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Low socioeconomic status (SES) is associated with increased risk for adverse health outcomes; those with low SES are thought to experience greater environmental disadvantage and exposure to chronic stress over the life course. The effects of chronic stress on health have been measured by cortisol levels and variations in their diurnal pattern. However, the patterns of association between SES and cortisol have been equivocal in older adults. This paper examined in 98 older adults participating in the Brain Health Substudy of the Baltimore Experience Corps Trial baseline patterns of diurnal variation in salivary cortisol associated with lower versus higher SES using total income and perceived SES relative to others. For each measure, participants stratified into lower versus higher SES showed a more blunted rate of decline in diurnal salivary cortisol over the day in adjusted models ( P values ≤ 0.05). There were no SES-related differences in awakening cortisol, cortisol-awakening response, or area under the curve. These findings confirm prior evidence of a biologic pathway through which socioeconomic disadvantage is linked to biologic vulnerability, and through which the impact of volunteer service in Experience Corps may be measured. [ABSTRACT FROM AUTHOR]

The 21st century will see improvements in the quality of human life. The development of new therapeutic technologies will prevent prevalent diseases and enable recovery from currently incurable diseases. The development of cell and tissue replacement therapies using stem cells and their progenitors will accelerate the development of causative treatments. The effort expended thus far in developing cell therapies has revealed many technical limitations. Thus, we must explore conceptual changes in the feasibility of stem cell therapy. This paper introduces the current limitations to stem cell engineering and ways to overcome these limitations, which will provide new insight into their clinical application. [ABSTRACT FROM AUTHOR]

Congestive heart failure accounts for tremendous morbidity and mortality worldwide. There are numerous causes of cardiomyopathy, the most common of which is coronary artery disease. Positron emission tomography (PET) has an established and expanding role in the evaluation of patients with cardiomyopathy. The specific application of PET to hypertrophic cardiomyopathy, cardiac sarcoidosis, and diabetic cardiomyopathy has been studied extensively and promises to be a useful tool for managing these patients. Furthermore, evaluating the efficacy of standard treatments for congestive heart failure is important as health care costs continue to rise. Recently, there have been significant developments in the field of cardiovascular stem cell research. Familiarity with the mechanisms by which stem cells benefit patientswith cardiovascular disease is the key to understanding these advances. Molecular imaging techniques including PET/CT imaging play an important role in monitoring stem cell therapy in both animals and humans. These noninvasive imaging techniques will be highlighted in this paper. [ABSTRACT FROM AUTHOR]

The scientific investigation of brains of different vertebrates, both extant and extinct, is of interest for several reasons: for translating medical research on rodent models into practice, for understanding the animals investigated in order to improve conservation and management strategies, and for understanding the evolution of the human brain. The African continent has vast resources that are incredibly valuable to this endeavor, including an enormous variety of extant species, as well as a rich fossil record covering human evolution and many aspects of vertebrate evolution. This paper briefly outlines the current situation in terms of collections in Africa, most of which are found in South Africa. It is hoped that these brief descriptions will increase international scientific interest in the available collections. [ABSTRACT FROM AUTHOR]

The pattern of myelination over the cerebral cortex, termed myeloarchitecture, is an established and often-used feature to visualize cortical organization with histology in a variety of primate species. In this paper, we use in vivo magnetic resonance imaging (MRI) and advanced image processing using surface rendering to visualize and characterize myeloarchitecture in a small nonhuman primate, the common marmoset ( Callithrix jacchus). Through images made in four female adult marmosets, we produce a representative 3D map of marmoset myeloarchitecture and flatten and annotate this map to show the location and extent of a variety of major areas of the cortex, including the primary visual, auditory, and somatosensory areas. By treating our MRI data as a surface, we can measure the surface area of cortical areas, and we present these measurements here to summarize cortical organization in the marmoset. [ABSTRACT FROM AUTHOR]

The rat vibrissal (whisker) system is an increasingly important model for the study of the sense of touch. This paper describes recent results obtained from high-speed videography of rat exploratory behavior and from modeling studies of vibrissal biomechanics. We review several features of vibrissal touch, including the mechanics of contact versus noncontact whisking, the coordination between head and whisker movements, and the use of information obtained from the whiskers to detect, localize, and extract the spatial properties of objects. This work highlights the idea that mechanics are critical to an understanding of sensory systems and describes some new tools to monitor the spatiotemporal patterns of whisker-object contact during natural tactile exploratory behavior. [ABSTRACT FROM AUTHOR]

The human brain is a complex network. An important first step toward understanding the function of such a network is to map its elements and connections, to create a comprehensive structural description of the network architecture. This paper reviews current empirical efforts toward generating a network map of the human brain, the human connectome, and explores how the connectome can provide new insights into the organization of the brain's structural connections and their role in shaping functional dynamics. Network studies of structural connectivity obtained from noninvasive neuroimaging have revealed a number of highly nonrandom network attributes, including high clustering and modularity combined with high efficiency and short path length. The combination of these attributes simultaneously promotes high specialization and high integration within a modular small-world architecture. Structural and functional networks share some of the same characteristics, although their relationship is complex and nonlinear. Future studies of the human connectome will greatly expand our knowledge of network topology and dynamics in the healthy, developing, aging, and diseased brain. [ABSTRACT FROM AUTHOR]

Thromboembolic conditions present a considerable challenge to healthcare services because they are associated with substantial morbidity and mortality. The mainstays of prevention and treatment are anticoagulants and antiplatelet agents. Established anticoagulants have drawbacks that make their use difficult to manage and sustain. This has stimulated the search for new oral anticoagulants that are more convenient and yet still effective. This paper describes the development and future potential of rivaroxaban (Xarelto™; Bayer Schering Pharma AG, Berlin, Germany)-the first oral, direct Factor Xa inhibitor to be approved for clinical use in the prevention of venous thromboembolism in adult patients undergoing elective hip or knee replacement surgery. [ABSTRACT FROM AUTHOR]

Rotavirus gastroenteritis (RVGE) is the leading cause of severe diarrhea in children worldwide. This paper provides an overview of the development, clinical evaluation, and postlicensure impact of RotaTeq™(Rotavirus Vaccine, Live, Oral, Pentavalent, Merck & Co., Inc.). RotaTeq, an oral vaccine, is uniquely designed to contain five human-bovine reassortant rotavirus strains expressing the human serotypes G1, G2, G3, G4, and P1A[8], which represent the most common human rotavirus serotypes responsible for ∼85% of RVGE worldwide. The development required novel solutions for manufacturing, testing, and formulation for each of the reassortants. In one of the largest vaccine clinical trials conducted, the vaccine was shown to be well tolerated and highly efficacious against severe RVGE. Efficacy has also been demonstrated in lower-income countries. In large U.S. postlicensure studies, there have been no safety signals identified, and RotaTeq has had a significant impact on reducing RVGE and its associated medical costs since licensure in 2006. [ABSTRACT FROM AUTHOR]

The human endometrium is exposed to repeated inflammation every month, culminating in tissue breakdown and menstruation. Subsequently, the endometrium has a remarkable capacity for efficient repair and remodeling to enable implantation if fertilization takes place. Endometrial function is known to be governed by the ovarian hormones estradiol and progesterone. This review paper focuses on hormonal control of the cyclical tissue injury and repair that takes place in the local endometrial environment at the time of menstruation. Progesterone levels decline premenstrually as the corpus luteum regresses in the absence of pregnancy, and estradiol levels increase during the postmenstrual phase. The functional impact of these significant changes is discussed, including their immediate and downstream effects. Finally, we examine the contribution of aberrant endometrial function to the presentation of heavy menstrual bleeding and identify potential therapeutic targets for the treatment of this common gynecological problem. [ABSTRACT FROM AUTHOR]

Infertility due to the inability of the uterus to carry a pregnancy ranks among the most unresolved issues in reproductive medicine. It affects millions of women worldwide who have congenital or acquired uterine affections, often requiring hysterectomy, and potentially represents a considerable fraction of the general infertile population. Patients suffering from severe uterine infertility are currently compelled to go through gestational surrogacy or adoption; both approaches, unfortunately, deprive them of the maternal experience of pregnancy and birth. Uterine transplantation represents an outstanding, yet complex, perspective to alleviating definitive uterine infertility. In the past decades, a number of scientific experiments conducted both in animals and women, focusing on uterine transplantation, have led to promising results. Collectively, these findings undoubtedly constitute a sound basis to clinically apply uterine transplantation in the near future. This paper is, however, an overview not only of the extent and limitations of accumulated scientific knowledge on uterine transplantation, but also its ethical implications, in an effort to define the actual place of such an approach among the therapeutic arsenal for alleviating infertility. [ABSTRACT FROM AUTHOR]

The hypothalamus, limbic system, and brainstem play an important role in the regulation of instinctive behavior. Many kinds of hypothalamic neuropeptides, such as orexin, ghrelin, neuropeptide Y, melanin-concentrating hormone, pituitary adenylate cyclase-activating polypeptide, corticotropin-releasing hormone, and diazepam-binding inhibitor-derived peptides, including the octadecaneuropeptide, have been implicated in the regulation of appetite and energy homeostasis in various models, including rodents and goldfish. Several of these neuropeptides also influence locomotor or psychomotor activity in rats and mice. The aim of this paper is to review the current knowledge on the psychophysiological effects of neuropeptides involved in the regulation of food intake in fish, and to examine their significance from a comparative point of view. [ABSTRACT FROM AUTHOR]

The functional role of secretin outside the gastrointestinal system has been a mystery to endocrinologists for many years. With the availability of secretin- and secretin receptor-knockout models and the advances of electrophysiological and immunohistochemical techniques, we are now in a good position to explore the functions of secretin outside the gastrointestinal system. There is growing evidence to support that secretin works pleiotropically at multiple levels in our body. In this paper, we review the recent findings regarding the physiological effects of secretin on extragastrointestinal sites including the cerebellum, the hippocampus, and the hypothalamus-pituitary-kidney axis. To understand the mechanisms underlying the site-specific expression of secretin and secretin receptors in the central nervous system, we also discuss the transcriptional regulation of secretin and secretin receptor genes in neuronal cell lines. [ABSTRACT FROM AUTHOR]

The contemporary world faces an unprecedented environmental challenge. Past international research has amply shown that we cannot afford to wait for a 'development path' that automatically takes us on a sustainable future. Whether we look at global or local problems, the international debate increasingly points to the importance of popular support for environmental protection by a broad spectrum of stakeholders. Because environmental sustainability questions the way we produce, consume, and distribute the product of our work, an economic analysis that is limited to one market is insufficient. In addressing Bromley's question, 'How do we wish the future to unfold for us?' this paper argues for the need to devote resources to understanding the spillovers between institutional settings and preferences toward the provision of global public goods. Here, this review focuses on labor-market institutions, as labor markets are traditionally the context in which inequality is created at the local and global levels. Labor-market institutional design, via its impact on risk and uncertainty and inequality, may have sizable implications on the provision of environmental care. [ABSTRACT FROM AUTHOR]

This paper reviews the mainstream, resource economics, and ecological economics models of growth. A possible synthesis of energy-based and mainstream models is presented. This shows that when energy is scarce it imposes a strong constraint on the growth of the economy; however, when energy is abundant, its effect on economic growth is much reduced. The industrial revolution released the constraints on economic growth by the development of new methods of using coal and the discovery of new fossil fuel resources. Time-series analysis shows that energy and GDP cointegrate, and energy use Granger causes GDP when capital and other production inputs are included in the vector autoregression model. However, various mechanisms can weaken the links between energy and growth. Energy used per unit of economic output has declined in developed and some developing countries, owing to both technological change and a shift from poorer quality fuels, such as coal, to the use of higher quality fuels, especially electricity. Substitution of other inputs for energy and sectoral shifts in economic activity play smaller roles. [ABSTRACT FROM AUTHOR]

Programmed death-1 (PD-1) is a surface receptor critical for the regulation of T cell function during immunity and tolerance. PD-1 interactions with its ligands PD-L1 and PD-L2 inhibit T cell effector functions in an antigen-specific manner. This paper examines the role of PD-1 in limiting autoreactivity and establishing self-tolerance and discusses the hypothesis that PD-1 ligand (PD-L) expression both spatially and temporally dictates the fate of self-reactive T cells during the breakdown of peripheral tolerance and development of autoimmunity. We focus our discussion on the role of PD-1/PD-L interactions during peripheral tolerance, the differential role for PD-L1 and PD-L2 in response to environmental or self-antigens, and the impact of PD-1 signaling on dynamic T cell motility and the T cell receptor (TCR) stop signal. Finally, we discuss the potential to selectively target the PD-1 pathway therapeutically to alter T cell function during autoimmunity. [ABSTRACT FROM AUTHOR]

Augmentation of cue exposure (extinction) therapy with cognitive-enhancing pharmacotherapy may constitute a rational strategy for the clinical management of drug relapse. While certain success has been reported for this form of therapy in anxiety disorders, in this paper we highlight several obstacles that may undermine the efficacy of exposure therapy for substance use disorders. We also review translational studies that have evaluated the facilitative effects of the cognitive enhancer -cycloserine on extinction targeting drug-related cues. Finally, important considerations for the design and implementation of future studies evaluating exposure therapy combined with pharmacotherapy for substance use disorders are discussed. [ABSTRACT FROM AUTHOR]

This paper reviews our current understanding of the absorption, bioavailability, and metabolism of resveratrol, with an emphasis on humans. The oral absorption of resveratrol in humans is about 75% and is thought to occur mainly by transepithelial diffusion. Extensive metabolism in the intestine and liver results in an oral bioavailability considerably less than 1%. Dose escalation and repeated dose administration of resveratrol does not appear to alter this significantly. Metabolic studies, both in plasma and in urine, have revealed major metabolites to be glucuronides and sulfates of resveratrol. However, reduced dihydroresveratrol conjugates, in addition to highly polar unknown products, may account for as much as 50% of an oral resveratrol dose. Although major sites of metabolism include the intestine and liver (as expected), colonic bacterial metabolism may be more important than previously thought. Deconjugation enzymes such as β-glucuronidase and sulfatase, as well as specific tissue accumulation of resveratrol, may enhance resveratrol efficacy at target sites. Resveratrol analogs, such as methylated derivatives with improved bioavailability, may be important in future research. [ABSTRACT FROM AUTHOR]

Cancer chemoprevention entails the ingestion of dietary or pharmaceutical agents that can prevent, delay, or reverse the process of carcinogenesis. With support provided by the National Cancer Institute, we have been actively engaged in the systematic discovery and characterization of natural chemopreventive agents. The typical approach involves identifying active crude substances such as extracts derived from terrestrial plants or marine organisms, utilizing in vitro bioassay systems, followed by the isolation of pure active components. As part of this project, an extract obtained from a nonedible Peruvian legume, Cassia quinquangulata Rich. (Leguminosae), was evaluated and found to be active as an inhibitor of cyclooxygenase. The active component was identified as resveratrol. Surprisingly broad spectrum activity was observed, indicative of potential to inhibit carcinogenesis at the stages of initiation, promotion, and progression. This discovery has led to many additional research efforts. There are now around 3,500 papers concerning some aspect of resveratrol action, yet the molecule is unusually promiscuous and specific mechanisms remain elusive. Considering the structural simplicity of this stilbene, the intensity of interest is phenomenal. [ABSTRACT FROM AUTHOR]

Stilbenoid compounds consist of a family of resveratrol derivatives. They have demonstrated promising activities in vitro and in vivo that indicate they may be useful in the prevention of a wide range of pathologies, such as cardiovascular diseases and cancers, as well have anti-aging effects. More recently stilbenoid compounds have shown promise in the treatment and prevention of neurodegenerative disorders, such as Huntington's, Parkinson's, and Alzheimer's diseases. This paper primarily focuses on the impact of stilbenoids in Alzheimer's disease and more specifically on the inhibition of β-amyloid peptide aggregation. [ABSTRACT FROM AUTHOR]

This paper provides a current review of existing evidence-based treatments for posttraumatic stress disorder (PTSD), with a description of psychopharmacologic options, prolonged exposure therapy, cognitive processing therapy, and eye movement desensitization and reprocessing, especially as they pertain to military populations. It further offers a brief summary of promising treatments with a developing evidence base, encompassing both psychotherapy and pharmacotherapy. Finally, challenges to the treatment of PTSD are summarized and future directions suggested. [ABSTRACT FROM AUTHOR]

Posttraumatic stress disorder (PTSD) is a chronic, debilitating, psychological condition that occurs in a subset of individuals who experience or witness life-threatening traumatic events. PTSD is highly prevalent in those who served in the military. In this paper, we present the underlying theoretical foundations and existing research on virtual reality exposure therapy, a recently emerging treatment for PTSD. Three virtual reality scenarios used to treat PTSD in active duty military and combat veterans and survivors of terrorism are presented: Virtual Vietnam, Virtual Iraq, and Virtual World Trade Center. Preliminary results of ongoing trials are presented. [ABSTRACT FROM AUTHOR]

The current conflicts in Iraq and Afghanistan have resulted in a large cohort of military personnel exposed to combat-related psychological trauma as well as biomechanical trauma, including proximity to blast events. Historically, the long-term effects of both types of trauma have been viewed as having different neural substrates, with some controversy over the proper attribution of such symptoms evident after each of the major conflicts of the last century. Recently, great effort has been directed toward distinguishing which neuropsychiatric sequelae are due to which type of trauma. Of interest, however, is that the chronic effects of exposure to either process are associated with a significant overlap in clinical symptoms. Furthermore, similar brain regions are vulnerable to the effects of either psychological or biomechanical trauma, raising the possibility that shared mechanisms may underlie the clinically observed overlap in symptom profile. This paper reviews the literature on the neural substrate of biomechanical and psychological injury and discusses the implications for evaluation and treatment of the neuropsychiatric sequelae of these processes. [ABSTRACT FROM AUTHOR]

Combat veterans with posttraumatic stress disorder (PTSD) demonstrate less robust improvement following treatments than do civilians with PTSD. This paper discusses a theoretical model for evaluating treatment response based on the extent of change in biological markers of symptom severity or resilience between treatment initiation and termination. Such analysis permits a determination of biological change associated with the liberal criteria commonly used to determine treatment response in combat PTSD, and a comparison of this to the biological change associated with clinical response determined according to the conservative definition more appropriate to civilian PTSD. Interim data supporting the utility of this approach is presented based on preliminary analyses from our work in progress. We propose that future studies consider the unique consequences of combat trauma and develop treatments that incorporate the complex nature of the exposure and response characteristic of a veteran population. [ABSTRACT FROM AUTHOR]

Recently, a common single nucleotide polymorphism (SNP) has been identified in the gene encoding brain-derived neurotrophic factor (BDNF). The variant BDNF has been shown to have decreased activity-dependent BDNF secretion from neurons and to lead to impairments in specific forms of learning and altered susceptibility to stress. A mouse model containing BDNF has also been linked to increased anxiety-like behavior. In a translational study, mice and human carriers of the BDNF allele were compared in their ability to extinguish a learned fear memory. Both showed slower suppression of the learned fear response. In humans, the neural correlates of this behavior were validated using fMRI. As anxiety and fear extinction lie at the core of symptoms and therapeutic approaches to posttraumatic stress disorder (PTSD), we propose that BDNF genotype and neuroimaging may be useful as biomarkers to provide guidance for more customized therapeutic directions. The aim of this paper is to review the available knowledge on the BDNF Val66Met SNP, with emphasis on anxiety- and fear-related endophenotypes and its potential implications for PTSD. [ABSTRACT FROM AUTHOR]

Numerous reports indicate that the growing incidence of posttraumatic stress disorder (PTSD) in returning Operation Enduring Freedom (OEF)/Operation Iraqi Freedom (OIF) military personnel is creating a significant health care and economic challenge. These findings have served to motivate research on how to better develop and disseminate evidence-based treatments for PTSD. Virtual reality-delivered exposure therapy for PTSD has been previously used with reports of positive outcomes. The current paper will detail the development and early results from use of the Virtual Iraq/Afghanistan exposure therapy system. The system consists of a series of customizable virtual scenarios designed to represent relevant Middle Eastern contexts for exposure therapy, including a city and desert road convoy environment. The process for gathering user-centered design feedback from returning OEF/OIF military personnel and from a system deployed in Iraq (as was needed to iteratively evolve the system) will be discussed, along with a brief summary of results from an open clinical trial using Virtual Iraq with 20 treatment completers, which indicated that 16 no longer met PTSD checklist-military criteria for PTSD after treatment. [ABSTRACT FROM AUTHOR]

Absorption is a critical component of the pharmacokinetics for solid dosage forms administered orally. Many barriers must be overcome in order for a drug molecule to reach its effect site. To effectively address each of these barriers, drug-specific properties, formulation issues, and (patho)physiological changes in the gastrointestinal tract must be considered. First-pass metabolism in the gut and/or liver can dictate the extent to which a drug reaches the systemic circulation. Drug-metabolizing enzymes in the gut and liver are very susceptible to inhibition by other drugs, increasing the risk of drug interactions. In this paper, we will discuss absorption-related issues for solid dosage forms used in the management of stroke patients. [ABSTRACT FROM AUTHOR]

Following the Women's Health Initiative (WHI) publication in mid 2002, a drastic decrease in hormone therapy for postmenopausal women has been observed worldwide. Since 2007, the reported incidence in breast cancer has declined. Most authors have linked this decline to the reduction in hormone treatment. In this paper we discuss why these ecological observations are not fully convincing and focus on the importance of screening and variations in other risk factors to interpret this decline in breast cancer. [ABSTRACT FROM AUTHOR]

Previous studies in postmenopausal women have reported that estrogen treatment (ET) modulates the risk for developing Alzheimer's disease (AD). It has recently been hypothesized that there may be a 'critical period' around the time of menopause during which the prescription of ET may reduce the risk of developing AD in later life. This effect may be most significant in women under 49 years old. Furthermore, prescription of ET after this point may have a neutral or negative effect, particularly when initiated in women over 60-65 years old. In this paper, we review recent studies that use in vivo techniques to analyze the neurobiological mechanisms that might underpin estrogen's effects on the brain postmenopause. Consistent with the 'critical period' hypothesis, these studies suggest that the positive effects of estrogen are most robust in young women and in older women who had initiated ET around the time of menopause. [ABSTRACT FROM AUTHOR]

Woman's sexuality encompasses sexual identity, sexual function, and sexual relationships. It is modulated throughout life by life and reproduction-related events, health, relationships, and sociocultural variables. The aging process and menopause are two potent contributors to female sexual dysfunction. The earlier the menopause, the more severe and complex the impact on sexuality is. The younger the woman, the less she realizes the different key goals of her life cycle (falling in love, having a satisfying sexual life, forming a stable couple, getting married, having a family) and the more pervasive the consequences on her sexual identity, sexual function, and sexual relationship can be. Premature menopause is an amplified paradigm of the complex impact menopause can have on women's and couple's sexuality. This paper will focus on biologically based sexual issues, namely desire, arousal, orgasm, and pain disorders, as well as key questions encountered in infertility. The concepts of 'symptom inducer' and 'symptom carrier' will also be addressed. [ABSTRACT FROM AUTHOR]

The need for doctors to develop in their profession and in science applies to all ages and at all hierarchical levels. This development can be sustained both via education and research. In this brief paper, we examine certain crucial aspects of education and research in obstetrics and gynecology (OB/GYN) as they are actually observed in Europe. The need for uniform development of continuing professional development (CPD) among all European countries is progressively becoming apparent. There is no single approach to CPD. Junior doctors should benefit from the teaching of senior obstetricians and gynecologists, especially those in a hierarchical system of training that must assure their progress. Hospital visiting organized by EBCOG enables OB/GYN departments of teaching hospitals to unify their teaching and learning approaches. Furthermore, improving the ability of trainees and specialists to conduct clinical research is vital, as this will transform the breakthroughs of basic science into clinical practice. A formal training period in research should be available to most competent trainees in OB/GYN in addition to their basic clinical training. [ABSTRACT FROM AUTHOR]

This paper presents a new two-sex learning- and skills-based theory for the evolution of human menopause. The theory proposes that the role of knowledge, skill acquisition, and transfers in determining economic productivity and resource distribution is the distinctive feature of the traditional human ecology that is responsible for the evolution of menopause. The theory also proposes that male reproductive cessation and post-reproductive investment in descendants is a fundamental characteristic of humans living in traditional foraging and simple horticultural economies. We present evidence relevant to the theory. The data show that whereas reproductive decline is linked to increasing risks of mortality in chimpanzees, human reproductive senescence precedes somatic senescence. Moreover under traditional conditions, most human males undergo reproductive cessation at the same time as their wives. We then present evidence that after ceasing to reproduce, both men and women provide net economic transfers to children and grandchildren. Given this pattern of economic productivity, delays in menopause would produce net economic deficits within families. [ABSTRACT FROM AUTHOR]

The broad objective of this paper is to present an overview and synthesis of selected studies on reproduction and aging in two model tephritid fruit fly species including the Mediterranean fruit fly, Ceratitis capitata, and the Mexican fruit fly, Anastrepha ludens. We summarize the research findings from empirical studies and modeling investigations involving reproduction in the two tephritid species. At the end we identify and discuss four general principles regarding reproductive aging in tephritids including reciprocity of reproductive and aging costs, qualitative tradeoffs, plasticity of lifespan and reproduction, and life history constraints and determinacy. [ABSTRACT FROM AUTHOR]

This commentary discusses the intersection of human ovarian and somatic aging. It argues for re-contextualizing estrogen's role in and impact on ovarian aging and, more broadly, on women's health, considering in particular the importance of timing, dose, and the broader endocrine milieu. Distinguishing between current clinical needs and optimizing women's future options, the paper outlines an approach to broadening the research agenda to better understand the role of ovarian aging in supporting the metabolic demands of longevity. Three overarching issues important to consider explicitly as we pursue research on the health correlates of reproductive aging are discussed, including implications of a lifespan approach, population diversity, and selection bias. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) bioavailability is crucial for normal vascular endothelial function and health. Recent studies have demonstrated an endocrine role for NO equivalents that may be transported in the blood to peripheral tissue beds, where under hypoxic conditions they can liberate NO and cause vasodilation. Exercise training improves endothelial function but its effect on NO bioavailability in peripheral tissues during acute exercise stress in CVD is unclear. This paper will present evidence and discuss possible mechanisms by which NO delivery to peripheral tissues may be dysfunctional in diabetic subjects. [ABSTRACT FROM AUTHOR]

Ambient air pollution has been linked to cardiovascular and respiratory morbidity and mortality in epidemiology studies. Frequently, oxidative and nitrosative stress are hypothesized to mediate these pollution effects, however precise mechanisms remain unclear. This paper describes the methodology for a major panel study to examine air pollution effects on these and other mechanistic pathways. The study took place during the drastic air pollution changes accompanying the 2008 Olympics in Beijing, China. After a general description of air pollution health effects, we provide a discussion of panel studies and describe the unique features of this study that make it likely to provide compelling results. This study should lead to a clearer and more precise definition of the role of oxidative and nitrosative stress, as well as other mechanisms, in determining acute morbidity and mortality from air pollution exposure. [ABSTRACT FROM AUTHOR]

Effective gene therapy for hemoglobinopathies will require high numbers of autologous gene-engineered hematopoetic stem cells to be reintroduced into the patients. Stem cell mobilization using G-CSF is the most convenient and effective approach to achieve this goal, but it can have severe side effects in sickle cell anemia and be potentially harmful in the case of severe thalassemia. Hence, the optimal way of collection of hematopoetic stem cells from patients with thalassemia and sickle cell disease needs to be determined. In this paper, we review the possible risks of G-CSF mobilization in hemoglobinopathies and we outline the approaches used in an on-going clinical trial in which pretreatment with hydroxyurea is used to reduce potential risks of G-CSF administration to patients with severe beta thalassemia. [ABSTRACT FROM AUTHOR]

Hepcidin (HAMP) negatively regulates iron absorption, degrading the iron exporter ferroportin at the level of enterocytes and macrophages. We showed that mice with β-thalassemia intermedia ( th3/+) have increased anemia and iron overload. However, their hepcidin expression is relatively low compared to their iron burden. We also showed that the iron metabolism gene Hfe is down-regulated in concert with hepcidin in th3/+ mice. These observations suggest that low hepcidin levels are responsible for abnormal iron absorption in thalassemic mice and that down-regulation of Hfe might be involved in the pathway that controls hepcidin synthesis in β-thalassemia. Therefore, these studies suggest that increasing hepcidin and/or Hfe expression could be a strategy to reduces iron overload in these animals. The goal of this paper is to review recent findings that correlate hepcidin, Hfe, and iron metabolism in β-thalassemia and to discuss potential novel therapeutic approaches based on these recent discoveries. [ABSTRACT FROM AUTHOR]

Improved technology and medical advances have increased the lifespan for people with thalassemia. As thalassemia is no longer exclusively a pediatric blood disorder, consideration must now be given to transition planning from pediatric to adult care. The complexity of thalassemia disease, coupled with the changing face of U.S. health care, creates barriers to transitional planning. Additional barriers develop because this chronic disease is less common in adults, leaving caregivers unprepared to facilitate proper adult treatment. This paper will discuss two common U.S. health care settings where care is provided to adults with thalassemia. It will also offer health care administrators, providers, policy makers, and the thalassemia community at large some recommendations on the provision of comprehensive, quality care to assure the best possible outcomes no matter what setting is available to adult patients living with thalassemia. [ABSTRACT FROM AUTHOR]

Primary afferent neurotransmission is the fundamental first step in the central processing of sensory stimuli and is controlled by pre- and postsynaptic inhibitory mechanisms. Presynaptic inhibition (PSI) is probably the more powerful form of inhibitory control in all primary afferent fibers. A major mechanism producing afferent PSI is via a channel-mediated depolarization of their intraspinal terminals, which can be recorded extracellularly as a dorsal root potential (DRP). Based on measures of DRP latency it has been inferred that this primary afferent depolarization (PAD) of low-threshold afferents is mediated by minimally trisynaptic pathways with pharmacologically identified GABAergic interneurons forming last-order axo-axonic synapses onto afferent terminals. There is still no “squeaky clean” evidence of this organization. This paper describes recent and historical work that supports the existence of PAD occurring by more direct pathways and with a complex pharmacology that questions the proprietary role of GABA and GABAA receptors in this process. Cholinergic transmission in particular may contribute significantly to PAD, including via direct release from primary afferents. [ABSTRACT FROM AUTHOR]

The American philosopher John Rawls describes a fair system of social cooperation as one that is both rational and reasonable. Is it rational and reasonable for societies that (1) are vulnerable to diverse risks of morbidity ( e.g., cancer, heart disease) and mortality and (2) are constrained by limited medical resources, to prioritize aging research? In this paper I make the case for answering “yes” on both accounts. Focusing on a plausible example of an applied gerontological intervention ( i.e., an antiaging pharmaceutical), I argue that the goal of decelerating the rate of human aging would be a more effective strategy for extending the human health span than the current strategy of just tackling each specific disease of aging. Furthermore, the aspiration to retard human aging is also a reasonable aspiration, for the principle that underlies it ( i.e., the duty to prevent harm) is one that no one could reasonably reject. [ABSTRACT FROM AUTHOR]

The relationship between species diversity and ecotope diversity has long been debated. But these debates seem meaningless because most of them were based on different definitions. In this paper, diversity has two components: richness based on the total number and evenness based on the relative abundance. Species diversity is distinguished into individual-counting diversity and biomass-based diversity. Ecotope diversity is divided into individual ecotope-counting diversity and ecotope-area based diversity. Under this definition, we make a comprehensive investigation into Dongzhi tableland of Loess Plateau by cooperating with local technicians. We find that individual-counting diversity is significantly correlated with biomass-based diversity in grassland ecosystems; individual ecotope-counting diversity and ecotope-area based diversity have a significant correlation. Therefore, it is unnecessary to divide species diversity into individual-counting diversity and biomass-based diversity in grassland ecosystems and to distinguish ecotope diversity into individual ecotope-counting and ecotope-area based diversity for the issues that have no special requirement for accuracy. But the analyses of the investigation data demonstrate that species diversity has no significant correlation with ecotope diversity. [ABSTRACT FROM AUTHOR]

In this paper, we consider the factors behind the growth of invasive species as a global problem, and the scope for international cooperation and coordination in addressing that problem. This is limited by the terms of the various international agreements governing trade, health, and biodiversity. The default strategy in most cases has two parts: border protection and the control of or adaptation to introduced species that have escaped detection at the border. Most invasive species policy involves unilateral national defensive action as opposed to coordinated international action. We argue that an important part of the solution to the problem lies in global coordination and cooperation in the management of both pathways and sanitary and phytosanitary risks at all scales. More particularly, because invasive species are an externality of trade, transport, and travel that involve public goods, they require collective regulation of international markets that goes beyond that admitted under the World Trade Organization's (WTO) Agreement on the Application of Sanitary and Phytosanitary Measures. We argue that it is important to bring that agreement into conformity with the International Health Regulations (IHR), and to develop an international mechanism to generate and disseminate information on invasive species risks and their impacts. [ABSTRACT FROM AUTHOR]

Studies in various animal models of disease and repair with thymosin β4 (Tβ4), the major actin-sequestering molecule in mammalian cells, have provided the scientific foundation for the ongoing dermal, corneal, and cardiac wound repair multicenter clinical trials. Tβ4 has of multiple biological activities, which include down-regulation of inflammatory chemokines and cytokines, and promotion of cell migration, blood vessel formation, cell survival, and stem cell maturation. All of these activities contribute to the multiple wound healing properties that have been observed in animal studies. This paper reviews and discusses the topical and systemic uses of Tβ4 in various animal models that demonstrate its potential for clinical use. [ABSTRACT FROM AUTHOR]

Thymosin alpha 1, originally isolated as the compound responsible for reconstitution of immune function in thymectomized animal models, has enjoyed a wide-ranging clinical development program over the past decades, extending across multiple companies, indications, countries, and continents. This paper provides an overview of this complex picture. The extensive clinical studies began with small studies conducted with an impure mixture of peptides under the aegis of physician-sponsored INDs submitted to the US FDA, in subjects with primary immune deficiency such as DiGeorge syndrome. Subsequent studies ranged all the way to large phase-3 trials conducted with synthetically produced thymosin alpha 1 and hundreds of patients, in many countries including the United States, Italy, and China. [ABSTRACT FROM AUTHOR]

Exposure of tissues to sulfur mustard (SM) results in the formation of protein and nucleotide adducts that disrupt cellular metabolism and cause cell death. Subsequent pathologies involve a significant proinflammatory response, disrupted healing, and long-term defects in tissue architecture. Following ocular exposure, acute corneal sequelae include epithelial erosions, necrosis, and corneal inflammation. Longer term, a progressive injury becomes distributed throughout the anterior chamber, which ultimately causes a profound remodeling of corneal tissues. In many cases, debilitating and vision-threatening injuries reoccur months to years after the initial exposure. Preliminary data in humans suffering from chronic epithelial lesions suggest that thymosin β4 (Tβ4) may be a viable candidate to mitigate acute or long-term ocular SM injury. To evaluate therapeutic candidates, we have developed a rabbit ocular exposure model system. In this paper, we report molecular, histological, ultrastructural, and clinical consequences of rabbit ocular SM injury, which can be used to assess Tβ4 efficacy, including timepoints at which Tβ4 will be assessed for therapeutic utility. [ABSTRACT FROM AUTHOR]

This paper examines the issue of what the self is by reviewing neuropsychological research, which converges on the idea that the self may be more complex and differentiated than previous treatments of the topic have suggested. Although some aspects of self-knowledge such as episodic recollection may be compromised in individuals, other aspects—for instance, semantic trait summaries—appear largely intact. Taken together, these findings support the idea that the self is not a single, unified entity. Rather, it is a set of interrelated, functionally independent systems. Implications for understanding the self in various areas of psychological research— e.g., neuroimaging, autism, amnesia, Alzheimer's disease, and mirror self-recognition—are discussed in brief. [ABSTRACT FROM AUTHOR]

Functional magnetic resonance imaging (fMRI) is one of the most important methods for in vivo investigation of cognitive processes in the human brain. Within the last two decades, an explosion of research has emerged using fMRI, revealing the underpinnings of everything from motor and sensory processes to the foundations of social cognition. While these results have revealed the potential of neuroimaging, important questions regarding the reliability of these results remain unanswered. In this paper, we take a close look at what is currently known about the reliability of fMRI findings. First, we examine the many factors that influence the quality of acquired fMRI data. We also conduct a review of the existing literature to determine if some measure of agreement has emerged regarding the reliability of fMRI. Finally, we provide commentary on ways to improve fMRI reliability and what questions remain unanswered. Reliability is the foundation on which scientific investigation is based. How reliable are the results from fMRI? [ABSTRACT FROM AUTHOR]

The papers in the session “Food Culture and Consumer Response,” show how important people's values, beliefs, aspirations and social context are to their dietary health. They also reveal several tensions that shape consumer responses to healthy food. This essay discusses the paradoxical nature of eating habits in general, and describes three paradoxes related specifically to the challenges of providing food for health in the 21st century: pleasure/health, technology/nature, innovation/nostalgia. [ABSTRACT FROM AUTHOR]

Microfluidics is an emerging technology with the potential to streamline workflows and processes in the food and health sciences. Because of extreme miniaturization, less reagent consumption and more efficient sample-to-answer protocols are not only attainable but in many cases demonstrated. In this article, we present some key examples of relevant research at the Micro/Nano Fluidics Fundamentals Focus (MF3) Center that has direct applications in food, environmental, and physiological health monitoring. [ABSTRACT FROM AUTHOR]