Effect of N-arachidonoyl-l-serine on human cerebromicrovascular endothelium

AbstractN-arachidonoyl-l-serine (ARA-S) is an endogenous lipid, chemically related to the endocannabinoid, N-arachidonoyl ethanolamine (i.e., anandamide) and with similar physiologic and pathophysiologic functions. Reports indicate that ARA-S possesses vasoactive and neuroprotective properties resembling those of cannabinoids. However, in contrast to cannabinoids, ARA-S binds weakly to its known classical receptors, CB1 and CB2, and is therefore considered to be a ‘cannabinoid-like’ substance. The originally described ARA-S induced-endothelial-dependent vasorelaxation was not abrogated by CB1, CB2 receptor antagonists or TRPV1 competitive inhibitor. The present report demonstrates that ARA-S enhances the fluorescence staining of both cannabinoid receptors (CB1 and CB2) in human brain endothelial cells (HBEC). This reaction is specific since it was reduced by respective selective receptor antagonist (SR141716A and SR141728A). ARA-S alone or in the presence of ET-1 was shown to alter the cytoskeleton (actin). Both ARA-S stimulated phosphorylation of various kinases (MAPK, Akt, JNK and c-JUN) and alteration of cytoskeleton are mediated via CB1, CB2 and TRPV1 receptors. The findings also showed the involvement of Rho/Rock and PI3/Akt/NO pathways in the ARA-S-induced phosphorylation of kinases and actin reorganization in HBEC. All of the above mentioned ARA-S-induced effects were reduced by the treatment with LY294002 (inhibitor of PI3/Akt kinase), except MAPK kinase. In addition, MAPK, JNK, c-JUN phosphorylation were inhibited by H1152 (inhibitor of Rho/ROCK kinase), except Akt kinase. Furthermore, PI3/Akt pathway was inhibited by pretreatment with l-NAME (inhibitor of NOS). The findings suggest that ARA-S is a modulator of Rho kinase and may play a critical role in the regulation of its activity and subsequent effects on the cytoskeleton and its role in supporting essential cell functions like vasodilation, proliferation and movement

The Next WHO Director-General’s Highest Priority: a Global Treaty on the Human Right to Health

Amidst the many challenges facing the next WHO Director-General, the new WHO head should find WHO’s foremost priority in its most important constitutional pillar: the right to health. The centerpiece of this endeavor should be leadership on the Framework Convention on Global Health (FCGH), the proposed global treaty based in the right to health and aimed at national and global health equity. The treaty would reform global governance for health to enhance accountability, transparency, and civil society participation and protect the right to health in trade, investment, climate change, and other international regimes, while catalyzing governments to institutionalize the right to health at community through to national levels. It would usher in a new era of global health with justice – vast improvements in health outcomes, equitably distributed. With the Framework Convention on Tobacco Control having served as a proof of concept, the FCGH would be an innovative treaty finding solutions to overcome global health failings in accountability, equality, financing, and inter-sectoral coherence. It would include a global health accountability framework, encompassing, civil society engagement, independent monitoring, and plans for redress, while catalyzing national health accountability strategies, accountability mechanisms, disaggregated data, and community participation. National health equity strategies, pro-poor pathways to universal health coverage, and robust non-discrimination provisions could elevate the voices, priorities, and ultimately power of marginalized populations. The FCGH would include a national and global health financing framework, while reaching beyond the health sector with right to health assessments, public health participation in developing international agreements, and responsibility for all sectors for improving health outcomes. The FCGH would reinvigorate WHO’s global health leadership, breathing new life into its founding principles. It could become the platform for reforming WHO as a rights-based 21st century institution, with badly-needed reforms, such as community participation, new priorities favouring social determinants of health, and a culture of transparency and accountability. The next Director-General should launch a historic effort to align national and global governance for with human rights through the FCGH, bringing the world closer to global health with justice

Access to lifesaving medical resources for African countries: COVID-19 testing and response, ethics, and politics

Coronavirus disease 2019 (COVID-19) has revealed how strikingly unprepared the world is for a pandemic and how easily viruses spread in our interconnected world. A governance crisis is unfolding alongside the pandemic as health officials around the world compete for access to scarce medical supplies. As governments of African countries, and those in low-income and middle-income countries around the world, seek to avoid potentially catastrophic epidemics and learn from what has worked in other countries, testing and other medical resources are of concern. With accelerating spread, funding is urgently needed. Yet even where there is enough money, many African health authorities are unable to obtain the supplies needed as geopolitically powerful countries mobilise economic, political, and strategic power to procure stocks for their populations. We have seen this before. In the AIDS pandemic lifesaving diagnostics and drugs came to many African countries long after they were available in Europe and North America. In 2020, this situation can be avoided. Although health system weakness remains acute in many places, investments by national governments, the African Union, and international initiatives to tackle AIDS, tuberculosis, malaria, polio, and post-Ebola global health security have built important public health capacities. Global leaders have an ethical obligation to avoid needless loss of life due to the foreseeable prospect of slow and inadequate access to supplies in Africa

The Associations Between Children's and Adolescents’ Suicidal and Self-Harming Behaviors, and Related Behaviors Within Their Social Networks: A Systematic Review

© 2017, Copyright © International Academy for Suicide Research.Social influences—including the suicidal and self-harming behaviors of others—have been highlighted as a risk factor for suicidal and self-harming behavior in young people, but synthesis of the evidence is lacking. A systematic review of 86 relevant papers was conducted. Considerable published evidence was obtained for positive associations between young people's suicidal and self-harming behavior and that of people they know, with those reporting knowing people who had engaged in suicidal or self-harming behaviors more likely to report engaging in similar behaviors themselves. Findings are discussed in relation to a number of methodological and measurement issues—including the role of normative perceptions—and implications for the prevention of suicidal and self-harming behavior are considered

Software project planning through comparison of Bio-inspired algorithms

Currently many organizations have adopted the development of software projects with agile methodologies, particularly Scrum, which has more than 20 years of development. In these methodologies, software is developed iteratively and delivered to the client in increments called releases. In the releases, the goal is to develop system functionality that quickly adds value to the client’s business. At the beginning of the project, one or more releases are planned. For solving the problem of replanning in the context of releases, a model is proposed considering the characteristics of agile development using Scrum. The results obtained show that the algorithm takes a little less than 7 min for solutions that propose replanning composed by 16 sprints, which is equivalent to 240 days of project. They show that applying a repair operator increases the hypervolume qualit

Assessment of Yellow Fever Epidemic Risk: An Original Multi-criteria Modeling Approach

This article describes the use of an original modeling approach to assess the risk of yellow fever (YF) epidemics. YF is a viral hemorrhagic fever responsible in past centuries for devastating outbreaks. Since the 1930s, a vaccine has been available that protects the individual for at least 10 years, if not for life. However, immunization of populations in African countries was gradually discontinued after the 1960s. With the decrease in immunity against YF in African populations the disease reemerged in the 1980s. In 2005, WHO, UNICEF, and the GAVI Alliance decided to support preventive vaccination of at-risk populations in West African endemic countries in order to tackle the reemergence of YF and reduce the risk of urban YF outbreaks. Financial resources were made available to scale up a global YF vaccine stockpile and to support countries with limited resources in the management of preventive vaccination campaigns. This article describes the process we used to determine the most at-risk populations using a mathematical model to prioritize targeted immunization campaigns. We believe that this approach could be useful for other diseases for which decision making process is difficult because of limited data availability, complex risk variables, and a need for rapid decisions and implementation

Perceived academic performance as an indicator of risk of attempted suicide in young adolescents

This study investigated perceived academic performance and self-reported suicidal behavior in adolescents (n=2,596), mean age 13 years, from 27 South Australian high schools. Groups perceiving their academic performance as failing, below average, average and above average were significantly different on measures of self-esteem, locus of control, depressive symptoms, suicidal thoughts, plans, threats, deliberate self-injury, and suicide attempts. Multivariate logistic regression analyses revealed that failing academic performance (compared to above average) is associated with a fivefold increased likelihood of a suicide attempt, controlling for self-esteem, locus of control and depressive symptoms. Teachers should note that a student presenting with low selfesteem, depressed mood and perceptions of failure may be at increased risk for suicidal thoughts and behaviors, and need referral for clinical assessment

Mental health related determinants of parenting stress among urban mothers of young children – results from a birth-cohort study in Ghana and Côte d’Ivoire

Background There are limited data on the parenting stress (PS) levels in sub-Saharan African mothers and on the association between ante- and postnatal depression and anxiety on PS. Methods A longitudinal birth cohort of 577 women from Ghana and Côte d’Ivoire was followed from the 3rd trimester in pregnancy to 2 years postpartum between 2010 and 2013. Depression and anxiety were assessed by the Patient Health Questionnaire depression module (PHQ-9) and the Generalized Anxiety Disorder (GAD-7) at baseline, 3 month, 12 month and 24 month postpartum. PS was measured using the Parenting Stress Index-Short Form (PSI-SF) at 3, 12 and 24 month. The mean total PS score and the subscale scores were compared among depressed vs. non-depressed and among anxious vs. non-anxious mothers at 3, 12 and 24 month postpartum. The proportions of clinical PS (PSI-SF raw score > 90) in depressed vs. non-depressed and anxious vs. non-anxious mothers were also compared. A generalized estimating equation (GEE) approach was used to estimate population-averaged associations between women’s depression/anxiety and PS adjusting for age, child sex, women’s anemia, education, occupation, spouse’s education, and number of sick child visits. Results A total of 577, 531 and 264 women completed the PS assessment at 3 month, 12 month and 24 month postpartum across the two sites and the prevalences of clinical PS at each time point was 33.1%, 24.4% and 14.9% in Ghana and 30.2%, 33.5% and 22.6% in Côte d’Ivoire, respectively. At all three time points, the PS scores were significantly higher among depressed mothers vs. non-depressed mothers. In the multivariate regression analyses, antepartum and postpartum depression were consistently associated with PS after adjusting for other variables. Conclusions Parenting stress is frequent and levels are high compared with previous studies from high-income countries. Antepartum and postpartum depression were both associated with PS, while antepartum and postpartum anxiety were not after adjusting for confounders. More quantitative and qualitative data are needed in sub-Saharan African populations to assess the burden of PS and understand associated mechanisms. Should our findings be replicated, it appears prudent to design and subsequently evaluate intervention strategies