4, which also increases monotonically with dimension, reaching 41.2% in D=10. We also present the wave forms and provide a physical interpretation for the observed peaks, in terms of the null generators of the shocks.Comment: 27 pages, 11 figures; v2 some corrections, including D dependent factor in epsilon; matches version accepted in JHE

Classical integrability in the BTZ black hole

Using the fact the BTZ black hole is a quotient of AdS_3 we show that classical string propagation in the BTZ background is integrable. We construct the flat connection and its monodromy matrix which generates the non-local charges. From examining the general behaviour of the eigen values of the monodromy matrix we determine the set of integral equations which constrain them. These equations imply that each classical solution is characterized by a density function in the complex plane. For classical solutions which correspond to geodesics and winding strings we solve for the eigen values of the monodromy matrix explicitly and show that geodesics correspond to zero density in the complex plane. We solve the integral equations for BMN and magnon like solutions and obtain their dispersion relation. Finally we show that the set of integral equations which constrain the eigen values of the monodromy matrix can be identified with the continuum limit of the Bethe equations of a twisted SL(2, R) spin chain at one loop.Comment: 45 pages, Reference added, typos corrected, discussion on geodesics improved to include all geodesic

Plasma glucose regulation and insulin secretion in hypertriglyceridemic mice

In this study, we examined glucose homeostasis and insulin secretion in transgenic mice overexpressing the human apolipoprotein CIII gene (apo CIII tg). These mice have elevated plasma levels of triglycerides, FFA and cholesterol compared to control mice. The body weight, plasma glucose, and insulin levels, glucose disappearance rates, areas under the ipGTT curve for adult (4-8 mo. old) and aged (20-24 mo. old) apo CIII tg mice and the determination of insulin during the ipGTT were riot different from those of control mice. However, an additional elevation of plasma FFA by treatment with heparin for 2-4h impaired the ipGTT responses in apo CIII tg mice compared to saline-treated mice. The glucose disappearance rate in heparin-treated transgenic mice was slightly lower than in heparin-treated controls. Glucose (22.2 mmol/l) stimulated insulin secretion in isolated islets to the same extent in saline-treated control and apo CIII tg mice. in islets from heparin-treated apo CIII tg mice, the insulin secretion at 2.8 and 22.2 mmol glucose/l was lower than in heparin-treated control mice. In conclusion, hypertriglyceridemia per se or a mild elevation in FFA did not affect insulin secretion or insulin resistance in adult or aged apo CIII tg mice. Nonetheless, an additional elevation of FFA induced by heparin in hypertriglyceridemic mice impaired the ipGTT by reducing insulin secretion.341212

Delayed diagnosis of intermittent mesenteroaxial volvulus of the stomach by computed tomography: a case report

10.1186/1752-1947-2-343Journal of Medical Case Reports234

Distributions of charged massive scalars and fermions from evaporating higher-dimensional black holes

A detailed numerical analysis is performed to obtain the Hawking spectrum for charged, massive brane scalars and fermions on the approximate background of a brane charged rotating higher-dimensional black hole constructed in arXiv:0907.5107. We formulate the problem in terms of a "spinor-like" first order system of differential wave equations not only for fermions, but for scalars as well and integrate it numerically. Flux spectra are presented for non-zero mass, charge and rotation, confirming and extending previous results based on analytic approximations. In particular we describe an inverted charge splitting at low energies, which is not present in four or five dimensions and increases with the number of extra dimensions. This provides another signature of the evaporation of higher-dimensional black holes in TeV scale gravity scenarios.Comment: 19 pages, 6 figures, minor typos corrected, 1 page added with a discussion on higher spins, added reference

Laparoscopic anterior gastropexy for chronic recurrent gastric volvulus: a case report

<p>Abstract</p> <p>Introduction</p> <p>Gastric volvulus is an uncommon clinical entity, first described by Berti in 1866. It is a rotation of all or part of the stomach through more than 180°. This rotation can occur on the longitudinal (organo-axial) or transverse (mesentero-axial) axis. This condition can lead to a closed-loop obstruction or strangulation. Traditional surgical therapy for gastric volvulus is based on an open approach. Here we report the case of a patient with chronic intermittent gastric volvulus who underwent a successful laparoscopic treatment.</p> <p>Case presentation</p> <p>A 34-year-old woman presented with multiple episodes of recurrent upper abdominal pain associated with retching and vomiting, treated unsuccessfully with intramuscular metoclopramide. Endoscopic examination of the upper digestive tract showed a suspected rotation of the stomach, and a chronic recurrent gastric volvulus was revealed by barium meal. The patient was operated on successfully, with an anterior laparoscopic gastropexy performed as the first surgical approach.</p> <p>Conclusion</p> <p>Experience with laparoscopic anterior gastropexy is limited only to a few described cases. Our patient was clinically and radiologically followed-up for 2 years with no evidence of recurrence, either radiological or symptomatic. Based on this result, laparoscopic gastropexy can be seen and considered as an initial 'gold standard' for the treatment of gastric volvulus.</p

Accreting Black Holes

This chapter provides a general overview of the theory and observations of black holes in the Universe and on their interpretation. We briefly review the black hole classes, accretion disk models, spectral state classification, the AGN classification, and the leading techniques for measuring black hole spins. We also introduce quasi-periodic oscillations, the shadow of black holes, and the observations and the theoretical models of jets.Comment: 41 pages, 18 figures. To appear in "Tutorial Guide to X-ray and Gamma-ray Astronomy: Data Reduction and Analysis" (Ed. C. Bambi, Springer Singapore, 2020). v3: fixed some typos and updated some parts. arXiv admin note: substantial text overlap with arXiv:1711.1025

Physics, Astrophysics and Cosmology with Gravitational Waves

Gravitational wave detectors are already operating at interesting sensitivity levels, and they have an upgrade path that should result in secure detections by 2014. We review the physics of gravitational waves, how they interact with detectors (bars and interferometers), and how these detectors operate. We study the most likely sources of gravitational waves and review the data analysis methods that are used to extract their signals from detector noise. Then we consider the consequences of gravitational wave detections and observations for physics, astrophysics, and cosmology.Comment: 137 pages, 16 figures, Published version <http://www.livingreviews.org/lrr-2009-2