Epigenetics and migraine; complex mitochondrial interactions contributing to disease susceptibility

Migraine is a common neurological disorder classified by the World Health Organisation (WHO) as one of the top twenty most debilitating diseases in the developed world. Current therapies are only effective for a proportion of sufferers and new therapeutic targets are desperately needed to alleviate this burden. Recently the role of epigenetics in the development of many complex diseases including migraine has become an emerging topic. By understanding the importance of acetylation, methylation and other epigenetic modifications, it then follows that this modification process is a potential target to manipulate epigenetic status with the goal of treating disease. Bisulphite sequencing and methylated DNA immunoprecipitation have been used to demonstrate the presence of methylated cytosines in the human D-loop of mitochondrial DNA (mtDNA), proving that the mitochondrial genome is methylated. For the first time, it has been shown that there is a difference in mtDNA epigenetic status between healthy controls and those with disease, especially for neurodegenerative and age related conditions. Given co-morbidities with migraine and the suggestive link between mitochondrial dysfunction and the lowered threshold for triggering a migraine attack, mitochondrial methylation may be a new avenue to pursue. Creative thinking and new approaches are needed to solve complex problems and a systems biology approach, where multiple layers of information are integrated is becoming more important in complex disease modelling.

The silent and apparent neurological injury in transcatheter aortic valve implantation study (SANITY) : concept, design and rationale

Background The incidence of clinically apparent stroke in transcatheter aortic valve implantation (TAVI) exceeds that of any other procedure performed by interventional cardiologists and, in the index admission, occurs more than twice as frequently with TAVI than with surgical aortic valve replacement (SAVR). However, this represents only a small component of the vast burden of neurological injury that occurs during TAVI, with recent evidence suggesting that many strokes are clinically silent or only subtly apparent. Additionally, insult may manifest as slight neurocognitive dysfunction rather than overt neurological deficits. Characterisation of the incidence and underlying aetiology of these neurological events may lead to identification of currently unrecognised neuroprotective strategies. Methods The Silent and Apparent Neurological Injury in TAVI (SANITY) Study is a prospective, multicentre, observational study comparing the incidence of neurological injury after TAVI versus SAVR. It introduces an intensive, standardised, formal neurologic and neurocognitive disease assessment for all aortic valve recipients, regardless of intervention (SAVR, TAVI), valve-type (bioprosthetic, Edwards SAPIEN-XT) or access route (sternotomy, transfemoral, transapical or transaortic). Comprehensive monitoring of neurological insult will also be recorded to more fully define and compare the neurological burden of the procedures and identify targets for harm minimisation strategies. Discussion The SANITY study undertakes the most rigorous assessment of neurological injury reported in the literature to date. It attempts to accurately characterise the insult and sustained injury associated with both TAVI and SAVR in an attempt to advance understanding of this complication and associations thus allowing for improved patient selection and procedural modification.

Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: A systematic analysis for the Global Burden of Disease Study 2010

BACKGROUND Measuring disease and injury burden in populations requires a composite metric that captures both premature mortality and the prevalence and severity of ill-health. The 1990 Global Burden of Disease study proposed disability-adjusted life years (DALYs) to measure disease burden. No comprehensive update of disease burden worldwide incorporating a systematic reassessment of disease and injury-specific epidemiology has been done since the 1990 study. We aimed to calculate disease burden worldwide and for 21 regions for 1990, 2005, and 2010 with methods to enable meaningful comparisons over time. METHODS We calculated DALYs as the sum of years of life lost (YLLs) and years lived with disability (YLDs). DALYs were calculated for 291 causes, 20 age groups, both sexes, and for 187 countries, and aggregated to regional and global estimates of disease burden for three points in time with strictly comparable definitions and methods. YLLs were calculated from age-sex-country-time-specific estimates of mortality by cause, with death by standardised lost life expectancy at each age. YLDs were calculated as prevalence of 1160 disabling sequelae, by age, sex, and cause, and weighted by new disability weights for each health state. Neither YLLs nor YLDs were age-weighted or discounted. Uncertainty around cause-specific DALYs was calculated incorporating uncertainty in levels of all-cause mortality, cause-specific mortality, prevalence, and disability weights. FINDINGS Global DALYs remained stable from 1990 (2·503 billion) to 2010 (2·490 billion). Crude DALYs per 1000 decreased by 23% (472 per 1000 to 361 per 1000). An important shift has occurred in DALY composition with the contribution of deaths and disability among children (younger than 5 years of age) declining from 41% of global DALYs in 1990 to 25% in 2010. YLLs typically account for about half of disease burden in more developed regions (high-income Asia Pacific, western Europe, high-income North America, and Australasia), rising to over 80% of DALYs in sub-Saharan Africa. In 1990, 47% of DALYs worldwide were from communicable, maternal, neonatal, and nutritional disorders, 43% from non-communicable diseases, and 10% from injuries. By 2010, this had shifted to 35%, 54%, and 11%, respectively. Ischaemic heart disease was the leading cause of DALYs worldwide in 2010 (up from fourth rank in 1990, increasing by 29%), followed by lower respiratory infections (top rank in 1990; 44% decline in DALYs), stroke (fifth in 1990; 19% increase), diarrhoeal diseases (second in 1990; 51% decrease), and HIV/AIDS (33rd in 1990; 351% increase). Major depressive disorder increased from 15th to 11th rank (37% increase) and road injury from 12th to 10th rank (34% increase). Substantial heterogeneity exists in rankings of leading causes of disease burden among regions. INTERPRETATION Global disease burden has continued to shift away from communicable to non-communicable diseases and from premature death to years lived with disability. In sub-Saharan Africa, however, many communicable, maternal, neonatal, and nutritional disorders remain the dominant causes of disease burden. The rising burden from mental and behavioural disorders, musculoskeletal disorders, and diabetes will impose new challenges on health systems. Regional heterogeneity highlights the importance of understanding local burden of disease and setting goals and targets for the post-2015 agenda taking such patterns into account. Because of improved definitions, methods, and data, these results for 1990 and 2010 supersede all previously published Global Burden of Disease results.

Environmental exposures : an underrecognized contribution to noncommunicable diseases

Previous attempts to determine the degree to which exposure to environmental factors contribute to noncommunicable diseases (NCDs) have been very conservative and have significantly underestimated the actual contribution of the environment for at least two reasons. Firstly, most previous reports have excluded the contribution of lifestyle behavioral risk factors, but these usually involve significant exposure to environmental chemicals that increase risk of disease. Secondly, early life exposure to chemical contaminants is now clearly associated with an elevated risk of several diseases later in life, but these connections are often difficult to discern. This is especially true for asthma and neurodevelopmental conditions, but there is also a major contribution to the development of obesity and chronic diseases. Most cancers are caused by environmental exposures in genetically susceptible individuals. In addition, new information shows significant associations between cardiovascular diseases and diabetes and exposure to environmental chemicals present in air, food, and water. These relationships likely reflect the combination of epigenetic effects and gene induction. Environmental factors contribute significantly more to NCDs than previous reports have suggested. Prevention needs to shift focus from individual responsibility to societal responsibility and an understanding that effective prevention of NCDs ultimately relies on improved environmental management to reduce exposure to modifiable risks.

Poverty and non-communicable diseases in South Africa

Background: High levels of wealth inequality with improved health statistics in South Africa (SA) provide an important opportunity to investigate non-communicable diseases (NCDs) among the poor. Aims: This paper uses two distinct national data sets to contrast patterns of mortality in rich and poor areas and explore the associations between poverty, risk factors, health care and selected NCDs diseases in South African adults. Methods: Causes of premature mortality in 1996 experienced in the poorest magisterial districts are compared with those in the richest, using average household wealth to classify districts. Logistic and multinomial regression are used to investigate the association of a household asset index and selected chronic conditions, related risk factors and healthcare indicators using data from the 1998 South African Demographic and Health Survey. Results: NCDs accounted for 39% and 33% of premature mortality in rich and poor districts respectively. The household survey data showed that the risk factors hypertension and obesity increased with increasing wealth, while most of the lifestyle factors, such as light smoking, domestic exposure to ``smoky'' fuels and alcohol dependence were associated with poverty. Treatment status for hypertension and asthma was worse for poor people than for rich people. Conclusions: The study suggests that NCDs and lifestyle-related risk factors are prevalent among the poor in SA and treatment for chronic diseases is lacking for poor people. The observed increase in hypertension and obesity with wealth suggests that unless comprehensive health promotion strategies are implemented, there will be an unmanageable chronic disease epidemic with future socioeconomic development in SA.

Using internet search queries for infectious disease surveillance: screening diseases for suitability

Background Internet-based surveillance systems provide a novel approach to monitoring infectious diseases. Surveillance systems built on internet data are economically, logistically and epidemiologically appealing and have shown significant promise. The potential for these systems has increased with increased internet availability and shifts in health-related information seeking behaviour. This approach to monitoring infectious diseases has, however, only been applied to single or small groups of select diseases. This study aims to systematically investigate the potential for developing surveillance and early warning systems using internet search data, for a wide range of infectious diseases. Methods Official notifications for 64 infectious diseases in Australia were downloaded and correlated with frequencies for 164 internet search terms for the period 2009–13 using Spearman’s rank correlations. Time series cross correlations were performed to assess the potential for search terms to be used in construction of early warning systems. Results Notifications for 17 infectious diseases (26.6%) were found to be significantly correlated with a selected search term. The use of internet metrics as a means of surveillance has not previously been described for 12 (70.6%) of these diseases. The majority of diseases identified were vaccine-preventable, vector-borne or sexually transmissible; cross correlations, however, indicated that vector-borne and vaccine preventable diseases are best suited for development of early warning systems. Conclusions The findings of this study suggest that internet-based surveillance systems have broader applicability to monitoring infectious diseases than has previously been recognised. Furthermore, internet-based surveillance systems have a potential role in forecasting emerging infectious disease events, especially for vaccine-preventable and vector-borne diseases

The potential impact of climate change and ultraviolet radiation on vaccine preventable infectious diseases and immunisation service delivery system

Climate change and solar ultraviolet radiation may affect vaccine-preventable infectious diseases (VPID), the human immune response process and the immunization service delivery system. We systematically reviewed the scientific literature and identified 37 relevant publications. Our study shows that climate variability and ultraviolet radiation may potentially affect VPID and the immunization delivery system through modulating vector reproduction and vaccination effectiveness, possibly influencing human immune response systems to the vaccination, and disturbing immunization service delivery. Further research is needed to determine these affects on climate-sensitive VPID and on human immune response to common vaccines. Such research will facilitate the development and delivery of optimal vaccination programs for target populations, to meet the goal of disease control and elimination.

Stories have the power to save us: A neurological framework for the imperative to tell stories

The evolutionary advantage of humans is in our unique ability to process stories – we have highly evolved ‘narrative organs.’ Through storytelling, vicarious knowledge, even guarded knowledge, is used to help our species to survive. We learn, regardless of whether the story being told is ‘truth’ or ‘fiction.’ This article discusses how humans place themselves in stories, as both observer and participant, to create a ‘neural balance’ or sweet spot that allows them to be immersed in a story without being entirely threatened by it – and how this involvement in story is the formation of empathy – an empathy that is integral to forging a future humanity. It is through empathy, we argue, that stories have the power to save us.

Role of big data in the early detection of Ebola and other emerging infectious diseases

The lack of adequate disease surveillance systems in Ebola-affected areas has both reduced the ability to respond locally and has increased global risk. There is a need to improve disease surveillance in vulnerable regions, and digital surveillance could present a viable approach.

Saliva diagnostics for oral diseases

Oral diseases, or stomatognathic diseases, denote the diseases of the mouth (“stoma”) and jaw (“gnath”). Dental caries and periodontal diseases have been traditionally considered as the most important global oral health burdens. It is important to note that in oral diagnostics, the greatest challenges are determining the clinical utility of potential biomarkers for screening (in asymptomatic people), predicting the early onset of disease (prognostic tests), and evaluating the disease activity and the efficacy of therapy through innovative diagnostic tests. An oral diagnostic test, in principle, should provide valuable information for differential diagnosis, localization of disease, and severity of infection. This information can then be incorporated by the physician when planning treatments and will provide means for assessing the effectiveness of therapy.