Global Chronic Diseases

Chronic diseases, particularly cardiovascular disease (CVD), type 2 diabetes, cancer, and chronic respiratory disease, account for more than 50% of all deaths worldwide. Tobacco use, poor diet, and physical inactivity are among the major risk factors contributing to this disease burden. Yet even as the harmful impact of these diseases on health and economies strengthens and spreads globally, there is still only limited public health, financial, and political support for programs aimed at their prevention.

One reason for this neglect has been the belief by governments and philanthropists that chronic diseases are afflictions of affluent populations who have led a life of sloth. In reality, these diseases are now global problems that have been driven by profound changes in consumption patterns. Ubiquitous marketing of tobacco and unhealthy food introduces children to (and in the case of tobacco, addicts them to) lifestyles that greatly elevate their disease risk. Rapid changes in transport, work, and leisure activities have led to a global collapse in physical activity levels. Overall, unhealthy choices have become the easy choices.

Already, chronic diseases exert a significant negative impact on the health and economies of developing countries. A recent World Bank analysis of how best to improve health in Europe and Central Asia concluded that measures to control CVD would produce more gains in life expectancy than would measures to address the Millennium Development Goals* that focus on selected infectious diseases and maternal and child health. This finding probably applies to many of the 4 billion people living in low- and middle-income countries. About 3 million deaths from CVD occur annually in both India and China. One million tobacco-related deaths occur annually in China and 700,000 in India. With 1 in 5 children in the world now smoking and 1 in 10 classified as overweight or obese, future prospects regarding CVD and type 2 diabetes are grim. Because chronic diseases diminish worker productivity, investor returns in developing countries will be affected, which in turn will likely affect the growth of countries within the Organization for Economic Co-operation and Development. Recent reports by investment banks have raised concerns that transnational corporations and pension funds face future risks from the rise in obesity rates.f

Governments internationally need to act more decisively. The implementation of two major strategies adopted by all governments at World Health Assemblies could make a huge difference in global prevention of the major risk factors driving the chronic disease epidemics: the Framework Convention on Tobacco Control (FCTC), adopted in 2003; and the Global Strategy on Diet, Physical Activity and Health (Global Strategy), adopted in 2004. The FCTC will carry the force of international law when it takes affect on 28 February 2005. Already, it has stimulated increases in tobacco excise taxes, the implementation of marketing bans, and the introduction of smoke-free public places in many countries. These actions have been well documented as effective. In contrast, because there are no long-term best practices against obesity or physical inactivity, applied research is needed to assess the effectiveness of the core educational, legislative, intersectoral, and financial elements of the Global Strategy as it is implemented.

Efforts in chronic disease prevention can often take decades to yield benefits. Potentially, these benefits could be achieved more rapidly by investing in clinically based primary care treatments that focus on people at elevated risk for chronic disease, particularly CVD and diabetes. The recent report by the World Health Organization on Priority Medicines for Europe and the World emphasizes the need to expand access to currently available smoking cessation products, antihypertensives, statins, and aspirin, while investing in research to develop heat-stable insulin and a "polypill" to prevent complications and recurrences in patients with CVD.

At the core, chronic disease prevention and health promotion require a shift in thinking and actions by governments and diverse stakeholders. Each society must decide what it is willing to do and pay to help make healthy choices become the easy choices. The gains for global health and economy could be profound.

Derek Yach, Stephen R. Leederjohn Bell, Barry Kistnasamy

Derek Yach is at the Yale University School of Public Health, New Haven, CT, USA. Stephen R. Leeder is at the University of Sydney, Australia. John Bell is at Oxford University, UK. Barry Kistnasamy is at the Nelson Mandela Medical School, South Africa. * World Bank, Millennium Development Goals for Health in Europe and Central Asia. Relevance and Policy Implications (World Bank,Washington, DC, 2004). f Too Big to Ignore:The Impact of Obesity on Mortality Trends (Swiss Reinsurance Company, Zurich, Switzerland, 2004).


Highlights of the Recent Literature

Editors' Choice genetics

Parental Contributions in Elephants

African forest elephants and their much larger savanna cousins are now recognized as two distinct species that underwent an evolutionary split some 2.6 million years ago. Still, the two species coexist in narrow transition zones between forest and savanna and can produce forest-savanna hybrids.

In order to study this mixing, Roca et al. have analyzed the nuclear and mitochon-drial (mt) DNA of the two species across sub-Saharan Africa. The distribution of nuclear alleles is, as expected, distinct between the two elephant species; however, several of the savanna populations have mtDNA typical of their forest counterparts, even though their nuclear DNA is clearly of the savanna. This striking dichotomy between nuclear and maternally inherited mtDNA can best be explained by repeated hydridization between forest/hybrid females and the more aggressive savanna bulls, who presumably out-compete the forest/hybrid males, with each backcross further diluting the forest females' nuclear DNA.The high degree of similarity of the mtDNA in the savanna populations with that of the forest elephants suggests that the mixing is the result of a recent event, and the location of some of these savanna populations provides a clue: Although they are relatively distant from extant forests, they are within the range of the extended forests of the Holocene or, in the case of the Southern African populations, in the region of a large paleo-lake. — GR

Nature Genet. 37,96 (2005).

Distinct haplotypes of three nuclear genes.

microbiology Breaking and Entering

Malaria begins when an infected Anopheline mosquito injects parasites into a potential host's bloodstream while feeding.The infective stage of the malaria parasite, the sporozoite, then travels to the liver through the bloodstream, where it invades hepato-cytes. One of the major sporozoite surface proteins, the circumsporo-zoite protein (CSP), has been studied as a potential vaccine candidate, but its physiological role for the parasite within the mammalian host is unclear. Coppi et al. observed that during the invasion r ^

CSP (top, green) on the surface of live sporozoites (bottom).

process, when the parasites came into contact with target cells, CSP was proteolytically cleaved by a parasite-derived papain-like cysteine protease. In the presence of inhibitors of CSP processing, invasion was blocked in vitro. Furthermore,

_ when mice were treated with a protease inhibitor specific for papain-like proteases, sporo-zoite infectivity was also completely inhibited. Thus, a specific proteolytic cleavage event is important in promoting the invasion process, and interfering with this process can prevent malaria infection. — SMH

materials science Disordered Strain

Many methods exist for the nondestructive measurement of strain in crystalline materials, where the regular ordering of atoms generates a sharp signal when probed with x-rays or neutrons. In amorphous materials, localized strain information can be obtained by using techniques that probe the surface, such as optical or electron microscopy, but behavior at the surface does not typically mimic that in bulk material. Further, the strain fields are usually governed by the behavior around inhomogeneities such as inclusions, voids, and cracks.

Poulsen et al. have developed a technique for measuring strain distributions in amorphous materials.They exposed a bulk metallic glass based on magnesium, copper, and yttrium to high-energy x-rays, and then compressed it in situ.Two meth edited by Gilbert Chin ods were used to analyze the nearly circular symmetric diffusion patterns, one based on Q space and the other on direct space, and both depend on the shift in the position of the first peak (relative to the uncompressed reading) for determining the strain in the sample.The experiments showed that the macroscopic stiffness of the material was less than one might expect from the nearest-neighbor bonding, due to rearrangement of the atoms on the scale of 4 to 10 A. For the Q-space method, it is possible that this technique can be applied to polymer glasses using laboratory x-ray sources, where absorption is not an issue. — MSL

evolution A Minimal Set of Folds

The application of technologies that allow the collection of large amounts of data (genomic and proteomic, expression and structure) has generated a demand for methods that can be used to interrogate and systematize these data sets—hence large-scale biology has marched arm in arm with sophisticated (and sometimes bordering on the abstruse) computational analysis. In a refreshing departure from this complexity, Yang et al. have used a simple nearest-neighbor kind of approach to overlay a catalog of 174 sequenced genomes with the three-dimensional structures of 1294 protein fold superfamilies.

Surprisingly, they can resurrect the phylogenies of Archaea, Bacteria, and Eukarya quite accurately within each kingdom and pretty well across them. They also find 50 fold superfamilies that are

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