An estimate of the prevalence of epilepsy in Sub-Saharan Africa:A systematic analysis

Epilepsy is a leading serious neurological condition worldwide and has particularly significant physical, economic and social consequences in Sub–Saharan Africa. This paper aims to contribute to the understanding of epilepsy prevalence in this region and how this varies by age and sex so as to inform understanding of the disease characteristics as well as the development of infrastructure, services and policies

Estimating the burden of non–communicable diseases in low– and middle–income countries

Non-communicable causes of death and disability will dominate global health agenda for the foreseeable future. The progress in addressing their burden and achieving measurable reduction in low– and middle– income countries (LMICs) will likely require similar steps that were effective in reducing maternal and child mortality globally: (i) defining the size of the burden and the main causes responsible for the majority of the burden; (ii) understanding the most important risk factors and their importance in different contexts; (iii) systematically assessing the effectiveness and cost of the interventions that are feasible and available in LMICs; and (iv) formulating evidence–based health policies that will define appropriate health care and health research priorities to tackle the burden in the most cost–effective way

Estimating the burden of non–communicable diseases in low– and middle–income countries

Non-communicable causes of death and disability will dominate global health agenda for the foreseeable future. The progress in addressing their burden and achieving measurable reduction in low– and middle– income countries (LMICs) will likely require similar steps that were effective in reducing maternal and child mortality globally: (i) defining the size of the burden and the main causes responsible for the majority of the burden; (ii) understanding the most important risk factors and their importance in different contexts; (iii) systematically assessing the effectiveness and cost of the interventions that are feasible and available in LMICs; and (iv) formulating evidence–based health policies that will define appropriate health care and health research priorities to tackle the burden in the most cost–effective way

An estimate of the prevalence of dementia in Africa:A systematic analysis

BACKGROUND: The burden of non–communicable diseases is growing, particularly in developing countries. The greatest economic burden is due to dementia, the prevalence of which is rising with increasing longevity. In Africa, where the rate of increase of elderly persons is the fastest in the world, dementia is normally dismissed as a part of normal ageing. The lack of awareness means that many patients are suffering undiagnosed. This review aims to assess the information on the prevalence of dementia in Africa in order to estimate the current burden. METHODS: A parallel search of Medline, EMBASE and Global Health limited to post–1980 found only 10 relevant studies. Data on prevalence and risk factors were extracted and analysed. We modelled the available information and used the UN population figures for Africa to determine the age–specific and overall burden of dementia. RESULTS: The overall prevalence of dementia in adults older than 50 years in Africa was estimated to be about 2.4%, which translates to 2.76 million people living with a disease in 2010. About 2.10 millions of them live in Sub–Saharan Africa. Prevalence was the highest among females aged 80 and over (19.7%) and there was little variation between regions. Alzheimer disease was the most prevalent cause of dementia (57.1%) followed by vascular dementia (26.9%). The main risk factors were increasing age, female sex and cardiovascular disease. CONCLUSIONS: Information on dementia prevalence in Africa is very limited. Further research will not only provide a more reliable estimate of prevalence, and consequently the burden of disease, but will also raise awareness of the problem. This is critical in promoting help–seeking behaviour and generating the political commitment to make dementia a public health priority in Africa

Estimating pneumonia deaths of post-neonatal children in countries of low or no death certification in 2008

BACKGROUND: Pneumonia is the leading cause of child deaths globally. The aims of this study were to: a) estimate the number and global distribution of pneumonia deaths for children 1-59 months for 2008 for countries with low (85% coverage of death certification countries was used. For 87 high child-mortality countries pneumonia death estimates were obtained by applying a regression model developed from published and unpublished verbal autopsy data from high child-mortality settings. The total number of 1-59 months pneumonia deaths for the year 2008 for these 122 countries was estimated to be 1.18 M (95% CI 0.77 M-1.80 M), which represented 23.27% (95% CI 17.15%-32.75%) of all 1-59 month child deaths. The country level estimation correlation coefficient between these two methods was 0.40. INTERPRETATION: Although the overall number of post-neonatal pneumonia deaths was similar irrespective to the method of estimation used, the country estimate correlation coefficient was low, and therefore country-specific estimates should be interpreted with caution. Pneumonia remains the leading cause of child deaths and is greatest in regions of poverty and high child-mortality. Despite the concerns about gender inequity linked with childhood mortality we could not estimate sex-specific pneumonia mortality rates due to the inadequate data. Life-saving interventions effective in preventing and treating pneumonia mortality exist but few children in high pneumonia disease burden regions are able to access them. To achieve the United Nations Millennium Development Goal 4 target to reduce child deaths by two-thirds in year 2015 will require the scale-up of access to these effective pneumonia interventions

Imatinib Treatment Induces CD5+ B Lymphocytes and IgM Natural Antibodies with Anti-Leukemic Reactivity in Patients with Chronic Myelogenous Leukemia

Imatinib mesylate is a first line treatment of Chronic Myelogenous Leukemia and of a rare form of gastrointestinal stromal cancer, where the response to the drug is also linked to the immune system activation with production of antineoplastic cytokines. In this study, forty patients in the chronic phase of disease, treated with imatinib mesylate, were analyzed. Bone marrow aspirates were drawn at diagnosis, after 3, 6, 12, 18 months for haematological, cytofluorimetric, cytogenetic, biomolecular evaluation and cytokine measurement. Responder and non responder patients were defined according to the European LeukemiaNet recommendations. In responder patients (n = 32), the percentage of bone marrow CD20+CD5+sIgM+ lymphocytes, and the plasma levels of IgM, were significantly higher, at 3 months and up to 9 months, than in non responders. These IgM reacted with O-linked sugars expressed by leukemic cells and could induce tumor cell apoptosis. In responeìder patients the stromal-derived factor-1 and the B-lymphocyte-activating factor of the tumor necrosis factor family significantly raised in the bone marrow after imatinib administration, together with the bone morphogenetic proteins-2 and −7. All patients with high number of CD20+CD5+sIgM+ cells and high stromal-derived factor-1 and B lymphocyte activating factor levels, underwent complete cytogenetic and/or molecular remission by 12 months. We propose that CD20+CD5+sIgM+ lymphocytes producing anti-carbohydrate antibodies with anti-tumor activity, might contribute to the response to imatinib treatment. As in multivariate analysis bone marrow CD20+CD5+sIgM+ cells and stromal-derived factor-1 and B-lymphocyte-activating factor levels were significantly related to cytogenetical and molecular changes, they might contribute to the definition of the pharmacological response

Innate immunity based cancer immunotherapy: B16-F10 murine melanoma model

Abstract Background Using killed microorganisms or their parts to stimulate immunity for cancer treatment dates back to the end of 19th century. Since then, it undergone considerable development. Our novel approach binds ligands to the tumor cell surface, which stimulates tumor phagocytosis. The therapeutic effect is further amplified by simultaneous application of agonists of Toll-like receptors. We searched for ligands that induce both a strong therapeutic effect and are safe for humans. Methods B16-F10 murine melanoma model was used. For the stimulation of phagocytosis, mannan or N-formyl-methionyl-leucyl-phenylalanine, was covalently bound to tumor cells or attached using hydrophobic anchor. The following agonists of Toll-like receptors were studied: monophosphoryl lipid A (MPLA), imiquimod (R-837), resiquimod (R-848), poly(I:C), and heat killed Listeria monocytogenes. Results R-848 proved to be the most suitable Toll-like receptor agonist for our novel immunotherapeutic approach. In combination with covalently bound mannan, R-848 significantly reduced tumor growth. Adding poly(I:C) and L. monocytogenes resulted in complete recovery in 83% of mice and in their protection from the re-transplantation of melanoma cells. Conclusion An efficient cancer treatment results from the combination of Toll-like receptor agonists and phagocytosis stimulating ligands bound to the tumor cells.http://deepblue.lib.umich.edu/bitstream/2027.42/134739/1/12885_2016_Article_2982.pd

A2ML1 and otitis media : novel variants, differential expression, and relevant pathways

A genetic basis for otitis media is established, however, the role of rare variants in disease etiology is largely unknown. Previously a duplication variant within A2ML1 was identified as a significant risk factor for otitis media in an indigenous Filipino population and in US children. In this report exome and Sanger sequencing was performed using DNA samples from the indigenous Filipino population, Filipino cochlear implantees, US probands, Finnish, and Pakistani families with otitis media. Sixteen novel, damaging A2ML1 variants identified in otitis media patients were rare or low-frequency in population-matched controls. In the indigenous population, both gingivitis and A2ML1 variants including the known duplication variant and the novel splice variant c.4061 + 1 G>C were independently associated with otitis media. Sequencing of salivary RNA samples from indigenous Filipinos demonstrated lower A2ML1 expression according to the carriage of A2ML1 variants. Sequencing of additional salivary RNA samples from US patients with otitis media revealed differentially expressed genes that are highly correlated with A2ML1 expression levels. In particular, RND3 is upregulated in both A2ML1 variant carriers and high-A2ML1 expressors. These findings support a role for A2ML1 in keratinocyte differentiation within the middle ear as part of otitis media pathology and the potential application of ROCK inhibition in otitis media.Peer reviewe

Mutations in SLC20A2 are a major cause of familial idiopathic basal ganglia calcification

Familial idiopathic basal ganglia calcification (IBGC) or Fahr's disease is a rare neurodegenerative disorder characterized by calcium deposits in the basal ganglia and other brain regions, which is associated with neuropsychiatric and motor symptoms. Familial IBGC is genetically heterogeneous and typically transmitted in an autosomal dominant fashion. We performed a mutational analysis of SLC20A2, the first gene found to cause IBGC, to assess its genetic contribution to familial IBGC. We recruited 218 subjects from 29 IBGC-affected families of varied ancestry and collected medical history, neurological exam, and head CT scans to characterize each patient's disease status. We screened our patient cohort for mutations in SLC20A2. Twelve novel (nonsense, deletions, missense, and splice site) potentially pathogenic variants, one synonymous variant, and one previously reported mutation were identified in 13 families. Variants predicted to be deleterious cosegregated with disease in five families. Three families showed nonsegregation with clinical disease of such variants, but retrospective review of clinical and neuroimaging data strongly suggested previous misclassification. Overall, mutations in SLC20A2 account for as many as 41 % of our familial IBGC cases. Our screen in a large series expands the catalog of SLC20A2 mutations identified to date and demonstrates that mutations in SLC20A2 are a major cause of familial IBGC. Non-perfect segregation patterns of predicted deleterious variants highlight the challenges of phenotypic assessment in this condition with highly variable clinical presentation