Philosophical transactions of the Royal Society of London. Series B, Biological sciences
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Philos. Trans. R. Soc. Lond., B, Biol. Sci. · Aug 2013
Preventive chemotherapy as a strategy for elimination of neglected tropical parasitic diseases: endgame challenges.
Global efforts to address neglected tropical diseases (NTDs) were stimulated in January 2012 by the London declaration at which 22 partners, including the Bill & Melinda Gates Foundation, World Bank, World Health Organization (WHO) and major pharmaceutical companies committed to sustaining and expanding NTD programmes to eliminate or eradicate 11 NTDs by 2020 to achieve the goals outlined in the recently published WHO road map. Here, we present the current context of preventive chemotherapy for some NTDs, and discuss the problems faced by programmes as they consider the 'endgame', such as difficulties of access to populations in post-conflict settings, limited human and financial resources, and the need to expand access to clean water and improved sanitation for schistosomiasis and soil-transmitted helminthiasis. In the case of onchocerciasis and lymphatic filariasis, ivermectin treatment carries a significant risk owing to serious adverse effects in some patients co-infected with the tropical eye worm Loa loa filariasis. We discuss the challenges of managing complex partnerships, and maintain advocacy messages for the continued support for elimination of these preventable diseases.
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Philos. Trans. R. Soc. Lond., B, Biol. Sci. · Jan 2013
ReviewImportance of the matriline for genomic imprinting, brain development and behaviour.
Mammalian brain development commences during foeto-placental development and is strongly influenced by the epigenetic regulation of imprinted genes. The foetal placenta exerts considerable influence over the functioning of the adult maternal hypothalamus, and this occurs at the same time as the foetus itself is developing a hypothalamus. Thus, the action and interaction of two genomes in one individual, the mother, has provided a template for co-adaptive functions across generations that are important for maternal care and resource transfer, while co-adaptively shaping the mothering capabilities of each subsequent generation. ⋯ The neocortex has evolved to be adaptable and sustain both short-term and long-term synaptic connections that underpin learning and memory. The adapted changes are not themselves inherited, but the predisposing mechanisms for such epigenetic changes are heritable. This provides each generation with the same ability to make new adaptations while constrained by a transgenerational knowledge-based predisposition to preserve others.
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Philos. Trans. R. Soc. Lond., B, Biol. Sci. · Jan 2013
The neurobiology of depression--revisiting the serotonin hypothesis. II. Genetic, epigenetic and clinical studies.
The serotonin system originates from a small number of neurons (a few hundred thousand of the 100 billion in man) located in the midbrain raphe nuclei, that project widely throughout the central nervous system to influence a large array of inter-related biological functions, not least of which are circuits involved in mood and emotion. The serotonin hypothesis of depression has postulated that a reduction in serotonin leads to increased predisposition to depression. ⋯ Many potential mechanisms known to alter the genes that regulate the serotonin system, including developmental epigenetic modifications, are presented, as additional evidence implicating the serotonin system. This second issue of two special issues of Philosophical Transactions B presents a series of reviews, perspectives and new findings that argue that the serotonin hypothesis remains an important idea that continues to guide research into the aetiology and treatment of depression.
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Philos. Trans. R. Soc. Lond., B, Biol. Sci. · Dec 2012
ReviewTargeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibilities.
Human tissues express cannabinoid CB(1) and CB(2) receptors that can be activated by endogenously released 'endocannabinoids' or exogenously administered compounds in a manner that reduces the symptoms or opposes the underlying causes of several disorders in need of effective therapy. Three medicines that activate cannabinoid CB(1)/CB(2) receptors are now in the clinic: Cesamet (nabilone), Marinol (dronabinol; Δ(9)-tetrahydrocannabinol (Δ(9)-THC)) and Sativex (Δ(9)-THC with cannabidiol). These can be prescribed for the amelioration of chemotherapy-induced nausea and vomiting (Cesamet and Marinol), stimulation of appetite (Marinol) and symptomatic relief of cancer pain and/or management of neuropathic pain and spasticity in adults with multiple sclerosis (Sativex). ⋯ These include other kinds of pain, epilepsy, anxiety, depression, Parkinson's and Huntington's diseases, amyotrophic lateral sclerosis, stroke, cancer, drug dependence, glaucoma, autoimmune uveitis, osteoporosis, sepsis, and hepatic, renal, intestinal and cardiovascular disorders. It also describes potential strategies for improving the efficacy and/or benefit-to-risk ratio of these agonists in the clinic. These are strategies that involve (i) targeting cannabinoid receptors located outside the blood-brain barrier, (ii) targeting cannabinoid receptors expressed by a particular tissue, (iii) targeting upregulated cannabinoid receptors, (iv) selectively targeting cannabinoid CB(2) receptors, and/or (v) adjunctive 'multi-targeting'.
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Philos. Trans. R. Soc. Lond., B, Biol. Sci. · May 2012
ReviewWhat failure in collective decision-making tells us about metacognition.
Condorcet (1785) proposed that a majority vote drawn from individual, independent and fallible (but not totally uninformed) opinions provides near-perfect accuracy if the number of voters is adequately large. Research in social psychology has since then repeatedly demonstrated that collectives can and do fail more often than expected by Condorcet. Since human collective decisions often follow from exchange of opinions, these failures provide an exquisite opportunity to understand human communication of metacognitive confidence. ⋯ Inverting the question, we ask: under what conditions can two brains integrate information about one sensory modality optimally? We review recent work that has taken this approach and report discoveries about the quantitative limits of collective perceptual decision-making, and the role of the mode of communication and feedback in collective decision-making. We propose that shared metacognitive confidence conveys the strength of an individual's opinion and its reliability inseparably. We further suggest that a functional role of shared metacognition is to provide substitute signals in situations where outcome is necessary for learning but unavailable or impossible to establish.