Permeability of dura mater: a possible link between cortical spreading depression and migraine pain? A comment

In the wake of cortical spreading depression (CSD) it has been suggested that noxious substances diffuse through the dura with resulting firing of epidural nerves. In my view this is unlikely because there are good reasons to suggest that there must be a dura-brain barrier. Alternatively collateral branches from the trigeminal nerve to the pia and the dura may signal what is happening with ions and substances on the brain surface during CSD to the epidural space

Community-based trial assessing the impact of annual versus semiannual mass drug administration with ivermectin plus albendazole and praziquantel on helminth infections in northwestern Liberia

We assessed the impact of three annual vs five semiannual rounds of mass drug administration (MDA) with ivermectin plus albendazole followed by praziquantel for the control or elimination of lymphatic filariasis (LF), onchocerciasis, soil-transmitted helminth (STH) infections and schistosomiasis in Lofa County, Liberia. The study started in 2012 and was interrupted in 2014 during the Ebola virus outbreak. Repeated cross-sectional surveys were conducted in individuals 5 years and older to measure infection markers. Wuchereria bancrofti antigenemia prevalences decreased from 12.5 to 1.2% (90% reduction) and from 13.6 to 4.2% (69% reduction) one year after three rounds of annual or five rounds of semiannual MDA, respectively. Mixed effects logistic regression models showed decreases in odds of antigenemia positivity were 91 and 74% at that time in the annual and semiannual treatment zones, respectively (p \u3c 0.001). Semiannual MDA was slightly more effective for reducing Onchocerca volvulus microfiladermia prevalence and at follow-up 3 were 74% (from 14.4 to 3.7%) and 83% (from 23.6 to 4.5%) in the annual and semiannual treatment zones, respectively. Both treatment schedules had similar beneficial effects on hookworm prevalence. Thus, annual and semiannual MDA with ivermectin and albendazole had similar beneficial impacts on LF, onchocerciasis, and STH in this setting. In contrast, MDA with praziquantel had little impact on hyperendemic Schistosoma mansoni in the study area. Results from a long-term follow-up survey showed that improvements in infection parameters were sustained by routine annual MDA provided by the Liberian Ministry of Health after our study endpoint

Clinical and radiographic spectrum of pathologically confirmed tumefactive multiple sclerosis

Atypical imaging features of multiple sclerosis lesions include size >2 cm, mass effect, oedema and/or ring enhancement. This constellation is often referred to as ‘tumefactive multiple sclerosis’. Previous series emphasize their unifocal and clinically isolated nature, however, evolution of these lesions is not well defined. Biopsy may be required for diagnosis. We describe clinical and radiographic features in 168 patients with biopsy confirmed CNS inflammatory demyelinating disease (IDD). Lesions were analysed on pre- and post-biopsy magnetic resonance imaging (MRI) for location, size, mass effect/oedema, enhancement, multifocality and fulfilment of Barkhof criteria. Clinical data were correlated to MRI. Female to male ratio was 1.2 : 1, median age at onset, 37 years, duration between symptom onset and biopsy, 7.1 weeks and total disease duration, 3.9 years. Clinical course prior to biopsy was a first neurological event in 61%, relapsing–remitting in 29% and progressive in 4%. Presentations were typically polysymptomatic, with motor, cognitive and sensory symptoms predominating. Aphasia, agnosia, seizures and visual field defects were observed. At follow-up, 70% developed definite multiple sclerosis, and 14% had an isolated demyelinating syndrome. Median time to second attack was 4.8 years, and median EDSS at follow-up was 3.0. Multiple lesions were present in 70% on pre-biopsy MRI, and in 83% by last MRI, with Barkhof criteria fulfilled in 46% prior to biopsy and 55% by follow-up. Only 17% of cases remained unifocal. Median largest lesion size on T2-weighted images was 4 cm (range 0.5–12), with a discernible size of 2.1 cm (range 0.5–7.5). Biopsied lesions demonstrated mass effect in 45% and oedema in 77%. A strong association was found between lesion size, and presence of mass effect and/or oedema (P < 0.001). Ring enhancement was frequent. Most tumefactive features did not correlate with gender, course or diagnosis. Although lesion size >5 cm was associated with a slightly higher EDSS at last follow-up, long-term prognosis in patients with disease duration >10 years was better (EDSS 1.5) compared with a population-based multiple sclerosis cohort matched for disease duration (EDSS 3.5; P < 0.001). Given the retrospective nature of the study, the precise reason for biopsy could not always be determined. This study underscores the diagnostically challenging nature of CNS IDDs that present with atypical clinical or radiographic features. Most have multifocal disease at onset, and develop RRMS by follow-up. Although increased awareness of this broad spectrum may obviate need for biopsy in many circumstances, an important role for diagnostic brain biopsy may be required in some cases

Reduced evolutionary rate in reemerged Ebola virus transmission chains

On 29 June 2015, Liberia’s respite from Ebola virus disease (EVD) was interrupted for the second time by a renewed outbreak (“flare-up”) of seven confirmed cases. We demonstrate that, similar to the March 2015 flare-up associated with sexual transmission, this new flare-up was a reemergence of a Liberian transmission chain originating from a persistently infected source rather than a reintroduction from a reservoir or a neighboring country with active transmission. Although distinct, Ebola virus (EBOV) genomes from both flare-ups exhibit significantly low genetic divergence, indicating a reduced rate of EBOV evolution during persistent infection. Using this rate of change as a signature, we identified two additional EVD clusters that possibly arose from persistently infected sources. These findings highlight the risk of EVD flare-ups even after an outbreak is declared over

Large-Scale Mass Spectrometry Imaging Investigation of Consequences of Cortical Spreading Depression in a Transgenic Mouse Model of Migraine

Cortical spreading depression (CSD) is the electrophysiological correlate of migraine aura. Transgenic mice carrying the R192Q missense mutation in the Cacna1a gene, which in patients causes familial hemiplegic migraine type 1 (FHM1), exhibit increased propensity to CSD. Herein, mass spectrometry imaging (MSI) was applied for the first time to an animal cohort of transgenic and wild type mice to study the biomolecular changes following CSD in the brain. Ninety-six coronal brain sections from 32 mice were analyzed by MALDI-MSI. All MSI datasets were registered to the Allen Brain Atlas reference atlas of the mouse brain so that the molecular signatures of distinct brain regions could be compared. A number of metabolites and peptides showed substantial changes in the brain associated with CSD. Among those, different mass spectral features showed significant (t-test, P < 0.05) changes in the cortex, 146 and 377 Da, and in the thalamus, 1820 and 1834 Da, of the CSD-affected hemisphere of FHM1 R192Q mice. Our findings reveal CSD- and genotype-specific molecular changes in the brain of FHM1 transgenic mice that may further our understanding about the role of CSD in migraine pathophysiology. The results also demonstrate the utility of aligning MSI datasets to a common reference atlas for large-scale MSI investigations. [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13361-015-1136-8) contains supplementary material, which is available to authorized users

Virus genomes reveal factors that spread and sustained the Ebola epidemic.

The 2013-2016 West African epidemic caused by the Ebola virus was of unprecedented magnitude, duration and impact. Here we reconstruct the dispersal, proliferation and decline of Ebola virus throughout the region by analysing 1,610 Ebola virus genomes, which represent over 5% of the known cases. We test the association of geography, climate and demography with viral movement among administrative regions, inferring a classic 'gravity' model, with intense dispersal between larger and closer populations. Despite attenuation of international dispersal after border closures, cross-border transmission had already sown the seeds for an international epidemic, rendering these measures ineffective at curbing the epidemic. We address why the epidemic did not spread into neighbouring countries, showing that these countries were susceptible to substantial outbreaks but at lower risk of introductions. Finally, we reveal that this large epidemic was a heterogeneous and spatially dissociated collection of transmission clusters of varying size, duration and connectivity. These insights will help to inform interventions in future epidemics

Kinetic study of poly(vynyl acetate) - calcium carbonate co-grinding in a ball mill

ISBN 085 825 794

Liquid chromatography-mass spectrometry method for quantification of caspofungin in clinical plasma samples

Caspofungin [(CASPO) MK-0991] is the first broad-spectrum anti-fungal agent of the echinocandin class approved for clinical use. Measurement of CASPO levels in blood might help monitor therapy in patients who are critically ill, in particular, if high-dose regimens or combinations of CASPO with other anti-fungals are used. The objective of this study was to develop a fast method for the measurement of CASPO levels in clinical blood samples using liquid chromatography coupled to a triple-quadrupole mass spectrometer. Stock solutions were prepared in plasma to avoid CASPO adsorption to glass and plastic surfaces during processing. CASPO and the internal standard (IS) were extracted from 100 microl of plasma using acetonitrile protein precipitation. The supernatant was diluted and directly injected into an analytical column (C8; 2.1 x 30 mm). The total run time was 15 min. CASPO was ionized by electrospray in the positive mode. CASPO and IS [M + 2H]2+ parent ions (m/z 547.3 and 547.8, respectively) and specific product ions (m/z 137.1 and 62.2, respectively) were used for the ion transitions. No carry over or cross-talk was observed on the column. The mean method recovery was 90 +/- 3%. Neither blood from different individuals (n = 6) nor the presence of concomitant drugs (n = 33) in plasma samples interfered with CASPO quantification. Quantification over time of the CASPO levels in plasma and whole blood was investigated at different pre-analysis storage conditions. The calibration curve included the clinically relevant CASPO concentration range from 0.04 to 20 microg/ml. Mean intra- and inter-day accuracy was 96.1 +/- 2.2% and 102.5 +/- 2.4%, respectively. Mean intra- and inter-day precision was 7.9 +/- 3.2% and 6.3 +/- 1.8%, respectively. This simple and robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) method may easily be implemented for monitoring CASPO therapy