Search

Biofortification of crops is being introduced in several countries as a strategy to reduce micronutrient deficiencies. Biofortified products, with increased contents of micronutrients, are currently produced by conventional plant breeding, genetic modification, or nutrient-enhanced fertilization. Corn, rice, wheat, beans, pearl millet, sweet potato, and cassava have been biofortified with increased contents of provitamin A carotenoids, iron, or zinc. However, regulatory considerations are rare or nonexistent. The objective of this paper is to review the regulatory framework for production and marketing of biofortified crops in countries that have adopted this strategy. The information was identified using Internet search engines and websites of health and nutrition organizations and nongovernmental organizations and by consulting scientists and government authorities. Thus far, biofortified products introduced in Latin America, Africa, and Asia have been produced only by conventional breeding. Cultivars using other techniques are still under testing. The production and marketing of these products have been conducted without regulatory framework and under limited government control or regulatory guidance. Nevertheless, some countries have integrated biofortified crops into their nutrition agendas. Although improvements by conventional breeding have not been subject to regulations, when biofortification becomes expanded by including other techniques, an appropriate regulatory framework will be necessary. [ABSTRACT FROM AUTHOR]

Biofortification of staple crops has been proposed as a strategy to address micronutrient malnutrition, particularly with respect to insufficient intake of vitamin A, iron, zinc, and folate. The World Health Organization, in collaboration with the Food and Agriculture Organization of the United Nations and the Sackler Institute for Nutrition Science at the New York Academy of Sciences, convened a technical consultation entitled 'Staple Crops Biofortified with Vitamins and Minerals: Considerations for a Public Health Strategy' in April 2016. Participants of the consultation reviewed the definition of biofortification of staple crops, patterns of crops production, processing, consumption, seed varieties, and micronutrient stability and bioavailability, as well as farmers' adoption and acceptability of the modified crops. Also discussed were economic, environmental, safety, and equity aspects of biofortified crops, as well as legal, policy, regulatory, and ethical issues for the implementation of biofortification strategies in agriculture and nutrition. Consultation working groups identified important and emerging technical issues, lessons learned, and research priorities to better support the evidence of improved nutrition and unintended adverse effects of biofortification. This paper provides the background and rationale of the technical consultation, synopsizes the presentations, and provides a summary of the main considerations proposed by the working groups. [ABSTRACT FROM AUTHOR]

The cross-species transmission of viruses into new host populations, termed virus emergence, is a significant issue in public health, agriculture, wildlife management, and related fields. Virus emergence requires overlap between host populations, alterations in virus genetics to permit infection of new hosts, and adaptation to novel hosts such that between-host transmission is sustainable, all of which are the purview of the fields of ecology and evolution. A firm understanding of the ecology of viruses and how they evolve is required for understanding how and why viruses emerge. In this paper, I address the evolutionary mechanisms of virus emergence and how they relate to virus ecology. I argue that, while virus acquisition of the ability to infect new hosts is not difficult, limited evolutionary trajectories to sustained virus between-host transmission and the combined effects of mutational meltdown, bottlenecking, demographic stochasticity, density dependence, and genetic erosion in ecological sinks limit most emergence events to dead-end spillover infections. Despite the relative rarity of pandemic emerging viruses, the potential of viruses to search evolutionary space and find means to spread epidemically and the consequences of pandemic viruses that do emerge necessitate sustained attention to virus research, surveillance, prophylaxis, and treatment. [ABSTRACT FROM AUTHOR]

Randomized controlled trials can benefit from proactive assessment of how well their participant selection strategies during the design of eligibility criteria can influence the study generalizability. In this paper, we present a quantitative metric called generalizability index for study traits 2.0 (GIST 2.0) to assess the a priori generalizability (based on population representativeness) of a clinical trial by accounting for the dependencies among multiple eligibility criteria. The metric was evaluated on 16 sepsis trials identified from ClinicalTrials.gov, with their adverse event reports extracted from the trial results sections. The correlation between GIST scores and adverse events was analyzed. We found that the GIST 2.0 score was significantly correlated with total adverse events and serious adverse events (weighted correlation coefficients of 0.825 and 0.709, respectively, with P < 0.01). This study exemplifies the promising use of Big Data in electronic health records and ClinicalTrials.gov for optimizing eligibility criteria design for clinical studies. [ABSTRACT FROM AUTHOR]

The study of human genomics is becoming a Big Data science, owing to recent biotechnological advances leading to availability of millions of personal genome sequences, which can be combined with biometric measurements from mobile apps and fitness trackers, and of human behavior data monitored from mobile devices and social media. With increasing research opportunities for integrative genomic studies through data sharing, genetic privacy emerges as a legitimate yet challenging concern that needs to be carefully addressed, not only for individuals but also for their families. In this paper, we present potential genetic privacy risks and relevant ethics and regulations for sharing and protecting human genomics data. We also describe the techniques for protecting human genetic privacy from three broad perspectives: controlled access, differential privacy, and cryptographic solutions. [ABSTRACT FROM AUTHOR]

Big Data is no longer solely the purview of big organizations with big resources. Today's routine tools and experimental methods can generate large slices of data. For example, high-throughput sequencing can quickly interrogate biological systems for the expression levels of thousands of different RNAs, examine epigenetic marks throughout the genome, and detect differences in the genomes of individuals. Multichannel electrophysiology platforms produce gigabytes of data in just a few minutes of recording. Imaging systems generate videos capturing biological behaviors over the course of days. Thus, any researcher now has access to a veritable wealth of data. However, the ability of any given researcher to utilize that data is limited by her/his own resources and skills for downloading, storing, and analyzing the data. In this paper, we examine the necessary resources required to engage Big Data, survey the state of modern data analysis pipelines, present a few data repository case studies, and touch on current institutions and programs supporting the work that relies on Big Data. [ABSTRACT FROM AUTHOR]

This paper presents a video-based eye-tracking method, ideally deployed via a mobile device or laptop-based webcam, as a tool for measuring brain function. Eye movements and pupillary motility are tightly regulated by brain circuits, are subtly perturbed by many disease states, and are measurable using video-based methods. Quantitative measurement of eye movement by readily available webcams may enable early detection and diagnosis, as well as remote/serial monitoring, of neurological and neuropsychiatric disorders. We successfully extracted computational and semantic features for 14 testing sessions, comprising 42 individual video blocks and approximately 17,000 image frames generated across several days of testing. Here, we demonstrate the feasibility of collecting video-based eye-tracking data from a standard webcam in order to assess psychomotor function. Furthermore, we were able to demonstrate through systematic analysis of this data set that eye-tracking features (in particular, radial and tangential variance on a circular visual-tracking paradigm) predict performance on well-validated psychomotor tests. [ABSTRACT FROM AUTHOR]

In biology, a missing link connecting data generation and data-driven discovery is the training that prepares researchers to effectively manage and analyze data. National and international cyberinfrastructure along with evolving private sector resources place biologists and students within reach of the tools needed for data-intensive biology, but training is still required to make effective use of them. In this concept paper, we review a number of opportunities and challenges that can inform the creation of a national bioinformatics training infrastructure capable of servicing the large number of emerging and existing life scientists. While college curricula are slower to adapt, grassroots startup-spirited organizations, such as Software and Data Carpentry, have made impressive inroads in training on the best practices of software use, development, and data analysis. Given the transformative potential of biology and medicine as full-fledged data sciences, more support is needed to organize, amplify, and assess these efforts and their impacts. [ABSTRACT FROM AUTHOR]

Population health decision makers must consider complex relationships between multiple concepts measured with differential accuracy from heterogeneous data sources. Population health information systems are currently limited in their ability to integrate data and present a coherent portrait of population health. Consequentially, these systems can provide only basic support for decision makers. The Population Health Record (PopHR) is a semantic web application that automates the integration and extraction of massive amounts of heterogeneous data from multiple distributed sources (e.g., administrative data, clinical records, and survey responses) to support the measurement and monitoring of population health and health system performance for a defined population. The design of the PopHR draws on the theories of the determinants of health and evidence-based public health to harmonize and explicitly link information about a population with evidence about the epidemiology and control of chronic diseases. Organizing information in this manner and linking it explicitly to evidence is expected to improve decision making related to the planning, implementation, and evaluation of population health and health system interventions. In this paper, we describe the PopHR platform and discuss the architecture, design, key modules, and its implementation and use. [ABSTRACT FROM AUTHOR]

Access to experimental X-ray diffraction image data is important for validation and reproduction of macromolecular models and indispensable for the development of structural biology processing methods. In response to the evolving needs of the structural biology community, we recently established a diffraction data publication system, the Structural Biology Data Grid (SBDG, data.sbgrid.org), to preserve primary experimental datasets supporting scientific publications. All datasets published through the SBDG are freely available to the research community under a public domain dedication license, with metadata compliant with the DataCite Schema (schema.datacite.org). A proof-of-concept study demonstrated community interest and utility. Publication of large datasets is a challenge shared by several fields, and the SBDG has begun collaborating with the Institute for Quantitative Social Science at Harvard University to extend the Dataverse (dataverse.org) open-source data repository system to structural biology datasets. Several extensions are necessary to support the size and metadata requirements for structural biology datasets. In this paper, we describe one such extension-functionality supporting preservation of file system structure within Dataverse-which is essential for both in-place computation and supporting non-HTTP data transfers. [ABSTRACT FROM AUTHOR]

This paper focuses on the relationship between the circadian system and glucose metabolism. Research across the translational spectrum confirms the importance of the circadian system for glucose metabolism and offers promising clues as to when and why these systems go awry. In particular, basic research has started to clarify the molecular and genetic mechanisms through which the circadian system regulates metabolism. The study of human behavior, especially in the context of psychiatric disorders, such as bipolar disorder and major depression, forces us to see how inextricably linked mental health and metabolic health are. We also emphasize the remarkable opportunities for advancing circadian science through big data and advanced analytics. Advances in circadian research have translated into environmental and pharmacological interventions with tremendous therapeutic potential. [ABSTRACT FROM AUTHOR]

In my original paper, I claimed that our moral obligations are real, objective, and grounded in the supernatural. In particular, I endorsed the claim that God's will is the basis or source of our moral obligations, where 'God' is to be understood as the theistic being who is omnibenevolent, omniscient, and omnipotent, who created the universe, and who is still actively involved in the universe after creating it. In his critical article, Michael Shermer has raised a number of important challenges to my view. Here I try to defend the position and respond to at least his most serious objections. [ABSTRACT FROM AUTHOR]

This is my critical commentary on Michael Shermer's paper 'Morality is real, objective, and natural.' Shermer and I agree that morality is both real and objective. Here I raise serious reservations about both Shermer's account of where morality comes from and his account of what morality tells us to do. His approach to the foundations of morality would allow some very disturbing behaviors to count as moral, and his approach to what morality says does not provide the action guidance we need from a moral theory. [ABSTRACT FROM AUTHOR]

Progranulin (PGRN) is a growth factor with a unique beads-on-a-string structure that is involved in multiple pathophysiological processes, including anti-inflammation, tissue repair, wound healing, neurodegenerative diseases, and tumorigenesis. This review presents up-to-date information concerning recent studies on the role of PGRN in inflammatory arthritis and osteoarthritis, with a special focus on the involvement of the interactions and interplay between PGRN and tumor necrosis factor receptor (TNFR) family members in regulating such musculoskeletal diseases. In addition, this paper highlights the applications of atsttrin, an engineered protein comprising three TNFR-binding fragments of PGRN, as a promising intervention in treating arthritis. [ABSTRACT FROM AUTHOR]

Rotator cuff (RC) injuries represent a significant source of pain, functional impairment, and morbidity. The large disease burden of RC pathologies necessitates rapid development of research methodologies to treat these conditions. Given their ability to model anatomic, biomechanical, cellular, and molecular aspects of the human RC, animal models have played an indispensable role in reducing injury burden and advancing this field of research for many years. The development of animal models in the musculoskeletal (MSK) research arena is uniquely different from that in other fields in that the similarity of macrostructures and functions is as critical to replicate as cellular and molecular functions. Traditionally, larger animals have been used because of their anatomic similarity to humans and the ease of carrying out realistic surgical procedures. However, refinement of current molecular methods, introduction of novel research tools, and advancements in microsurgical techniques have increased the applicability of small animal models in MSK research. In this paper, we review RC animal models and emphasize a murine model that may serve as a valuable instrument for future RC tendon repair investigations. [ABSTRACT FROM AUTHOR]

The expansion in the geographical distribution of vector-borne diseases is a much emphasized consequence of climate change, as are the consequences of urbanization for diseases that are already endemic, which may be even more important for public health. In this paper, we focus on dengue, the most widespread urban vector-borne disease. Largely urban with a tropical/subtropical distribution and vectored by a domesticated mosquito, Aedes aegypti, dengue poses a serious public health threat. Temperature plays a determinant role in dengue epidemic potential, affecting crucial parts of the mosquito and viral life cycles. The urban predilection of the mosquito species will further exacerbate the impact of global temperature change because of the urban heat island effect. Even within a city, temperatures can vary by 10 °C according to urban land use, and diurnal temperature range (DTR) can be even greater. DTR has been shown to contribute significantly to dengue epidemic potential. Unraveling the importance of within-city temperature is as important for dengue as for the negative health consequences of high temperatures that have thus far been emphasized, for example, pollution and heat stroke. Urban and landscape planning designed to mitigate the non-infectious negative effects of temperature should additionally focus on dengue, which is currently spreading worldwide with no signs of respite. [ABSTRACT FROM AUTHOR]

Can environmental factors, such as air-transported preformed toxins, be of key relevance to the health outcomes of poorly understood human ailments (e.g., rheumatic diseases such as vasculitides, some inflammatory diseases, or even severe childhood acquired heart diseases)? Can the physical, chemical, or biological features of air masses be linked to the emergence of diseases such as Kawasaki disease (KD), Henoch-Schönlein purpura, Takayasu's aortitis, and ANCA-associated vasculitis? These diseases surprisingly share some common epidemiological features. For example, they tend to appear as clusters of cases grouped geographically and temporarily progress in nonrandom sequences that repeat every year in a similar way. They also show concurrent trend changes within regions in countries and among different world regions. In this paper, we revisit transdisciplinary research on the role of environmental and climate factors in the epidemiology of KD as a paradigmatic example of this group of diseases. Early-warning systems based on environmental alerts, if successful, could be implemented as a way to better inform patients who are predisposed to, or at risk for, developing KD. Further research on the etiology of KD could facilitate the development of vaccines and specific medical therapies. [ABSTRACT FROM AUTHOR]

Urbanization and climate change are the two major environmental challenges of the 21st century. The dramatic expansion of cities around the world creates new conditions for the spread, surveillance, and control of infectious diseases. In particular, urban growth generates pronounced spatial heterogeneity within cities, which can modulate the effect of climate factors at local spatial scales in large urban environments. Importantly, the interaction between environmental forcing and socioeconomic heterogeneity at local scales remains an open area in infectious disease dynamics, especially for urban landscapes of the developing world. A quantitative and conceptual framework on urban health with a focus on infectious diseases would benefit from integrating aspects of climate forcing, population density, and level of wealth. In this paper, we review what is known about these drivers acting independently and jointly on urban infectious diseases; we then outline elements that are missing and would contribute to building such a framework. [ABSTRACT FROM AUTHOR]

Extreme heat is a leading weather-related cause of morbidity and mortality, with heat exposure becoming more widespread, frequent, and intense as climates change. The use of heat early warning and response systems (HEWSs) that integrate weather forecasts with risk assessment, communication, and reduction activities is increasingly widespread. HEWSs are frequently touted as an adaptation to climate change, but little attention has been paid to the question of how best to ensure effectiveness of HEWSs as climates change further. In this paper, we discuss findings showing that HEWSs satisfy the tenets of an intervention that facilitates adaptation, but climate change poses challenges infrequently addressed in heat action plans, particularly changes in the onset, duration, and intensity of dangerously warm temperatures, and changes over time in the relationships between temperature and health outcomes. Iterative management should be central to a HEWS, and iteration cycles should be of 5 years or less. Climate change adaptation and implementation science research frameworks can be used to identify HEWS modifications to improve their effectiveness as temperature continues to rise, incorporating scientific insights and new understanding of effective interventions. We conclude that, at a minimum, iterative management activities should involve planned reassessment at least every 5 years of hazard distribution, population-level vulnerability, and HEWS effectiveness. [ABSTRACT FROM AUTHOR]

Esophageal cancer is the eighth most common cancer worldwide, and the incidence of esophageal carcinoma is rapidly increasing. With the advent of new staging and treatment techniques, esophageal cancer can now be managed through various strategies. A good understanding of the advances and limitations of new staging techniques and how these can guide in individualizing treatment is important to improve outcomes for esophageal cancer patients. This paper outlines the recent progress in staging and treatment of esophageal cancer, with particularly attention to endoscopic techniques for early-stage esophageal cancer, multimodality treatment for locally advanced esophageal cancer, assessment of response to neoadjuvant treatment, and the role of cervical lymph node dissection. Furthermore, advances in robot-assisted surgical techniques and postoperative recovery protocols that may further improve outcomes after esophagectomy are discussed. [ABSTRACT FROM AUTHOR]

Fortification of condiments or seasonings may be useful for delivering micronutrients if they are consumed consistently by most of the population, as occurs in many countries. The World Health Organization, in collaboration with the Micronutrient Initiative and the Sackler Institute for Nutrition Science at the New York Academy of Sciences, convened a technical consultation on 'Fortification of Condiments and Seasonings with Vitamins and Minerals in Public Health: from Proof of Concept to Scaling Up' to review the role of condiments and seasonings in improving micronutrient status, as constituents of regular diets and patterns of production and consumption worldwide. The consultation covered aspects related to implementation, monitoring, evaluation, and legal frameworks of fortification programs, as well as food safety and policy coherence for condiment fortification in the context of other public health strategies. This paper introduces the background and rationale of the technical consultation, synopsizes the presentations, and provides a summary of the main considerations proposed by the working groups. [ABSTRACT FROM AUTHOR]

Spices and condiments are an important part of human history and nutrition, and have played an important role in the development of most cultures around the world. According to the Codex Alimentarius, the category of salts, spices, soups, sauces, salads, and protein products includes substances added to foods to enhance aroma and taste. Spices have been reported to have health benefits as antioxidant, antibiotic, antiviral, anticoagulant, anticarcinogenic, and anti-inflammatory agents. Health claims about the benefits of condiments for disease prevention or health improvement need to be science based and extensively supported by evidence; data on their preventive or protective potential in humans are currently limited. The condiments market has been growing continuously over the last few years, with the quantity of products sold under the category of sauces, dressings, and condiments during the period 2008-2013 increasing from 31,749,000 to 35,795,000 metric tons. About 50 of the 86 spices produced in the world are grown in India. From 2008 to 2013, the United States was the largest importer of spices, followed by Australia, the United Kingdom, Canada, and Russia. The main buyers of fish sauce are Vietnam and Thailand, with purchases of 333,000 and 284,000 metric tons in 2013, respectively. The sauces and condiments category is dynamic, with large differences in consumption in habits and practices among countries. This paper aims to establish definitions and discuss potential health benefits, consumption patterns, and global markets for sauces, spices, and condiments. [ABSTRACT FROM AUTHOR]

Fortification of staple foods with vitamins and minerals is an effective approach to increase micronutrient intake and improve nutritional status. The specific use of condiments and seasonings as vehicles in large-scale fortification programs is a relatively new public health strategy. This paper underscores equity considerations for the implementation of large-scale fortification of condiments and seasonings as a public health strategy by examining nonexhaustive examples of programmatic experiences and pilot projects in various settings. An overview of conceptual elements in implementation research and equity is presented, followed by an examination of equity considerations for five implementation strategies: (1) enhancing the capabilities of the public sector, (2) improving the performance of implementing agencies, (3) strengthening the capabilities and performance of frontline workers, (3) empowering communities and individuals, and (4) supporting multiple stakeholders engaged in improving health. Finally, specific considerations related to intersectoral action are considered. Large-scale fortification of condiments and seasonings cannot be a standalone strategy and needs to be implemented with concurrent and coordinated public health strategies, which should be informed by a health equity lens. [ABSTRACT FROM AUTHOR]

Condiments and seasonings have been considered as potential vehicles for fortification in place of, or in addition to, fortifiable staple foods. Methodologies for establishing fortification programs focus primarily on use of staple foods, which are consumed in larger portions than condiments and seasonings. Some fortification models assume self-limiting consumption relative to the maximum energy consumed by target populations. However, this assumption may prove incorrect for estimating fortification concentrations of condiments and seasonings because they may only provide negligible energy. Although flavor or color may limit consumption, these limits would vary across each condiment or seasoning vehicle. In addition, the small volume of condiments and seasonings consumed relative to staple foods can lead to proportionally larger potential errors than with staple foods when measuring usual dietary intakes for establishing safe and effective fortification concentrations. This paper reviews available methods for setting fortification levels, whether or how available methods or conceptual frameworks could be adapted to condiments and seasonings, and gaps in knowledge for appropriately using condiments and seasonings as vehicles for fortification in public health. [ABSTRACT FROM AUTHOR]

Many federal definitions and popular theories of giftedness specify creativity as a core component. Nevertheless, states rely primarily on measures of intelligence for giftedness identification. As minority and culturally diverse students continue to be underrepresented in gifted programs, it is reasonable to ask if increasing the prominence of creativity in gifted identification may help increase balance and equity. In this paper, we explore both layperson and psychometric conceptions of bias and suggest that adding creativity measures to the identification process alleviates both perceptions and the presence of bias. We recognize, however, the logistic and measurement-related challenges to including creativity assessments. [ABSTRACT FROM AUTHOR]

We read the paper by Gomes I et al i . with great interest.1 They showed the existence of patients with thiamine deficiency unrelated to alcohol consumption even in high-income countries, and that alerting healthcare professionals working in clinical practice to this fact contributed to improving the quality of medical care. Wernicke encephalopathy presented in the form of postoperative delirium in a patient with hepatocellular carcinoma and liver cirrhosis: a case report and review of the literature. Early detection and successful treatment of Wernicke encephalopathy in a patient with advanced carcinoma of the external genitalia during chemotherapy. [Extracted from the article]

This paper draws from three different bodies of research to discuss the hypothesis that age-appropriate experiences enhance brain and cognitive development throughout the life span. These age-appropriate experiences could be considered as the drivers of development at each age, including drivers to foster development beyond adult abstract thinking, as described in Piaget's formal operational stage. We explore how a nurturing caregiver is the driver in the first 2 years of life, how language learning is the driver from 3 to 10 years, and how problem solving is the driver in the teenage years. To develop beyond adult rational thinking, we suggest that the driver is transcending thought, which can result when practicing meditations in the automatic self-transcending category, such as Transcendental Meditation. [ABSTRACT FROM AUTHOR]

Work in the development and evaluation of mindfulness-based interventions (MBIs) for cancer care has been underway for the last 20 years, and a growing body of literature now supports their efficacy. MBIs are particularly helpful in dealing with common experiences related to cancer diagnosis, treatment, and survivorship, including loss of control, uncertainty about the future, and fears of recurrence, as well as a range of physical and psychological symptoms, including depression, anxiety, insomnia, and fatigue. Our adaptation, mindfulness-based cancer recovery (MBCR), has resulted in improvements across a range of psychological and biological outcomes, including cortisol slopes, blood pressure, and telomere length, in various groups of cancer survivors. In this paper, I review the rationale for MBIs in cancer care and provide an overview of the state of the current literature, with a focus on results from three recent clinical trials conducted by our research group. These include a comparative efficacy trial comparing MBCR to supportive-expressive therapy in distressed breast cancer survivors, a non-inferiority trial comparing MBCR to cognitive behavioral therapy for insomnia in cancer survivors with clinical insomnia, and an online adaptation of MBCR for rural and remote cancer survivors without access to in-person groups. I conclude by outlining work in progress and future directions for MBI research and applications in cancer care. [ABSTRACT FROM AUTHOR]

Over the last 20 years, the Nestl'e Research Center in Switzerland and the International Center for Diarrhoeal Diseases Research in Bangladesh have explored the efficacy of alternative biological agents for the treatment of diarrheal diseases. This paper reviews the work of this collaborative effort, particularly on Escherichia coli phage therapy (PT), and discusses the development of the project, starting with the isolation of T4-like coliphages from the stool of diarrhea patients, their pilot plant amplification and purification, and the constitution and testing of a cocktail of T4-like phages in mice. A series of phase I clinical trials has demonstrated the safety of PT. Oral phage given without protection survived gastric passage and was recovered in the feces. Oral T4 phage cocktail was then tested in parallel to a commercial phage product in a phase II randomized, placebo-controlled single-center trial in Bangladeshi children hospitalized with acute E. coli diarrhea. It was found that oral phage did not perform better than the current standard of care by oral rehydration/zinc treatment. Furthermore, fecal E. coli pathogen titers were low and mixed infections were found to be frequent. Microbiota analysis showed a correlation between diarrhea and increased levels of Streptococcus, which raises fundamental questions on the causative agent of diarrhea that may explain PT clinical failure. [ABSTRACT FROM AUTHOR]

Diet has been known to play an important role in human health since at least the time period of the ancient Greek physician Hippocrates. In the last decade, research has revealed that microorganisms inhabiting the digestive tract, known as the gut microbiota, are critical factors in human health. This paper draws on concepts of cooperation and conflict from ecology and evolutionary biology to make predictions about host-microbiota interactions involving nutrients. To optimally extract energy from some resources (e.g., fiber), hosts require cooperation from microbes. Other nutrients can be utilized by both hosts and microbes (e.g., simple sugars, iron) in their ingested form, which may lead to greater conflict over these resources. This framework predicts that some negative health effects of foods are driven by the direct effects of these foods on human physiology and by indirect effects resulting frommicrobiome-host competition and conflict (e.g., increased invasiveness and inflammation). Similarly, beneficial effects of some foods on host health may be enhanced by resource sharing and other cooperative behaviors between host and microbes that may downregulate inflammation and virulence. Given that some foods cultivate cooperation between hosts and microbes while others agitate conflict, host-microbe interactions may be novel targets for interventions aimed at improving nutrition and human health. [ABSTRACT FROM AUTHOR]

Fecal microbiota transplantation (FMT) is an emerging therapeutic option for Clostridium difficile infections that are refractory to conventional treatment. FMT introduces fecal microbes into the patient's intestine that prevent the recurrence of C. difficile, leading to rapid expansion of bacteria characteristic of healthy microbiota. However, the long-termeffects of FMT remain largely unknown. The C. difficile patient described in this paper revealed protracted microbiota adaptation processes from 6 to 42 months post-FMT. Ultimately, bacterial communities were donor similar, suggesting sustainable stool engraftment. Since little is known about the consequences of transmitted viruses during C. difficile infection, we also interrogated virome changes. Our approach allowed identification of about 10 phage types per sample that represented larger viral communities, and phages were found to be equally abundant in the cured patient and donor. The healthy microbiota appears to be characterized by low phage abundance. Although viruses were likely transferred, the patient established a virome distinct from the donor. Surprisingly, the patient had sequences of algal giant viruses (chloroviruses) that have not previously been reported for the human gut. Chloroviruses have not been associated with intestinal disease, but their presence in the oropharynx may influence cognitive abilities. The findings suggest that the virome is an important indicator of health or disease. A better understanding of the role of viruses in the gut ecosystem may uncover novel microbiota-modulating therapeutic strategies. [ABSTRACT FROM AUTHOR]

Lysosomal storage diseases (LSDs) are a group of rare diseases in which the function of the lysosome is disrupted by the accumulation of macromolecules. The complexity underlying the pathogenesis of LSDs and the small, often pediatric, population of patients make the development of therapies for these diseases challenging. Current treatments are only available for a small subset of LSDs and have not been effective at treating neurological symptoms. Disease-relevant cellular and animal models with high clinical predictability are critical for the discovery and development of new treatments for LSDs. In this paper, we review how LSD patient primary cells and induced pluripotent stem cell-derived cellular models are providing novel assay systems in which phenotypes are more similar to those of the human LSD physiology. Furthermore, larger animal disease models are providing additional tools for evaluation of the efficacy of drug candidates. Early predictors of efficacy and better understanding of disease biology can significantly affect the translational process by focusing efforts on those therapies with the higher probability of success, thus decreasing overall time and cost spent in clinical development and increasing the overall positive outcomes in clinical trials. [ABSTRACT FROM AUTHOR]

The majority of hematopoietic stem cells (HSCs) are maintained in a quiescent state to minimize premature exhaustion induced by various stresses. However, quiescent HSCs are vulnerable to mutagenesis because of attenuated DNA repair and DNA damage response programs. Basal abundant expression of prosurvival BCL-2 proteins further endows HSCs with high resistance to apoptosis. In contrast, HSCs elicit strong activation of p53 upon DNA damage, resulting in enhanced activation of proapoptotic BCL-2 signals through p53. ASPP1, an apoptosis-stimulating protein of p53, is highly expressed in HSCs and preserves HSC pool integrity via selective induction of apoptosis. In this paper, we discuss the role of p53 and mitochondrial apoptosis in HSC regulation and introduce the current understanding of how p53 activity is regulated to achieve a good balance between maintaining the HSC pool and preventing hematological malignancies. [ABSTRACT FROM AUTHOR]

A broad set of brain regions has been associated with the experience and training of mindfulness. Many of these regions lie within key intrinsic brain networks, including the executive control, salience, and default networks. In this paper, we review the existing literature on the cognitive neuroscience of mindfulness through the lens of network science. We describe the characteristics of the intrinsic brain networks implicated in mindfulness and summarize the relevant findings pertaining to changes in functional connectivity (FC) within and between these networks. Convergence across these findings suggests that mindfulness may be associated with increased FC between two regions within the default network: the posterior cingulate cortex and the ventromedial prefrontal cortex. Additionally, extensive meditation experience may be associated with increased FC between the insula and the dorsolateral prefrontal cortex. However, little consensus has emerged within the existing literature owing to the diversity of operational definitions of mindfulness, neuroimaging methods, and network characterizations. We describe several challenges to develop a coherent cognitive neuroscience of mindfulness and to provide detailed recommendations for future research. [ABSTRACT FROM AUTHOR]

Increased organismic complexity in metazoans was achieved via the specialization of certain parts of the body involved in different faculties (structure-function complexes). One of the most basic metabolic demands of animals in general is a sufficient supply of all tissues with oxygen. Specialized structures for gas exchange (and transport) consequently evolved many times and in great variety among bilaterians. This review focuses on some of the latest advancements that morphological research has added to our understanding of how the respiratory apparatus of the primarily terrestrial vertebrates (amniotes) works and how it evolved. Two main components of the respiratory apparatus, the lungs as the 'exchanger' and the ventilatory apparatus as the 'active pump,' are the focus of this paper. Specific questions related to the exchanger concern the structure of the lungs of the first amniotes and the efficiency of structurally simple snake lungs in health and disease, as well as secondary functions of the lungs in heat exchange during the evolution of sauropod dinosaurs. With regard to the active pump, I discuss how the unique ventilatory mechanism of turtles evolved and how understanding the avian ventilatory strategy affects animal welfare issues in the poultry industry. [ABSTRACT FROM AUTHOR]

Interventions that improve health are often associated with longevity. Reduced growth hormone signaling has been shown to increase life span in mice by over 50%. Similarly, reductions in dietary intake of methionine, in rats and mice, result in life-span extension. Many factors affect metabolic health, mitochondrial function, and resistance to stressors, each of which influence aging and life span. This paper presents a comparison of these two interventions, as well as the results of a study combining these interventions, to understand potential mechanisms underlying their effectiveness in enhancing healthy aging. [ABSTRACT FROM AUTHOR]

Mouse B-1 cells are not only major producers of steady-state natural antibodies but also rapid responders to infections and inflammation. These discrete functions may be the outcomes of distinct environmental or developmental triggers that drive B-1 cells toward IgM production or an effector cell fate. Alternatively, distinct B-1 cell subsets may exist, which differ in their functional plasticity. In this paper, we summarize existing data suggesting that B-1 cells form a heterogeneous group of cells with distinct developmental requirements and nonoverlapping functions. Most spleen B-1 cells differ in development from that of bone marrow and peritoneal cavity B-1 cells, in that they develop in the absence of natural IgM. Functional heterogeneity is revealed by findings that B-1 cells in the bone marrow and spleen, but not the peritoneal cavity, generate natural serum IgM, while the latter are rapid responders to inflammatory and infectious insults, resulting in their relocation to secondary lymphoid tissues. A clearer understanding of the developmental and functional differences within the B-1 cell pool may reveal how they might be harnessed for prophylaxis or therapy. [ABSTRACT FROM AUTHOR]

From the discovery of new galaxies and nearly undetectable dark energy to the quantum entanglement of particles across the universe, new findings in physics naturally elicit a sense of awe and wonder. For the founders of modern physics--from Einstein and Bohr to Heisenberg, Pauli, and Bohm--a fascination with deeper questions of meaning and ultimate reality led some of them to explore esoteric traditions and metaphysics. More recently, however, physicists have largely shunned such philosophical and spiritual associations.What can contemporary physics offer us in the quest to understand our place in the universe? Has physics in some ways become a religion unto itself that rejects the search for existential meaning? Discussion of these and related questions is presented in this paper. [ABSTRACT FROM AUTHOR]

The holy grail of physics has been to merge each of its fundamental branches into a unified "theory of everything" that would explain the functioning and existence of the universe. The last step toward this goal is to reconcile general relativity with the principles of quantum mechanics, a quest that has thus far eluded physicists.Will physics ever be able to develop an all-encompassing theory, or should we simply acknowledge that science will always have inherent limitations as to what can be known? Should new theories be validated solely on the basis of calculations that can never be empirically tested? Can we ever truly grasp the implications of modern physics when the basic laws of nature do not always operate according to our standard paradigms? These and other questions are discussed in this paper. [ABSTRACT FROM AUTHOR]

Perhaps the greatest mystery is why the universe exists in the first place. How is it possible for something to emerge from nothing, or has a universe in some form always existed? This question of origins--both of the universe as a whole and of the fundamental laws of physics--raises profound scientific, philosophical, and religious questions, culminating in the most basic existential question of all:Why are we here? Discussion of this and related questions is presented in this paper. [ABSTRACT FROM AUTHOR]

The nucleotide analog NS5 B polymerase inhibitor sofosbuvir was approved by the U.S. Food and Drug Administration (FDA) in December 2013 for the treatment of chronic hepatitis C virus (HCV) infection in combination with ribavirin or peginterferon and ribavirin. Sofosbuvir was developed to meet an urgent medical need for shorter, safer, simplified, more effective HCV treatment regimens and to reduce or eliminate the need for peginterferon. New treatment regimens were especially required for patient populations with limited treatment options, including patients who had failed prior HCV therapy, those with compensated and decompensated cirrhosis, and those who were either intolerant of or had contraindications to interferon. Sofosbuvir plus ribavirin for patients with genotype 2 or 3 HCV infection was the first approved all-oral treatment option. Sofosbuvir is also the backbone of the first regimen available for patients awaiting liver transplantation to prevent HCV recurrence, as well as the first oral interferon-free regimen for patients coinfected with HCV and HIV. This paper describes the development of sofosbuvir up to its original FDA approval. [ABSTRACT FROM AUTHOR]

Opportunities exist for micronutrient fortification of condiments and seasonings to combat vitamin or mineral deficiencies. This paper reviews the available technologies for industrial processing of condiments and seasonings and their fortification with micronutrients. The industrial processes to manufacture commonly consumed condiments and seasonings, such as soy sauce, bouillon cubes, fish sauce, spices, and other relevant products, are described. The impact of processing on fortification is evaluated, considering both the type of vehicle and the fortificant used. The analyzed technologies represent effective strategies for mineral fortification, particularly with iodine and iron. However, fortification with vitamins has been more challenging, owing to sensory changes of the finished product and a poor stability of the fortificant when using certain vehicles. Therefore, more studies are needed in this area in collaboration with governments, the food industry, and vitamin suppliers. Despite the technical difficulties encountered, the current processing technologies for the production of condiments and seasonings can be adapted and refined to allow their successful fortification with micronutrients. [ABSTRACT FROM AUTHOR]

The growing base of information about ecosystem services generated by ecologists, economists, and other scientists could improve the implementation, monitoring, and evaluation of commodity-sourcing standards being adopted by corporations to mitigate risk in their supply chains and achieve sustainability goals. This review examines various ways that information about ecosystem services could facilitate compliance with and auditing of commodity-sourcing standards. We also identify gaps in the current state of knowledge on the ecological effectiveness of sustainability standards and demonstrate how ecosystem-service information could complement existing monitoring efforts to build credible evidence. This paper is a call to the ecosystem-service scientists to engage in this decision context and tailor the information they are generating to the needs of the standards community, which we argue would offer greater efficiency of standards implementation for producers and enhanced effectiveness for standard scheme owners and corporations, and should thus lead to more sustainable outcomes for people and nature. [ABSTRACT FROM AUTHOR]

Type 1 narcolepsy is a sleep disorder characterized by excessive daytime sleepiness with unintentional sleep attacks and cataplexy. The disorder is caused by a loss of hypocretinergic neurons in the brain. The specific loss of these neurons in narcolepsy is thought to result from an autoimmune attack, and this is supported by evidence of both environmental and genetic factors pointing toward an involvement of the immune system. However, definitive proof of an autoimmune etiology is still missing. Several different immune-mediated disorders targeting neurons are known, and many of these are believed to be caused by autoreactive CD8+ T cells. In this paper, we review the current knowledge on CD8+ T cell-mediated neuronal damage on the basis of our understanding of other autoimmune disorders and experimental studies. We identify major histocompatibility complex class I presentation of autoantigens on neurons as a possiblemechanism in the development of the disease, and propose T cell-mediated pathogenesis, with cytotoxic CD8+ T cells targeting the hypocretinergic neurons, as a central element. [ABSTRACT FROM AUTHOR]

Type 1 narcolepsy is a sleep disorder characterized by excessive daytime sleepiness with unintentional sleep attacks and cataplexy. The disorder is caused by a loss of hypocretinergic neurons in the brain. The specific loss of these neurons in narcolepsy is thought to result from an autoimmune attack, and this is supported by evidence of both environmental and genetic factors pointing toward an involvement of the immune system. However, definitive proof of an autoimmune etiology is still missing. Several different immune-mediated disorders targeting neurons are known, and many of these are believed to be caused by autoreactive CD8+ T cells. In this paper, we review the current knowledge on CD8+ T cell-mediated neuronal damage on the basis of our understanding of other autoimmune disorders and experimental studies. We identify major histocompatibility complex class I presentation of autoantigens on neurons as a possible mechanism in the development of the disease, and propose T cell-mediated pathogenesis, with cytotoxic CD8+ T cells targeting the hypocretinergic neurons, as a central element. [ABSTRACT FROM AUTHOR]

Chemoresistance enables cancer cells to evade apoptotic stimuli and leads to poor clinical prognosis. It arises from dysregulation of signaling factors responsible for inducing cell proliferation and death and for modulating the microenvironment. In gynecologic cancers, p53 is a pivotal determinant of cisplatin sensitivity, while BCL-2 family members are associated with taxane sensitivity. Mitochondria fusion and fission dynamics are required for many mitochondrial functions and are also involved in mitochondria-mediated apoptosis, which is closely associated with chemosensitivity. Mitochondrial dynamics are controlled by a number of intracellular proteins, including fusion (Opa1 and mitofusion 1 and 2) and fission proteins (Drp1 and Fis1), which can be proapoptotic or antiapoptotic, depending on the cell types, status, and stimuli from the microenvironment. This paper describes the role of mitochondrial dynamics in the mechanism of chemoresistance and the evidence supporting a significant contribution of a hyperfusion state to chemoresistance in gynecological cancers. Moreover, we discuss our findings showing that enforced fission induces apoptosis of cancer cells and sensitizes them to chemotherapeutic agents. Understanding the regulation of mitochondrial dynamics inchemoresistancemay provide insight intonewbiomarkers that better predict cancer chemosensitivity and may aid the development of effective therapeutic strategies for clinical management of gynecologic cancers. [ABSTRACT FROM AUTHOR]

Human cell adhesion molecules (CAMs) are essential for proper development, modulation, and maintenance of interactions between cells and cell-to-cell (and matrix-to-cell) communication about these interactions. Despite the differential functional significance of these roles, there have been surprisingly few systematic studies to enumerate the universe of CAMs and identify specific CAMs in distinct functions. In this paper, we update and review the set of human genes likely to encode CAMs with searches of databases, literature reviews, and annotations. We describe likely CAMs and functional subclasses, including CAMs that have a primary function in information exchange (iCAMs), CAMs involved in focal adhesions, CAM gene products that are preferentially involved with stereotyped and morphologically identifiable connections between cells (e.g., adherens junctions, gap junctions), and smaller numbers of CAM genes in other classes. We discuss a novel proposed mechanism involving selective anchoring of the constituents of iCAM-containing lipid rafts in zones of close neuronal apposition to membranes expressing iCAM binding partners. We also discuss data from genetic and genomic studies of addiction in humans and mouse models to highlight the ways in which CAM variation may contribute to a specific brain-based disorder such as addiction. Specific examples include changes in CAM mRNA splicing mediated by differences in the addiction-associated splicing regulator RBFOX1/A2BP1 and CAM expression in dopamine neurons. [ABSTRACT FROM AUTHOR]

The development of new antidepressants has had mixed results over the past decade, with several notable failures. This paper reviews a number of major initiatives in the development of new antidepressant agents. Traditional strategies to build on agents that have monoaminergic effects at the synapse (e.g., vilazodone and ketamine) have been complemented with efforts that have emphasized devices and brain circuits (e.g., deep brain stimulation and transcranial magnetic stimulation) or chemical agents that modulate neuroendocrine systems (e.g., glucocorticoid antagonists, mixed melatonin agonists/serotonin type-2 receptor antagonists). Interestingly, chemical agents, such as onabotulinumtoxin A, may affect brain circuits as well. We present data from recent studies in drug and device development--reviewing progress made, stumbling blocks encountered, and issues that need to be addressed in future studies. [ABSTRACT FROM AUTHOR]

Bipolar disorders are common psychiatric disorders that affect 1-5% of the population worldwide. Major advances in the epidemiology, pathophysiology, and treatment of the disorders have recently occurred. The majority of published reports, however, originate from theWestern hemisphere, mostly Europe and the United States. There is a shortage of data from the Arab world on bipolar disorders. In an era of globalization and rapid communication, it is not clear to what extent research findings pertaining to one part of the world are by necessity applicable to other parts. Psychiatric disorders are known to be affected by the culture in which they occur, and knowledge of variations in illness presentation in different ethnic groups is also increasing. However, knowledge of variations affecting Arab populations remains quite limited. This paper provides a critical review of the literature on bipolar affective disorders in the Arab world, pointing to major gaps in knowledge and future opportunities to fill these gaps. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is one of the most disabling diseases worldwide and is becoming a significant public health threat. Current treatments forMDDprimarily consist of monoamine-targeting agents and have limited efficacy. However, the glutamate neurotransmitter system has recently come into focus as a promising alternative for novel antidepressant treatments. We review the current data on the glutamate NMDA receptor antagonist ketamine, which has been shown in clinical trials to act as a rapid antidepressant inMDD.We also examine ketamine efficacy on dimensions of psychopathology, including anhedonia, cognition, and suicidality, consistent with theNIMH Research Domain Criteria initiative. Other aspects of ketamine reviewed in this paper include safety and efficacy, different administration methods, and the risks of misuse of ketamine outside of medical settings. Finally, we conclude with a discussion of glutamatergic agents other than ketamine currently being tested as novel antidepressants. [ABSTRACT FROM AUTHOR]