Stem cells for enhancing recovery after stroke: a review

The potential application for stem cell therapy is vast, and development for use in ischaemic stroke is still in its infancy. Access to stem cells for research is contentious; however, stem cells are obtainable from both animal and human. Despite a limited understanding of their mechanisms of action, clinical trials assessing stem cells in human stroke have been performed. Trials are also underway evaluating haematopoietic precursors mobilised with granulocyte-colony stimulating factor, an approach offering an autologous means of administrating stem cells for therapeutic purposes. This review summarises current knowledge in regard to stem cells and their potential for helping improve recovery after stroke

Poverty and Parenthood across Modern Nations: Findings from the Luxembourg Income Study

All modern societies face the issue of how to best support its children when labor and capital markets fail to produce adequate levels of income for their parents. Public and private means of economic and social support are mixed in rich nations to provide for both a minimally adequate level of economic and social support for families with children, and an equal opportunity for economic and social success amongst all children in the society. If we accept these goals, we might then measure failure to achieve the first outcome (adequacy) by the child poverty rate, and progress toward the second goal (equal opportunity) by the narrowness of the spread in incomes between the rich and poor in any a society. However, not all nations equally achieve these goals. If we create such measures as this, previous research has established that the United States has both the highest child poverty rate (20 percent or more) and the widest economic distance from poor to rich children of any modern (OECD) society. Others have published repeatedly on the high economic and social costs of child poverty in the United States and its social consequences. In fact, this disturbing outcome has provoked us to begin a set of wider and more complete studies designed to isolate the factors which produce poor child outcomes in the United States in comparison to those found in other nations. This paper is the second in a series of three related papers which try to examine why we find this outcome. The general rubric under which we are operating is termed 'the cost of children.' The rest of this introductory section of the paper discusses this project, the findings of our first paper on differences in poverty amongst men and women, and subsequent papers to follow. The second part of the paper presents our thoughts on the piece of the puzzle which we address here: the economic situation of parents and the poverty cost of parenthood. Next we discuss our definitions, data and methods (section III), results (section IV) and finally a summary discussion and conclusions (section V)

Cannabinoids in experimental stroke: a systematic review and meta-analysis

Cannabinoids (CBs) show promise as neuroprotectants with some agents already licensed in humans for other conditions. We systematically reviewed CBs in preclinical stroke to guide further experimental protocols. We selected controlled studies assessing acute administration of CBs for experimental stroke, identified through systematic searches. Data were extracted on lesion volume, outcome and quality, and analyzed using random effect models. Results are expressed as standardized mean difference (SMD) with 95% confidence intervals (CIs). In all, 144 experiments (34 publications) assessed CBs on infarct volume in 1,473 animals. Cannabinoids reduced infarct volume in transient (SMD −1.41 (95% CI −1.71), −1.11) P<0.00001) and permanent (−1.67 (−2.08, −1.27), P<0.00001) ischemia and in all subclasses: endocannabinoids (−1.72 (−2.62, −0.82), P=0.0002), CB1/CB2 ligands (−1.75 (−2.19, −1.31), P<0.00001), CB2 ligands (−1.65 (−2.09, −1.22), P<0.00001), cannabidiol (−1.20 (−1.63, −0.77), P<0.00001), Δ9-tetrahydrocannabinol (−1.43 (−2.01, −0.86), P<0.00001), and HU-211 (−2.90 (−4.24, −1.56), P<0.0001). Early and late neuroscores significantly improved with CB use (−1.27 (−1.58, −0.95), P<0.00001; −1.63 (−2.64, −0.62), P<0.002 respectively) and there was no effect on survival. Statistical heterogeneity and publication bias was present, median study quality was 4 (range 1 to 6/8). Overall, CBs significantly reduced infarct volume and improve functional outcome in experimental stroke. Further studies in aged, female and larger animals, with other co-morbidities are required

Global mean surface temperature response to large-scale patterns of variability in observations and CMIP5

Global mean surface temperature (GMST) fluctuates over decadal to multidecadal time-scales. Patterns of internal variability are partly responsible, but the relationships can be conflated by anthropogenically-forced signals. Here we adopt a physically-based method of separating internal variability from forced responses to examine how trends in large-scale patterns, specifically the Interdecadal Pacific Oscillation (IPO) and Atlantic Multidecadal Variability (AMV), influence GMST. After removing the forced responses, observed variability of GMST is close to the central estimates of Coupled Model Intercomparison Project Phase 5 (CMIP5) simulations, but models tend to underestimate IPO variability at time-scales >10 years, and AMV at time-scales >20 years. Correlations between GMST trends and these patterns are also underrepresented, most strongly at 10- and 35-year time-scales, for IPO and AMV respectively. Strikingly, models that simulate stronger variability of IPO and AMV also exhibit stronger relationships between these patterns and GMST, predominately at the 10- and 35-year time-scales, respectively

Granulocyte-colony stimulating factor in experimental stroke and its effects on infarct size and functional outcome: a systematic review

Background Granulocyte-colony stimulating factor (G-CSF) shows promise as a treatment for stroke. This systematic review assesses G-CSF in experimental ischaemic stroke. Methods Relevant studies were identified with searches of Medline, Embase and PubMed. Data were extracted on stroke lesion size, neurological outcome and quality, and analysed using Cochrane Review Manager using random effects models; results are expressed as standardised mean difference (SMD) and odds ratio (OR). Results Data were included from 19 publications incorporating 666 animals. G-CSF reduced lesion size significantly in transient (SMD -1.63, p4 weeks post ischaemia) was not (SMD 0.76, p=0.35). Death (OR 0.27, p<0.0001) was reduced with G-CSF. Median study quality was 4 (range 0-7/8); Egger’s test suggested significant publication bias (p=0.001). Conclusions G-CSF significantly reduced lesion size in transient but not permanent models of ischaemic stroke. Motor impairment and death were also reduced. Further studies assessing dose-response, administration time, length of ischaemia and long-term functional recovery are needed

A systematic review and meta-analysis of the in vivo haemodynamic effects of Δ9-Tetrahydrocannabinol

∆9-Tetrahydrocannabinol (THC) has complex effects on the cardiovascular system. We aimed to systematically review studies of THC and haemodynamic alterations. PubMed, Medline, and EMBASE were searched for relevant studies. Changes in blood pressure (BP), heart rate (HR), and blood flow (BF) were analysed using the Cochrane Review Manager Software. Thirty-one studies met the eligibility criteria. Fourteen publications assessed BP (number, n = 541), 22 HR (n = 567), and 3 BF (n = 45). Acute THC dosing reduced BP and HR in anaesthetised animals (BP, mean difference (MD) −19.7 mmHg, p < 0.00001; HR, MD −53.49 bpm, p < 0.00001), conscious animals (BP, MD −12.3 mmHg, p = 0.0007; HR, MD −30.05 bpm, p < 0.00001), and animal models of stress or hypertension (BP, MD −61.37 mmHg, p = 0.03) and increased cerebral BF in murine stroke models (MD 32.35%, p < 0.00001). Chronic dosing increased BF in large arteries in anaesthetised animals (MD 21.95 mL/min, p = 0.05) and reduced BP in models of stress or hypertension (MD −22.09 mmHg, p < 0.00001). In humans, acute administration increased HR (MD 8.16 bpm, p < 0.00001). THC acts differently according to species and experimental conditions, causing bradycardia, hypotension and increased BF in animals; and causing increased HR in humans. Data is limited, and further studies assessing THC-induced haemodynamic changes in humans should be considered

Decision-making in television newsrooms : the rationale for live-on-the-scene news reports

The purpose of this study was to find out why television news managers include live-on-the-scene reports in their newscasts when other story treatments are available. Live reporting from the scene of news events is made possible by electronic news gathering technologies, including microwave-equipped vehicles and satellite uplinks. Reporting live enables television stations to deliver news stories as they happen, but immediacy is not the only reason for going live. This research examined the television news decision- makers\u27 rationale for including live reports in television newscasts. The study employed a qualitative method of inquiry. Field research was conducted to provide the data needed to analyze how and why live technologies were used. Sixty-two news managers who worked for television stations in six markets were interviewed and observed. The news managers included news directors, assistant news directors, executive producers, news operations managers, assignment editors, managing editors, and producers. The news managers who participated in this study said live reports were often included in their newscasts to create an illusion or sense of immediacy rather than actually covering events that were occurring or unfolding at the time of their newscasts. They said the coverage of breaking news.was limited to less than one-third of the live shots produced. Whereas, the news managers said immediacy and logistical considerations were important reasons to go live, they also based many of their decisions on competitiveness (e.g., to show viewers the station\u27s presence in the community) and presentation (e.g., to improve the flow or pacing of their newscasts.) This study lends support to past research that showed television news is shaped in large measure by organizational influences. Most television stations are fighting to survive in highly competitive marketplaces, and their survival is linked to attracting viewers. And many of the news managers. who participated in this study said live-on-the-scene news reporting is an element of television newscasts that, according to the market research their stations have conducted, attracts and holds audience attention whether breaking news is being shown or not

Pressor therapy in acute ischaemic stroke: an updated systematic review.

BACKGROUND: Low blood pressure (BP) in acute ischaemic stroke (AIS) is associated with poor functional outcome, death, or severe disability. Increasing BP might benefit patients with post-stroke hypotension including those with potentially salvageable ischaemic penumbra. This updated systematic review considers the present evidence regarding the use of vasopressors in AIS. METHODS: We searched the Cochrane Database of Systematic Reviews, MEDLINE, EMBASE and trial databases using a structured search strategy. We examined reference lists of relevant publications for additional studies examining BP elevation in AIS. RESULTS: We included 27 studies involving 1886 patients. Nine studies assessed increasing BP during acute reperfusion therapy (intravenous thrombolysis, mechanical thrombectomy, intra-arterial thrombolysis or combined). Eighteen studies tested BP elevation alone. Phenylephrine was the most commonly used agent to increase BP (n = 16 studies), followed by norepinephrine (n = 6), epinephrine (n = 3) and dopamine (n = 2). Because of small patient numbers and study heterogeneity, a meta-analysis was not possible. Overall, BP elevation was feasible in patients with fluctuating or worsening neurological symptoms, large vessel occlusion with labile BP, sustained post-stroke hypotension and ineligible for intravenous thrombolysis or after acute reperfusion therapy. The effects on functional outcomes were largely unknown and close monitoring is advised if such intervention is undertaken. CONCLUSION: Although theoretical arguments support increasing BP to improve cerebral blood flow and sustain the ischaemic penumbra in selected AIS patients, the data are limited and results largely inconclusive. Large, randomised controlled trials are needed to identify the optimal BP target, agent, duration of treatment and effects on clinical outcomes

Granulocyte Colony Stimulating Factor and Physiotherapy after Stroke: Results of a Feasibility Randomised Controlled Trial: Stem Cell Trial of Recovery EnhanceMent after Stroke-3 (STEMS-3 ISRCTN16714730)

Background: Granulocyte-colony stimulating factor (G-CSF) mobilises endogenous haematopoietic stem cells and enhances recovery in experimental stroke. Recovery may also be dependent on an enriched environment and physical activity. G-CSF may have the potential to enhance recovery when used in combination with physiotherapy, in patients with disability late after stroke. Methods: A pilot 2 x 2 factorial randomised (1:1) placebo-controlled trial of G-CSF (double-blind), and/or a 6 week course of physiotherapy, in 60 participants with disability (mRS >1), at least 3 months after stroke. Primary outcome was feasibility, acceptability and tolerability. Secondary outcomes included death, dependency, motor function and quality of life measured 90 and 365 days after enrolment. Results: Recruitment to the trial was feasible and acceptable; of 118 screened patients, 92 were eligible and 32 declined to participate. 60 patients were recruited between November 2011 and July 2013. All participants received some allocated treatment. Although 29 out of 30 participants received all 5 G-CSF/placebo injections, only 7 of 30 participants received all 18 therapy sessions. G-CSF was well tolerated but associated with a tendency to more adverse events than placebo (16 vs 10 patients, p=0.12) and serious adverse events (SAE) (9 vs 3, p=0.10). On average, patients received 14 (out of 18 planned) therapy sessions, interquartile range [12, 17]. Only a minority (23%) of participants completed all physiotherapy sessions, a large proportion of sessions (114 of 540, 21%) were cancelled due to patient (94, 17%) and therapist factors (20, 4%). No significant differences in functional outcomes were detected in either the G-CSF or physiotherapy group at day 90 or 365. Conclusions – Delivery of G-CSF is feasible in chronic stroke. However, the study failed to demonstrate feasibility for delivering additional physiotherapy sessions late after stroke. Future work should occur earlier after stroke, alongside on-going clinical rehabilitation

Serum amyloid protein is associated with outcome following acute ischaemic stroke: data from the REmote ischaemic Conditioning After Stroke Trial (RECAST)

Background: Remote ischaemic per-conditioning (RIC) in experimental ischaemic stroke is neuroprotective. Several neurohumoral, vascular and inflammatory mediators are implicated. Methods: The REmote ischaemic Conditioning After Stroke Trial (RECAST) was a pilot blinded sham-controlled trial in patients with ischaemic stroke, randomised to receive four 5-minute cycles of RIC within 24 hours of ictus. Plasma taken pre-intervention, immediately post-intervention and on day 4 was analysed for nitric oxide (nitrate/nitrite) levels using chemiluminescence and other biomarkers were analysed by enzyme-linked immunosorbent assay (ELISA): alpha-2-macroglobulin (A2M), serum amyloid protein (SAP), e-selectin, vascular endothelial growth factor (VEGF). Biomarkers were correlated with outcome (Day 90 National Institutes of Health Stroke Scale [NIHSS], modified Rankin scale [mRS], Barthel index [BI]) using Pearson’s correlation coefficient. Results: In all 26 patients, an increase in SAP (pre- to post-intervention) positively correlated with worse day 90 mRS (r=0.429, p=0.029) and negatively with worse BI (r=-0.392, p=0.048), whilst an increase in SAP from day 0 to 4 positively correlated with worse day 90 NIHSS (r=0.400, p=0.043), mRS (r=0.505, p=0.008) and negatively with worse BI (r=-0.439, p=0.025). RIC reduced SAP levels from pre- to post-intervention (n=13, 2-way ANOVA, p<0.05), whilst sham did not. No significant changes over time or by treatment, or correlations with outcome were seen for A2M, e-selectin, nitric oxide or VEGF. Conclusion: Increased plasma levels of SAP are associated with worse clinical outcomes after ischaemic stroke. RIC reduced SAP levels from pre- to post-intervention. Larger studies assessing biomarkers and efficacy of RIC in acute ischaemic stroke are warranted