Imaging muscle as a potential biomarker of denervation in motor neuron disease

Objective To assess clinical, electrophysiological and whole-body muscle MRI measurements of progression in patients with motor neuron disease (MND), as tools for future clinical trials, and to probe pathophysiological mechanisms in vivo. Methods A prospective longitudinal observational clinico-electrophysiological and radiological cohort study was performed. Twenty-nine MND patients and 22 age and gender-matched healthy controls were assessed with clinical measures, electrophysiological motor unit number index (MUNIX) and T2-weighted whole-body muscle MRI, at first clinic presentation and four months later. Between-group differences and associations were assessed using age and gender-adjusted multivariable regression models. Within-subject longitudinal changes were assessed using paired t-tests. Patterns of disease spread were modelled using mixed-effects multivariable regression, assessing associations between muscle relative T2 signal and anatomical adjacency to site of clinical onset. Results MND patients had 30% higher relative T2 muscle signal than controls at baseline (all-regions mean, 95%CI 15%, 45%, p<0.001). Higher T2 signal was associated with greater overall disability (coefficient -0.009, 95%CI -0.017, -0.001, p=0.023), and with clinical weakness and lower MUNIX in multiple individual muscles. Relative T2 signal in bilateral tibialis anterior increased over four months in MND patients (right: 10.2%, 95%CI 2.0%, 18.4%, p=0.017; left: 14.1%, 95%CI 3.4%, 24.9%, p=0.013). Anatomically contiguous disease spread on MRI was not apparent in this model. Conclusions Whole-body muscle MRI offers a new approach to objective assessment of denervation over short timescales in MND, and enables investigation of patterns of disease spread in vivo. Muscles inaccessible to conventional clinical and electrophysiological assessment may be investigated using this methodology

The cortical focus in childhood absence epilepsy; evidence from nonlinear analysis of scalp EEG recordings

OBJECTIVE: To determine the origin and dynamic characteristics of the generalised hyper-synchronous spike and wave (SW) discharges in childhood absence epilepsy (CAE). METHODS: We applied nonlinear methods, the error reduction ratio (ERR) causality test and cross-frequency analysis, with a nonlinear autoregressive exogenous (NARX) model, to electroencephalograms (EEGs) from CAE, selected with stringent electro-clinical criteria (17 cases, 42 absences). We analysed the pre-ictal and ictal strength of association between homologous and heterologous EEG derivations and estimated the direction of synchronisation and corresponding time lags. RESULTS: A frontal/fronto-central onset of the absences is detected in 13 of the 17 cases with the highest ictal strength of association between homologous frontal followed by centro-temporal and fronto-central areas. Delays consistently in excess of 4 ms occur at the very onset between these regions, swiftly followed by the emergence of "isochronous" (0-2 ms) synchronisation but dynamic time lag changes occur during SW discharges. CONCLUSIONS: In absences an initial cortico-cortical spread leads to dynamic lag changes to include periods of isochronous interhemispheric synchronisation, which we hypothesize is mediated by the thalamus. SIGNIFICANCE: Absences from CAE show ictal epileptic network dynamics remarkably similar to those observed in WAG/Rij rats which guided the formulation of the cortical focus theory

Canine respiratory coronavirus employs caveolin-1-mediated pathway for internalization to HRT-18G cells

Canine respiratory coronavirus (CRCoV), identified in 2003, is a member of the Coronaviridae family. The virus is a betacoronavirus and a close relative of human coronavirus OC43 and bovine coronavirus. Here, we examined entry of CRCoV into human rectal tumor cells (HRT-18G cell line) by analyzing co-localization of single virus particles with cellular markers in the presence or absence of chemical inhibitors of pathways potentially involved in virus entry. We also targeted these pathways using siRNA. The results show that the virus hijacks caveolin-dependent endocytosis to enter cells via endocytic internalization

Imaging denervation in motor neuron disease for future clinical trials: a longitudinal cohort study

A key area-of-need in motor neuron disease/amyotrophic lateral sclerosis (MND/ALS) translational research is a tool to objectively track disease progression over short timescales, to reduce duration and cost of clinical trials. Previous studies have focused on the central nervous system

A Pilot Study Investigating a Novel Non-Linear Measure of Eyes Open versus Eyes Closed EEG Synchronization in People with Alzheimer’s Disease and Healthy Controls

Background: The incidence of Alzheimer disease (AD) is increasing with the ageing population. The development of low cost non-invasive diagnostic aids for AD is a research priority. This pilot study investigated whether an approach based on a novel dynamic quantitative parametric EEG method could detect abnormalities in people with AD. Methods: 20 patients with probable AD, 20 matched healthy controls (HC) and 4 patients with probable fronto temporal dementia (FTD) were included. All had detailed neuropsychology along with structural, resting state fMRI and EEG. EEG data were analyzed using the Error Reduction Ratio-causality (ERR-causality) test that can capture both linear and nonlinear interactions between different EEG recording areas. The 95% confidence intervals of EEG levels of bi-centroparietal synchronization were estimated for eyes open (EO) and eyes closed (EC) states. Results: In the EC state, AD patients and HC had very similar levels of bi-centro parietal synchronization; but in the EO resting state, patients with AD had significantly higher levels of synchronization (AD = 0.44; interquartile range (IQR) 0.41 vs. HC = 0.15; IQR 0.17, p < 0.0001). The EO/EC synchronization ratio, a measure of the dynamic changes between the two states, also showed significant differences between these two groups (AD ratio 0.78 versus HC ratio 0.37 p < 0.0001). EO synchronization was also significantly different between AD and FTD (FTD = 0.075; IQR 0.03, p < 0.0001). However, the EO/EC ratio was not informative in the FTD group due to very low levels of synchronization in both states (EO and EC). Conclusion: In this pilot work, resting state quantitative EEG shows significant differences between healthy controls and patients with AD. This approach has the potential to develop into a useful non-invasive and economical diagnostic aid in AD

Badania historycznych przemian przyklasztornego ogrodu oo. Bernardynów w Krakowie jako podstawa projektu jego rekompozycji

Characteristics rules of composition of the Polish monastic geometric gardens, combined with the information on the history and the spatial changes in the Bernardine monastery garden in Kraków and the iconographic research on the discussed garden design, show its clear architectural and landscape character. The study indicates that there are no de facto differences in the views on its original form and underlying principles of composition. The Bernardine monastery garden was similar to other such garden designs in Poland, and its composition was based on the earlier medieval idea of the division of space into quarters planted with trees. Although over the centuries, modifications were made to the course of the borders and the general form of the garden, it remains in the very same location and invariably presents its geometric layout. Currently, the original composition is less intelligible, and the land use is different from the historical one. This fact justifies the need to redesign the garden based on the spatial studies of its historical transformations.Charakterystyka zasad kompozycji polskich geometrycznych ogrodów klasztornych, połączona z wiadomościami dotyczącymi historii oraz zmian przestrzennych ogrodu OO. Bernardynów w Krakowie oraz badaniami materiałów ikonograficznych dotyczących omawianego założenia, ukazują jego klarowną architektoniczno-krajobrazową postać. Przeprowadzone badania wskazują, iż nie ma de facto rozbieżności w poglądach na temat jego pierwotnej formy oraz podstawowych założeń kompozycji. Ogród klasztoru Bernardynów był podobny do innych tego typu założeń w Polsce, a jego kompozycja była oparta o wcześniejszą, średniowieczną ideę podziału przestrzeni na obsadzone drzewami kwatery. Choć na przestrzeni wieków dokonywano zmian w przebiegu granic oraz ogólnej postaci ogrodu, nieustająco znajduje się on w tej samej lokalizacji i niezmiennie prezentuje geometryczny charakter układu. Obecnie dawny zarys kompozycyjny jest słabiej odczytywalny, zaś sposób zagospodarowania różni się od historycznego; uzasadnia to konieczność wykonania projektu jego rekompozycji na bazie badań przestrzennych przemian ogrodu

The location and conditions of the calligraphic parks in Matwijowce, Horodyszcze and Rybczynce in Ukraina

Calligraphic parks - it is a large group of realizations, unfortunately almost unknown in the history of the landscape. Hundreds of them were designed on the turn of 19th century, but only about one hundred still exist. They are recognized as the most subtle forms of the naturalistic style. The characteristic shape of curved paths, streams and the lakeside - calling associations with Polish calligraphic writing, recognized as a canon of beauty - was distinctive for this style. Some of the parks were realized in the territory of the Ukraine. The description of their location and status quo may contribute to their restoration and to better management of the surrounding landscape

Projekt rekompozycji ogrodu przyklasztornego oo. Bernardynów w Krakowie przy uwzględnieniu wytycznych wynikających z historycznych przemian oraz współczesnych uwarunkowań funkcjonalnych

Bernardine monastery garden in Kraków boasts a history of several centuries, while the spatial changes that occurred therein have been described and illustrated by many authors. The present state of the compound in question is not contrary to the general principles of monastic gardens’ composition or to historical sources about this particular garden realisation. As a result, it was possible to develop a project for the redesign of the garden (approved by the Małopolska Regional Monument Conservation Authority), under which specific design solutions were adopted, legitimised by the data contained in written sources or resulting from the analysis of the historical plans of the garden.Celem niniejszej pracy była próba wyznaczenia obszarów predysponowanych do lokowania działalności gospodarczej w powiecie wielickim w oparciu o przyjęty zestaw kryteriów wykluczających oraz analiza ich atrakcyjności inwestycyjnej. Działalność gospodarcza obejmuje swym zagadnieniem obiekty inwestycyjne, mogące negatywnie oddziaływać na środowisko i zdrowie ludzi. Zastosowany zestaw cech przestrzennych wynikał z dostępności pozyskanego materiału i obejmował 39 warstw tematycznych, podzielonych merytorycznie na 12 grup. Dane w postaci map cyfrowych pozyskano z Małopolskiej Biblioteki Cyfrowej. Delimitacji przestrzennej jednostek dokonano za pomocą Systemu Informacji Geograficznej (GIS), w programie MapInfo Professional 8. W wyniku przeprowadzonej delimitacji otrzymano dwie lokalizacje obszarów predysponowanych w obrębie gmin: Gdów i Wieliczka. Uznano, że istnieje możliwość lokowania działalności gospodarczej na wyodrębnionych terenach a wyróżnione lokalizacje charakteryzuje bogata infrastruktura inwestycyjna, świadcząca o ich atrakcyjności gospodarczej