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Ann N Y Acad Sci [journal]
- Population screening for Wilson's disease. [JOURNAL ARTICLE]
- Ann N Y Acad Sci 2014 Apr 14.
Wilson's disease is an autosomal recessive disorder of copper transport caused by mutations in the gene encoding an ATPase, ATP7B. Early detection of Wilson's disease is critical because effective medical treatments such as chelating agents and zinc salts are available, which can prevent lifelong neurological disabilities and/or cirrhosis. It is unfortunate that most patients are brought to our attention after they have developed serious complications such as brain damage or cirrhosis, despite the availability of effective treatments. The diagnosis is usually made through copper measurement in the liver tissue, followed by confirmation with genetic testing of the ATP7B gene. Currently, there are no effective biomarkers or methods suitable for newborn screening for Wilson's disease. Ceruloplasmin has been tested for pediatric and newborn screening with limited outcome. Recently, liquid chromatography-multiple reaction monitoring-mass spectrometry (LC-MRM-MS) has emerged as a robust technology that may enable multiplex quantification of signature proteotypic peptides with low abundance. The application of this technology may help facilitate the research on Wilson's disease for protein expression, biomarker study, diagnosis, and, hopefully, screening.
- Diverse strategies targeting α7 homomeric and α6β2* heteromeric nicotinic acetylcholine receptors for smoking cessation. [JOURNAL ARTICLE]
- Ann N Y Acad Sci 2014 Apr 14.
Preclinical studies suggest that a diversity of nicotinic acetylcholine receptors (nAChRs) with different sensitivities to nicotine may contribute to tobacco addiction. Using rodent intravenous nicotine self-administration as a preclinical model with good predictive validity for therapeutic efficacy for tobacco cessation, investigators have identified heteromeric α6β2* and homomeric α7 nAChRs as promising novel therapeutic targets to promote smoking abstinence (*denotes possible assembly with other subunits). The data suggest that diverse strategies that target these subclasses of nAChRs, namely inhibition of α6β2* nAChRs and stimulation of α7 nAChRs, will support tobacco cessation. α6β2* nAChRs, members of the high-affinity family of β2* nAChRs, function similarly to α4β2* nAChRs, the primary target of the FDA-approved drug varenicline, but have a much more selective neuroanatomical pattern of expression in catecholaminergic nuclei. Although activation of β2* nAChRs facilitates nicotine self-administration, stimulation of α7 nAChRs appears to negatively modulate both nicotine reinforcement and β2* nAChR function in the mesolimbic dopamine system. Although challenges and caveats must be considered in the development of therapeutics that target these nAChR subpopulations, an accumulation of data suggests that α7 nAChR agonists, partial agonists, or positive allosteric modulators and α6β2* nAChR antagonists, partial agonists, or negative allosteric modulators may prove to be effective therapeutics for tobacco cessation.
- Technical considerations for maize flour and corn meal fortification in public health: consultation rationale and summary. [Journal Article]
- Ann N Y Acad Sci 2014 Apr; 1312(1):1-7.
Fortification is the purposeful addition of vitamins and minerals to foods during their industrial processing, as a way to improve the nutrition and health of populations who consume these foods. Twelve countries have mandatory maize (Zea mays subsp. Mays) flour or meal fortification. The World Health Organization (WHO) is updating evidence-informed guidelines for the fortification of staple foods in public health, including the fortification of maize flour and corn meal with iron and other micronutrients. Although there is limited experience with fortification of maize, mass fortification of maize flour with at least iron has been practiced for many years in several countries in the Americas and Africa: Brazil, Costa Rica, El Salvador, Kenya, Mexico, Nigeria, Rwanda, South Africa, Tanzania, Uganda, the United States, and Venezuela. The WHO, in collaboration with the Sackler Institute for Nutrition Science and the Flour Fortification Initiative (FFI), convened a consultation on technical considerations for fortification of maize flour and corn meal in public health in New York, New York on April 8-9, 2013 to provide input into the guideline-development process and to discuss technical considerations of the fortification processes for maize flour and corn meal.
- Issue information. [Journal Article]
- Ann N Y Acad Sci 2014 Apr; 1311(1):i.
- The artificial pancreas: current status and future prospects in the management of diabetes. [Journal Article]
- Ann N Y Acad Sci 2014 Apr; 1311(1):102-23.
Recent advances in insulins, insulin pumps, continuous glucose-monitoring systems, and control algorithms have resulted in an acceleration of progress in the development of artificial pancreas devices. This review discusses progress in the development of external systems that are based on subcutaneous drug delivery and subcutaneous continuous glucose monitoring. There are two major system-level approaches to achieving closed-loop control of blood glucose in diabetic individuals. The unihormonal approach uses insulin to reduce blood glucose and relies on complex safety mitigation algorithms to reduce the risk of hypoglycemia. The bihormonal approach uses both insulin to lower blood glucose and glucagon to raise blood glucose, and also relies on complex algorithms to provide for safety of the user. There are several major strategies for the design of control algorithms and supervision control for application to the artificial pancreas: proportional-integral-derivative, model predictive control, fuzzy logic, and safety supervision designs. Advances in artificial pancreas research in the first decade of this century were based on the ongoing computer revolution and miniaturization of electronic technology. The advent of modern smartphones has created the ability to utilize smartphone technology as the engineering centerpiece of an artificial pancreas. With these advances, an artificial or bionic pancreas is within reach.
- Obesity and the nutrition transition in Sub-Saharan Africa. [Journal Article]
- Ann N Y Acad Sci 2014 Apr; 1311(1):88-101.
This review illustrates the outcomes of the nutrition transition in Sub-Saharan Africa (SSA) and its association with overweight and obesity; the relationship with the double burden of malnutrition is also explored. We describe the increase in overweight in nearly all Sub-Saharan African countries and present data on associated increased gross domestic product, and availability of energy, protein, fat, and sugar at country national levels. Predictors of overweight are described by means of various studies undertaken in SSA, and dietary intakes of numerous countries are presented. Overall, we show that socioeconomic status, gender, age, parity, physical inactivity, and increased energy, fat, and sugar intake are powerful predictors of overweight and/or obesity. The urgency for health interventions in countries in the early stages of the nutrition transition is emphasized, particularly in view of the fact that fat intake is still less than 30% of energy intake in nearly all Sub-Saharan African countries.
- Obesity and cancer pathogenesis. [Journal Article]
- Ann N Y Acad Sci 2014 Apr; 1311(1):57-76.
Overweight and obesity have reached pandemic levels on a worldwide basis and are associated with increased risk and worse prognosis for many but not all malignancies. Pathophysiologic processes that affect this association are reviewed, with a focus on the relationship between type 2 diabetes mellitus and cancer, lessons learned from the use of murine models to study the association, the impact of obesity on pancreatic cancer, the effects of dietary fats and cholesterol on cancer promotion, and the mechanisms by which the intestinal microbiome affects obesity and cancer.
- The power of poison: pesticide poisoning of Africa's wildlife. [JOURNAL ARTICLE]
- Ann N Y Acad Sci 2014 Apr 9.
Poisons have long been used to kill wildlife throughout the world. An evolution has occurred from the use of plant- and animal-based toxins to synthetic pesticides to kill wildlife, a method that is silent, cheap, easy, and effective. The use of pesticides to poison wildlife began in southern Africa, and predator populations were widely targeted and eliminated. A steep increase has recently been observed in the intensity of wildlife poisonings, with corresponding population declines. However, the majority of poisonings go unreported. Under national laws, it is illegal to hunt wildlife using poisons in 83% of African countries. Pesticide regulations are inadequate, and enforcement of existing legislation is poor. Few countries have forensic field protocols, and most lack storage and testing facilities. Methods used to poison wildlife include baiting carcasses, soaking grains in pesticide solution, mixing pesticides to form salt licks, and tainting waterholes. Carbofuran is the most widely abused pesticide in Africa. Common reasons for poisoning are control of damage-causing animals, harvesting fish and bushmeat, harvesting animals for traditional medicine, poaching for wildlife products, and killing wildlife sentinels (e.g., vultures because their aerial circling alerts authorities to poachers' activities). Populations of scavengers, particularly vultures, have been decimated by poisoning. Recommendations include banning pesticides, improving pesticide regulations and controlling distribution, better enforcement and stiffer penalties for offenders, increasing international support and awareness, and developing regional pesticide centers.
- A new perspective on the perceptual selectivity of attention under load. [JOURNAL ARTICLE]
- Ann N Y Acad Sci 2014 Apr 9.
The human attention system helps us cope with a complex environment by supporting the selective processing of information relevant to our current goals. Understanding the perceptual, cognitive, and neural mechanisms that mediate selective attention is a core issue in cognitive neuroscience. One prominent model of selective attention, known as load theory, offers an account of how task demands determine when information is selected and an account of the efficiency of the selection process. However, load theory has several critical weaknesses that suggest that it is time for a new perspective. Here we review the strengths and weaknesses of load theory and offer an alternative biologically plausible computational account that is based on the neural theory of visual attention. We argue that this new perspective provides a detailed computational account of how bottom-up and top-down information is integrated to provide efficient attentional selection and allocation of perceptual processing resources.
- Modifying factors and phenotypic diversity in Wilson's disease. [JOURNAL ARTICLE]
- Ann N Y Acad Sci 2014 Apr 4.
Wilson's disease (WD) is a human disorder of copper homeostasis caused by mutations in the copper-transporting ATPase ATP7B. WD is characterized by copper accumulation, predominantly in the liver and brain, hepatic pathology, and wide differences between patients in the age of onset and the spectrum of symptoms. Several factors contribute to the phenotypic variability of WD. The WD-causing mutations produce a wide range of changes in stability, activity, intracellular localization, and trafficking of ATP7B; the nonpathogenic genetic polymorphisms may contribute to the phenotype. In Atp7b(-/-) mice, a mouse model of WD, an abnormal intracellular distribution of copper in the liver triggers distinct changes in the transcriptome; these mRNA profiles might be used to more specifically define disease progression. The major effect of accumulating copper on lipid metabolism and especially cholesterol homeostasis in mice and humans suggests the importance of fat and cholesterol metabolism as modifying factors in WD.