Treatment of acute migraine by a partial rebreathing device : A randomized controlled pilot study

Background Impaired brain oxygen delivery can trigger and exacerbate migraine attacks. Normoxic hypercapnia increases brain oxygen delivery markedly by vasodilation of the cerebral vasculature, and hypercapnia has been shown to abort migraine attacks. Stable normoxic hypercapnia can be induced by a compact partial rebreathing device. This pilot study aimed to provide initial data on the device's efficacy and safety. Methods Using a double-blinded, randomized, cross-over study design, adult migraine-with-aura patients self-administered the partial rebreathing device or a sham device for 20 minutes at the onset of aura symptoms. Results Eleven participants (mean age 35.5, three men) self-treated 41 migraine attacks (20 with the partial rebreathing device, 21 with sham). The partial rebreathing device increased mean End Tidal CO2 by 24%, while retaining mean oxygen saturation above 97%. The primary end point (headache intensity difference between first aura symptoms and two hours after treatment (0-3 scale) - active/sham difference) did not reach statistical significance (-0.55 (95% CI: -1.13-0.04), p=0.096), whereas the difference in percentage of attacks with pain relief at two hours was significant (p=0.043), as was user satisfaction (p=0.022). A marked efficacy increase was seen from first to second time use of the partial rebreathing device. No adverse events occurred, and side effects were absent or mild. Conclusion Normoxic hypercapnia shows promise as an adjunctive/alternative migraine treatment, meriting further investigation in a larger population. Clinical study registered at ClinicalTrials.gov with identifier NCT03472417Peer reviewe

Quasielastic neutron scattering and molecular dynamics simulation studies of the melting transition in butane and hexane monolayers adsorbed on graphite

Quasielastic neutron scattering experiments and molecular dynamics (MD) simulations have been used to investigate molecular diffusive motion near the melting transition of monolayers of flexible rod-shaped molecules. The experiments were conducted on butane and hexane monolayers adsorbed on an exfoliated graphite substrate, For butane, quasielastic scattering broader than the experimental energy resolution width of 70 mu eV appears abruptly at the monolayer melting point of T-m = 116 K, whereas, for the hexane monolayer, it appears 20 K below the melting transition (T-m = 170 K). To facilitate comparison with experiment, quasielastic spectra calculated from the MD simulations were analyzed using the same models and fitting algorithms as for the neutron spectra. This combination of techniques gives a microscopic picture of the melting process in these two monolayers which is consistent with earlier neutron diffraction experiments. Butane melts abruptly to a liquid phase where the molecules in the trans conformation translationally diffuse while rotating about their center of mass. In the case of the hexane monolayer, the MD simulations show that the appearance of quasielastic scattering below T-m coincides with transformation of Some molecules from trans to gauche conformations. Furthermore, if gauche molecules are prevented from forming in the simulation, the calculated incoherent scattering function contains no quasielastic component below T-m. Modeling of both the neutron and simulated hexane monolayer spectra below T-m favors a plastic phase in which there is nearly isotropic rotational diffusion of the gauche molecules about their center of mass, but no translational diffusion, The elastic scattering observed above T-m is consistent with the coexistence of solid monolayer clusters with a fluid phase, as predicted by the simulations. For T/T-m greater than or equal to 1.3, the elastic scattering vanishes from the neutron spectra where the simulation indicates the presence of a fluid phase alone, The qualitative similarities between the observed and simulated quasielastic spectra lend support to a previously proposed ''footprint reduction'' mechanism of melting in monolayers of flexible, rod-shaped molecules. (C) 1997 American Institute of Physics

Effects of erythropoietin in murine-induced pluripotent cell-derived panneural progenitor cells

Induced cell fate changes by reprogramming of somatic cells offers an efficient strategy to generate autologous pluripotent stem (iPS) cells from any adult cell type. The potential of iPS cells to differentiate into various cell types is well established, however the efficiency to produce functional neurons from iPS cells remains modest. Here, we generated panneural progenitor cells (pNPCs) from mouse iPS cells and investigated the effect of the neurotrophic growth factor erythropoietin (EPO) on their survival, proliferation and neurodifferentiation. Under neural differentiation conditions, iPS-derived pNPCs gave rise to microtubule-associated protein-2 positive neuronlike cells (34% to 43%) and platelet-derived growth factor receptor positive oligodendrocytelike cells (21% to 25%) while less than 1% of the cells expressed the astrocytic marker glial fibrillary acidic protein. Neuronlike cells generated action potentials and developed active presynaptic terminals. The pNPCs expressed EPO receptor (EPOR) mRNA and displayed functional EPOR signaling. In proliferating cultures, EPO (0.1–3 U/mL) slightly improved pNPC survival but reduced cell proliferation and neurosphere formation in a concentration-dependent manner. In differentiating cultures EPO facilitated neurodifferentiation as assessed by the increased number of β-III-tubulin positive neurons. Our results show that EPO inhibits iPS pNPC self-renewal and promotes neurogenesis

Oligopeptide Sequences of the Metal Binding Domain of CueR Metalloregulatory Proteins as Candidates for Toxic Metal Ion Capture

Various toxic metal ion resistance systems operate from bacterial level up to higher plants and animals. In bacteria, metalloregulatory proteins are key factors in the control of metal ion level. Inspired by the metal binding domain of these highly sensitive metal ion sensor proteins we have designed artificial oligopeptides, containing two cysteine residues, and investigated their interaction with cadmium(II) and mercury(II) ions. The studied ligands bound both metal ions with a rather high stability. The composition and solution structure of the various metal ion complexes have been determined. The genetic code of one of the oligopeptide sequences has been introduced into E. coli BL21 cells and (over)produced in the form of a fusion protein. Preliminary investigation of the viability and potential metal ion accumulation of the modified bacteria, compared to control cells, in the presence of cadmium(II) and mercury(II) has also been performed

Black carbon as an additional indicator of the adverse health effects of airborne particles compared with PM10 and PM2.5.

Current air quality standards for particulate matter (PM) use the PM mass concentration [PM with aerodynamic diameters ≤ 10 μm (PM(10)) or ≤ 2.5 μm (PM(2.5))] as a metric. It has been suggested that particles from combustion sources are more relevant to human health than are particles from other sources, but the impact of policies directed at reducing PM from combustion processes is usually relatively small when effects are estimated for a reduction in the total mass concentration

Necessary conditions for variational regularization schemes

We study variational regularization methods in a general framework, more precisely those methods that use a discrepancy and a regularization functional. While several sets of sufficient conditions are known to obtain a regularization method, we start with an investigation of the converse question: How could necessary conditions for a variational method to provide a regularization method look like? To this end, we formalize the notion of a variational scheme and start with comparison of three different instances of variational methods. Then we focus on the data space model and investigate the role and interplay of the topological structure, the convergence notion and the discrepancy functional. Especially, we deduce necessary conditions for the discrepancy functional to fulfill usual continuity assumptions. The results are applied to discrepancy functionals given by Bregman distances and especially to the Kullback-Leibler divergence.Comment: To appear in Inverse Problem

Magneto-optical Trapping of Cadmium

We report the laser-cooling and confinement of Cd atoms in a magneto-optical trap, and characterize the loading process from the background Cd vapor. The trapping laser drives the 1S0-1P1 transition at 229 nm in this two-electron atom and also photoionizes atoms directly from the 1P1 state. This photoionization overwhelms the other loss mechanisms and allows a direct measurement of the photoionization cross section, which we measure to be 2(1)x10^(-16)cm^(2) from the 1P1 state. When combined with nearby laser-cooled and trapped Cd^(+) ions, this apparatus could facilitate studies in ultracold interactions between atoms and ions.Comment: 8 pages, 11 figure