bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient Safety
Authors: Waring Justin
Published: February 2014

Patient safety has become a global health policy priority. Over two decades of research suggest that between 10 and 20 percent of hospital patients encounter some form of adverse event, incident, or mishap in their care delivery. The human cost of these is difficult to estimate but it remains significant, whilst the financial burden of remedial care and compensation also represents a major concern for policymakers and funders. Given such evidence, there have been major advances in policy and research centered on the reconceptualization of safety, the promotion of organizational learning, and the implementation and evaluation of safety interventions. For the wider social science community, the developments in patient safety touch on often long‐standing debates related to the social organization of health care or offer new connections with research in related disciplines.
Optometrists
Authors: Grit Feike
Published: February 2014

Optometry finds its origin in most countries in the practice of opticians. The optician was initially an artisan, a craftsman who ground lenses for spectacles and instruments such as microscopes and telescopes. With the advent of mass production of lenses during the second part of the nineteenth century, the lens grinder became an assembler of frames and lenses, dispenser of spectacles, and tester of sight. Since the invention of spectacles at the end of the thirteenth century in Italy, the optometrist has developed in many countries from an artisan, peddler, technician, and optician into a full‐fledged health care professional.
Stress, Coping, and Social Support Processes
Authors: Hatteberg Sarah J.
Published: February 2014

Despite being used to signify a number of negative occurrences or feelings in everyday life, the term “stress” has become a very specific and frequently examined concept in social scientific research. Similarly, coping and social support have been identified in this empirical literature as the ways in which individuals deal with stressful life experiences. This entry defines these terms as they are discussed in the academic literature, reviews the current state of research on this topic, and identifies promising new directions.
Hospital Director
Authors: Schweyer François‐Xavier
Published: February 2014

Not all hospital directors are chief executives and the hospital director's management duties cover a wide range of diverse environments. Three elements of hospital governance have a major effect on the role of hospital director: the autonomy of the hospital, the type of hospital board, and the notion of checks and balances. Hospital chief executives are usually not from a medical background.
Health, Education, and Gender
Authors: Powell Mary Ann
Published: February 2014

Higher levels of education are associated with better health outcomes throughout the world, but this occurs differently for men and women. In developed countries, men generally are better able to translate the benefit of education into better jobs with benefits that promote health. In developed countries, women often achieve as much or even more education than men, but without the employment benefits. However, women's health benefits more than men's from the intrinsic rewards of education, such as health promoting behaviors. In less developed countries, women's education still lags behind men's. When women are able to achieve more education, their health improves, sometimes at a faster rate than men's. This occurs, in part, because educational gains are more likely to decrease health damaging behaviors for women than for men. Also, higher levels of education are associated with decreased fertility, benefiting women's health.
Specialty Choice
Authors: Heiligers Phil J. M.
Published: February 2014

Specialty choice is a major issue for medical students. The earliest studies on this topic presented an overview of specialties as an aid to students. The role of gender in particular is explored in studies of motivation. Balancing life and work is a second issue. Male and female students experience limitations in their choice because of the conflict between the demands of family and work. This is also one of the most obvious reasons why students change their choice of specialty. Factors related to organization also influence specialty choices. Some specialties are characterized by inflexible organization of care, while others allow work to be organized in relation to family duties. It is mostly women who face difficulties in the inflexible organization of care. Since doctors in the future are likely to be mostly female, it is important to improve working conditions and the attractiveness of specialties. Studies of specialty choice are rarely longitudinal or cohort studies. Cohort studies offer a more specific causal insight into the reasons for change during a medical career.
Aging and Health
Authors: Watkins Ivan , Xie Bo , Jervis Lori L.
Published: February 2014

Aging refers to the psychological, cognitive, and physiological processes and changes that occur in people as they grow older, while health refers to the absence of disease, and may be extended to include broader notions of well‐being. Older adults face physical challenges not present in younger age groups, and differences exist between genders and ethnicities in threats to physical health in old age. An increase in global population aging places stressors on formal health care systems, informal caregivers, and retirement/pension systems, many of which are not prepared to meet upcoming challenges. Technological advances offer older adults new ways to cope with health challenges, maintain their independence, and access health information, but effective interventions are often necessary for older adults to make use of these resources. In recent years, the concept of successful aging has gained prominence, which can emphasize physical health and functioning, the preservation of social relations, and engagement in productive activities.
Non‐Communicable Diseases
Authors: Singer Merrill
Published: February 2014

Non‐communicable diseases constitute an important class of health conditions that are not directly transmitted from one person to another and commonly involve hereditary predispositions, environmental exposures, lifestyle factors, gender, aging, birth defects, and malnutrition (including deficiencies and overeating). Also of importance are socioeconomic status and the social conditions that impact the behavior aspects of many diseases. “Non‐communicable disease” and “chronic disease” are not synonymous terms because some infectious disease can become chronic (e.g., HIV infection). Among the most impactful non‐communicable diseases are cardiovascular diseases, cancers, diabetes, chronic respiratory disease, asthma, chronic kidney disease, arthritis, allergies, cataracts, osteoporosis, and mental illnesses such as Alzheimer's disease. Four of these – cardiovascular disease, cancer, chronic respiratory disease, and diabetes – are the primary causes of death from non‐communicable disease globally.
Needs Assessment
Authors: Wang May C.
Published: February 2014

Needs assessment is a part of the program planning process. It is a systematic process used to identify health, educational, resource, and other needs for health promotion so as to close the gap between the current and desired health status of a population. Several frameworks are available to guide the needs assessment process. This entry briefly discusses the reasons, and describes the steps needed, for conducting a needs assessment within the context of health promotion.
Anthropology of Child Health
Authors: Robinson Gary
Published: February 2014

Ethnographies of child health have illuminated the wide variation in patterns of childhood life, and their relationship to child health. In conjunction with demographic and epidemiological research, anthropology has helped create understanding of the social and cultural determinants of fertility and child mortality and patterns of care. Above and beyond the effects of nutrition, psychological stimulus is critical to social‐emotional and cognitive development. While policy at the population level focuses on extension of health care and early education systems, it is crucially important that at the local level intervention take into account the diversity patterns of parental care and childrearing in specific sociocultural settings. There is great diversity in systems of early childhood caregiving and diverse family strategies for survival. These cultural systems shape early attachment and social‐emotional learning in ways that need to be understood if intervention is to be effective.
Medical Education, Assessment in
Authors: Govaerts Marjan J. B.
Published: February 2014

Assessment in medical education is any (systematic) method of obtaining information from tests and other sources, used to draw inferences about trainees’ or professionals’ performance and competence development. The main goals of assessment are to protect the public, to guide future learning, and to serve as a basis for selection and promotion. Validity, reliability, and utility are key concepts in the design and evaluation of assessment. Assessment design always involves careful balancing of utility factors and compromises depending on assessment purposes. A broad range of assessment methods has been developed and implemented, covering all four levels of Miller's assessment pyramid. Until the end of the twentieth century, developments have focused on the standardization and objectification of assessment. Current developments show the growing importance of more authentic, work‐based assessments to evaluate physicians’ habitual performance. Future challenges in competence assessment include programmatic approaches to assessment design, the use of assessment for learning, and the development of new conceptual frameworks for assessment evaluation.
Medicine, Sociology of
Authors: Usher Carey L.
Published: February 2014

“Sociology of medicine” describes the work of the medical sociologist who employs a sociological perspective to study medicine, health, and illness. Typically working within an academic setting, the sociologist of medicine examines the medical system as a social institution, focusing on organizational and professional structures, roles, and values; on the functions of medicine; and on the social psychology of health and illness. The term was first used by Robert Straus in 1957.
Modernity
Authors: Wasserman Jason Adam , Cockerham William C.
Published: February 2014

This entry discusses the characteristics of modernity as a social epoch in the context of health and medicine. In sociological terms, modernity is a period characterized by particular social values and dominant ways of thinking that underpin social institutions, including medicine. The Enlightenment gave birth to new forms of thinking that made societies more advanced and modern medicine possible. The application of improved empirical techniques of observation and rational forms of thinking enabled the countless miracles of modern medicine that have undeniably benefitted humanity. Modern medicine has cured diseases, improved health, and extended life beyond what any pre‐modern physician could ever have imagined. However, it is precisely because of these successes that we now face new challenges, for which another revolution in medicine may be required.
Food Deserts
Authors: Cummins Steven
Published: February 2014

The term “food desert” was reputedly first used by a resident of a public sector housing scheme in the west of Scotland in the early 1990s to capture the experience of living in a deprived neighborhood where food was expensive and relatively unobtainable. The phrase first appeared in an “official” publication in 1995, as part of a report from a policy working group investigating grocery distribution and food retailing on behalf of the Low Income Project Team of the UK government's Nutrition Task Force. Since then the term has been increasingly used by academics, policymakers, and community groups as shorthand to describe populated urban areas where residents do not have access to an affordable and healthy diet. Government reports in the United Kingdom and elsewhere have since suggested that food deserts may damage public health by restricting the availability and affordability of foods that form the components of a healthy diet. These reports have resulted in several health and social policy initiatives designed to promote adequate retail provision of food for those on low incomes, or who live in the poorest neighborhoods.
Happiness, Flourishing, and Life Satisfaction
Authors: Keyes Corey L. M.
Published: February 2014

Happiness, subjective well‐being, and a sense of flourishing reflect positive levels of mental health. They are evaluations that people make about the quality of their lives and have been used as measures in several studies to assess how people feel, either positively or negatively, about their state of psychological well‐being and overall life satisfaction.
Community‐Based and Family Support Mental Health Services
Authors: Ritter Christian , Bonfine Natalie , Neubrander Mary , Munetz Mark R.
Published: February 2014

Community‐based and family support mental health services make up a system of care in which social and clinical resources in the community are the primary sources of care for people with mental illness. These services provide care for people with mental illness in the community instead of in psychiatric hospitals. Community‐based and family support mental health services encompass a broad range of therapeutic and psychosocial services, treatments, and practices. Such services promote illness management, encourage independent living, and enhance life skills, with the ultimate goal of helping people recover from mental illness and engage in community life in a meaningful and productive way.
Health Maintenance Organization (HMO)
Authors: Tajeu Gabriel
Published: February 2014

A health maintenance organization (HMO) is a type of managed care health insurance plan. HMOs operate similarly to other types of health insurance plans in several ways. In exchange for a monthly health insurance premium payment, the HMO provides customers with health insurance that pays for approved health care services. Similar to traditional health insurance, the price customers pay for their monthly premium is adjusted based on the health risk of the particular patient. An HMO is also different from traditional health insurance in several ways. Unlike traditional plans that generally allow customers to seek care from any licensed provider of their choice, an HMO uses a predetermined network of approved physicians and health care providers. Customers have the option of using physicians and health care providers outside of this network; however the HMO is not responsible for the cost of these services. All customers of an HMO are required to designate a primary care physician (PCP) that acts as their “gatekeeper.” In the HMO model, all visits to specialists and access to medical services must be approved by this PCP, otherwise the HMO is not responsible for paying for the health care services.
Cardiovascular Diseases
Authors: Pan An , Odegaard Andrew O. , Koh Woon‐Puay
Published: February 2014

The global disease burden of cardiovascular disease (CVD) is substantial. In the United States and other highly developed countries and populations, although the rates of CVD mortality have fallen since the initial epidemic, CVD remains the number one cause of morbidity and mortality. Current and future concerns mostly relate to developing populations as they are experiencing a sharp increase in CVD burden. Evidence from research has shown that CVD is largely preventable through adoption of healthy lifestyle factors, as well as through adequate control and treatment of clinical risk factors in the population. The success of this combined approach will require extensive and fundamental changes and developments related to policies that promote optimal CVD health, government–industry cooperation, and overall improvement in health care systems.
Childhood
Authors: Robinson Gary
Published: February 2014

Childhood is more than a period of scientifically observable growth and maturation or of legally defined immaturity; from some perspectives, it is understood in terms of what people ought to be like as future adults, and from others, as a time to be valued in and for itself, involving distinctive freedoms, forms of expression, and ways of being. The social and cultural elaboration of childhood and the institutional forces shaping it vary widely from society to society and between communities and groups, and through the lifespan, from early childhood through adolescence. Childhood today is subject to continuing rationalization, as states apply national and international norms to the definition of childhood, recognize children as beings with rights and agency, and seek to protect children from harm and vulnerability to exploitation.
General Practitioners
Authors: Puustinen Raimo
Published: February 2014

The title “general practitioner” originated in the early nineteenth century in Britain to denote physicians crossing the traditional professional boundaries and widening their therapeutic repertoire to surgical procedures. For the next 100 years the title stood for non‐specialist physicians working outside hospital premises. The creation of the British National Health Service in the 1950s forced general practitioners to evaluate their professional competence within the new health care system and to raise general practitioner to the status of a distinct medical specialty. Similar developments took place in other industrialized countries under different titles, such as “family physician” in the United States. In 1972 general practitioners representing 18 countries founded the World Organization of National Colleges, Academies and Academic Associations of General Practitioners/Family Physicians, shortened to WONCA, which now includes 126 member organizations in 102 countries with a membership of 300,000 general practitioners and family physicians.
Health and Religion
Authors: Idler Ellen L.
Published: February 2014

With its origins rooted in the earliest thinkers of the discipline, the sociological study of religion and health is a theoretically and empirically significant area of contemporary research. One body of work shows physical health and mortality to be partly determined by the religious practices of individuals and groups. The other shows the role of religious beliefs and institutions in helping individuals face the experiences of serious illness and death.
Absolute Deprivation
Authors: Ladin Keren
Published: February 2014

Absolute deprivation is generally defined as encompassing a minimal level of need rendering a person able to subsist and to participate actively in society. In practice, absolute deprivation is often synonymous with absolute poverty, defined as the absence of the minimal resources to afford the basic necessities for life. These basic needs usually refer to a minimal standard of a set of goods, which often include food, clean water, clothing, sanitation facilities, shelter, education, information, and health care. This broader definition of absolute deprivation or absolute poverty reflects an expanded notion of minimal living standards. This conception of poverty grew out of a more traditional definition of poverty, meaning income insufficient to obtain the minimum necessities for the maintenance of physical survival. These absolute measures of poverty are important in estimating the effect of disadvantage, often measured by prevalence or average intensity of poverty, on an array of population‐level outcomes, including health, well‐being, productivity, and social cohesion, as well as individual‐level measures of health, productivity, and well‐being.
Latin Americans, Health of
Authors: Mayfield Carlene A.
Published: February 2014

Several factors that have historically affected health in Latin America continue to challenge the population. These include both acute and chronic factors, but also the need for improved public health surveillance systems and infrastructure. While recent economic growth has promoted gains in health similar to other developed nations, particular health challenges remain in Latin America.
Western Europeans, Health of
Authors: Mayfield Carlene A.
Published: February 2014

The health of Western Europeans is associated with a complex network of factors. Rates of mortality, morbidity, and disability are highest among the lowest socioeconomic groups. Also chronic disease is on the rise in Western Europe, due in part to poor health behaviors. Contributing risk factors include tobacco smoking, alcohol abuse, drug abuse, poor diet, sedentary lifestyles, and unsafe sexual behavior. Efforts have been made to improve motor vehicle driver education to reduce mortality rate in young individuals, and to reduce maternal smoking.
Nurse Practitioners
Authors: Vrijhoef Hubertus J. M.
Published: February 2014

A nurse practitioner is a registered nurse who has acquired the expert knowledge base, complex decision‐making skills, and clinical competencies for expanded practice, the characteristics of which are shaped by the context and/or country in which he or she is credentialed to practice. Advanced practice in nursing is characterized not by job description, job title, or setting, but by knowledge and expertise, clinical judgment, skilled and self‐initiated care, and scholarly inquiry. It has been estimated that approximately 70 countries now have established nurse practitioner roles or are exploring the possibility of introducing them. The future for nurse practitioners looks promising. Much will depend on the success of patients, nurses, physicians, payers, policymakers, and other stakeholders in health care in collaboratively shaping its future, and on nurse practitioners being able to practice to the full extent of their training and education
Stress across the Life Course
Authors: Berkowsky Ronald W.
Published: February 2014

Discussions of social stress cannot be easily distinguished from discussions of the life course. Stressors that can contribute to negative health outcomes, whether in the form of major life events and transitions, chronic strains, or daily hassles, are different depending on where an individual currently resides along the life course and on the historical context of his or her experiences. The effect of stress on health can also be mediated or moderated by resources that change over time, such as coping ability, mastery, and social support. The stress process and the life course perspective are thus intertwined in that they inform one another, and understanding how stress affects human development and how aging affects the experience of stress can contribute to social scientists’ understanding of the relationship between stress and physical/mental health.
Pharmacists
Authors: Dingwall Robert
Published: February 2014

Pharmacy has struggled to find an identity as a health profession. This reflects the diversity of its work sites and the impact of technological and organizational change. Contemporary pharmacists rarely assemble medicines from raw, or even pre‐packaged, ingredients. As a result, the focus of their work has changed considerably into the provision of advice to both patients and prescribers, seeking to improve the efficiency and effectiveness of prescribing and to ensure that recipients use the medicines as directed. These new areas, collectively described as pharmacy practice, draw extensively on a knowledge base from the social and behavioral sciences – and have generated considerable tensions within a profession that has traditionally derived its authority from chemistry and the life sciences.
Mental Illness, Social Construction of
Authors: Olafsdottir Sigrun , Bakhtiari Elyas
Published: February 2014

Sociologists have long been interested in understanding how our world is socially constructed. This perspective views the world as created (and recreated) through human interaction over time, and stands in contrast to essentialism. While it can be argued that our understanding and responses to health in general are, at least in part, socially constructed, mental illness provides an especially interesting window to understand the social construction of reality. Given the contested nature of what constitutes a “mental” illness, specifically whether it constitutes a real biological problem or a socially constructed cultural problem, much of the early writings on social construction in medical sociology, and even psychiatry, focused on the social construction of mental illness.
Extrusion of YAG Tubes Shows that Bottom‐up Processing is Not Always Optimal
Authors: Taylor Nathan J. , Laine Richard M.
Published: February 2014

Liquid‐feed flame spray pyrolysis provides easily dispersed, unaggregated nanopowders with average particle sizes of 20–70 nm depending on the processing conditions. Their chemical compositions can be controlled to ppm levels via control of the initial precursor solution. In this paper, Y3Al5O12 composition nanopowders are produced that are atomically mixed but offer a hexagonal crystal structure rather than a YAG structure. Y2O3 and δ‐Al2O3 nanopowders are also produced and mixed to evaluate reactive sintering. It is shown that nanopowder/polymer mixtures permit the extrusion of tubes that retain their shape on debindering and sintering to ≥95% theoretical density. More importantly, the sintering behavior of hex‐Y3Al5O12 is compared with that of tubes formed using 3:5 Y2O3:δ‐Al2O3 mixtures to test the so‐called bottom‐up paradigm, which suggests that mixing on the finest length scales should provide optimal control of sintering rates, final densities, and grain sizes. Instead, it is found that reactive sintering is faster and offers better control of final grain sizes. Dense sintered tubes are translucent, and dimensional uniformity is maintained from extrusion through sintering.
The natural history of parkinson's disease
Authors: Poewe W. H. , Wenning G. K.
Published: February 2014

There are still insufficient data on the natural course of Parkinson's disease (PD) owing to lack of standardized longitudinal follow‐up studies. Reported progression rates in early PD vary considerably by a factor of 2 to 3. Similarly, data from sequential [18F]dopa PET studies in PD patients have produced variable decline rates of PET indices ranging between 7 and 70% per decade. Risk factors for rapid progression include old age at onset, concomitant major depression, dementia, and akinetic‐rigid symptom presentation. The introduction of levodopa into the routine treatment of PD patients had a dramatic impact on symptomatic control without affecting the underlying rate of disease progression. By contrast, monoamine oxidase (MAO) B inhibition by deprenyl monotherapy in early PD was shown to delay the need for levodopa by around 9 months. However, the neuroprotective action disappeared after 2 years of follow‐up. Furthermore, deprenyl also failed to influence the subsequent development of levodopa‐induced motor complications. Available studies on mortality in PD provide heterogeneous mortality rates, probably because of discrepancies between patient populations with respect to co‐morbidity, disease stage at study entry, and diagnostic accuracy. However, the most recent follow‐up from the DATATOP cohort suggests normal life expectancy in carefully selected patients without significant co‐morbidity and with adequate treatment and expert follow‐up.
The early diagnosis of parkinson's disease
Authors: Brooks David J.
Published: February 2014

Current accepted clinical criteria for the diagnosis of Parkinson's disease (PD) provide high sensitivity for detecting parkinsonism but generally show poor specificity for identifying brainstem Lewy body disease. Biochemical markers that can be used to reliably diagnose clinical and preclinical PD have thus far been sought unsuccessfully. It is now known that some PD kindreds have a mutation of the α‐synuclein gene, but this cannot be used as a genetic marker for most familial and sporadic cases. Functional imaging provides a means of discriminating typical from atypical PD, revealing characteristic patterns of loss of dopaminergic function. In addition, PET and SPECT show preserved levels of striatal metabolism and dopamine receptor binding in PD, whereas levels are reduced in the atypical variants. [18F]Dopa PET can also detect preclinical PD. In one series there was a reported 40% prevalence of preclinical dopaminergic dysfunction in asymptomatic adult relatives of familial PD patients. Finally, PET and SPECT can both be used to follow PD progression objectively. Such studies suggest an annual 4 to 12% loss of dopamine terminal function in early PD and a preclinical disease window of only a few years. In the future, functional imaging is likely to play an increasingly important role in assessing the efficacy of putative neuroprotective agents.
Genetics of parkinson's disease
Authors: Gasser Thomas
Published: February 2014

A genetic contribution to the etiology of Lewy body Parkinson's disease (PD) is now well established, based on the demonstration of a familial aggregation of the disease by case‐control and twin studies and on the description of large multigenerational families in whom clinically and pathologically typical PD is inherited in an autosomal dominant fashion. In the largest of these families, a gene locus has been mapped to the long arm of chromosome 4 and a putative disease‐causing mutation has been identified in the gene for α‐synuclein. However, analysis of a large number of individuals with sporadic and familial PD suggests that a mutation in this gene is a very rare cause of the disorder, either familial or sporadic. Another locus for autosomal dominantly inherited Lewy body PD has recently been mapped to chromosome 2p13. Possible strategies for the identification of further PD genes are discussed.
Genetic risk factors in parkinson's disease
Authors: Wood Nicholas W.
Published: February 2014

There is now overwhelming evidence for a role of genetic factors in susceptibility to Parkinson's disease. This review concentrates only on the evidence from candidate association studies because the role of linkage analysis and the successes of positional cloning are dealt with by others in this supplement. Candidate gene studies are a useful and powerful adjunct to the armamentarium of the researcher, but the robustness of the data is difficult to achieve. This is illustrated by the large literature on this subject, only a relatively small proportion of which has been reproduced. A recent study by our group is used to illustrate some of these difficulties, and the possible ways around some of the inherent biases in most of the studies are also discussed.
Autosomal dominant parkinson's disease and α‐synuclein
Authors: Polymeropoulos Mihael H.
Published: February 2014

Multiple factors have been hypothesized over the years to be contributory and/or causative for Parkinson's disease (PD). Hereditary factors, although originally discounted, have recently emerged in the focus of PD research. The study of a large Italian family with PD using a genome scan approach led to the mapping of a PD susceptibility gene to the 4q21–q23 genomic region, where the gene for α‐synuclein was previously mapped. Mutation analysis of the α‐synuclein in four unrelated families with PD revealed a missense mutation segregating with the illness. α‐Synuclein is an abundant presynaptic protein in the human brain with unknown function. It is conceivable that the mutation identified in the PD families may result in self‐aggregation and/or decreased degradation of the protein, leading to the development of intracytoplasmic inclusion bodies and eventually to neuronal cell death. Moreover, the discovery of a mutation in the synuclein gene may offer us new insights in the understanding of the pathways that lead to neuronal degeneration.
Structure/function in neuroprotection and apoptosis
Authors: Borden Katherine L.B.
Published: February 2014

The three‐dimensional conformation of proteins influences their potential to function correctly within the cell. Protein conformational issues are particularly important in neurodegeneration, as has been shown by misfolded protein forming the basis of plaques in Alzheimer's disease and prion diseases. This article focuses on protein structure/function specifically for proteins important in the pathogenesis of neurodegenerative conditions and those involved in apoptosis. The proteins used as examples in this review include α‐synuclein, the promyelocytic leukemia protein, and glyceraldehyde 3‐phosphate dehydrogenase.
Advanced glycation end products in neurodegeneration: More than early markers of oxidative stress?
Authors: Münch G. , Gerlach M. , Sian J. , Wong A. , Riederer P.
Published: February 2014

Oxidative stress is believed to play a decisive role in the pathogenesis of Parkinson's disease (PD). In addition, Lewy bodies, densely crosslinked intracellular protein deposits formed from cytoskeletal components, accumulate in presymptomatic stages of the disease. Recent findings indicate that “advanced glycation end products” (AGEs) are the major structural crosslinkers that cause the transformation of soluble neurofilament proteins to insoluble Lewy bodies. AGE formation is increased under conditions of oxidative stress, such as early GSH depletion, that are evident in the substantia nigra of PD patients, and is inhibited by radical scavengers and thiol antioxidants. Because AGEs not only are markers of oxidative stress but are also active participants in cell signaling by activation of glial cells to produce superoxide and nitric oxide, they can be considered part of a vicious cycle, which finally leads to neuronal cell death in the substantia nigra in PD.
Glial cells and inflammation in parkinson's disease: A role in neurodegeneration?
Authors: Hirsch E. C. , Hunot S. , Damier P. , Faucheux B.
Published: February 2014

The data reviewed here show that, in Parkinson's disease (PD), some dopaminergic neurons are more vulnerable than others to the pathologic process. The glial cells surrounding dopaminergic neurons may be involved in this selective vulnerability. One subpopulation of glial cells, in particular, may play a neuroprotective role by metabolizing dopamine and scavenging oxygen free radicals that are associated with dopamine metabolism. Another subpopulation of glial cells may be deleterious to dopaminergic neurons. This effect may be mediated by the production of nitric oxide and cytokines, which may in turn account for the oxidative stress observed in the substantia nigra of patients with PD. Finally, this inflammatory reaction may result in the induction of apoptosis.
Programmed cell death: Does it play a role in parkinson's disease?
Authors: Burke Robert E. , Kholodilov Nikolai G.
Published: February 2014

In recent years, the possibility that programmed cell death (PCD), which is mediated by genetic programs intrinsic to the cell, may underlie the degeneration of neurons that occurs in Parkinson's disease (PD) and allied disorders has become an important hypothesis. Although PCD was originally identified in tissues as a normal developmental phenomenon, there is no question that it can also occur in neurologic disease and models thereof. The possibility that PCD could occur in dopamine neurons in degenerative disease is made plausible by the observations that natural cell death, with the morphology of apoptosis, does occur in these neurons and that this event is regulated by developmental target interactions. In addition, it has been shown that apoptotic death can be induced in these neurons in some animal models of parkinsonism. We have shown, for example, that apoptosis can be induced during development by intrastriatal injection of the neurotoxin 6‐hydroxydopamine. Other investigators have shown that apoptosis can be induced in a chronic model of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyride toxicity. However, investigations in human PD brains have yielded mixed results thus far, with some investigators identifying evidence of apoptotic death but others not. Further investigation of human postmortem tissue will benefit from a more complete understanding of the molecular basis of PCD in dopamine neurons, such that its molecular features can be investigated, rather than strictly relying on the morphologic markers presently available.
Mitochondria in neurodegenerative apoptosis: An opportunity for therapy?
Authors: Tatton William G. , Chalmers‐Redman Ruth M. E.
Published: February 2014

Apoptotic cell death has been shown to constitute the terminal process in some neurodegenerative diseases, notably Alzheimer's disease and Parkinson's disease (PD). A decrease in mitochondrial membrane potential (ΔψM) causing opening of the permeability transition pore (PTP) in mitochondrial membranes has been implicated as a critical effector of apoptosis in a variety of non‐neural cells. Opening of the PTP leads to the release of so‐called apoptosis initiation factors that induce the degradative events of apoptosis, such as nuclear chromatin condensation and DNA fragmentation. We have extended those findings to a neuronal model of apoptosis caused by trophic withdrawal, by showing that a decrease in ΔψM is an early event occurring 2 to 6 hours before the degradative events of apoptosis. A deficiency in mitochondrial complex I activity has been demonstrated in the substantia nigra of postmortem brains and several peripheral tissues obtained from PD patients. Because ΔψM is generated by the pumping of protons out across the inner mitochondrial membrane at the mitochondrial complexes, particularly complex I, we hypothesized that the decrease in complex activity could result in a decrease in ΔψM that would render PD substantia nigra neurons vulnerable to apoptosis. In preliminary studies, we have found a decrease in ΔψM in fibroblasts obtained from some PD patients. If a decrease in ΔψM consequent on decreased complex activity is an intrinsic defect in some PD patients, it would open a number of new avenues for the reduction of neuronal apoptosis in PD. The oncoprotein BCL‐2 and the scavenger protein SOD‐1 have been shown to reduce apoptosis by facilitating closure of the PTP. A number of agents have been shown to maintain BCL‐2 and/or SOD‐1 synthesis in damaged nerve cells and thereby reduce apoptosis. Other agents, such as cyclosporin A and some benzodiazepine receptor‐binding agents, have been found to act directly on the PTP to reduce apoptosis. Accordingly, agents that maintain ΔψM and PTP closure may offer new and effective means of treating neurodegenerative apoptosis.
A fluorescent double‐labeling method to detect and confirm apoptotic nuclei in parkinson's disease
Authors: Tatton Nadine A. , Maclean‐Fraser A. , Tatton William G. , Perl Daniel P. , Warren C. Olanow
Published: February 2014

In situ end‐labeling (ISEL) has become a widely used method to determine whether cells die via apoptosis by detecting double‐stranded DNA breaks that are the result of endonuclease digestion. The enzyme terminal deoxynucleotidyl transferase can be used to label the digested 3′‐OH ends of DNA with biotin‐, digoxigenin‐, or fluorescent probe‐conjugated nucleotides. However, both single‐stranded and double‐stranded DNA breaks can be labeled by this method and therefore ISEL cannot unequivocally demonstrate apoptosis when used alone. We have developed a fluorescent double‐labeling method using ISEL combined with the cyanine dye YOYO‐1 that binds to DNA. When combined with confocal laser microscopy and deconvolution analysis, YOYO‐1 can demonstrate the presence or absence of nuclear chromatin condensation and thus confirm that ISEL‐positive nuclei are indeed apoptotic. Preliminary findings indicate that dopaminergic neurons in the substantia nigra compacta die via apoptosis in Parkinson's disease.
Levodopa Toxicity and Apoptosis
Authors: Melamed Eldad , Offen Daniel , Shirvan Anat , Djaldetti Ruth , Barzilai Ari , Ziv Ilan
Published: February 2014

Many in vitro studies have shown that levodopa is a potent toxin which is lethal to various cultured neuronal and non‐neuronal cells. The in vitro toxicity of levodopa is linked mainly to its auto‐oxidation, which generates a variety of harmful free radical species including superoxide, hydrogen peroxide, and hydroxyl radicals, and also semiquinones and quinones produced via the dopa—melanin metabolic route. Such toxic effects of levodopa can be blocked by co‐treatment with antioxidants, particularly thiol‐containing compounds. Several studies have shown that levodopa kills cells by triggering apoptosis, an active, intrinsic cell suicide program. Exposure of cultured neurons to levodopa induced the characteristic apoptotic cascade, including cell shrinkage, membrane blebbing, and nuclear and DNA fragmentation. Although levodopa is extremely toxic in vitro, there is no evidence that it damages nigrostriatal dopaminergic neurons in vivo in experimental animals and in patients with Parkinson's disease (PD). Likewise, although there is some evidence for the occurrence of apoptosis in the parkinsonian substantia nigra, it is not known whether levodopa administration is capable of inducing or accelerating programmed cell death of residual pigmented nigral neurons in PD.
DATATOP: A decade of neuroprotective inquiry
Authors: Shoulson Ira ,   Parkinson Study Group
Published: February 2014

In 1987, the DATATOP clinical trial was initiated to examine the benefits of deprenyl (selegiline) and α‐tocopherol in slowing the progression of Parkinson's disease (PD). After 14 ± 6 (mean ± SD) months of controlled observation, deprenyl 10 mg/day was found to significantly delay the time until enough disability developed to warrant the initiation of levodopa therapy. This effect was largely sustained during the overall 8.2 years of observation, including open‐label deprenyl treatment and a second treatment randomization to continue deprenyl or switch to placebo. There were no accompanying benefits of deprenyl in postponing levodopa‐related adverse effects or extending life. α‐Tocopherol produced no benefits. The 2.1% per year mortality rate of the DATATOP cohort was remarkably low, about the same as an age‐matched population without PD. Neuroprotective therapy remains an elusive goal for the experimental therapeutics of PD. Advances in understanding pathogenesis, a robust pipeline of rational treatments, and the advent of valid and reliable biologic markers hold promise in the coming decade for developing and achieving neuroprotective therapies for PD.
Dopamine agonists and neuroprotection in parkinson's disease
Authors: C. Warren Olanow  , Jenner Peter , Brooks David
Published: February 2014

There is increasing interest in the potential of dopamine agonists to provide a neuroprotective effect and to alter the natural course of levodopa‐treated Parkinson's disease (PD). Theoretically, such a protective effect might derive from (a) a levodopa sparing effect, (b) stimulation dopamine autoreceptors resulting in decreased dopamine synthesis, release, and turnover, (c) direct anti‐oxidant effects, and (d) restoration of dopaminergic tone to the dopamine‐denervated brain so as to restore inhibition to the subthalamic nucleus and thereby diminish STN‐mediated excitotoxicity. Preclinical studies have demonstrated that dopamine agonists reduce dopamine formation in comparison to levodopa, protect cultured dopaminergic neurons from a variety of toxins including levodopa, and protect dopaminergic neurons from toxins and age‐related degeneration in some rodent models of parkinsonism. Based on these findings, several clinical trials have been initiated in patients with early PD to test the effect of dopamine agonists on clinical and neuroimaging markers of disease progression.
Subthalamic nucleus‐mediated excitotoxicity in parkinson's disease: A target for neuroprotection
Authors: Rodriguez M. C. , Obeso J. A. , Olanow C. Warren
Published: February 2014

Dopamine deficiency causes disinhibition and overactivity of the subthalamic nucleus (STN). Output neurons from the STN are excitatory and use glutamate as a neurotransmitter. They project to the external and internal segments of the globus pallidum (GPe and GPi), the substantia nigra pars reticulata (SNr), and the pedunculopontine nucleus (PPN). In addition, STN neurons provide excitatory innervation to dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) that contain glutamate receptors. Stimulation of the STN induces bursting activity in SNc dopaminergic neurons. This raises the possibility that the disinhibition of STN neurons that occurs as a result of a dopamine lesion might induce excitotoxic damage in target structures, including the SNc. In addition, the reduction in complex I activity found in the nigra in Parkinson's disease (PD) may cause mitochondrial dysfunction and make SNc dopaminergic neurons vulnerable to even physiologic concentrations of glutamate. We postulate that the dopamine loss that occurs in PD produces augmented STN activity which, in turn, causes further damage to vulnerable dopaminergic neurons, thereby creating a scenario for an increasing cycle of neuronal loss in the SNc. In addition, STN overactivity could, in theory, cause damage to the GPi, SNr, and PPN and thereby account for the development of parkinsonian features that do not respond to levodopa in patients with advanced disease. This hypothesis suggests that pharmacologic or surgical therapies that reduce STN neuronal overactivity or block glutamate receptors in the SNc and other target structures might be neuroprotective and might slow or halt the progression of neurodegeneration in PD.
A High‐Pressure Polymorph of Phosphorus Nitride Imide
Authors: Marchuk Alexey , Pucher Florian J. , Karau Friedrich W. , Schnick Wolfgang
Published: February 2014

Phosphorus nitride imide, PN(NH), is of great scientific importance because it is isosteric with silica (SiO2). Accordingly, a varied structural diversity could be expected. However, only one polymorph of PN(NH) has been reported thus far. Herein, we report on the synthesis and structural investigation of the first high‐pressure polymorph of phosphorus nitride imide, β‐PN(NH); the compound has been synthesized using the multianvil technique. By adding catalytic amounts of NH4Cl as a mineralizer, it became possible to grow single crystals of β‐PN(NH), which allowed the first complete structural elucidation of a highly condensed phosphorus nitride from single‐crystal X‐ray diffraction data. The structure was confirmed by FTIR and 31P and 1H solid‐state NMR spectroscopy. We are confident that high‐pressure/high‐temperature reactions could lead to new polymorphs of PN(NH) containing five‐fold‐ or even six‐fold‐coordinated phosphorus atoms and thus rivalling or even surpassing the structural variety of SiO2.
Direct Solvothermal Synthesis of B/N‐Doped Graphene
Authors: Jung Sun‐Min , Lee Eun Kwang , Choi Min , Shin Dongbin , Jeon In‐Yup , Seo Jeong‐Min , Jeong Hu Young , Park Noejung , Oh Joon Hak , Baek Jong‐Beom
Published: February 2014

Heteroatom‐doping into graphitic networks has been utilized for opening the band gap of graphene. However, boron‐doping into the graphitic framework is extremely limited, whereas nitrogen‐doping is relatively feasible. Herein, boron/nitrogen co‐doped graphene (BCN‐graphene) is directly synthesized from the reaction of CCl4, BBr3, and N2 in the presence of potassium. The resultant BCN‐graphene has boron and nitrogen contents of 2.38 and 2.66 atom %, respectively, and displays good dispersion stability in N‐methyl‐2‐pyrrolidone, allowing for solution casting fabrication of a field‐effect transistor. The device displays an on/off ratio of 10.7 with an optical band gap of 3.3 eV. Considering the scalability of the production method and the benefits of solution processability, BCN‐graphene has high potential for many practical applications.