Resveratrol prevents CA1 neurons against ischemic injury by parallel modulation of both GSK‐3β and CREB through PI3‐K/Akt pathways

Accumulating evidence indicates that resveratrol potently protects against cerebral ischemia damage due to its oxygen free radicals scavenging and antioxidant properties. However, cellular mechanisms that may underlie the neuroprotective effects of resveratrol in brain ischemia are not fully understood yet. This study aimed to investigate the potential association between the neuroprotective effect of resveratrol and the apoptosis/survival signaling pathways, in particular the glycogen synthase kinase 3 (GSK‐3β) and cAMP response element‐binding protein (CREB) through phosphatidylinositol 3‐kinase (PI3‐K)‐dependent pathway. An experimental model of global cerebral ischemia was induced in rats by the four‐vessel occlusion method for 10 min and followed by different periods of reperfusion. Nissl staining indicated extensive neuronal death at 7 days after ischemia/reperfusion. Administration of resveratrol by i.p. injections (30 mg/kg) for 7 days before ischemia significantly attenuated neuronal death. Both GSK‐3β and CREB appear to play a critical role in resveratrol neuroprotection through the PI3‐K/Akt pathway, as resveratrol pretreatment increased the phosphorylation of Akt, GSK‐3β and CREB in 1 h in the CA1 hippocampus after ischemia/reperfusion. Furthermore, administration of LY294002, an inhibitor of PI3‐K, compromised the neuroprotective effect of resveratrol and decreased the level of p‐Akt, p‐GSK‐3β and p‐CREB after ischemic injury. Taken together, the results suggest that resveratrol protects against delayed neuronal death in the hippocampal CA1 by maintaining the pro‐survival states of Akt, GSK‐3β and CREB pathways. These data suggest that the neuroprotective effect of resveratrol may be mediated through activation of the PI3‐K/Akt signaling pathway, subsequently downregulating expression of GSK‐3β and CREB, thereby leading to prevention of neuronal death after brain ischemia in rats.     

The state of psychiatry in Europe: Facing the challenges, developing consensus

Abstract All European countries are facing the challenge to address the very high prevalence of mental disorders with limited mental health resources, resulting in a treatment gap. Countries have drafted mental health strategies, replacing institutions with community based models of care with the aim to offer good and decent care. Psychiatry across Europe is very diverse, whether one considers models of care, resources, ways of working or training. Variation within countries, due to regionalization, can be as large as across frontiers. Valid comparisons of service delivery and their outcomes is essential for identification and dissemination of effective and efficient practice, but hampered by widely used but poorly defined terminology such as 'primary care' and 'community services', or assumptions about common ways of working. There is also still a lack of standardisation of outcome indicators. The combination of high morbidity and low supply in the presence of effective interventions is a strong argument in favour of investment, especially at times of growing need. It is necessary to support this argument with consistent evidence of improved outcome. It is essential that international groups now accept the challenge to reach consensus in order to advocate for more mental health resources.     

Circadian patterns of generalized tonic-clonic evolutions in pediatric epilepsy patients

ObjectiveTo investigate the sleep/wake, day/night, and 24-h periodicity of pediatric evolution to generalized tonic–clonic seizures (GTC).MethodsCharts of 407 consecutive patients aged 0–21 years undergoing continuous video-EEG monitoring for epilepsy were reviewed for the presence of GTC evolution. Seizures were characterized according to 2001 ILAE terminology. Charts were reviewed for EEG seizure localization, MRI lesion, and for seizure occurrence in 3-h time blocks, out of sleep or wakefulness, and during the day (6 AM–6 PM) or night. Analysis was done with binomial testing. Regression models were fitted using generalized estimating equations with patients as the cluster level variable.Results71 patients (32 girls, mean age 12.63 ± 5.3 years) had 223 seizures with GTC evolution. Sleep/wake seizure distribution predicted tonic–clonic evolution better than time of day, with more occurring during sleep (p < 0.001). Tonic–clonic evolution occurred most frequently between 12–3 AM and 6–9 AM (p < 0.05). Patients with generalized EEG onset had more tonic–clonic evolution between 9 AM and 12 PM (p < 0.05). Patients with extratemporal focal seizures were more likely to evolve during sleep (p < 0.001); this pattern was not found in patients with temporal or generalized seizure onset on EEG. Patients without MRI lesions were more likely to evolve between 12 AM and 3 AM (p < 0.05), in the sleeping state (p < 0.001), and at night (p < 0.05). Logistic regression revealed that sleep and older patient age were the most important predictors of GTC evolution.ConclusionGTC evolution occurs most frequently out of sleep and in older patients. Our results may assist in seizure prediction, individualized treatment patterns, and potentially complication and SUDEP prevention.     

A systematic review of system dynamics and agent‐based obesity models: Evaluating obesity as part of the global syndemic

The problem of obesity has recently been reframed as part of the global syndemic—the co‐occurring, interacting pandemics of obesity, undernutrition, and climate change that are driven by common underlying societal drivers. System science modeling approaches may help clarify how these shared drivers operate and the best ways to address them. The objective of this paper was to determine to what extent existing agent‐based and system dynamics computational models of obesity provide insights into the shared drivers of the global syndemic. Peer‐reviewed studies published until July 2018 were identified from Scopus, Web of Science, and PubMed databases. Thirty‐eight studies representing 30 computational models were included. They show a growing use of system dynamics and agent‐based modeling in the past decade. They most often examined mechanisms and interventions in the areas of social network‐based influences on obesity, physiology and disease state mechanics, and the role of food and physical activity environments. Usefulness for identifying common drivers of the global syndemic was mixed; most models represented Western settings and focused on obesity determinants close to the person (eg, social circles, school settings, and neighborhood environments), with a relative paucity in models at mesolevel and macrolevel and in developing country contexts.     

WormBot,an open-source robotics platform for survival and behavior analysis in C. elegans

GeroScience - Caenorhabditis elegans is a popular organism for aging research owing to its highly conserved molecular pathways, short lifespan, small size, and extensive genetic and reverse genetic...     

Validation of a new symptom outcome for knee osteoarthritis: the Ambulation Adjusted Score for Knee pain

Clinical Rheumatology - Validation of a symptom measure for early knee OA may help identify new treatments and modifiable risk factors. Symptom measures that consider pain in the context of...     

Evaluating the impact of individual alcohol licensing decisions on local health and crime: a natural experiment with synthetic controls

BackgroundLocal authorities in England can influence the local alcohol environment by contributing to the licensing process and controlling the enforcement of existing licenses. However, a gap remains in the availability of quantitative evidence of effectiveness and impact of these local interventions, including a shortage of public health evidence around individual premises. Natural experiments offer the opportunity to evaluate these interventions where formal randomisation is not possible. We aimed to assess whether it is possible to quantitatively evaluate three natural experiments of alcohol licensing decisions at small spatial scale.MethodsThree situations presenting a natural experiment were identified in different English Local Authority areas by public health or licensing practitioners: (i) the closure of a nightclub in 2013, (ii) the closure of a restaurant-nightclub following reviews in 2016, and (iii) the implementation of new local licensing guidance (LLG) in 2013/14. We obtained monthly numbers of reported incidents of emergency department admissions for alcohol-related reasons, ambulance call-outs, and various crimes at lower/middle-super-output-area level (from 2010–14 for case i, 2015–17 for case ii, and 2008–14 for case iii). Bayesian structural timeseries were used to compare trends to their counterfactuals, approximated by synthetic controls based on time series of the same outcomes in other, comparable, areas.FindingsClosure of the nightclub was associated with temporary reductions in antisocial behaviour (–18%; 95% Bayesian Credible Interval [BCI] –37 to –4); equivalent to 60 averted incidents in 4 months. Closure of the restaurant-nightclub was not associated with measurable changes in outcomes. There was some evidence that the LLG introduction was associated with a reduction in drunk and disorderly behaviour (–42%, 95% BCI –109 to 23), but this reduction equated to less than one incident per month. The unplanned end of the LLG might have contributed to an increase in domestic violence (11%, 95% BCI –10 to 35), corresponding to two additional incidents per month.InterpretationIt is possible to evaluate the impact of local alcohol policies, even at the level of individual premises, using this methodology. We provide quantitative evidence that local government actions to influence the local alcohol environment can have a positive impact on health and crime in the area but could also have unintended consequences.FundingThis work was funded by the National Institute for Health Research School for Public Health Research (NIHR SPHR), a partnership between the Universities of Sheffield, Bristol, Cambridge, Exeter, and University College London); the London School for Hygiene and Tropical Medicine; the LiLaC collaboration between the Universities of Liverpool and Lancaster and Fuse; and the Centre for Translational Research in Public Health, a collaboration between Newcastle, Durham, Northumbria, Sunderland and Teesside Universities. The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR, or the UK Department of Health.