Effects of magnesium treatment in a model of internal capsule lesion in spontaneously hypertensive rats

<p><b>Background and Purpose:</b> The study aim was to assess the effects of magnesium sulfate (MgSO4) administration on white matter damage in vivo in spontaneously hypertensive rats.</p> <p><b>Methods:</b> The left internal capsule was lesioned by a local injection of endothelin-1 (ET-1; 200 pmol) in adult spontaneously hypertensive rats. MgSO4 was administered (300 mg/kg SC) 30 minutes before injection of ET-1, plus 200 mg/kg every hour thereafter for 4 hours. Infarct size was measured by T2-weighted magnetic resonance imaging (day 2) and histology (day 11), and functional recovery was assessed on days 3 and 10 by the cylinder and walking-ladder tests.</p> <p><b>Results:</b> ET-1 application induced a small, localized lesion within the internal capsule. Despite reducing blood pressure, MgSO4 did not significantly influence infarct volume (by magnetic resonance imaging: median, 2.1 mm3; interquartile range, 1.3 to 3.8, vs 1.6 mm3 and 1.2 to 2.1, for the vehicle-treated group; by histology: 0.3 mm3 and 0.2 to 0.9 vs 0.3 mm3 and 0.2 to 0.5, respectively). Significant forelimb and hindlimb motor deficits were evident in the vehicle-treated group as late as day 10. These impairments were significantly ameliorated by MgSO4 in both cylinder (left forelimb use, P<0.01 and both-forelimb use, P<0.03 vs vehicle) and walking-ladder (right hindlimb score, P<0.02 vs vehicle) tests.</p> <p><b>Conclusions:</b> ET-1–induced internal capsule ischemia in spontaneously hypertensive rats represents a good model of lacunar infarct with small lesion size, minimal adverse effects, and a measurable motor deficit. Despite inducing mild hypotension, MgSO4 did not significantly influence infarct size but reduced motor deficits, supporting its potential utility for the treatment of lacunar infarct.</p&gt

Ada Nield Chew: England’s forgotten suffragist

An open access essay on Ada Nield Chew, author, activist, suffragist, examining her work and her legacy, published in this popular online Magazine, an extension of the BBC History Magazine

Biomass burning and urban air pollution over the Central Mexican Plateau

Observations during the 2006 dry season of highly elevated concentrations of cyanides in the atmosphere above Mexico City (MC) and the surrounding plains demonstrate that biomass burning (BB) significantly impacted air quality in the region. We find that during the period of our measurements, fires contribute more than half of the organic aerosol mass and submicron aerosol scattering, and one third of the enhancement in benzene, reactive nitrogen, and carbon monoxide in the outflow from the plateau. The combination of biomass burning and anthropogenic emissions will affect ozone chemistry in the MC outflow

Fate and transport of volatile organic compounds in glacial till and groundwater at an industrial site in Northern Ireland

Volatile organic compound (VOC) contamination of subsurface geological material and groundwater was discovered on the Nortel Monkstown industrial site, Belfast, Northern Ireland. The objectives of this study were to (1) investigate the characteristics of the geological material and its influences on contaminated groundwater flow across the site using borehole logs and hydrological evaluations, and (2) identify the contaminants and examine their distribution in the subsurface geological material and groundwater using chemical analysis. This report focuses on the eastern car park (ECP) which was a former storage area associated with trichloroethene (TCE) degreasing operations. This is where the greatest amount of volatile organic compounds (VOCs), particularly TCE, were detected. The study site is on a complex deposit of clayey glacial till with discontinuous coarser grained lenses, mainly silts, sands and gravel, which occur at 0.45-7.82 m below ground level (bgl). The lenses overall form an elongated formation that acts as a small unconfined shallow aquifer. There is a continuous low permeable stiff clayey till layer beneath the lenses that performs as an aquitard to the groundwater. Highest concentrations of VOCs, mainly TCE, in the geological material and groundwater are in these coarser lenses at similar to 4.5-7 m bgl. Highest TCE measurements at 390,000 mu g L-1 for groundwater and at 39,000 mu g kg(-1) at 5.7 m for geological material were in borehole GA19 in the coarse lens zone. It is assumed that TCE gained entrance to the subsurface near this borehole where the clayey till was thin to absent above coarse lenses which provided little retardation to the vertical migration of this dense non-aqueous phase liquid (DNAPL) into the groundwater. However, TCE is present in low concentrations in the geological material overlying the coarse lens zone. Additionally, VOCs appear to be associated with poorly drained layers and in peat < 3.0 m bgl in the ECP. Some indication of natural attenuation as VOCs degradation products vinyl chloride (VC) and dichloromethane (DCM) also occur on the site

CCL3 and MMP-9 are induced by TL1A during death receptor 3 (TNFRSF25)-dependent osteoclast function and systemic bone loss

FLC was funded by an Arthritis Research UK PhD studentship (Grant code: 18598) awarded to ASW, ECYW and MDS. JOW was funded by a British Heart Foundation PhD studentship (Reference: FS/11/26/ 28750). ACB's PhD studentship was jointly funded by the School of Medicine and Rheumatology Research Fund (Cardiff University) and LJ's PhD studentship was jointly funded by the School of Medicine and the President's Scholarship Fund (Cardiff University) awarded to ASW. ECYW was additionally funded by MRC Project Grant G0901119.Peer reviewedPublisher PD

Report 36: Modelling ICU capacity under different epidemiological scenarios of the COVID-19 pandemic in three western European countries

The coronavirus disease 2019 (COVID-19) pandemic has placed enormous strain on healthcare systems, particularly intensive care units (ICUs), with COVID-19 patient care being a key concern of healthcare system planning for winter 2020/21. Ensuring that all patients who require intensive care, irrespective of COVID-19 status, can access it during this time is essential. This study uses an integrated model of hospital capacity planning and epidemiological projections of COVID-19 patients to estimate the spare capacity of key ICU resources under different epidemic scenarios in France, Germany and Italy across the winter period of 2020/21. In particular, we examine the effect of implementing suppression strategies of varying effectiveness, triggered by different numbers of COVID-19 patients in ICU. The use of a ‘dual-demand’ (COVID-19 and non-COVID-19) patient model and the consideration of multiple ICU resources that determine capacity (beds, doctors, nurses and ventilators) and the interdependencies between them, provides a detailed insight into potential capacity constraints this winter. Without sufficient mitigation, we estimate that COVID-19 ICU patient numbers will exceed those seen in the first peak, resulting in substantial capacity deficits, with beds being consistently found to be the most constrained resource across countries. Lockdowns triggered based on ICU capacity could lead to large improvements in spare capacity during the winter season, with pressure being most effectively alleviated when lockdown is triggered early and implemented at a higher level of suppression. In many cases, maximum deficits are reduced to lower levels which can then be managed by expanding supply-side hospital capacity, to ensure that all patients can receive treatment. The success of such interventions also depends on baseline ICU bed numbers and average non-COVID-19 patient occupancy. We find that lockdowns of longer duration reduce the total number of days in deficit, but triggering lockdown earlier when COVID-19 ICU occupancy is lower is more effective in minimising deficits. Our results highlight the dependencies between different metrics, suggesting that absolute benefits of different strategies must be weighed against the feasibility and drawbacks of different amounts of time spent in lockdown

Attention-dependent modulation of cortical taste circuits revealed by granger causality with signal-dependent noise

We show, for the first time, that in cortical areas, for example the insular, orbitofrontal, and lateral prefrontal cortex, there is signal-dependent noise in the fMRI blood-oxygen level dependent (BOLD) time series, with the variance of the noise increasing approximately linearly with the square of the signal. Classical Granger causal models are based on autoregressive models with time invariant covariance structure, and thus do not take this signal-dependent noise into account. To address this limitation, here we describe a Granger causal model with signal-dependent noise, and a novel, likelihood ratio test for causal inferences. We apply this approach to the data from an fMRI study to investigate the source of the top-down attentional control of taste intensity and taste pleasantness processing. The Granger causality with signal-dependent noise analysis reveals effects not identified by classical Granger causal analysis. In particular, there is a top-down effect from the posterior lateral prefrontal cortex to the insular taste cortex during attention to intensity but not to pleasantness, and there is a top-down effect from the anterior and posterior lateral prefrontal cortex to the orbitofrontal cortex during attention to pleasantness but not to intensity. In addition, there is stronger forward effective connectivity from the insular taste cortex to the orbitofrontal cortex during attention to pleasantness than during attention to intensity. These findings indicate the importance of explicitly modeling signal-dependent noise in functional neuroimaging, and reveal some of the processes involved in a biased activation theory of selective attention

Nel positively regulates the genesis of retinal ganglion cells by promoting their differentiation and survival during development

Peer reviewedPublisher PD