Health and human rights in today’s fight against HIV/AIDS

PubMed Central

Stemple, Lara

2012-01-01

The development of the health and human rights framework coincided with the beginning of the rapid spread of HIV/AIDS. Since then, the international community has increasingly turned to human rights language and instruments to address the disease. Not only are human rights essential to addressing a disease that impacts marginalized groups most severely, but the spread of HIV/AIDS itself exacerbates inequality and impedes the realization of a range of human rights. Policy developments of the past decade include the United Nations (UN) Committee on Economic, Social and Cultural Rights’ General Comment on the ‘Right to Health’, the UN Declaration of Commitment on HIV/AIDS, and the UN’s International Guidelines on HIV/AIDS and Human Rights, among others. Rights-related setbacks include the failure of the Declaration and its 5-year follow-up specifically to address men who have sex with men, sex workers, and intravenous drug users, political restrictions placed on urgently needed US President’s Emergency Plan for AIDS Relief (PEPFAR) funds, and the failure of many countries to decriminalize same-sex sex and outlaw discrimination against people living with HIV/AIDS. Male circumcision as an HIV prevention measure is a topic around which important debate, touching on gender, informed consent and children’s rights, serves to illustrate the ongoing vitality of the health and human rights dialogue. Mechanisms to increase state accountability for addressing HIV/AIDS should be explored in greater depth. Such measures might include an increase in the use of treaty-based judicial mechanisms, the linking of human rights compliance with preferential trade agreements, and rights requirements tied to HIV/ AIDS funding. PMID:18641463

Human cognition and mobility in aging: a model for berry fruit interventions

USDA-ARS?s Scientific Manuscript database

Changes in motor function in aging, in both animals and humans, include decrements in balance, strength, and coordination, even in the absence of specific movement disorders such as Parkinson’s disease. In humans, these alterations can increase fall risk, often leading to injury and premature nursin...

Fragmentation and Isolation

EPA Science Inventory

Landscapes are being modified by humans at ever-increasing rates worldwide. This landscape level modification has resulted in changes in ecological patterns and processes, including species distributions. The rate at which humans are altering both terrestrial and aquatic habitats...

Non-animal methodologies within biomedical research and toxicity testing.

PubMed

Knight, Andrew

2008-01-01

Laboratory animal models are limited by scientific constraints on human applicability, and increasing regulatory restrictions, driven by social concerns. Reliance on laboratory animals also incurs marked - and in some cases, prohibitive - logistical challenges, within high-throughput chemical testing programmes, such as those currently underway within Europe and the US. However, a range of non-animal methodologies is available within biomedical research and toxicity testing. These include: mechanisms to enhance the sharing and assessment of existing data prior to conducting further studies, and physicochemical evaluation and computerised modelling, including the use of structure-activity relationships and expert systems. Minimally-sentient animals from lower phylogenetic orders or early developmental vertebral stages may be used, as well as microorganisms and higher plants. A variety of tissue cultures, including immortalised cell lines, embryonic and adult stem cells, and organotypic cultures, are also available. In vitro assays utilising bacterial, yeast, protozoal, mammalian or human cell cultures exist for a wide range of toxic and other endpoints. These may be static or perfused, and may be used individually, or combined within test batteries. Human hepatocyte cultures and metabolic activation systems offer potential assessment of metabolite activity and organ-organ interaction. Microarray technology may allow genetic expression profiling, increasing the speed of toxin detection, well prior to more invasive endpoints. Enhanced human clinical trials utilising micro- dosing, staggered dosing, and more representative study populations and durations, as well as surrogate human tissues, advanced imaging modalities and human epidemiological, sociological and psycho- logical studies, may increase our understanding of illness aetiology and pathogenesis, and facilitate the development of safe and effective pharmacologic interventions. Particularly when human tissues are used, non-animal models may generate faster, cheaper results, more reliably predictive for humans, whilst yielding greater insights into human biochemical processes. Greater commitment to their development and implementation is necessary, however, to efficiently meet the needs of high-throughput chemical testing programmes, important emerging testing needs, and the ongoing development of human clinical interventions.

Olive oil phenolics are dose-dependently absorbed in humans.

PubMed

Visioli, F; Galli, C; Bornet, F; Mattei, A; Patelli, R; Galli, G; Caruso, D

2000-02-25

Olive oil phenolic constituents have been shown, in vitro, to be endowed with potent biological activities including, but not limited to, an antioxidant action. To date, there is no information on the absorption and disposition of such compounds in humans. We report that olive oil phenolics, namely tyrosol and hydroxytyrosol, are dose-dependently absorbed in humans after ingestion and that they are excreted in the urine as glucuronide conjugates. Furthermore, an increase in the dose of phenolics administered increased the proportion of conjugation with glucuronide.

Incorporating a Human-Computer Interaction Course into Software Development Curriculums

ERIC Educational Resources Information Center

Janicki, Thomas N.; Cummings, Jeffrey; Healy, R. Joseph

2015-01-01

Individuals have increasing options on retrieving information related to hardware and software. Specific hardware devices include desktops, tablets and smart devices. Also, the number of software applications has significantly increased the user's capability to access data. Software applications include the traditional web site, smart device…

Dehumanization increases instrumental violence, but not moral violence.

PubMed

Rai, Tage S; Valdesolo, Piercarlo; Graham, Jesse

2017-08-08

Across five experiments, we show that dehumanization-the act of perceiving victims as not completely human-increases instrumental, but not moral, violence. In attitude surveys, ascribing reduced capacities for cognitive, experiential, and emotional states to victims predicted support for practices where victims are harmed to achieve instrumental goals, including sweatshop labor, animal experimentation, and drone strikes that result in civilian casualties, but not practices where harm is perceived as morally righteous, including capital punishment, killing in war, and drone strikes that kill terrorists. In vignette experiments, using dehumanizing compared with humanizing language increased participants' willingness to harm strangers for money, but not participants' willingness to harm strangers for their immoral behavior. Participants also spontaneously dehumanized strangers when they imagined harming them for money, but not when they imagined harming them for their immoral behavior. Finally, participants humanized strangers who were low in humanity if they imagined harming them for immoral behavior, but not money, suggesting that morally motivated perpetrators may humanize victims to justify violence against them. Our findings indicate that dehumanization enables violence that perpetrators see as unethical, but instrumentally beneficial. In contrast, dehumanization does not contribute to moral violence because morally motivated perpetrators wish to harm complete human beings who are capable of deserving blame, experiencing suffering, and understanding its meaning.

Seeing Minds in Others – Can Agents with Robotic Appearance Have Human-Like Preferences?

PubMed Central

Martini, Molly C.; Gonzalez, Christian A.; Wiese, Eva

2016-01-01

Ascribing mental states to non-human agents has been shown to increase their likeability and lead to better joint-task performance in human-robot interaction (HRI). However, it is currently unclear what physical features non-human agents need to possess in order to trigger mind attribution and whether different aspects of having a mind (e.g., feeling pain, being able to move) need different levels of human-likeness before they are readily ascribed to non-human agents. The current study addresses this issue by modeling how increasing the degree of human-like appearance (on a spectrum from mechanistic to humanoid to human) changes the likelihood by which mind is attributed towards non-human agents. We also test whether different internal states (e.g., being hungry, being alive) need different degrees of humanness before they are ascribed to non-human agents. The results suggest that the relationship between physical appearance and the degree to which mind is attributed to non-human agents is best described as a two-linear model with no change in mind attribution on the spectrum from mechanistic to humanoid robot, but a significant increase in mind attribution as soon as human features are included in the image. There seems to be a qualitative difference in the perception of mindful versus mindless agents given that increasing human-like appearance alone does not increase mind attribution until a certain threshold is reached, that is: agents need to be classified as having a mind first before the addition of more human-like features significantly increases the degree to which mind is attributed to that agent. PMID:26745500

Using Cocoa and Chocolate to Teach Human Geography

ERIC Educational Resources Information Center

Alberts, Heike C.

2010-01-01

Food topics are uniquely suited to increase students' interest in human geography. A highly processed food like chocolate can be studied in a variety of different ways, making it possible to include chocolate examples and activities at various points in a human geography class. The goals of this article are to provide sufficient background…

Building human resilience: the role of public health preparedness and response as an adaptation to climate change.

PubMed

Keim, Mark E

2008-11-01

Global climate change will increase the probability of extreme weather events, including heatwaves, drought, wildfire, cyclones, and heavy precipitation that could cause floods and landslides. Such events create significant public health needs that can exceed local capacity to respond, resulting in excess morbidity or mortality and in the declaration of disasters. Human vulnerability to any disaster is a complex phenomenon with social, economic, health, and cultural dimensions. Vulnerability to natural disasters has two sides: the degree of exposure to dangerous hazards (susceptibility) and the capacity to cope with or recover from disaster consequences (resilience). Vulnerability reduction programs reduce susceptibility and increase resilience. Susceptibility to disasters is reduced largely by prevention and mitigation of emergencies. Emergency preparedness and response and recovery activities--including those that address climate change--increase disaster resilience. Because adaptation must occur at the community level, local public health agencies are uniquely placed to build human resilience to climate-related disasters. This article discusses the role of public health in reducing human vulnerability to climate change within the context of select examples for emergency preparedness and response.

An evaluation of NASA's program in human factors research: Aircrew-vehicle system interaction

NASA Technical Reports Server (NTRS)

1982-01-01

Research in human factors in the aircraft cockpit and a proposed program augmentation were reviewed. The dramatic growth of microprocessor technology makes it entirely feasible to automate increasingly more functions in the aircraft cockpit; the promise of improved vehicle performance, efficiency, and safety through automation makes highly automated flight inevitable. An organized data base and validated methodology for predicting the effects of automation on human performance and thus on safety are lacking and without such a data base and validated methodology for analyzing human performance, increased automation may introduce new risks. Efforts should be concentrated on developing methods and techniques for analyzing man machine interactions, including human workload and prediction of performance.

How the Human Eye Focuses.

ERIC Educational Resources Information Center

Koretz, Jane F.; Handelman, George H.

1988-01-01

Describes the decline in people's ability to focus their eyes as their age increases. Discusses probable causes of this effect including changes in the eye's geometry and biochemistry. Diagrammatically illustrates age related changes in the lens of the human eye. (CW)

Designing coastal conservation to deliver ecosystem and human well-being benefits.

PubMed

Annis, Gust M; Pearsall, Douglas R; Kahl, Katherine J; Washburn, Erika L; May, Christopher A; Franks Taylor, Rachael; Cole, James B; Ewert, David N; Game, Edward T; Doran, Patrick J

2017-01-01

Conservation scientists increasingly recognize that incorporating human values into conservation planning increases the chances for success by garnering broader project acceptance. However, methods for defining quantitative targets for the spatial representation of human well-being priorities are less developed. In this study we employ an approach for identifying regionally important human values and establishing specific spatial targets for their representation based on stakeholder outreach. Our primary objective was to develop a spatially-explicit conservation plan that identifies the most efficient locations for conservation actions to meet ecological goals while sustaining or enhancing human well-being values within the coastal and nearshore areas of the western Lake Erie basin (WLEB). We conducted an optimization analysis using 26 features representing ecological and human well-being priorities (13 of each), and included seven cost layers. The influence that including human well-being had on project results was tested by running five scenarios and setting targets for human well-being at different levels in each scenario. The most important areas for conservation to achieve multiple goals are clustered along the coast, reflecting a concentration of existing or potentially restorable coastal wetlands, coastal landbird stopover habitat and terrestrial biodiversity, as well as important recreational activities. Inland important areas tended to cluster around trails and high quality inland landbird stopover habitat. Most concentrated areas of importance also are centered on lands that are already conserved, reflecting the lower costs and higher benefits of enlarging these conserved areas rather than conserving isolated, dispersed areas. Including human well-being features in the analysis only influenced the solution at the highest target levels.

Designing coastal conservation to deliver ecosystem and human well-being benefits

PubMed Central

Pearsall, Douglas R.; Kahl, Katherine J.; Washburn, Erika L.; May, Christopher A.; Franks Taylor, Rachael; Cole, James B.; Ewert, David N.; Game, Edward T.; Doran, Patrick J.

2017-01-01

Conservation scientists increasingly recognize that incorporating human values into conservation planning increases the chances for success by garnering broader project acceptance. However, methods for defining quantitative targets for the spatial representation of human well-being priorities are less developed. In this study we employ an approach for identifying regionally important human values and establishing specific spatial targets for their representation based on stakeholder outreach. Our primary objective was to develop a spatially-explicit conservation plan that identifies the most efficient locations for conservation actions to meet ecological goals while sustaining or enhancing human well-being values within the coastal and nearshore areas of the western Lake Erie basin (WLEB). We conducted an optimization analysis using 26 features representing ecological and human well-being priorities (13 of each), and included seven cost layers. The influence that including human well-being had on project results was tested by running five scenarios and setting targets for human well-being at different levels in each scenario. The most important areas for conservation to achieve multiple goals are clustered along the coast, reflecting a concentration of existing or potentially restorable coastal wetlands, coastal landbird stopover habitat and terrestrial biodiversity, as well as important recreational activities. Inland important areas tended to cluster around trails and high quality inland landbird stopover habitat. Most concentrated areas of importance also are centered on lands that are already conserved, reflecting the lower costs and higher benefits of enlarging these conserved areas rather than conserving isolated, dispersed areas. Including human well-being features in the analysis only influenced the solution at the highest target levels. PMID:28241018

Logistics Needs for Potential Deep Space Mission Scenarios Post Asteroid Redirect Crewed Mission

NASA Technical Reports Server (NTRS)

Lopez, Pedro, Jr.; Shultz, Eric; Mattfeld, Bryan; Stromgren, Chel; Goodliff, Kandyce

2015-01-01

The Asteroid Redirect Mission (ARM) is currently being explored as the next step towards deep space human exploration, with the ultimate goal of reaching Mars. NASA is currently investigating a number of potential human exploration missions, which will progressively increase the distance and duration that humans spend away from Earth. Missions include extended human exploration in cis-lunar space which, as conceived, would involve durations of around 60 days, and human missions to Mars, which are anticipated to be as long as 1000 days. The amount of logistics required to keep the crew alive and healthy for these missions is significant. It is therefore important that the design and planning for these missions include accurate estimates of logistics requirements. This paper provides a description of a process and calculations used to estimate mass and volume requirements for crew logistics, including consumables, such as food, personal items, gasses, and liquids. Determination of logistics requirements is based on crew size, mission duration, and the degree of closure of the environmental control life support system (ECLSS). Details are provided on the consumption rates for different types of logistics and how those rates were established. Results for potential mission scenarios are presented, including a breakdown of mass and volume drivers. Opportunities for mass and volume reduction are identified, along with potential threats that could possibly increase requirements.

UK policy initiatives and the effect on increasing organ donation.

PubMed

Hall, Bethany; Parkin, Matthew Sw

Organ donation has developed since the Human Tissue Act 1961, and even since the Human Tissue Act 2004, which replaced it. Given the demand for organ transplants, there have been various attempts to increase the number of people on the Organ Donation Register, including awareness campaigns and celebrity endorsement. However, as the UK-wide strategy Taking Organ Transplantation to 2020 indicates, increasing the number of donations will require more than simply increasing the number of registered donors. This article reviews the changes in policies relating to organ donation and the associated issues.

Utility of arterial blood gas, CBC, biochemistry and cardiac hormones as evaluation parameters of cardiovascular disease in nonhuman primates.

PubMed

Nakayama, Shunya; Koie, Hiroshi; Kanayama, Kiichi; Katakai, Yuko; Ito-Fujishiro, Yasuyo; Sankai, Tadashi; Yasutomi, Yasuhiro; Ageyama, Naohide

2018-06-11

Cardiovascular disease (CVD) has a tremendous impact on the quality of life of humans. While experimental animals are valuable to medical research as models of human diseases, cardiac systems differ widely across various animal species. Thus, we examined a CVD model in cynomolgus monkeys. Laboratory primates are precious resources, making it imperative that symptoms of diseases and disorders are detected as early as possible. Thus, in this study we comprehensively examined important indicators of CVD in cynomolgus monkeys, including arterial blood gas, complete blood count (CBC), biochemistry, and cardiac hormones. The control group included 20 healthy macaques showing non-abnormal findings in screening tests, whereas the CVD group included 20 macaques with valvular disease and cardiomyopathy. An increase of red blood cell distribution width was observed in the CBC, indicating chronic inflammation related to CVD. An increase of HCO 3 was attributed to the correction of acidosis. Furthermore, development of the CVD model was supported by significant increases in natriuretic peptides. It is suggested that these results indicated a correlation between human CVD and the model in monkeys. Moreover, blood tests including arterial blood gas are non-invasive and can be performed more easily than other technical tests. CVD affected animals easily change their condition by anesthesia and surgical invasion. Pay attention to arterial blood gas and proper respond to their condition are important for research. This data may facilitate human research and aid in the management and veterinary care of nonhuman primates.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Laulicht, Freda; Brocato, Jason; Cartularo, Laura

Metals such as arsenic, cadmium, beryllium, and nickel are known human carcinogens; however, other transition metals, such as tungsten (W), remain relatively uninvestigated with regard to their potential carcinogenic activity. Tungsten production for industrial and military applications has almost doubled over the past decade and continues to increase. Here, for the first time, we demonstrate tungsten's ability to induce carcinogenic related endpoints including cell transformation, increased migration, xenograft growth in nude mice, and the activation of multiple cancer-related pathways in transformed clones as determined by RNA sequencing. Human bronchial epithelial cell line (Beas-2B) exposed to tungsten developed carcinogenic properties. Inmore » a soft agar assay, tungsten-treated cells formed more colonies than controls and the tungsten-transformed clones formed tumors in nude mice. RNA-sequencing data revealed that the tungsten-transformed clones altered the expression of many cancer-associated genes when compared to control clones. Genes involved in lung cancer, leukemia, and general cancer genes were deregulated by tungsten. Taken together, our data show the carcinogenic potential of tungsten. Further tests are needed, including in vivo and human studies, in order to validate tungsten as a carcinogen to humans. - Highlights: • Tungsten (W) induces cell transformation and increases migration in vitro. • W increases xenograft growth in nude mice. • W altered the expression of cancer-related genes such as those involved in leukemia. • Some of the dysregulated leukemia genes include, CD74, CTGF, MST4, and HOXB5. • For the first time, data is presented that demonstrates tungsten's carcinogenic potential.« less

The Internet and the Humanities: The Human Side of Networking. The Future of Networking Technologies for Learning.

ERIC Educational Resources Information Center

Riel, Margaret

This paper focuses on the human side of networking in education, emphasizing that people working together can create new solutions to old problems. Discussion includes increased links to information through the Internet and new resources entering the classroom; team-teaching, cooperative learning, and learner-centered instruction; and distance…

Inhibition of the Human ABC Efflux Transporters P-gp and BCRP by the BDE-47 Hydroxylated Metabolite 6-OH-BDE-47: Considerations for Human Exposure

EPA Science Inventory

High body burdens of polybrominated diphenyl ethers (PBDEs) in infants and young children have led to increased concern over their potential impact on human development. PBDE exposure can alter the expression of genes involved in thyroid homeostasis, including those of ATP-bindin...

Direct action of endocrine disrupting chemicals on human sperm

PubMed Central

Schiffer, Christian; Müller, Astrid; Egeberg, Dorte L; Alvarez, Luis; Brenker, Christoph; Rehfeld, Anders; Frederiksen, Hanne; Wäschle, Benjamin; Kaupp, U Benjamin; Balbach, Melanie; Wachten, Dagmar; Skakkebaek, Niels E; Almstrup, Kristian; Strünker, Timo

2014-01-01

Synthetic endocrine disrupting chemicals (EDCs), omnipresent in food, household, and personal care products, have been implicated in adverse trends in human reproduction, including infertility and increasing demand for assisted reproduction. Here, we study the action of 96 ubiquitous EDCs on human sperm. We show that structurally diverse EDCs activate the sperm-specific CatSper channel and, thereby, evoke an intracellular Ca2+ increase, a motility response, and acrosomal exocytosis. Moreover, EDCs desensitize sperm for physiological CatSper ligands and cooperate in low-dose mixtures to elevate Ca2+ levels in sperm. We conclude that EDCs interfere with various sperm functions and, thereby, might impair human fertilization. PMID:24820036

A call to include medical humanities in the curriculum of colleges of osteopathic medicine and in applicant selection.

PubMed

Hoff, Gary; Hirsch, Norma J; Means, J Jeffrey; Streyffeler, Lisa

2014-10-01

Medicine stands at a crossroad. Disruptive physician behavior has increased, and patient satisfaction has decreased. A growing body of knowledge demonstrates that the medical humanities assist in the creation of compassionate, resilient physicians. Incorporating medical humanities into the medical school curriculum promotes the development of compassionate, culturally sensitive physicians, and also encourages the development of resilience in health care professionals at a time when internal and external pressures on physicians are increasing. © 2014 The American Osteopathic Association.

Deployment Area Selection and Land Withdrawal/Acquisition. Chapter 4. M-X/MPS (M-X/Multiple Protective Shelter). Volume 1. Environmental Consequences to the Study Regions and Operating Base Vicinities.

DTIC Science & Technology

1981-10-02

to the point of energy imbalance and declining reproductive rates. Increased human population would also increase poaching of pronghorn in areas...reduced. Such effects, however, could be mitigated as discussed below and in ETR-38. Increased human activity, including poaching , harassment, habitat...when intense activity would be widespread in their habitat. Mortality resulting from habitat loss and poaching would decrease herd size during 4-205 4

Ebola Virus Glycoprotein with Increased Infectivity Dominated the 2013-2016 Epidemic.

PubMed

Diehl, William E; Lin, Aaron E; Grubaugh, Nathan D; Carvalho, Luiz Max; Kim, Kyusik; Kyawe, Pyae Phyo; McCauley, Sean M; Donnard, Elisa; Kucukural, Alper; McDonel, Patrick; Schaffner, Stephen F; Garber, Manuel; Rambaut, Andrew; Andersen, Kristian G; Sabeti, Pardis C; Luban, Jeremy

2016-11-03

The magnitude of the 2013-2016 Ebola virus disease (EVD) epidemic enabled an unprecedented number of viral mutations to occur over successive human-to-human transmission events, increasing the probability that adaptation to the human host occurred during the outbreak. We investigated one nonsynonymous mutation, Ebola virus (EBOV) glycoprotein (GP) mutant A82V, for its effect on viral infectivity. This mutation, located at the NPC1-binding site on EBOV GP, occurred early in the 2013-2016 outbreak and rose to high frequency. We found that GP-A82V had heightened ability to infect primate cells, including human dendritic cells. The increased infectivity was restricted to cells that have primate-specific NPC1 sequences at the EBOV interface, suggesting that this mutation was indeed an adaptation to the human host. GP-A82V was associated with increased mortality, consistent with the hypothesis that the heightened intrinsic infectivity of GP-A82V contributed to disease severity during the EVD epidemic. Copyright © 2016 Elsevier Inc. All rights reserved.

An Emerging Tick-Borne Disease of Humans Is Caused by a Subset of Strains with Conserved Genome Structure

PubMed Central

Barbet, Anthony F.; Al-Khedery, Basima; Stuen, Snorre; Granquist, Erik G.; Felsheim, Roderick F.; Munderloh, Ulrike G.

2013-01-01

The prevalence of tick-borne diseases is increasing worldwide. One such emerging disease is human anaplasmosis. The causative organism, Anaplasma phagocytophilum, is known to infect multiple animal species and cause human fatalities in the U.S., Europe and Asia. Although long known to infect ruminants, it is unclear why there are increasing numbers of human infections. We analyzed the genome sequences of strains infecting humans, animals and ticks from diverse geographic locations. Despite extensive variability amongst these strains, those infecting humans had conserved genome structure including the pfam01617 superfamily that encodes the major, neutralization-sensitive, surface antigen. These data provide potential targets to identify human-infective strains and have significance for understanding the selective pressures that lead to emergence of disease in new species. PMID:25437207

Metaproteomics Reveals Functional Shifts in Microbial and Human Proteins During Infant Gut Colonization Case

DOE PAGES

Young, Jacque C.; Pan, Chongle; Adams, Rachel M.; ...

2015-01-01

The microbial colonization of the human gastrointestinal tract plays an important role in establishing health and homeostasis. However, the time-dependent functional signatures of microbial and human proteins during early colonization of the gut have yet to be determined. Thus, we employed shotgun proteomics to simultaneously monitor microbial and human proteins in fecal samples from a preterm infant during the first month of life. Microbial community complexity and functions increased over time, with compositional changes that were consistent with previous metagenomic and rRNA gene data indicating three distinct colonization phases. Overall microbial community functions were established relatively early in development andmore » remained stable. Human proteins detected included those responsible for epithelial barrier function and antimicrobial activity. Some neutrophil-derived proteins increased in abundance early in the study period, suggesting activation of the innate immune system. Moreover, abundances of cytoskeletal and mucin proteins increased later in the time course, suggestive of subsequent adjustment to the increased microbial load. Our study provides the first snapshot of coordinated human and microbial protein expression in the infant gut during early development.« less

Incidence of cervical human papillomavirus infection in systemic lupus erythematosus women.

PubMed

Mendoza-Pinto, C; García-Carrasco, M; Vallejo-Ruiz, V; Méndez-Martínez, S; Taboada-Cole, A; Etchegaray-Morales, I; Muñóz-Guarneros, M; Reyes-Leyva, J; López-Colombo, A

2017-08-01

Objectives Our objective was to study the incidence, persistence and clearance of human papillomavirus infection in systemic lupus erythematosus women and assess risk factors for persistence of human papillomavirus infection. Methods We carried out a prospective, observational cohort study of 127 systemic lupus erythematosus women. Patients were evaluated at baseline and at three years. Traditional and systemic lupus erythematosus women-related disease risk factors were collected. Gynaecological evaluations and cervical cytology screening were made. Human papillomavirus detection and genotyping were made by polymerase chain reaction and linear array. Results The cumulative prevalence of human papillomavirus infection increased from 22.8% at baseline to 33.8% at three years; p = < 0.001: 20.1% of patients experienced 43 incident infections. The risk of any human papillomavirus infection was 10.1 per 1000 patient-months. At three years, 47 (88.6%) prevalent infections were cleared. Independent risk factors associated with incident human papillomavirus infection included more lifetime sexual partners (odds ratio = 1.8, 95% confidence interval = 1.11-3.0) and cumulative cyclophosphamide dose (odds ratio = 3.9, 95% confidence interval = 1.2-12.8). Conclusions In systemic lupus erythematosus women, the cumulative prevalence of human papillomavirus infection, including high risk-human papillomavirus and multiple human papillomavirus infections, may increase over time. Most persistent infections were low risk-human papillomavirus. The number of lifetime sexual partners and the cumulative cyclophosphamide dose were independently associated with incident human papillomavirus infection.

Nonprofit Human Milk Banking in the United States.

PubMed

Updegrove, Kimberly

2013-01-01

Human milk, widely understood to be beneficial for infants, can be lifesaving for preterm neonates, especially in reducing the risk of necrotizing enterocolitis. Donor human milk (DHM) is an option when mothers are unable to provide milk or have an inadequate supply for their infants. Nonprofit donor human milk banks are established to provide safe, processed human milk from milk donated by healthy lactating mothers who have undergone a rigorous screening process. These milk banks, operating under the auspices of the Human Milk Banking Association of North America, obtain, process, and dispense human milk under strict guidelines set by the association. Increasing the supply of donor human milk to meet a dramatic increase in demand poses a significant challenge for nonprofit milk banks. Efforts to increase supply nationwide include education of providers, use of social media to engage potential donors, and outreach to news media. In parallel, milk banks are establishing regional depots to collect donations, and additional milk banks are being developed. This article describes the current nonprofit milk bank industry in the United States, its challenges, and its future prospects. © 2013 by the American College of Nurse‐Midwives.

A Novel Strategy to Increase the Proliferative Potential of Adult Human β-Cells While Maintaining Their Differentiated Phenotype

PubMed Central

Aly, Haytham; Rohatgi, Nidhi; Marshall, Connie A.; Grossenheider, Tiffani C.; Miyoshi, Hiroyuki; Stappenbeck, Thaddeus S.; Matkovich, Scot J.; McDaniel, Michael L.

2013-01-01

Our previous studies demonstrated that Wnt/GSK-3/β-catenin and mTOR signaling are necessary to stimulate proliferative processes in adult human β-cells. Direct inhibition of GSK-3, that engages Wnt signaling downstream of the Wnt receptor, increases β-catenin nuclear translocation and β-cell proliferation but results in lower insulin content. Our current goal was to engage canonical and non-canonical Wnt signaling at the receptor level to significantly increase human β-cell proliferation while maintaining a β-cell phenotype in intact islets. We adopted a system that utilized conditioned medium from L cells that expressed Wnt3a, R-spondin-3 and Noggin (L-WRN conditioned medium). In addition we used a ROCK inhibitor (Y-27632) and SB-431542 (that results in RhoA inhibition) in these cultures. Treatment of intact human islets with L-WRN conditioned medium plus inhibitors significantly increased DNA synthesis ∼6 fold in a rapamycin-sensitive manner. Moreover, this treatment strikingly increased human β-cell proliferation ∼20 fold above glucose alone. Only the combination of L-WRN conditioned medium with RhoA/ROCK inhibitors resulted in substantial proliferation. Transcriptome-wide gene expression profiling demonstrated that L-WRN medium provoked robust changes in several signaling families, including enhanced β-catenin-mediated and β-cell-specific gene expression. This treatment also increased expression of Nr4a2 and Irs2 and resulted in phosphorylation of Akt. Importantly, glucose-stimulated insulin secretion and content were not downregulated by L-WRN medium treatment. Our data demonstrate that engaging Wnt signaling at the receptor level by this method leads to necessary crosstalk between multiple signaling pathways including activation of Akt, mTOR, Wnt/β-catenin, PKA/CREB, and inhibition of RhoA/ROCK that substantially increase human β-cell proliferation while maintaining the β-cell phenotype. PMID:23776620

A novel strategy to increase the proliferative potential of adult human β-cells while maintaining their differentiated phenotype.

PubMed

Aly, Haytham; Rohatgi, Nidhi; Marshall, Connie A; Grossenheider, Tiffani C; Miyoshi, Hiroyuki; Stappenbeck, Thaddeus S; Matkovich, Scot J; McDaniel, Michael L

2013-01-01

Our previous studies demonstrated that Wnt/GSK-3/β-catenin and mTOR signaling are necessary to stimulate proliferative processes in adult human β-cells. Direct inhibition of GSK-3, that engages Wnt signaling downstream of the Wnt receptor, increases β-catenin nuclear translocation and β-cell proliferation but results in lower insulin content. Our current goal was to engage canonical and non-canonical Wnt signaling at the receptor level to significantly increase human β-cell proliferation while maintaining a β-cell phenotype in intact islets. We adopted a system that utilized conditioned medium from L cells that expressed Wnt3a, R-spondin-3 and Noggin (L-WRN conditioned medium). In addition we used a ROCK inhibitor (Y-27632) and SB-431542 (that results in RhoA inhibition) in these cultures. Treatment of intact human islets with L-WRN conditioned medium plus inhibitors significantly increased DNA synthesis ∼6 fold in a rapamycin-sensitive manner. Moreover, this treatment strikingly increased human β-cell proliferation ∼20 fold above glucose alone. Only the combination of L-WRN conditioned medium with RhoA/ROCK inhibitors resulted in substantial proliferation. Transcriptome-wide gene expression profiling demonstrated that L-WRN medium provoked robust changes in several signaling families, including enhanced β-catenin-mediated and β-cell-specific gene expression. This treatment also increased expression of Nr4a2 and Irs2 and resulted in phosphorylation of Akt. Importantly, glucose-stimulated insulin secretion and content were not downregulated by L-WRN medium treatment. Our data demonstrate that engaging Wnt signaling at the receptor level by this method leads to necessary crosstalk between multiple signaling pathways including activation of Akt, mTOR, Wnt/β-catenin, PKA/CREB, and inhibition of RhoA/ROCK that substantially increase human β-cell proliferation while maintaining the β-cell phenotype.

Resurgence of target responding does not exceed increases in inactive responding in a forced-choice alternative reinforcement procedure in humans

PubMed Central

Sweeney, Mary M.; Shahan, Timothy A.

2016-01-01

Resurgence following removal of alternative reinforcement has been studied in non-human animals, children with developmental disabilities, and typically functioning adults. Adult human laboratory studies have included responses without a controlled history of reinforcement, included only two response options, or involved extensive training. Arbitrary responses allow for control over history of reinforcement. Including an inactive response never associated with reinforcement allows the conclusion that resurgence exceeds extinction-induced variability. Although procedures with extensive training produce reliable resurgence, a brief procedure with the same experimental control would allow more efficient examination of resurgence in adult humans. We tested the acceptability of a brief, single-session, three-alternative forced-choice procedure as a model of resurgence in undergraduates. Selecting a shape was the target response (reinforced in Phase I), selecting another shape was the alternative response (reinforced in Phase II), and selecting a third shape was never reinforced. Despite manipulating number of trials and probability of reinforcement, resurgence of the target response did not consistently exceed increases in the inactive response. Our findings reiterate the importance of an inactive control response and call for reexamination of resurgence studies using only two response options. We discuss potential approaches to generate an acceptable, brief human laboratory resurgence procedure. PMID:26724752

ASSESSING RISKS TO WILDLIFE POPULATIONS FROM MULTIPLE STRESSORS: OVERVIEW OF PROBLEM AND RESEARCH NEEDS

EPA Science Inventory

Wildlife populations are experiencing increasing pressure from human-induced changes in the landscape. Stressors including agricultural and urban land use, introduced invasive and exotic species, nutrient enrichment, direct human disturbance, and toxic chemicals directly or indi...

Dehumanization increases instrumental violence, but not moral violence

PubMed Central

Rai, Tage S.; Valdesolo, Piercarlo; Graham, Jesse

2017-01-01

Across five experiments, we show that dehumanization—the act of perceiving victims as not completely human—increases instrumental, but not moral, violence. In attitude surveys, ascribing reduced capacities for cognitive, experiential, and emotional states to victims predicted support for practices where victims are harmed to achieve instrumental goals, including sweatshop labor, animal experimentation, and drone strikes that result in civilian casualties, but not practices where harm is perceived as morally righteous, including capital punishment, killing in war, and drone strikes that kill terrorists. In vignette experiments, using dehumanizing compared with humanizing language increased participants’ willingness to harm strangers for money, but not participants’ willingness to harm strangers for their immoral behavior. Participants also spontaneously dehumanized strangers when they imagined harming them for money, but not when they imagined harming them for their immoral behavior. Finally, participants humanized strangers who were low in humanity if they imagined harming them for immoral behavior, but not money, suggesting that morally motivated perpetrators may humanize victims to justify violence against them. Our findings indicate that dehumanization enables violence that perpetrators see as unethical, but instrumentally beneficial. In contrast, dehumanization does not contribute to moral violence because morally motivated perpetrators wish to harm complete human beings who are capable of deserving blame, experiencing suffering, and understanding its meaning. PMID:28739935

Human migration and pig/pork import in the European Union: What are the implications for Taenia solium infections?

PubMed

Gabriël, S; Johansen, M V; Pozio, E; Smit, G S A; Devleesschauwer, B; Allepuz, A; Papadopoulos, E; van der Giessen, J; Dorny, P

2015-09-30

Taenia solium taeniasis/cysticercosis is a neglected zoonotic disease complex occurring primarily in developing countries. Though claimed eradicated from the European Union (EU), an increasing number of human neurocysticercosis cases is being detected. Risk factors such as human migration and movement of pigs/pork, as well as the increasing trend in pig rearing with outside access are discussed in this review. The entry of a tapeworm carrier into the EU seems a lot more plausible than the import of infected pork. The establishment of local transmission in the EU is presently very unlikely. However, considering the potential changes in risk factors, such as the increasing trend in pig farming with outdoor access, the increasing human migration from endemic areas into the EU, this situation might change, warranting the establishment of an early warning system, which should include disease notification of taeniasis/cysticercosis both in human and animal hosts. As currently human-to-human transmission is the highest risk, prevention strategies should focus on the early detection and treatment of tapeworm carriers, and should be designed in a concerted way, across the EU and across the different sectors. Copyright © 2015 Elsevier B.V. All rights reserved.

Modeling recent human evolution in mice by expression of a selected EDAR variant

PubMed Central

Kamberov, Yana G.; Wang, Sijia; Tan, Jingze; Gerbault, Pascale; Wark, Abigail; Tan, Longzhi; Yang, Yajun; Li, Shilin; Tang, Kun; Chen, Hua; Powell, Adam; Itan, Yuval; Fuller, Dorian; Lohmueller, Jason; Mao, Junhao; Schachar, Asa; Paymer, Madeline; Hostetter, Elizabeth; Byrne, Elizabeth; Burnett, Melissa; McMahon, Andrew P.; Thomas, Mark G.; Lieberman, Daniel E.; Jin, Li; Tabin, Clifford J.; Morgan, Bruce A.; Sabeti, Pardis C.

2013-01-01

Summary An adaptive variant of the human Ectodysplasin receptor, EDARV370A, is one of the strongest candidates of recent positive selection from genome-wide scans. We have modeled EDAR370A in mice and characterized its phenotype and evolutionary origins in humans. Our computational analysis suggests the allele arose in Central China approximately 30,000 years ago. Although EDAR370A has been associated with increased scalp hair thickness and changed tooth morphology in humans, its direct biological significance and potential adaptive role remain unclear. We generated a knock-in mouse model and find that, as in humans, hair thickness is increased in EDAR370A mice. We identify novel biological targets affected by the mutation, including mammary and eccrine glands. Building on these results, we find that EDAR370A is associated with an increased number of active eccrine glands in the Han Chinese. This interdisciplinary approach yields unique insight into the generation of adaptive variation among modern humans. PMID:23415220

The Role of International Human Rights Norms in the Liberalization of Abortion Laws Globally.

PubMed

Fine, Johanna B; Mayall, Katherine; Sepúlveda, Lilian

2017-06-01

International and regional human rights norms have evolved significantly to recognize that the denial of abortion care in a range of circumstances violates women's and girls' fundamental human rights. These increasingly progressive standards have played a critical role in transforming national-level abortion laws by both influencing domestic high court decisions on abortion and serving as a critical resource in advancing law and policy reform. Courts in countries such as Argentina, Bolivia, Brazil, Colombia, and Nepal have directly incorporated these standards into groundbreaking cases liberalizing abortion laws and increasing women's access to safe abortion services, demonstrating the influence of these human rights standards in advancing women's reproductive freedom. These norms have also underpinned national-level abortion law and policy reform, including in countries such as Spain, Rwanda, Uruguay, and Peru. As these human rights norms further evolve and increasingly recognize abortion as a human rights imperative, these standards have the potential to bolster transformative jurisprudence and law and policy reform advancing women's and girls' full reproductive autonomy.

The right to enjoy the benefits of scientific progress: in search of state obligations in relation to health.

PubMed

Donders, Yvonne

2011-11-01

After having received little attention over the past decades, one of the least known human rights--the right to enjoy the benefits of scientific progress and its applications--has had its dust blown off. Although included in the Universal Declaration of Human Rights (UDHR) and in the International Covenant on Economic, Social and Cultural Rights (ICESCR)--be it at the very end of both instruments -this right hardly received any attention from States, UN bodies and programmes and academics. The role of science in societies and its benefits and potential danger were discussed in various international fora, but hardly ever in a human rights context. Nowadays, within a world that is increasingly turning to science and technology for solutions to persistent socio-economic and development problems, the human dimension of science also receives increased attention, including the human right to enjoy the benefits of scientific progress and its applications. This contribution analyses the possible legal obligations of States in relation to the right to enjoy the benefits of scientific progress and its applications, in particular as regards health.

The Evolution of Lineage-Specific Regulatory Activities in the Human Embryonic Limb

PubMed Central

Cotney, Justin; Leng, Jing; Yin, Jun; Reilly, Steven K.; DeMare, Laura E.; Emera, Deena; Ayoub, Albert E.; Rakic, Pasko; Noonan, James P.

2013-01-01

SUMMARY The evolution of human anatomical features likely involved changes in gene regulation during development. However, the nature and extent of human-specific developmental regulatory functions remain unknown. We obtained a genome-wide view of cis-regulatory evolution in human embryonic tissues by comparing the histone modification H3K27ac, which provides a quantitative readout of promoter and enhancer activity, during human, rhesus, and mouse limb development. Based on increased H3K27ac, we find that 13% of promoters and 11% of enhancers have gained activity on the human lineage since the human-rhesus divergence. These gains largely arose by modification of ancestral regulatory activities in the limb or potential co-option from other tissues and are likely to have heterogeneous genetic causes. Most enhancers that exhibit gain of activity in humans originated in mammals. Gains at promoters and enhancers in the human limb are associated with increased gene expression, suggesting they include molecular drivers of human morphological evolution. PMID:23827682

Comparative Pathology of Aging Great Apes: Bonobos, Chimpanzees, Gorillas, and Orangutans.

PubMed

Lowenstine, L J; McManamon, R; Terio, K A

2016-03-01

The great apes (chimpanzees, bonobos, gorillas, and orangutans) are our closest relatives. Despite the many similarities, there are significant differences in aging among apes, including the human ape. Common to all are dental attrition, periodontitis, tooth loss, osteopenia, and arthritis, although gout is uniquely human and spondyloarthropathy is more prevalent in apes than humans. Humans are more prone to frailty, sarcopenia, osteoporosis, longevity past reproductive senescence, loss of brain volume, and Alzheimer dementia. Cerebral vascular disease occurs in both humans and apes. Cardiovascular disease mortality increases in aging humans and apes, but coronary atherosclerosis is the most significant type in humans. In captive apes, idiopathic myocardial fibrosis and cardiomyopathy predominate, with arteriosclerosis of intramural coronary arteries. Similar cardiac lesions are occasionally seen in wild apes. Vascular changes in heart and kidneys and aortic dissections in gorillas and bonobos suggest that hypertension may be involved in pathogenesis. Chronic kidney disease is common in elderly humans and some aging apes and is linked with cardiovascular disease in orangutans. Neoplasms common to aging humans and apes include uterine leiomyomas in chimpanzees, but other tumors of elderly humans, such as breast, prostate, lung, and colorectal cancers, are uncommon in apes. Among the apes, chimpanzees have been best studied in laboratory settings, and more comparative research is needed into the pathology of geriatric zoo-housed and wild apes. Increasing longevity of humans and apes makes understanding aging processes and diseases imperative for optimizing quality of life in all the ape species. © The Author(s) 2015.

Cigarette smoke increases Staphylococcus aureus biofilm formation via oxidative stress.

PubMed

Kulkarni, Ritwij; Antala, Swati; Wang, Alice; Amaral, Fábio E; Rampersaud, Ryan; Larussa, Samuel J; Planet, Paul J; Ratner, Adam J

2012-11-01

The strong epidemiological association between cigarette smoke (CS) exposure and respiratory tract infections is conventionally attributed to immunosuppressive and irritant effects of CS on human cells. Since pathogenic bacteria such as Staphylococcus aureus are members of the normal microbiota and reside in close proximity to human nasopharyngeal cells, we hypothesized that bioactive components of CS might affect these organisms and potentiate their virulence. Using Staphylococcus aureus as a model organism, we observed that the presence of CS increased both biofilm formation and host cell adherence. Analysis of putative molecular pathways revealed that CS exposure decreased expression of the quorum-sensing agr system, which is involved in biofilm dispersal, and increased transcription of biofilm inducers such as sarA and rbf. CS contains bioactive compounds, including free radicals and reactive oxygen species, and we observed transcriptional induction of bacterial oxidoreductases, including superoxide dismutase, following exposure. Moreover, pretreatment of CS with an antioxidant abrogated CS-mediated enhancement of biofilms. Exposure of bacteria to hydrogen peroxide alone increased biofilm formation. These observations are consistent with the hypothesis that CS induces staphylococcal biofilm formation in an oxidant-dependent manner. CS treatment induced transcription of fnbA (encoding fibronectin binding protein A), leading to increased binding of CS-treated staphylococci to immobilized fibronectin and increased adherence to human cells. These observations indicate that the bioactive effects of CS may extend to the resident microbiota of the nasopharynx, with implications for the pathogenesis of respiratory infection in CS-exposed humans.

We have AN Increasing Need to Model Ourselves

NASA Astrophysics Data System (ADS)

Farmer, J. Doyne

Pierre Teilhard de Chardin referred to the fusion of biological life, human culture, and technology as the noosphere. Technological improvement is causing the noosphere to evolve rapidly, driving the enormous increase in human population over the last 10,000 years and the transformation (and devastation) of the biosphere. The rapid proliferation of the internet is changing human culture, including everything from the way we find mates to the way democracy functions, or fails to function. The emergence of the BINC (Bio, Info, Nano, Cogno) technologies promises to further accelerate this change. We are acquiring an ever-increasing ability to engineer devices at a molecular level, to control the genome, and to create new forms of life and intelligence...

Neural and hormonal control of food hoarding

PubMed Central

Keen-Rhinehart, E.; Dailey, M. J.; Teubner, B. J.

2011-01-01

Many animals hoard food, including humans, but despite its pervasiveness, little is known about the physiological mechanisms underlying this appetitive behavior. We summarize studies of food hoarding in humans and rodents with an emphasis on mechanistic laboratory studies of species where this behavior importantly impacts their energy balance (hamsters), but include laboratory rat studies although their wild counterparts do not hoard food. The photoperiod and cold can affect food hoarding, but food availability is the most significant environmental factor affecting food hoarding. Food-deprived/restricted hamsters and humans exhibit large increases in food hoarding compared with their fed counterparts, both doing so without overeating. Some of the peripheral and central peptides involved in food intake also affect food hoarding, although many have not been tested. Ad libitum-fed hamsters given systemic injections of ghrelin, the peripheral orexigenic hormone that increases with fasting, mimics food deprivation-induced increases in food hoarding. Neuropeptide Y or agouti-related protein, brain peptides stimulated by ghrelin, given centrally to ad libitum-fed hamsters, duplicates the early and prolonged postfood deprivation increases in food hoarding, whereas central melanocortin receptor agonism tends to inhibit food deprivation and ghrelin stimulation of hoarding. Central or peripheral leptin injection or peripheral cholecystokinin-33, known satiety peptides, inhibit food hoarding. Food hoarding markedly increases with pregnancy and lactation. Because fasted and/or obese humans hoard more food in general, and more high-density/high-fat foods specifically, than nonfasted and/or nonobese humans, understanding the mechanisms underlying food hoarding could provide another target for behavioral/pharmacological approaches to curb obesity. PMID:21653877

Spacecraft and propulsion technician error

NASA Astrophysics Data System (ADS)

Schultz, Daniel Clyde

Commercial aviation and commercial space similarly launch, fly, and land passenger vehicles. Unlike aviation, the U.S. government has not established maintenance policies for commercial space. This study conducted a mixed methods review of 610 U.S. space launches from 1984 through 2011, which included 31 failures. An analysis of the failure causal factors showed that human error accounted for 76% of those failures, which included workmanship error accounting for 29% of the failures. With the imminent future of commercial space travel, the increased potential for the loss of human life demands that changes be made to the standardized procedures, training, and certification to reduce human error and failure rates. Several recommendations were made by this study to the FAA's Office of Commercial Space Transportation, space launch vehicle operators, and maintenance technician schools in an effort to increase the safety of the space transportation passengers.

Investigation of human-robot interface performance in household environments

NASA Astrophysics Data System (ADS)

Cremer, Sven; Mirza, Fahad; Tuladhar, Yathartha; Alonzo, Rommel; Hingeley, Anthony; Popa, Dan O.

2016-05-01

Today, assistive robots are being introduced into human environments at an increasing rate. Human environments are highly cluttered and dynamic, making it difficult to foresee all necessary capabilities and pre-program all desirable future skills of the robot. One approach to increase robot performance is semi-autonomous operation, allowing users to intervene and guide the robot through difficult tasks. To this end, robots need intuitive Human-Machine Interfaces (HMIs) that support fine motion control without overwhelming the operator. In this study we evaluate the performance of several interfaces that balance autonomy and teleoperation of a mobile manipulator for accomplishing several household tasks. Our proposed HMI framework includes teleoperation devices such as a tablet, as well as physical interfaces in the form of piezoresistive pressure sensor arrays. Mobile manipulation experiments were performed with a sensorized KUKA youBot, an omnidirectional platform with a 5 degrees of freedom (DOF) arm. The pick and place tasks involved navigation and manipulation of objects in household environments. Performance metrics included time for task completion and position accuracy.

Survival of the Friendliest: Homo sapiens Evolved via Selection for Prosociality.

PubMed

Hare, Brian

2017-01-03

The challenge of studying human cognitive evolution is identifying unique features of our intelligence while explaining the processes by which they arose. Comparisons with nonhuman apes point to our early-emerging cooperative-communicative abilities as crucial to the evolution of all forms of human cultural cognition, including language. The human self-domestication hypothesis proposes that these early-emerging social skills evolved when natural selection favored increased in-group prosociality over aggression in late human evolution. As a by-product of this selection, humans are predicted to show traits of the domestication syndrome observed in other domestic animals. In reviewing comparative, developmental, neurobiological, and paleoanthropological research, compelling evidence emerges for the predicted relationship between unique human mentalizing abilities, tolerance, and the domestication syndrome in humans. This synthesis includes a review of the first a priori test of the self-domestication hypothesis as well as predictions for future tests.

Ecology and Evolution of the Human Microbiota: Fire, Farming and Antibiotics

PubMed Central

Gillings, Michael R.; Paulsen, Ian T.; Tetu, Sasha G.

2015-01-01

Human activities significantly affect all ecosystems on the planet, including the assemblages that comprise our own microbiota. Over the last five million years, various evolutionary and ecological drivers have altered the composition of the human microbiota, including the use of fire, the invention of agriculture, and the increasing availability of processed foods after the Industrial Revolution. However, no factor has had a faster or more direct effect than antimicrobial agents. Biocides, disinfectants and antibiotics select for individual cells that carry resistance genes, immediately reducing both overall microbial diversity and within-species genetic diversity. Treated individuals may never recover their original diversity, and repeated treatments lead to a series of genetic bottlenecks. The sequential introduction of diverse antimicrobial agents has selected for increasingly complex DNA elements that carry multiple resistance genes, and has fostered their spread through the human microbiota. Practices that interfere with microbial colonization, such as sanitation, Caesarian births and bottle-feeding, exacerbate the effects of antimicrobials, generating species-poor and less resilient microbial assemblages in the developed world. More and more evidence is accumulating that these perturbations to our internal ecosystems lie at the heart of many diseases whose frequency has shown a dramatic increase over the last half century. PMID:26371047

Ecology and Evolution of the Human Microbiota: Fire, Farming and Antibiotics.

PubMed

Gillings, Michael R; Paulsen, Ian T; Tetu, Sasha G

2015-09-08

Human activities significantly affect all ecosystems on the planet, including the assemblages that comprise our own microbiota. Over the last five million years, various evolutionary and ecological drivers have altered the composition of the human microbiota, including the use of fire, the invention of agriculture, and the increasing availability of processed foods after the Industrial Revolution. However, no factor has had a faster or more direct effect than antimicrobial agents. Biocides, disinfectants and antibiotics select for individual cells that carry resistance genes, immediately reducing both overall microbial diversity and within-species genetic diversity. Treated individuals may never recover their original diversity, and repeated treatments lead to a series of genetic bottlenecks. The sequential introduction of diverse antimicrobial agents has selected for increasingly complex DNA elements that carry multiple resistance genes, and has fostered their spread through the human microbiota. Practices that interfere with microbial colonization, such as sanitation, Caesarian births and bottle-feeding, exacerbate the effects of antimicrobials, generating species-poor and less resilient microbial assemblages in the developed world. More and more evidence is accumulating that these perturbations to our internal ecosystems lie at the heart of many diseases whose frequency has shown a dramatic increase over the last half century.

All y'all need to know 'bout retroelements in cancer.

PubMed

Belancio, Victoria P; Roy-Engel, Astrid M; Deininger, Prescott L

2010-08-01

Genetic instability is one of the principal hallmarks and causative factors in cancer. Human transposable elements (TE) have been reported to cause human diseases, including several types of cancer through insertional mutagenesis of genes critical for preventing or driving malignant transformation. In addition to retrotransposition-associated mutagenesis, TEs have been found to contribute even more genomic rearrangements through non-allelic homologous recombination. TEs also have the potential to generate a wide range of mutations derivation of which is difficult to directly trace to mobile elements, including double strand breaks that may trigger mutagenic genomic rearrangements. Genome-wide hypomethylation of TE promoters and significantly elevated TE expression in almost all human cancers often accompanied by the loss of critical DNA sensing and repair pathways suggests that the negative impact of mobile elements on genome stability should increase as human tumors evolve. The biological consequences of elevated retroelement expression, such as the rate of their amplification, in human cancers remain obscure, particularly, how this increase translates into disease-relevant mutations. This review is focused on the cellular mechanisms that control human TE-associated mutagenesis in cancer and summarizes the current understanding of TE contribution to genetic instability in human malignancies. Copyright © 2010 Elsevier Ltd. All rights reserved.

Bisphenol A and human health: a review of the literature.

PubMed

Rochester, Johanna R

2013-12-01

There is growing evidence that bisphenol A (BPA) may adversely affect humans. BPA is an endocrine disruptor that has been shown to be harmful in laboratory animal studies. Until recently, there were relatively few epidemiological studies examining the relationship between BPA and health effects in humans. However, in the last year, the number of these studies has more than doubled. A comprehensive literature search found 91 studies linking BPA to human health; 53 published within the last year. This review outlines this body of literature, showing associations between BPA exposure and adverse perinatal, childhood, and adult health outcomes, including reproductive and developmental effects, metabolic disease, and other health effects. These studies encompass both prenatal and postnatal exposures, and include several study designs and population types. While it is difficult to make causal links with epidemiological studies, the growing human literature correlating environmental BPA exposure to adverse effects in humans, along with laboratory studies in many species including primates, provides increasing support that environmental BPA exposure can be harmful to humans, especially in regards to behavioral and other effects in children. Copyright © 2013 Elsevier Inc. All rights reserved.

Alternative Sources of Adult Stem Cells: Human Amniotic Membrane

NASA Astrophysics Data System (ADS)

Wolbank, Susanne; van Griensven, Martijn; Grillari-Voglauer, Regina; Peterbauer-Scherb, Anja

Human amniotic membrane is a highly promising cell source for tissue engineering. The cells thereof, human amniotic epithelial cells (hAEC) and human amniotic mesenchymal stromal cells (hAMSC), may be immunoprivileged, they represent an early developmental status, and their application is ethically uncontroversial. Cell banking strategies may use freshly isolated cells or involve in vitro expansion to increase cell numbers. Therefore, we have thoroughly characterized the effect of in vitro cultivation on both phenotype and differentiation potential of hAEC. Moreover, we present different strategies to improve expansion including replacement of animal-derived supplements by human platelet products or the introduction of the catalytic subunit of human telomerase to extend the in vitro lifespan of amniotic cells. Characterization of the resulting cultures includes phenotype, growth characteristics, and differentiation potential, as well as immunogenic and immunomodulatory properties.

Human impacts drive a global topographic signature in tree cover.

PubMed

Sandel, Brody; Svenning, Jens-Christian

2013-01-01

The Anthropocene is a geological epoch marked by major human influences on processes in the atmosphere, biosphere, hydrosphere and geosphere. One of the most dramatic features of the Anthropocene is the massive alteration of the Earth's vegetation, including forests. Here we investigate the role of topography in shaping human impacts on tree cover from local to global scales. We show that human impacts have resulted in a global tendency for tree cover to be constrained to sloped terrain and losses to be concentrated on flat terrain. This effect increases in strength with increasing human pressure and is most pronounced in countries with rapidly growing economies, limited human population stress and highly effective governments. These patterns likely reflect the relative inaccessibility of sloped topography and have important implications for conservation and modelling of future tree cover.

Metabolic acceleration and the evolution of human brain size and life history.

PubMed

Pontzer, Herman; Brown, Mary H; Raichlen, David A; Dunsworth, Holly; Hare, Brian; Walker, Kara; Luke, Amy; Dugas, Lara R; Durazo-Arvizu, Ramon; Schoeller, Dale; Plange-Rhule, Jacob; Bovet, Pascal; Forrester, Terrence E; Lambert, Estelle V; Thompson, Melissa Emery; Shumaker, Robert W; Ross, Stephen R

2016-05-19

Humans are distinguished from the other living apes in having larger brains and an unusual life history that combines high reproductive output with slow childhood growth and exceptional longevity. This suite of derived traits suggests major changes in energy expenditure and allocation in the human lineage, but direct measures of human and ape metabolism are needed to compare evolved energy strategies among hominoids. Here we used doubly labelled water measurements of total energy expenditure (TEE; kcal day(-1)) in humans, chimpanzees, bonobos, gorillas and orangutans to test the hypothesis that the human lineage has experienced an acceleration in metabolic rate, providing energy for larger brains and faster reproduction without sacrificing maintenance and longevity. In multivariate regressions including body size and physical activity, human TEE exceeded that of chimpanzees and bonobos, gorillas and orangutans by approximately 400, 635 and 820 kcal day(-1), respectively, readily accommodating the cost of humans' greater brain size and reproductive output. Much of the increase in TEE is attributable to humans' greater basal metabolic rate (kcal day(-1)), indicating increased organ metabolic activity. Humans also had the greatest body fat percentage. An increased metabolic rate, along with changes in energy allocation, was crucial in the evolution of human brain size and life history.

Technology support of the handover: promoting observability, flexibility and efficiency.

PubMed

Patterson, Emily S

2012-12-01

Efforts to standardise data elements and increase the comprehensiveness of information included in patient handovers have produced a growing interest in augmenting the verbal exchange of information with written communications conducted through health information technology (HIT). The aim of this perspective is to offer recommendations to optimise technology support of handovers, based on a review of the relevant scientific literature. Review of the literature on human factors and the study of communication produced three recommendations. The first entails making available "shared knowledge" relevant to the handover and subsequent clinical management with intended and unintended recipients. The second is to create a flexible narrative structure (unstructured text fields) for human-human communications facilitated by technology. The third recommendation is to avoid reliance on real-time data entry during busy periods. Implementing these recommendations is anticipated to increase the observability (the ability to readily determine current status), flexibility, and efficiency of HIT-supported patient handovers. Anticipated benefits of technology-supported handovers include reducing reliance on human memory, increasing the efficiency and structure of the verbal exchange, avoiding readbacks of numeric data, and aiding clinical management following the handover. In cases when verbal handovers are delayed, do not occur, or involve members of the health care team without first-hand access to critical information, making 'common ground' observable for all recipients, creating a flexible narrative structure for communication and avoiding reliance on real-time data entry during the busiest times has implications for HIT design and day to day data entry and management operations. Benefits include increased observability, flexibility, and efficiency of HIT-supported patient handovers.

Nitrogen trading tool

USDA-ARS?s Scientific Manuscript database

The nitrogen cycle is impacted by human activities, including those that increase the use of nitrogen in agricultural systems, and this impact can be seen in effects such as increased nitrate (NO3) levels in groundwater or surface water resources, increased concentration of nitrous oxide (N2O) in th...

Impacts of Extreme Events on Human Health. Chapter 4

NASA Technical Reports Server (NTRS)

Bell, Jesse E.; Herring, Stephanie C.; Jantarasami, Lesley; Adrianopoli, Carl; Benedict, Kaitlin; Conlon, Kathryn; Escobar, Vanessa; Hess, Jeremy; Luvall, Jeffrey; Garcia-Pando, Carlos Perez;

The redox protein thioredoxin-1 (Trx-1) increases hypoxia-inducible factor 1alpha protein expression: Trx-1 overexpression results in increased vascular endothelial growth factor production and enhanced tumor angiogenesis.

PubMed

Welsh, Sarah J; Bellamy, William T; Briehl, Margaret M; Powis, Garth

2002-09-01

Hypoxia-inducible factor 1 (HIF-1), a heterodimer of HIF-1alpha and HIF-1beta subunits, is a transcriptional activator central to the cellular response to low oxygen that includes metabolic adaptation, angiogenesis, metastasis, and inhibited apoptosis. Thioredoxin-1 (Trx-1) is a small redox protein overexpressed in a number of human primary tumors. We have examined the effects of Trx-1 on HIF activity and the activation of downstream genes. Stable transfection of human breast carcinoma MCF-7 cells with human Trx-1 caused a significant increase in HIF-1alpha protein levels under both normoxic (20% oxygen) and hypoxic (1% oxygen) conditions. Trx-1 increased hypoxia-induced HIF-1 transactivation activity measured using a luciferase reporter under the control of the hypoxia response element. Changes in HIF-1alpha mRNA levels did not account for the changes observed at the protein level, and HIF-1beta protein levels did not change. Trx-1 transfection also caused a significant increase in the protein products of hypoxia-responsive genes, including vascular endothelial growth factor (VEGF) and nitric oxide synthase 2 in a number of different cell lines (MCF-7 human breast and HT29 human colon carcinomas and WEHI7.2 mouse lymphoma cells) under both normoxic and hypoxic conditions. The pattern of expression of the different isoforms of VEGF was not changed by Trx-1. Transfection of a redox-inactive Trx-1 (C32S/C35S) markedly decreased levels of HIF-1alpha protein, HIF-1 transactivating activity, and VEGF protein in MCF-7 cells compared with empty vector controls. In vivo studies using WEHI7.2 cells transfected with Trx-1 showed significantly increased tumor VEGF and angiogenesis. The results suggest that Trx-1 increases HIF-1alpha protein levels in cancer cells and increases VEGF production and tumor angiogenesis.

Intestinal, extra-intestinal and systemic sequelae of Toxoplasma gondii induced acute ileitis in mice harboring a human gut microbiota.

PubMed

von Klitzing, Eliane; Ekmekciu, Ira; Kühl, Anja A; Bereswill, Stefan; Heimesaat, Markus M

2017-01-01

Within seven days following peroral high dose infection with Toxoplasma gondii susceptible conventionally colonized mice develop acute ileitis due to an underlying T helper cell (Th) -1 type immunopathology. We here addressed whether mice harboring a human intestinal microbiota developed intestinal, extra-intestinal and systemic sequelae upon ileitis induction. Secondary abiotic mice were generated by broad-spectrum antibiotic treatment and associated with a complex human intestinal microbiota following peroral fecal microbiota transplantation. Within three weeks the human microbiota had stably established in the murine intestinal tract as assessed by quantitative cultural and culture-independent (i.e. molecular 16S rRNA based) methods. At day 7 post infection (p.i.) with 50 cysts of T. gondii strain ME49 by gavage human microbiota associated (hma) mice displayed severe clinical, macroscopic and microscopic sequelae indicating acute ileitis. In diseased hma mice increased numbers of innate and adaptive immune cells within the ileal mucosa and lamina propria and elevated intestinal secretion of pro-inflammatory mediators including IFN-γ, IL-12 and nitric oxide could be observed at day 7 p.i. Ileitis development was accompanied by substantial shifts in intestinal microbiota composition of hma mice characterized by elevated total bacterial loads and increased numbers of intestinal Gram-negative commensals such as enterobacteria and Bacteroides / Prevotella species overgrowing the small and large intestinal lumen. Furthermore, viable bacteria translocated from the inflamed ileum to extra-intestinal including systemic compartments. Notably, pro-inflammatory immune responses were not restricted to the intestinal tract as indicated by increased pro-inflammatory cytokine secretion in extra-intestinal (i.e. liver and kidney) and systemic compartments including spleen and serum. With respect to the intestinal microbiota composition "humanized" mice display acute ileitis following peroral high dose T. gondii infection. Thus, hma mice constitute a suitable model to further dissect the interactions between pathogens, human microbiota and vertebrate host immunity during acute intestinal inflammation.

Architects of the Future--Managing Change.

ERIC Educational Resources Information Center

Conner, Daryl; Hughes, K. Scott

1988-01-01

Some of the basic principles involved in successfully managing organizational change in higher education are described. Change factors include: human resources demands, cost containment pressure, global competitive economic society, increasing technological innovation, and increasing capital investment requirements. (MLW)

Variable responses of human and non-human primate gut microbiomes to a Western diet.

PubMed

Amato, Katherine R; Yeoman, Carl J; Cerda, Gabriela; Schmitt, Christopher A; Cramer, Jennifer Danzy; Miller, Margret E Berg; Gomez, Andres; Turner, Trudy R; Wilson, Brenda A; Stumpf, Rebecca M; Nelson, Karen E; White, Bryan A; Knight, Rob; Leigh, Steven R

2015-11-16

The human gut microbiota interacts closely with human diet and physiology. To better understand the mechanisms behind this relationship, gut microbiome research relies on complementing human studies with manipulations of animal models, including non-human primates. However, due to unique aspects of human diet and physiology, it is likely that host-gut microbe interactions operate differently in humans and non-human primates. Here, we show that the human microbiome reacts differently to a high-protein, high-fat Western diet than that of a model primate, the African green monkey, or vervet (Chlorocebus aethiops sabaeus). Specifically, humans exhibit increased relative abundance of Firmicutes and reduced relative abundance of Prevotella on a Western diet while vervets show the opposite pattern. Predictive metagenomics demonstrate an increased relative abundance of genes associated with carbohydrate metabolism in the microbiome of only humans consuming a Western diet. These results suggest that the human gut microbiota has unique properties that are a result of changes in human diet and physiology across evolution or that may have contributed to the evolution of human physiology. Therefore, the role of animal models for understanding the relationship between the human gut microbiota and host metabolism must be re-focused.

Plasmacytoid Dendritic Cells Suppress HIV-1 Replication but Contribute to HIV-1 Induced Immunopathogenesis in Humanized Mice

PubMed Central

Li, Guangming; Cheng, Menglan; Nunoya, Jun-ichi; Cheng, Liang; Guo, Haitao; Yu, Haisheng; Liu, Yong-jun; Su, Lishan; Zhang, Liguo

2014-01-01

The role of plasmacytoid dendritic cells (pDC) in human immunodeficiency virus type 1 (HIV-1) infection and pathogenesis remains unclear. HIV-1 infection in the humanized mouse model leads to persistent HIV-1 infection and immunopathogenesis, including type I interferons (IFN-I) induction, immune-activation and depletion of human leukocytes, including CD4 T cells. We developed a monoclonal antibody that specifically depletes human pDC in all lymphoid organs in humanized mice. When pDC were depleted prior to HIV-1 infection, the induction of IFN-I and interferon-stimulated genes (ISGs) were abolished during acute HIV-1 infection with either a highly pathogenic CCR5/CXCR4-dual tropic HIV-1 or a standard CCR5-tropic HIV-1 isolate. Consistent with the anti-viral role of IFN-I, HIV-1 replication was significantly up-regulated in pDC-depleted mice. Interestingly, the cell death induced by the highly pathogenic HIV-1 isolate was severely reduced in pDC-depleted mice. During chronic HIV-1 infection, depletion of pDC also severely reduced the induction of IFN-I and ISGs, associated with elevated HIV-1 replication. Surprisingly, HIV-1 induced depletion of human immune cells including T cells in lymphoid organs, but not the blood, was reduced in spite of the increased viral replication. The increased cell number in lymphoid organs was associated with a reduced level of HIV-induced cell death in human leukocytes including CD4 T cells. We conclude that pDC play opposing roles in suppressing HIV-1 replication and in promoting HIV-1 induced immunopathogenesis. These findings suggest that pDC-depletion and IFN-I blockade will provide novel strategies for treating those HIV-1 immune non-responsive patients with persistent immune activation despite effective anti-retrovirus treatment. PMID:25077616

No increased cancer risks from nuclear facilities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1990-11-08

This article reports the results of a US Department of Health and Human Services (HHS) and National Cancer Institute (NCI) two-year survey that shows no increased risk of death from cancer for people living in counties containing or close to nuclear plants. 62 plants and their surrounding counties were included in the survey including commercial, US DOE and fuel reprocessing plants.

Ecosystem services: a new NRS-FIA analytical science initiative

Treesearch

Brian G. Tavernia; Mark D. Nelson; James D. Garner

2015-01-01

Forest ecosystem services (ES) are linked to sustaining human well-being. Recognizing an inappropriate economic valuation of ecosystem properties and processes, many ecologists, economists, and political scientists have pushed for an increasing awareness and appreciation of ES. Many definitions of ES include both direct and indirect benefits humans derive from...

History of nutrient inputs to the northeastern United States, 1930-2000

NASA Astrophysics Data System (ADS)

Hale, Rebecca L.; Hoover, Joseph H.; Wollheim, Wilfred M.; Vörösmarty, Charles J.

2013-04-01

Humans have dramatically altered nutrient cycles at local to global scales. We examined changes in anthropogenic nutrient inputs to the northeastern United States (NE) from 1930 to 2000. We created a comprehensive time series of anthropogenic N and P inputs to 437 counties in the NE at 5 year intervals. Inputs included atmospheric N deposition, biological N2 fixation, fertilizer, detergent P, livestock feed, and human food. Exports included exports of feed and food and volatilization of ammonia. N inputs to the NE increased throughout the study period, primarily due to increases in atmospheric deposition and fertilizer. P inputs increased until 1970 and then declined due to decreased fertilizer and detergent inputs. Livestock consistently consumed the majority of nutrient inputs over time and space. The area of crop agriculture declined during the study period but consumed more nutrients as fertilizer. We found that stoichiometry (N:P) of inputs and absolute amounts of N matched nutritional needs (livestock, humans, crops) when atmospheric components (N deposition, N2 fixation) were not included. Differences between N and P led to major changes in N:P stoichiometry over time, consistent with global trends. N:P decreased from 1930 to 1970 due to increased inputs of P, and increased from 1970 to 2000 due to increased N deposition and fertilizer and decreases in P fertilizer and detergent use. We found that nutrient use is a dynamic product of social, economic, political, and environmental interactions. Therefore, future nutrient management must take into account these factors to design successful and effective nutrient reduction measures.

Architecting Systems for Human Space Flight

NASA Technical Reports Server (NTRS)

Wocken, Gerald

2002-01-01

Human-system interactions have been largely overlooked in the traditional systems engineering process. Awareness of human factors (HF) has increased in the past few years, but the involvement of HF specialists is still often too little and too late. In systems involving long-duration human space flight, it is essential that the human component be properly considered in the initial architectural definition phase, as well as throughout the system design process. HF analysis must include not only the strengths and limitations of humans in general, but the variability between individuals and within an individual over time, and the dynamics of group interactions.

Cancers Associated with Overweight and Obesity Infographic

Cancer.gov

Overweight and obesity are linked to an increased risk of 13 types of cancer. See a diagram of the human body highlighting the organs or tissues at increased cancer risk, including the breast, colon and rectum, kidney, and liver.

Economic growth and marine biodiversity: influence of human social structure on decline of marine trophic levels.

PubMed

Clausen, Rebecca; York, Richard

2008-04-01

We assessed the effects of economic growth, urbanization, and human population size on marine biodiversity. We used the mean trophic level (MTL) of marine catch as an indicator of marine biodiversity and conducted cross-national time-series analyses (1960-2003) of 102 nations to investigate human social influences on fish catch and trends in MTL. We constructed path models to examine direct and indirect effects relating to marine catch and MTL. Nations' MTLs declined with increased economic growth, increased urbanization, and increased population size, in part because of associated increased catch. These findings contradict the environmental Kuznets curve hypothesis, which claims that economic modernization will reduce human impact on the environment. To make informed decisions on issues of marine resource management, policy makers, nonprofit entities, and professional societies must recognize the need to include social analyses in overall conservation-research strategies. The challenge is to utilize the socioeconomic and ecological research in the service of a comprehensive marine-conservation movement.

Toward a Mechanistic Understanding of Environmentally Forced Zoonotic Disease Emergence: Sin Nombre Hantavirus

PubMed Central

Carver, Scott; Mills, James N.; Parmenter, Cheryl A.; Parmenter, Robert R.; Richardson, Kyle S.; Harris, Rachel L.; Douglass, Richard J.; Kuenzi, Amy J.; Luis, Angela D.

2015-01-01

Understanding the environmental drivers of zoonotic reservoir and human interactions is crucial to understanding disease risk, but these drivers are poorly predicted. We propose a mechanistic understanding of human–reservoir interactions, using hantavirus pulmonary syndrome as a case study. Crucial processes underpinning the disease's incidence remain poorly studied, including the connectivity among natural and peridomestic deer mouse host activity, virus transmission, and human exposure. We found that disease cases were greatest in arid states and declined exponentially with increasing precipitation. Within arid environments, relatively rare climatic conditions (e.g., El Niño) are associated with increased rainfall and reservoir abundance, producing more frequent virus transmission and host dispersal. We suggest that deer mice increase their occupancy of peridomestic structures during spring–summer, amplifying intraspecific transmission and human infection risk. Disease incidence in arid states may increase with predicted climatic changes. Mechanistic approaches incorporating reservoir behavior, reservoir–human interactions, and pathogen spillover could enhance our understanding of global hantavirus ecology, with applications to other directly transmitted zoonoses. PMID:26955081

Hospice in a zoologic medicine setting.

PubMed

Jessup, David A; Scott, Cheryl A

2011-06-01

Forty years ago, Dr. Elizabeth Kubler-Ross in her landmark book On death and dying observed "maybe at the end of our days, when we have worked and given, enjoyed ourselves and suffered, we are going back to the stage that we started out with and the circle of life is closed." Just as human life expectancy has steadily increased over the last 4 or 5 decades, animal life expectancy has increased, including that of zoologic species. With this has come a need for humans to openly and frankly deal with end-of-life issues for themselves and for their animals, including those in zoos. By necessity, zoos have been dealing with problems such as aggressive pain management and triage, and efforts to incorporate end-of-life care into zoologic medicine. But these efforts have yet to include formal acknowledgment that they are a basic form of hospice. Hospice for humans, and now for companion animals, includes much more than pain relief and geriatric care. This article reviews the concepts and basic practices of hospice and the closely related field of palliative care, their relatively recent application to companion animal care, potential applications to zoologic medicine, and the ways this could provide opportunities for personal growth of zoo visitors and staff, including veterinary staff.

The Role of International Human Rights Norms in the Liberalization of Abortion Laws Globally

PubMed Central

Fine, Johanna B.; Mayall, Katherine; Sepúlveda, Lilian

2017-01-01

Abstract International and regional human rights norms have evolved significantly to recognize that the denial of abortion care in a range of circumstances violates women’s and girls’ fundamental human rights. These increasingly progressive standards have played a critical role in transforming national-level abortion laws by both influencing domestic high court decisions on abortion and serving as a critical resource in advancing law and policy reform. Courts in countries such as Argentina, Bolivia, Brazil, Colombia, and Nepal have directly incorporated these standards into groundbreaking cases liberalizing abortion laws and increasing women’s access to safe abortion services, demonstrating the influence of these human rights standards in advancing women’s reproductive freedom. These norms have also underpinned national-level abortion law and policy reform, including in countries such as Spain, Rwanda, Uruguay, and Peru. As these human rights norms further evolve and increasingly recognize abortion as a human rights imperative, these standards have the potential to bolster transformative jurisprudence and law and policy reform advancing women’s and girls’ full reproductive autonomy. PMID:28630542

Assessing Gale Crater as an Exploration Zone for the First Human Mission to Mars

NASA Technical Reports Server (NTRS)

Calef, A. F. J., III; Archer, D.; Clark, B.; Day, M.; Goetz, W.; Lasue, J.; Martin-Torres, J.; Zorzano-Mier, M.; Navarro-Gonzalez, R.

2016-01-01

Mars is the "horizon goal" for human space flight [1]. Towards that endeavor, one must consider several factors in regards to choosing a landing site suitable for a human-rated mission including: entry, descent, and landing (EDL) characteristics, scientific diversity, and possible insitu resources [2]. Selecting any one place is a careful balance of reducing risks and increasing scientific return for the mission.

Update on the Human Broad Tapeworm (Genus Diphyllobothrium), Including Clinical Relevance

PubMed Central

Scholz, Tomáš; Garcia, Hector H.; Kuchta, Roman; Wicht, Barbara

2009-01-01

Summary: Tapeworms (Cestoda) continue to be an important cause of morbidity in humans worldwide. Diphyllobothriosis, a human disease caused by tapeworms of the genus Diphyllobothrium, is the most important fish-borne zoonosis caused by a cestode parasite. Up to 20 million humans are estimated to be infected worldwide. Besides humans, definitive hosts of Diphyllobothrium include piscivorous birds and mammals, which represent a significant zoonotic reservoir. The second intermediate hosts include both freshwater and marine fish, especially anadromous species such as salmonids. The zoonosis occurs most commonly in countries where the consumption of raw or marinated fish is a frequent practice. Due to the increasing popularity of dishes utilizing uncooked fish, numerous cases of human infections have appeared recently, even in the most developed countries. As many as 14 valid species of Diphyllobothrium can cause human diphyllobothriosis, with D. latum and D. nihonkaiense being the most important pathogens. In this paper, all taxa from humans reported are reviewed, with brief information on their life history and their current distribution. Data on diagnostics, epidemiology, clinical relevance, and control of the disease are also summarized. The importance of reliable identification of human-infecting species with molecular tools (sequences of mitochondrial genes) as well as the necessity of epidemiological studies aimed at determining the sources of infections are pointed out. PMID:19136438

Human Physiological Responses to Acute and Chronic Cold Exposure

NASA Technical Reports Server (NTRS)

Stocks, Jodie M.; Taylor, Nigel A. S.; Tipton, Michael J.; Greenleaf, John E.

2001-01-01

When inadequately protected humans are exposed to acute cold, excessive body heat is lost to the environment and unless heat production is increased and heat loss attenuated, body temperature will decrease. The primary physiological responses to counter the reduction in body temperature include marked cutaneous vasoconstriction and increased metabolism. These responses, and the hazards associated with such exposure, are mediated by a number of factors which contribute to heat production and loss. These include the severity and duration of the cold stimulus; exercise intensity; the magnitude of the metabolic response; and individual characteristics such as body composition, age, and gender. Chronic exposure to a cold environment, both natural and artificial, results in physiological alterations leading to adaptation. Three quite different, but not necessarily exclusive, patterns of human cold adaptation have been reported: metabolic, hypothermic, and insulative. Cold adaptation has also been associated with an habituation response, in which there is a desensitization, or damping, of the normal response to a cold stress. This review provides a comprehensive analysis of the human physiological and pathological responses to cold exposure. Particular attention is directed to the factors contributing to heat production and heat loss during acute cold stress, and the ability of humans to adapt to cold environments.

Identification of conserved pathways of DNA-damage response and radiation protection by genome-wide RNAi.

PubMed

van Haaften, Gijs; Romeijn, Ron; Pothof, Joris; Koole, Wouter; Mullenders, Leon H F; Pastink, Albert; Plasterk, Ronald H A; Tijsterman, Marcel

2006-07-11

Ionizing radiation is extremely harmful for human cells, and DNA double-strand breaks (DSBs) are considered to be the main cytotoxic lesions induced. Improper processing of DSBs contributes to tumorigenesis, and mutations in DSB response genes underlie several inherited disorders characterized by cancer predisposition. Here, we performed a comprehensive screen for genes that protect animal cells against ionizing radiation. A total of 45 C. elegans genes were identified in a genome-wide RNA interference screen for increased sensitivity to ionizing radiation in germ cells. These genes include orthologs of well-known human cancer predisposition genes as well as novel genes, including human disease genes not previously linked to defective DNA-damage responses. Knockdown of eleven genes also impaired radiation-induced cell-cycle arrest, and seven genes were essential for apoptosis upon exposure to irradiation. The gene set was further clustered on the basis of increased sensitivity to DNA-damaging cancer drugs cisplatin and camptothecin. Almost all genes are conserved across animal phylogeny, and their relevance for humans was directly demonstrated by showing that their knockdown in human cells results in radiation sensitivity, indicating that this set of genes is important for future cancer profiling and drug development.

Climate change and epidemiology of human parasitosis in Egypt: A review.

PubMed

Lotfy, Wael M

2014-11-01

Climate change is an emerging global issue. It is expected to have significant impacts both in Egypt and around the world. Thus, the country is in need for taking action to prepare for the unavoidable effects of climate change, including the increase in water stress, the rise in sea level, and the rapidly increasing gap between the limited water availability and the escalating demand for water in the country. Also, weather and climate play a significant role in people's health. Direct impacts of climate change on the Egyptians public health may include also increased prevalence of human parasitic diseases. Climate could strongly influence parasitic diseases transmitted through intermediate hosts. The present work reviews the future of such parasitic diseases in the view of the current available evidence and scenarios for climate change in the Egypt.

Climate change and epidemiology of human parasitosis in Egypt: A review

PubMed Central

Lotfy, Wael M.

2013-01-01

Climate change is an emerging global issue. It is expected to have significant impacts both in Egypt and around the world. Thus, the country is in need for taking action to prepare for the unavoidable effects of climate change, including the increase in water stress, the rise in sea level, and the rapidly increasing gap between the limited water availability and the escalating demand for water in the country. Also, weather and climate play a significant role in people’s health. Direct impacts of climate change on the Egyptians public health may include also increased prevalence of human parasitic diseases. Climate could strongly influence parasitic diseases transmitted through intermediate hosts. The present work reviews the future of such parasitic diseases in the view of the current available evidence and scenarios for climate change in the Egypt. PMID:25685530

Delphinidin, a dietary antioxidant, induces human epidermal keratinocyte differentiation but not apoptosis: studies in submerged and three-dimensional epidermal equivalent models.

PubMed

Chamcheu, Jean Christopher; Afaq, Farrukh; Syed, Deeba N; Siddiqui, Imtiaz A; Adhami, Vaqar M; Khan, Naghma; Singh, Sohinderjit; Boylan, Brendan T; Wood, Gary S; Mukhtar, Hasan

2013-05-01

Delphinidin (Del), [3,5,7,3'-,4'-,5'-hexahydroxyflavylium], an anthocyanidin and a potent antioxidant abundantly found in pigmented fruits and vegetables exhibits proapoptotic effects in many cancer cells. Here, we determined the effect of Del on growth, apoptosis and differentiation of normal human epidermal keratinocytes (NHEKs) in vitro in submerged cultures and examined its effects in a three-dimensional (3D) epidermal equivalent (EE) model that permits complete differentiation reminiscent of in vivo skin. Treatment of NHEKs with Del (10-40 μm; 24-48 h) significantly enhanced keratinocyte differentiation. In Del-treated cells, there was marked increase in human involucrin (hINV) promoter activity with simultaneous increase in the mRNA and protein expressions of involucrin and other epidermal differentiation markers including procaspase-14 and transglutaminase-1 (TGM1), but without any effect on TGM2. Del treatment of NHEKs was associated with minimal decrease in cell viability, which was not associated with apoptosis as evident by lack of modulation of caspases, apoptosis-related proteins including Bcl-2 family of proteins and poly(ADP-ribose) polymerase cleavage. To establish the in vivo relevance of our observations in submerged cultures, we then validated these effects in a 3D EE model, where Del was found to significantly enhance cornification and increase the protein expression of cornification markers including caspase-14 and keratin 1. For the first time, we show that Del induces epidermal differentiation using an experimental system that closely mimics in vivo human skin. These observations suggest that Del could be a useful agent for dermatoses associated with epidermal barrier defects including aberrant keratinization, hyperproliferation or inflammation observed in skin diseases like psoriasis and ichthyoses. © 2013 John Wiley & Sons A/S.

Gasdermin C is induced by ultraviolet light and contributes to MMP-1 expression via activation of ERK and JNK pathways.

PubMed

Kusumaningrum, Novi; Lee, Dong Hun; Yoon, Hyun-Sun; Kim, Yeon Kyung; Park, Chi-Hyun; Chung, Jin Ho

2018-05-01

Ultraviolet (UV) radiation plays important roles in various skin diseases including premature aging and cancer. UV has been shown to regulate the expressions of many genes including matrix metalloproteinases (MMPs). Gasdermin C (GSDMC) belongs to Gasdermin family and is known to be expressed in the epithelial cells of many tissues including the skin. However, the functions of GSDMC remain poorly understood. We aimed to investigate the role of GSDMC in UV-induced MMP-1, MMP-3, and MMP-9 expressions in human skin keratinocytes. Primary human skin keratinocytes and an immortalized human skin keratinocyte cell line (HaCaT cells) were irradiated with UV. Knockdown and overexpression of GSDMC were performed to study the effect of GSDMC. The mRNA and protein levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting, respectively. We found that GSDMC expression is increased by UV irradiation in human skin keratinocytes. Further studies showed that GSDMC expression is increased at relatively late time points after UV irradiation and that this GSDMC induction plays important roles in the expressions of MMP-1, but not of MMP-3 and MMP-9, and the activations of ERK and JNK induced by UV. In addition, we found that overexpression of GSDMC increases the MMP-1 expression and the activities of ERK and JNK and that GSDMC-induced MMP-1 expression is suppressed by inhibition of ERK or JNK activities. Our results suggest that GSDMC is increased by UV radiation and contributes to UV-induced MMP-1 expression through the activation of ERK and JNK pathways. Copyright © 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Science Education Notes.

ERIC Educational Resources Information Center

School Science Review, 1983

1983-01-01

Discusses current topics in science education including increasing adult education through innovation in course planning/recruitment methods, a course in microelectronics/digital control, and need for increased human genetics topics in biology/health education. Also discusses changing role of biology teachers, preschool science, and teaching a…

In-Vehicle Information Systems Demand Model (Research Update)

DOT National Transportation Integrated Search

2000-04-01

The goal of in-vehicle information system (IVIS) technologies is to increase the mobility, improve the efficiency, and increase the safety and/or convenience of the motoring public. To achieve this goal, IVISs must be designed to include good human f...

[Kinetics of Cu crossing human erythrocyte membrane].

PubMed

Dun, Zhu Ci Ren

2014-12-01

This study was aimed to investigate various factors influencing the proceduction of Cu(II) crossing human erythrocyte membrane, including concentration of Cu²⁺, pH value of the medium, temperature and time of incubation, and to derive kinetic equation of Cu(II) crossing human erythrocyte membrane. Suspension red blood cells were incubated by Cu²⁺, then content of Cu²⁺ crossed human erythrocyte membrane was determined by atomic absorption spectrometry under various conditions after digestion. The results showed that content of Cu²⁺ crossed human erythrocyte membrane increased with the increase of extracellular Cu²⁺ and enhancement of incubation temperature, and the content of Cu²⁺ crossed human erythrocyte membrane showed a increasing tendency when pH reached to 6.2-7.4, and to maximum at pH 7.4, then gradually decreased at range of pH 7.4-9.2. It is concluded that the Cu²⁺ crossing human erythrocyte has been confirmed to be the first order kinetics characteristics within 120 min, and the linear equation is 10³ × Y = 0.0497t +6.5992.

HIV epidemic and human rights among men who have sex with men in sub-Saharan Africa: Implications for HIV prevention, care, and surveillance.

PubMed

Abara, Winston E; Garba, Ibrahim

2017-04-01

Recent research has presented evidence that men who have sex with men (MSM) bear a disproportionate burden of HIV and are at increased risk for HIV in sub-Saharan Africa (SSA). However, many countries in SSA have failed to address the needs of MSM in national HIV/AIDS programmes. Furthermore, many MSM face structural barriers to HIV prevention and care, the most significant of which include laws that criminalise male-to-male sexual contact and facilitate stigma and discrimination. This in turn increases the vulnerability of MSM to acquiring HIV and presents barriers to HIV prevention, care, and surveillance. This relationship illustrates the link between human rights, social justice, and health outcomes and presents considerable challenges to addressing the HIV epidemic among MSM in SSA. The response to the HIV epidemic in SSA requires a non-discriminatory human rights approach to all at-risk groups, including MSM. Existing international human rights treaties, to which many SSA countries are signatories, and a 'health in all policies' approach provides a strong basis to reduce structural barriers to HIV prevention, care, surveillance, and research, and to ensure that all populations in SSA, including MSM, have access to the full range of rights that help ensure equal opportunities for health and wellness.

Examination of Oral Microbiota Diversity in Adults and Older Adults as an Approach to Prevent Spread of Risk Factors for Human Infections.

PubMed

Zawadzki, Paweł J; Perkowski, Konrad; Padzik, Marcin; Mierzwińska-Nastalska, Elżbieta; Szaflik, Jacek P; Conn, David Bruce; Chomicz, Lidia

2017-01-01

The oral cavity environment may be colonized by polymicrobial communities with complex, poorly known interrelations. The aim of this study was to determine oral microbiota diversity in order to prevent the spread of infectious microorganisms that are risk factors for human health complications in patients requiring treatment due to various disabilities. The study examined Polish adults aged between 40 and 70 years; parasitological, microbiological, and mycological data collected before treatment were analyzed. The diversity of oral microbiota, including relatively high prevalences of some opportunistic, potentially pathogenic strains of bacteria, protozoans, and fungi detected in the patients analyzed, may result in increasing risk of disseminated infections from the oral cavity to neighboring structures and other organs. Increasing ageing of human populations is noted in recent decades in many countries, including Poland. The growing number of older adults with different oral health disabilities, who are more prone to development of oral and systemic pathology, is an increasing medical problem. Results of this retrospective study showed the urgent need to pay more attention to the pretreatment examination of components of the oral microbiome, especially to the strains, which are etiological agents of human opportunistic infections and are particularly dangerous for older adults.

The human milk project: a quality improvement initiative to increase human milk consumption in very low birth weight infants.

PubMed

Ward, Laura; Auer, Christine; Smith, Carrie; Schoettker, Pamela J; Pruett, Raymond; Shah, Nilesh Y; Kotagal, Uma R

2012-08-01

Human milk has well-established health benefits for preterm infants. We conducted a multidisciplinary quality improvement effort aimed at providing at least 500 mL of human milk/kg in the first 14 days of life to very low birth weight (VLBW) (< 1,500 g) infants in the neonatal intensive care unit. Improvement activities included antenatal consults with at-risk mothers, staff and parent education, a breast pump loaner program for uninsured/underinsured mothers, pump logs, establishment of a donor milk program, and twice-daily physician evaluation of infants' ability to tolerate feedings. The number of infants receiving at least 500 mL of human milk/kg in their first 14 days of life increased from 50% to 80% within 11 months of implementation, and this increase has been sustained for 4 years. Infants who met the feeding goal because they received donor milk increased each year. Since September 2007, infants have received, on average, 1,111 mL of human milk/kg. Approximately 4% of infants did not receive any human milk. Respiratory instability was the most frequent physiological reason given by clinicians for not initiating or advancing feedings in the first 14 days of life. Our quality improvement initiative resulted in a higher consumption of human milk in VLBW infants in the first 14 days of life. Other clinicians can use these described quality improvement methods and techniques to improve their VLBW babies' consumption of human milk.

Intergenerational Neuroimaging of Human Brain Circuitry

PubMed Central

Ho, Tiffany C.; Sanders, Stephan J.; Gotlib, Ian H.; Hoeft, Fumiko

2016-01-01

Neuroscientists are increasingly using advanced neuroimaging methods to elucidate the intergenerational transmission of human brain circuitry. This new line of work promises to shed insight into the ontogeny of complex behavioral traits, including psychiatric disorders, and possible mechanisms of transmission. Here, we highlight recent intergenerational neuroimaging studies and provide recommendations for future work. PMID:27623194

Student Performance in and Perceptions of a High Structure Undergraduate Human Anatomy Course

ERIC Educational Resources Information Center

Shaffer, Justin F.

2016-01-01

Human anatomy has usually been taught in a didactic fashion in colleges and universities. However, recent calls from United States governmental agencies have called for the transformation of undergraduate life sciences education to include active learning in the classroom. In addition, high structure courses have been shown to increase student…

Integrating Global Poverty into Mainstream Business Classrooms

ERIC Educational Resources Information Center

Paton, Bruce; Harris-Boundy, Jason; Melhus, Peter

2012-01-01

Most of the products and services discussed in business curricula serve a small portion of humanity. But the great majority of economic growth over the next few decades is expected to occur in emerging and frontier markets. This emerging reality increases the urgency for including topics related to global poverty, unmet human needs, and emergence…

Catalyzing sustainability: Cornell University's field practicum in conservation and sustainable development

Treesearch

John Schelhas

2000-01-01

Human society is increasingly facing a variety of complex, intertwined environmental conservation and rural development issues. For example, national park objectives have expanded from the conservation of biological diversity to also include contributing to the livelihood and development needs of local people. Human settlements in fragile uplands create conflicts...

Recognizing and Accommodating Employees with PTSD: The Intersection of Human Resource Development, Rehabilitation, and Psychology

ERIC Educational Resources Information Center

Hughes, Claretha; Lusk, Stephanie L.; Strause, Stephanie

2016-01-01

All employees within the workplace must be treated fairly and equitably including those with disabilities who may require accommodations that serve to increase access to and maintenance of competitive employment. Human Resource Development (HRD) researchers and practitioners have experience in accommodating employees with disabilities but are now…

Human Cutaneous Anthrax, Georgia 2010–2012

PubMed Central

Kracalik, Ian; Malania, Lile; Tsertsvadze, Nikoloz; Manvelyan, Julietta; Bakanidze, Lela; Imnadze, Paata; Tsanava, Shota

2014-01-01

We assessed the occurrence of human cutaneous anthrax in Georgia during 2010–-2012 by examining demographic and spatial characteristics of reported cases. Reporting increased substantially, as did clustering of cases near urban centers. Control efforts, including education about anthrax and livestock vaccination, can be directed at areas of high risk. PMID:24447721

Increased Attention to Human Sexuality Can Improve HIV-AIDS Prevention Efforts: Key Research Issues and Directions.

ERIC Educational Resources Information Center

Kelly, Jeffrey A.; Kalichman, Seth C.

1995-01-01

Discusses curtailing the human immunodeficiency virus (HIV) by helping people reduce high-risk sexual behavior. Reviews research in the relationship contexts of sexuality, including variations in monogamy, condom use in affectionate versus casual relationships, sexual communication, and coercion. Notes policy and training issues related to human…

[THE MICROSCOPIC ALGAE AS HUMAN PATHOGENS].

PubMed

Roman, Manuel Casal

2014-01-01

Some microscopic algae can cause different infectious diseases in humans, including skin, bone, and disseminated. These little-known emerging disease are more severe in immunocompromised patients. The confirmatory microbiological diagnosis must be done differential with yeast-like fungi that can be confused. Anti-fungal drugs and surgery, being quite frequent treatment failure have been used in the treatment. Given the increase of immunosuppression in the current medicine and new possibilities of microbiological diagnostics, it is logical that these diseases tend to increase, by which all physician should know them.

The space station: Human factors and productivity

NASA Technical Reports Server (NTRS)

Gillan, D. J.; Burns, M. J.; Nicodemus, C. L.; Smith, R. L.

1986-01-01

Human factor researchers and engineers are making inputs into the early stages of the design of the Space Station to improve both the quality of life and work on-orbit. Effective integration of the human factors information related to various Intravehicular Activity (IVA), Extravehicular Activity (EVA), and teletobotics systems during the Space Station design will result in increased productivity, increased flexibility of the Space Stations systems, lower cost of operations, improved reliability, and increased safety for the crew onboard the Space Station. The major features of productivity examined include the cognitive and physical effort involved in work, the accuracy of worker output and ability to maintain performance at a high level of accuracy, the speed and temporal efficiency with which a worker performs, crewmember satisfaction with their work environment, and the relation between performance and cost.

Computational Model for Oxygen Transport and Consumption in Human Vitreous

PubMed Central

Filas, Benjamen A.; Shui, Ying-Bo; Beebe, David C.

2013-01-01

Purpose. Previous studies that measured liquefaction and oxygen content in human vitreous suggested that exposure of the lens to excess oxygen causes nuclear cataracts. Here, we developed a computational model that reproduced available experimental oxygen distributions for intact and degraded human vitreous in physiologic and environmentally perturbed conditions. After validation, the model was used to estimate how age-related changes in vitreous physiology and structure alter oxygen levels at the lens. Methods. A finite-element model for oxygen transport and consumption in the human vitreous was created. Major inputs included ascorbate-mediated oxygen consumption in the vitreous, consumption at the posterior lens surface, and inflow from the retinal vasculature. Concentration-dependent relations were determined from experimental human data or estimated from animal studies, with the impact of all assumptions explored via parameter studies. Results. The model reproduced experimental data in humans, including oxygen partial pressure (Po2) gradients (≈15 mm Hg) across the anterior-posterior extent of the vitreous body, higher oxygen levels at the pars plana relative to the vitreous core, increases in Po2 near the lens after cataract surgery, and equilibration in the vitreous chamber following vitrectomy. Loss of the antioxidative capacity of ascorbate increases oxygen levels 3-fold at the lens surface. Homogeneous vitreous degeneration (liquefaction), but not partial posterior vitreous detachment, greatly increases oxygen exposure to the lens. Conclusions. Ascorbate content and the structure of the vitreous gel are critical determinants of lens oxygen exposure. Minimally invasive surgery and restoration of vitreous structure warrant further attention as strategies for preventing nuclear cataracts. PMID:24008409

Computational model for oxygen transport and consumption in human vitreous.

PubMed

Filas, Benjamen A; Shui, Ying-Bo; Beebe, David C

2013-10-15

Previous studies that measured liquefaction and oxygen content in human vitreous suggested that exposure of the lens to excess oxygen causes nuclear cataracts. Here, we developed a computational model that reproduced available experimental oxygen distributions for intact and degraded human vitreous in physiologic and environmentally perturbed conditions. After validation, the model was used to estimate how age-related changes in vitreous physiology and structure alter oxygen levels at the lens. A finite-element model for oxygen transport and consumption in the human vitreous was created. Major inputs included ascorbate-mediated oxygen consumption in the vitreous, consumption at the posterior lens surface, and inflow from the retinal vasculature. Concentration-dependent relations were determined from experimental human data or estimated from animal studies, with the impact of all assumptions explored via parameter studies. The model reproduced experimental data in humans, including oxygen partial pressure (Po2) gradients (≈15 mm Hg) across the anterior-posterior extent of the vitreous body, higher oxygen levels at the pars plana relative to the vitreous core, increases in Po2 near the lens after cataract surgery, and equilibration in the vitreous chamber following vitrectomy. Loss of the antioxidative capacity of ascorbate increases oxygen levels 3-fold at the lens surface. Homogeneous vitreous degeneration (liquefaction), but not partial posterior vitreous detachment, greatly increases oxygen exposure to the lens. Ascorbate content and the structure of the vitreous gel are critical determinants of lens oxygen exposure. Minimally invasive surgery and restoration of vitreous structure warrant further attention as strategies for preventing nuclear cataracts.

Intestinal, extra-intestinal and systemic sequelae of Toxoplasma gondii induced acute ileitis in mice harboring a human gut microbiota

PubMed Central

von Klitzing, Eliane; Ekmekciu, Ira; Kühl, Anja A.; Bereswill, Stefan

2017-01-01

Background Within seven days following peroral high dose infection with Toxoplasma gondii susceptible conventionally colonized mice develop acute ileitis due to an underlying T helper cell (Th) -1 type immunopathology. We here addressed whether mice harboring a human intestinal microbiota developed intestinal, extra-intestinal and systemic sequelae upon ileitis induction. Methodology/Principal findings Secondary abiotic mice were generated by broad-spectrum antibiotic treatment and associated with a complex human intestinal microbiota following peroral fecal microbiota transplantation. Within three weeks the human microbiota had stably established in the murine intestinal tract as assessed by quantitative cultural and culture-independent (i.e. molecular 16S rRNA based) methods. At day 7 post infection (p.i.) with 50 cysts of T. gondii strain ME49 by gavage human microbiota associated (hma) mice displayed severe clinical, macroscopic and microscopic sequelae indicating acute ileitis. In diseased hma mice increased numbers of innate and adaptive immune cells within the ileal mucosa and lamina propria and elevated intestinal secretion of pro-inflammatory mediators including IFN-γ, IL-12 and nitric oxide could be observed at day 7 p.i. Ileitis development was accompanied by substantial shifts in intestinal microbiota composition of hma mice characterized by elevated total bacterial loads and increased numbers of intestinal Gram-negative commensals such as enterobacteria and Bacteroides / Prevotella species overgrowing the small and large intestinal lumen. Furthermore, viable bacteria translocated from the inflamed ileum to extra-intestinal including systemic compartments. Notably, pro-inflammatory immune responses were not restricted to the intestinal tract as indicated by increased pro-inflammatory cytokine secretion in extra-intestinal (i.e. liver and kidney) and systemic compartments including spleen and serum. Conclusion/Significance With respect to the intestinal microbiota composition “humanized” mice display acute ileitis following peroral high dose T. gondii infection. Thus, hma mice constitute a suitable model to further dissect the interactions between pathogens, human microbiota and vertebrate host immunity during acute intestinal inflammation. PMID:28414794

A link between FTO, ghrelin, and impaired brain food-cue responsivity

PubMed Central

Karra, Efthimia; O’Daly, Owen G.; Choudhury, Agharul I.; Yousseif, Ahmed; Millership, Steven; Neary, Marianne T.; Scott, William R.; Chandarana, Keval; Manning, Sean; Hess, Martin E.; Iwakura, Hiroshi; Akamizu, Takashi; Millet, Queensta; Gelegen, Cigdem; Drew, Megan E.; Rahman, Sofia; Emmanuel, Julian J.; Williams, Steven C.R.; Rüther, Ulrich U.; Brüning, Jens C.; Withers, Dominic J.; Zelaya, Fernando O.; Batterham, Rachel L.

2013-01-01

Polymorphisms in the fat mass and obesity-associated gene (FTO) are associated with human obesity and obesity-prone behaviors, including increased food intake and a preference for energy-dense foods. FTO demethylates N6-methyladenosine, a potential regulatory RNA modification, but the mechanisms by which FTO predisposes humans to obesity remain unclear. In adiposity-matched, normal-weight humans, we showed that subjects homozygous for the FTO “obesity-risk” rs9939609 A allele have dysregulated circulating levels of the orexigenic hormone acyl-ghrelin and attenuated postprandial appetite reduction. Using functional MRI (fMRI) in normal-weight AA and TT humans, we found that the FTO genotype modulates the neural responses to food images in homeostatic and brain reward regions. Furthermore, AA and TT subjects exhibited divergent neural responsiveness to circulating acyl-ghrelin within brain regions that regulate appetite, reward processing, and incentive motivation. In cell models, FTO overexpression reduced ghrelin mRNA N6-methyladenosine methylation, concomitantly increasing ghrelin mRNA and peptide levels. Furthermore, peripheral blood cells from AA human subjects exhibited increased FTO mRNA, reduced ghrelin mRNA N6-methyladenosine methylation, and increased ghrelin mRNA abundance compared with TT subjects. Our findings show that FTO regulates ghrelin, a key mediator of ingestive behavior, and offer insight into how FTO obesity-risk alleles predispose to increased energy intake and obesity in humans. PMID:23867619

A link between FTO, ghrelin, and impaired brain food-cue responsivity.

PubMed

Karra, Efthimia; O'Daly, Owen G; Choudhury, Agharul I; Yousseif, Ahmed; Millership, Steven; Neary, Marianne T; Scott, William R; Chandarana, Keval; Manning, Sean; Hess, Martin E; Iwakura, Hiroshi; Akamizu, Takashi; Millet, Queensta; Gelegen, Cigdem; Drew, Megan E; Rahman, Sofia; Emmanuel, Julian J; Williams, Steven C R; Rüther, Ulrich U; Brüning, Jens C; Withers, Dominic J; Zelaya, Fernando O; Batterham, Rachel L

2013-08-01

Polymorphisms in the fat mass and obesity-associated gene (FTO) are associated with human obesity and obesity-prone behaviors, including increased food intake and a preference for energy-dense foods. FTO demethylates N6-methyladenosine, a potential regulatory RNA modification, but the mechanisms by which FTO predisposes humans to obesity remain unclear. In adiposity-matched, normal-weight humans, we showed that subjects homozygous for the FTO "obesity-risk" rs9939609 A allele have dysregulated circulating levels of the orexigenic hormone acyl-ghrelin and attenuated postprandial appetite reduction. Using functional MRI (fMRI) in normal-weight AA and TT humans, we found that the FTO genotype modulates the neural responses to food images in homeostatic and brain reward regions. Furthermore, AA and TT subjects exhibited divergent neural responsiveness to circulating acyl-ghrelin within brain regions that regulate appetite, reward processing, and incentive motivation. In cell models, FTO overexpression reduced ghrelin mRNA N6-methyladenosine methylation, concomitantly increasing ghrelin mRNA and peptide levels. Furthermore, peripheral blood cells from AA human subjects exhibited increased FTO mRNA, reduced ghrelin mRNA N6-methyladenosine methylation, and increased ghrelin mRNA abundance compared with TT subjects. Our findings show that FTO regulates ghrelin, a key mediator of ingestive behavior, and offer insight into how FTO obesity-risk alleles predispose to increased energy intake and obesity in humans.

Oyster Reef Restoration and Aquaculture Impacts on Denitrification and the Benthic Community

EPA Science Inventory

Human impacts have greatly altered coastal ecosystems through a variety of processes including nutrient enrichment and overfishing. The negative consequences of these actions are well known and include increased macroalgae blooms, low oxygen conditions, and losses of biodiversity...

U.S. Army Medical Department Journal (January-March 2004)

DTIC Science & Technology

2004-03-01

posted is relevant to both audiences. Posted information includes: (1) a warning against human use of flea and tick collars meant for animals; (2...Radiologic Chemistry team of the Center’s Directorate of Laboratory Sciences has developed a highly sensitive method for detecting depleted uranium in human ...Disease,” and the human form of the disease variant Creutzfeld-Jacob Disease (vCJD).1 At the time, European health officials were growing increasingly

Air Force Research Laboratory Warfighter Readiness Research Division Participation in the 2008 IITSEC

DTIC Science & Technology

2008-12-15

of the underlying behaviors that led to each element being cited. The AFSC Human Factors Database listed all human factors cited in the Life...situations of increased pressure. Through an understanding of the causal factors of human behavior , and by analysis of one’s own behavioral patterns...JTAC training and overall lessons learned from modeling and simulation of the JTAC environment to include behavior scripting, artillery models

Rise of Human Intelligence: Comments on Howard (1999).

ERIC Educational Resources Information Center

Gobet, Fernand; Campitelli, Guillermo; Waters, Andrew J.

2002-01-01

Finds several difficulties with the theory advanced by R. Howard and shows that alternative explanations relating to changes in the chess environment, including increased access to chess knowledge, offer better explanations for the increased presence of young players at top-level chess. (SLD)

The neurotropic parasite Toxoplasma gondii increases dopamine metabolism

USDA-ARS?s Scientific Manuscript database

The common parasite Toxoplasma gondii induces behavioral alterations in its hosts including phenotypes increasing the likelihood of its transmission in rodents and reports of psychobehavioral alterations in humans. We have found that elevated levels of dopamine are associated with the encysted stage...

FXR activation by obeticholic acid or nonsteroidal agonists induces a human-like lipoprotein cholesterol change in mice with humanized chimeric liver.

PubMed

Papazyan, Romeo; Liu, Xueqing; Liu, Jingwen; Dong, Bin; Plummer, Emily M; Lewis, Ronald D; Roth, Jonathan D; Young, Mark A

2018-06-01

Obeticholic acid (OCA) is a selective farnesoid X receptor (FXR) agonist that regulates bile acid and lipid metabolism. FXR activation induces distinct changes in circulating cholesterol among animal models and humans. The mechanistic basis of these effects has been elusive because of difficulties in studying lipoprotein homeostasis in mice, which predominantly package circulating cholesterol in HDLs. Here, we tested the effects of OCA in chimeric mice whose livers are mostly composed (≥80%) of human hepatocytes. Chimeric mice exhibited a human-like ratio of serum LDL cholesterol (LDL-C) to HDL cholesterol (HDL-C) at baseline. OCA treatment in chimeric mice increased circulating LDL-C and decreased circulating HDL-C levels, demonstrating that these mice closely model the cholesterol effects of FXR activation in humans. Mechanistically, OCA treatment increased hepatic cholesterol in chimeric mice but not in control mice. This increase correlated with decreased SREBP-2 activity and target gene expression, including a significant reduction in LDL receptor protein. Cotreatment with atorvastatin reduced total cholesterol, rescued LDL receptor protein levels, and normalized serum LDL-C. Treatment with two clinically relevant nonsteroidal FXR agonists elicited similar lipoprotein and hepatic changes in chimeric mice, suggesting that the increase in circulating LDL-C is a class effect of FXR activation.

Tracing the peopling of the world through genomics

PubMed Central

Nielsen, Rasmus; Akey, Joshua M.; Jakobsson, Mattias; Pritchard, Jonathan K.; Tishkoff, Sarah; Willerslev, Eske

2018-01-01

Advances in the sequencing and the analysis of the genomes of both modern and ancient peoples have facilitated a number of breakthroughs in our understanding of human evolutionary history. These include the discovery of interbreeding between anatomically modern humans and extinct hominins; the development of an increasingly detailed description of the complex dispersal of modern humans out of Africa and their population expansion worldwide; and the characterization of many of the genetic adaptions of humans to local environmental conditions. Our interpretation of the evolutionary history and adaptation of humans is being transformed by analyses of these new genomic data. PMID:28102248

Numerically abnormal chromosome constitutions in humans

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1993-12-31

Chapter 24, discusses numerically abnormal chromosome constitutions in humans. This involves abnormalities of human chromosome number, including polyploidy (when the number of sets of chromosomes increases) and aneuploidy (when the number of individual normal chromosomes changes). Chapter sections discuss the following chromosomal abnormalities: human triploids, imprinting and uniparental disomy, human tetraploids, hydatidiform moles, anomalies caused by chromosomal imbalance, 13 trisomy (D{sub 1} trisomy, Patau syndrome), 21 trisomy (Down syndrome), 18 trisomy syndrome (Edwards syndrome), other autosomal aneuploidy syndromes, and spontaneous abortions. The chapter concludes with remarks on the nonrandom participation of chromosomes in trisomy. 69 refs., 3 figs., 4 tabs.

Water-Energy-Food Nexus in Asia-Pacific Ring of Fire

NASA Astrophysics Data System (ADS)

Taniguchi, M.; Endo, A.; Gurdak, J. J.; Allen, D. M.; Siringan, F.; Delinom, R.; Shoji, J.; Fujii, M.; Baba, K.

2013-12-01

Climate change and economic development are causing increased pressure on water, energy and food resources, presenting communities with increased levels of tradeoffs and potential conflicts among these resources. Therefore, the water-energy-food nexus is one of the most important and fundamental global environmental issues facing the world. For the purposes of this research project, we define human-environmental security as the joint optimization between human and environmental security as well as the water-energy-food nexus. To optimize the governance and management within these inter-connected needs, it is desirable to increase human-environmental security by improving social managements for the water-energy-food nexus. In this research project, we intend to establish a method to manage and optimize the human-environmental security of the water-energy-food nexus by using integrated models, indices, and maps as well as social and natural investigations with stakeholder analyses. We base our approach on the viewpoint that it is important for a sustainable society to increase human-environmental security with decreasing risk and increasing resilience by optimizing the connections within the critical water-energy and water-food clusters. We will take a regional perspective to address these global environmental problems. The geological and geomorphological conditions in our proposed study area are heavily influenced by the so-called 'Ring of Fire,' around the Pacific Ocean. Within these areas including Japan and Southeast Asia, the hydro-meteorological conditions are dominated by the Asia monsoon. The populations that live under these natural conditions face elevated risk and potential disaster as negative impacts, while also benefitting from positive ecological goods and services. There are therefore tradeoffs and conflicts within the water-energy-food nexus, as well as among various stakeholders in the region. The objective of this project is to maximize human-environmental security (minimize the risk) by choosing management structures and policies that optimize both the water-food-energy nexus in Asia-Pacific coastal regions. We define joint security approach as optimized policy. Optimal policies will develop joint security approaches for human-environmental security in the coastal region of the Ring of Fire, including stakeholders and decision-makers.

The Blacklegged Tick, Ixodes scapularis: An Increasing Public Health Concern.

PubMed

Eisen, Rebecca J; Eisen, Lars

2018-04-01

In the United States, the blacklegged tick, Ixodes scapularis, is a vector of seven human pathogens, including those causing Lyme disease, anaplasmosis, babesiosis, Borrelia miyamotoi disease, Powassan virus disease, and ehrlichiosis associated with Ehrlichia muris eauclarensis. In addition to an accelerated rate of discovery of I. scapularis-borne pathogens over the past two decades, the geographic range of the tick, and incidence and range of I. scapularis-borne disease cases, have increased. Despite knowledge of when and where humans are most at risk of exposure to infected ticks, control of I. scapularis-borne diseases remains a challenge. Human vaccines are not available, and we lack solid evidence for other prevention and control methods to reduce human disease. The way forward is discussed. Published by Elsevier Ltd.

One Health, emerging infectious diseases and wildlife: two decades of progress?

PubMed

Cunningham, Andrew A; Daszak, Peter; Wood, James L N

2017-07-19

Infectious diseases affect people, domestic animals and wildlife alike, with many pathogens being able to infect multiple species. Fifty years ago, following the wide-scale manufacture and use of antibiotics and vaccines, it seemed that the battle against infections was being won for the human population. Since then, however, and in addition to increasing antimicrobial resistance among bacterial pathogens, there has been an increase in the emergence of, mostly viral, zoonotic diseases from wildlife, sometimes causing fatal outbreaks of epidemic proportions. Concurrently, infectious disease has been identified as an increasing threat to wildlife conservation. A synthesis published in 2000 showed common anthropogenic drivers of disease threats to biodiversity and human health, including encroachment and destruction of wildlife habitat and the human-assisted spread of pathogens. Almost two decades later, the situation has not changed and, despite improved knowledge of the underlying causes, little has been done at the policy level to address these threats. For the sake of public health and wellbeing, human-kind needs to work better to conserve nature and preserve the ecosystem services, including disease regulation, that biodiversity provides while also understanding and mitigating activities which lead to disease emergence. We consider that holistic, One Health approaches to the management and mitigation of the risks of emerging infectious diseases have the greatest chance of success.This article is part of the themed issue 'One Health for a changing world: zoonoses, ecosystems and human well-being'. © 2017 The Authors.

Humanlike robots: the upcoming revolution in robotics

NASA Astrophysics Data System (ADS)

Bar-Cohen, Yoseph

2009-08-01

Humans have always sought to imitate the human appearance, functions and intelligence. Human-like robots, which for many years have been a science fiction, are increasingly becoming an engineering reality resulting from the many advances in biologically inspired technologies. These biomimetic technologies include artificial intelligence, artificial vision and hearing as well as artificial muscles, also known as electroactive polymers (EAP). Robots, such as the vacuum cleaner Rumba and the robotic lawnmower, that don't have human shape, are already finding growing use in homes worldwide. As opposed to other human-made machines and devices, this technology raises also various questions and concerns and they need to be addressed as the technology advances. These include the need to prevent accidents, deliberate harm, or their use in crime. In this paper the state-of-the-art of the ultimate goal of biomimetics, the development of humanlike robots, the potentials and the challenges are reviewed.

Binary Asteroids and Human Exploration Considerations

NASA Technical Reports Server (NTRS)

Abell, P. A.

2013-01-01

In 2009 the Augustine Commission identified near-Earth asteroids (NEAs) as high profile destinations for human exploration missions beyond the Earth-Moon system as part of the Flexible Path. Subsequently, the U.S. presidential administration directed NASA on April 15, 2010 to include NEAs as destinations for future human exploration with the goal of sending astronauts to a NEA in the mid to late 2020s. This directive became part of the official National Space Policy of the United States of America as of June 28, 2010. Current NASA plans to explore NEAs do not include binary systems. However, with a few in situ robotic precursor missions to binary NEAs, and increased confidence in human mission capabilities, the scientific and hazard mitigation benefits, along with the programmatic and operational benefits of a human venture beyond the Earth-Moon system, make a mission to a binary NEA using NASA's proposed exploration systems a compelling endeavor.

Humanlike Robots - The Upcoming Revolution in Robotics

NASA Technical Reports Server (NTRS)

Bar-Cohen, Yoseph

2009-01-01

Humans have always sought to imitate the human appearance, functions and intelligence. Human-like robots, which for many years have been a science fiction, are increasingly becoming an engineering reality resulting from the many advances in biologically inspired technologies. These biomimetic technologies include artificial intelligence, artificial vision and hearing as well as artificial muscles, also known as electroactive polymers (EAP). Robots, such as the vacuum cleaner Rumba and the robotic lawnmower, that don't have human shape, are already finding growing use in homes worldwide. As opposed to other human-made machines and devices, this technology raises also various questions and concerns and they need to be addressed as the technology advances. These include the need to prevent accidents, deliberate harm, or their use in crime. In this paper the state-of-the-art of the ultimate goal of biomimetics, the development of humanlike robots, the potentials and the challenges are reviewed.

Human-like robots as platforms for electroactive polymers (EAP)

NASA Astrophysics Data System (ADS)

Bar-Cohen, Yoseph

2008-03-01

Human-like robots, which have been a science fiction for many years, are increasingly becoming an engineering reality thanks to many technology advances in recent years. Humans have always sought to imitate the human appearance, functions and intelligence and as the capability progresses they may become our household appliance or even companion. Biomimetic technologies are increasingly becoming common tools to support the development of such robots. As artificial muscles, electroactive polymers (EAP) are offering important actuation capability for making such machines lifelike. The current limitations of EAP are hampering the possibilities that can be adapted in such robots but progress is continually being made. As opposed to other human made machines and devices, this technology raises various questions and concerns that need to be addressed. These include the need to prevent accidents, deliberate harm, or their use in crimes. In this paper the state-of-the-art and the challenges will be reviewed.

Lateralized hippocampal oscillations underlie distinct aspects of human spatial memory and navigation.

PubMed

Miller, Jonathan; Watrous, Andrew J; Tsitsiklis, Melina; Lee, Sang Ah; Sheth, Sameer A; Schevon, Catherine A; Smith, Elliot H; Sperling, Michael R; Sharan, Ashwini; Asadi-Pooya, Ali Akbar; Worrell, Gregory A; Meisenhelter, Stephen; Inman, Cory S; Davis, Kathryn A; Lega, Bradley; Wanda, Paul A; Das, Sandhitsu R; Stein, Joel M; Gorniak, Richard; Jacobs, Joshua

2018-06-21

The hippocampus plays a vital role in various aspects of cognition including both memory and spatial navigation. To understand electrophysiologically how the hippocampus supports these processes, we recorded intracranial electroencephalographic activity from 46 neurosurgical patients as they performed a spatial memory task. We measure signals from multiple brain regions, including both left and right hippocampi, and we use spectral analysis to identify oscillatory patterns related to memory encoding and navigation. We show that in the left but not right hippocampus, the amplitude of oscillations in the 1-3-Hz "low theta" band increases when viewing subsequently remembered object-location pairs. In contrast, in the right but not left hippocampus, low-theta activity increases during periods of navigation. The frequencies of these hippocampal signals are slower than task-related signals in the neocortex. These results suggest that the human brain includes multiple lateralized oscillatory networks that support different aspects of cognition.

Sources, factors, mechanisms and possible solutions to pollutants in marine ecosystems.

PubMed

Mostofa, Khan M G; Liu, Cong-Qiang; Vione, Davide; Gao, Kunshan; Ogawa, Hiroshi

2013-11-01

Algal toxins or red-tide toxins produced during algal blooms are naturally-derived toxic emerging contaminants (ECs) that may kill organisms, including humans, through contaminated fish or seafood. Other ECs produced either naturally or anthropogenically ultimately flow into marine waters. Pharmaceuticals are also an important pollution source, mostly due to overproduction and incorrect disposal. Ship breaking and recycle industries (SBRIs) can also release various pollutants and substantially deteriorate habitats and marine biodiversity. Overfishing is significantly increasing due to the global food crisis, caused by an increasing world population. Organic matter (OM) pollution and global warming (GW) are key factors that exacerbate these challenges (e.g. algal blooms), to which acidification in marine waters should be added as well. Sources, factors, mechanisms and possible remedial measures of these challenges to marine ecosystems are discussed, including their eventual impact on all forms of life including humans. Copyright © 2013 Elsevier Ltd. All rights reserved.

Human Papillomavirus Vaccination Requirements in US Schools: Recommendations for Moving Forward.

PubMed

North, Anna L; Niccolai, Linda M

2016-10-01

Safe and effective human papillomavirus (HPV) vaccines have been available and recommended for adolescents for a decade in the United States, yet vaccination rates remain suboptimal. School entry requirements have increased uptake of other vaccines for adolescents and made coverage more equitable. However, only 3 jurisdictions require HPV vaccine for school. We summarize the current status of HPV vaccine requirements and discuss the rationales for and against these policies. The rationales for requirements include HPV vaccine efficacy and safety, effectiveness of requirements for increasing vaccine uptake and making it more equitable, and use of requirements as "safety nets" and to achieve herd immunity. The rationales against requirements include low parental acceptance of HPV vaccine, the financial burden on educational systems and health departments, and the possibility for alternatives to increase vaccine uptake. Many challenges to HPV vaccine requirements are addressable, and we conclude with recommendations on how to approach these challenges.

Maternal Obesity: Lifelong Metabolic Outcomes for Offspring from Poor Developmental Trajectories During the Perinatal Period.

PubMed

Zambrano, Elena; Ibáñez, Carlos; Martínez-Samayoa, Paola M; Lomas-Soria, Consuelo; Durand-Carbajal, Marta; Rodríguez-González, Guadalupe L

2016-01-01

The prevalence of obesity in women of reproductive age is increasing in developed and developing countries around the world. Human and animal studies indicate that maternal obesity adversely impacts both maternal health and offspring phenotype, predisposing them to chronic diseases later in life including obesity, dyslipidemia, type 2 diabetes mellitus, and hypertension. Several mechanisms act together to produce these adverse health effects including programming of hypothalamic appetite-regulating centers, increasing maternal, fetal and offspring glucocorticoid production, changes in maternal metabolism and increasing maternal oxidative stress. Effective interventions during human pregnancy are needed to prevent both maternal and offspring metabolic dysfunction due to maternal obesity. This review addresses the relationship between maternal obesity and its negative impact on offspring development and presents some maternal intervention studies that propose strategies to prevent adverse offspring metabolic outcomes. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

Neglected Parasitic Infections in the United States: Trichomoniasis

PubMed Central

Secor, W. Evan; Meites, Elissa; Starr, Michelle C.; Workowski, Kimberly A.

2014-01-01

Trichomonas vaginalis is one of the most common human parasitic infections in the United States, as well as the most prevalent non-viral sexually transmitted infection. However, it has long received much less consideration than other parasitic and sexually transmitted diseases. Much of this inattention can be attributed to a poor understanding of the public health impact of trichomoniasis. Increasing recognition of the sequelae of infection, including increased risk of infection with human immunodeficiency virus and adverse outcomes of pregnancy, has led to increased interest in T. vaginalis. Recent innovations include development of diagnostic tests that could improve detection of the parasite. A number of important questions, such as the epidemiology among men and women, the true public health burden of symptomatic and asymptomatic T. vaginalis infections, and whether current treatments will be adequate to reduce the substantial health disparities and costs associated with trichomoniasis, need consideration to remedy neglect of this important disease. PMID:24808247

Nomenclature for the KIR of non-human species.

PubMed

Robinson, James; Guethlein, Lisbeth A; Maccari, Giuseppe; Blokhuis, Jeroen; Bimber, Benjamin N; de Groot, Natasja G; Sanderson, Nicholas D; Abi-Rached, Laurent; Walter, Lutz; Bontrop, Ronald E; Hammond, John A; Marsh, Steven G E; Parham, Peter

2018-06-04

The increasing number of Killer Immunoglobulin-like Receptor (KIR) sequences available for non-human primate species and cattle has prompted development of a centralized database, guidelines for a standardized nomenclature, and minimum requirements for database submission. The guidelines and nomenclature are based on those used for human KIR and incorporate modifications made for inclusion of non-human species in the companion IPD-NHKIR database. Included in this first release are the rhesus macaque (Macaca mulatta), chimpanzee (Pan troglodytes), orangutan (Pongo abelii and Pongo pygmaeus), and cattle (Bos taurus).

Aviation and the environment : aviation's effects on the global atmosphere are potentially significant and expected to grow

DOT National Transportation Integrated Search

2000-02-01

Concerns about global warming are focusing increasingly on the contribution of human activities, including aviation. Jet aircraft are among many sources of greenhouse gases-gases that can trap heat, potentially increasing the temperature of the earth...

Human Nav1.8: enhanced persistent and ramp currents contribute to distinct firing properties of human DRG neurons

PubMed Central

Han, Chongyang; Estacion, Mark; Huang, Jianying; Vasylyev, Dymtro; Zhao, Peng; Dib-Hajj, Sulayman D.

2015-01-01

Although species-specific differences in ion channel properties are well-documented, little has been known about the properties of the human Nav1.8 channel, an important contributor to pain signaling. Here we show, using techniques that include voltage clamp, current clamp, and dynamic clamp in dorsal root ganglion (DRG) neurons, that human Nav1.8 channels display slower inactivation kinetics and produce larger persistent current and ramp current than previously reported in other species. DRG neurons expressing human Nav1.8 channels unexpectedly produce significantly longer-lasting action potentials, including action potentials with half-widths in some cells >10 ms, and increased firing frequency compared with the narrower and usually single action potentials generated by DRG neurons expressing rat Nav1.8 channels. We also show that native human DRG neurons recapitulate these properties of Nav1.8 current and the long-lasting action potentials. Together, our results demonstrate strikingly distinct properties of human Nav1.8, which contribute to the firing properties of human DRG neurons. PMID:25787950

Human Na(v)1.8: enhanced persistent and ramp currents contribute to distinct firing properties of human DRG neurons.

PubMed

Han, Chongyang; Estacion, Mark; Huang, Jianying; Vasylyev, Dymtro; Zhao, Peng; Dib-Hajj, Sulayman D; Waxman, Stephen G

2015-05-01

Although species-specific differences in ion channel properties are well-documented, little has been known about the properties of the human Nav1.8 channel, an important contributor to pain signaling. Here we show, using techniques that include voltage clamp, current clamp, and dynamic clamp in dorsal root ganglion (DRG) neurons, that human Na(v)1.8 channels display slower inactivation kinetics and produce larger persistent current and ramp current than previously reported in other species. DRG neurons expressing human Na(v)1.8 channels unexpectedly produce significantly longer-lasting action potentials, including action potentials with half-widths in some cells >10 ms, and increased firing frequency compared with the narrower and usually single action potentials generated by DRG neurons expressing rat Na(v)1.8 channels. We also show that native human DRG neurons recapitulate these properties of Na(v)1.8 current and the long-lasting action potentials. Together, our results demonstrate strikingly distinct properties of human Na(v)1.8, which contribute to the firing properties of human DRG neurons.

Aspects of human biometeorology in past, present and future.

PubMed

Höppe, P

1997-02-01

Human biometeorology is quite an old science: during the times of Hippokrates in ancient Greece the influence of weather changes on physiological processes in the human body were considered to exist. However, not until the progress in modern statistics, physics and physiology in the course of this century provided quantitative methods did human-biometeorology become an acknowledged natural science. In the first half of this century primarily the explanation of the phenomena of reactions of the body to weather changes was the general objective. In the second half of this century quantitative descriptions of thermal interchanges between the human body and the environment by means of energy balance models of the human body have gained increasing importance. The methods of modern human biometeorology increasingly are acknowledged by workers in disciplines of potential application, such as urban or regional planners or air conditioning engineers. Human biometeorology tries to assess all atmospheric influences in its entirety, including the air pollution pattern. The discipline considers itself as branch of science which is tied closely to environmental meteorology and environmental medicine.

A study of a steering system algorithm for pleasure boats based on stability analysis of a human-machine system model

NASA Astrophysics Data System (ADS)

Ikeda, Fujio; Toyama, Shigehiro; Ishiduki, Souta; Seta, Hiroaki

2016-09-01

Maritime accidents of small ships continue to increase in number. One of the major factors is poor manoeuvrability of the Manual Hydraulic Steering Mechanism (MHSM) in common use. The manoeuvrability can be improved by using the Electronic Control Steering Mechanism (ECSM). This paper conducts stability analyses of a pleasure boat controlled by human models in view of path following on a target course, in order to establish design guidelines for the ECSM. First, to analyse the stability region, the research derives the linear approximated model in a planar global coordinate system. Then, several human models are assumed to develop closed-loop human-machine controlled systems. These human models include basic proportional, derivative, integral and time-delay actions. The stability analysis simulations for those human-machine systems are carried out. The results show that the stability region tends to spread as a ship's velocity increases in the case of the basic proportional human model. The derivative action and time-delay action of human models are effective in spreading the stability region in their respective ranges of frontal gazing points.

Structures and Technology Encouraging Discussion in Human Sexuality Courses: Strategies to Engage a Range of Students

ERIC Educational Resources Information Center

Angera, Jeffrey J.; Latty, Christopher R.

2015-01-01

Human sexuality courses are common across many college/university campuses. The methods of instruction typically encourage discussion to increase knowledge and critical thinking about self, relationships, and professional pathways. However, often the pedagogical practices do not include methods to draw out students with a range of personalities,…

Nitrogen-induced terrestrial eutrophication: cascading effects and impacts on ecosystem services

Treesearch

Christopher M. Clark; Michael D. Bell; James W. Boyd; Jana E. Compton; Eric A. Davidson; Christine Davis; Mark E. Fenn; Linda Geiser; Laurence Jones; Tamara F. Blett

2017-01-01

Human activity has significantly increased the deposition of nitrogen (N) on terrestrial ecosystems over pre-industrial levels leading to a multitude of effects including losses of biodiversity, changes in ecosystem functioning, and impacts on human well-being. It is challenging to explicitly link the level of deposition on an ecosystem to the cascade of...

Coalescent genealogy samplers: windows into population history

PubMed Central

Kuhner, Mary K.

2016-01-01

Coalescent genealogy samplers attempt to estimate past qualities of a population, such as its size, growth rate, patterns of gene flow or time of divergence from another population, based on samples of molecular data. Genealogy samplers are increasingly popular because of their potential to disentangle complex population histories. In the last decade they have been widely applied to systems ranging from humans to viruses. Findings include detection of unexpected reproductive inequality in fish, new estimates of historical whale abundance, exoneration of humans for the prehistoric decline of bison and inference of a selective sweep on the human Y chromosome. This review summarizes available genealogy-sampler software, including data requirements and limitations on the use of each program. PMID:19101058

Coalescent genealogy samplers: windows into population history.

PubMed

Kuhner, Mary K

2009-02-01

Coalescent genealogy samplers attempt to estimate past qualities of a population, such as its size, growth rate, patterns of gene flow or time of divergence from another population, based on samples of molecular data. Genealogy samplers are increasingly popular because of their potential to disentangle complex population histories. In the last decade they have been widely applied to systems ranging from humans to viruses. Findings include detection of unexpected reproductive inequality in fish, new estimates of historical whale abundance, exoneration of humans for the prehistoric decline of bison and inference of a selective sweep on the human Y chromosome. This review summarizes available genealogy-sampler software, including data requirements and limitations on the use of each program.

Effective antigen presentation to helper T cells by human eosinophils.

PubMed

Farhan, Ruhaifah K; Vickers, Mark A; Ghaemmaghami, Amir M; Hall, Andrew M; Barker, Robert N; Walsh, Garry M

2016-12-01

Although eosinophils are inflammatory cells, there is increasing attention on their immunomodulatory roles. For example, murine eosinophils can present antigen to CD4 + T helper (Th) cells, but it remains unclear whether human eosinophils also have this ability. This study determined whether human eosinophils present a range of antigens, including allergens, to activate Th cells, and characterized their expression of MHC class II and co-stimulatory molecules required for effective presentation. Human peripheral blood eosinophils purified from non-allergic donors were pulsed with the antigens house dust mite extract (HDM), Timothy Grass extract (TG) or Mycobacterium tuberculosis purified protein derivative (PPD), before co-culture with autologous CD4 + Th cells. Proliferative and cytokine responses were measured, with eosinophil expression of HLA-DR/DP/DQ and the co-stimulatory molecules CD40, CD80 and CD86 determined by flow cytometry. Eosinophils pulsed with HDM, TG or PPD drove Th cell proliferation, with the response strength dependent on antigen concentration. The cytokine responses varied with donor and antigen, and were not biased towards any particular Th subset, often including combinations of pro- and anti-inflammatory cytokines. Eosinophils up-regulated surface expression of HLA-DR/DP/DQ, CD80, CD86 and CD40 in culture, increases that were sustained over 5 days when incubated with antigens, including HDM, or the major allergens it contains, Der p I or Der p II. Human eosinophils can, therefore, act as effective antigen-presenting cells to stimulate varied Th cell responses against a panel of antigens including HDM, TG or PPD, an ability that may help to determine the development of allergic disease. © 2016 John Wiley & Sons Ltd.

Gene Expression Profiles of Human Dendritic Cells Interacting with Aspergillus fumigatus in a Bilayer Model of the Alveolar Epithelium/Endothelium Interface

PubMed Central

Morton, Charles Oliver; Fliesser, Mirjam; Dittrich, Marcus; Mueller, Tobias; Bauer, Ruth; Kneitz, Susanne; Hope, William; Rogers, Thomas Richard; Einsele, Hermann; Loeffler, Juergen

2014-01-01

The initial stages of the interaction between the host and Aspergillus fumigatus at the alveolar surface of the human lung are critical in the establishment of aspergillosis. Using an in vitro bilayer model of the alveolus, including both the epithelium (human lung adenocarcinoma epithelial cell line, A549) and endothelium (human pulmonary artery epithelial cells, HPAEC) on transwell membranes, it was possible to closely replicate the in vivo conditions. Two distinct sub-groups of dendritic cells (DC), monocyte-derived DC (moDC) and myeloid DC (mDC), were included in the model to examine immune responses to fungal infection at the alveolar surface. RNA in high quantity and quality was extracted from the cell layers on the transwell membrane to allow gene expression analysis using tailored custom-made microarrays, containing probes for 117 immune-relevant genes. This microarray data indicated minimal induction of immune gene expression in A549 alveolar epithelial cells in response to germ tubes of A. fumigatus. In contrast, the addition of DC to the system greatly increased the number of differentially expressed immune genes. moDC exhibited increased expression of genes including CLEC7A, CD209 and CCL18 in the absence of A. fumigatus compared to mDC. In the presence of A. fumigatus, both DC subgroups exhibited up-regulation of genes identified in previous studies as being associated with the exposure of DC to A. fumigatus and exhibiting chemotactic properties for neutrophils, including CXCL2, CXCL5, CCL20, and IL1B. This model closely approximated the human alveolus allowing for an analysis of the host pathogen interface that complements existing animal models of IA. PMID:24870357

Neurodevelopmental Outcomes of Preterm Infants Fed Human Milk: A Systematic Review.

PubMed

Lechner, Beatrice E; Vohr, Betty R

2017-03-01

The neurodevelopmental benefits of breast milk feedings for preterm infants have been controversial. However, the effect on preterm infant neurodevelopment is sustained into childhood. The effects of breast milk feeding during the neonatal period and the duration of breastfeeding display effects on cognition into adolescence. The volume of breast milk received is a key factor in these effects. Additionally, emerging studies support the effects of human milk on structural brain development, such as increased white matter development and increased cortical thickness. The components of breast milk thought to mediate improved cognitive outcomes include long-chain polyunsaturated fatty acids and human milk oligosaccharides. Copyright © 2016 Elsevier Inc. All rights reserved.

The impact of globalisation on the distribution of Echinococcus multilocularis.

PubMed

Davidson, Rebecca K; Romig, Thomas; Jenkins, Emily; Tryland, Morten; Robertson, Lucy J

2012-06-01

In the past three decades, Echinococcus multilocularis, the cause of human alveolar echinococcosis, has been reported in several new countries both in definitive hosts (canids) as well as in people. Unless treated, infection with this cestode in people is fatal. In previously endemic countries throughout the Northern Hemisphere, geographic ranges and human and animal prevalence levels seem to be increasing. Anthropogenic influences, including increased globalisation of animals and animal products, and altered human/animal interfaces are thought to play a vital role in the global emergence of this pathogenic cestode. Molecular epidemiological techniques are a useful tool for detecting and tracing introductions, and differentiating these from range expansions. Copyright © 2012 Elsevier Ltd. All rights reserved.

The Genetic Variant I148M in PNPLA3 Is Associated With Increased Hepatic Retinyl-Palmitate Storage in Humans.

PubMed

Kovarova, Marketa; Königsrainer, Ingmar; Königsrainer, Alfred; Machicao, Fausto; Häring, Hans-Ulrich; Schleicher, Erwin; Peter, Andreas

2015-12-01

Previous studies revealed that the common sequence variant I148M in patatin-like phospholipase domain-containing protein 3 (PNPLA3) is associated with liver fat content and liver diseases, but not with insulin resistance. Recent data suggest that the PNPLA3 I148M variant has reduced retinyl-palmitate lipase activity in hepatic stellate cells. We hypothesized that the PNPLA3 I148M variant is associated with elevated retinyl-palmitate storage in human liver as a potential link to the clinical pathology. Design/Setting and Participants: Using HPLC, we quantified the retinoid metabolites in liver tissue extracts obtained from 42 human subjects, including 13 heterozygous and six homozygous carriers of the minor PNPLA3 I148M variant. Retinyl-palmitate is elevated in human livers of homozygous PNPLA3 I148M allele carriers Results: The PNPLA3 I148M variant was associated with a significant increase (1.4-fold) in liver fat. The content of retinyl-palmitate was elevated and the ratio of retinol/retinyl-palmitate was reduced in liver extracts obtained from homozygous PNPLA3 I148M minor allele carriers. In a multivariate model including liver fat content, these differences remained significant independent of liver fat content. The content of the minor retinyl-fatty acid esters was similarly increased in homozygous PNPLA3 I148M carriers. The increased content of hepatic retinyl-palmitate and the reduced ratio of retinol/retinyl-palmitate in PNPLA3 I148M minor allele carriers support in vitro findings of an altered retinyl-palmitate lipase activity. Our results indicate that the PNPLA3 I148M variant is relevant for the retinyl-palmitate content in human liver, providing a possible link to chronic liver disease.

Negative Emissions Technologies, the Paris Agreement, and the Need for a Human-Rights Based Approach

NASA Astrophysics Data System (ADS)

Burns, W. C. G.

2016-12-01

The new Paris Agreement under the United Nations Framework Convention on Climate Change contemplates that its prospective Parties will balance emissions and sinks by 2050 as a means to effectuate the goal of holding temperature increases to well below 2°C from pre-industrial levels, as well as the more aspirational goal of holding temperature increases to 1.5°C. Most of the IPCC's AR5 scenarios that achieve these objectives contemplate the large-scale deployment of so-called "negative emissions technologies," with an emphasis on bioenergy and carbon capture and storage (BECCS), and to a lesser degree afforestation. BECCS could assuredly help society avoid passing critical climatic thresholds, or address overshoot scenarios in this century and beyond. However, it could also profound implications for food production, the status of forests, access to lands for livelihoods by vulnerable populations, and the integrity of critical ecosystems. This, in turn could have serious ramifications for human rights of some of the world's most vulnerable populations, including the rights to food, water, livelihoods and the benefits of biodiversity. The Preamble to the Paris Agreement acknowledges the need to take into consideration the potential impact of responses to climate change, providing that "Parties should, when taking action to address climate change, respect, promote and consider their respective obligations on human rights." This presentation will outline how application of a human rights-based approach to assessing such options could help to reconcile the objectives of ameliorating potential climatic impacts while protecting the human rights of potentially affected individuals and groups. This will include the potential role of Human Rights Impacts Assessments and potential configuration of HRIAs at the national and international level. It will also briefly suggest how to operationalize this approach within the Paris Agreement framework, including institutional considerations, such as coordination with international human rights bodies. Finally, the presentation will suggest how the human rights-based framework might be applied in the context of other negative emissions technologies, including Direct Air Capture and silicate and carbon weathering.

Growth Hormone and Insulin-Like Growth Factor-1.

PubMed

Nicholls, Adam R; Holt, Richard I G

2016-01-01

Human growth hormone (GH) was first isolated from the human pituitary gland in 1945 and found to promote the growth of children with hypopituitarism. Since the formation of the World Anti-Doping Association, human GH has appeared on the list of forbidden substances. There is a significant amount of anecdotal evidence that human GH is misused by athletes to enhance performance, and there have been a number of high-profile cases of GH use in professional sport. GH secretagogues (GH-Ss), which increase GH secretion, and insulin-like growth factor (IGF-1), which mediates many of the effects of GH, are also misused, although there is less evidence for this. The effectiveness of GH, IGF-1, and GH-Ss as performance-enhancing drugs remains unclear. Evidence from studies of GH use in people with hypopituitarism show several desirable outcomes, including increased lean body mass, increased strength, and increased exercise capacity. These anabolic and metabolic properties, coupled with the difficulty in detecting them, make them attractive as agents of misuse. Studies in healthy young adults have also demonstrated a performance benefit with GH and IGF-1. © 2016 S. Karger AG, Basel.

Endocrine Disruptors

MedlinePlus

... cans, detergents, flame retardants, food, toys, cosmetics, and pesticides. NIEHS supports studies to determine whether exposure to endocrine disruptors may result in human health effects including lowered fertility and an increased incidence ...

Exercise-induced neuroplasticity in human Parkinson's disease: What is the evidence telling us?

PubMed

Hirsch, Mark A; Iyer, Sanjay S; Sanjak, Mohammed

2016-01-01

While animal models of exercise and PD have pushed the field forward, few studies have addressed exercise-induced neuroplasticity in human PD. As a first step toward promoting greater international collaboration on exercise-induced neuroplasticity in human PD, we present data on 8 human PD studies (published between 2008 and 2015) with 144 adults with PD of varying disease severity (Hoehn and Yahr stage 1 to stage 3), using various experimental (e.g., randomized controlled trial) and quasi-experimental designs on the effects of cognitive and physical activity on brain structure or function in PD. We focus on plasticity mechanisms of intervention-induced increases in maximal corticomotor excitability, exercise-induced changes in voxel-based gray matter volume changes and increases in exercise-induced serum levels of brain derived neurotrophic factor (BDNF). Finally, we provide a future perspective for promoting international, collaborative research on exercise-induced neuroplasticity in human PD. An emerging body of evidence suggests exercise triggers several plasticity related events in the human PD brain including corticomotor excitation, increases and decreases in gray matter volume and changes in BDNF levels. Copyright © 2015 Elsevier Ltd. All rights reserved.

The effects of oxytocin on eating behaviour and metabolism in humans.

PubMed

Lawson, Elizabeth A

2017-12-01

Oxytocin, a hypothalamic hormone that is secreted directly into the brain and enters the peripheral circulation through the posterior pituitary gland, regulates a range of physiologic processes, including eating behaviour and metabolism. In rodents and nonhuman primates, chronic oxytocin administration leads to sustained weight reduction by reducing food intake, increasing energy expenditure and inducing lipolysis. Oxytocin might improve glucose homeostasis, independently of its effects on weight. Clinical studies are beginning to translate these important preclinical findings to humans. This Review describes key data linking oxytocin to eating behaviour and metabolism in humans. For example, a single intranasal dose of oxytocin can reduce caloric intake, increase fat oxidation and improve insulin sensitivity in men. Furthermore, a pilot study of 8 weeks of oxytocin treatment in adults with obesity or overweight led to substantial weight loss. Together, these data support further investigation of interventions that target pathways involving oxytocin as potential therapeutics in metabolic disorders, including obesity and diabetes mellitus. Therapeutic considerations and areas for further research are also discussed.

Ozone Exposure Increases Circulating Stress Hormones and Lipid Metabolites in Humans

PubMed Central

Miller, Desinia B.; Ghio, Andrew J.; Karoly, Edward D.; Bell, Lauren N.; Snow, Samantha J.; Madden, Michael C.; Soukup, Joleen; Cascio, Wayne E.; Gilmour, M. Ian

2016-01-01

Rationale: Air pollution has been associated with increased prevalence of type 2 diabetes; however, the mechanisms remain unknown. We have shown that acute ozone exposure in rats induces release of stress hormones, hyperglycemia, leptinemia, and glucose intolerance that are associated with global changes in peripheral glucose, lipid, and amino acid metabolism. Objectives: To examine ozone-induced metabolic derangement in humans using serum metabolomic assessment, establish human-to-rodent coherence, and identify novel nonprotein biomarkers. Methods: Serum samples were obtained from a crossover clinical study that included two clinic visits (n = 24 each) where each subject was blindly exposed in the morning to either filtered air or 0.3 parts per million ozone for 2 hours during 15-minute on-off exercise. Serum samples collected within 1 hour after exposure were assessed for changes in metabolites using a metabolomic approach. Measurements and Main Results: Metabolomic analysis revealed that ozone exposure markedly increased serum cortisol and corticosterone together with increases in monoacylglycerol, glycerol, and medium- and long-chain free fatty acids, reflective of lipid mobilization and catabolism. Additionally, ozone exposure increased serum lysolipids, potentially originating from membrane lipid breakdown. Ozone exposure also increased circulating mitochondrial β-oxidation–derived metabolites, such as acylcarnitines, together with increases in the ketone body 3-hydroxybutyrate. These changes suggested saturation of β-oxidation by ozone in exercising humans. Conclusions: As in rodents, acute ozone exposure increased stress hormones and globally altered peripheral lipid metabolism in humans, likely through activation of a neurohormonally mediated stress response pathway. The metabolomic assessment revealed new biomarkers and allowed for establishment of rodent-to-human coherence. Clinical trial registered with www.clinicaltrials.gov (NCT 01492517). PMID:26745856

Cow's milk increases the activities of human nuclear receptors peroxisome proliferator-activated receptors alpha and delta and retinoid X receptor alpha involved in the regulation of energy homeostasis, obesity, and inflammation.

PubMed

Suhara, W; Koide, H; Okuzawa, T; Hayashi, D; Hashimoto, T; Kojo, H

2009-09-01

The nuclear peroxisome proliferator-activated receptors (PPAR) have been shown to play crucial roles in regulating energy homeostasis including lipid and carbohydrate metabolism, inflammatory responses, and cell proliferation, differentiation, and survival. Because PPAR agonists have the potential to prevent or ameliorate diseases such as hyperlipidemia, diabetes, atherosclerosis, and obesity, we have explored new natural agonists for PPAR. For this purpose, cow's milk was tested for agonistic activity toward human PPAR subtypes using a reporter gene assay. Milk increased human PPARalpha activity in a dose-dependent manner with a 3.2-fold increase at 0.5% (vol/vol). It also enhanced human PPARdelta activity in a dose-dependent manner with an 11.5-fold increase at 0.5%. However, it only slightly affected human PPARgamma activity. Ice cream, butter, and yogurt also increased the activities of PPARalpha and PPARdelta, whereas vegetable cream affected activity of PPARdelta but not PPARalpha. Skim milk enhanced the activity of PPAR to a lesser degree than regular milk. Milk and fresh cream increased the activity of human retinoid X receptor (RXR)alpha as well as PPARalpha and PPARdelta, whereas neither affected vitamin D3 receptor, estrogen receptors alpha and beta, or thyroid receptors alpha and beta. Both milk and fresh cream were shown by quantitative real-time PCR to increase the quantity of mRNA for uncoupling protein 2 (UCP2), an energy expenditure gene, in a dose-dependent manner. The increase in UCP2 mRNA was found to be reduced by treatment with PPARdelta-short interfering (si)RNA. This study unambiguously clarified at the cellular level that cow's milk increased the activities of human PPARalpha, PPARdelta, and RXRalpha. The possible role in enhancing the activities of PPARalpha, PPARdelta, and RXRalpha, and the health benefits of cow's milk were discussed.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Radi, Zaher, E-mail: zaher.radi@pfizer.com; Bartholomew, Phillip, E-mail: phillip.m.bartholomew@pfizer.com; Elwell, Michael, E-mail: michael.elwell@covance.com

In humans, hibernoma is a very rare, benign neoplasm of brown adipose tissue (BAT) that typically occurs at subcutaneous locations and is successfully treated by surgical excision. No single cause has been accepted to explain these very rare human tumors. In contrast, spontaneous hibernoma in rats is rare, often malignant, usually occurs in the thoracic or abdominal cavity, and metastases are common. In recent years, there has been an increased incidence of spontaneous hibernomas in rat carcinogenicity studies, but overall the occurrence remains relatively low and highly variable across studies. There have only been four reported examples of pharmaceutical-induced hibernomamore » in rat carcinogenicity studies. These include phentolamine, an alpha-adrenergic antagonist; varenicline, a nicotine partial agonist; tofacitinib, a Janus kinase (JAK) inhibitor; and hydromorphone, an opiod analgesic. Potential non-genotoxic mechanisms that may contribute to the pathogenesis of BAT activation/proliferation and/or subsequent hibernoma development in rats include: (1) physiological stimuli, (2) sympathetic stimulation, (3) peroxisome proliferator-activated receptor (PPAR) agonism, and/or (4) interference or inhibition of JAK/Signal Transducer and Activator of Transcription (JAK/STAT) signaling. The evaluation of an apparent increase of hibernoma in rats from 2-year carcinogenicity studies of novel pharmaceutical therapeutics and its relevance to human safety risk assessment is complex. One should consider: the genotoxicity of the test article, dose/exposure and safety margins, and pathophysiologic and morphologic differences and similarities of hibernoma between rats and humans. Hibernomas observed to date in carcinogenicity studies of pharmaceutical agents do not appear to be relevant for human risk at therapeutic dosages. - Highlights: • Highly variable incidence of spontaneous hibernoma in carcinogenicity studies • Recent increase in the spontaneous incidence of hibernomas in Sprague–Dawley rats • Pharmaceutical-related hibernoma has been observed in rats, but not in humans. • Pathophysiologic and morphologic differences of hibernoma between rats and 7 humans. • Hibernomas are unlikely to be relevant to human risk assessment.« less

The Role of Communications, Socio-Psychological, and Personality Factors in the Maintenance of Crew Coordination

NASA Technical Reports Server (NTRS)

Foushee, H. Clayton

1982-01-01

There is increasing evidence that many air transport incidents and accidents are the result of the improper or inadequate utilization of the resources accessible to flight dock crew members. These resources obviously include the hardware and technical information necessary for the safe and efficient conduct of the flight, but they also Include the human resources which must be coordinated effectively. The focus of this paper is upon the human resources, and how communication styles, socio-psychological factors, and personality characteristics can affect crew coordination.

Effect of Catalase and Sodium Fluoride on Human Enamel bleached with 35% Carbamide Peroxide.

PubMed

Thakur, Ruchi; Shigli, Anand L; Sharma, Divya S; Thakur, Gagan

2015-01-01

To evaluate the effects of postbleaching antioxidant application fluoridation treatment on the surface morphology and microhardness of human enamel. Ten freshly extracted human maxillary central incisors were cut at cementoenamel junction. Crown portion was sectioned into six slabs which were divided into five groups: group A - untreated controls; group B - 35% carbamide peroxide (CP); group C - 35% CP and catalase; group D - treatment with 35% CP and 5% sodium fluoride; group E - 35% CP, catalase and 5% sodium fluoride. Thirty-five percent carbamide peroxide application included two applications of 30 minutes each at a 5-day interval. After treatment, the slabs were thoroughly washed with water for 10 seconds and stored in artificial saliva at 37°C until the next treatment. Two percent sodium fluoride included application for 5 minutes. Three catalase included application for 3 minutes. After 5 days, groups B and C showed significantly decreased enamel microhardness compared to control. Group D specimens showed relatively less reduction in enamel micro-hardness than group C specimens. There is a marked increase in enamel microhardness in group E specimens. Fluoride take up was comparatively enhanced after catalase application resulting in less demineralization and increased microhardness. How to cite this article: Thakur R, Shigli AL, Sharma DS, Thakur G. Effect of Catalase and Sodium Fluoride on Human Enamel bleached with 35% Carbamide Peroxide. Int J Clin Pediatr Dent 2015;8(1):12-17.

Modelling Interactions between Forest Pest Invasions and Human Decisions Regarding Firewood Transport Restrictions

PubMed Central

Barlow, Lee-Ann; Cecile, Jacob; Bauch, Chris T.; Anand, Madhur

2014-01-01

The invasion of nonnative, wood-boring insects such as the Asian longhorned beetle (A. glabripennis) and the emerald ash borer (A. planipennis) is a serious ecological and economic threat to Canadian deciduous and mixed-wood forests. Humans act as a major vector for the spread of these pests via firewood transport, although existing models do not explicitly capture human decision-making regarding firewood transport. In this paper we present a two-patch coupled human-environment system model that includes social influence and long-distance firewood transport and examines potential strategies for mitigating pest spread. We found that increasing concern regarding infestations (f) significantly reduced infestation. Additionally it resulted in multiple thresholds at which the intensity of infestation in a patch was decreased. It was also found that a decrease in the cost of firewood purchased in the area where it is supposed to be burned (C l) resulted in an increased proportion of local-firewood strategists, and a 67% decrease in C l from $6.75 to $4.50 was sufficient to eliminate crosspatch infestation. These effects are synergistic: increasing concern through awareness and education campaigns acts together with reduced firewood costs, thereby reducing the required threshold of both awareness and economic incentives. Our results indicate that the best management strategy includes a combination of public education paired with firewood subsidization. PMID:24736497

Compounding Impacts of Climate Change and Increased Human Water Withdrawal on Urmia Lake Water Availability

NASA Astrophysics Data System (ADS)

Alborzi, A.; Moftakhari, H.; Azaranfar, A.; Mallakpour, I.; Ashraf, B.; AghaKouchak, A.

2017-12-01

In recent decades, climate change and increase in human water withdrawal, combined, have caused ecological degradation in several terminal lakes worldwide. Among them, the shallow and hyper-saline Urmia Lake in Iran has experienced about 6 meters drawdown in lake level and 80% reduction in surface area. Here, we assess the imposed stress on Urmia Basin's water availability and Lake's ecological condition in response to coupled climate change and human-induced water withdrawal. A generalized river basin decision support system model consisting network flow is developed to simulate the basin-lake interactions under a wide range of scenarios. This model explicitly includes water management infrastructure, reservoirs, and irrigation and municipal water use. Studied scenarios represent a wide range of historic climate and water use scenarios including a historical baseline, future increase in water demand, and also improved water efficiency. In this presentation, we show the lake's water level, as a measure of lake's ecological health, under the compounding effects of the climate condition (top-down) and water use (bottom-up) scenarios. This method illustrates what combinations lead to failure in meeting the lake's ecological level.

Theodore E. Woodward Award: Global Warming and the Human Stomach: Microecology Follows Macroecology

PubMed Central

Blaser, Martin J

2005-01-01

Just as there have been 20th century changes in our “macroecology,” including global warming, there have been alterations in our “microecology,” involving the microbial populations that colonize the human body. Helicobacter pylori, an ancient inhabitant of the human stomach, has been disappearing over the course of the 20th century. As such, by comparing H. pylori+ and H. pylori− persons, the consequences of its colonization can be determined. The presence of H. pylori is associated with increased risk for development of gastric cancer and peptic ulceration, and with decreased risk for gastroesophageal reflux disease (GERD) and its sequelae, including esophageal adenocarcinoma. The disappearance of H. pylori (especially cag+ strains), possibly contributing to the risk of these esophageal diseases, may be an indicator for changing human microecology. PMID:16555606

The Fruit Fly Drosophila melanogaster as a Model for Aging Research.

PubMed

Brandt, Annely; Vilcinskas, Andreas

2013-01-01

: Average human life expectancy is increasing and so is the impact on society of aging and age-related diseases. Here we highlight recent advances in the diverse and multidisciplinary field of aging research, focusing on the fruit fly Drosophila melanogaster, an excellent model system in which to dissect the genetic and molecular basis of the aging processes. The conservation of human disease genes in D. melanogaster allows the functional analysis of orthologues implicated in human aging and age-related diseases. D. melanogaster models have been developed for a variety of age-related processes and disorders, including stem cell decline, Alzheimer's disease, and cardiovascular deterioration. Understanding the detailed molecular events involved in normal aging and age-related diseases could facilitate the development of strategies and treatments that reduce their impact, thus improving human health and increasing longevity.

DROP: Durable Reconnaissance and Observation Platform

NASA Technical Reports Server (NTRS)

Parness, Aaron; McKenzie, Clifford F.

2012-01-01

Robots have been a valuable tool for providing a remote presence in areas that are either inaccessible or too dangerous for humans. Having a robot with a high degree of adaptability becomes crucial during such events. The adaptability that comes from high mobility and high durability greatly increases the potential uses of a robot in these situations, and therefore greatly increases its usefulness to humans. DROP is a lightweight robot that addresses these challenges with the capability to survive large impacts, carry a usable payload, and traverse a variety of surfaces, including climbing vertical surfaces like wood, stone, and concrete. The platform is crash-proof, allowing it to be deployed in ways including being dropped from an unmanned aerial vehicle or thrown from a large MSL-class (Mars Science Laboratory) rover.

The perspectives for porcine-to-human xenografts.

PubMed

Petersen, Bjoern; Carnwath, Joseph W; Niemann, Heiner

2009-03-01

The shortage of donated human organs for transplantation continues to be a life threatening problem for patients suffering from complete organ failure. Although this gap is increasing due to the demographic changes in aging Western populations, it is generally accepted that international trading in human organ is not an ethical solution. Alternatives to the use of human organs for transplantation must be developed and these alternatives include stem cell therapy, artificial organs and organs from other species, i.e. xenografts. For practical reasons but most importantly because of its physiological similarity with humans, the pig is generally accepted as the species of choice for xenotransplantation. Nevertheless, before porcine organs can be used in human xenotransplantation, it is necessary to make a series of precise genetic modifications to the porcine genome, including the addition of genes for factors which suppress the rejection of transplanted porcine tissues and the inactivation or removal of undesirable genes which can only be accomplished at this time by targeted recombination and somatic nuclear transfer. This review will give an insight into the advances in transgenic manipulation and cloning in pigs--in the context of porcine-to-human xenotransplantation.

Time Orientation and Human Performance

DTIC Science & Technology

2004-06-01

Work with Computing Systems 2004. H.M. Khalid, M.G. Helander, A.W. Yeo (Editors) . Kuala Lumpur: Damai Sciences. 1 Time Orientation and Human...Multi-tasking. 1 . Introduction With increased globalization, understanding the various cultures and people’s attitudes and behaviours is crucial...reporting burden for the collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching

Environmental and anthropogenic factors affecting the increasing occurrence of shark-human interactions around a fast-developing Indian Ocean island.

PubMed

Lagabrielle, Erwann; Allibert, Agathe; Kiszka, Jeremy J; Loiseau, Nicolas; Kilfoil, James P; Lemahieu, Anne

2018-02-27

Understanding the environmental drivers of interactions between predators and humans is critical for public safety and management purposes. In the marine environment, this issue is exemplified by shark-human interactions. The annual shark bite incidence rate (SBIR) in La Réunion (Indian Ocean) is among the highest in the world (up to 1 event per 24,000 hours of surfing) and has experienced a 23-fold increase over the 2005-2016 period. Since 1988, 86% of shark bite events on ocean-users involved surfers off the leeward coast, where 96% of surfing activities took place. We modeled the SBIR as a function of environmental variables, including benthic substrate, sea temperature and period of day. The SBIR peaked in winter, during the afternoon and dramatically increased on coral substrate since the mid-2000s. Seasonal patterns of increasing SBIR followed similar fluctuations of large coastal shark occurrences (particularly the bull shark Carcharhinus leucas), consistent with the hypothesis that higher shark presence may result in an increasing likelihood of shark bite events. Potential contributing factors and adaptation of ocean-users to the increasing shark bite hazard are discussed. This interdisciplinary research contributes to a better understanding of shark-human interactions. The modeling method is relevant for wildlife hazard management in general.

A mixed-methods observational study of human milk sharing communities on Facebook.

PubMed

Perrin, Maryanne Tigchelaar; Goodell, L Suzanne; Allen, Jonathan C; Fogleman, April

2014-04-01

The Food and Drug Administration discourages the casual sharing of human milk because of the risk of pathogen transmission. No information is currently available on the prevalence of this practice. The purpose of this mixed-methods observational study is to describe the size and activity of online milk sharing communities. Data for 3 months were extracted from nine public Facebook pages that facilitate the exchange of human milk. The numbers of participants, interactions, and comments were analyzed. We observed 954 individuals participating in milk sharing. The number of interactions per individual ranged from none to 16 (mean, 1.74 ± 1.65). Top reasons that participants requested milk included "lactation problems" (69.4%) and "child health problems" (48.5%). Nearly half of donors were offering 100 ounces or more, which is the minimum to be eligible to donate to nonprofit milk banks. Milk sharing networks in the United States are active, with thousands of individuals participating in the direct exchange of raw human milk. Public health issues include increasing the supply of pasteurized donor milk for fragile infants, increasing breastfeeding support, and helping milk sharing families appropriately manage risks.

Neurotoxicants are in the air: convergence of human, animal, and in vitro studies on the effects of air pollution on the brain.

PubMed

Costa, Lucio G; Cole, Toby B; Coburn, Jacki; Chang, Yu-Chi; Dao, Khoi; Roque, Pamela

2014-01-01

In addition to increased morbidity and mortality caused by respiratory and cardiovascular diseases, air pollution may also negatively affect the brain and contribute to central nervous system diseases. Air pollution is a mixture comprised of several components, of which ultrafine particulate matter (UFPM; <100 nm) is of much concern, as these particles can enter the circulation and distribute to most organs, including the brain. A major constituent of ambient UFPM is represented by traffic-related air pollution, mostly ascribed to diesel exhaust (DE). Human epidemiological studies and controlled animal studies have shown that exposure to air pollution may lead to neurotoxicity. In addition to a variety of behavioral abnormalities, two prominent effects caused by air pollution are oxidative stress and neuroinflammation, which are seen in both humans and animals and are confirmed by in vitro studies. Among factors which can affect neurotoxic outcomes, age is considered the most relevant. Human and animal studies suggest that air pollution (and DE) may cause developmental neurotoxicity and may contribute to the etiology of neurodevelopmental disorders, including autistic spectrum disorders. In addition, air pollution exposure has been associated with increased expression of markers of neurodegenerative disease pathologies.

Impact of anthropogenic and natural environmental changes on Echinococcus transmission in Ningxia Hui Autonomous Region, the People’s Republic of China

PubMed Central

2012-01-01

Echinococcus transmission is known to be affected by various environmental factors, which may be modified by human influence or natural events including global warming. Considerable population growth in the last fifty years in Ningxia Hui Autonomous Region (NHAR), the People’s Republic of China (PRC), has led to dramatic increases in deforestation and modified agricultural practices. In turn, this has resulted in many changes in the habitats for the definitive and intermediate hosts of both Echinococcus granulosus and E. multilocularis, which have increased the risks for transmission of both parasites, affecting echinococcosis prevalence and human disease. Ecological environmental changes due to anthropogenic activities and natural events drive Echinococcus transmission and NHAR provides a notable example illustrating how human activity can impact on a parasitic infection of major public health significance. It is very important to continually monitor these environmental (including climatic) factors that drive the distribution of Echinococcus spp. and their impact on transmission to humans because such information is necessary to formulate reliable future public health policy for echinococcosis control programs and to prevent disease spread. PMID:22827890

Dietary blueberry improves cognition among older adults in a randomized, double-blind, placebo-controlled trial

USDA-ARS?s Scientific Manuscript database

As populations shift to include a larger proportion of older adults, the necessity of research targeting older populations is becoming increasingly apparent. Changes in motor coordination during ‘normal’ aging, in animals and humans, include decrements in balance and locomotion. Parallel to alterati...

78 FR 38097 - Publication of General License Related to the Syria Sanctions Program

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-25

... projects to meet basic human needs in Syria, including, but not limited to, drought relief, assistance to... projects; (3) Activities to support education in Syria, including, but not limited to, combating illiteracy, increasing access to education, and assisting education reform projects; (4) Activities to support non...

Biological invasions in forest ecosystems

Treesearch

Andrew M. Liebhold; Eckehard G. Brockerhoff; Susan Kalisz; Martin A. Nuñez; David A. Wardle; Michael J. Wingfield

2017-01-01

Forests play critical roles in global ecosystem processes and provide numerous services to society. But forests are increasingly affected by a variety of human influences, especially those resulting from biological invasions. Species invading forests include woody and herbaceous plants, many animal species including mammals and invertebrates, as well as a variety of...

The Human Factor in Innovation and Productivity Including an Analysis of Hearings on the Human Factor. Report by the Subcommittee on Science, Research and Technology, Transmitted to the Committee on Science and Technology, U.S. House of Representatives, Ninety-Seventh Congress, Second Session. Serial FF.

ERIC Educational Resources Information Center

Congress of the U.S., Washington, DC. House Committee on Science and Technology.

The House Committee on Science and Technology, Subcommittee on Science, Research and Technology, sponsored an American Association for the Advancement of Science seminar (July 28, 1981) and 6 days of hearings (September 9-17, 1981) on "The Human Factor in Innovation and Productivity." These hearings were designed to increase knowledge…

The Protection of the Right to Education by International Law: Including a Systematic Analysis of Article 13 of the International Covenant on Economic, Social and Cultural Rights. International Studies in Human Rights, 82

ERIC Educational Resources Information Center

Beiter, Klaus Dieter

2006-01-01

A trend has emerged of not defining education as a "human right" anymore, but of rather calling it a "human need". This has paved the way for an ever increasing commercialisation of education, excluding the poor from access to education. A problem at a different level is that states often do not know what is expected of them…

Increasing Awareness of Group Privilege with College Students

ERIC Educational Resources Information Center

Stark-Rose, Rose M.; Lokken, Jayne M.; Zarghami, Fatemeh

2009-01-01

A qualitative study was conducted with 850 participants in 36 different classes including Child and Family Studies, Human Relations, Aviation, and Community Studies in a university in the Midwest. The study conducted was based on a simulated discrimination exercise to increase awareness of group privilege and preferential treatment among college…

A Sexual Learning Curriculum for Parents of Young Children.

ERIC Educational Resources Information Center

Green, Kathryn F.; And Others

The aims of this sexual learning curriculum are to increase parents' emotional and intellectual understanding of human sexuality and to improve their ability to talk about sexuality with their children. Specifically, the curriculum attempts to increase parents' awareness that (1) sexuality includes lifestyle choices, body image, gender role,…

Conservation practices to mitigate and adapt to the effects of climate change

USDA-ARS?s Scientific Manuscript database

Greenhouse gases (GHGs) emitted into the atmosphere by human activities have increased radiative forcing and caused an increase in the global mean temperature of approximately 0.74°C over the past century. In terms of soil conservation, expected consequences of future climate change include changes ...

The Gut Microbiota in Immune-Mediated Inflammatory Diseases

PubMed Central

Forbes, Jessica D.; Van Domselaar, Gary; Bernstein, Charles N.

2016-01-01

The collection of microbes and their genes that exist within and on the human body, collectively known as the microbiome has emerged as a principal factor in human health and disease. Humans and microbes have established a symbiotic association over time, and perturbations in this association have been linked to several immune-mediated inflammatory diseases (IMID) including inflammatory bowel disease, rheumatoid arthritis, and multiple sclerosis. IMID is a term used to describe a group of chronic, highly disabling diseases that affect different organ systems. Though a cornerstone commonality between IMID is the idiopathic nature of disease, a considerable portion of their pathobiology overlaps including epidemiological co-occurrence, genetic susceptibility loci and environmental risk factors. At present, it is clear that persons with an IMID are at an increased risk for developing comorbidities, including additional IMID. Advancements in sequencing technologies and a parallel explosion of 16S rDNA and metagenomics community profiling studies have allowed for the characterization of microbiomes throughout the human body including the gut, in a myriad of human diseases and in health. The main challenge now is to determine if alterations of gut flora are common between IMID or, if particular changes in the gut community are in fact specific to a single disease. Herein, we review and discuss the relationships between the gut microbiota and IMID. PMID:27462309

The nutritive and immunoprotective quality of human milk beyond 1 year postpartum: are lactation-duration-based donor exclusions justified?

PubMed

Perrin, Maryanne Tigchelaar; Fogleman, April; Allen, Jonathan C

2013-08-01

Donor human milk is critical for the fragile preterm infant who does not have access to his or her mother's milk, improving survival rates and quality of survival and decreasing hospital stay. Despite the opening of donor milk banks around the world, shortages continue as demand for donor milk exceeds supply. One potential means of increasing supply is by reducing exclusion criteria that prohibit mothers from donating milk based on duration of lactation. Minimal research has been done on the composition of human milk during the second year of lactation, with most research focusing on the nutritive compounds and not the immunoprotective compounds. Several immunoprotective compounds, including lysozyme, lactoferrin, secretory immunoglobulin A, and oligosaccharides, are abundant in human milk compared to bovine-based infant formula and are partially or fully retained during Holder pasteurization, making them an important differentiating feature of donor milk. A PubMed search was conducted to review studies in human milk composition during the second year of lactation. Limitations of existing research include sample collection protocols, small study sizes, and use of populations that may have been at risk for nutritional deficiencies. Stable concentrations of several components were reported including protein, lactose, iron, copper, lactoferrin, and secretory immunoglobulin A. Lysozyme concentration increased during extended lactation, while zinc and calcium concentrations declined into the second year. Conflicting findings were reported on fat content, and no information was available regarding oligosaccharide content. More research is needed to create evidence-based guidelines regarding the nutritive and immunoprotective value of donor milk throughout the course of lactation.

Human-carnivore conflict in China: a review of current approaches with recommendations for improved management.

PubMed

Pettigrew, Melissa; Xie, Yan; Kang, Aili; Rao, Madhu; Goodrich, John; Liu, Tong; Berger, Joshua

2012-06-01

Human-wildlife conflict (HWC) is a conservation concern that increasingly threatens the continued existence of some of the world's most endangered species. With an increase in human population, urban sprawl and subsequent encroachment on wild land, human and wildlife interaction has become inevitable. In the majority of cases, this interaction results in a negative outcome for humans, wildlife or both. In China, these key elements, along with a decrease in wild prey species, have resulted in the expansion of HWC encounters, and the need for alleviating this conflict has become a conservation priority. Loss of human life, livestock and/or crops is most often the catalysts that fuel HWC. Techniques to alleviate conflict around the world have included preventative measures and mitigation techniques, such as financial compensation and other incentive programs. Both types of measures have had variable success. We review the current status of human-carnivore conflict management in China, and, drawing lessons from around the globe, we make recommendations for improving conservation management in China. For example, an increase in law enforcement in nature reserves is vital to reducing human disturbance in prime carnivore habitat, thereby reducing conflict encounters. Also, modifications to current wildlife compensation programs, so that they are linked with preventative measures, will ensure that moral hazards are avoided. Furthermore, investigating the potential for a community self-financed insurance scheme to fund compensation and increasing efforts to restore wild prey populations will improve the outcome for wildlife conservation. Ultimately, HWC management in China will greatly benefit from an integrative approach. © 2012 ISZS, Blackwell Publishing and IOZ/CAS.

Buried waste integrated demonstration human engineered control station. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1994-09-01

This document describes the Human Engineered Control Station (HECS) project activities including the conceptual designs. The purpose of the HECS is to enhance the effectiveness and efficiency of remote retrieval by providing an integrated remote control station. The HECS integrates human capabilities, limitations, and expectations into the design to reduce the potential for human error, provides an easy system to learn and operate, provides an increased productivity, and reduces the ultimate investment in training. The overall HECS consists of the technology interface stations, supporting engineering aids, platform (trailer), communications network (broadband system), and collision avoidance system.

Regulation of human bone sialoprotein gene transcription by platelet-derived growth factor-BB.

PubMed

Mezawa, Masaru; Araki, Shouta; Takai, Hideki; Sasaki, Yoko; Wang, Shuang; Li, Xinyue; Kim, Dong-Soon; Nakayama, Youhei; Ogata, Yorimasa

2009-04-15

Platelet-derived growth factor (PDGF) is produced by mesenchymal cells and released by platelets following aggregation and is synthesized by osteoblasts. In bone, PDGF stimulates proliferation and differentiation of osteoblasts. PDGF also increases bone resorption, most likely by increasing the number of osteoclasts. Bone sialoprotein (BSP) is thought to function in the initial mineralization of bone, selectively expressed by differentiated osteoblast. To determine the molecular mechanisms PDGF regulation of human BSP gene transcription, we have analyzed the effects of PDGF-BB on osteoblast-like Saos2 and ROS17/2.8 cells. PDGF-BB (5 ng/ml) increased BSP mRNA and protein levels at 12 h in Saos2 cells, and induced BSP mRNA expression at 3 h, reached maximal at 12 h in ROS17/2.8 cells. Transient transfection analyses were performed using chimeric constructs of the human BSP gene promoter linked to a luciferase reporter gene. Treatment of Saos2 cells with PDGF-BB (5 ng/ml, 12 h) increased luciferase activities of all constructs between -184LUC to -2672LUC including the human BSP gene promoter. Effects of PDGF-BB abrogated in constructs included 2 bp mutations in the two cAMP response elements (CRE1 and CRE2), activator protein 1(3) (AP1(3)) and shear stress response element 1 (SSRE1). Luciferase activities induced by PDGF-BB were blocked by protein kinase A inhibitor H89 and tyrosine kinase inhibitor herbimycin A. Gel mobility shift analyses showed that PDGF-BB increased binding of CRE1, CRE2, AP1(3) and SSRE1 elements. CRE1- and CRE2-protein complexes were supershifted by CREB1 and phospho-CREB1 antibodies. Notably, AP1(3)-protein complexes were supershifted by c-Fos and JunD, and disrupted by CREB1, phospho-CREB1, c-Jun and Fra2 antibodies. These studies, therefore, demonstrate that PDGF-BB stimulates human BSP transcription by targeting the CRE1, CRE2, AP1(3) and SSRE1 elements in the human BSP gene promoter.

Bayesian Safety Risk Modeling of Human-Flightdeck Automation Interaction

NASA Technical Reports Server (NTRS)

Ancel, Ersin; Shih, Ann T.

2015-01-01

Usage of automatic systems in airliners has increased fuel efficiency, added extra capabilities, enhanced safety and reliability, as well as provide improved passenger comfort since its introduction in the late 80's. However, original automation benefits, including reduced flight crew workload, human errors or training requirements, were not achieved as originally expected. Instead, automation introduced new failure modes, redistributed, and sometimes increased workload, brought in new cognitive and attention demands, and increased training requirements. Modern airliners have numerous flight modes, providing more flexibility (and inherently more complexity) to the flight crew. However, the price to pay for the increased flexibility is the need for increased mode awareness, as well as the need to supervise, understand, and predict automated system behavior. Also, over-reliance on automation is linked to manual flight skill degradation and complacency in commercial pilots. As a result, recent accidents involving human errors are often caused by the interactions between humans and the automated systems (e.g., the breakdown in man-machine coordination), deteriorated manual flying skills, and/or loss of situational awareness due to heavy dependence on automated systems. This paper describes the development of the increased complexity and reliance on automation baseline model, named FLAP for FLightdeck Automation Problems. The model development process starts with a comprehensive literature review followed by the construction of a framework comprised of high-level causal factors leading to an automation-related flight anomaly. The framework was then converted into a Bayesian Belief Network (BBN) using the Hugin Software v7.8. The effects of automation on flight crew are incorporated into the model, including flight skill degradation, increased cognitive demand and training requirements along with their interactions. Besides flight crew deficiencies, automation system failures and anomalies of avionic systems are also incorporated. The resultant model helps simulate the emergence of automation-related issues in today's modern airliners from a top-down, generalized approach, which serves as a platform to evaluate NASA developed technologies

Advanced Good Cell Culture Practice for human primary, stem cell-derived and organoid models as well as microphysiological systems.

PubMed

Pamies, David; Bal-Price, Anna; Chesné, Christophe; Coecke, Sandra; Dinnyes, Andras; Eskes, Chantra; Grillari, Regina; Gstraunthaler, Gerhard; Hartung, Thomas; Jennings, Paul; Leist, Marcel; Martin, Ulrich; Passier, Robert; Schwamborn, Jens C; Stacey, Glyn N; Ellinger-Ziegelbauer, Heidrun; Daneshian, Mardas

2018-04-13

A major reason for the current reproducibility crisis in the life sciences is the poor implementation of quality control measures and reporting standards. Improvement is needed, especially regarding increasingly complex in vitro methods. Good Cell Culture Practice (GCCP) was an effort from 1996 to 2005 to develop such minimum quality standards also applicable in academia. This paper summarizes recent key developments in in vitro cell culture and addresses the issues resulting for GCCP, e.g. the development of induced pluripotent stem cells (iPSCs) and gene-edited cells. It further deals with human stem-cell-derived models and bioengineering of organo-typic cell cultures, including organoids, organ-on-chip and human-on-chip approaches. Commercial vendors and cell banks have made human primary cells more widely available over the last decade, increasing their use, but also requiring specific guidance as to GCCP. The characterization of cell culture systems including high-content imaging and high-throughput measurement technologies increasingly combined with more complex cell and tissue cultures represent a further challenge for GCCP. The increasing use of gene editing techniques to generate and modify in vitro culture models also requires discussion of its impact on GCCP. International (often varying) legislations and market forces originating from the commercialization of cell and tissue products and technologies are further impacting on the need for the use of GCCP. This report summarizes the recommendations of the second of two workshops, held in Germany in December 2015, aiming map the challenge and organize the process or developing a revised GCCP 2.0.

Human Immunodeficiency Virus, Other Sexually Transmitted Infections, and Sexual and Reproductive Health in Lesbian, Gay, Bisexual, Transgender Youth.

PubMed

Wood, Sarah M; Salas-Humara, Caroline; Dowshen, Nadia L

2016-12-01

Lesbian, gay, bisexual, transgender (LGBT), and questioning youth represent a diverse population who are affected by many sexual health inequities, including increased risk for human immunodeficiency virus (HIV) and sexually transmitted infections (STIs). To provide comprehensive sexual health care for LGBT youth, providers should set the stage with a nonjudgmental, respectful tone. Providers should be competent in recognizing symptoms of STIs and HIV and aware of the most up-to-date screening guidelines for LGBT youth. Sexual health visits should also focus on prevention, including safer sex practices, HIV pre-exposure and post-exposure prophylaxis, family planning, and immunization for hepatitis and human papillomavirus. Copyright © 2016 Elsevier Inc. All rights reserved.

Staphylococcus aureus Shifts toward Commensalism in Response to Corynebacterium Species

PubMed Central

Ramsey, Matthew M.; Freire, Marcelo O.; Gabrilska, Rebecca A.; Rumbaugh, Kendra P.; Lemon, Katherine P.

2016-01-01

Staphylococcus aureus–human interactions result in a continuum of outcomes from commensalism to pathogenesis. S. aureus is a clinically important pathogen that asymptomatically colonizes ~25% of humans as a member of the nostril and skin microbiota, where it resides with other bacteria including commensal Corynebacterium species. Commensal Corynebacterium spp. are also positively correlated with S. aureus in chronic polymicrobial diabetic foot infections, distinct from acute monomicrobial S. aureus infections. Recent work by our lab and others indicates that microbe–microbe interactions between S. aureus and human skin/nasal commensals, including Corynebacterium species, affect S. aureus behavior and fitness. Thus, we hypothesized that S. aureus interactions with Corynebacterium spp. diminish S. aureus virulence. We tested this by assaying for changes in S. aureus gene expression during in vitro mono- versus coculture with Corynebacterium striatum, a common skin and nasal commensal. We observed a broad shift in S. aureus gene transcription during in vitro growth with C. striatum, including increased transcription of genes known to exhibit increased expression during human nasal colonization and decreased transcription of virulence genes. S. aureus uses several regulatory pathways to transition between commensal and pathogenic states. One of these, the quorum signal accessory gene regulator (agr) system, was strongly inhibited in response to Corynebacterium spp. Phenotypically, S. aureus exposed to C. striatum exhibited increased adhesion to epithelial cells, reflecting a commensal state, and decreased hemolysin activity, reflecting an attenuation of virulence. Consistent with this, S. aureus displayed diminished fitness in experimental in vivo coinfection with C. striatum when compared to monoinfection. These data support a model in which S. aureus shifts from virulence toward a commensal state when exposed to commensal Corynebacterium species. PMID:27582729

Characterization of the Humoral Immune Response during Staphylococcus aureus Bacteremia and Global Gene Expression by Staphylococcus aureus in Human Blood

PubMed Central

den Reijer, Paul Martijn; Lemmens-den Toom, Nicole; Kant, Samantha; Snijders, Susan V.; Boelens, Hélène; Tavakol, Mehri; Verkaik, Nelianne J.; van Belkum, Alex; Verbrugh, Henri A.; van Wamel, Willem J. B.

2013-01-01

Attempts to develop an efficient anti-staphylococcal vaccine in humans have so far been unsuccessful. Therefore, more knowledge of the antigens that are expressed by Staphylococcus aureus in human blood and induce an immune response in patients is required. In this study we further characterize the serial levels of IgG and IgA antibodies against 56 staphylococcal antigens in multiple serum samples of 21 patients with a S. aureus bacteremia, compare peak IgG levels between patients and 30 non-infected controls, and analyze the expression of 3626 genes by two genetically distinct isolates in human blood. The serum antibody levels were measured using a bead-based flow cytometry technique (xMAP®, Luminex corporation). Gene expression levels were analyzed using a microarray (BµG@s microarray). The initial levels and time taken to reach peak IgG and IgA antibody levels were heterogeneous in bacteremia patients. The antigen SA0688 was associated with the highest median initial-to-peak antibody fold-increase for IgG (5.05-fold) and the second highest increase for IgA (2.07-fold). Peak IgG levels against 27 antigens, including the antigen SA0688, were significantly elevated in bacteremia patients versus controls (P≤0.05). Expression of diverse genes, including SA0688, was ubiquitously high in both isolates at all time points during incubation in blood. However, only a limited number of genes were specifically up- or downregulated in both isolates when cultured in blood, compared to the start of incubation in blood or during incubation in BHI broth. In conclusion, most staphylococcal antigens tested in this study, including many known virulence factors, do not induce uniform increases in the antibody levels in bacteremia patients. In addition, the expression of these antigens by S. aureus is not significantly altered by incubation in human blood over time. One immunogenic and ubiquitously expressed antigen is the putative iron-regulated ABC transporter SA0688. PMID:23308212

Humans to Mars: The Greatest Adventure in Human History

NASA Technical Reports Server (NTRS)

Levine, Joel S.; Schild,Rudy

2011-01-01

The reasons for a human mission to Mars are many and include (1) World technological leadership, (2) Enhanced national security, (3) Enhanced economic vitality, (4) The human urge to explore new and distant frontiers, (5) Scientific discovery (how did Mars evolve from an early Earth-like, hospitable planet to its present inhospitable state? Is there life on Mars?) (6) Inspiring the American public and the next generation of scientists and engineers (following the launch of Sputnik I by the USSR on October 4, 1957, the U. S. and the rest of the world witnessed a significant increase in the number of students going into science and engineering), (7) Develop new technologies for potential non-space spin-off applications, and, (8) Enhanced national prestige, etc. Other reasons for colonizing the Red Planet are more catastrophic in nature, including Mars as a safe haven for the survival of the human species in the event of an impact with a large asteroid (remember the demise of the dinosaurs 65-million years as a result of an asteroid impact!). Some have also suggested that the colonization of Mars may be a solution to the global exponential population explosion on our planet! A human mission to and the colonization of the Red Planet requires multi-disciplined expertise in many areas including engineering, technology, science, human health and medicine and the human psychological and behavior. To capture the relevant areas of needed expertise, we have invited a group of more than 70 U. S. and foreign experts in these areas, including astronauts, scientists, engineers, technologists, medical doctors, psychologists and economists to share their views and thoughts on a human mission to Mars.

Linking environmental nutrient enrichment and disease emergence in humans and wildlife

PubMed Central

Johnson, Pieter T. J.; Townsend, Alan R.; Cleveland, Cory C.; Glibert, Patricia M.; Howarth, Robert W.; McKenzie, Valerie J.; Rejmankova, Eliska; Ward, Mary H.

2009-01-01

Worldwide increases in the numbers of human and wildlife diseases present ecologists with the challenge of understanding how large-scale environmental changes affect host-parasite interactions. One of the most profound changes to Earth’s ecosystems is the alteration of global nutrient cycles, including those of phosphorus (P) and especially nitrogen (N). Alongside the obvious direct benefits of nutrient application for food production, growing evidence suggests that anthropogenic inputs of N and P can indirectly affect the abundance of infectious and noninfectious pathogens, sometimes leading to epidemic conditions. However, the mechanisms underpinning observed correlations, and how such patterns vary with disease type, have long remained conjectural. Here, we discuss recent experimental advances in this area to critically evaluate the relationship between environmental nutrient enrichment and disease. Given the inter-related nature of human and wildlife disease emergence, we include a broad range of human and wildlife examples from terrestrial, marine and freshwater ecosystems. We examine the consequences of nutrient pollution on directly transmitted, vector-borne, complex life cycle, and noninfectious pathogens, including West Nile virus, malaria, harmful algal blooms, coral reef diseases and amphibian malformations. Our synthetic examination suggests that the effects of environmental nutrient enrichment on disease are complex and multifaceted, varying with the type of pathogen, host species and condition, attributes of the ecosystem and the degree of enrichment; some pathogens increase in abundance whereas others decline or disappear. Nevertheless, available evidence indicates that ecological changes associated with nutrient enrichment often exacerbate infection and disease caused by generalist parasites with direct or simple life cycles. Observed mechanisms include changes in host/vector density, host distribution, infection resistance, pathogen virulence or toxicity, or the direct supplementation of pathogens. Collectively, these pathogens may be particularly dangerous because they can continue to cause mortality even as their hosts decline, potentially leading to sustained epidemics or chronic pathology. We suggest that interactions between nutrient enrichment and disease will become increasingly important in tropical and subtropical regions, where forecasted increases in nutrient application will occur in an environment rich with infectious pathogens. We emphasize the importance of careful disease management in conjunction with continued intensification of global nutrient cycles. PMID:20349828

Synthesis, structural characterization and effect on human granulocyte intracellular cAMP levels of abscisic acid analogs.

PubMed

Bellotti, Marta; Salis, Annalisa; Grozio, Alessia; Damonte, Gianluca; Vigliarolo, Tiziana; Galatini, Andrea; Zocchi, Elena; Benatti, Umberto; Millo, Enrico

2015-01-01

The phytohormone abscisic acid (ABA), in addition to regulating physiological functions in plants, is also produced and released by several mammalian cell types, including human granulocytes, where it stimulates innate immune functions via an increase of the intracellular cAMP concentration ([cAMP]i). We synthesized several ABA analogs and evaluated the structure-activity relationship, by the systematical modification of selected regions of these analogs. The resulting molecules were tested for their ability to inhibit the ABA-induced increase of [cAMP]i in human granulocytes. The analogs with modified configurations at C-2' and C-3' abrogated the ABA-induced increase of the [cAMP]i and also inhibited several pro-inflammatory effects induced by exogenous ABA on granulocytes and monocytes. Accordingly, these analogs could be suitable as novel putative anti-inflammatory compounds. Copyright © 2014 Elsevier Ltd. All rights reserved.

Climate Change, Human Rights, and Social Justice.

PubMed

Levy, Barry S; Patz, Jonathan A

2015-01-01

The environmental and health consequences of climate change, which disproportionately affect low-income countries and poor people in high-income countries, profoundly affect human rights and social justice. Environmental consequences include increased temperature, excess precipitation in some areas and droughts in others, extreme weather events, and increased sea level. These consequences adversely affect agricultural production, access to safe water, and worker productivity, and, by inundating land or making land uninhabitable and uncultivatable, will force many people to become environmental refugees. Adverse health effects caused by climate change include heat-related disorders, vector-borne diseases, foodborne and waterborne diseases, respiratory and allergic disorders, malnutrition, collective violence, and mental health problems. These environmental and health consequences threaten civil and political rights and economic, social, and cultural rights, including rights to life, access to safe food and water, health, security, shelter, and culture. On a national or local level, those people who are most vulnerable to the adverse environmental and health consequences of climate change include poor people, members of minority groups, women, children, older people, people with chronic diseases and disabilities, those residing in areas with a high prevalence of climate-related diseases, and workers exposed to extreme heat or increased weather variability. On a global level, there is much inequity, with low-income countries, which produce the least greenhouse gases (GHGs), being more adversely affected by climate change than high-income countries, which produce substantially higher amounts of GHGs yet are less immediately affected. In addition, low-income countries have far less capability to adapt to climate change than high-income countries. Adaptation and mitigation measures to address climate change needed to protect human society must also be planned to protect human rights, promote social justice, and avoid creating new problems or exacerbating existing problems for vulnerable populations. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Historical review of the causes of cancer

PubMed Central

Blackadar, Clarke Brian

2016-01-01

In the early 1900s, numerous seminal publications reported that high rates of cancer occurred in certain occupations. During this period, work with infectious agents produced only meager results which seemed irrelevant to humans. Then in the 1980s ground breaking evidence began to emerge that a variety of viruses also cause cancer in humans. There is now sufficient evidence of carcinogenicity in humans for human T-cell lymphotrophic virus, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, human papillomavirus, Epstein-Barr virus, and human herpes virus 8 according to the International Agency for Research on Cancer (IARC). Many other causes of cancer have also been identified by the IARC, which include: Sunlight, tobacco, pharmaceuticals, hormones, alcohol, parasites, fungi, bacteria, salted fish, wood dust, and herbs. The World Cancer Research Fund and the American Institute for Cancer Research have determined additional causes of cancer, which include beta carotene, red meat, processed meats, low fibre diets, not breast feeding, obesity, increased adult height and sedentary lifestyles. In brief, a historical review of the discoveries of the causes of human cancer is presented with extended discussions of the difficulties encountered in identifying viral causes of cancer. PMID:26862491

Historical review of the causes of cancer.

PubMed

Blackadar, Clarke Brian

2016-02-10

In the early 1900s, numerous seminal publications reported that high rates of cancer occurred in certain occupations. During this period, work with infectious agents produced only meager results which seemed irrelevant to humans. Then in the 1980s ground breaking evidence began to emerge that a variety of viruses also cause cancer in humans. There is now sufficient evidence of carcinogenicity in humans for human T-cell lymphotrophic virus, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, human papillomavirus, Epstein-Barr virus, and human herpes virus 8 according to the International Agency for Research on Cancer (IARC). Many other causes of cancer have also been identified by the IARC, which include: Sunlight, tobacco, pharmaceuticals, hormones, alcohol, parasites, fungi, bacteria, salted fish, wood dust, and herbs. The World Cancer Research Fund and the American Institute for Cancer Research have determined additional causes of cancer, which include beta carotene, red meat, processed meats, low fibre diets, not breast feeding, obesity, increased adult height and sedentary lifestyles. In brief, a historical review of the discoveries of the causes of human cancer is presented with extended discussions of the difficulties encountered in identifying viral causes of cancer.

Frontier In-Situ Resource Utilization for Enabling Sustained Human Presence on Mars

NASA Technical Reports Server (NTRS)

Moses, Robert W.; Bushnell, Dennis M.

2016-01-01

The currently known resources on Mars are massive, including extensive quantities of water and carbon dioxide and therefore carbon, hydrogen and oxygen for life support, fuels and plastics and much else. The regolith is replete with all manner of minerals. In Situ Resource Utilization (ISRU) applicable frontier technologies include robotics, machine intelligence, nanotechnology, synthetic biology, 3-D printing/additive manufacturing and autonomy. These technologies combined with the vast natural resources should enable serious, pre- and post-human arrival ISRU to greatly increase reliability and safety and reduce cost for human colonization of Mars. Various system-level transportation concepts employing Mars produced fuel would enable Mars resources to evolve into a primary center of trade for the inner solar system for eventually nearly everything required for space faring and colonization. Mars resources and their exploitation via extensive ISRU are the key to a viable, safe and affordable, human presence beyond Earth. The purpose of this paper is four-fold: 1) to highlight the latest discoveries of water, minerals, and other materials on Mars that reshape our thinking about the value and capabilities of Mars ISRU; 2) to summarize the previous literature on Mars ISRU processes, equipment, and approaches; 3) to point to frontier ISRU technologies and approaches that can lead to safe and affordable human missions to Mars; and 4) to suggest an implementation strategy whereby the ISRU elements are phased into the mission campaign over time to enable a sustainable and increasing human presence on Mars.

Targeting PIM kinase as a therapeutic strategy in human hepatoblastoma

PubMed Central

Stafman, Laura L.; Mruthyunjayappa, Smitha; Waters, Alicia M.; Garner, Evan F.; Aye, Jamie M.; Stewart, Jerry E.; Yoon, Karina J.; Whelan, Kimberly; Mroczek-Musulman, Elizabeth; Beierle, Elizabeth A.

2018-01-01

Increasing incidence coupled with poor prognosis and treatments that are virtually unchanged over the past 20 years have made the need for the development of novel therapeutics for hepatoblastoma imperative. PIM kinases have been implicated as drivers of tumorigenesis in multiple cancers, including hepatocellular carcinoma. We hypothesized that PIM kinases, specifically PIM3, would play a role in hepatoblastoma tumorigenesis and that PIM kinase inhibition would affect hepatoblastoma in vitro and in vivo. Parameters including cell survival, proliferation, motility, and apoptosis were assessed in human hepatoblastoma cells following PIM3 knockdown with siRNA or treatment with the PIM inhibitor AZD1208. An in vivo model of human hepatoblastoma was utilized to study the effects of PIM inhibition alone and in combination with cisplatin. PIM kinases were found to be present in the human hepatoblastoma cell line, HuH6, and in a human hepatoblastoma patient-derived xenograft, COA67. PIM3 knockdown or inhibition with AZD1208 decreased cell survival, attachment independent growth, and motility. Additionally, inhibition of tumor growth was observed in a hepatoblastoma xenograft model in mice treated with AZD1208. Combination therapy with AZD1208 and cisplatin resulted in a significant increase in animal survival when compared to either treatment alone. The current studies showed that PIM kinase inhibition decreased human hepatoblastoma tumorigenicity both in vitro and in vivo, implying that PIM inhibitors may be useful as a novel therapeutic for children with hepatoblastoma.

The Big Picture.

ERIC Educational Resources Information Center

Naturescope, 1987

1987-01-01

Contains a series of activities which focus on the process of extinction, how the increasing human population affects other species, and on the reasons for helping endangered species. Includes diagrams and illustrations of endangered species. (ML)

Trimeprazine increases IRS2 in human islets and promotes pancreatic β cell growth and function in mice

PubMed Central

Kuznetsova, Alexandra; Yu, Yue; Hollister-Lock, Jennifer; Opare-Addo, Lynn; Rozzo, Aldo; Sadagurski, Marianna; Norquay, Lisa; Reed, Jessica E.; El Khattabi, Ilham; Bonner-Weir, Susan; Weir, Gordon C.; Sharma, Arun

2016-01-01

The capacity of pancreatic β cells to maintain glucose homeostasis during chronic physiologic and immunologic stress is important for cellular and metabolic homeostasis. Insulin receptor substrate 2 (IRS2) is a regulated adapter protein that links the insulin and IGF1 receptors to downstream signaling cascades. Since strategies to maintain or increase IRS2 expression can promote β cell growth, function, and survival, we conducted a screen to find small molecules that can increase IRS2 mRNA in isolated human pancreatic islets. We identified 77 compounds, including 15 that contained a tricyclic core. To establish the efficacy of our approach, one of the tricyclic compounds, trimeprazine tartrate, was investigated in isolated human islets and in mouse models. Trimeprazine is a first-generation antihistamine that acts as a partial agonist against the histamine H1 receptor (H1R) and other GPCRs, some of which are expressed on human islets. Trimeprazine promoted CREB phosphorylation and increased the concentration of IRS2 in islets. IRS2 was required for trimeprazine to increase nuclear Pdx1, islet mass, β cell replication and function, and glucose tolerance in mice. Moreover, trimeprazine synergized with anti-CD3 Abs to reduce the progression of diabetes in NOD mice. Finally, it increased the function of human islet transplants in streptozotocin-induced (STZ-induced) diabetic mice. Thus, trimeprazine, its analogs, or possibly other compounds that increase IRS2 in islets and β cells without adverse systemic effects might provide mechanism-based strategies to prevent the progression of diabetes. PMID:27152363

Amphetamine increases activity but not exploration in humans and mice

PubMed Central

Minassian, Arpi; Young, Jared W.; Cope, Zackary A.; Henry, Brook L.; Geyer, Mark A.; Perry, William

2015-01-01

Rationale Cross-species quantification of physiological behavior enables a better understanding of the biological systems underlying neuropsychiatric diseases such as Bipolar Disorder (BD). Cardinal symptoms of manic BD include increased motor activity and goal-directed behavior, thought to be related to increased catecholamine activity, potentially selective to dopamine homeostatic dysregulation. Objectives The objective of this study was to test whether acute administration of amphetamine, a norepinephrine/dopamine transporter inhibitor and dopamine releaser, would replicate the profile of activity and exploration observed in both humans with manic BD and mouse models of mania. Methods Healthy volunteers with no psychiatric history were randomized to a one-time dose of placebo (n=25), 10 mg d-amphetamine (n=18), or 20 mg amphetamine (n=23). 80 mice were administered one of 4 doses of d-amphetamine or vehicle. Humans and mice were tested in the Behavioral Pattern Monitor (BPM), which quantifies motor activity, exploratory behavior, and spatial patterns of behavior. Results In humans, the 20-mg dose of amphetamine increased motor activity as measured by acceleration without marked effects on exploration or spatial patterns of activity. In mice, amphetamine increased activity, decreased specific exploration, and caused straighter, one-dimensional movements in a dose-dependent manner. Conclusions Consistent with mice, amphetamine increased motoric activity in humans without increasing exploration. Given that BD patients exhibit heightened exploration, these data further emphasize the limitation of amphetamine-induced hyperactivity as a suitable model for BD. Further, these studies highlight the utility of cross-species physiological paradigms in validating biological mechanisms of psychiatric diseases. PMID:26449721

Porcine models of digestive disease: the future of large animal translational research

PubMed Central

Gonzalez, Liara M.; Moeser, Adam J.; Blikslager, Anthony T.

2015-01-01

There is increasing interest in non-rodent translational models for the study of human disease. The pig, in particular, serves as a useful animal model for the study of pathophysiological conditions relevant to the human intestine. This review assesses currently used porcine models of gastrointestinal physiology and disease and provides a rationale for the use of these models for future translational studies. The pig has proven its utility for the study of fundamental disease conditions such as ischemia/ reperfusion injury, stress-induced intestinal dysfunction, and short bowel syndrome. Pigs have also shown great promise for the study of intestinal barrier function, surgical tissue manipulation and intervention, as well as biomaterial implantation and tissue transplantation. Advantages of pig models highlighted by these studies include the physiological similarity to human intestine as well as to mechanisms of human disease. Emerging future directions for porcine models of human disease include the fields of transgenics and stem cell biology, with exciting implications for regenerative medicine. PMID:25655839

Adipogenic Effects and Gene Expression Profiling of Firemaster® 550 Components in Human Primary Preadipocytes

PubMed Central

Tung, Emily W.Y.; Peshdary, Vian; Gagné, Remi; Rowan-Carroll, Andrea; Yauk, Carole L.; Boudreau, Adéle

2017-01-01

Background: Exposure to flame retardants has been associated with negative health outcomes including metabolic effects. As polybrominated diphenyl ether flame retardants were pulled from commerce, human exposure to new flame retardants such as Firemaster® 550 (FM550) has increased. Although previous studies in murine systems have shown that FM550 and its main components increase adipogenesis, the effects of FM550 in human models have not been elucidated. Objectives: The objectives of this study were to determine if FM550 and its components are active in human preadipocytes, and to further investigate their mode of action. Methods: Human primary preadipocytes were differentiated in the presence of FM550 and its components. Differentiation was assessed by lipid accumulation and expression of peroxisome proliferator-activated receptor γ (PPARG), fatty acid binding protein (FABP) 4 and lipoprotein lipase (LPL). mRNA was collected for Poly (A) RNA sequencing and was used to identify differentially expressed genes (DEGs). Functional analysis of DEGs was undertaken in Ingenuity Pathway Analysis. Results: FM550 triphenyl phosphate (TPP) and isopropylated triphenyl phosphates (IPTP), increased adipogenesis in human primary preadipocytes as assessed by lipid accumulation and mRNA expression of regulators of adipogenesis such as PPARγ, CCAAT enhancer binding protein (C/EBP) α and sterol regulatory element binding protein (SREBP) 1 as well as the adipogenic markers FABP4 LPL and perilipin. Poly (A) RNA sequencing analysis revealed potential modes of action including liver X receptor/retinoid X receptor (LXR/RXR) activation, thyroid receptor (TR)/RXR, protein kinase A, and nuclear receptor subfamily 1 group H members activation. Conclusions: We found that FM550, and two of its components, induced adipogenesis in human primary preadipocytes. Further, using global gene expression analysis we showed that both TPP and IPTP likely exert their effects through PPARG to induce adipogenesis. In addition, IPTP perturbed signaling pathways that were not affected by TPP. https://doi.org/10.1289/EHP1318 PMID:28934090

By the Year 2000: First in the World. Report of the FCCSET Committee on Education and Human Resources. FY 1992.

ERIC Educational Resources Information Center

Department of Energy, Washington, DC.

President Bush's budget for fiscal year (FY) 1992 includes $1.94 billion for mathematics, science, and engineering education at the precollege through postdoctoral levels. This is an increase of $225 million or 13 percent over FY 1991. This report from the Committee on Education and Human Resources of the Federal Coordinating Council for Science,…

Continual re-introduction of human pandemic H1N1 influenza A viruses into US swine, 2009-2014

USDA-ARS?s Scientific Manuscript database

Human-to-swine transmission of pandemic H1N1 influenza viruses (pH1N1) increased the genetic diversity of influenza A viruses in swine (swIAVs) globally and is linked to the emergence of new pandemic threats, including H3N2v variants. Through phylogenetic analysis of contemporary swIAVs in the Unit...

Genetics of SLE: evidence from mouse models.

PubMed

Morel, Laurence

2010-06-01

Great progress has been made in the field of lupus genetics in the past few years, notably with the publication of genome-wide association studies in humans and the identification of susceptibility genes (including Fcgr2b, Ly108, Kallikrein genes and Coronin-1A) in mouse models of spontaneous lupus. This influx of new information has revealed an ever-increasing interdependence between the mouse and human systems for unraveling the genetic basis of lupus susceptibility. Studies in the 1980s and 1990s established that mice prone to spontaneous lupus constitute excellent models of the genetic architecture of human systemic lupus erythematosus (SLE). This notion has been greatly strengthened by the convergence of the functional pathways that are defective in both human and murine lupus. Within these pathways, variants in a number of genes have now been shown to be directly associated with lupus in both species. Consequently, mouse models will continue to serve a pre-eminent role in lupus genetics research, with an increased emphasis on mechanistic and molecular studies of human susceptibility alleles.

Animal models of aging research: implications for human aging and age-related diseases.

PubMed

Mitchell, Sarah J; Scheibye-Knudsen, Morten; Longo, Dan L; de Cabo, Rafael

2015-01-01

Aging is characterized by an increasing morbidity and functional decline that eventually results in the death of an organism. Aging is the largest risk factor for numerous human diseases, and understanding the aging process may thereby facilitate the development of new treatments for age-associated diseases. The use of humans in aging research is complicated by many factors, including ethical issues; environmental and social factors; and perhaps most importantly, their long natural life span. Although cellular models of human disease provide valuable mechanistic information, they are limited in that they may not replicate the in vivo biology. Almost all organisms age, and thus animal models can be useful for studying aging. Herein, we review some of the major models currently used in aging research and discuss their benefits and pitfalls, including interventions known to extend life span and health span. Finally, we conclude by discussing the future of animal models in aging research.

Dietary fiber and prebiotics and the gastrointestinal microbiota

PubMed Central

Holscher, Hannah D.

2017-01-01

ABSTRACT The gastrointestinal microbiota has an important role in human health, and there is increasing interest in utilizing dietary approaches to modulate the composition and metabolic function of the microbial communities that colonize the gastrointestinal tract to improve health, and prevent or treat disease. One dietary strategy for modulating the microbiota is consumption of dietary fiber and prebiotics that can be metabolized by microbes in the gastrointestinal tract. Human alimentary enzymes are not able to digest most complex carbohydrates and plant polysaccharides. Instead, these polysaccharides are metabolized by microbes which generate short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate. This article reviews the current knowledge of the impact of fiber and prebiotic consumption on the composition and metabolic function of the human gastrointestinal microbiota, including the effects of physiochemical properties of complex carbohydrates, adequate intake and treatment dosages, and the phenotypic responses related to the composition of the human microbiota. PMID:28165863

The Shigella human challenge model.

PubMed

Porter, C K; Thura, N; Ranallo, R T; Riddle, M S

2013-02-01

Shigella is an important bacterial cause of infectious diarrhoea globally. The Shigella human challenge model has been used since 1946 for a variety of objectives including understanding disease pathogenesis, human immune responses and allowing for an early assessment of vaccine efficacy. A systematic review of the literature regarding experimental shigellosis in human subjects was conducted. Summative estimates were calculated by strain and dose. While a total of 19 studies evaluating nine strains at doses ranging from 10 to 1 × 1010 colony-forming units were identified, most studies utilized the S. sonnei strain 53G and the S. flexneri strain 2457T. Inoculum solution and pre-inoculation buffering has varied over time although diarrhoea attack rates do not appear to increase above 75-80%, and dysentery rates remain fairly constant, highlighting the need for additional dose-ranging studies. Expansion of the model to include additional strains from different serotypes will elucidate serotype and strain-specific outcome variability.

Space engineering

NASA Technical Reports Server (NTRS)

Alexander, Harold L.

1991-01-01

Human productivity was studied for extravehicular tasks performed in microgravity, particularly including in-space assembly of truss structures and other large objects. Human factors research probed the anthropometric constraints imposed on microgravity task performance and the associated workstation design requirements. Anthropometric experiments included reach envelope tests conducted using the 3-D Acoustic Positioning System (3DAPS), which permitted measuring the range of reach possible for persons using foot restraints in neutral buoyancy, both with and without space suits. Much neutral buoyancy research was conducted using the support of water to simulate the weightlessness environment of space. It became clear over time that the anticipated EVA requirement associated with the Space Station and with in-space construction of interplanetary probes would heavily burden astronauts, and remotely operated robots (teleoperators) were increasingly considered to absorb the workload. Experience in human EVA productivity led naturally to teleoperation research into the remote performance of tasks through human controlled robots.

Problems with mitigation translocation of herpetofauna.

PubMed

Sullivan, Brian K; Nowak, Erika M; Kwiatkowski, Matthew A

2015-02-01

Mitigation translocation of nuisance animals is a commonly used management practice aimed at resolution of human-animal conflict by removal and release of an individual animal. Long considered a reasonable undertaking, especially by the general public, it is now known that translocated subjects are negatively affected by the practice. Mitigation translocation is typically undertaken with individual adult organisms and has a much lower success rate than the more widely practiced conservation translocation of threatened and endangered species. Nonetheless, the public and many conservation practitioners believe that because population-level conservation translocations have been successful that mitigation translocation can be satisfactorily applied to a wide variety of human-wildlife conflict situations. We reviewed mitigation translocations of reptiles, including our own work with 3 long-lived species (Gila monsters [Heloderma suspectum], Sonoran desert tortoises [Gopherus morafkai], and western diamond-backed rattlesnakes [Crotalus atrox]). Overall, mitigation translocation had a low success rate when judged either by effects on individuals (in all studies reviewed they exhibited increased movement or increased mortality) or by the success of the resolution of the human-animal conflict (translocated individuals often returned to the capture site). Careful planning and identification of knowledge gaps are critical to increasing success rates in mitigation translocations in the face of increasing pressure to find solutions for species threatened by diverse anthropogenic factors, including climate change and exurban and energy development. © 2014 Society for Conservation Biology.

Cellular uptake of polymeric nanocapsules loaded with ICG by human blood monocytes and human spleen macrophages

NASA Astrophysics Data System (ADS)

Bahmani, Baharak; Jung, Bongsu; Gupta, Sharad; Anvari, Bahman

2010-02-01

Indocyanine green (ICG) is an FDA approved near infrared dye used in assessment of hepatic function and ophthalmological vascular imaging. However, given the rapid clearance of ICG from the blood stream, its imaging and phototherapeutic applications remain very limited. As a potential method to increase circulation time of ICG, and extend its clinical applications, we have encapsulated ICG within polymeric based nanoconstructs whose surface can be coated with various materials including polyethylene glycol (PEG). To gain an understanding of the interaction between ICG-containing nanocapsules (ICG-NCs) and vascular cells, we are characterizing the uptake of the nanocapsules coated with various materials by human peripheral blood monocytes and human spleen macrophages using fluorescence microscopy. Results of these studies will be useful in identifying the appropriate coating material that will result in increased circulation time of ICG-NCs within the vasculature.

The Biology of Aging: Citizen Scientists and Their Pets as a Bridge Between Research on Model Organisms and Human Subjects.

PubMed

Kaeberlein, M

2016-03-01

A fundamental goal of research into the basic mechanisms of aging is to develop translational strategies that improve human health by delaying the onset and progression of age-related pathology. Several interventions have been discovered that increase life span in invertebrate organisms, some of which have similar effects in mice. These include dietary restriction and inhibition of the mechanistic target of rapamycin by treatment with rapamycin. Key challenges moving forward will be to assess the extent to which these and other interventions improve healthy longevity and increase life span in mice and to develop practical strategies for extending this work to the clinic. Companion animals may provide an optimal intermediate between laboratory models and humans. By improving healthy longevity in companion animals, important insights will be gained regarding human aging while improving the quality of life for people and their pets. © The Author(s) 2015.

Potential mechanisms for cancer resistance in elephants and comparative cellular response to DNA damage in humans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abegglen, Lisa M.; Caulin, Aleah F.; Chan, Ashley

Here, evolutionary medicine may provide insights into human physiology and pathophysiology, including tumor biology. To identify mechanisms for cancer resistance in elephants and compare cellular response to DNA damage among elephants, healthy human controls, and cancer-prone patients with Li-Fraumeni syndrome (LFS). Design, Setting, and Participants A comprehensive survey of necropsy data was performed across 36 mammalian species to validate cancer resistance in large and long-lived organisms, including elephants (n=644). The African and Asian elephant genomes were analyzed for potential mechanisms of cancer resistance. Peripheral blood lymphocytes from elephants, healthy human controls, and patients with LFS were tested in vitro inmore » the laboratory for DNA damage response. The study included African and Asian elephants (n=8), patients with LFS (n=10), and age-matched human controls (n=11). Human samples were collected at the University of Utah between June 2014 and July 2015. Exposures Ionizing radiation and doxorubicin. Cancer mortality across species was calculated and compared by body size and life span. The elephant genome was investigated for alterations in cancer-related genes. DNA repair and apoptosis were compared in elephant vs human peripheral blood lymphocytes. Across mammals, cancer mortality did not increase with body size and/or maximum life span (eg, for rock hyrax, 1% [95% CI, 0%-5%]; African wild dog, 8% [95% CI, 0%-16%]; lion, 2% [95% CI, 0%-7%]). Despite their large body size and long life span, elephants remain cancer resistant, with an estimated cancer mortality of 4.81% (95% CI, 3.14%-6.49%), compared with humans, who have 11% to 25% cancer mortality. While humans have 1 copy (2 alleles) of TP53, African elephants have at least 20 copies (40 alleles), including 19 retrogenes (38 alleles) with evidence of transcriptional activity measured by reverse transcription polymerase chain reaction. In response to DNA damage, elephant lymphocytes underwent p53-mediated apoptosis at higher rates than human lymphocytes proportional to TP53 status (ionizing radiation exposure: patients with LFS, 2.71% [95% CI, 1.93%-3.48%] vs human controls, 7.17% [95% CI, 5.91%-8.44%] vs elephants, 14.64% [95% CI, 10.91%-18.37%]; P<.001; doxorubicin exposure: human controls, 8.10% [95% CI, 6.55%-9.66%] vs elephants, 24.77% [95% CI, 23.0%-26.53%]; P<.001). Compared with other mammalian species, elephants appeared to have a lower-than-expected rate of cancer, potentially related to multiple copies of TP53. Compared with human cells, elephant cells demonstrated increased apoptotic response following DNA damage. These findings, if replicated, could represent an evolutionary-based approach for understanding mechanisms related to cancer suppression.« less

Potential mechanisms for cancer resistance in elephants and comparative cellular response to DNA damage in humans

DOE PAGES

Abegglen, Lisa M.; Caulin, Aleah F.; Chan, Ashley; ...

2015-10-08

Here, evolutionary medicine may provide insights into human physiology and pathophysiology, including tumor biology. To identify mechanisms for cancer resistance in elephants and compare cellular response to DNA damage among elephants, healthy human controls, and cancer-prone patients with Li-Fraumeni syndrome (LFS). Design, Setting, and Participants A comprehensive survey of necropsy data was performed across 36 mammalian species to validate cancer resistance in large and long-lived organisms, including elephants (n=644). The African and Asian elephant genomes were analyzed for potential mechanisms of cancer resistance. Peripheral blood lymphocytes from elephants, healthy human controls, and patients with LFS were tested in vitro inmore » the laboratory for DNA damage response. The study included African and Asian elephants (n=8), patients with LFS (n=10), and age-matched human controls (n=11). Human samples were collected at the University of Utah between June 2014 and July 2015. Exposures Ionizing radiation and doxorubicin. Cancer mortality across species was calculated and compared by body size and life span. The elephant genome was investigated for alterations in cancer-related genes. DNA repair and apoptosis were compared in elephant vs human peripheral blood lymphocytes. Across mammals, cancer mortality did not increase with body size and/or maximum life span (eg, for rock hyrax, 1% [95% CI, 0%-5%]; African wild dog, 8% [95% CI, 0%-16%]; lion, 2% [95% CI, 0%-7%]). Despite their large body size and long life span, elephants remain cancer resistant, with an estimated cancer mortality of 4.81% (95% CI, 3.14%-6.49%), compared with humans, who have 11% to 25% cancer mortality. While humans have 1 copy (2 alleles) of TP53, African elephants have at least 20 copies (40 alleles), including 19 retrogenes (38 alleles) with evidence of transcriptional activity measured by reverse transcription polymerase chain reaction. In response to DNA damage, elephant lymphocytes underwent p53-mediated apoptosis at higher rates than human lymphocytes proportional to TP53 status (ionizing radiation exposure: patients with LFS, 2.71% [95% CI, 1.93%-3.48%] vs human controls, 7.17% [95% CI, 5.91%-8.44%] vs elephants, 14.64% [95% CI, 10.91%-18.37%]; P<.001; doxorubicin exposure: human controls, 8.10% [95% CI, 6.55%-9.66%] vs elephants, 24.77% [95% CI, 23.0%-26.53%]; P<.001). Compared with other mammalian species, elephants appeared to have a lower-than-expected rate of cancer, potentially related to multiple copies of TP53. Compared with human cells, elephant cells demonstrated increased apoptotic response following DNA damage. These findings, if replicated, could represent an evolutionary-based approach for understanding mechanisms related to cancer suppression.« less

Potential Mechanisms for Cancer Resistance in Elephants and Comparative Cellular Response to DNA Damage in Humans.

PubMed

Abegglen, Lisa M; Caulin, Aleah F; Chan, Ashley; Lee, Kristy; Robinson, Rosann; Campbell, Michael S; Kiso, Wendy K; Schmitt, Dennis L; Waddell, Peter J; Bhaskara, Srividya; Jensen, Shane T; Maley, Carlo C; Schiffman, Joshua D

2015-11-03

Evolutionary medicine may provide insights into human physiology and pathophysiology, including tumor biology. To identify mechanisms for cancer resistance in elephants and compare cellular response to DNA damage among elephants, healthy human controls, and cancer-prone patients with Li-Fraumeni syndrome (LFS). A comprehensive survey of necropsy data was performed across 36 mammalian species to validate cancer resistance in large and long-lived organisms, including elephants (n = 644). The African and Asian elephant genomes were analyzed for potential mechanisms of cancer resistance. Peripheral blood lymphocytes from elephants, healthy human controls, and patients with LFS were tested in vitro in the laboratory for DNA damage response. The study included African and Asian elephants (n = 8), patients with LFS (n = 10), and age-matched human controls (n = 11). Human samples were collected at the University of Utah between June 2014 and July 2015. Ionizing radiation and doxorubicin. Cancer mortality across species was calculated and compared by body size and life span. The elephant genome was investigated for alterations in cancer-related genes. DNA repair and apoptosis were compared in elephant vs human peripheral blood lymphocytes. Across mammals, cancer mortality did not increase with body size and/or maximum life span (eg, for rock hyrax, 1% [95% CI, 0%-5%]; African wild dog, 8% [95% CI, 0%-16%]; lion, 2% [95% CI, 0%-7%]). Despite their large body size and long life span, elephants remain cancer resistant, with an estimated cancer mortality of 4.81% (95% CI, 3.14%-6.49%), compared with humans, who have 11% to 25% cancer mortality. While humans have 1 copy (2 alleles) of TP53, African elephants have at least 20 copies (40 alleles), including 19 retrogenes (38 alleles) with evidence of transcriptional activity measured by reverse transcription polymerase chain reaction. In response to DNA damage, elephant lymphocytes underwent p53-mediated apoptosis at higher rates than human lymphocytes proportional to TP53 status (ionizing radiation exposure: patients with LFS, 2.71% [95% CI, 1.93%-3.48%] vs human controls, 7.17% [95% CI, 5.91%-8.44%] vs elephants, 14.64% [95% CI, 10.91%-18.37%]; P < .001; doxorubicin exposure: human controls, 8.10% [95% CI, 6.55%-9.66%] vs elephants, 24.77% [95% CI, 23.0%-26.53%]; P < .001). Compared with other mammalian species, elephants appeared to have a lower-than-expected rate of cancer, potentially related to multiple copies of TP53. Compared with human cells, elephant cells demonstrated increased apoptotic response following DNA damage. These findings, if replicated, could represent an evolutionary-based approach for understanding mechanisms related to cancer suppression.

Colloquium paper: uniquely human evolution of sialic acid genetics and biology.

PubMed

Varki, Ajit

2010-05-11

Darwinian evolution of humans from our common ancestors with nonhuman primates involved many gene-environment interactions at the population level, and the resulting human-specific genetic changes must contribute to the "Human Condition." Recent data indicate that the biology of sialic acids (which directly involves less than 60 genes) shows more than 10 uniquely human genetic changes in comparison with our closest evolutionary relatives. Known outcomes are tissue-specific changes in abundant cell-surface glycans, changes in specificity and/or expression of multiple proteins that recognize these glycans, and novel pathogen regimes. Specific events include Alu-mediated inactivation of the CMAH gene, resulting in loss of synthesis of the Sia N-glycolylneuraminic acid (Neu5Gc) and increase in expression of the precursor N-acetylneuraminic acid (Neu5Ac); increased expression of alpha2-6-linked Sias (likely because of changed expression of ST6GALI); and multiple changes in SIGLEC genes encoding Sia-recognizing Ig-like lectins (Siglecs). The last includes binding specificity changes (in Siglecs -5, -7, -9, -11, and -12); expression pattern changes (in Siglecs -1, -5, -6, and -11); gene conversion (SIGLEC11); and deletion or pseudogenization (SIGLEC13, SIGLEC14, and SIGLEC16). A nongenetic outcome of the CMAH mutation is human metabolic incorporation of foreign dietary Neu5Gc, in the face of circulating anti-Neu5Gc antibodies, generating a novel "xeno-auto-antigen" situation. Taken together, these data suggest that both the genes associated with Sia biology and the related impacts of the environment comprise a relative "hot spot" of genetic and physiological changes in human evolution, with implications for uniquely human features both in health and disease.

Bridging Education for Foreign-Trained Professionals: The International Pharmacy Graduate (IPQ) Program in Canada

ERIC Educational Resources Information Center

Austin, Zubin; Dean, Marie Rocchi

2006-01-01

Demand for well-qualified health care professionals (including pharmacists) is projected to increase over the next 10 to 20 years. In many jurisdictions, immigration will become an increasingly important human resource to replace aging, retiring workers and drive ongoing economic prosperity and growth. Higher education has been an underutilized…

The Intrusion of Human Population into Forest and Range Lands of California

Treesearch

Ted D. Bradshaw

1987-01-01

Demographic and economic growth are pushing deeper into California's forest and range lands, making effective fire protection and traditional industrial uses of the land more difficult. Urban forces that will increase the difficulties in the future include: increasing urban population pressures, selective migration, low-priced housing, adequate infrastructure,...

Developing Curriculum for Education of Youth in Meeting Modern Problems.

ERIC Educational Resources Information Center

Dayton Public Schools, OH.

The objectives of this program are to develop, field test, and evaluate a K-12 curriculum containing learner objectives of the following types: (1) increased student knowledge of probable effects resulting from the use, misuse, and abuse of drug substances including alcohol and nicotine; (2) increased student understanding of human behavior; and…

Macro- and Micronutrients of Human Milk Composition: Are They Related to Maternal Diet? A Comprehensive Systematic Review.

PubMed

Keikha, Mojtaba; Bahreynian, Maryam; Saleki, Mohammad; Kelishadi, Roya

2017-11-01

This study aims at systematically reviewing the observational and interventional studies on the association of maternal macro- and micronutrient intake with breast milk content. We systematically searched the Medline via PubMed, Scopus, and ISI Web of Knowledge till October 2016 with the following search strategy: ("human milk" OR "breast milk" OR "breast milk composition" OR "human breast milk composition" OR "composition breast milk" OR "mother milk" OR "human breast milk") AND ("maternal diet" OR "maternal nutrition"). We also searched Google scholar for increasing the sensitivity of our search. The search was not limited to title and abstract due to the possibility that the desired outcome might have been considered a secondary aim. We excluded conference papers, editorials, letters, commentary, short survey, and notes. The search was refined to English language, and we did not consider any time limitation. To increase the sensitivity and to select more studies, the reference list of the published studies was checked as well. This review included 59 observational and 43 interventional studies on maternal diet related to breast milk composition. Different studies determined the associations and effects of some maternal dietary intake of micro and macronutrients and its reflection in human milk. Maternal dietary intake, particularly fatty acids, and some micronutrients, including fat soluble vitamins, vitamin B 1 , and vitamin C, was related to their content in breast milk composition.

The globalization of education in medical ethics and humanities: evolving pedagogy at Weill Cornell Medical College in Qatar.

PubMed

del Pozo, Pablo Rodríguez; Fins, Joseph J

2005-02-01

The authors discuss their experience in implementing a Medical Ethics and Humanities course for premedical students at Weill Cornell Medical College in the Arabian Gulf emirate of Qatar. The course, first offered in 2003, is designed to prepare these students for the medical school curriculum to follow and to make global medical knowledge meaningful for their local context. Pedagogical challenges included the cross-cultural tensions that could emerge when introducing themes from Western medical ethics and humanities into this overwhelmingly Islamic context. The authors outline the response to this challenge and strategies to broaden student inquiry without engaging in indoctrination. This seminar-based course was designed around seven thematic areas of increasing biopsychosocial complexity, from nature and biology, to the patient, the physician, and the family, to broader questions of hospital care, the health care system, and the place of law in modern medicine. Readings from the literature of the Western and Arabic traditions were used, including selections by Hippocrates, Thomas, Kafka, Mahfouz, and Pellegrino. It is too early to know the ultimate impact of the course, but students demonstrated enthusiasm for ethics and the medical humanities and a willingness to consider new and novel ways of knowing. The authors anticipate that this grounding in the humanities will complement the students' work in the sciences and help further develop their nascent professional identities in an increasingly global medical community.

Issues in protection of human subjects in internet research.

PubMed

Im, Eun-Ok; Chee, Wonshik

2002-01-01

Despite the increasing use of the Internet among nurses, the use of the Internet in nursing research has been rarely discussed and critiqued in terms of issues in protection of human subjects. In this article, issues in protection of human subjects in Internet research are explored by analyzing an Internet study to propose directions for human protection in Internet research. Issues raised through the study include those related to (a) anonymity and confidentiality, (b) security, (c) self-determination and authenticity, (d) full disclosure, and (e) fair treatment. Based on discussion of the five issues, development of standardized guidelines, investigator triangulation, and information sharing are proposed as directions for protection of human subjects in Internet research.

Insights into Modern Human Prehistory Using Ancient Genomes.

PubMed

Yang, Melinda A; Fu, Qiaomei

2018-03-01

The genetic relationship of past modern humans to today's populations and each other was largely unknown until recently, when advances in ancient DNA sequencing allowed for unprecedented analysis of the genomes of these early people. These ancient genomes reveal new insights into human prehistory not always observed studying present-day populations, including greater details on the genetic diversity, population structure, and gene flow that characterized past human populations, particularly in early Eurasia, as well as increased insight on the relationship between archaic and modern humans. Here, we review genetic studies on ∼45000- to 7500-year-old individuals associated with mainly preagricultural cultures found in Eurasia, the Americas, and Africa. Copyright © 2017 Elsevier Ltd. All rights reserved.

Agronomic Approach of Zinc Biofortification Can Increase Zinc Bioavailability in Wheat Flour and thereby Reduce Zinc Deficiency in Humans

PubMed Central

Liu, Dunyi; Liu, Yumin; Zhang, Wei; Chen, Xinping; Zou, Chunqin

2017-01-01

Zinc (Zn) deficiency is a common disorder of humans in developing countries. The effect of Zn biofortification (via application of six rates of Zn fertilizer to soil) on Zn bioavailability in wheat grain and flour and its impacts on human health was evaluated. Zn bioavailability was estimated with a trivariate model that included Zn homeostasis in the human intestine. As the rate of Zn fertilization increased, the Zn concentration increased in all flour fractions, but the percentages of Zn in standard flour (25%) and bran (75%) relative to total grain Zn were constant. Phytic acid (PA) concentrations in grain and flours were unaffected by Zn biofortification. Zn bioavailability and the health impact, as indicated by disability-adjusted life years (DALYs) saved, increased with the Zn application rate and were greater in standard and refined flour than in whole grain and coarse flour. The biofortified standard and refined flour obtained with application of 50 kg/ha ZnSO4·7H2O met the health requirement (3 mg of Zn obtained from 300 g of wheat flour) and reduced DALYs by >20%. Although Zn biofortification increased Zn bioavailability in standard and refined flour, it did not reduce the bioavailability of iron, manganese, or copper in wheat flour. PMID:28481273

Agronomic Approach of Zinc Biofortification Can Increase Zinc Bioavailability in Wheat Flour and thereby Reduce Zinc Deficiency in Humans.

PubMed

Liu, Dunyi; Liu, Yumin; Zhang, Wei; Chen, Xinping; Zou, Chunqin

2017-05-06

Zinc (Zn) deficiency is a common disorder of humans in developing countries. The effect of Zn biofortification (via application of six rates of Zn fertilizer to soil) on Zn bioavailability in wheat grain and flour and its impacts on human health was evaluated. Zn bioavailability was estimated with a trivariate model that included Zn homeostasis in the human intestine. As the rate of Zn fertilization increased, the Zn concentration increased in all flour fractions, but the percentages of Zn in standard flour (25%) and bran (75%) relative to total grain Zn were constant. Phytic acid (PA) concentrations in grain and flours were unaffected by Zn biofortification. Zn bioavailability and the health impact, as indicated by disability-adjusted life years (DALYs) saved, increased with the Zn application rate and were greater in standard and refined flour than in whole grain and coarse flour. The biofortified standard and refined flour obtained with application of 50 kg/ha ZnSO₄·7H₂O met the health requirement (3 mg of Zn obtained from 300 g of wheat flour) and reduced DALYs by >20%. Although Zn biofortification increased Zn bioavailability in standard and refined flour, it did not reduce the bioavailability of iron, manganese, or copper in wheat flour.

Altered Virome and Bacterial Microbiome in Human Immunodeficiency Virus-Associated Acquired Immunodeficiency Syndrome

PubMed Central

Monaco, Cynthia L.; Gootenberg, David B.; Zhao, Guoyan; Handley, Scott A.; Ghebremichael, Musie S.; Lim, Efrem S.; Lankowski, Alex; Baldridge, Megan T.; Wilen, Craig B.; Flagg, Meaghan; Norman, Jason M.; Keller, Brian C.; Luévano, Jesús Mario; Wang, David; Boum, Yap; Martin, Jeffrey N.; Hunt, Peter W.; Bangsberg, David R.; Siedner, Mark J.; Kwon, Douglas S.; Virgin, Herbert W.

2016-01-01

SUMMARY Human immunodeficiency virus (HIV) infection is associated with increased intestinal translocation of microbial products and enteropathy as well as alterations in gut bacterial communities. However, whether the enteric virome contributes to this infection and resulting immunodeficiency remains unknown. We characterized the enteric virome and bacterial microbiome in a cohort of Ugandan patients, including HIV-uninfected or HIV-infected subjects and those either treated with anti-retroviral therapy (ART) or untreated. Low peripheral CD4 T cell counts were associated with an expansion of enteric adenovirus sequences and this increase was independent of ART treatment. Additionally, the enteric bacterial microbiome of patients with lower CD4 T counts exhibited reduced phylogenetic diversity and richness with specific bacteria showing differential abundance, including increases in Enterobacteriaceae, which have been associated with inflammation. Thus, immunodeficiency in progressive HIV infection is associated with alterations in the enteric virome and bacterial microbiome, which may contribute to AIDS-associated enteropathy and disease progression. PMID:26962942

Altered Virome and Bacterial Microbiome in Human Immunodeficiency Virus-Associated Acquired Immunodeficiency Syndrome.

PubMed

Monaco, Cynthia L; Gootenberg, David B; Zhao, Guoyan; Handley, Scott A; Ghebremichael, Musie S; Lim, Efrem S; Lankowski, Alex; Baldridge, Megan T; Wilen, Craig B; Flagg, Meaghan; Norman, Jason M; Keller, Brian C; Luévano, Jesús Mario; Wang, David; Boum, Yap; Martin, Jeffrey N; Hunt, Peter W; Bangsberg, David R; Siedner, Mark J; Kwon, Douglas S; Virgin, Herbert W

2016-03-09

Human immunodeficiency virus (HIV) infection is associated with increased intestinal translocation of microbial products and enteropathy as well as alterations in gut bacterial communities. However, whether the enteric virome contributes to this infection and resulting immunodeficiency remains unknown. We characterized the enteric virome and bacterial microbiome in a cohort of Ugandan patients, including HIV-uninfected or HIV-infected subjects and those either treated with anti-retroviral therapy (ART) or untreated. Low peripheral CD4 T cell counts were associated with an expansion of enteric adenovirus sequences and this increase was independent of ART treatment. Additionally, the enteric bacterial microbiome of patients with lower CD4 T counts exhibited reduced phylogenetic diversity and richness with specific bacteria showing differential abundance, including increases in Enterobacteriaceae, which have been associated with inflammation. Thus, immunodeficiency in progressive HIV infection is associated with alterations in the enteric virome and bacterial microbiome, which may contribute to AIDS-associated enteropathy and disease progression. Copyright © 2016 Elsevier Inc. All rights reserved.

Bioaccessibility, release kinetics, and molecular speciation of arsenic and lead in geo-dusts from the Iron King Mine Federal Superfund site in Humboldt, Arizona.

PubMed

Menka, Nazune; Root, Rob; Chorover, Jon

2014-01-01

Mine tailings contain multiple toxic metal(loid)s that pose a threat to human health via inhalation and ingestion. The goals of this research include understanding the speciation and molecular environment of these toxic metal(loid)s (arsenic and lead) as well as the impacts particle size and residence time have on their bioaccessibilty in simulated gastric and lung fluid. Additionally, future work will include smaller size fractions (PM10 and PM2.5) of surface mine tailings, with the goal of increasing our understanding of multi-metal release from contaminated geo-dusts in simulated bio-fluids. This research is important to environmental human health risk assessment as it increases the accuracy of exposure estimations to toxic metal(loid)s.

Epigenetics in Paediatric Gastroenterology, Hepatology, and Nutrition: Present Trends and Future Perspectives.

PubMed

Zilbauer, Matthias; Zellos, Aglaia; Heuschkel, Robert; Gasparetto, Marco; Kraiczy, Judith; Postberg, Jan; Greco, Luigi; Auricchio, Renata; Galatola, Martina; Embleton, Nicholas; Wirth, Stefan; Jenke, Andreas

2016-04-01

Epigenetics can be defined as stable, potentially heritable changes in the cellular phenotype caused by mechanisms other than alterations to the underlying DNA sequence. As such, any observed phenotypic changes including organ development, aging, and the occurrence of disease could be driven by epigenetic mechanisms in the presence of stable cellular DNA sequences. Indeed, with the exception of rare mutations, the human genome-sequence has remained remarkably stable over the past centuries. In contrast, substantial changes to our environment as part of our modern life style have not only led to a significant reduction of certain infectious diseases but also seen the exponential increase in complex traits including obesity and multifactorial diseases such as autoimmune disorders. It is becoming increasingly clear that epigenetic mechanisms operate at the interface between the genetic code and our environment, and a large body of existing evidence supports the importance of environmental factors such as diet and nutrition, infections, and exposure to toxins on human health. This seems to be particularly the case during vulnerable periods of human development such as pregnancy and early life. Importantly, as the first point of contact for many of such environmental factors including nutrition, the digestive system is being increasingly linked to a number of "modern" pathologies. In this review article, we aim to give a brief introduction to the basic molecular principals of epigenetics and provide a concise summary of the existing evidence for the role of epigenetic mechanisms in gastrointestinal health and disease, hepatology, and nutrition.

Trend of toxocariasis in Iran: a review on human and animal dimensions

PubMed Central

Zibaei, M.; Sadjjadi, S. M.

2017-01-01

One of the neglected soil and/or food-borne diseases with international public health importance is toxocariasis. Human cases are being increasingly reported from Asian, African, Oceania, European and the American countries. Hence, human toxocariasis (HT) is now considered as a major zoonosis with global and regional importance. In Iran, human and animal toxocariasis is an endemic disease with clinical and epidemiologic health problem aspects. Doubtless, understanding the epidemiology and the trend of this important parasitic disease and its affecting factors will provide the establishment of effective prevention and control programs. To better understand the trend of toxocariasis researches in Iran, this study was performed to analyze different aspects of this zoonotic disease including history, life cycle, species, human animals and environmental studies, diagnostic aspects and treatments to find out the gaps, including different aspects of clinical sings in human patients, new and specific recombinant antigens based on the native antigens, new diagnostic tools, especially rapid diagnostic tests, paratenic hosts status and new treatment procedures which is necessary to be investigated in the future studies on this important zoonotic disease. PMID:29387094

Nous sommes tous des bacteries: implications for medicine, pharmacology and public health.

PubMed

Triggle, David J

2012-12-15

As a species we humans are outnumbered by bacteria in both cell and gene count. This somewhat humbling observation is key to the increasing recognition that the long-standing symbiotic and commensal relations between Homo sapiens and bacteria are of great significance to basic human physiology and health. Knowledge of our human bacterial environment is contributing to an understanding of a variety of disorders including obesity and metabolic syndrome, cardiovascular disease, immunity, and neuronal development and behavior. The Human Microbiome Project is providing a genetic and ecological analysis and will serve as a parallel to the Human Genome Project. Exploration of the chemical space utilized by bacteria will contribute to the development of new small molecule therapeutic agents, including new antibiotics. And genetically re-engineered bacteria are proving to be of potential value as actual therapeutic entities. Our understanding of our bacterial world has the capability to transform radically our current approach to human health diverting it from an emphasis on acute treatments to living in healthy harmony with both our internal and external environments. Copyright © 2012 Elsevier Inc. All rights reserved.

Human babesiosis in Europe: what clinicians need to know.

PubMed

Hildebrandt, A; Gray, J S; Hunfeld, K-P

2013-12-01

Although best known as an animal disease, human babesiosis is attracting increasing attention as a worldwide emerging zoonosis. Humans are commonly infected by the bite of ixodid ticks. Rare ways of transmission are transplacental, perinatal and transfusion-associated. Infection of the human host can cause a very severe host-mediated pathology including fever, and hemolysis leading to anemia, hyperbilirubinuria, hemoglobinuria and possible organ failure. In recent years, apparently owing to increased medical awareness and better diagnostic methods, the number of reported cases in humans is rising steadily worldwide. Hitherto unknown zoonotic Babesia spp. are now being reported from geographic areas where babesiosis was not previously known to occur and the growing numbers of travelers and immunocompromised individuals suggest that the frequency of cases in Europe will also continue to rise. Our review is intended to provide clinicians with practical information on the clinical management of this rare, but potentially life-threatening zoonotic disease. It covers epidemiology, phylogeny, diagnostics and treatment of human babesiosis and the potential risk of transfusion-transmitted disease with a special focus on the European situation.

A systematic review on the herbal extract Tribulus terrestris and the roots of its putative aphrodisiac and performance enhancing effect.

PubMed

Qureshi, Ahmed; Naughton, Declan P; Petroczi, Andrea

2014-03-01

Tribulus terrestris (TT) is a dicotyledonous herbal plant of the Zygophyllaceae family. In ancient medicine, extracts of the aerial parts and fruits have been used for its diuretic, tonic, and aphrodisiac properties. Today, TT is widely used by athletes and bodybuilders based on the belief, fueled by claims in marketing information, that it can enhance testosterone concentrations. To assess TT's effect on testosterone levels in human and animals, an electronic literature search out using seven databases and the patent database up to August 2013 was carried out. Randomized control trials, which included healthy human subjects ingesting TT as sole or combined supplement, along with animal studies with TT as a sole treatment across a number of species were included. Eleven studies met the inclusion criteria, including one patent application. The results showed that trials varied in duration, dosage and supplementation with TT as sole or combined treatment, rendering meta-analysis impossible. A limited number of animal studies displayed a significant increase in serum testosterone levels after TT administration, but this effect was only noted in humans when TT was part of a combined supplement administration. Literature available for the effectiveness of TT on enhancing testosterone concentrations is limited. Evidence to date suggests that TT is ineffective for increasing testosterone levels in humans, thus marketing claims are unsubstantiated. The nitric oxide release effect of TT may offer a plausible explanation for the observed physiological responses to TT supplementation, independent of the testosterone level.

Effect of Catalase and Sodium Fluoride on Human Enamel bleached with 35% Carbamide Peroxide

PubMed Central

Shigli, Anand L; Sharma, Divya S; Thakur, Gagan

2015-01-01

ABSTRACT Aim: To evaluate the effects of postbleaching antioxidant application fluoridation treatment on the surface morphology and microhardness of human enamel. Materials and methods: Ten freshly extracted human maxillary central incisors were cut at cementoenamel junction. Crown portion was sectioned into six slabs which were divided into five groups: group A – untreated controls; group B – 35% carbamide peroxide (CP); group C – 35% CP and catalase; group D – treatment with 35% CP and 5% sodium fluoride; group E – 35% CP, catalase and 5% sodium fluoride. Thirty-five percent carbamide peroxide application included two applications of 30 minutes each at a 5-day interval. After treatment, the slabs were thoroughly washed with water for 10 seconds and stored in artificial saliva at 37°C until the next treatment. Two percent sodium fluoride included application for 5 minutes. Three catalase included application for 3 minutes. Results: After 5 days, groups B and C showed significantly decreased enamel microhardness compared to control. Group D specimens showed relatively less reduction in enamel micro-hardness than group C specimens. There is a marked increase in enamel microhardness in group E specimens. Conclusions: Fluoride take up was comparatively enhanced after catalase application resulting in less demineralization and increased microhardness. How to cite this article: Thakur R, Shigli AL, Sharma DS, Thakur G. Effect of Catalase and Sodium Fluoride on Human Enamel bleached with 35% Carbamide Peroxide. Int J Clin Pediatr Dent 2015;8(1):12-17. PMID:26124575

Indirubin, a component of Ban-Lan-Gen, activates CYP3A4 gene transcription through the human pregnane X receptor.

PubMed

Kumagai, Takeshi; Aratsu, Yusuke; Sugawara, Ryosuke; Sasaki, Takamitsu; Miyairi, Shinichi; Nagata, Kiyoshi

2016-04-01

Ban-Lan-Gen is the common name for the dried roots of indigo plants, including Polygonum tinctorium, Isatis indigotica, Isatis tinctoria, and Strobilanthes cusia. Ban-Lan-Gen is frequently used as an anti-inflammatory and an anti-viral for the treatment of hepatitis, influenza, and various types of inflammation. One of the cytochrome P450 (CYP) enzymes, CYP3A4, is responsible for the metabolism of a wide variety of xenobiotics, including an estimated 60% of all clinically used drugs. In this study, we investigated the effect of Ban-Lan-Gen on the transcriptional activation of the CYP3A4 gene. Ban-Lan-Gen extract increased CYP3A4 gene reporter activity in a dose-dependent manner. Indirubin, one of the biologically active ingredients in the Ban-Lan-Gen, also dose-dependently increased CYP3A4 gene reporter activity. Expression of short hairpin RNA for the human pregnane X receptor (hPXR-shRNA) inhibited CYP3A4 gene reporter activity, and overexpression of human PXR increased indirubin- and rifampicin-induced CYP3A4 gene reporter activity. Furthermore, indirubin induced CYP3A4 mRNA expression in HepG2 cells. Taken together, these results indicate that indirubin, a component of Ban-Lan-Gen, activated CYP3A4 gene transcription through the activation of the human PXR. Copyright © 2016. Published by Elsevier Ltd.

Three-Dimensionally Engineered Normal Human Lung Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

NASA Technical Reports Server (NTRS)

Goodwin, Thomas J.; McCarthy, M.; Lin, Y-H.; Deatly, A. M.

2008-01-01

In vitro three-dimensional (3D) human lung epithelio-mesenchymal tissue-like assemblies (3D hLEM TLAs) from this point forward referred to as TLAs were engineered in Rotating Wall Vessel (RWV) technology to mimic the characteristics of in vivo tissues thus providing a tool to study human respiratory viruses and host cell interactions. The TLAs were bioengineered onto collagen-coated cyclodextran microcarriers using primary human mesenchymal bronchial-tracheal cells (HBTC) as the foundation matrix and an adult human bronchial epithelial immortalized cell line (BEAS-2B) as the overlying component. The resulting TLAs share significant characteristics with in vivo human respiratory epithelium including polarization, tight junctions, desmosomes, and microvilli. The presence of tissue-like differentiation markers including villin, keratins, and specific lung epithelium markers, as well as the production of tissue mucin, further confirm these TLAs differentiated into tissues functionally similar to in vivo tissues. Increasing virus titers for human respiratory syncytial virus (wtRSVA2) and the detection of membrane bound glycoproteins over time confirm productive infection with the virus. Therefore, we assert TLAs mimic aspects of the human respiratory epithelium and provide a unique capability to study the interactions of respiratory viruses and their primary target tissue independent of the host s immune system.

Opening our eyes to a critical approach to medicine: The humanities in medical education.

PubMed

Liao, Lester

2017-02-01

This paper examines a recent medical graduate's perspective on how undergraduate education tends to focus on imparting medical knowledge with little reference to the human aspects in clinical medicine. This is problematic because medicine is both about people and practiced by people. Students often have minimal exposure to the humanities prior to and in medical school and are frequently unaware of the societal trends that impact their view of medical practice. Familiarity with the humanities is a crucial means to understanding human nature, recognizing personal sociocultural biases, and practicing patient-centered medicine. This gap in knowledge may be due to the increase in medical information and optimistic ideologies related to medical progress. Philosophical paradigms and historical examples are considered to demonstrate the relevance of both fields in the humanities in understanding the role of moral human agents in applying medical knowledge. Educational changes in the humanities are proposed as a potential solution to our current deficits. Informal changes include mentorship relationships and shifting the general underpinning attitude in medical culture. Formal changes include specific courses teaching a critical approach to medicine. Changes in competency-based education and admissions are also suggested. These amendments are proposed to practice a fuller, truly human medicine.

Three-Dimensionally Engineered Normal Human Broncho-epithelial Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

NASA Technical Reports Server (NTRS)

Goodwin, T. J.; McCarthy, M.; Lin, Y-H

2006-01-01

In vitro three-dimensional (3D) human broncho-epithelial (HBE) tissue-like assemblies (3D HBE TLAs) from this point forward referred to as TLAs were engineered in Rotating Wall Vessel (RWV) technology to mimic the characteristics of in vivo tissues thus providing a tool to study human respiratory viruses and host cell interactions. The TLAs were bioengineered onto collagen-coated cyclodextran microcarriers using primary human mesenchymal bronchial-tracheal cells (HBTC) as the foundation matrix and an adult human bronchial epithelial immortalized cell line (BEAS-2B) as the overlying component. The resulting TLAs share significant characteristics with in vivo human respiratory epithelium including polarization, tight junctions, desmosomes, and microvilli. The presence of tissue-like differentiation markers including villin, keratins, and specific lung epithelium markers, as well as the production of tissue mucin, further confirm these TLAs differentiated into tissues functionally similar to in vivo tissues. Increasing virus titers for human respiratory syncytial virus (wtRSVA2) and parainfluenza virus type 3 (wtPIV3 JS) and the detection of membrane bound glycoproteins over time confirm productive infections with both viruses. Therefore, TLAs mimic aspects of the human respiratory epithelium and provide a unique capability to study the interactions of respiratory viruses and their primary target tissue independent of the host's immune system.

Potential future scenarios for Australia's native biodiversity given on-going increases in human population.

PubMed

Pepper, D A; Lada, Hania; Thomson, James R; Bakar, K Shuvo; Lake, P S; Mac Nally, Ralph

2017-01-15

Most natural assets, including native biodiversity (our focus), are under increasing threat from direct (loss of habitat, hunting) and indirect (climate change) human actions. Most human impacts arise from increasing human populations coupled with rises in per capita resource use. The rates of change of human actions generally outpace those to which the biota can respond or adapt. If we are to maintain native biodiversity, then we must develop ways to envisage how the biota may be affected over the next several decades to guide management and policy responses. We consider the future for Australia's native biodiversity in the context of two assumptions. First, the human population in Australia will be 40million by 2050, which has been mooted by federal government agencies. Second, greenhouse gas emissions will track the highest rates considered by the Intergovernmental Panel on Climate Change. The scenarios are based on major drivers of change, which were constructed from seven key drivers of change pertinent to native biodiversity. Five scenarios deal with differing distributions of the human population driven by uncertainties in climate change and in the human responses to climate change. Other scenarios are governed largely by global change and explore different rates of resource use, unprecedented rates of technological change, capabilities and societal values. A narrative for each scenario is provided. The set of scenarios spans a wide range of possible future paths for Australia, with different implications for the future of native biodiversity. Copyright © 2016 Elsevier B.V. All rights reserved.

From bedside to bench and back again: research issues in animal models of human disease.

PubMed

Tkacs, Nancy C; Thompson, Hilaire J

2006-07-01

To improve outcomes for patients with many serious clinical problems, multifactorial research approaches by nurse scientists, including the use of animal models, are necessary. Animal models serve as analogies for clinical problems seen in humans and must meet certain criteria, including validity and reliability, to be useful in moving research efforts forward. This article describes research considerations in the development of rodent models. As the standard of diabetes care evolves to emphasize intensive insulin therapy, rates of severe hypoglycemia are increasing among patients with type 1 and type 2 diabetes mellitus. A consequence of this change in clinical practice is an increase in rates of two hypoglycemia-related diabetes complications: hypoglycemia-associated autonomic failure (HAAF) and resulting hypoglycemia unawareness. Work on an animal model of HAAF is in an early developmental stage, with several labs reporting different approaches to model this complication of type 1 diabetes mellitus. This emerging model serves as an example illustrating how evaluation of validity and reliability is critically important at each stage of developing and testing animal models to support inquiry into human disease.

Parathyroid hormone regulation of the human bone sialoprotein gene transcription is mediated through two cAMP response elements.

PubMed

Araki, Shouta; Mezawa, Masaru; Sasaki, Yoko; Yang, Li; Li, Zhengyang; Takai, Hideki; Nakayama, Youhei; Ogata, Yorimasa

2009-03-01

Parathyroid hormone (PTH) regulates serum calcium and inorganic phosphate levels through its actions on kidney and bone. Bone sialoprotein (BSP) is an early marker of osteoblast differentiation and bone metabolism. We here report that two cAMP response elements (CRE) in the human BSP gene promoter are target of PTH. In human osteoblast-like Saos2 cells, PTH (human 1-34 PTH, 10 nM) increased BSP mRNA and protein levels at 3 h. From transient transfection assays, 2- to 2.5-fold increase in transcription by PTH was observed at 3 and 6 h in -184, -211, -428, -868, and -927 luciferase constructs that included the human BSP gene promoter. Effect of PTH was abrogated by 2 bp mutations in either the CRE1 (-79 to -72) or CRE2 (-674 to -667). Luciferase activities induced by PTH were blocked by protein kinase A inhibitor H89 and tyrosine kinase inhibitor herbimycin A. Gel shift analyses showed that PTH increased binding of nuclear proteins to the CRE1 and CRE2 elements. The CRE1-protein and CRE2-protein complexes were disrupted by CRE binding protein 1 (CREB1) antibodies and supershifted by phospho-CREB1 antibody. ChIP assays detected binding of CREB1 and phospho-CREB1 to a chromatin fragment containing CRE1 and CRE2, and increased binding of phospho-CREB1 to the both sites. These studies demonstrate that PTH stimulates human BSP gene transcription by targeting the two CREs in the promoter of the human BSP gene.

A multi-scale study of Orthoptera species richness and human population size controlling for sampling effort

NASA Astrophysics Data System (ADS)

Cantarello, Elena; Steck, Claude E.; Fontana, Paolo; Fontaneto, Diego; Marini, Lorenzo; Pautasso, Marco

2010-03-01

Recent large-scale studies have shown that biodiversity-rich regions also tend to be densely populated areas. The most obvious explanation is that biodiversity and human beings tend to match the distribution of energy availability, environmental stability and/or habitat heterogeneity. However, the species-people correlation can also be an artefact, as more populated regions could show more species because of a more thorough sampling. Few studies have tested this sampling bias hypothesis. Using a newly collated dataset, we studied whether Orthoptera species richness is related to human population size in Italy’s regions (average area 15,000 km2) and provinces (2,900 km2). As expected, the observed number of species increases significantly with increasing human population size for both grain sizes, although the proportion of variance explained is minimal at the provincial level. However, variations in observed Orthoptera species richness are primarily associated with the available number of records, which is in turn well correlated with human population size (at least at the regional level). Estimated Orthoptera species richness (Chao2 and Jackknife) also increases with human population size both for regions and provinces. Both for regions and provinces, this increase is not significant when controlling for variation in area and number of records. Our study confirms the hypothesis that broad-scale human population-biodiversity correlations can in some cases be artefactual. More systematic sampling of less studied taxa such as invertebrates is necessary to ascertain whether biogeographical patterns persist when sampling effort is kept constant or included in models.

Rapid evolution of the cerebellum in humans and other great apes.

PubMed

Barton, Robert A; Venditti, Chris

2014-10-20

Humans' unique cognitive abilities are usually attributed to a greatly expanded neocortex, which has been described as "the crowning achievement of evolution and the biological substrate of human mental prowess". The human cerebellum, however, contains four times more neurons than the neocortex and is attracting increasing attention for its wide range of cognitive functions. Using a method for detecting evolutionary rate changes along the branches of phylogenetic trees, we show that the cerebellum underwent rapid size increase throughout the evolution of apes, including humans, expanding significantly faster than predicted by the change in neocortex size. As a result, humans and other apes deviated significantly from the general evolutionary trend for neocortex and cerebellum to change in tandem, having significantly larger cerebella relative to neocortex size than other anthropoid primates. These results suggest that cerebellar specialization was a far more important component of human brain evolution than hitherto recognized and that technical intelligence was likely to have been at least as important as social intelligence in human cognitive evolution. Given the role of the cerebellum in sensory-motor control and in learning complex action sequences, cerebellar specialization is likely to have underpinned the evolution of humans' advanced technological capacities, which in turn may have been a preadaptation for language. Copyright © 2014 Elsevier Ltd. All rights reserved.

Global effects of local human population density and distance to markets on the condition of coral reef fisheries.

PubMed

Cinner, Joshua E; Graham, Nicholas A J; Huchery, Cindy; Macneil, M Aaron

2013-06-01

Coral reef fisheries support the livelihoods of millions of people but have been severely and negatively affected by anthropogenic activities. We conducted a systematic review of published data on the biomass of coral reef fishes to explore how the condition of reef fisheries is related to the density of local human populations, proximity of the reef to markets, and key environmental variables (including broad geomorphologic reef type, reef area, and net productivity). When only population density and environmental covariates were considered, high variability in fisheries conditions at low human population densities resulted in relatively weak explanatory models. The presence or absence of human settlements, habitat type, and distance to fish markets provided a much stronger explanatory model for the condition of reef fisheries. Fish biomass remained relatively low within 14 km of markets, then biomass increased exponentially as distance from reefs to markets increased. Our results suggest the need for an increased science and policy focus on markets as both a key driver of the condition of reef fisheries and a potential source of solutions. © 2012 Society for Conservation Biology.

Similarity increases altruistic punishment in humans

PubMed Central

Mussweiler, Thomas; Ockenfels, Axel

2013-01-01

Humans are attracted to similar others. As a consequence, social networks are homogeneous in sociodemographic, intrapersonal, and other characteristics—a principle called homophily. Despite abundant evidence showing the importance of interpersonal similarity and homophily for human relationships, their behavioral correlates and cognitive foundations are poorly understood. Here, we show that perceived similarity substantially increases altruistic punishment, a key mechanism underlying human cooperation. We induced (dis)similarity perception by manipulating basic cognitive mechanisms in an economic cooperation game that included a punishment phase. We found that similarity-focused participants were more willing to punish others’ uncooperative behavior. This influence of similarity is not explained by group identity, which has the opposite effect on altruistic punishment. Our findings demonstrate that pure similarity promotes reciprocity in ways known to encourage cooperation. At the same time, the increased willingness to punish norm violations among similarity-focused participants provides a rationale for why similar people are more likely to build stable social relationships. Finally, our findings show that altruistic punishment is differentially involved in encouraging cooperation under pure similarity vs. in-group conditions. PMID:24218611

Patient safety - the role of human factors and systems engineering.

PubMed

Carayon, Pascale; Wood, Kenneth E

2010-01-01

Patient safety is a global challenge that requires knowledge and skills in multiple areas, including human factors and systems engineering. In this chapter, numerous conceptual approaches and methods for analyzing, preventing and mitigating medical errors are described. Given the complexity of healthcare work systems and processes, we emphasize the need for increasing partnerships between the health sciences and human factors and systems engineering to improve patient safety. Those partnerships will be able to develop and implement the system redesigns that are necessary to improve healthcare work systems and processes for patient safety.

Early convergence research and education supported by the National Science Foundation.

PubMed

Bainbridge, William Sims

2004-05-01

The following pages describe research grants awarded by the National Science Foundation that illustrate how different fields of science and technology can converge in order to increase human potential. Technological convergence involves the unification of the sciences of Nanotechnology, Biotechnology, Information Technology, and new technologies based on Cognitive Science (NBIC). Because it supports research across all major branches of science and technology, including the social and behavioral sciences, the NSF has been a focus of discussions about converging technologies to enhance human capabilities and serve human needs.

Human factors in spacecraft design

NASA Technical Reports Server (NTRS)

Harrison, Albert A.; Connors, Mary M.

1990-01-01

This paper describes some of the salient implications of evolving mission parameters for spacecraft design. Among the requirements for future spacecraft are new, higher standards of living, increased support of human productivity, and greater accommodation of physical and cultural variability. Design issues include volumetric allowances, architecture and layouts, closed life support systems, health maintenance systems, recreational facilities, automation, privacy, and decor. An understanding of behavioral responses to design elements is a precondition for critical design decisions. Human factors research results must be taken into account early in the course of the design process.

Role of tachykinins in bronchial hyper-responsiveness.

PubMed

Reynolds, P N; Holmes, M D; Scicchitano, R

1997-01-01

1. Sensory afferent fibres mediate important protective reflexes in the lung. Small, unmyelinated C-fibre nerves have both sensory afferent and effector functions. C-fibres contain a number of neuropeptides, including the tachykinins, which have pro-inflammatory effects in the airways. Following stimulation with capsaicin and other stimuli, neuropeptides are released from the nerve endings, either directly or by axonal reflexes. 2. Important tachykinin effects include smooth muscle contraction, vasodilatation and oedema, mucus secretion and inflammatory cell activation. There are also trophic effects, including proliferation of fibroblasts, smooth muscle and epithelial cells. 3. Tachykinins mediate their effects by binding to G-proteinlinked receptors. Receptor-specific agonists and antagonists are available, which have helped clarify the effects of tachykinins. These agents may have therapeutic potential. 4. Tachykinins are degraded by the enzyme neutral endo-peptidase. 5. Studies in humans in vivo show an increase in airways resistance following challenge with tachykinins. There is some evidence for an increase in tachykinins and their receptors in airway inflammation, but this has not been found in all studies. A reduction in neutral endopeptidase has been seen in some animal models of airway inflammation, but this has not been shown in human disease. 6. Trials of tachykinin receptor antagonists in human asthma have begun, but it is too early to say what their therapeutic impact will be.

Genome Comparison of Human and Non-Human Malaria Parasites Reveals Species Subset-Specific Genes Potentially Linked to Human Disease

PubMed Central

Frech, Christian; Chen, Nansheng

2011-01-01

Genes underlying important phenotypic differences between Plasmodium species, the causative agents of malaria, are frequently found in only a subset of species and cluster at dynamically evolving subtelomeric regions of chromosomes. We hypothesized that chromosome-internal regions of Plasmodium genomes harbour additional species subset-specific genes that underlie differences in human pathogenicity, human-to-human transmissibility, and human virulence. We combined sequence similarity searches with synteny block analyses to identify species subset-specific genes in chromosome-internal regions of six published Plasmodium genomes, including Plasmodium falciparum, Plasmodium vivax, Plasmodium knowlesi, Plasmodium yoelii, Plasmodium berghei, and Plasmodium chabaudi. To improve comparative analysis, we first revised incorrectly annotated gene models using homology-based gene finders and examined putative subset-specific genes within syntenic contexts. Confirmed subset-specific genes were then analyzed for their role in biological pathways and examined for molecular functions using publicly available databases. We identified 16 genes that are well conserved in the three primate parasites but not found in rodent parasites, including three key enzymes of the thiamine (vitamin B1) biosynthesis pathway. Thirteen genes were found to be present in both human parasites but absent in the monkey parasite P. knowlesi, including genes specifically upregulated in sporozoites or gametocytes that could be linked to parasite transmission success between humans. Furthermore, we propose 15 chromosome-internal P. falciparum-specific genes as new candidate genes underlying increased human virulence and detected a currently uncharacterized cluster of P. vivax-specific genes on chromosome 6 likely involved in erythrocyte invasion. In conclusion, Plasmodium species harbour many chromosome-internal differences in the form of protein-coding genes, some of which are potentially linked to human disease and thus promising leads for future laboratory research. PMID:22215999

Zoonotic infections in Alaska: disease prevalence, potential impact of climate change and recommended actions for earlier disease detection, research, prevention and control.

PubMed

Hueffer, Karsten; Parkinson, Alan J; Gerlach, Robert; Berner, James

2013-01-01

Over the last 60 years, Alaska's mean annual temperature has increased by 1.6°C, more than twice the rate of the rest of the United States. As a result, climate change impacts are more pronounced here than in other regions of the United States. Warmer temperatures may allow some infected host animals to survive winters in larger numbers, increase their population and expand their range of habitation thus increasing the opportunity for transmission of infection to humans. Subsistence hunting and gathering activities may place rural residents of Alaska at a greater risk of acquiring zoonotic infections than urban residents. Known zoonotic diseases that occur in Alaska include brucellosis, toxoplasmosis, trichinellosis, giardiasis/cryptosporidiosis, echinococcosis, rabies and tularemia. Actions for early disease detection, research and prevention and control include: (1) determining baseline levels of infection and disease in both humans and host animals; (2) conducting more research to understand the ecology of infection in the Arctic environment; (3) improving active and passive surveillance systems for infection and disease in humans and animals; (4) improving outreach, education and communication on climate-sensitive infectious diseases at the community, health and animal care provider levels; and (5) improving coordination between public health and animal health agencies, universities and tribal health organisations.

Climate-water quality relationships in Texas reservoirs

USGS Publications Warehouse

Gelca, Rodica; Hayhoe, Katharine; Scott-Fleming, Ian; Crow, Caleb; Dawson, D.; Patino, Reynaldo

2015-01-01

Water temperature, dissolved oxygen, and concentrations of salts in surface water bodies can be affected by the natural environment, local human activities such as surface and ground water withdrawals, land use, and energy extraction, and variability and long-term trends in atmospheric conditions including temperature and precipitation. Here, we quantify the relationship between 121 indicators of mean and extreme temperature and precipitation and 24 water quality parameters in 57 Texas reservoirs using observational data records covering the period 1960 to 2010. We find that water temperature, dissolved oxygen, pH, specific conductance, chloride, sulfate, and phosphorus all show consistent correlations with atmospheric predictors, including high and low temperature extremes, dry days, heavy precipitation events, and mean temperature and precipitation over time scales ranging from one week to two years. Based on this analysis and published future projections for this region, we expect climate change to increase water temperatures, decrease dissolved oxygen levels, decrease pH, increase specific conductance, and increase levels of sulfate, chloride in Texas reservoirs. Over decadal time scales, this may affect aquatic ecosystems in the reservoirs, including altering the risk of conditions conducive to algae occurrence, as well as affecting the quality of water available for human consumption and recreation.

Training trainers in health and human rights: implementing curriculum change in South African health sciences institutions.

PubMed

Ewert, Elena G; Baldwin-Ragaven, Laurel; London, Leslie

2011-07-25

The complicity of the South African health sector in apartheid and the international relevance of human rights as a professional obligation prompted moves to include human rights competencies in the curricula of health professionals in South Africa. A Train-the-Trainers course in Health and Human Rights was established in 1998 to equip faculty members from health sciences institutions nationwide with the necessary skills, attitudes and knowledge to teach human rights to their students. This study followed up participants to determine the extent of curriculum implementation, support needed as well as barriers encountered in integrating human rights into health sciences teaching and learning. A survey including both quantitative and qualitative components was distributed in 2007 to past course participants from 1998-2006 via telephone, fax and electronic communication. Out of 162 past participants, 46 (28%) completed the survey, the majority of whom were still employed in academic settings (67%). Twenty-two respondents (48%) implemented a total of 33 formal human rights courses into the curricula at their institutions. Respondents were nine times more likely (relative risk 9.26; 95% CI 5.14-16.66) to implement human rights education after completing the training. Seventy-two extracurricular activities were offered by 21 respondents, many of whom had successfully implemented formal curricula. Enabling factors for implementation included: prior teaching experience in human rights, general institutional support and the presence of allies - most commonly coworkers as well as deans. Frequently cited barriers to implementation included: budget restrictions, time constraints and perceived apathy of colleagues or students. Overall, respondents noted personal enrichment and optimism in teaching human rights. This Train-the-Trainer course provides the historical context, educational tools, and collective motivation to incorporate human rights educational initiatives at health sciences institutions. Increased implementation of human rights instruction, both formally and extracurricularly, has demonstrated the training's significance not only within academic institutions but more broadly across the health sector. Coworkers are vital allies in teaching human rights to health sciences students, helping to alleviate institutional barriers. Training fellow staff members and those in key leadership roles is noted as vital to the sustainability of human rights education.

Training Trainers in health and human rights: Implementing curriculum change in South African health sciences institutions

PubMed Central

2011-01-01

Background The complicity of the South African health sector in apartheid and the international relevance of human rights as a professional obligation prompted moves to include human rights competencies in the curricula of health professionals in South Africa. A Train-the-Trainers course in Health and Human Rights was established in 1998 to equip faculty members from health sciences institutions nationwide with the necessary skills, attitudes and knowledge to teach human rights to their students. This study followed up participants to determine the extent of curriculum implementation, support needed as well as barriers encountered in integrating human rights into health sciences teaching and learning. Methods A survey including both quantitative and qualitative components was distributed in 2007 to past course participants from 1998-2006 via telephone, fax and electronic communication. Results Out of 162 past participants, 46 (28%) completed the survey, the majority of whom were still employed in academic settings (67%). Twenty-two respondents (48%) implemented a total of 33 formal human rights courses into the curricula at their institutions. Respondents were nine times more likely (relative risk 9.26; 95% CI 5.14-16.66) to implement human rights education after completing the training. Seventy-two extracurricular activities were offered by 21 respondents, many of whom had successfully implemented formal curricula. Enabling factors for implementation included: prior teaching experience in human rights, general institutional support and the presence of allies - most commonly coworkers as well as deans. Frequently cited barriers to implementation included: budget restrictions, time constraints and perceived apathy of colleagues or students. Overall, respondents noted personal enrichment and optimism in teaching human rights. Conclusion This Train-the-Trainer course provides the historical context, educational tools, and collective motivation to incorporate human rights educational initiatives at health sciences institutions. Increased implementation of human rights instruction, both formally and extracurricularly, has demonstrated the training's significance not only within academic institutions but more broadly across the health sector. Coworkers are vital allies in teaching human rights to health sciences students, helping to alleviate institutional barriers. Training fellow staff members and those in key leadership roles is noted as vital to the sustainability of human rights education. PMID:21787421

Human body burdens of chemicals used in plastic manufacture

PubMed Central

Koch, Holger M.; Calafat, Antonia M.

2009-01-01

In the last decades, the availability of sophisticated analytical chemistry techniques has facilitated measuring trace levels of multiple environmental chemicals in human biological matrices (i.e. biomonitoring) with a high degree of accuracy and precision. As biomonitoring data have become readily available, interest in their interpretation has increased. We present an overview on the use of biomonitoring in exposure and risk assessment using phthalates and bisphenol A as examples of chemicals used in the manufacture of plastic goods. We present and review the most relevant research on biomarkers of exposure for phthalates and bisphenol A, including novel and most comprehensive biomonitoring data from Germany and the United States. We discuss several factors relevant for interpreting and understanding biomonitoring data, including selection of both biomarkers of exposure and human matrices, and toxicokinetic information. PMID:19528056

Evidence of a chimpanzee-sized ancestor of humans but a gibbon-sized ancestor of apes.

PubMed

Grabowski, Mark; Jungers, William L

2017-10-12

Body mass directly affects how an animal relates to its environment and has a wide range of biological implications. However, little is known about the mass of the last common ancestor (LCA) of humans and chimpanzees, hominids (great apes and humans), or hominoids (all apes and humans), which is needed to evaluate numerous paleobiological hypotheses at and prior to the root of our lineage. Here we use phylogenetic comparative methods and data from primates including humans, fossil hominins, and a wide sample of fossil primates including Miocene apes from Africa, Europe, and Asia to test alternative hypotheses of body mass evolution. Our results suggest, contrary to previous suggestions, that the LCA of all hominoids lived in an environment that favored a gibbon-like size, but a series of selective regime shifts, possibly due to resource availability, led to a decrease and then increase in body mass in early hominins from a chimpanzee-sized LCA.The pattern of body size evolution in hominids can provide insight into historical human ecology. Here, Grabowski and Jungers use comparative phylogenetic analysis to reconstruct the likely size of the ancestor of humans and chimpanzees and the evolutionary history of selection on body size in primates.

Human organoid cultures: transformative new tools for human virus studies.

PubMed

Ramani, Sasirekha; Crawford, Sue E; Blutt, Sarah E; Estes, Mary K

2018-04-01

Studies of human infectious diseases have been limited by the paucity of functional models that mimic normal human physiology and pathophysiology. Recent advances in the development of multicellular, physiologically active organotypic cultures produced from embryonic and pluripotent stem cells, as well as from stem cells isolated from biopsies and surgical specimens are allowing unprecedented new studies and discoveries about host-microbe interactions. Here, we summarize recent developments in the use of organoids for studying human viral pathogens, including intestinal infections with human rotavirus, norovirus, enteroviruses and adenoviruses (intestinal organoids and enteroids), neuronal infections with Zika virus (cerebral organoids) and respiratory infections with respiratory syncytial virus in (lung bud organoids). Biologic discovery of host-specific genetic and epigenetic factors affecting infection, and responses to infection that lead to disease are possible with the use of organoid cultures. Continued development to increase the complexity of these cultures by including components of the normal host tissue microenvironment such as immune cells, blood vessels and microbiome, will facilitate studies on human viral pathogenesis, and advance the development of platforms for pre-clinical evaluation of vaccines, antivirals and therapeutics. Copyright © 2018 Elsevier B.V. All rights reserved.

Frog decline, frog malformations, and a comparison of frog and human health.

PubMed

Cohen, M M

2001-11-22

The decline in frog populations and the increase in the frequency of frog malformations are discussed. Topics considered for analysis include chytridiomycosis, retinoids, UV-B radiation, chemical contaminants, environmental threats, introduced invasive species and predation, unsustainable use, and enigmatic decline. Care must be taken to distinguish between hypotheses, laboratory experiments, and the findings in feral frog populations. Clearly, the causes of population decline and malformations are heterogeneous. The subject of frogs and humans is addressed under three subheadings: the importance of frogs to human societies, medical implications of frog studies, and a comparison of frog and human disease factors. Copyright 2001 Wiley-Liss, Inc.

The effects of gut microbiota on CNS function in humans

PubMed Central

Tillisch, Kirsten

2014-01-01

The role of the gastrointestinal microbiota in human brain development and function is an area of increasing interest and research. Preclinical models suggest a role for the microbiota in broad aspects of human health, including mood, cognition, and chronic pain. Early human studies suggest that altering the microbiota with beneficial bacteria, or probiotics, can lead to changes in brain function, as well as subjective reports of mood. As the mechanisms of bidirectional communication between the brain and microbiota are better understood, it is expected that these pathways will be harnessed to provide novel methods to enhance health and treat disease. PMID:24838095

"Bird biting" mosquitoes and human disease: a review of the role of Culex pipiens complex mosquitoes in epidemiology.

PubMed

Farajollahi, Ary; Fonseca, Dina M; Kramer, Laura D; Marm Kilpatrick, A

2011-10-01

The transmission of vector-borne pathogens is greatly influenced by the ecology of their vector, which is in turn shaped by genetic ancestry, the environment, and the hosts that are fed on. One group of vectors, the mosquitoes in the Culex pipiens complex, play key roles in the transmission of a range of pathogens including several viruses such as West Nile and St. Louis encephalitis viruses, avian malaria (Plasmodium spp.), and filarial worms. The Cx. pipiens complex includes Culex pipiens pipiens with two forms, pipiens and molestus, Culex pipiens pallens, Culex quinquefasciatus, Culex australicus, and Culex globocoxitus. While several members of the complex have limited geographic distributions, Cx. pipienspipiens and Cx. quinquefasciatus are found in all known urban and sub-urban temperate and tropical regions, respectively, across the world, where they are often principal disease vectors. In addition, hybrids are common in areas of overlap. Although gaps in our knowledge still remain, the advent of genetic tools has greatly enhanced our understanding of the history of speciation, domestication, dispersal, and hybridization. We review the taxonomy, genetics, evolution, behavior, and ecology of members of the Cx. pipiens complex and their role in the transmission of medically important pathogens. The adaptation of Cx. pipiens complex mosquitoes to human-altered environments led to their global distribution through dispersal via humans and, combined with their mixed feeding patterns on birds and mammals (including humans), increased the transmission of several avian pathogens to humans. We highlight several unanswered questions that will increase our ability to control diseases transmitted by these mosquitoes. Copyright © 2011 Elsevier B.V. All rights reserved.

Multidrug-resistant pathogens in the food supply.

PubMed

Doyle, Marjorie E

2015-04-01

Antimicrobial resistance, including multidrug resistance (MDR), is an increasing problem globally. MDR bacteria are frequently detected in humans and animals from both more- and less-developed countries and pose a serious concern for human health. Infections caused by MDR microbes may increase morbidity and mortality and require use of expensive drugs and prolonged hospitalization. Humans may be exposed to MDR pathogens through exposure to environments at health-care facilities and farms, livestock and companion animals, human food, and exposure to other individuals carrying MDR microbes. The Centers for Disease Control and Prevention classifies drug-resistant foodborne bacteria, including Campylobacter, Salmonella Typhi, nontyphoidal salmonellae, and Shigella, as serious threats. MDR bacteria have been detected in both meat and fresh produce. Salmonellae carrying genes coding for resistance to multiple antibiotics have caused numerous foodborne MDR outbreaks. While there is some level of resistance to antimicrobials in environmental bacteria, the widespread use of antibiotics in medicine and agriculture has driven the selection of a great variety of microbes with resistance to multiple antimicrobials. MDR bacteria on meat may have originated in veterinary health-care settings or on farms where animals are given antibiotics in feed or to treat infections. Fresh produce may be contaminated by irrigation or wash water containing MDR bacteria. Livestock, fruits, and vegetables may also be contaminated by food handlers, farmers, and animal caretakers who carry MDR bacteria. All potential sources of MDR bacteria should be considered and strategies devised to reduce their presence in foods. Surveillance studies have documented increasing trends in MDR in many pathogens, although there are a few reports of the decline of certain multidrug pathogens. Better coordination of surveillance programs and strategies for controlling use of antimicrobials need to be implemented in both human and animal medicine and agriculture and in countries around the world.

Pathology of the Aging Brain in Domestic and Laboratory Animals, and Animal Models of Human Neurodegenerative Diseases.

PubMed

Youssef, S A; Capucchio, M T; Rofina, J E; Chambers, J K; Uchida, K; Nakayama, H; Head, E

2016-03-01

According to the WHO, the proportion of people over 60 years is increasing and expected to reach 22% of total world's population in 2050. In parallel, recent animal demographic studies have shown that the life expectancy of pet dogs and cats is increasing. Brain aging is associated not only with molecular and morphological changes but also leads to different degrees of behavioral and cognitive dysfunction. Common age-related brain lesions in humans include brain atrophy, neuronal loss, amyloid plaques, cerebrovascular amyloid angiopathy, vascular mineralization, neurofibrillary tangles, meningeal osseous metaplasia, and accumulation of lipofuscin. In aging humans, the most common neurodegenerative disorder is Alzheimer's disease (AD), which progressively impairs cognition, behavior, and quality of life. Pathologic changes comparable to the lesions of AD are described in several other animal species, although their clinical significance and effect on cognitive function are poorly documented. This review describes the commonly reported age-associated neurologic lesions in domestic and laboratory animals and the relationship of these lesions to cognitive dysfunction. Also described are the comparative interspecies similarities and differences to AD and other human neurodegenerative diseases including Parkinson's disease and progressive supranuclear palsy, and the spontaneous and transgenic animal models of these diseases. © The Author(s) 2016.

Neurotoxicants Are in the Air: Convergence of Human, Animal, and In Vitro Studies on the Effects of Air Pollution on the Brain

PubMed Central

Costa, Lucio G.; Cole, Toby B.; Coburn, Jacki; Chang, Yu-Chi; Dao, Khoi; Roque, Pamela

2014-01-01

In addition to increased morbidity and mortality caused by respiratory and cardiovascular diseases, air pollution may also negatively affect the brain and contribute to central nervous system diseases. Air pollution is a mixture comprised of several components, of which ultrafine particulate matter (UFPM; <100 nm) is of much concern, as these particles can enter the circulation and distribute to most organs, including the brain. A major constituent of ambient UFPM is represented by traffic-related air pollution, mostly ascribed to diesel exhaust (DE). Human epidemiological studies and controlled animal studies have shown that exposure to air pollution may lead to neurotoxicity. In addition to a variety of behavioral abnormalities, two prominent effects caused by air pollution are oxidative stress and neuroinflammation, which are seen in both humans and animals and are confirmed by in vitro studies. Among factors which can affect neurotoxic outcomes, age is considered the most relevant. Human and animal studies suggest that air pollution (and DE) may cause developmental neurotoxicity and may contribute to the etiology of neurodevelopmental disorders, including autistic spectrum disorders. In addition, air pollution exposure has been associated with increased expression of markers of neurodegenerative disease pathologies. PMID:24524086

Structural and Biochemical Consequences of Disease-Causing Mutations in the Ankyrin Repeat Domain of the Human TRPV4 Channel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Inada, Hitoshi; Procko, Erik; Sotomayor, Marcos

2012-10-23

The TRPV4 calcium-permeable cation channel plays important physiological roles in osmosensation, mechanosensation, cell barrier formation, and bone homeostasis. Recent studies reported that mutations in TRPV4, including some in its ankyrin repeat domain (ARD), are associated with human inherited diseases, including neuropathies and skeletal dysplasias, probably because of the increased constitutive activity of the channel. TRPV4 activity is regulated by the binding of calmodulin and small molecules such as ATP to the ARD at its cytoplasmic N-terminus. We determined structures of ATP-free and -bound forms of human TRPV4-ARD and compared them with available TRPV-ARD structures. The third inter-repeat loop region (Fingermore » 3 loop) is flexible and may act as a switch to regulate channel activity. Comparisons of TRPV-ARD structures also suggest an evolutionary link between ARD structure and ATP binding ability. Thermal stability analyses and molecular dynamics simulations suggest that ATP increases stability in TRPV-ARDs that can bind ATP. Biochemical analyses of a large panel of TRPV4-ARD mutations associated with human inherited diseases showed that some impaired thermal stability while others weakened ATP binding ability, suggesting molecular mechanisms for the diseases.« less

A Single-Batch Fermentation System to Simulate Human Colonic Microbiota for High-Throughput Evaluation of Prebiotics

PubMed Central

Sasaki, Daisuke; Fukuda, Itsuko; Tanaka, Kosei; Yoshida, Ken-ichi; Kondo, Akihiko; Osawa, Ro

2016-01-01

We devised a single-batch fermentation system to simulate human colonic microbiota from fecal samples, enabling the complex mixture of microorganisms to achieve densities of up to 1011 cells/mL in 24 h. 16S rRNA gene sequence analysis of bacteria grown in the system revealed that representatives of the major phyla, including Bacteroidetes, Firmicutes, and Actinobacteria, as well as overall species diversity, were consistent with those of the original feces. On the earlier stages of fermentation (up to 9 h), trace mixtures of acetate, lactate, and succinate were detectable; on the later stages (after 24 h), larger amounts of acetate accumulated along with some of propionate and butyrate. These patterns were similar to those observed in the original feces. Thus, this system could serve as a simple model to simulate the diversity as well as the metabolism of human colonic microbiota. Supplementation of the system with several prebiotic oligosaccharides (including fructo-, galacto-, isomalto-, and xylo-oligosaccharides; lactulose; and lactosucrose) resulted in an increased population in genus Bifidobacterium, concomitant with significant increases in acetate production. The results suggested that this fermentation system may be useful for in vitro, pre-clinical evaluation of the effects of prebiotics prior to testing in humans. PMID:27483470

Spatiotemporal dynamics of urban green spaces and human-wildlife conflicts in Tokyo

NASA Astrophysics Data System (ADS)

Hosaka, Tetsuro; Numata, Shinya

2016-08-01

Although urban green spaces are increasingly important both for humans and wildlife, an increase in urban green spaces may also increase human-wildlife conflicts in urban areas. However, few studies have examined the relationship between the size of green spaces and the level of conflicts with wildlife in multiple taxa, including invertebrates and vertebrates. To better understand current pest statistics and predict changes that will occur as the area of green spaces increases, we analysed a dataset compiling the number of pest consultations in 53 metropolitan districts in Tokyo over a 20-year period and its relationships with the area of green space. Stinging insects (e.g., wasps) made up over 50% of pest consultations, followed (in order) by rats and other nuisance animals (e.g., snakes). The number of consultations per unit population did not correlate, or was even negatively correlated, with the proportions of green spaces (mainly forest) for many indoor pests, but did positively correlate for some outdoor pests, such as wasps and snakes. Therefore, wasps and snakes can increase when urban green spaces increase. Because even minor nuisances are relevant for urban lifestyles, considerations of ways to minimise conflicts with wildlife are critical for urban green space management.

Global modeling of withdrawal, allocation and consumptive use of surface water and groundwater resources

NASA Astrophysics Data System (ADS)

Wada, Y.; Wisser, D.; Bierkens, M. F. P.

2014-01-01

To sustain growing food demand and increasing standard of living, global water withdrawal and consumptive water use have been increasing rapidly. To analyze the human perturbation on water resources consistently over large scales, a number of macro-scale hydrological models (MHMs) have been developed in recent decades. However, few models consider the interaction between terrestrial water fluxes, and human activities and associated water use, and even fewer models distinguish water use from surface water and groundwater resources. Here, we couple a global water demand model with a global hydrological model and dynamically simulate daily water withdrawal and consumptive water use over the period 1979-2010, using two re-analysis products: ERA-Interim and MERRA. We explicitly take into account the mutual feedback between supply and demand, and implement a newly developed water allocation scheme to distinguish surface water and groundwater use. Moreover, we include a new irrigation scheme, which works dynamically with a daily surface and soil water balance, and incorporate the newly available extensive Global Reservoir and Dams data set (GRanD). Simulated surface water and groundwater withdrawals generally show good agreement with reported national and subnational statistics. The results show a consistent increase in both surface water and groundwater use worldwide, with a more rapid increase in groundwater use since the 1990s. Human impacts on terrestrial water storage (TWS) signals are evident, altering the seasonal and interannual variability. This alteration is particularly large over heavily regulated basins such as the Colorado and the Columbia, and over the major irrigated basins such as the Mississippi, the Indus, and the Ganges. Including human water use and associated reservoir operations generally improves the correlation of simulated TWS anomalies with those of the GRACE observations.

Global Modeling of Withdrawal, Allocation and Consumptive Use of Surface Water and Groundwater Resources

NASA Astrophysics Data System (ADS)

Wada, Y.; Wisser, D.; Bierkens, M. F.

2014-12-01

To sustain growing food demand and increasing standard of living, global water withdrawal and consumptive water use have been increasing rapidly. To analyze the human perturbation on water resources consistently over large scales, a number of macro-scale hydrological models (MHMs) have been developed in recent decades. However, few models consider the interaction between terrestrial water fluxes, and human activities and associated water use, and even fewer models distinguish water use from surface water and groundwater resources. Here, we couple a global water demand model with a global hydrological model and dynamically simulate daily water withdrawal and consumptive water use over the period 1979-2010, using two re-analysis products: ERA-Interim and MERRA. We explicitly take into account the mutual feedback between supply and demand, and implement a newly developed water allocation scheme to distinguish surface water and groundwater use. Moreover, we include a new irrigation scheme, which works dynamically with a daily surface and soil water balance, and incorporate the newly available extensive global reservoir data set (GRanD). Simulated surface water and groundwater withdrawals generally show good agreement with reported national and sub-national statistics. The results show a consistent increase in both surface water and groundwater use worldwide, with a more rapid increase in groundwater use since the 1990s. Human impacts on terrestrial water storage (TWS) signals are evident, altering the seasonal and inter-annual variability. This alteration is particularly large over heavily regulated basins such as the Colorado and the Columbia, and over the major irrigated basins such as the Mississippi, the Indus, and the Ganges. Including human water use and associated reservoir operations generally improves the correlation of simulated TWS anomalies with those of the GRACE observations.

Incorporating Anthropogenic Influences into Fire Probability Models: Effects of Human Activity and Climate Change on Fire Activity in California.

PubMed

Mann, Michael L; Batllori, Enric; Moritz, Max A; Waller, Eric K; Berck, Peter; Flint, Alan L; Flint, Lorraine E; Dolfi, Emmalee

2016-01-01

The costly interactions between humans and wildfires throughout California demonstrate the need to understand the relationships between them, especially in the face of a changing climate and expanding human communities. Although a number of statistical and process-based wildfire models exist for California, there is enormous uncertainty about the location and number of future fires, with previously published estimates of increases ranging from nine to fifty-three percent by the end of the century. Our goal is to assess the role of climate and anthropogenic influences on the state's fire regimes from 1975 to 2050. We develop an empirical model that integrates estimates of biophysical indicators relevant to plant communities and anthropogenic influences at each forecast time step. Historically, we find that anthropogenic influences account for up to fifty percent of explanatory power in the model. We also find that the total area burned is likely to increase, with burned area expected to increase by 2.2 and 5.0 percent by 2050 under climatic bookends (PCM and GFDL climate models, respectively). Our two climate models show considerable agreement, but due to potential shifts in rainfall patterns, substantial uncertainty remains for the semiarid inland deserts and coastal areas of the south. Given the strength of human-related variables in some regions, however, it is clear that comprehensive projections of future fire activity should include both anthropogenic and biophysical influences. Previous findings of substantially increased numbers of fires and burned area for California may be tied to omitted variable bias from the exclusion of human influences. The omission of anthropogenic variables in our model would overstate the importance of climatic ones by at least 24%. As such, the failure to include anthropogenic effects in many models likely overstates the response of wildfire to climatic change.

Incorporating Anthropogenic Influences into Fire Probability Models: Effects of Human Activity and Climate Change on Fire Activity in California

PubMed Central

Batllori, Enric; Moritz, Max A.; Waller, Eric K.; Berck, Peter; Flint, Alan L.; Flint, Lorraine E.; Dolfi, Emmalee

2016-01-01

The costly interactions between humans and wildfires throughout California demonstrate the need to understand the relationships between them, especially in the face of a changing climate and expanding human communities. Although a number of statistical and process-based wildfire models exist for California, there is enormous uncertainty about the location and number of future fires, with previously published estimates of increases ranging from nine to fifty-three percent by the end of the century. Our goal is to assess the role of climate and anthropogenic influences on the state’s fire regimes from 1975 to 2050. We develop an empirical model that integrates estimates of biophysical indicators relevant to plant communities and anthropogenic influences at each forecast time step. Historically, we find that anthropogenic influences account for up to fifty percent of explanatory power in the model. We also find that the total area burned is likely to increase, with burned area expected to increase by 2.2 and 5.0 percent by 2050 under climatic bookends (PCM and GFDL climate models, respectively). Our two climate models show considerable agreement, but due to potential shifts in rainfall patterns, substantial uncertainty remains for the semiarid inland deserts and coastal areas of the south. Given the strength of human-related variables in some regions, however, it is clear that comprehensive projections of future fire activity should include both anthropogenic and biophysical influences. Previous findings of substantially increased numbers of fires and burned area for California may be tied to omitted variable bias from the exclusion of human influences. The omission of anthropogenic variables in our model would overstate the importance of climatic ones by at least 24%. As such, the failure to include anthropogenic effects in many models likely overstates the response of wildfire to climatic change. PMID:27124597

Climate Change, Soils, and Human Health

NASA Astrophysics Data System (ADS)

Brevik, Eric C.

2013-04-01

According to the Intergovernmental Panel on Climate Change, global temperatures are expected to increase 1.1 to 6.4 degrees C during the 21st century and precipitation patterns will be altered by climate change (IPCC, 2007). Soils are intricately linked to the atmospheric/climate system through the carbon, nitrogen, and hydrologic cycles. Altered climate will, therefore, have an effect on soil processes and properties. Studies into the effects of climate change on soil processes and properties are still incomplete, but have revealed that climate change will impact soil organic matter dynamics including soil organisms and the multiple soil properties that are tied to organic matter, soil water, and soil erosion. The exact direction and magnitude of those impacts will be dependent on the amount of change in atmospheric gases, temperature, and precipitation amounts and patterns. Recent studies give reason to believe at least some soils may become net sources of atmospheric carbon as temperatures rise; this is particularly true of high latitude regions with permanently frozen soils. Soil erosion by both wind and water is also likely to increase. These soil changes will lead to both direct and indirect impacts on human health. Possible indirect impacts include temperature extremes, food safety and air quality issues, increased and/or expanded disease incidences, and occupational health issues. Potential direct impacts include decreased food security and increased atmospheric dust levels. However, there are still many things we need to know more about. How climate change will affect the nitrogen cycle and, in turn, how the nitrogen cycle will affect carbon sequestration in soils is a major research need, as is a better understanding of soil water-CO2 level-temperature relationships. Knowledge of the response of plants to elevated atmospheric CO2 given limitations in nutrients like nitrogen and phosphorus and how that affects soil organic matter dynamics is a critical need. There is also a great need for a better understanding of how soil organisms will respond to climate change because those organisms are incredibly important in a number of soil processes, including the carbon and nitrogen cycles. All of these questions are important in trying to understand human health impacts. More information on climate change, soils, and human health issues can be found in Brevik (2012). References Brevik, E.C. 2012. Climate change, soils, and human health. In: E.C. Brevik and L. Burgess (Eds). Soils and human health. CRC Press, Boca Raton, FL. in press. IPCC. 2007. Summary for policymakers. pp. 1-18. In S. Solomon, D. Qin, M. Manning, Z. Chen, M. Marquis, K.B. Averyt, M.Tignor and H.L. Miller (eds). Climate change 2007: the physical science basis. Contribution of Working Group I to the Fourth Assessment Report of the Intergovernmental Panel on Climate Change. Cambridge University Press, Cambridge, UK.

Bird migration through Middle Rio Grande riparian forests, 1994 to 1997

Treesearch

Michael D. Means; Deborah M. Finch

1999-01-01

Expanding human populations in the middle Rio Grande have increased demands on water, land, and other resources, potentially disrupting bird migration activities. From 1994 to 1997, a total of 26,350 birds of 157 species were banded and studied. Results include species composition, timing of migration, and habitat use. Recommendations for managers are included.

Prenatal exposure to bisphenol A and hyperactivity in children: a systematic review and meta-analysis.

PubMed

Rochester, Johanna R; Bolden, Ashley L; Kwiatkowski, Carol F

2018-05-01

Attention-deficit hyperactivity disorder (ADHD) has increased in prevalence in the past decade. Studies attempting to identify a specific genetic component have not been able to account for much of the heritability of ADHD, indicating there may be gene-environment interactions underlying the disorder, including early exposure to environmental chemicals. Based on several relevant studies, we chose to examine bisphenol A (BPA) as a possible contributor to ADHD in humans. BPA is a widespread environmental chemical that has been shown to disrupt neurodevelopment in rodents and humans. Using the Office of Health Assessment and Translation (OHAT) framework, a systematic review and meta-analysis was designed to determine the relationship between early life exposure to BPA and hyperactivity, a key diagnostic criterion of ADHD. Searches of PubMed, Web of Science, and Toxline were completed for all literature to January 1, 2017. For inclusion, the studies had to publish original data, be in the English language, include a measure of BPA exposure, and assess if BPA exposure affected hyperactive behaviors in mice, rats or humans. Exposure to BPA had to occur at <3 months of age for humans, up to postnatal day 35 for rats and up to postnatal day 40 for mice. Exposure could occur either gestationally (via maternal exposure) or directly to the offspring. Studies were evaluated using the OHAT risk of bias tool. The effects in humans were assessed qualitatively. For rodents exposed to 20 μg/kg/day BPA, we evaluated the study findings in a random effects meta-analytical model. A review of the literature identified 29 rodent and 3 human studies. A random effects meta-analysis showed significantly increased hyperactivity in male rodents. In humans, early BPA exposure was associated with hyperactivity in boys and girls. We concluded that early life BPA exposure is a presumed human hazard for the development of hyperactivity. Possible limitations of this systematic review include deficiencies in author reporting, exclusion of some literature based on language, and insufficient similarity between human studies. SRs that result in hazard-based conclusions are the first step in assessing and mitigating risks. Given the widespread exposure of BPA and increasing diagnoses of ADHD, we recommend immediate actions to complete such risk analyses and take next steps for the protection of human health. In the meantime, precautionary measures should be taken to reduce exposure in pregnant women, infants and children. The present analysis also discusses potential mechanisms by which BPA affects hyperactivity, and the most effective avenues for future research. Not available. Copyright © 2017. Published by Elsevier Ltd.

HSC extrinsic sex-related and intrinsic autoimmune disease-related human B-cell variation is recapitulated in humanized mice.

PubMed

Borsotti, Chiara; Danzl, Nichole M; Nauman, Grace; Hölzl, Markus A; French, Clare; Chavez, Estefania; Khosravi-Maharlooei, Mohsen; Glauzy, Salome; Delmotte, Fabien R; Meffre, Eric; Savage, David G; Campbell, Sean R; Goland, Robin; Greenberg, Ellen; Bi, Jing; Satwani, Prakash; Yang, Suxiao; Bathon, Joan; Winchester, Robert; Sykes, Megan

2017-10-24

B cells play a major role in antigen presentation and antibody production in the development of autoimmune diseases, and some of these diseases disproportionally occur in females. Moreover, immune responses tend to be stronger in female vs male humans and mice. Because it is challenging to distinguish intrinsic from extrinsic influences on human immune responses, we used a personalized immune (PI) humanized mouse model, in which immune systems were generated de novo from adult human hematopoietic stem cells (HSCs) in immunodeficient mice. We assessed the effect of recipient sex and of donor autoimmune diseases (type 1 diabetes [T1D] and rheumatoid arthritis [RA]) on human B-cell development in PI mice. We observed that human B-cell levels were increased in female recipients regardless of the source of human HSCs or the strain of immunodeficient recipient mice. Moreover, mice injected with T1D- or RA-derived HSCs displayed B-cell abnormalities compared with healthy control HSC-derived mice, including altered B-cell levels, increased proportions of mature B cells and reduced CD19 expression. Our study revealed an HSC-extrinsic effect of recipient sex on human B-cell reconstitution. Moreover, the PI humanized mouse model revealed HSC-intrinsic defects in central B-cell tolerance that recapitulated those in patients with autoimmune diseases. These results demonstrate the utility of humanized mouse models as a tool to better understand human immune cell development and regulation.

The Arctic Human Health Initiative: a legacy of the International Polar Year 2007–2009

PubMed Central

Parkinson, Alan J.

2013-01-01

Background The International Polar Year (IPY) 2007–2008 represented a unique opportunity to further stimulate cooperation and coordination on Arctic health research and increase the awareness and visibility of Arctic regions. The Arctic Human Health Initiative (AHHI) was a US-led Arctic Council IPY coordinating project that aimed to build and expand on existing International Union for Circumpolar Health (IUCH) and Arctic Council human health interests. The project aimed to link researchers with potential international collaborators and to serve as a focal point for human health research, education, outreach and communication activities during the IPY. The progress of projects conducted as part of this initiative up until the end of the Arctic Council Swedish chairmanship in May 2013 is summarized in this report. Design The overall goals of the AHHI was to increase awareness and visibility of human health concerns of Arctic peoples, foster human health research, and promote health strategies that will improve health and well-being of all Arctic residents. Proposed activities to be recognized through the initiative included: expanding research networks that will enhance surveillance and monitoring of health issues of concern to Arctic peoples, and increase collaboration and coordination of human health research; fostering research that will examine the health impact of anthropogenic pollution, rapid modernization and economic development, climate variability, infectious and chronic diseases, intentional and unintentional injuries, promoting education, outreach and communication that will focus public and political attention on Arctic health issues, using a variety of publications, printed and electronic reports from scientific conferences, symposia and workshops targeting researchers, students, communities and policy makers; promoting the translation of research into health policy and community action including implementation of prevention strategies and health promotion; and promoting synergy and strategic direction of Arctic human health research and health promotion. Results As of 31 March, 2009, the official end of the IPY, AHHI represented a total of 38 proposals, including 21 individual Expressions of Intent (EoI), and 9 full proposals (FP), submitted to the IPY Joint Committee for review and approval from lead investigators from the US, Canada, Greenland, Norway, Finland, Sweden and the Russian Federation. In addition, there were 10 National Initiatives (NI-projects undertaken during IPY beyond the IPY Joint Committee review process). Individual project details can be viewed at www.arctichealth.org. The AHHI currently monitors the progress of 28 individual active human health projects in the following thematic areas: health network expansion (5 projects), infectious disease research (7 projects), environmental health research (7 projects), behavioral and mental health research (4 projects), and outreach education and communication (5 projects). Conclusions While some projects have been completed, others will continue well beyond the IPY. The IPY 2007–2008 represented a unique opportunity to further stimulate cooperation and coordination on Arctic health research and increase the awareness and visibility of Arctic regions. PMID:23971017

The Arctic Human Health Initiative: a legacy of the International Polar Year 2007-2009.

PubMed

Parkinson, Alan J

2013-01-01

The International Polar Year (IPY) 2007-2008 represented a unique opportunity to further stimulate cooperation and coordination on Arctic health research and increase the awareness and visibility of Arctic regions. The Arctic Human Health Initiative (AHHI) was a US-led Arctic Council IPY coordinating project that aimed to build and expand on existing International Union for Circumpolar Health (IUCH) and Arctic Council human health interests. The project aimed to link researchers with potential international collaborators and to serve as a focal point for human health research, education, outreach and communication activities during the IPY. The progress of projects conducted as part of this initiative up until the end of the Arctic Council Swedish chairmanship in May 2013 is summarized in this report. The overall goals of the AHHI was to increase awareness and visibility of human health concerns of Arctic peoples, foster human health research, and promote health strategies that will improve health and well-being of all Arctic residents. Proposed activities to be recognized through the initiative included: expanding research networks that will enhance surveillance and monitoring of health issues of concern to Arctic peoples, and increase collaboration and coordination of human health research; fostering research that will examine the health impact of anthropogenic pollution, rapid modernization and economic development, climate variability, infectious and chronic diseases, intentional and unintentional injuries, promoting education, outreach and communication that will focus public and political attention on Arctic health issues, using a variety of publications, printed and electronic reports from scientific conferences, symposia and workshops targeting researchers, students, communities and policy makers; promoting the translation of research into health policy and community action including implementation of prevention strategies and health promotion; and promoting synergy and strategic direction of Arctic human health research and health promotion. As of 31 March, 2009, the official end of the IPY, AHHI represented a total of 38 proposals, including 21 individual Expressions of Intent (EoI), and 9 full proposals (FP), submitted to the IPY Joint Committee for review and approval from lead investigators from the US, Canada, Greenland, Norway, Finland, Sweden and the Russian Federation. In addition, there were 10 National Initiatives (NI-projects undertaken during IPY beyond the IPY Joint Committee review process). Individual project details can be viewed at www.arctichealth.org. The AHHI currently monitors the progress of 28 individual active human health projects in the following thematic areas: health network expansion (5 projects), infectious disease research (7 projects), environmental health research (7 projects), behavioral and mental health research (4 projects), and outreach education and communication (5 projects). While some projects have been completed, others will continue well beyond the IPY. The IPY 2007-2008 represented a unique opportunity to further stimulate cooperation and coordination on Arctic health research and increase the awareness and visibility of Arctic regions.

A compelling practice: empowering future leaders in the medical humanities.

PubMed

Runyan, Aliye; Ellington, Katherine; Wershof Schwartz, Andrea

2013-12-01

Medical students and faculty explore the medical humanities for diverse reasons: as a medium for self-reflection, a means to cultivate professionalism and humanism, and a way to gain an appreciation for the broader contexts in which illness and health occur. One important area for development is increasing the exposure of learners and clinicians of various levels of training to the medical humanities and to role models in the field. Student-led programs in the medical humanities at the American Medical Student Association (AMSA) address these needs by offering unique opportunities for learning and sharing experiences. AMSA programs connect physicians-in-training using technology to create virtual communication and learning opportunities. These include monthly book discussion webinars, the Writers' Institute and the Medical Humanities Scholars Program (MHSP).

Critical linkages between land-use transition and human health in the Himalayan region.

PubMed

Xu, Jianchu; Sharma, Rita; Fang, Jing; Xu, Yufen

2008-02-01

This article reviews critical linkages between land-use transition and human health in the Himalayan region by applying ecosystem approaches to human health (or EcoHealth). Land-use transition in the Himalayan and similar regions includes sedentarization, agricultural intensification, habitat modification, migration, change of livelihoods and lifestyles, biodiversity loss, and increasing flash floods. These transitions, which can have impacts on human health, are driven by state policies, a market economy, and climate change. Human health is dependent on access to ecosystem services for food, nutrition, medicine, fiber and shelter, fresh water, and clear air. Ecosystem management has been a key means of controlling disease vectors and creating suitable habitats for human well-being. The paper identifies the web of environmental factors that influence human health. Institutional and policy issues for land-use and health transitions are also discussed.

Characteristics of hyperthermia-induced hyperventilation in humans

PubMed Central

Tsuji, Bun; Hayashi, Keiji; Kondo, Narihiko; Nishiyasu, Takeshi

2016-01-01

ABSTRACT In humans, hyperthermia leads to activation of a set of thermoregulatory responses that includes cutaneous vasodilation and sweating. Hyperthermia also increases ventilation in humans, as is observed in panting dogs, but the physiological significance and characteristics of the hyperventilatory response in humans remain unclear. The relative contribution of respiratory heat loss to total heat loss in a hot environment in humans is small, and this hyperventilation causes a concomitant reduction in arterial CO2 pressure (hypocapnia), which can cause cerebral hypoperfusion. Consequently, hyperventilation in humans may not contribute to the maintenance of physiological homeostasis (i.e., thermoregulation). To gain some insight into the physiological significance of hyperthermia-induced hyperventilation in humans, in this review, we discuss 1) the mechanisms underlying hyperthermia-induced hyperventilation, 2) the factors modulating this response, and 3) the physiological consequences of the response. PMID:27227102

Understanding and seasonal forecasting of hydrological drought in the Anthropocene

NASA Astrophysics Data System (ADS)

Yuan, Xing; Zhang, Miao; Wang, Linying; Zhou, Tian

2017-11-01

Hydrological drought is not only caused by natural hydroclimate variability but can also be directly altered by human interventions including reservoir operation, irrigation, groundwater exploitation, etc. Understanding and forecasting of hydrological drought in the Anthropocene are grand challenges due to complicated interactions among climate, hydrology and humans. In this paper, five decades (1961-2010) of naturalized and observed streamflow datasets are used to investigate hydrological drought characteristics in a heavily managed river basin, the Yellow River basin in north China. Human interventions decrease the correlation between hydrological and meteorological droughts, and make the hydrological drought respond to longer timescales of meteorological drought. Due to large water consumptions in the middle and lower reaches, there are 118-262 % increases in the hydrological drought frequency, up to 8-fold increases in the drought severity, 21-99 % increases in the drought duration and the drought onset is earlier. The non-stationarity due to anthropogenic climate change and human water use basically decreases the correlation between meteorological and hydrological droughts and reduces the effect of human interventions on hydrological drought frequency while increasing the effect on drought duration and severity. A set of 29-year (1982-2010) hindcasts from an established seasonal hydrological forecasting system are used to assess the forecast skill of hydrological drought. In the naturalized condition, the climate-model-based approach outperforms the climatology method in predicting the 2001 severe hydrological drought event. Based on the 29-year hindcasts, the former method has a Brier skill score of 11-26 % against the latter for the probabilistic hydrological drought forecasting. In the Anthropocene, the skill for both approaches increases due to the dominant influence of human interventions that have been implicitly incorporated by the hydrological post-processing, while the difference between the two predictions decreases. This suggests that human interventions can outweigh the climate variability for the hydrological drought forecasting in the Anthropocene, and the predictability for human interventions needs more attention.

Inhaled oxytocin increases positive social behaviors in newborn macaques

PubMed Central

Simpson, Elizabeth A.; Sclafani, Valentina; Paukner, Annika; Hamel, Amanda F.; Novak, Melinda A.; Meyer, Jerrold S.; Suomi, Stephen J.; Ferrari, Pier Francesco

2014-01-01

Early caregiver–infant interactions are critical for infants’ socioemotional and cognitive development. Several hormones and neuromodulators, including oxytocin, affect these interactions. Exogenous oxytocin promotes social behaviors in several species, including human and nonhuman primates. Although exogenous oxytocin increases social function in adults—including expression recognition and affiliation—it is unknown whether oxytocin can increase social interactions in infants. We hypothesized that nebulized oxytocin would increase affiliative social behaviors and such effects would be modulated by infants’ social skills, measured earlier in development. We also hypothesized that oxytocin’s effects on social behaviors may be due to its anxiolytic effects. We tested these hypotheses in a blind study by nebulizing 7- to 14-d-old macaques (n = 28) with oxytocin or saline. Following oxytocin administration, infants’ facial gesturing at a human caregiver increased, and infants’ salivary oxytocin was positively correlated with the time spent in close proximity to a caregiver. Infants’ imitative skill (measured earlier in development: 1–7 d of age) predicted oxytocin-associated increases in affiliative behaviors—lip smacking, visual attention to a caregiver, and time in close proximity to a caregiver—suggesting that infants with higher propensities for positive social interactions are more sensitive to exogenous oxytocin. Oxytocin also decreased salivary cortisol, but not stress-related behaviors (e.g., scratching), suggesting the possibility of some anxiolytic effects. To our knowledge, this study provides the first evidence that oxytocin increases positive social behaviors in newborns. This information is of critical importance for potential interventions aimed at ameliorating inadequate social behaviors in infants with higher likelihood of developing neurodevelopmental disorder. PMID:24778211

Climate, CO2 and human population impacts on global wildfire emissions

NASA Astrophysics Data System (ADS)

Knorr, W.; Jiang, L.; Arneth, A.

2016-01-01

Wildfires are by far the largest contributor to global biomass burning and constitute a large global source of atmospheric traces gases and aerosols. Such emissions have a considerable impact on air quality and constitute a major health hazard. Biomass burning also influences the radiative balance of the atmosphere and is thus not only of societal, but also of significant scientific interest. There is a common perception that climate change will lead to an increase in emissions as hot and dry weather events that promote wildfire will become more common. However, even though a few studies have found that the inclusion of CO2 fertilisation of photosynthesis and changes in human population patterns will tend to somewhat lower predictions of future wildfire emissions, no such study has included full ensemble ranges of both climate predictions and population projections, including the effect of different degrees of urbanisation.

Here, we present a series of 124 simulations with the LPJ-GUESS-SIMFIRE global dynamic vegetation-wildfire model, including a semi-empirical formulation for the prediction of burned area based on fire weather, fuel continuity and human population density. The simulations use Climate Model Intercomparison Project 5 (CMIP5) climate predictions from eight Earth system models. These were combined with two Representative Concentration Pathways (RCPs) and five scenarios of future human population density based on the series of Shared Socioeconomic Pathways (SSPs) to assess the sensitivity of emissions to the effect of climate, CO2 and humans. In addition, two alternative parameterisations of the semi-empirical burned-area model were applied. Contrary to previous work, we find no clear future trend of global wildfire emissions for the moderate emissions and climate change scenario based on the RCP 4.5. Only historical population change introduces a decline by around 15 % since 1900. Future emissions could either increase for low population growth and fast urbanisation, or continue to decline for high population growth and slow urbanisation. Only for high future climate change (RCP8.5), wildfire emissions start to rise again after ca. 2020 but are unlikely to reach the levels of 1900 by the end of the 21st century. We find that climate warming will generally increase the risk of fire, but that this is only one of several equally important factors driving future levels of wildfire emissions, which include population change, CO2 fertilisation causing woody thickening, increased productivity and fuel load and faster litter turnover in a warmer climate.

A potent human anti-eotaxin1 antibody, CAT-213: isolation by phage display and in vitro and in vivo efficacy.

PubMed

Main, Sarah; Handy, Rachel; Wilton, Jane; Smith, Stephen; Williams, Liz; Fou, Leila Du; Andrews, John; Conroy, Louise A; May, Richard; Anderson, Ian; Vaughan, Tristan J

2006-12-01

The CC chemokine, eotaxin1 (CCL11) is an important regulator of eosinophil function. A marked accumulation of eosinophils in tissues has been correlated with the up-regulation of eotaxin1 expression in several diseases. The potential therapeutic value of neutralizing the effects of eotaxin1 in inflammatory conditions (including asthma) is under investigation. A human single-chain fragment variable antibody that neutralizes human eotaxin1 (CAT-212) was produced using antibody phage display and converted to whole antibody IgG4 format (CAT-213). A novel approach to lead optimization in which the length of the variable heavy chain complementarity-determining region 3 was reduced by one amino acid resulted in an increase in potency of >1000-fold compared with the parent anti-eotaxin1 antibody. The optimized antibody binds eotaxin1 with high affinity (80.4 pM) and specificity. CAT-213 and CAT-212 do not bind or neutralize a range of other human proteins including human monocyte chemoattractant protein-1, a structurally similar chemokine. CAT-213 neutralizes the ability of eotaxin1 to cause an increase in intracellular calcium signaling (with an IC(50) value of 2.86 nM), migration of CCR3-expressing L1.2 cells (with an IC(50) value of 0.48 nM), and inhibition of the eotaxin1-evoked shape change of human eosinophils in vitro (with an IC(50) of 0.71 nM). Local administration of CAT-213 to mice (1-100 microg kg(-1)) attenuates dermal eosinophilia induced by human eotaxin1, achieving >90% inhibition of eosinophil influx. CAT-213 may therefore be of therapeutic value in inhibiting diseases in which eotaxin1 and eosinophils play a major role, for example, severe asthma.

Assessment of the national antimicrobial resistance monitoring system (NARMS) and its value in critical decision-making.

PubMed

Ginevan, Michael E

2002-12-01

This paper reviews the United States National Antimicrobial Resistance Monitoring System (NARMS). The data from this system have been used as the core basis of a recent proposal to stop the use of fluoroquinolones in poultry production, in an effort to reduce or remove a perceived threat to human health due to alleged increasing fluoroquinolone resistance among human Campylobacter isolates. An increase in resistance has the potential to render fluoroquinolone therapy of human gastrointestinal infections less effective. This review finds no evidence in the NARMS data to suggest that a rise in resistant Campylobacter isolates has occurred since fluoroquinolones were introduced for use in poultry. In addition, this review identifies a number of shortcomings in the NARMS program. These include lack of an overall sampling design, biases in the collection of isolates from animal samples, noncompliance of state departments of public health with NARMS protocols, lack of such basic data as genotype information on the organisms isolated, and, for animal samples, lack of measurements of bacterial load. Taken together, these problems indicate that the present NARMS data very likely overestimate resistance levels, and, at best, do not provide reliable information to quantify the extent and temporal trends of antimicrobial resistance in Campylobacter and other enteric organisms from human and animal populations. Ways to improve the quantitative rigor of the NARMS program and identify other data such as 'meta' data for human and animal samples, and data on the magnitude of other potential reservoirs of infection, including healthy humans, are suggested. Implementing these proposals would greatly enhance the value of the NARMS program as a tool for quantitative decision-making and aid in improving the quality of our food supply and human health care.

Metal status in human endometrium: Relation to cigarette smoking and histological lesions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rzymski, Piotr, E-mail: rzymskipiotr@ump.edu.pl; Rzymski, Paweł; Tomczyk, Katarzyna

Human endometrium is a thick, blood vessel-rich, glandular tissue which undergoes cyclic changes and is potentially sensitive to the various endogenous and exogenous compounds supplied via the hematogenous route. As recently indicated, several metals including Cd, Pb, Cr and Ni represent an emerging class of potential metalloestrogens and can be implicated in alterations of the female reproductive system including endometriosis and cancer. In the present study, we investigated the content of five metals: Cd, Cr, Ni, Pb and Zn in 25 samples of human endometrium collected from Polish females undergoing diagnostic or therapeutic curettage of the uterine cavity. The overallmore » mean metal concentration (analyzed using microwave induced plasma atomic emission spectrometry MIP-OES) decreased in the following order: Cr>Pb>Zn>Ni>Cd. For the first time it was demonstrated that cigarette smoking significantly increases the endometrial content of Cd and Pb. Concentration of these metals was also positively correlated with years of smoking and the number of smoked cigarettes. Tissue samples with recognized histologic lesions (simple hyperplasia, polyposis and atrophy) were characterized by a 2-fold higher Cd level. No relation between the age of the women and metal content was found. Our study shows that human endometrium can be a potential target of metal accumulation within the human body. Quantitative analyses of endometrial metal content could serve as an additional indicator of potential impairments of the menstrual cycle and fertility. - Highlights: • Cd, Cr, Ni, Pb and Zn are detectable in human endometrium. • Mean metal content in human endometrium decreases in Cr>Pb>Zn>Ni>Cd order. • Cigarettes smoking increases endometrial content of Cd and Pb. • Lesioned endometrial tissue was characterized by higher metal contents.« less

Effects of Age on Bone mRNA Levels of Sclerostin and Other Genes Relevant to Bone Metabolism in Humans

PubMed Central

Roforth, Matthew M.; Fujita, Koji; McGregor, Ulrike I.; Kirmani, Salman; McCready, Louise K.; Peterson, James M.; Drake, Matthew T.; Monroe, David G.; Khosla, Sundeep

2013-01-01

Although aging is associated with a decline in bone formation in humans, the molecular pathways contributing to this decline remain unclear. Several previous clinical studies have shown that circulating sclerostin levels increase with age, raising the possibility that increased production of sclerostin by osteocytes leads to the age-related impairment in bone formation. Thus, in the present study, we examined circulating sclerostin levels as well as bone mRNA levels of sclerostin using quantitative polymerase chain reaction (QPCR) analyses in needle bone biopsies from young (mean age, 30.0 years) versus old (mean age, 72.9 years) women. In addition, we analyzed the expression of genes in a number of pathways known to be altered with skeletal aging, based largely on studies in mice. While serum sclerostin levels were 46% higher (p < 0.01) in the old as compared to the young women, bone sclerostin mRNA levels were no different between the two groups (p = 0.845). However, genes related to notch signaling were significantly upregulated (p = 0.003 when analyzed as a group) in the biopsies from the old women. In an additional analysis of 118 genes including those from genome-wide association studies related to bone density and/or fracture, BMP/TGFβ family genes, selected growth factors and nuclear receptors, and Wnt/Wnt-related genes, we found that mRNA levels of the Wnt inhibitor, SFRP1, were significantly increased (by 1.6-fold, p = 0.0004, false discovery rate [q] = 0.04) in the biopsies from the old as compared to the young women. Our findings thus indicate that despite increases in circulating sclerostin levels, bone sclerostin mRNA levels do not increase in elderly women. However, aging is associated with alterations in several key pathways and genes in humans that may contribute to the observed impairment in bone formation. These include notch signaling, which represents a potential therapeutic target for increasing bone formation in humans. Our studies further identified mRNA levels of SFRP1 as being increased in aging bone in humans, suggesting that this may also represent a viable target for the development of anabolic therapies for age-related bone loss and osteoporosis. PMID:24184314

Comparative Proteomics of Human and Macaque Milk Reveals Species-Specific Nutrition during Postnatal Development.

PubMed

Beck, Kristen L; Weber, Darren; Phinney, Brett S; Smilowitz, Jennifer T; Hinde, Katie; Lönnerdal, Bo; Korf, Ian; Lemay, Danielle G

2015-05-01

Milk has been well established as the optimal nutrition source for infants, yet there is still much to be understood about its molecular composition. Therefore, our objective was to develop and compare comprehensive milk proteomes for human and rhesus macaques to highlight differences in neonatal nutrition. We developed a milk proteomics technique that overcomes previous technical barriers including pervasive post-translational modifications and limited sample volume. We identified 1606 and 518 proteins in human and macaque milk, respectively. During analysis of detected protein orthologs, we identified 88 differentially abundant proteins. Of these, 93% exhibited increased abundance in human milk relative to macaque and include lactoferrin, polymeric immunoglobulin receptor, alpha-1 antichymotrypsin, vitamin D-binding protein, and haptocorrin. Furthermore, proteins more abundant in human milk compared with macaque are associated with development of the gastrointestinal tract, the immune system, and the brain. Overall, our novel proteomics method reveals the first comprehensive macaque milk proteome and 524 newly identified human milk proteins. The differentially abundant proteins observed are consistent with the perspective that human infants, compared with nonhuman primates, are born at a slightly earlier stage of somatic development and require additional support through higher quantities of specific proteins to nurture human infant maturation.

Drosophila Melanogaster as an Emerging Translational Model of Human Nephrolithiasis

PubMed Central

Miller, Joe; Chi, Thomas; Kapahi, Pankaj; Kahn, Arnold J.; Kim, Man Su; Hirata, Taku; Romero, Michael F.; Dow, Julian A.T.; Stoller, Marshall L.

2013-01-01

Purpose The limitations imposed by human clinical studies and mammalian models of nephrolithiasis have hampered the development of effective medical treatments and preventative measures for decades. The simple but elegant Drosophila melanogaster is emerging as a powerful translational model of human disease, including nephrolithiasis and may provide important information essential to our understanding of stone formation. We present the current state of research using D. melanogaster as a model of human nephrolithiasis. Materials and Methods A comprehensive review of the English language literature was performed using PUBMED. When necessary, authoritative texts on relevant subtopics were consulted. Results The genetic composition, anatomic structure and physiologic function of Drosophila Malpighian tubules are remarkably similar to those of the human nephron. The direct effects of dietary manipulation, environmental alteration, and genetic variation on stone formation can be observed and quantified in a matter of days. Several Drosophila models of human nephrolithiasis, including genetically linked and environmentally induced stones, have been developed. A model of calcium oxalate stone formation is among the most recent fly models of human nephrolithiasis. Conclusions The ability to readily manipulate and quantify stone formation in D. melanogaster models of human nephrolithiasis presents the urologic community with a unique opportunity to increase our understanding of this enigmatic disease. PMID:23500641

Quantifying human impact on hydrological drought using an Earth System Model

NASA Astrophysics Data System (ADS)

van Huijgevoort, Marjolein; Chaney, Nathaniel; Malyshev, Sergey; Shevliakova, Elena; Milly, Chris

2017-04-01

Predicting the human impact on the present and future hydrological cycle remains a significant scientific challenge. Anthropogenic impact includes water management practices like diverting water for irrigation, abstraction of groundwater, and reservoirs. Hydrological extremes, in particular, are heavily affected by water management practices, due to the existing stress on the system during droughts and floods. Therefore, to prepare adaptation plans for hydrological extremes in the future, it is essential to account for water management and other human influences in Earth System Models. In this study we have implemented water management practices in the state-of-the-art GFDL land model, which includes terrestrial water, energy, and carbon balances. Both irrigation practices and reservoirs have been added in the land surface model component of the model. Irrigation amounts are determined from the soil water balance, the evaporative demand of the vegetation and fractional coverage of croplands. The resulting water demand is fulfilled by abstractions from surface water and groundwater. Reservoir outflow is dynamically coupled to the downstream water demand and available reservoir storage. Retrospective model simulations over the contiguous United States indicate a strong human influence on hydrological drought. A water management attribution analysis shows a significant impact on the water availability, mostly in the Midwest of the United States and California. Implementation of reservoirs alters the flow regime, thereby decreasing the short-term drought impact, however, in the case of multi-year drought, impacts are delayed due to the dependency on the reservoir outflow. Irrigation, on the other hand, decreases the water availability in rivers due to increased evapotranspiration leading to a higher drought impact. The average increase in evapotranspiration amounted up to 2 mm/day for cropland areas in California and Texas. Overall, the results show the importance of including water management in global scale models. This new modelling framework can be used to understand how humans will impact future water availability, water scarcity, and drought. Next steps will include coupled model simulations to investigate the human impact on feedbacks in land-atmosphere interactions.

Statistical aspects and risks of human-caused earthquakes

NASA Astrophysics Data System (ADS)

Klose, C. D.

2013-12-01

The seismological community invests ample human capital and financial resources to research and predict risks associated with earthquakes. Industries such as the insurance and re-insurance sector are equally interested in using probabilistic risk models developed by the scientific community to transfer risks. These models are used to predict expected losses due to naturally occurring earthquakes. But what about the risks associated with human-caused earthquakes? Such risk models are largely absent from both industry and academic discourse. In countries around the world, informed citizens are becoming increasingly aware and concerned that this economic bias is not sustainable for long-term economic growth, environmental and human security. Ultimately, citizens look to their government officials to hold industry accountable. In the Netherlands, for example, the hydrocarbon industry is held accountable for causing earthquakes near Groningen. In Switzerland, geothermal power plants were shut down or suspended because they caused earthquakes in canton Basel and St. Gallen. The public and the private non-extractive industry needs access to information about earthquake risks in connection with sub/urban geoengineeing activities, including natural gas production through fracking, geothermal energy production, carbon sequestration, mining and water irrigation. This presentation illuminates statistical aspects of human-caused earthquakes with respect to different geologic environments. Statistical findings are based on the first catalog of human-caused earthquakes (in Klose 2013). Findings are discussed which include the odds to die during a medium-size earthquake that is set off by geomechanical pollution. Any kind of geoengineering activity causes this type of pollution and increases the likelihood of triggering nearby faults to rupture.

Human activities change marine ecosystems by altering predation risk.

PubMed

Madin, Elizabeth M P; Dill, Lawrence M; Ridlon, April D; Heithaus, Michael R; Warner, Robert R

2016-01-01

In ocean ecosystems, many of the changes in predation risk - both increases and decreases - are human-induced. These changes are occurring at scales ranging from global to local and across variable temporal scales. Indirect, risk-based effects of human activity are known to be important in structuring some terrestrial ecosystems, but these impacts have largely been neglected in oceans. Here, we synthesize existing literature and data to explore multiple lines of evidence that collectively suggest diverse human activities are changing marine ecosystems, including carbon storage capacity, in myriad ways by altering predation risk. We provide novel, compelling evidence that at least one key human activity, overfishing, can lead to distinct, cascading risk effects in natural ecosystems whose magnitude exceeds that of presumed lethal effects and may account for previously unexplained findings. We further discuss the conservation implications of human-caused indirect risk effects. Finally, we provide a predictive framework for when human alterations of risk in oceans should lead to cascading effects and outline a prospectus for future research. Given the speed and extent with which human activities are altering marine risk landscapes, it is crucial that conservation and management policy considers the indirect effects of these activities in order to increase the likelihood of success and avoid unfortunate surprises. © 2015 John Wiley & Sons Ltd.

Using human factors engineering to improve the effectiveness of infection prevention and control.

PubMed

Anderson, Judith; Gosbee, Laura Lin; Bessesen, Mary; Williams, Linda

2010-08-01

Human factors engineering is a discipline that studies the capabilities and limitations of humans and the design of devices and systems for improved performance. The principles of human factors engineering can be applied to infection prevention and control to study the interaction between the healthcare worker and the system that he or she is working with, including the use of devices, the built environment, and the demands and complexities of patient care. Some key challenges in infection prevention, such as delayed feedback to healthcare workers, high cognitive workload, and poor ergonomic design, are explained, as is how human factors engineering can be used for improvement and increased compliance with practices to prevent hospital-acquired infections.

Molecular networks and the evolution of human cognitive specializations.

PubMed

Fontenot, Miles; Konopka, Genevieve

2014-12-01

Inroads into elucidating the origins of human cognitive specializations have taken many forms, including genetic, genomic, anatomical, and behavioral assays that typically compare humans to non-human primates. While the integration of all of these approaches is essential for ultimately understanding human cognition, here, we review the usefulness of coexpression network analysis for specifically addressing this question. An increasing number of studies have incorporated coexpression networks into brain expression studies comparing species, disease versus control tissue, brain regions, or developmental time periods. A clearer picture has emerged of the key genes driving brain evolution, as well as the developmental and regional contributions of gene expression patterns important for normal brain development and those misregulated in cognitive diseases. Copyright © 2014 Elsevier Ltd. All rights reserved.

Forensic genetics and genomics: Much more than just a human affair.

PubMed

Arenas, Miguel; Pereira, Filipe; Oliveira, Manuela; Pinto, Nadia; Lopes, Alexandra M; Gomes, Veronica; Carracedo, Angel; Amorim, Antonio

2017-09-01

While traditional forensic genetics has been oriented towards using human DNA in criminal investigation and civil court cases, it currently presents a much wider application range, including not only legal situations sensu stricto but also and, increasingly often, to preemptively avoid judicial processes. Despite some difficulties, current forensic genetics is progressively incorporating the analysis of nonhuman genetic material to a greater extent. The analysis of this material-including other animal species, plants, or microorganisms-is now broadly used, providing ancillary evidence in criminalistics in cases such as animal attacks, trafficking of species, bioterrorism and biocrimes, and identification of fraudulent food composition, among many others. Here, we explore how nonhuman forensic genetics is being revolutionized by the increasing variety of genetic markers, the establishment of faster, less error-burdened and cheaper sequencing technologies, and the emergence and improvement of models, methods, and bioinformatics facilities.

Epigenetics and child abuse: Modern-day Darwinism--The miraculous ability of the human genome to adapt, and then adapt again.

PubMed

Gershon, Naomi B; High, Pamela C

2015-12-01

It has long been recognized that early adversity can have life-long consequences, and the extent to which this is true is gaining increasing attention. A growing body of literature implicates Adverse Childhood Experiences, including physical, sexual, and emotional abuse, in a broad range of negative health consequences including adult psychopathology, cardiovascular, and immune disease. Increasing evidence from animal, clinical, and epidemiological studies highlight the critical role of epigenetic programing, such as DNA methylation and histone modification, in altering gene expression, brain structure and function, and ultimately life-course trajectories. This review outlines our developing insight into the interplay between our human biology and our changing environment, and explores the growing evidence base for how interventions may prevent and ameliorate damage inflicted by toxic stress in early life. © 2015 Wiley Periodicals, Inc.

[The role of the Committee for Medicinal Products for Human Use (CHMP) in the European centralised procedure].

PubMed

Enzmann, Harald; Schneider, C

2008-07-01

The centralised procedure for marketing authorisation at the European Medicines Agency (EMEA) started more than 10 years ago, offering marketing authorisation for all member states of the European Union in a single procedure. Originally it was a purely optional alternative to the established national procedures; however, its importance has been growing ever since. The introduction of the mandatory scope for several important indications was a crucial step. The increasing importance of the centralised procedure was paralleled by the increasing weight of the EMEA and of the Committee for Human Medicinal Products (CHMP) who is responsible for scientific evaluation in the centralised procedure. This paper describes the basic principles of the centralised procedure including the definitions of the mandatory and optional scope, and how the CHMP works including its responsibility in European referrals that provide a link to national procedures.

Forensic genetics and genomics: Much more than just a human affair

PubMed Central

Oliveira, Manuela; Pinto, Nadia; Carracedo, Angel

2017-01-01

While traditional forensic genetics has been oriented towards using human DNA in criminal investigation and civil court cases, it currently presents a much wider application range, including not only legal situations sensu stricto but also and, increasingly often, to preemptively avoid judicial processes. Despite some difficulties, current forensic genetics is progressively incorporating the analysis of nonhuman genetic material to a greater extent. The analysis of this material—including other animal species, plants, or microorganisms—is now broadly used, providing ancillary evidence in criminalistics in cases such as animal attacks, trafficking of species, bioterrorism and biocrimes, and identification of fraudulent food composition, among many others. Here, we explore how nonhuman forensic genetics is being revolutionized by the increasing variety of genetic markers, the establishment of faster, less error-burdened and cheaper sequencing technologies, and the emergence and improvement of models, methods, and bioinformatics facilities. PMID:28934201

The potential for dietary restriction to increase longevity in humans: extrapolation from monkey studies.

PubMed

Ingram, Donald K; Roth, George S; Lane, Mark A; Ottinger, Mary Ann; Zou, Sige; de Cabo, Rafael; Mattison, Julie A

2006-06-01

Based on results emerging from long-term studies of dietary restriction in rhesus monkeys, we offer our views regarding whether dietary restriction can increase longevity in humans. Because lifespan data in monkeys remain inconclusive currently, we respond that "we do not for sure". Based on the vast literature regarding the effects of healthy, low calorie diets on health and longevity in a wide range of species, including humans, and based on data emerging from monkey studies suggesting that dietary restriction improves markers of disease risk and health, we respond that "we think so." Because it is unlikely that an experimental study will ever be designed to address this question in humans, we respond that "we think we will never know for sure." We suggest that debate of this question is clearly an academic exercise; thus, we would suggest that the more compelling discussion should focus on whether basic mechanisms of DR can be discovered and if such discoveries can lead to the development of effective DR mimetics. Even if proof that DR or DR mimetics can increase longevity in humans will likely never emerge, we would suggest that endpoints regarding disease risk and disease incidence as well as maintenance of function can be examined in human clinical trials, and that these will be highly relevant for evaluating the effectiveness of such treatments.

Bio-environmental factors associated with myopia: An updated review.

PubMed

Galvis, V; Tello, A; Camacho, P A; Parra, M M; Merayo-Lloves, J

2017-07-01

Experimental studies in animals, as well as observational and intervention studies in humans, seem to support the premise that the development of juvenile myopia is promoted by a combination of the effect of genetic and environmental factors, with a complex interaction between them. The very rapid increase in myopia rates in some parts of the world, such as Southeast Asia, supports a significant environmental effect. Several lines of evidence suggest that humans might respond to various external factors, such as increased activity in near vision, increased educational pressure, decreased exposure to sunlight outdoors, dietary changes (including increased intake of carbohydrates), as well as low light levels indoors. All these factors could be associated with a higher prevalence of myopia. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

Ending political abuse of psychiatry: where we are at and what needs to be done

PubMed Central

van Voren, Robert

2016-01-01

The number of reports of political activists falling victim to the political abuse of psychiatry is increasing. When the USSR first disintegrated, this practice virtually ceased to occur. What came in its place, however, was a disturbing collection of other forms of abuses, including human rights abuses, caused by a lack of resources, outdated treatment methods, a lack of understanding of individual human rights and a growing lack of tolerance in society. The number of cases of political abuse of psychiatry has increased since the 21st century began, particularly over the past few years in Russia, Belarus and Kazakhstan. PMID:26958357

Tree physiology research in a changing world.

PubMed

Kaufmann, Merrill R.; Linder, Sune

1996-01-01

Changes in issues and advances in methodology have contributed to substantial progress in tree physiology research during the last several decades. Current research focuses on process interactions in complex systems and the integration of processes across multiple spatial and temporal scales. An increasingly important challenge for future research is assuring sustainability of production systems and forested ecosystems in the face of increased demands for natural resources and human disturbance of forests. Meeting this challenge requires significant shifts in research approach, including the study of limitations of productivity that may accompany achievement of system sustainability, and a focus on the biological capabilities of complex land bases altered by human activity.

Pet ownership increases human risk of encountering ticks.

PubMed

Jones, E H; Hinckley, A F; Hook, S A; Meek, J I; Backenson, B; Kugeler, K J; Feldman, K A

2018-02-01

We examined whether pet ownership increased the risk for tick encounters and tickborne disease among residents of three Lyme disease-endemic states as a nested cohort within a randomized controlled trial. Information about pet ownership, use of tick control for pets, property characteristics, tick encounters and human tickborne disease were captured through surveys, and associations were assessed using univariate and multivariable analyses. Pet-owning households had 1.83 times the risk (95% CI = 1.53, 2.20) of finding ticks crawling on and 1.49 times the risk (95% CI = 1.20, 1.84) of finding ticks attached to household members compared to households without pets. This large evaluation of pet ownership, human tick encounters and tickborne diseases shows that pet owners, whether of cats or dogs, are at increased risk of encountering ticks and suggests that pet owners are at an increased risk of developing tickborne disease. Pet owners should be made aware of this risk and be reminded to conduct daily tick checks of all household members, including the pets, and to consult their veterinarian regarding effective tick control products. © 2017 Blackwell Verlag GmbH.

Body-composition changes in the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE)-2 study: A 2-y randomized controlled trial of calorie restriction in nonobese humans

USDA-ARS?s Scientific Manuscript database

Calorie restriction (CR) retards aging and increases longevity in many animal models. However, it is unclear whether CR can be implemented in humans without adverse effects on body composition. We evaluated the effect of a 2-year CR regimen on body composition including the influence of sex and body...

Cell sources for in vitro human liver cell culture models.

PubMed

Zeilinger, Katrin; Freyer, Nora; Damm, Georg; Seehofer, Daniel; Knöspel, Fanny

2016-09-01

In vitro liver cell culture models are gaining increasing importance in pharmacological and toxicological research. The source of cells used is critical for the relevance and the predictive value of such models. Primary human hepatocytes (PHH) are currently considered to be the gold standard for hepatic in vitro culture models, since they directly reflect the specific metabolism and functionality of the human liver; however, the scarcity and difficult logistics of PHH have driven researchers to explore alternative cell sources, including liver cell lines and pluripotent stem cells. Liver cell lines generated from hepatomas or by genetic manipulation are widely used due to their good availability, but they are generally altered in certain metabolic functions. For the past few years, adult and pluripotent stem cells have been attracting increasing attention, due their ability to proliferate and to differentiate into hepatocyte-like cells in vitro However, controlling the differentiation of these cells is still a challenge. This review gives an overview of the major human cell sources under investigation for in vitro liver cell culture models, including primary human liver cells, liver cell lines, and stem cells. The promises and challenges of different cell types are discussed with a focus on the complex 2D and 3D culture approaches under investigation for improving liver cell functionality in vitro Finally, the specific application options of individual cell sources in pharmacological research or disease modeling are described. © 2016 by the Society for Experimental Biology and Medicine.

Cell sources for in vitro human liver cell culture models

PubMed Central

Freyer, Nora; Damm, Georg; Seehofer, Daniel; Knöspel, Fanny

2016-01-01

In vitro liver cell culture models are gaining increasing importance in pharmacological and toxicological research. The source of cells used is critical for the relevance and the predictive value of such models. Primary human hepatocytes (PHH) are currently considered to be the gold standard for hepatic in vitro culture models, since they directly reflect the specific metabolism and functionality of the human liver; however, the scarcity and difficult logistics of PHH have driven researchers to explore alternative cell sources, including liver cell lines and pluripotent stem cells. Liver cell lines generated from hepatomas or by genetic manipulation are widely used due to their good availability, but they are generally altered in certain metabolic functions. For the past few years, adult and pluripotent stem cells have been attracting increasing attention, due their ability to proliferate and to differentiate into hepatocyte-like cells in vitro. However, controlling the differentiation of these cells is still a challenge. This review gives an overview of the major human cell sources under investigation for in vitro liver cell culture models, including primary human liver cells, liver cell lines, and stem cells. The promises and challenges of different cell types are discussed with a focus on the complex 2D and 3D culture approaches under investigation for improving liver cell functionality in vitro. Finally, the specific application options of individual cell sources in pharmacological research or disease modeling are described. PMID:27385595

Size of clinical trials and Introductory prices of prophylactic vaccine series

PubMed Central

Weinberg, Steven H.; Butchart, Amy T.; Davis, Matthew M.

2012-01-01

Costs of completing the recommended immunization schedule have increased over the last decade. Access to prophylactic vaccines may become limited due to financing obstacles within current delivery systems. Vaccine prices reflect research and development expenses incurred by vaccine manufacturers, including costs associated with evaluating candidate vaccines in human subjects. If the number of subjects in clinical trials is increasing over time and associated with vaccine price, this may help explain increases in prices of vaccine series. We examined whether: (A) the initial public- and private-sector prices for recommended prophylactic vaccine series licensed and recommended in the US increased from 2000–2011, (B) the number of human subjects per licensed vaccine increased during the time period, and (C) the number of human subjects was associated with the initial public–and private–sector prices of the vaccine series. In regression analyses of 13 vaccines, approval year was not significantly associated with the number of human subjects, initial public-sector prices, or initial private-sector prices. While the number of phase II subjects was not significantly associated with prices, the numbers of phase III and combined late phase (phases II + III) subjects were significantly associated with initial public- and private-sector series prices (p < 0.05). The association between number of subjects and initial prices demonstrated diminishing marginal increases in price with increasing numbers of subjects. These findings may help guide the number of subjects required by the FDA in clinical trials, in order to reduce expenses for manufacturers and thereby help mitigate increases in initial vaccine series prices. PMID:22854668

Size of clinical trials and Introductory prices of prophylactic vaccine series.

PubMed

Weinberg, Steven H; Butchart, Amy T; Davis, Matthew M

2012-08-01

Costs of completing the recommended immunization schedule have increased over the last decade. Access to prophylactic vaccines may become limited due to financing obstacles within current delivery systems. Vaccine prices reflect research and development expenses incurred by vaccine manufacturers, including costs associated with evaluating candidate vaccines in human subjects. If the number of subjects in clinical trials is increasing over time and associated with vaccine price, this may help explain increases in prices of vaccine series. We examined whether: (A) the initial public- and private-sector prices for recommended prophylactic vaccine series licensed and recommended in the US increased from 2000-2011, (B) the number of human subjects per licensed vaccine increased during the time period, and (C) the number of human subjects was associated with the initial public-and private-sector prices of the vaccine series. In regression analyses of 13 vaccines, approval year was not significantly associated with the number of human subjects, initial public-sector prices, or initial private-sector prices. While the number of phase II subjects was not significantly associated with prices, the numbers of phase III and combined late phase (phases II + III) subjects were significantly associated with initial public- and private-sector series prices (p < 0.05). The association between number of subjects and initial prices demonstrated diminishing marginal increases in price with increasing numbers of subjects. These findings may help guide the number of subjects required by the FDA in clinical trials, in order to reduce expenses for manufacturers and thereby help mitigate increases in initial vaccine series prices.

Potential Mechanisms for Cancer Resistance in Elephants and Comparative Cellular Response to DNA Damage in Humans

PubMed Central

Abegglen, Lisa M.; Caulin, Aleah F.; Chan, Ashley; Lee, Kristy; Robinson, Rosann; Campbell, Michael S.; Kiso, Wendy K.; Schmitt, Dennis L.; Waddell, Peter J; Bhaskara, Srividya; Jensen, Shane T.; Maley, Carlo C.; Schiffman, Joshua D.

2016-01-01

IMPORTANCE Evolutionary medicine may provide insights into human physiology and pathophysiology, including tumor biology. OBJECTIVE To identify mechanisms for cancer resistance in elephants and compare cellular response to DNA damage among elephants, healthy human controls, and cancer-prone patients with Li-Fraumeni syndrome (LFS). DESIGN, SETTING, AND PARTICIPANTS A comprehensive survey of necropsy data was performed across 36 mammalian species to validate cancer resistance in large and long-lived organisms, including elephants (n = 644). The African and Asian elephant genomes were analyzed for potential mechanisms of cancer resistance. Peripheral blood lymphocytes from elephants, healthy human controls, and patients with LFS were tested in vitro in the laboratory for DNA damage response. The study included African and Asian elephants (n = 8), patients with LFS (n = 10), and age-matched human controls (n = 11). Human samples were collected at the University of Utah between June 2014 and July 2015. EXPOSURES Ionizing radiation and doxorubicin. MAIN OUTCOMES AND MEASURES Cancer mortality across species was calculated and compared by body size and life span. The elephant genome was investigated for alterations in cancer-related genes. DNA repair and apoptosis were compared in elephant vs human peripheral blood lymphocytes. RESULTS Across mammals, cancer mortality did not increase with body size and/or maximum life span (eg, for rock hyrax, 1% [95%CI, 0%–5%]; African wild dog, 8%[95%CI, 0%–16%]; lion, 2%[95%CI, 0% –7%]). Despite their large body size and long life span, elephants remain cancer resistant, with an estimated cancer mortality of 4.81% (95%CI, 3.14%–6.49%), compared with humans, who have 11% to 25%cancer mortality. While humans have 1 copy (2 alleles) of TP53, African elephants have at least 20 copies (40 alleles), including 19 retrogenes (38 alleles) with evidence of transcriptional activity measured by reverse transcription polymerase chain reaction. In response to DNA damage, elephant lymphocytes underwent p53-mediated apoptosis at higher rates than human lymphocytes proportional to TP53 status (ionizing radiation exposure: patients with LFS, 2.71% [95%CI, 1.93%–3.48%] vs human controls, 7.17%[95%CI, 5.91%–8.44%] vs elephants, 14.64%[95%CI, 10.91%–18.37%]; P < .001; doxorubicin exposure: human controls, 8.10% [95%CI, 6.55%–9.66%] vs elephants, 24.77%[95%CI, 23.0%–26.53%]; P < .001). CONCLUSIONS AND RELEVANCE Compared with other mammalian species, elephants appeared to have a lower-than-expected rate of cancer, potentially related to multiple copies of TP53. Compared with human cells, elephant cells demonstrated increased apoptotic response following DNA damage. These findings, if replicated, could represent an evolutionary-based approach for understanding mechanisms related to cancer suppression. PMID:26447779

Imprinted and X-linked non-coding RNAs as potential regulators of human placental function

PubMed Central

Buckberry, Sam; Bianco-Miotto, Tina; Roberts, Claire T

2014-01-01

Pregnancy outcome is inextricably linked to placental development, which is strictly controlled temporally and spatially through mechanisms that are only partially understood. However, increasing evidence suggests non-coding RNAs (ncRNAs) direct and regulate a considerable number of biological processes and therefore may constitute a previously hidden layer of regulatory information in the placenta. Many ncRNAs, including both microRNAs and long non-coding transcripts, show almost exclusive or predominant expression in the placenta compared with other somatic tissues and display altered expression patterns in placentas from complicated pregnancies. In this review, we explore the results of recent genome-scale and single gene expression studies using human placental tissue, but include studies in the mouse where human data are lacking. Our review focuses on the ncRNAs epigenetically regulated through genomic imprinting or X-chromosome inactivation and includes recent evidence surrounding the H19 lincRNA, the imprinted C19MC cluster microRNAs, and X-linked miRNAs associated with pregnancy complications. PMID:24081302

Influence of the chopped frequency of light on optical transport characteristics of human skin including at acupuncture points

NASA Astrophysics Data System (ADS)

Yang, Hong-qin; Xie, Shu-sen; Liu, Song-hao; Li, Hui; Wang, Yu-hua; Guo, Zhou-yi

2007-11-01

An experimental protocol was established for noninvasively measuring the optical transport characteristics of skin tissue along human meridian direction over body surface including at acupuncture points. The diffuse remittance for 658 nm light radiation along the pericardium meridian and non-meridian directions were measured respectively. The influence of the chopped frequency of light on the detected light signal was investigated. It is shown that the optical transport characteristics of skin tissue accords with the Beer's exponential attenuation law along the meridian including at acupuncture points and non-median directions. However there is an obvious difference between the propagations along the meridian direction and non-meridian direction (P<0.05). Furthermore, the chopped frequency can affect the detected signal. The diffuse remittance signal decreased with the chopped frequency's increase and it was different between the meridian and non-meridian directions. These findings are important and meaningful for interpreting the human meridian phenomena by biomedical optics.

The Increase of Exotic Zoonotic Helminth Infections: The Impact of Urbanization, Climate Change and Globalization.

PubMed

Gordon, Catherine A; McManus, Donald P; Jones, Malcolm K; Gray, Darren J; Gobert, Geoffrey N

2016-01-01

Zoonotic parasitic diseases are increasingly impacting human populations due to the effects of globalization, urbanization and climate change. Here we review the recent literature on the most important helminth zoonoses, including reports of incidence and prevalence. We discuss those helminth diseases which are increasing in endemic areas and consider their geographical spread into new regions within the framework of globalization, urbanization and climate change to determine the effect these variables are having on disease incidence, transmission and the associated challenges presented for public health initiatives, including control and elimination. Copyright © 2016 Elsevier Ltd. All rights reserved.

Human-water interactions in Myanmar's Dry Zone under climate change

NASA Astrophysics Data System (ADS)

Taft, Linda; Evers, Mariele

2016-04-01

Understanding human-water interactions is particularly essential in countries where the economy and the people's well-being and income strongly depend on the availability and quality of sufficient water resources. Such a strong dependency on water is existent in Myanmar's Dry Zone located in the central Ayeyarwady River basin. In this area, rainfall is associated with high heterogeneity across space and time. Precipitation amounts in the Dry Zone (500-1000 mm annually) are generally less compared to other regions in Myanmar (up to 4000-6000 mm). Following the Global Climate Risk Index, Myanmar is one of the countries which were most affected by extreme weather events between 1994 and 2013. Severe drought periods e.g in the years 1997-1998, 2010 and 2014 led to crop failures and water shortage in the Dry Zone, where more than 14 mio people predominantly practice agriculture. Due to the high variability of rainfalls, farming is only possible with irrigation, mainly conducted by canal systems from the rivers and groundwater withdrawal. Myanmar is recently facing big challenges which result from comprehensive political and economic reforms since 2011. These may also include increasing water use by new industrial zones and urbanization. However, not only policy and economy modify the need for water. Variability of river runoff and changes in seasonality are expected as a result of climate change. The overarching goal of the study is to understand and increase the knowledge on human-water-climate interactions and to elaborate possible future scenarios for Myanmar's Dry Zone. It is not well studied yet how current and future climate change and increasing human impact will influence the country's abundant water resources including groundwater. Therefore, the first step of this study is to identify the major drivers within the central Ayeyarwady River basin. We are in the process of collecting and analyzing data sets and information including hydrologic and eco-hydrologic (discharge, sediment load, river biology), climatic (precipitation, temperature, evaporation) and anthropologic (water use, water management, dam projects) aspects. We identified key study sites in the Dry Zone, in order to assess and study the interplays, dependencies and feedbacks within the human-water system. First results based on meteorological data sets and literature survey indicate, that the central Dry Zone is affected by increasing interannual rainfall variability. Additionally, human impacts in this region are increasing due to numerous pumping (both river and groundwater) activities which will possibly alter water availability, river ecology and hydraulic processes in the near future. At the current state, the main course of the Ayeyarwady River is still unregulated but several larger dam projects are in the planning phase in the central area which will also impact the rich river biodiversity as well as the society. Our research will contribute to understand human-water-climate interactions in Myanmar's central Dry Zone with possible transferability to other large river basins in Asia.

Changes in the dissolved nitrogen pool across land cover gradients in Wisconsin streams.

PubMed

Stanley, Emily H; Maxted, Jeffrey T

2008-10-01

Increases in anthropogenic nitrogen fixation have resulted in wide-scale enrichment of aquatic ecosystems. Existing biogeochemical theory suggests that N enrichment is associated with increasing concentrations of nitrate; however, dissolved organic nitrogen (DON) is often a major component of the total dissolved nitrogen (TDN) pool in streams and rivers, and its concentration can be significantly elevated in human-influenced basins. We examined N concentrations during summer base flow conditions in 324 Wisconsin streams to determine whether DON was a significant component of TDN and how its relative contribution changed across a gradient of increasing human (agriculture and urban) land use for 84 of these sites. Total dissolved nitrogen varied from 0.09 to 20.74 mg/L, and although DON was significantly higher in human-dominated basins relative to forested and mixed-cover basins, its concentration increased relatively slowly in response to increasing human land cover. This limited response reflected a replacement of wetland-derived DON in low-N streams by anthropogenic sources in human-dominated sites, such that net changes in DON were small across the land use gradient. Nitrate-N increased exponentially in response to greater human land cover, and NH4-N and NO2-N were present at low levels. Nitrite-N exceeded NH4-N at 20% of sites and reached a maximum concentration of 0.10 mg/L. This examination suggests that basic mechanisms driving N losses from old-growth forests subject to N saturation also shape the summertime N pool in Wisconsin streams, in addition to other processes dictated by landscape context. The overwhelming role of human land use in determining the relative and absolute composition of the summertime N pool included (1) rapid increases in NO3-N, (2) limited changes in DON, and (3) the unexpected occurrence of NO2-N. High (>3 mg/L) TDN conditions dominated by NO3-N, regardless of landscape context or forms of N inputs, indicate a state of "N hypersaturation", which appears to be increasingly common in human-influenced streams and rivers. Many sites in agriculturally rich areas had NO2-N and NO3-N concentrations that, if sustained, are at chronically toxic levels for sensitive aquatic biota, suggesting that N enrichment now has local consequences for resident stream biota in addition to contributing to coastal eutrophication.

Superior pattern processing is the essence of the evolved human brain

PubMed Central

Mattson, Mark P.

2014-01-01

Humans have long pondered the nature of their mind/brain and, particularly why its capacities for reasoning, communication and abstract thought are far superior to other species, including closely related anthropoids. This article considers superior pattern processing (SPP) as the fundamental basis of most, if not all, unique features of the human brain including intelligence, language, imagination, invention, and the belief in imaginary entities such as ghosts and gods. SPP involves the electrochemical, neuronal network-based, encoding, integration, and transfer to other individuals of perceived or mentally-fabricated patterns. During human evolution, pattern processing capabilities became increasingly sophisticated as the result of expansion of the cerebral cortex, particularly the prefrontal cortex and regions involved in processing of images. Specific patterns, real or imagined, are reinforced by emotional experiences, indoctrination and even psychedelic drugs. Impaired or dysregulated SPP is fundamental to cognitive and psychiatric disorders. A broader understanding of SPP mechanisms, and their roles in normal and abnormal function of the human brain, may enable the development of interventions that reduce irrational decisions and destructive behaviors. PMID:25202234

Cyclic strain alters the expression and release of angiogenic factors by human tendon cells.

PubMed

Mousavizadeh, Rouhollah; Khosravi, Shahram; Behzad, Hayedeh; McCormack, Robert G; Duronio, Vincent; Scott, Alex

2014-01-01

Angiogenesis is associated with the tissue changes underlying chronic overuse tendinopathy. We hypothesized that repetitive, cyclic loading of human tendon cells would lead to increased expression and activity of angiogenic factors. We subjected isolated human tendon cells to overuse tensile loading using an in vitro model (1 Hz, 10% equibiaxial strain). We found that mechanically stimulated human tendon cells released factors that promoted in vitro proliferation and tube formation by human umbilical vein endothelial cells (HUVEC). In response to cyclic strain, there was a transient increase in the expression of several angiogenic genes including ANGPTL4, FGF-2, COX-2, SPHK1, TGF-alpha, VEGF-A and VEGF-C, with no change in anti-angiogenic genes (BAI1, SERPINF1, THBS1 and 2, TIMP1-3). Cyclic strain also resulted in the extracellular release of ANGPTL4 protein by tendon cells. Our study is the first report demonstrating the induction of ANGPTL4 mRNA and release of ANGPTL4 protein in response to cyclic strain. Tenocytes may contribute to the upregulation of angiogenesis during the development of overuse tendinopathy.

Cyclic Strain Alters the Expression and Release of Angiogenic Factors by Human Tendon Cells

PubMed Central

Mousavizadeh, Rouhollah; Khosravi, Shahram; Behzad, Hayedeh; McCormack, Robert G.; Duronio, Vincent; Scott, Alex

2014-01-01

Angiogenesis is associated with the tissue changes underlying chronic overuse tendinopathy. We hypothesized that repetitive, cyclic loading of human tendon cells would lead to increased expression and activity of angiogenic factors. We subjected isolated human tendon cells to overuse tensile loading using an in vitro model (1 Hz, 10% equibiaxial strain). We found that mechanically stimulated human tendon cells released factors that promoted in vitro proliferation and tube formation by human umbilical vein endothelial cells (HUVEC). In response to cyclic strain, there was a transient increase in the expression of several angiogenic genes including ANGPTL4, FGF-2, COX-2, SPHK1, TGF-alpha, VEGF-A and VEGF-C, with no change in anti-angiogenic genes (BAI1, SERPINF1, THBS1 and 2, TIMP1-3). Cyclic strain also resulted in the extracellular release of ANGPTL4 protein by tendon cells. Our study is the first report demonstrating the induction of ANGPTL4 mRNA and release of ANGPTL4 protein in response to cyclic strain. Tenocytes may contribute to the upregulation of angiogenesis during the development of overuse tendinopathy. PMID:24824595

Multilayer modeling and analysis of human brain networks

PubMed Central

2017-01-01

Abstract Understanding how the human brain is structured, and how its architecture is related to function, is of paramount importance for a variety of applications, including but not limited to new ways to prevent, deal with, and cure brain diseases, such as Alzheimer’s or Parkinson’s, and psychiatric disorders, such as schizophrenia. The recent advances in structural and functional neuroimaging, together with the increasing attitude toward interdisciplinary approaches involving computer science, mathematics, and physics, are fostering interesting results from computational neuroscience that are quite often based on the analysis of complex network representation of the human brain. In recent years, this representation experienced a theoretical and computational revolution that is breaching neuroscience, allowing us to cope with the increasing complexity of the human brain across multiple scales and in multiple dimensions and to model structural and functional connectivity from new perspectives, often combined with each other. In this work, we will review the main achievements obtained from interdisciplinary research based on magnetic resonance imaging and establish de facto, the birth of multilayer network analysis and modeling of the human brain. PMID:28327916

Respiratory transmission of an avian H3N8 influenza virus isolated from a harbour seal

USGS Publications Warehouse

Karlsson, Erik A.; Ip, Hon S.; Hall, Jeffrey S.; Yoon, Sun W.; Johnson, Jordan; Beck, Melinda A.; Webby, Richard J.; Schultz-Cherry, Stacey

2014-01-01

The ongoing human H7N9 influenza infections highlight the threat of emerging avian influenza viruses. In 2011, an avian H3N8 influenza virus isolated from moribund New England harbour seals was shown to have naturally acquired mutations known to increase the transmissibility of highly pathogenic H5N1 influenza viruses. To elucidate the potential human health threat, here we evaluate a panel of avian H3N8 viruses and find that the harbour seal virus displays increased affinity for mammalian receptors, transmits via respiratory droplets in ferrets and replicates in human lung cells. Analysis of a panel of human sera for H3N8 neutralizing antibodies suggests that there is no population-wide immunity to these viruses. The prevalence of H3N8 viruses in birds and multiple mammalian species including recent isolations from pigs and evidence that it was a past human pandemic virus make the need for surveillance and risk analysis of these viruses of public health importance.

Defining the Relationship Between Biomarkers of Oxidative and Inflammatory Stress and the Risk for Atherosclerosis in Astronauts During and After Long-Duration Spaceflight

NASA Technical Reports Server (NTRS)

Lee, S. M. C.; Martin, D. S.; Smith, S. M.; Zwart, S. R.; Laurie, S. S; Ribeiro, L. C.; Stenger, M. B.

2017-01-01

Current human space travel consists primarily of long-duration missions onboard the International Space Station (ISS), but in the future may include exploration-class missions to nearby asteroids, Mars, or its moons. These missions will expose astronauts to increased risk of oxidative and inflammatory damage from a variety of sources, including radiation, psychological stress, reduced physical activity, diminished nutritional status, and hyperoxic exposure during extravehicular activity. Evidence exists that increased oxidative stress and inflammation can accelerate the development of atherosclerosis.

Global climate change and children's health: threats and strategies for prevention.

PubMed

Sheffield, Perry E; Landrigan, Philip J

2011-03-01

Global climate change will have multiple effects on human health. Vulnerable populations-children, the elderly, and the poor-will be disproportionately affected. We reviewed projected impacts of climate change on children's health, the pathways involved in these effects, and prevention strategies. We assessed primary studies, review articles, and organizational reports. Climate change is increasing the global burden of disease and in the year 2000 was responsible for > 150,000 deaths worldwide. Of this disease burden, 88% fell upon children. Documented health effects include changing ranges of vector-borne diseases such as malaria and dengue; increased diarrheal and respiratory disease; increased morbidity and mortality from extreme weather; changed exposures to toxic chemicals; worsened poverty; food and physical insecurity; and threats to human habitation. Heat-related health effects for which research is emerging include diminished school performance, increased rates of pregnancy complications, and renal effects. Stark variation in these outcomes is evident by geographic region and socioeconomic status, and these impacts will exacerbate health disparities. Prevention strategies to reduce health impacts of climate change include reduction of greenhouse gas emissions and adaptation through multiple public health interventions. Further quantification of the effects of climate change on children's health is needed globally and also at regional and local levels through enhanced monitoring of children's environmental health and by tracking selected indicators. Climate change preparedness strategies need to be incorporated into public health programs.

Education, training, and human engineering in aerospace; SAE Aerotech '93, Costa Mesa, CA, Sep. 27-30, 1993

NASA Technical Reports Server (NTRS)

Shapiro, Diane C. (Editor); Norman, R. Michael (Editor)

1993-01-01

Advances in simulation technology are discussed by a number of government and industry experts, for both training and research and development applications. Advanced techniques, such as helmet-mounted information displays, neurocontrollers, automated training systems, and simulation for space-based systems are included. Advances in training methodology for air transportation are covered by a group of experts in that field, including discussions of advanced flight deck transition training, new training tools, and effective low cost alternatives for part-task training. With the ever-increasing emphasis on human factors in cockpit and cabin design, the section on research, advances, and certification criteria in that field is pertinent. NASA, aircraft manufacturing, and FAA representatives have compiled an informative group of presentations concerning active topics and considerations in human factors design.

Science versus (?) Art: Human Perception of Other Worlds

NASA Astrophysics Data System (ADS)

Hartmann, William K.

1998-09-01

At the time of the Renaissance, science and art were mixed together as a way to understand the human relation to the larger cosmos. Leonardo da Vinci exemplifies this approach. In modern times, the two have become separate, and even antagonistic, ``two cultures." Scientists have increasingly been satisfied to present quantitative measures of phenomena, without ever asking what the measures mean in human terms. Examples include the nature of the lunar surface, asteroid colors and brightness of the Io aurora, as will be discussed. However, in presenting the "big picture" to the public, and even to other working scientists, it is useful to revisit the Renaissance paradigm. Artists are increasingly working with scientists to translate the understanding of other worlds to the public, and this creates many opportunities for education projects in schools, and for careers in public outreach and science journalism.

Understanding complexities in coupled dynamics of human-water and food security

NASA Astrophysics Data System (ADS)

Usmani, M.; Kondal, A.; Lin, L.; Colwell, R. R.; Jutla, A.

2017-12-01

Traditional premise of food security is associated with satisfying human hunger by providing sufficient calories to population. Water is the key variable associated with the growth of crops, which is then used as a metric of success for abundance of food across globe. The current framework often negates complex coupled interaction between availability of food nutrients and human well-being (such as productivity, work efficiency, low birth weight, physical and mental growth). Our analysis suggests that 1 in 3 humans suffer from malnutrition across the globe. In last five decades, most of the countries have a decreasing availability trend in at least one of the twenty-three essential food nutrients required for human well-being. We argue that food security can only be achieved if information on use of water for crops and consumption of food must include availability of nutrients for humans. Here, we propose a new concept of "consumptive nutrients" that include constant feedback mechanism between water-human and societal processes- essential for growth, distribution and consumption of food nutrients. Using Ethiopia as a signature rain-fed agricultural region, we will show how decreasing precipitation has led to an increase in crop productivity, but decreased availability of nutrients for humans. This in turn has destabilizing impact on overall regional economy. We will demonstrate why inclusion of nutrients must be a part of discussion for ensuring food security to human population.

Relatively low prevalence of Babesia microti and Anaplasma phagocytophilum in Ixodes scapularis ticks collected in the Lehigh Valley region of eastern Pennsylvania.

PubMed

Edwards, Marten J; Barbalato, Laura A; Makkapati, Amulya; Pham, Katerina D; Bugbee, Louise M

2015-09-01

Several human pathogens are transmitted by the blacklegged tick, Ixodes scapularis. These include the spirochetes that cause Lyme disease (Borrelia burgdorferi) which is endemic to the Lehigh Valley region of eastern Pennsylvania. Emerging and currently rare tick-borne diseases have been of increasing concern in this region, including tick-borne relapsing fever (caused by Borrelia miyamotoi), human granulocytic anaplasmosis (caused by Anaplasma phagocytophilum), and human babesiosis (caused by Babesia microti). Real-time PCR assays and in some instances, conventional PCR followed by DNA sequencing, were used to screen 423 DNA samples that were prepared from questing adult and nymph stage I. scapularis ticks for infection with four tick-borne human pathogens. B. burgdorferi was detected in 23.2% of the sampled ticks, while B. miyamotoi, B. microti and a human variant of A. phagocytophilum were detected in less than 0.5% of the ticks. Our results are consistent with those expected in a region where Lyme disease is prevalent and human cases of tick-borne relapsing fever, babesiosis and human granulocytic anaplasmosis are not currently widespread. It is expected that this study will serve as a baseline for future studies of tick-borne pathogens in an area that is in close proximity to regions of high endemicity for Lyme disease, human granulocytic anaplasmosis and human babesiosis. Copyright © 2015 Elsevier GmbH. All rights reserved.

Genetic control of the alternative pathway of complement in humans and age-related macular degeneration

PubMed Central

Hecker, Laura A.; Edwards, Albert O.; Ryu, Euijung; Tosakulwong, Nirubol; Baratz, Keith H.; Brown, William L.; Issa, Peter Charbel; Scholl, Hendrik P.; Pollok-Kopp, Beatrix; Schmid-Kubista, Katharina E.; Bailey, Kent R.; Oppermann, Martin

2010-01-01

Activation of the alternative pathway of complement is implicated in common neurodegenerative diseases including age-related macular degeneration (AMD). We explored the impact of common variation in genes encoding proteins of the alternative pathway on complement activation in human blood and in AMD. Genetic variation across the genes encoding complement factor H (CFH), factor B (CFB) and component 3 (C3) was determined. The influence of common haplotypes defining transcriptional and translational units on complement activation in blood was determined in a quantitative genomic association study. Individual haplotypes in CFH and CFB were associated with distinct and novel effects on plasma levels of precursors, regulators and activation products of the alternative pathway of complement in human blood. Further, genetic variation in CFH thought to influence cell surface regulation of complement did not alter plasma complement levels in human blood. Plasma markers of chronic activation (split-products Ba and C3d) and an activating enzyme (factor D) were elevated in AMD subjects. Most of the elevation in AMD was accounted for by the genetic variation controlling complement activation in human blood. Activation of the alternative pathway of complement in blood is under genetic control and increases with age. The genetic variation associated with increased activation of complement in human blood also increased the risk of AMD. Our data are consistent with a disease model in which genetic variation in the complement system increases the risk of AMD by a combination of systemic complement activation and abnormal regulation of complement activation in local tissues. PMID:19825847

Effects of HIV and Methamphetamine on Brain and Behavior: Evidence from Human Studies and Animal Models

PubMed Central

Soontornniyomkij, Virawudh; Kesby, James P.; Morgan, Erin E.; Bischoff-Grethe, Amanda; Minassian, Arpi; Brown, Gregory G.; Grant, Igor

2016-01-01

Methamphetamine (Meth) use is frequent among HIV-infected persons. Combined HIV and Meth insults may exacerbate neural injury in vulnerable neuroanatomic structures or circuitries in the brain, leading to increased behavioral disturbance and cognitive impairment. While acute and chronic effects of Meth in humans and animal models have been studied for decades, the neurobehavioral effects of Meth in the context of HIV infection are much less explored. In-depth understanding of the scope of neurobehavioral phenotypes and mechanisms in HIV/Meth intersection is needed. The present report summarizes published research findings, as well as unpublished data, in humans and animal models with regard to neurobehavioral disturbance, neuroimaging, and neuropathology, and in vitro experimental systems, with an emphasis on findings emerging from the National Institute on Drug Abuse (NIDA) funded Translational Methamphetamine AIDS Research Center (TMARC). Results from human studies and animal (primarily HIV-1 gp120 transgenic mouse) models thus far suggest that combined HIV and Meth insults increase the likelihood of neural injury in the brain. The neurobehavioral effects include cognitive impairment and increased tendencies toward impaired behavioral inhibition and social cognition. These impairments are relevant to behaviors that affect personal and social risks, e.g. worse medication adherence, riskier behaviors, and greater likelihood of HIV transmission. The underlying mechanisms may include electrochemical changes in neuronal circuitries, injury to white matter microstructures, synaptodendritic damage, and selective neuronal loss. Utilization of research methodologies that are valid across species is instrumental in generating new knowledge with clinical translational value. PMID:27484318

Effects of HIV and Methamphetamine on Brain and Behavior: Evidence from Human Studies and Animal Models.

PubMed

Soontornniyomkij, Virawudh; Kesby, James P; Morgan, Erin E; Bischoff-Grethe, Amanda; Minassian, Arpi; Brown, Gregory G; Grant, Igor

2016-09-01

Methamphetamine (Meth) use is frequent among HIV-infected persons. Combined HIV and Meth insults may exacerbate neural injury in vulnerable neuroanatomic structures or circuitries in the brain, leading to increased behavioral disturbance and cognitive impairment. While acute and chronic effects of Meth in humans and animal models have been studied for decades, the neurobehavioral effects of Meth in the context of HIV infection are much less explored. In-depth understanding of the scope of neurobehavioral phenotypes and mechanisms in HIV/Meth intersection is needed. The present report summarizes published research findings, as well as unpublished data, in humans and animal models with regard to neurobehavioral disturbance, neuroimaging, and neuropathology, and in vitro experimental systems, with an emphasis on findings emerging from the National Institute on Drug Abuse (NIDA) funded Translational Methamphetamine AIDS Research Center (TMARC). Results from human studies and animal (primarily HIV-1 gp120 transgenic mouse) models thus far suggest that combined HIV and Meth insults increase the likelihood of neural injury in the brain. The neurobehavioral effects include cognitive impairment and increased tendencies toward impaired behavioral inhibition and social cognition. These impairments are relevant to behaviors that affect personal and social risks, e.g. worse medication adherence, riskier behaviors, and greater likelihood of HIV transmission. The underlying mechanisms may include electrochemical changes in neuronal circuitries, injury to white matter microstructures, synaptodendritic damage, and selective neuronal loss. Utilization of research methodologies that are valid across species is instrumental in generating new knowledge with clinical translational value.

Social and environmental risk factors in the emergence of infectious diseases.

PubMed

Weiss, Robin A; McMichael, Anthony J

2004-12-01

Fifty years ago, the age-old scourge of infectious disease was receding in the developed world in response to improved public health measures, while the advent of antibiotics, better vaccines, insecticides and improved surveillance held the promise of eradicating residual problems. By the late twentieth century, however, an increase in the emergence and re-emergence of infectious diseases was evident in many parts of the world. This upturn looms as the fourth major transition in human-microbe relationships since the advent of agriculture around 10,000 years ago. About 30 new diseases have been identified, including Legionnaires' disease, human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), hepatitis C, bovine spongiform encephalopathy (BSE)/variant Creutzfeldt-Jakob disease (vCJD), Nipah virus, several viral hemorrhagic fevers and, most recently, severe acute respiratory syndrome (SARS) and avian influenza. The emergence of these diseases, and resurgence of old ones like tuberculosis and cholera, reflects various changes in human ecology: rural-to-urban migration resulting in high-density peri-urban slums; increasing long-distance mobility and trade; the social disruption of war and conflict; changes in personal behavior; and, increasingly, human-induced global changes, including widespread forest clearance and climate change. Political ignorance, denial and obduracy (as with HIV/AIDS) further compound the risks. The use and misuse of medical technology also pose risks, such as drug-resistant microbes and contaminated equipment or biological medicines. A better understanding of the evolving social dynamics of emerging infectious diseases ought to help us to anticipate and hopefully ameliorate current and future risks.

CHEMICAL CHARACTERIZATION & SPECIATION OF MOBILE SOURCE EMISSIONS: HUMAN EXPOSURE IMPLICATIONS & IMPLEMENTATION PERSPECTIVES

EPA Science Inventory

A significant number of epidemiological studies have identified an increase in occurrence of adverse health effects associated with exposures to mobile source emissions. These adverse effects include asthma, other respiratory diseases, cardiovascular effects, cancer, development...

Ultrasound measurement of transcranial distance during head-down tilt

NASA Technical Reports Server (NTRS)

Torikoshi, S.; Wilson, M. H.; Ballard, R. E.; Watenpaugh, D. E.; Murthy, G.; Yost, W. T.; Cantrell, J. H.; Chang, D. S.; Hargens, A. R.

1995-01-01

Exposure to microgravity elevates blood pressure and flow in the head, which may increase intracranial volume (ICV) and intracranial pressure (ICP). Rhesus monkeys exposed to simulated microgravity in the form of 6 degree head-down tilt (HDT) experience elevated ICP. With humans, twenty-four hours of 6 degree HDT bed rest increases cerebral blood flow velocity relative to pre-HDT upright posture. Humans exposed to acute 6 degree HDT experiments increased ICP, measured with the tympanic membrane displacement (TMD) technique. Other studies suggest that increased ICP in humans and cats causes measurable cranial bone movement across the sagittal suture. Due to the slightly compliant nature of the cranium, elevation of the ICP will increase ICV and transcranial distance. Currently, several non-invasive approaches to monitor ICP are being investigated. Such techniques include TMD and modal analysis of the skull. TMD may not be reliable over a large range of ICP and neither method is capable of measuring the small changes in pressure. Ultrasound, however, may reliably measure small distance changes that accompany ICP fluctuations. The purpose of our study was to develop and evaluate an ultrasound technique to measure transcranial distance changes during HDT.

Animal and human models to understand ageing.

PubMed

Lees, Hayley; Walters, Hannah; Cox, Lynne S

2016-11-01

Human ageing is the gradual decline in organ and tissue function with increasing chronological time, leading eventually to loss of function and death. To study the processes involved over research-relevant timescales requires the use of accessible model systems that share significant similarities with humans. In this review, we assess the usefulness of various models, including unicellular yeasts, invertebrate worms and flies, mice and primates including humans, and highlight the benefits and possible drawbacks of each model system in its ability to illuminate human ageing mechanisms. We describe the strong evolutionary conservation of molecular pathways that govern cell responses to extracellular and intracellular signals and which are strongly implicated in ageing. Such pathways centre around insulin-like growth factor signalling and integration of stress and nutritional signals through mTOR kinase. The process of cellular senescence is evaluated as a possible underlying cause for many of the frailties and diseases of human ageing. Also considered is ageing arising from systemic changes that cannot be modelled in lower organisms and instead require studies either in small mammals or in primates. We also touch briefly on novel therapeutic options arising from a better understanding of the biology of ageing. Copyright © 2016. Published by Elsevier Ireland Ltd.

Isolation and characterization of canine perivascular stem/stromal cells for bone tissue engineering.

PubMed

James, Aaron W; Zhang, Xinli; Crisan, Mihaela; Hardy, Winters R; Liang, Pei; Meyers, Carolyn A; Lobo, Sonja; Lagishetty, Venu; Childers, Martin K; Asatrian, Greg; Ding, Catherine; Yen, Yu-Hsin; Zou, Erin; Ting, Kang; Peault, Bruno; Soo, Chia

2017-01-01

For over 15 years, human subcutaneous adipose tissue has been recognized as a rich source of tissue resident mesenchymal stem/stromal cells (MSC). The isolation of perivascular progenitor cells from human adipose tissue by a cell sorting strategy was first published in 2008. Since this time, the interest in using pericytes and related perivascular stem/stromal cell (PSC) populations for tissue engineering has significantly increased. Here, we describe a set of experiments identifying, isolating and characterizing PSC from canine tissue (N = 12 canine adipose tissue samples). Results showed that the same antibodies used for human PSC identification and isolation are cross-reactive with canine tissue (CD45, CD146, CD34). Like their human correlate, canine PSC demonstrate characteristics of MSC including cell surface marker expression, colony forming unit-fibroblast (CFU-F) inclusion, and osteogenic differentiation potential. As well, canine PSC respond to osteoinductive signals in a similar fashion as do human PSC, such as the secreted differentiation factor NEL-Like Molecule-1 (NELL-1). Nevertheless, important differences exist between human and canine PSC, including differences in baseline osteogenic potential. In summary, canine PSC represent a multipotent mesenchymogenic cell source for future translational efforts in tissue engineering.

Human hepatocytes derived from pluripotent stem cells: a promising cell model for drug hepatotoxicity screening.

PubMed

Gómez-Lechón, María José; Tolosa, Laia

2016-09-01

Drug-induced liver injury (DILI) is a frequent cause of failure in both clinical and post-approval stages of drug development, and poses a key challenge to the pharmaceutical industry. Current animal models offer poor prediction of human DILI. Although several human cell-based models have been proposed for the detection of human DILI, human primary hepatocytes remain the gold standard for preclinical toxicological screening. However, their use is hindered by their limited availability, variability and phenotypic instability. In contrast, pluripotent stem cells, which include embryonic and induced pluripotent stem cells (iPSCs), proliferate extensively in vitro and can be differentiated into hepatocytes by the addition of soluble factors. This provides a stable source of hepatocytes for multiple applications, including early preclinical hepatotoxicity screening. In addition, iPSCs also have the potential to establish genotype-specific cells from different individuals, which would increase the predictivity of toxicity assays allowing more successful clinical trials. Therefore, the generation of human hepatocyte-like cells derived from pluripotent stem cells seems to be promising for overcoming limitations of hepatocyte preparations, and it is expected to have a substantial repercussion in preclinical hepatotoxicity risk assessment in early drug development stages.

Theatre of the Oppressed in medical humanities education: the road less travelled.

PubMed

Gupta, Setu; Agrawal, Abhinav; Singh, Satendra; Singh, Navjeevan

2013-01-01

Internationally, there is an increasing awareness of the need to include humanities in the medical curriculum. The Medical Humanities Group at the University College of Medical Sciences, Delhi, organised a series of events to explore this area. This paper describes our experience with Augusto Boal's "Theatre of the Oppressed" (TO). Twenty-six participants attended a 2-day workshop culminating in a "forum theatre", in which the spectators are transformed from passive observers to active participants or spect-actors. The participants' responses to our workshop indicate that TO provides a multitude of experiences and addresses a wide range of learning domains. TO challenges the senses and offers a promising and enjoyable option for learning medical humanities.

Considerations in representing human individuals in social ecological models

USGS Publications Warehouse

Manfredo, Michael J.; Teel, Tara L.; Gavin, Michael C.; Fulton, David C.

2017-01-01

In this chapter we focus on how to integrate the human individual into social-ecological systems analysis, and how to improve research on individual thought and action regarding the environment by locating it within the broader social-ecological context. We discuss three key questions as considerations for future research: (1) is human thought conceptualized as a dynamic and adaptive process, (2) is the individual placed in a multi-level context (including within-person levels, person-group interactions, and institutional and structural factors), and (3) is human thought seen as mutually constructed with the social and natural environment. Increased emphasis on the individual will be essential if we are to understand agency, innovation, and adaptation in social-ecological systems.

The Importance of Human Milk for Immunity in Preterm Infants.

PubMed

Lewis, Erin D; Richard, Caroline; Larsen, Bodil M; Field, Catherine J

2017-03-01

The immune system of preterm infants is immature, placing them at increased risk for serious immune-related complications. Human milk provides a variety of immune protective and immune maturation factors that are beneficial to the preterm infant's poorly developed immune system. The most studied immune components in human milk include antimicrobial proteins, maternal leukocytes, immunoglobulins, cytokines and chemokines, oligosaccharides, gangliosides, nucleotides, and long-chain polyunsaturated fatty acids. There is growing evidence that these components contribute to the lower incidence of immune-related conditions in the preterm infant. Therefore, provision of these components in human milk, donor milk, or formula may provide immunologic benefits. Copyright © 2016 Elsevier Inc. All rights reserved.

Transfer of interferon alfa into human breast milk.

PubMed

Kumar, A R; Hale, T W; Mock, R E

2000-08-01

Originally assumed to be antiviral substances, the efficacy of interferons in a number of pathologies, including malignancies, multiple sclerosis, and other immune syndromes, is increasingly recognized. This study provides data on the transfer of interferon alfa (2B) into human milk of a patient receiving massive intravenous doses for the treatment of malignant melanoma. Following an intravenous dose of 30 million IU, the amount of interferon transferred into human milk was only slightly elevated (1551 IU/mL) when compared to control milk (1249 IU/mL). These data suggest that even following enormous doses, interferon is probably too large in molecular weight to transfer into human milk in clinically relevant amounts.

Fear of humans and its relationships with productivity in laying hens at commercial farms.

PubMed

Barnett, J L; Hemsworth, P H; Newman, E A

1992-09-01

1. The relationship between the behavioural responses of laying hens to humans and productivity was determined at 16 commercial sheds from 14 farms. 2. A number of behaviour variables were moderately to highly correlated with production variables; for example, the proportion of birds that moved away from an approaching experimenter in an unfamiliar environment ('shute test') was negatively correlated with peak hen day production, (PKHDP). 3. Behavioural responses to humans accounted for between 23 and 63% of the variation in a number of production variables, including PKHDP and the duration of a high level of production. 4. Inclusion of farm factor variables increased the amount of variation accounted for by the behaviour variables. For example, adding the variable 'time/day spent in the shed by stockpeople' to the behaviour variables 'the proportion of birds that moved away from an approaching human' in the shute test and 'the number of times birds in cages adopted an erect posture' in response to an approaching human increased the variation accounted for in PKHDP from 53 to 61%. 5. The results suggest that fear of humans may be a factor that limits the productivity of commercial laying hens.

Ethnographic Approaches in Primatology.

PubMed

Dore, Kerry M; Radford, Lucy; Alexander, Sherrie; Waters, Siân

2018-01-01

The shared evolutionary histories and anatomical similarities between humans and non-human primates create dynamic interconnections between these alloprimates. In this foreword to Folia Primatologica's special issue on "Ethnographic Approaches in Primatology," we review the ethnographic method and existing literature at the intersection of primatology and ethnography. We summarize, compare and contrast the 5 contributions to this special issue to highlight why the human-non-human primate interface is a compelling area to investigate via ethnographic approaches and to encourage increased incorporation of ethnography into the discipline of primatology. Ethnography is a valuable and increasingly popular tool with its use no longer limited to anthropological practitioners investigating traditional, non-Western peoples. Scholars from many disciplines now use ethnographic methods to investigate all members of our globalised world, including non-humans. As our closest living relatives, non-human primates (hereafter "primates") are compelling subjects and thus appear in a range of contexts within ethnographic investigations. The goal of this special issue is to highlight the trajectory of research at the intersection of primatology and ethnography and to illustrate the importance of ethnographic methods for the advancement of primatology as a discipline. © 2018 S. Karger AG, Basel.

Using the storm water management model to predict urban headwater stream hydrological response to climate and land cover change

Treesearch

J.Y. Wu; J.R. Thompson; R.K. Kolka; K.J. Franz; T.W. Stewart

2013-01-01

Streams are natural features in urban landscapes that can provide ecosystem services for urban residents. However, urban streams are under increasing pressure caused by multiple anthropogenic impacts, including increases in human population and associated impervious surface area, and accelerated climate change. The ability to anticipate these changes and better...

Off-target effects of sulforaphane include the derepression of long terminal repeats through histone acetylation events.

PubMed

Baier, Scott R; Zbasnik, Richard; Schlegel, Vicki; Zempleni, Janos

2014-06-01

Sulforaphane is a naturally occurring isothiocyanate in cruciferous vegetables. Sulforaphane inhibits histone deacetylases, leading to the transcriptional activation of genes including tumor suppressor genes. The compound has attracted considerable attention in the chemoprevention of prostate cancer. Here we tested the hypothesis that sulforaphane is not specific for tumor suppressor genes but also activates loci such as long terminal repeats (LTRs), which might impair genome stability. Studies were conducted using chemically pure sulforaphane in primary human IMR-90 fibroblasts and in broccoli sprout feeding studies in healthy adults. Sulforaphane (2.0 μM) caused an increase in LTR transcriptional activity in cultured cells. Consumption of broccoli sprouts (34, 68 or 102 g) by human volunteers caused a dose dependent elevation in LTR mRNA in circulating leukocytes, peaking at more than a 10-fold increase. This increase in transcript levels was associated with an increase in histone H3 K9 acetylation marks in LTR 15 in peripheral blood mononuclear cells from subjects consuming sprouts. Collectively, this study suggests that sulforaphane has off-target effects that warrant further investigation when recommending high levels of sulforaphane intake, despite its promising activities in chemoprevention. Copyright © 2014 Elsevier Inc. All rights reserved.

Detecting Candida albicans in human milk.

PubMed

Morrill, Jimi Francis; Pappagianis, Demosthenes; Heinig, M Jane; Lönnerdal, Bo; Dewey, Kathryn G

2003-01-01

Procedures for diagnosis of mammary candidosis, including laboratory confirmation, are not well defined. Lactoferrin present in human milk can inhibit growth of Candida albicans, thereby limiting the ability to detect yeast infections. The inhibitory effect of various lactoferrin concentrations on the growth of C. albicans in whole human milk was studied. The addition of iron to the milk led to a two- to threefold increase in cell counts when milk contained 3.0 mg of lactoferrin/ml and markedly reduced the likelihood of false-negative culture results. This method may provide the necessary objective support needed for diagnosis of mammary candidosis.

Patient Safety: The Role of Human Factors and Systems Engineering

PubMed Central

Carayon, Pascale; Wood, Kenneth E.

2011-01-01

Patient safety is a global challenge that requires knowledge and skills in multiple areas, including human factors and systems engineering. In this chapter, numerous conceptual approaches and methods for analyzing, preventing and mitigating medical errors are described. Given the complexity of healthcare work systems and processes, we emphasize the need for increasing partnerships between the health sciences and human factors and systems engineering to improve patient safety. Those partnerships will be able to develop and implement the system redesigns that are necessary to improve healthcare work systems and processes for patient safety. PMID:20543237

Human telomerase: biogenesis, trafficking, recruitment, and activation.

PubMed

Schmidt, Jens C; Cech, Thomas R

2015-06-01

Telomerase is the ribonucleoprotein enzyme that catalyzes the extension of telomeric DNA in eukaryotes. Recent work has begun to reveal key aspects of the assembly of the human telomerase complex, its intracellular trafficking involving Cajal bodies, and its recruitment to telomeres. Once telomerase has been recruited to the telomere, it appears to undergo a separate activation step, which may include an increase in its repeat addition processivity. This review covers human telomerase biogenesis, trafficking, and activation, comparing key aspects with the analogous events in other species. © 2015 Schmidt and Cech Published by Cold Spring Harbor Laboratory Press.

Viral entry mechanisms: the increasing diversity of paramyxovirus entry

PubMed Central

Smith, Everett Clinton; Popa, Andreea; Chang, Andres; Masante, Cyril; Dutch, Rebecca Ellis

2009-01-01

The paramyxovirus family contains established human pathogens such as measles virus and human respiratory syncytial virus, and emerging pathogens including the Hendra and Nipah viruses and the recently identified human metapneumovirus. Two major envelope glycoproteins, the attachment protein and the fusion protein, promote the processes of viral attachment and virus-cell membrane fusion required for entry. While common mechanisms of fusion protein proteolytic activation and the mechanism of membrane fusion promotion have been shown in recent years, considerable diversity exists in the family related to receptor binding and the potential mechanisms of fusion triggering. PMID:19878307

Predicting the Consequences of Workload Management Strategies with Human Performance Modeling

NASA Technical Reports Server (NTRS)

Mitchell, Diane Kuhl; Samma, Charneta

2011-01-01

Human performance modelers at the US Army Research Laboratory have developed an approach for establishing Soldier high workload that can be used for analyses of proposed system designs. Their technique includes three key components. To implement the approach in an experiment, the researcher would create two experimental conditions: a baseline and a design alternative. Next they would identify a scenario in which the test participants perform all their representative concurrent interactions with the system. This scenario should include any events that would trigger a different set of goals for the human operators. They would collect workload values during both the control and alternative design condition to see if the alternative increased workload and decreased performance. They have successfully implemented this approach for military vehicle. designs using the human performance modeling tool, IMPRINT. Although ARL researches use IMPRINT to implement their approach, it can be applied to any workload analysis. Researchers using other modeling and simulations tools or conducting experiments or field tests can use the same approach.

Preliminary thoughts on research in medical humanities.

PubMed

Yun, Xiaojing; Guo, Jiawei; Qian, Haihong

2017-05-23

Medical humanities (MH) is an interdisciplinary field of medicine which includes the humanities (literature, philosophy, ethics, history, and religion), social sciences (anthropology, cultural studies, psychology, sociology, and health geography), and the arts (literature, theater, film, and visual arts) and their application to medical education and practice. Studies of MH should not be limited to theoretical discussions. Research results must be translated into use of methodologies to formulate medical policies, guide clinical practices, and help resolve physical or mental problems. MH has a critical role in addressing medicine-related issues, such as human cloning legislation and the treatment of Ebola virus infection. Recently, MH has also been included in the "Healthy China 2030" project, indicating that MH has garnered more attention in China. Medical colleges, research institutes, and non-profit organizations are focusing on MH studies. Over the past few years, financial support for MH studies has also increased. Although the development of MH currently lags behind medicine and health sciences, MH has promise.

Artificial consciousness and the consciousness-attention dissociation.

PubMed

Haladjian, Harry Haroutioun; Montemayor, Carlos

2016-10-01

Artificial Intelligence is at a turning point, with a substantial increase in projects aiming to implement sophisticated forms of human intelligence in machines. This research attempts to model specific forms of intelligence through brute-force search heuristics and also reproduce features of human perception and cognition, including emotions. Such goals have implications for artificial consciousness, with some arguing that it will be achievable once we overcome short-term engineering challenges. We believe, however, that phenomenal consciousness cannot be implemented in machines. This becomes clear when considering emotions and examining the dissociation between consciousness and attention in humans. While we may be able to program ethical behavior based on rules and machine learning, we will never be able to reproduce emotions or empathy by programming such control systems-these will be merely simulations. Arguments in favor of this claim include considerations about evolution, the neuropsychological aspects of emotions, and the dissociation between attention and consciousness found in humans. Ultimately, we are far from achieving artificial consciousness. Copyright © 2016 Elsevier Inc. All rights reserved.

Emerging infectious diseases at the beginning of the 21st century.

PubMed

Lashley, Felissa R

2006-01-31

The emergence and re-emergence of infectious diseases involves many interrelated factors. Global interconnectedness continues to increase with international travel and trade; economic, political, and cultural interactions; and human-to-human and animal-to-human interactions. These interactions include the accidental and deliberate sharing of microbial agents and antimicrobial resistance and allow the emergence of new and unrecognized microbial disease agents. As the 21st century begins, already new agents have been identified, and new outbreaks have occurred. Solutions to limiting the spread of emerging infectious diseases will require cooperative efforts among many disciplines and entities worldwide. This article defines emerging infectious diseases, summarizes historical background, and discusses factors that contribute to emergence. Seven agents that have made a significant appearance, particularly in the 21st century, are reviewed, including: Ebola and Marburg hemorrhagic fevers, human monkeypox, bovine spongiform encephalopathy, severe acute respiratory syndrome (SARS), West Nile virus, and avian influenza. The article provides for each agent a brief historical background, case descriptions, and health care implications.

Aquaculture as yet another environmental gateway to the development and globalisation of antimicrobial resistance.

PubMed

Cabello, Felipe C; Godfrey, Henry P; Buschmann, Alejandro H; Dölz, Humberto J

2016-07-01

Aquaculture uses hundreds of tonnes of antimicrobials annually to prevent and treat bacterial infection. The passage of these antimicrobials into the aquatic environment selects for resistant bacteria and resistance genes and stimulates bacterial mutation, recombination, and horizontal gene transfer. The potential bridging of aquatic and human pathogen resistomes leads to emergence of new antimicrobial-resistant bacteria and global dissemination of them and their antimicrobial resistance genes into animal and human populations. Efforts to prevent antimicrobial overuse in aquaculture must include education of all stakeholders about its detrimental effects on the health of fish, human beings, and the aquatic ecosystem (the notion of One Health), and encouragement of environmentally friendly measures of disease prevention, including vaccines, probiotics, and bacteriophages. Adoption of these measures is a crucial supplement to efforts dealing with antimicrobial resistance by developing new therapeutic agents, if headway is to be made against the increasing problem of antimicrobial resistance in human and veterinary medicine. Copyright © 2016 Elsevier Ltd. All rights reserved.

A pilot study on the feasibility of European harmonized human biomonitoring: Strategies towards a common approach, challenges and opportunities.

PubMed

Casteleyn, L; Dumez, B; Becker, K; Kolossa-Gehring, M; Den Hond, E; Schoeters, G; Castaño, A; Koch, H M; Angerer, J; Esteban, M; Exley, K; Sepai, O; Bloemen, L; Horvat, M; Knudsen, L E; Joas, A; Joas, R; Biot, P; Koppen, G; Dewolf, M-C; Katsonouri, A; Hadjipanayis, A; Cerná, M; Krsková, A; Schwedler, G; Fiddicke, U; Nielsen, J K S; Jensen, J F; Rudnai, P; Közepésy, S; Mulcahy, M; Mannion, R; Gutleb, A C; Fischer, M E; Ligocka, D; Jakubowski, M; Reis, M F; Namorado, S; Lupsa, I-R; Gurzau, A E; Halzlova, K; Jajcaj, M; Mazej, D; Tratnik Snoj, J; Posada, M; López, E; Berglund, M; Larsson, K; Lehmann, A; Crettaz, P; Aerts, D

2015-08-01

In 2004 the European Commission and Member States initiated activities towards a harmonized approach for Human Biomonitoring surveys throughout Europe. The main objective was to sustain environmental health policy by building a coherent and sustainable framework and by increasing the comparability of data across countries. A pilot study to test common guidelines for setting up surveys was considered a key step in this process. Through a bottom-up approach that included all stakeholders, a joint study protocol was elaborated. From September 2011 till February 2012, 17 European countries collected data from 1844 mother-child pairs in the frame of DEMOnstration of a study to COordinate and Perform Human Biomonitoring on a European Scale (DEMOCOPHES).(1) Mercury in hair and urinary cadmium and cotinine were selected as biomarkers of exposure covered by sufficient analytical experience. Phthalate metabolites and Bisphenol A in urine were added to take into account increasing public and political awareness for emerging types of contaminants and to test less advanced markers/markers covered by less analytical experience. Extensive efforts towards chemo-analytical comparability were included. The pilot study showed that common approaches can be found in a context of considerable differences with respect to experience and expertize, socio-cultural background, economic situation and national priorities. It also evidenced that comparable Human Biomonitoring results can be obtained in such context. A European network was built, exchanging information, expertize and experiences, and providing training on all aspects of a survey. A key challenge was finding the right balance between a rigid structure allowing maximal comparability and a flexible approach increasing feasibility and capacity building. Next steps in European harmonization in Human Biomonitoring surveys include the establishment of a joint process for prioritization of substances to cover and biomarkers to develop, linking biomonitoring surveys with health examination surveys and with research, and coping with the diverse implementations of EU regulations and international guidelines with respect to ethics and privacy. Copyright © 2014 Elsevier Inc. All rights reserved.

Erythropoietin regulations in humans under different environmental and experimental conditions.

PubMed

Gunga, H-C; Kirsch, K A; Roecker, L; Kohlberg, E; Tiedemann, J; Steinach, M; Schobersberger, W

2007-09-30

In the adult human, the kidney is the main organ for the production and release of erythropoietin (EPO). EPO is stimulating erythropoiesis by increasing the proliferation, differentiation and maturation of the erythroid precursors. In the last decades, enormous efforts were made in the purification, molecular encoding and description of the EPO gene. This led to an incredible increase in the understanding of the EPO-feedback-regulation loop at a molecular level, especially the oxygen-dependent EPO gene expression, a key function in the regulation loop. However, studies in humans at a systemic level are still very scanty. Therefore, it is the purpose of the present review to report on the main recent investigations on EPO production and release in humans under different environmental and experimental conditions, including: (i) studies on EPO circadian, monthly and even annual variations, (ii) studies in connection with short-, medium- and long-term exercise at sea-level which will be followed (iii) by studies performed at moderate and high altitude.

Prevalence and correlates of human immunodeficiency virus testing and posttest counseling among outpatients with serious mental illness.

PubMed

Desai, Mayur M; Rosenheck, Robert A; Desai, Rani A

2007-09-01

This study examined the prevalence and correlates of receipt of human immunodeficiency virus (HIV) testing, test results, and posttest counseling among outpatients with serious mental illness at 3 public-sector facilities in Connecticut (N = 487). A substantial proportion (41.9%) reported never having been tested for HIV, including fully one-third of those who were "very afraid" of getting acquired immune deficiency syndrome. Independent correlates of HIV testing included younger age, felony criminal history, stronger therapeutic alliance with one's primary clinician, and increased drug problems and psychological distress. Of those tested, nearly all (96.5%) reported receiving the test results; however, only half (50.5%) reported receiving any posttest counseling. Independent correlates of posttest counseling included higher educational level, felony criminal history, and receipt of community-based case management services. Greater efforts are needed to increase HIV testing and counseling among persons with serious mental illness to better identify and care for HIV-positive individuals and potentially reduce future transmission of the virus in this vulnerable, at-risk population.

Medical considerations for extending human presence in space

NASA Technical Reports Server (NTRS)

Leach, C. S.; Dietlein, L. F.; Pool, S. L.; Nicogossian, A. E.

1990-01-01

The prospects for extending the length of time that humans can safely remain in space depend partly on resolution of a number of medical issues. Physiologic effects of weightlessness that may affect health during flight include loss of body fluid, functional alterations in the cardiovascular system, loss of red blood cells and bone mineral, compromised immune system function, and neurosensory disturbances. Some of the physiologic adaptations to weightlessness contribute to difficulties with readaptation to Earth's gravity. These include cardiovascular deconditioning and loss of body fluids and electrolytes; red blood cell mass; muscle mass, strength, and endurance; and bone mineral. Potentially harmful factors in space flight that are not related to weightlessness include radiation, altered circadian rhythms and rest/work cycles, and the closed, isolated environment of the spacecraft. There is no evidence that space flight has long-term effects on humans, except that bone mass lost during flight may not be replaced, and radiation damage is cumulative. However, the number of people who have spent several months or longer in space is still small. Only carefully-planned experiments in space preceded by thorough ground-based studies can provide the information needed to increase the amount of time humans can safely spend in space.

Sodium phenylbutyrate reverses lysosomal dysfunction and decreases amyloid-β42 in an in vitro-model of inclusion-body myositis.

PubMed

Nogalska, Anna; D'Agostino, Carla; Engel, W King; Askanas, Valerie

2014-05-01

Sporadic inclusion-body myositis (s-IBM) is a severe, progressive muscle disease for which there is no enduring treatment. Pathologically characteristic are vacuolated muscle fibers having: accumulations of multi-protein aggregates, including amyloid-β(Aβ) 42 and its toxic oligomers; increased γ-secretase activity; and impaired autophagy. Cultured human muscle fibers with experimentally-impaired autophagy recapitulate some of the s-IBM muscle abnormalities, including vacuolization and decreased activity of lysosomal enzymes, accompanied by increased Aβ42, Aβ42 oligomers, and increased γ-secretase activity. Sodium phenylbutyrate (NaPB) is an orally bioavailable small molecule approved by the FDA for treatment of urea-cycle disorders. Here we describe that NaPB treatment reverses lysosomal dysfunction in an in vitro model of inclusion-body myositis, involving cultured human muscle fibers. NaPB treatment improved lysosomal activity, decreased Aβ42 and its oligomers, decreased γ-secretase activity, and virtually prevented muscle-fiber vacuolization. Accordingly, NaPB might be considered a potential treatment of s-IBM patients. Copyright © 2014 Elsevier Inc. All rights reserved.

Farm Fairs and Petting Zoos: A Review of Animal Contact as a Source of Zoonotic Enteric Disease.

PubMed

Conrad, Cheyenne C; Stanford, Kim; Narvaez-Bravo, Claudia; Callaway, Todd; McAllister, Tim

2017-02-01

Many public venues such as farms, fairs, and petting zoos encourage animal contact for both educational and entertainment purposes. However, healthy farm animals, including cattle, small ruminants, and poultry, can be reservoirs for enteric zoonotic pathogens, with human infections resulting in nausea, vomiting, diarrhea, and, in some cases, severe complications that can lead to death. As animals shed these organisms in their feces, contamination of themselves and their surroundings is unavoidable. The majority of North Americans reside in urban and suburban settings, and the general public often possess limited knowledge of agricultural practices and minimal contact with farm animals. Furthermore, there is a lack of understanding of zoonotic pathogens, particularly how these pathogens are spread and the human behaviors that may increase the risk of infection. Human risk behaviors include hand-to-mouth contact immediately after physical contact with animals and their environments, a practice that facilitates the ingestion of pathogens. It is often young children who become ill due to their under-developed immune systems and poorer hygienic practices compared with adults, such as more frequent hand-to-mouth behaviors, and infrequent or improper hand washing. These illnesses are often preventable, simply through adequate hygiene and hand washing. Our objective was to use a structured approach to review the main causal organisms responsible for human illnesses acquired in petting zoo and open farm environments, Shiga toxin-producing Escherichia coli, nontyphoidal Salmonella, Campylobacter, and Cryptosporidium. Notable outbreaks involving direct contact with farm animals and farm, fair, or petting zoo environments are discussed and recommendations for how public venues can increase safety and hand hygiene compliance among visitors are proposed. The most effective protective measures against enteric illnesses include education of the public, increasing overall awareness of the risks and the importance of hand hygiene, as well as access to hand-washing facilities.

Omega-3 fatty acids in health and disease and in growth and development.

PubMed

Simopoulos, A P

1991-09-01

Several sources of information suggest that man evolved on a diet with a ratio of omega 6 to omega 3 fatty acids of approximately 1 whereas today this ratio is approximately 10:1 to 20-25:1, indicating that Western diets are deficient in omega 3 fatty acids compared with the diet on which humans evolved and their genetic patterns were established. Omega-3 fatty acids increase bleeding time; decrease platelet aggregation, blood viscosity, and fibrinogen; and increase erythrocyte deformability, thus decreasing the tendency to thrombus formation. In no clinical trial, including coronary artery graft surgery, has there been any evidence of increased blood loss due to ingestion of omega 3 fatty acids. Many studies show that the effects of omega 3 fatty acids on serum lipids depend on the type of patient and whether the amount of saturated fatty acids in the diet is held constant. In patients with hyperlipidemia, omega 3 fatty acids decrease low-density-lipoprotein (LDL) cholesterol if the saturated fatty acid content is decreased, otherwise there is a slight increase, but at high doses (32 g) they lower LDL cholesterol; furthermore, they consistently lower serum triglycerides in normal subjects and in patients with hypertriglyceridemia whereas the effect on high-density lipoprotein (HDL) varies from no effect to slight increases. The discrepancies between animal and human studies most likely are due to differences between animal and human metabolism. In clinical trials eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the form of fish oils along with antirheumatic drugs improve joint pain in patients with rheumatoid arthritis; have a beneficial effect in patients with ulcerative colitis; and in combination with drugs, improve the skin lesions, lower the hyperlipidemia from etretinates, and decrease the toxicity of cyclosporin in patients with psoriasis. In various animal models omega 3 fatty acids decrease the number and size of tumors and increase the time elapsed before appearance of tumors. Studies with nonhuman primates and human newborns indicate that DHA is essential for the normal functional development of the retina and brain, particularly in premature infants. Because omega 3 fatty acids are essential in growth and development throughout the life cycle, they should be included in the diets of all humans. Omega-3 and omega 6 fatty acids are not interconvertible in the human body and are important components of practically all cell membranes. Whereas cellular proteins are genetically determined, the polyunsaturated fatty acid (PUFA) composition of cell membranes is to a great extent dependent on the dietary intake.(ABSTRACT TRUNCATED AT 400 WORDS)

Designing Oversight for Nanomedicine Research in Human Subjects: Systematic Analysis of Exceptional Oversight for Emerging Technologies

PubMed Central

Wolf, Susan M.; Jones, Cortney

2012-01-01

The basic procedures and rules for oversight of U.S. human subjects research have been in place since 1981. Certain types of human subjects research, however, have provoked creation of additional mechanisms and rules beyond the Department of Health & Human Services (DHHS) Common Rule and Food and Drug Administration (FDA) equivalent. Now another emerging domain of human subjects research—nanomedicine—is prompting calls for extra oversight. However, in 30 years of overseeing research on human beings, we have yet to specify what makes a domain of scientific research warrant extra oversight. This failure to systematically evaluate the need for extra measures, the type of extra measures appropriate for different challenges, and the usefulness of those measures hampers efforts to respond appropriately to emerging science such as nanomedicine. This article evaluates the history of extra oversight, extracting lessons for oversight of nanomedicine research in human beings. We argue that a confluence of factors supports the need for extra oversight, including heightened uncertainty regarding risks, fast-evolving science yielding complex and increasingly active materials, likelihood of research on vulnerable participants including cancer patients, and potential risks to others beyond the research participant. We suggest the essential elements of the extra oversight needed. PMID:23226969

Designing oversight for nanomedicine research in human subjects: systematic analysis of exceptional oversight for emerging technologies

NASA Astrophysics Data System (ADS)

Wolf, Susan M.; Jones, Cortney M.

2011-04-01

The basic procedures and rules for oversight of U.S. human subjects research have been in place since 1981. Certain types of human subjects research, however, have provoked creation of additional mechanisms and rules beyond the Department of Health & Human Services (DHHS) Common Rule and Food and Drug Administration (FDA) equivalent. Now another emerging domain of human subjects research—nanomedicine—is prompting calls for extra oversight. However, in 30 years of overseeing research on human beings, we have yet to specify what makes a domain of scientific research warrant extra oversight. This failure to systematically evaluate the need for extra measures, the type of extra measures appropriate for different challenges, and the usefulness of those measures hampers efforts to respond appropriately to emerging science such as nanomedicine. This article evaluates the history of extra oversight, extracting lessons for oversight of nanomedicine research in human beings. We argue that a confluence of factors supports the need for extra oversight, including heightened uncertainty regarding risks, fast-evolving science yielding complex and increasingly active materials, likelihood of research on vulnerable participants including cancer patients, and potential risks to others beyond the research participant. We suggest the essential elements of the extra oversight needed.

Life Support and Habitation Systems: Crew Support and Protection for Human Exploration Missions Beyond Low Earth Orbit

NASA Technical Reports Server (NTRS)

Barta, Daniel J.; McQuillan, Jeffrey

2011-01-01

The National Aeronautics and Space Administration (NASA) has recently expanded its mission set for possible future human exploration missions. With multiple options there is interest in identifying technology needs across these missions to focus technology investments. In addition to the Moon and other destinations in cis-lunar space, other destinations including Near Earth Objects and Mars have been added for consideration. Recently, technology programs and projects have been re-organizing to better meet the Agency s strategic goals and address needs across these potential future missions. Life Support and Habitation Systems (LSHS) is one of 10 Foundational Domains as part of the National Aeronautics and Space Administration s Exploration Technology Development Program. The chief goal of LSHS is to develop and mature advanced technologies to sustain human life on missions beyond Low Earth Orbit (LEO) to increase reliability, reduce dependency on resupply and increase vehicle self-sufficiency. For long duration exploration missions, further closure of life support systems is of interest. Focus includes key technologies for atmosphere revitalization, water recovery, waste management, thermal control and crew accommodations. Other areas of focus include technologies for radiation protection, environmental monitoring and fire protection. The aim is to recover additional consumable mass, reduce requirements for power, volume, heat rejection, crew involvement, and meet exploration vehicle requirements. This paper provides a brief description of the LSHS Foundational Domain as defined for fiscal year 2011.

Glycobiology simplified: diverse roles of glycan recognition in inflammation

PubMed Central

Schnaar, Ronald L.

2016-01-01

Glycans and complementary glycan-binding proteins are essential components in the language of cell-cell interactions in immunity. The study of glycan function is the purview of glycobiology, which has often been presented as an unusually complex discipline. In fact, the human glycome, composed of all of its glycans, is built primarily from only 9 building blocks that are combined by enzymes (writers) with specific and limited biosynthetic capabilities into a tractable and increasingly accessible number of potential glycan patterns that are functionally read by several dozen human glycan-binding proteins (readers). Nowhere is the importance of glycan recognition better understood than in infection and immunity, and knowledge in this area has already led to glycan mimetic anti-infective and anti-inflammatory drugs. This review includes a brief tutorial on human glycobiology and a limited number of specific examples of glycan-binding protein-glycan interactions that initiate and regulate inflammation. Examples include representatives from different glycan-binding protein families, including the C-type lectins (E-selectin, P-selectin, dectin-1, and dectin-2), sialic acid-binding immunoglobulin-like lectins (sialic acid-binding immunoglobulin-like lectins 8 and 9), galectins (galectin-1, galectin-3, and galectin-9), as well as hyaluronic acid-binding proteins. As glycoscience technologies advance, opportunities for enhanced understanding of glycans and their roles in leukocyte cell biology provide increasing opportunities for discovery and therapeutic intervention. PMID:27004978

Stress markers in relation to job strain in human service organizations.

PubMed

Ohlson, C G; Söderfeldt, M; Söderfeldt, B; Jones, I; Theorell, T

2001-01-01

Workers in human service organizations are often confronted with conflicting demands in providing care or education. The aim of this cross-sectional study was to relate levels of endocrine stress markers to perceived job strain in two human service organizations. Employees in two local units of the social insurance organization and two local units of the individual and family care sections of the social welfare in Sweden were selected and 103 employees participated (56% participation rate). The perceived job strain was assessed with a standardized questionnaire containing questions of the demand-control model. Questions specially designed to measure emotional demands were also included. The stress markers cortisol, prolactin, thyroid-stimulating hormone, testosterone and IgA and IgG were analysed in blood samples. The main finding was an association between high emotional strain and increased levels of prolactin. The levels of cortisol, but none of the other four stress markers, increased slightly with emotional strain. Emotional strain experienced in human service work may cause psychological stress. The increase in prolactin was modest but consistent with findings in other published studies on stress-related endocrine alterations. Copyright 2001 S. Karger AG, Basel.

Stratospheric ozone loss, ultraviolet effects and action spectroscopy

NASA Astrophysics Data System (ADS)

Coohill, Thomas P.

The major effect of stratospheric ozone loss will be an increase in the amount of ultraviolet radiation reaching the ground. This increase will be entirely contained within the UV-B (290-320nm). How this will impact life on Earth will be determined by the UV-B photobiology of exposed organisms, including humans. One of the analytical methods useful in estimating these effects is Action Spectroscopy (biological effect as a function of wavelength). Carefully constructed action spectra will allow us to partially predict the increase in bio-effect due to additional UV exposure. What effect this has on the organism and the system in which the organism resides is of paramount importance. Suitable action spectra already exist for human skin cancer, human cell mutation and killing, and for one immune response. Comprehensive and widely applicable action spectra for terrestrial and aquatic plant responses are being generated but are not yet suitable for extensive analysis. There is little data available for animals, other than those experiments completed in the laboratory as model systems for human studies. Some polychromatic action spectra have proven useful in determining the possible impact of ozone loss on biological systems. The pitfalls and limits of this approach will be addressed.

Selenium Enrichment of Horticultural Crops.

PubMed

Puccinelli, Martina; Malorgio, Fernando; Pezzarossa, Beatrice

2017-06-04

The ability of some crops to accumulate selenium (Se) is crucial for human nutrition and health. Selenium has been identified as a cofactor of the enzyme glutathione peroxidase, which is a catalyzer in the reduction of peroxides that can damage cells and tissues, and can act as an antioxidant. Plants are the first link in the food chain, which ends with humans. Increasing the Se quantity in plant products, including leafy and fruity vegetables, and fruit crops, without exceeding the toxic threshold, is thus a good way to increase animal and human Se intake, with positive effects on long-term health. In many Se-enriched plants, most Se is in its major organic form. Given that this form is more available to humans and more efficient in increasing the selenium content than inorganic forms, the consumption of Se-enriched plants appears to be beneficial. An antioxidant effect of Se has been detected in Se-enriched vegetables and fruit crops due to an improved antioxidative status and to a reduced biosynthesis of ethylene, which is the hormone with a primary role in plant senescence and fruit ripening. This thus highlights the possible positive effect of Se in preserving a longer shelf-life and longer-lasting quality.

The effects of exercise on human articular cartilage

PubMed Central

Eckstein, F; Hudelmaier, M; Putz, R

2006-01-01

The effects of exercise on articular hyaline articular cartilage have traditionally been examined in animal models, but until recently little information has been available on human cartilage. Magnetic resonance imaging now permits cartilage morphology and composition to be analysed quantitatively in vivo. This review briefly describes the methodological background of quantitative cartilage imaging and summarizes work on short-term (deformational behaviour) and long-term (functional adaptation) effects of exercise on human articular cartilage. Current findings suggest that human cartilage deforms very little in vivo during physiological activities and recovers from deformation within 90 min after loading. Whereas cartilage deformation appears to become less with increasing age, sex and physical training status do not seem to affect in vivo deformational behaviour. There is now good evidence that cartilage undergoes some type of atrophy (thinning) under reduced loading conditions, such as with postoperative immobilization and paraplegia. However, increased loading (as encountered by elite athletes) does not appear to be associated with increased average cartilage thickness. Findings in twins, however, suggest a strong genetic contribution to cartilage morphology. Potential reasons for the inability of cartilage to adapt to mechanical stimuli include a lack of evolutionary pressure and a decoupling of mechanical competence and tissue mass. PMID:16637874

Decrease in cortisol reverses human hippocampal atrophy following treatment of Cushing's disease.

PubMed

Starkman, M N; Giordani, B; Gebarski, S S; Berent, S; Schork, M A; Schteingart, D E

1999-12-15

Decreased hippocampal volume is observed in patients with Cushing's syndrome and other conditions associated with elevated cortisol levels, stress, or both. Reversibility of hippocampal neuronal atrophy resulting from stress occurs in animals. Our study investigated the potential for reversibility of human hippocampal atrophy. The study included 22 patients with Cushing's disease. Magnetic resonance brain imaging was performed prior to transsphenoidal microadenomectomy and again after treatment. Following treatment, hippocampal formation volume (HFV) increased by up to 10%. The mean percent change (3.2 +/- 2.5) was significantly greater (p < .04) than that of the comparison structure, caudate head volume (1.5 +/- 3.4). Increase in HFV was significantly associated with magnitude of decrease in urinary free cortisol (r = -.61, p < .01). This relationship strengthened after adjustments for age, duration of disease, and months elapsed since surgery (r = -.70, p < .001). There was no significant correlation between caudate head volume change and magnitude of cortisol decrease. Changes in human HFV associated with sustained hypercortisolemia are reversible, at least in part, once cortisol levels decrease. While many brain regions are likely affected by hypercortisolemia, the human hippocampus exhibits increased sensitivity to cortisol, affecting both volume loss and recovery.

Care giving and nursing, work conditions and Humanitude®.

PubMed

Biquand, Sylvain; Zittel, Benoit

2012-01-01

Increased lifespan in western societies causes the increase of hospitalization in the old age, notably for patient showing forms of dementia including Altzheimer disease. These patients relate poorly to care givers and nurses, and cases of maltreatment have repeatedly been reported. To prevent abuse and increase patient's quality of life, Gineste and Pelissier (2007) proposed a philosophy of care based on the Humanitude® concept. Acknowledging that being human is being vertical and related to other humans, the pillars of Humanitude® are gaze, touch, talk, and standing. These modes of relation are systematically developed in care giving techniques derived from the concept. After several studies in geriatric hospitals, to assess psychosocial and ergonomic aspects of work, we present an analysis of the gap between the logic of human care and the logic of hospital organization, impacting employees work conditions and psychological welfare. Care giving is not only a "one to one" relation with the patient but needs to be integrated in the whole organization. Psychologists and ergonomists should be instrumental in defining the project and the organization linking human care giving towards the patients and better work conditions for healthcare employees.

The effects of exercise on human articular cartilage.

PubMed

Eckstein, F; Hudelmaier, M; Putz, R

2006-04-01

The effects of exercise on articular hyaline articular cartilage have traditionally been examined in animal models, but until recently little information has been available on human cartilage. Magnetic resonance imaging now permits cartilage morphology and composition to be analysed quantitatively in vivo. This review briefly describes the methodological background of quantitative cartilage imaging and summarizes work on short-term (deformational behaviour) and long-term (functional adaptation) effects of exercise on human articular cartilage. Current findings suggest that human cartilage deforms very little in vivo during physiological activities and recovers from deformation within 90 min after loading. Whereas cartilage deformation appears to become less with increasing age, sex and physical training status do not seem to affect in vivo deformational behaviour. There is now good evidence that cartilage undergoes some type of atrophy (thinning) under reduced loading conditions, such as with postoperative immobilization and paraplegia. However, increased loading (as encountered by elite athletes) does not appear to be associated with increased average cartilage thickness. Findings in twins, however, suggest a strong genetic contribution to cartilage morphology. Potential reasons for the inability of cartilage to adapt to mechanical stimuli include a lack of evolutionary pressure and a decoupling of mechanical competence and tissue mass.

Zoonotic infections in Alaska: disease prevalence, potential impact of climate change and recommended actions for earlier disease detection, research, prevention and control

PubMed Central

Hueffer, Karsten; Parkinson, Alan J.; Gerlach, Robert

2013-01-01

Over the last 60 years, Alaska's mean annual temperature has increased by 1.6°C, more than twice the rate of the rest of the United States. As a result, climate change impacts are more pronounced here than in other regions of the United States. Warmer temperatures may allow some infected host animals to survive winters in larger numbers, increase their population and expand their range of habitation thus increasing the opportunity for transmission of infection to humans. Subsistence hunting and gathering activities may place rural residents of Alaska at a greater risk of acquiring zoonotic infections than urban residents. Known zoonotic diseases that occur in Alaska include brucellosis, toxoplasmosis, trichinellosis, giardiasis/cryptosporidiosis, echinococcosis, rabies and tularemia. Actions for early disease detection, research and prevention and control include: (1) determining baseline levels of infection and disease in both humans and host animals; (2) conducting more research to understand the ecology of infection in the Arctic environment; (3) improving active and passive surveillance systems for infection and disease in humans and animals; (4) improving outreach, education and communication on climate-sensitive infectious diseases at the community, health and animal care provider levels; and (5) improving coordination between public health and animal health agencies, universities and tribal health organisations. PMID:23399790

Sleep intensity and the evolution of human cognition.

PubMed

Samson, David R; Nunn, Charles L

2015-01-01

Over the past four decades, scientists have made substantial progress in understanding the evolution of sleep patterns across the Tree of Life. Remarkably, the specifics of sleep along the human lineage have been slow to emerge. This is surprising, given our unique mental and behavioral capacity and the importance of sleep for individual cognitive performance. One view is that our species' sleep architecture is in accord with patterns documented in other mammals. We promote an alternative view, that human sleep is highly derived relative to that of other primates. Based on new and existing evidence, we specifically propose that humans are more efficient in their sleep patterns than are other primates, and that human sleep is shorter, deeper, and exhibits a higher proportion of REM than expected. Thus, we propose the sleep intensity hypothesis: Early humans experienced selective pressure to fulfill sleep needs in the shortest time possible. Several factors likely served as selective pressures for more efficient sleep, including increased predation risk in terrestrial environments, threats from intergroup conflict, and benefits arising from increased social interaction. Less sleep would enable longer active periods in which to acquire and transmit new skills and knowledge, while deeper sleep may be critical for the consolidation of those skills, leading to enhanced cognitive abilities in early humans. © 2015 Wiley Periodicals, Inc.

Quantitative Risk Assessment of Antimicrobial-Resistant Foodborne Infections in Humans Due to Recombinant Bovine Somatotropin Usage in Dairy Cows.

PubMed

Singer, Randall S; Ruegg, Pamela L; Bauman, Dale E

2017-07-01

Recombinant bovine somatotropin (rbST) is a production-enhancing technology that allows the dairy industry to produce milk more efficiently. Concern has been raised that cows supplemented with rbST are at an increased risk of developing clinical mastitis, which would potentially increase the use of antimicrobial agents and increase human illnesses associated with antimicrobial-resistant bacterial pathogens delivered through the dairy beef supply. The purpose of this study was to conduct a quantitative risk assessment to estimate the potential increased risk of human infection with antimicrobial-resistant bacteria and subsequent adverse health outcomes as a result of rbST usage in dairy cattle. The quantitative risk assessment included the following steps: (i) release of antimicrobial-resistant organisms from the farm, (ii) exposure of humans via consumption of contaminated beef products, and (iii) consequence of the antimicrobial-resistant infection. The model focused on ceftiofur (parenteral and intramammary) and oxytetracycline (parenteral) treatment of clinical mastitis in dairy cattle and tracked the bacteria Campylobacter spp., Salmonella enterica subsp. enterica, and Escherichia coli in the gastrointestinal tract of the cow. Parameter estimates were developed to be maximum risk to overestimate the risk to humans. The excess number of cows in the U.S. dairy herd that were predicted to carry resistant bacteria at slaughter due to rbST administration was negligible. The total number of excess human illnesses caused by resistant bacteria due to rbST administration was also predicted to be negligible with all risks considerably less than one event per 1 billion people at risk per year for all bacteria. The results indicate a high probability that the use of rbST according to label instructions presents a negligible risk for increasing the number of human illnesses and subsequent adverse outcomes associated with antimicrobial-resistant Campylobacter, Salmonella, or E. coli .

Increased Survival after Gemfibrozil Treatment of Severe Mouse Influenza▿

PubMed Central

Budd, Alison; Alleva, Lisa; Alsharifi, Mohammed; Koskinen, Aulikki; Smythe, Victoria; Müllbacher, Arno; Wood, Jeff; Clark, Ian

2007-01-01

Gemfibrozil, an agent that inhibits production of proinflammatory cytokines in addition to its clinically useful lipid-lowering activity, increased survival in BALB/c mice that were already ill from infection by influenza virus A/Japan/305/57 (H2N2). Gemfibrozil was administered intraperitoneally once daily from days 4 to 10 after intranasal exposure to the virus. Survival increased from 26% in vehicle-treated mice (n = 50) to 52% in mice given gemfibrozil at 60 mg/kg/day (n = 46) (P = 0.0026). If this principle translates to patients, a drug already approved for human use, albeit by a different route for another purpose, might be adapted relatively fast for use against influenza, conceivably including human infection with a derivative of the avian H5N1 strain. PMID:17562808

Consequences of human modification of the global nitrogen cycle.

PubMed

Erisman, Jan Willem; Galloway, James N; Seitzinger, Sybil; Bleeker, Albert; Dise, Nancy B; Petrescu, A M Roxana; Leach, Allison M; de Vries, Wim

2013-07-05

The demand for more food is increasing fertilizer and land use, and the demand for more energy is increasing fossil fuel combustion, leading to enhanced losses of reactive nitrogen (Nr) to the environment. Many thresholds for human and ecosystem health have been exceeded owing to Nr pollution, including those for drinking water (nitrates), air quality (smog, particulate matter, ground-level ozone), freshwater eutrophication, biodiversity loss, stratospheric ozone depletion, climate change and coastal ecosystems (dead zones). Each of these environmental effects can be magnified by the 'nitrogen cascade': a single atom of Nr can trigger a cascade of negative environmental impacts in sequence. Here, we provide an overview of the impact of Nr on the environment and human health, including an assessment of the magnitude of different environmental problems, and the relative importance of Nr as a contributor to each problem. In some cases, Nr loss to the environment is the key driver of effects (e.g. terrestrial and coastal eutrophication, nitrous oxide emissions), whereas in some other situations nitrogen represents a key contributor exacerbating a wider problem (e.g. freshwater pollution, biodiversity loss). In this way, the central role of nitrogen can remain hidden, even though it actually underpins many trans-boundary pollution problems.

Calorie restriction and cardiometabolic health.

PubMed

Fontana, Luigi

2008-02-01

An epidemic of overweight/obesity and type 2 diabetes, caused by overeating nutrient-poor energy-dense foods and a sedentary lifestyle, is spreading rapidly throughout the world. Abdominal obesity represents a serious threat to health because it increases the risk of developing many chronic diseases, including cardiovascular disease and cancer. Calorie restriction (CR) with adequate nutrition improves cardiometabolic health, prevents tumorigenesis and increases life span in experimental animals. The purpose of this review is to evaluate the metabolic and clinical implications of CR with adequate nutrition in humans, within the context of data obtained in animal models. It is unlikely that information regarding the effect of CR on maximal life span in humans will become available in the foreseeable future. In young and middle-aged healthy individuals, however, CR causes many of the same cardiometabolic adaptations that occur in long-lived CR rodents, including decreased metabolic, hormonal and inflammatory risk factors for diabetes, hypertension, cardiovascular disease and cancer. Unraveling the mechanisms that link calorie intake and body composition with metabolism and aging will be a major step in understanding the age-dependency of a wide range of human diseases and will also contribute to improve the general quality of life at old ages.

The natural history of violence.

PubMed Central

Russell, C; Russell, W M

1979-01-01

In the past, human violence was associated with food shortage, but recently it has increased even in relatively well-fed societies. The reason appears from studies of monkeys under relaxed, spacious conditions and under crowding stress. Uncrowded monkeys have unaggressive leaders, rarely quarrel, and protect females and young. Crowded monkeys (even well-fed) have brutal bosses, often quarrel, and wound and kill each other, including females and young. Crowding has similar behaviour effects on other mammals, with physiological disturbances including greater susceptibility to infections. All this appears to be a regular response to overpopulation, reducing the population before it has depleted its natural resources. Human beings, like monkeys and other mammals, need ample space, and become more violent when crowded. Human history is marked by population cycles: population outgrows resources, the resulting violence, stress and disease mortality cuts down the population, leading to a relief period of social and cultural progress, till renewed population growth produces the next crisis. The modern population crisis is world-wide, and explains the increase of violence even in well-fed societies. The solution to the problem of violence is to substitute voluntary birth control for involuntary death control, and bring about relaxed conditions for a reduced world population. PMID:114662

[The global climate: a sick patient].

PubMed

Lidegaard, Øjvind; Lidegaard, Martin

2008-08-25

Over the last 100 years the human use of fossil fuel has increased the atmospheric CO2 content from 280 parts per million (ppm) to 380 ppm. This increase is expected to increase the global average temperature by a few degrees. The global climate is very sensitive to an increase in temperature, and major climatic disasters, including health threats to millions of people, are probable if the CO2 emission increases further. Therefore, serious global initiatives should be taken now in order to prevent global over heating. Denmark should be at the forefront of these initiatives.

Modulation of endothelin receptors in the failing right ventricle of the heart and vasculature of the lung in human pulmonary arterial hypertension.

PubMed

Kuc, Rhoda E; Carlebur, Myrna; Maguire, Janet J; Yang, Peiran; Long, Lu; Toshner, Mark; Morrell, Nicholas W; Davenport, Anthony P

2014-11-24

In pulmonary arterial hypertension (PAH), increases in endothelin-1 (ET-1) contribute to elevated pulmonary vascular resistance which ultimately causes death by right ventricular (RV) heart failure. ET antagonists are effective in treating PAH but lack efficacy in treating left ventricular (LV) heart failure, where ETA receptors are significantly increased. The aim was to quantify the density of ETA and ETB receptors in cardiopulmonary tissue from PAH patients and the monocrotaline (MCT) rat, which recapitulates some of the pathophysiological features, including increased RV pressure. Radioligand binding assays were used to quantify affinity, density and ratio of ET receptors. In RV from human PAH hearts, there was a significant increase in the ratio of ETA to ETB receptors compared with normal hearts. In the RV of the MCT rat, the ratio also changed but was reversed. In both human and rat, there was no change in LV. In human PAH lungs, ETA receptors were significantly increased in the medial layer of small pulmonary arteries with no change detectable in MCT rat vessels. Current treatments for PAH focus mainly on pulmonary vasodilatation. The increase in ETA receptors in arteries provides a mechanism for the beneficial vasodilator actions of ET antagonists. The increase in the ratio of ETA in RV also implicates changes to ET signalling although it is unclear if ET antagonism is beneficial but the results emphasise the unexploited potential for therapies that target the RV, to improve survival in patients with PAH. Copyright © 2014. Published by Elsevier Inc.

Oceans and human health: Emerging public health risks n the marine environment

PubMed Central

Fleming, L.E.; Broad, K.; Clement, A.; Dewailly, E.; Elmir, S.; Knap, A.; Pomponi, S.A.; Smith, S.; Gabriele, H. Solo; Walsh, P.

2008-01-01

There has been an increasing recognition of the inter-relationship between human health and the oceans. Traditionally, the focus of research and concern has been on the impact of human activities on the oceans, particularly through anthropogenic pollution and the exploitation of marine resources. More recently, there has been recognition of the potential direct impact of the oceans on human health, both detrimental and beneficial. Areas identified include: global change, harmful algal blooms (HABs), microbial and chemical contamination of marine waters and seafood, and marine models and natural products from the seas. It is hoped that through the recognition of the inter-dependence of the health of both humans and the oceans, efforts will be made to restore and preserve the oceans. PMID:16996542

The Effect on Ecological Systems of Remediation to Protect Human Health

PubMed Central

Burger, Joanna

2007-01-01

Environmental remediation of contaminated eco-sytems reduces stresses to these ecosystems, including stresses caused by the production, use, and storage of weapons of mass destruction. The effects of these various stressors on humans can be reduced by remediation or by blocking the exposure of humans, but blocking the exposure of resident biota is almost impossible. Remediation may involve trade-offs between reducing a minor risk to public health and increasing risks to workers and ecosystems. Remediation practices such as soil removal disrupt ecosystems, which take decades to recover. Without further human disturbances, and with low levels of exposure to stress-ors, ecosystems can recover from physical disruptions and spills. Remediation to remove negligible risk to humans can destroy delicate ecosystems for very little gain in public health. PMID:17666693

Perfluorinated Compounds in House Dust from Ohio and North Carolina, USA

EPA Science Inventory

The perfluoroalkyl acids (PFAAs), including perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), have come under increasing scrutiny due to their persistence in the environment, global distribution, and animal toxicity. Given that human exposure routes for these c...

World Population Crisis.

ERIC Educational Resources Information Center

Ehrlich, Paul R.; Ehrlich, Anne H.

1986-01-01

Rapid population growth, rising competition for resources, and increasing environmental deterioration are intertwined factors in the human predicament that feed political tensions and conflicts of the late twentieth century. Outlines dimensions of this predicament (including data on population, growth, military spending, quality of life, and…

CURRENT ISSUES REGARDING ENDOCRINE DISRUPTING CHEMICALS AND ANTIBIOTIC RESISTANCE

EPA Science Inventory

Recently public concern has increased regarding industrial and environmental substances that may have adverse hormonal effects in human and wildlife populations. This concern has also been expanded to include antibiotic-resistant bacteria and the presence of various antibiotics a...

The Kept University.

ERIC Educational Resources Information Center

Press, Eyal; Washburn, Jennifer

2000-01-01

Examines the trend of increasing collaboration between American universities and corporations, including issues such as the academic-industrial complex, secrecy and science, the university as a business/commercial enterprise, who controls the research agenda, downsizing the humanities, and on-line marketing of course material. Expresses concerns…

Inactivation of NADPH oxidases NOX4 and NOX5 protects human primary fibroblasts from ionizing radiation-induced DNA damage.

PubMed

Weyemi, Urbain; Redon, Christophe E; Aziz, Towqir; Choudhuri, Rohini; Maeda, Daisuke; Parekh, Palak R; Bonner, Michael Y; Arbiser, Jack L; Bonner, William M

2015-03-01

Human exposure to ionizing radiation from medical procedures has increased sharply in the last three decades. Recent epidemiological studies suggest a direct relationship between exposure to ionizing radiation and health problems, including cancer incidence. Therefore, minimizing the impact of radiation exposure in patients has become a priority in the development of future clinical practices. Crucial players in radiation-induced DNA damage include reactive oxygen species (ROS), but the sources of these have remained elusive. To the best of our knowledge, we show here for the first time that two members of the ROS-generating NADPH oxidase family (NOXs), NOX4 and NOX5, are involved in radiation-induced DNA damage. Depleting these two NOXs in human primary fibroblasts resulted in reduced levels of DNA damage as measured by levels of radiation-induced foci, a marker of DNA double-strand breaks (DSBs) and the comet assay coupled with increased cell survival. NOX involvement was substantiated with fulvene-5, a NOXs-specific inhibitor. Moreover, fulvene-5 mitigated radiation-induced DNA damage in human peripheral blood mononuclear cells ex vivo. Our results provide evidence that the inactivation of NOXs protects cells from radiation-induced DNA damage and cell death. These findings suggest that NOXs inhibition may be considered as a future pharmacological target to help minimize the negative effects of radiation exposure for millions of patients each year.

Inactivation of NADPH Oxidases NOX4 and NOX5 Protects Human Primary Fibroblasts from Ionizing Radiation-Induced DNA Damage

PubMed Central

Weyemi, Urbain; Redon, Christophe E.; Aziz, Towqir; Choudhuri, Rohini; Maeda, Daisuke; Parekh, Palak R.; Bonner, Michael Y.; Arbiser, Jack L.; Bonner, William M.

2015-01-01

Human exposure to ionizing radiation from medical procedures has increased sharply in the last three decades. Recent epidemiological studies suggest a direct relationship between exposure to ionizing radiation and health problems, including cancer incidence. Therefore, minimizing the impact of radiation exposure in patients has become a priority in the development of future clinical practices. Crucial players in radiation-induced DNA damage include reactive oxygen species (ROS), but the sources of these have remained elusive. To the best of our knowledge, we show here for the first time that two members of the ROS-generating NADPH oxidase family (NOXs), NOX4 and NOX5, are involved in radiation-induced DNA damage. Depleting these two NOXs in human primary fibroblasts resulted in reduced levels of DNA damage as measured by levels of radiation-induced foci, a marker of DNA double-strand breaks (DSBs) and the comet assay coupled with increased cell survival. NOX involvement was substantiated with fulvene-5, a NOXs-specific inhibitor. Moreover, fulvene-5 mitigated radiation-induced DNA damage in human peripheral blood mononuclear cells ex vivo. Our results provide evidence that the inactivation of NOXs protects cells from radiation-induced DNA damage and cell death. These findings suggest that NOXs inhibition may be considered as a future pharmacological target to help minimize the negative effects of radiation exposure for millions of patients each year. PMID:25706776

Contributions of Nonhuman Primates to Research on Aging

PubMed Central

Didier, E. S.; MacLean, A. G.; Mohan, M.; Didier, P. J.; Lackner, A. A.; Kuroda, M. J.

2016-01-01

Aging is the biological process of declining physiologic function associated with increasing mortality rate during advancing age. Humans and higher nonhuman primates exhibit unusually longer average life spans as compared with mammals of similar body mass. Furthermore, the population of humans worldwide is growing older as a result of improvements in public health, social services, and health care systems. Comparative studies among a wide range of organisms that include nonhuman primates contribute greatly to our understanding about the basic mechanisms of aging. Based on their genetic and physiologic relatedness to humans, nonhuman primates are especially important for better understanding processes of aging unique to primates, as well as for testing intervention strategies to improve healthy aging and to treat diseases and disabilities in older people. Rhesus and cynomolgus macaques are the predominant monkeys used in studies on aging, but research with lower nonhuman primate species is increasing. One of the priority topics of research about aging in nonhuman primates involves neurologic changes associated with cognitive decline and neurodegenerative diseases. Additional areas of research include osteoporosis, reproductive decline, caloric restriction, and their mimetics, as well as immune senescence and chronic inflammation that affect vaccine efficacy and resistance to infections and cancer. The purpose of this review is to highlight the findings from nonhuman primate research that contribute to our understanding about aging and health span in humans. PMID:26869153

Contributions of Nonhuman Primates to Research on Aging.

PubMed

Didier, E S; MacLean, A G; Mohan, M; Didier, P J; Lackner, A A; Kuroda, M J

2016-03-01

Aging is the biological process of declining physiologic function associated with increasing mortality rate during advancing age. Humans and higher nonhuman primates exhibit unusually longer average life spans as compared with mammals of similar body mass. Furthermore, the population of humans worldwide is growing older as a result of improvements in public health, social services, and health care systems. Comparative studies among a wide range of organisms that include nonhuman primates contribute greatly to our understanding about the basic mechanisms of aging. Based on their genetic and physiologic relatedness to humans, nonhuman primates are especially important for better understanding processes of aging unique to primates, as well as for testing intervention strategies to improve healthy aging and to treat diseases and disabilities in older people. Rhesus and cynomolgus macaques are the predominant monkeys used in studies on aging, but research with lower nonhuman primate species is increasing. One of the priority topics of research about aging in nonhuman primates involves neurologic changes associated with cognitive decline and neurodegenerative diseases. Additional areas of research include osteoporosis, reproductive decline, caloric restriction, and their mimetics, as well as immune senescence and chronic inflammation that affect vaccine efficacy and resistance to infections and cancer. The purpose of this review is to highlight the findings from nonhuman primate research that contribute to our understanding about aging and health span in humans. © The Author(s) 2016.

Monitoring of Microbial Loads During Long Duration Missions as a Risk Reduction Tool

NASA Technical Reports Server (NTRS)

Roman, Monsi C.

2011-01-01

Humans have been exploring space for more than 40 years. For all those years microorganisms have accompanied, first un-manned spacecraft/cargo and later manned vessels. Microorganisms are everywhere on Earth, could easily adapt to new environments and/or can rapidly mutate to survive in very harsh conditions. Their presence in spacecraft and cargo have caused a few inconveniences over the years of humans spaceflight, ranging from crew health, life support systems challenges and material degradation. The sterilization of spacecraft that will host humans in long duration mission would be a costly operation that will not provide a long-term solution to the microbial colonization of the vessels. As soon as a human is exposed to the spacecraft, during the mission, microorganisms will start to populate the new environment. As the hum an presence in space increases in length, the risk from the microbial load, to hardware and crew will also increase. Mitigation of this risk includes several different strategies that will include minimizing the microbial load (in numbers and diversity) and monitoring. This presentation will provide a list of the risk mitigation strategies that should be implemented during ground processing, and during the mission. It will also discuss the areas that should be discussed before an effective in-flight microbial monitoring regimen is implemented. Microbial monitoring technologies will also be presented.

Zinc and its importance for human health: An integrative review

PubMed Central

Roohani, Nazanin; Hurrell, Richard; Kelishadi, Roya; Schulin, Rainer

2013-01-01

Since its first discovery in an Iranian male in 1961, zinc deficiency in humans is now known to be an important malnutrition problem world-wide. It is more prevalent in areas of high cereal and low animal food consumption. The diet may not necessarily be low in zinc, but its bio-availability plays a major role in its absorption. Phytic acid is the main known inhibitor of zinc. Compared to adults, infants, children, adolescents, pregnant, and lactating women have increased requirements for zinc and thus, are at increased risk of zinc depletion. Zinc deficiency during growth periods results in growth failure. Epidermal, gastrointestinal, central nervous, immune, skeletal, and reproductive systems are the organs most affected clinically by zinc deficiency. Clinical diagnosis of marginal Zn deficiency in humans remains problematic. So far, blood plasma/serum zinc concentration, dietary intake, and stunting prevalence are the best known indicators of zinc deficiency. Four main intervention strategies for combating zinc deficiency include dietary modification/diversification, supplementation, fortification, and bio-fortification. The choice of each method depends on the availability of resources, technical feasibility, target group, and social acceptance. In this paper, we provide a review on zinc biochemical and physiological functions, metabolism including, absorption, excretion, and homeostasis, zinc bio-availability (inhibitors and enhancers), human requirement, groups at high-risk, consequences and causes of zinc deficiency, evaluation of zinc status, and prevention strategies of zinc deficiency. PMID:23914218

Human ES cells – haematopoiesis and transplantation strategies*

PubMed Central

Kaufman, DS; Thomson, JA

2002-01-01

Human embryonic stem (ES) cells provide a novel opportunity to study early developmental events in a human system. We have used human ES cell lines, including clonally derived lines, to evaluate haematopoiesis. Co-culture of the human ES cells with irradiated bone marrow stromal cell lines in the presence of fetal bovine serum (FBS), but without other exogenous cytokines, leads to differentiation of the human ES cells within a matter of days. A portion of these differentiated cells express CD34, the best-defined marker for early haematopoietic cells. Haematopoietic colony-forming cells (CFCs) are demonstrated by methylcellulose assay. Myeloid, erythroid, megakaryocyte and multipotential CFCs can all be derived under these conditions. Enrichment of CD34+ cells derived from the human ES cells markedly increases the yield of CFCs, as would be expected for cells derived from adult bone marrow or umbilical cord blood. Transcription factors are also expressed in a manner consistent with haematopoietic differentiation. This system now presents the potential to evaluate specific conditions needed to induce or support events in early human blood development. Human ES cells are also a novel source of cells for transplantation therapies. The immunogenicity of ES cell-derived cells is unknown. The unique properties of ES cells afford the opportunity to explore novel mechanisms to prevent immune-mediated rejection. Potential strategies to overcome rejection will be presented, including creation of haematopoietic chimerism as a means to successfully transplant cells and tissues derived from human ES cells. PMID:12033728

Trends and molecular mechanisms of antimicrobial resistance in clinical staphylococci isolated from companion animals over a 16 year period.

PubMed

Couto, Natacha; Monchique, Cláudia; Belas, Adriana; Marques, Cátia; Gama, Luís T; Pomba, Constança

2016-06-01

The objective of this study was to investigate the evolution of resistance to antimicrobials, corresponding mechanisms and molecular characteristics of Staphylococcus spp., between 1999 and 2014. Susceptibility to 38 antimicrobials was determined for 632 clinical staphylococcal isolates obtained from companion animals (dogs, cats, horses and other animals). Twenty antimicrobial resistance genes, including mecA and mecC, were screened by PCR. Methicillin-resistant staphylococci were characterized by spa (Staphylococcus aureus), SCCmec, MLST and PFGE typing. Statistical analyses were performed using SAS v9.3 and differences were considered relevant if P ≤ 0.05. The mecA gene was identified in 74 staphylococcal isolates (11.6%): 11 MRSA (40.7%), 40 methicillin-resistant Staphylococcus pseudintermedius (MRSP; 8.7%) and 23 methicillin-resistant CoNS (26.7%). Resistance to the majority of antimicrobials and the number of mecA-positive isolates increased significantly over time. Eighteen spa types were identified, including two new ones. MRSA isolates were divided into three PFGE clusters that included ST22-IV, ST105-II, ST398-V and ST5-VI. Most methicillin-resistant Staphylococcus epidermidis isolates were of clonal complex (CC) 5, including a new ST, and clustered in eight PFGE clusters. MRSP were grouped into five PFGE clusters and included ST45-NT, ST71-II-III, ST195-III, ST196-V, ST339-NT, ST342-IV and the new ST400-III. Methicillin-resistant Staphylococcus haemolyticus clustered in two PFGE clusters. The significant increase in antimicrobial-resistant and mecA-positive isolates in recent years is worrying. Furthermore, several isolates are MDR, which complicates antimicrobial treatment and increases the risk of transfer to humans or human isolates. Several clonal lineages of MRSA and methicillin-resistant S. epidermidis circulating in human hospitals and the community were found, suggesting that companion animals can become infected with and contribute to the dissemination of highly successful human clones. Urgent measures, such as determination of clinical breakpoints and guidelines for antimicrobial use, are needed. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Paradoxical Regulation of Human FGF21 by Both Fasting and Feeding Signals: Is FGF21 a Nutritional Adaptation Factor?

PubMed Central

Uebanso, Takashi; Taketani, Yutaka; Yamamoto, Hironori; Amo, Kikuko; Ominami, Hirokazu; Arai, Hidekazu; Takei, Yuichiro; Masuda, Masashi; Tanimura, Ayako; Harada, Nagakatsu; Yamanaka-Okumura, Hisami; Takeda, Eiji

2011-01-01

Fibroblast growth factor 21 (FGF21) has recently emerged as a metabolic hormone involved in regulating glucose and lipid metabolism in mouse, but the regulatory mechanisms and actions of FGF21 in humans remain unclear. Here we have investigated the regulatory mechanisms of the human FGF21 gene at the transcriptional level. A deletion study of the human FGF21 promoter (−1672 to +230 bp) revealed two fasting signals, including peroxisome proliferator-activated receptor α (PPARα) and glucagon signals, that independently induced human FGF21 gene transcription in mouse primary hepatocytes. In addition, two feeding signals, glucose and xylitol, also dose-dependently induced human FGF21 gene transcription and mRNA expression in both human HepG2 cells and mouse primary hepatocytes. FGF21 protein expression and secretion were also induced by high glucose stimulation. The human FGF21 promoter (−1672 to +230 bp) was found to have a carbohydrate-responsive element at −380 to −366 bp, which is distinct from the PPAR response element (PPRE). Knock-down of the carbohydrate response element binding protein by RNAi diminished glucose-induced human FGF21 transcription. Moreover, we found that a region from −555 to −443 bp of the human FGF21 promoter region exerts an important role in the activation of basic transcription. In conclusion, human FGF21 gene expression is paradoxically and independently regulated by both fasting and feeding signals. These regulatory mechanisms suggest that human FGF21 is increased with nutritional crisis, including starvation and overfeeding. PMID:21829679

Gadolinium compounds signaling through TLR4 and TLR7 in normal human macrophages: establishment of a proinflammatory phenotype and implications for the pathogenesis of nephrogenic systemic fibrosis.

PubMed

Wermuth, Peter J; Jimenez, Sergio A

2012-07-01

Nephrogenic systemic sibrosis is a progressive disorder occurring in some renal insufficiency patients exposed to gadolinium-based contrast agents (GdBCA). Previous studies demonstrated that the GdBCA Omniscan upregulated several innate immunity pathways in normal differentiated human macrophages, induced rapid nuclear localization of the transcription factor NF-κB, and increased the expression and production of numerous profibrotic/proinflammatory cytokines, chemokines, and growth factors. To further examine GdBCA stimulation of the innate immune system, cultured human embryonic kidney 293 cells expressing one of seven different human TLRs or one of two human nucleotide-binding oligomerization domain-like receptors were exposed in vitro for 24 h to various GdBCA. The signaling activity of each compound was evaluated by its ability to activate an NF-κB-inducible reporter gene. Omniscan and gadodiamide induced strong TLR4- and TLR7-mediated reporter gene activation. The other Gd compounds examined failed to induce reporter gene activation. TLR pathway inhibition using chloroquine or an inhibitor of IL-1R-associated kinases 1 and 4 in normal differentiated human macrophages abrogated Omniscan-induced gene expression. Omniscan and gadodiamide signaling via TLRs 4 and 7 resulted in increased production and expression of numerous proinflammatory/profibrotic cytokines, chemokines, and growth factors, including CXCL10, CCL2, CCL8, CXCL12, IL-4, IL-6, TGF-β, and vascular endothelial growth factor. These observations suggest that TLR activation by environmental stimuli may participate in the pathogenesis of nephrogenic systemic fibrosis and of other fibrotic disorders including systemic sclerosis.

Microphthalmia-associated transcription factor as the molecular target of cadmium toxicity in human melanocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chantarawong, Wipa; Inter Departmental Multidisciplinary Graduate Program in Bioscience, Faculty of Science, Kasetsart University, Bangkok; Takeda, Kazuhisa

Highlights: • In human melanocytes, cadmium decreases the expression of MITF-M and tyrosinase and their mRNAs. • In human melanoma cells, cadmium decreases the expression of MITF-M protein and tyrosinase mRNA. • Expression of MITF-H is less sensitive to cadmium toxicity in melanocyte-linage cells. • Cadmium does not decrease the expression of MITF-H in retinal pigment epithelial cells. • MITF-M is the molecular target of cadmium toxicity in melanocytes. - Abstract: Dietary intake of cadmium is inevitable, causing age-related increase in cadmium accumulation in many organs, including hair, choroid and retinal pigment epithelium (RPE). Cadmium has been implicated in themore » pathogenesis of hearing loss and macular degeneration. The functions of cochlea and retina are maintained by melanocytes and RPE, respectively, and the differentiation of these pigment cells is regulated by microphthalmia-associated transcription factor (MITF). In the present study, we explored the potential toxicity of cadmium in the cochlea and retina by using cultured human melanocytes and human RPE cell lines. MITF consists of multiple isoforms, including melanocyte-specific MITF-M and widely expressed MITF-H. Levels of MITF-M protein and its mRNA in human epidermal melanocytes and HMV-II melanoma cells were decreased significantly by cadmium. In parallel with the MITF reduction, mRNA levels of tyrosinase, the key enzyme of melanin biosynthesis that is regulated by MITF-M, were also decreased. In RPE cells, however, the levels of total MITF protein, constituting mainly MITF-H, were not decreased by cadmium. We thus identify MITF-M as the molecular target of cadmium toxicity in melanocytes, thereby accounting for the increased risk of disability from melanocyte malfunction, such as hearing and vision loss among people with elevated cadmium exposure.« less

Development of steroid signaling pathways during primordial follicle formation in the human fetal ovary.

PubMed

Fowler, Paul A; Anderson, Richard A; Saunders, Philippa T; Kinnell, Hazel; Mason, J Ian; Evans, Dean B; Bhattacharya, Siladitya; Flannigan, Samantha; Franks, Stephen; Monteiro, Ana; O'Shaughnessy, Peter J

2011-06-01

Ovarian primordial follicle formation is critical for subsequent human female fertility. It is likely that steroid, and especially estrogen, signaling is required for this process, but details of the pathways involved are currently lacking. The aim was to identify and characterize key members of the steroid-signaling pathway expressed in the second trimester human fetal ovary. We conducted an observational study of the female fetus, quantifying and localizing steroid-signaling pathway members. The study was conducted at the Universities of Aberdeen, Edinburgh, and Glasgow. Ovaries were collected from 43 morphologically normal human female fetuses from women undergoing elective termination of second trimester pregnancies. We measured mRNA transcript levels and immunolocalized key steroidogenic enzymes and steroid receptors, including those encoded by ESR2, AR, and CYP19A1. Levels of mRNA encoding the steroidogenic apparatus and steroid receptors increased across the second trimester. CYP19A1 transcript increased 4.7-fold during this period with intense immunostaining for CYP19A detected in pregranulosa cells around primordial follicles and somatic cells around oocyte nests. ESR2 was localized primarily to germ cells, but androgen receptor was exclusively expressed in somatic cells. CYP17A1 and HSD3B2 were also localized to oocytes, whereas CYP11A1 was detected in oocytes and some pregranulosa cells. The human fetal ovary expresses the machinery to produce and detect multiple steroid signaling pathways, including estrogenic signaling, with the oocyte acting as a key component. This study provides a step-change in our understanding of local dynamics of steroid hormone signaling during the key period of human primordial follicle formation.

The chorioallantoic membrane (CAM) assay for the study of human bone regeneration: a refinement animal model for tissue engineering

NASA Astrophysics Data System (ADS)

Moreno-Jiménez, Inés; Hulsart-Billstrom, Gry; Lanham, Stuart A.; Janeczek, Agnieszka A.; Kontouli, Nasia; Kanczler, Janos M.; Evans, Nicholas D.; Oreffo, Richard Oc

2016-08-01

Biomaterial development for tissue engineering applications is rapidly increasing but necessitates efficacy and safety testing prior to clinical application. Current in vitro and in vivo models hold a number of limitations, including expense, lack of correlation between animal models and human outcomes and the need to perform invasive procedures on animals; hence requiring new predictive screening methods. In the present study we tested the hypothesis that the chick embryo chorioallantoic membrane (CAM) can be used as a bioreactor to culture and study the regeneration of human living bone. We extracted bone cylinders from human femoral heads, simulated an injury using a drill-hole defect, and implanted the bone on CAM or in vitro control-culture. Micro-computed tomography (μCT) was used to quantify the magnitude and location of bone volume changes followed by histological analyses to assess bone repair. CAM blood vessels were observed to infiltrate the human bone cylinder and maintain human cell viability. Histological evaluation revealed extensive extracellular matrix deposition in proximity to endochondral condensations (Sox9+) on the CAM-implanted bone cylinders, correlating with a significant increase in bone volume by μCT analysis (p < 0.01). This human-avian system offers a simple refinement model for animal research and a step towards a humanized in vivo model for tissue engineering.

Developmental origins of NAFLD: a womb with a clue

PubMed Central

Wesolowski, Stephanie R.; El Kasmi, Karim C.; Jonscher, Karen R.; Friedman, Jacob E.

2017-01-01

Changes in the maternal environment leading to an altered intrauterine milieu can result in subtle insults to the fetus, promoting increased lifetime disease risk and/or disease acceleration in childhood and later in life. Particularly worrisome is that the prevalence of NAFLD is rapidly increasing among children and adults, and is being diagnosed at increasingly younger ages, pointing towards an early-life origin. A wealth of evidence, in humans and non-human primates, suggests that maternal nutrition affects the placenta and fetal tissues, leading to persistent changes in hepatic metabolism, mitochondrial function, the intestinal microbiota, liver macrophage activation and susceptibility to NASH postnatally. Deleterious exposures in utero include fetal hypoxia, increased nutrient supply, inflammation and altered gut microbiota that might produce metabolic clues, including fatty acids, metabolites, endotoxins, bile acids and cytokines, which prime the infant liver for NAFLD in a persistent manner and increase susceptibility to NASH. Mechanistic links to early disease pathways might involve shifts in lipid metabolism, mitochondrial dysfunction, pioneering gut microorganisms, macrophage programming and epigenetic changes that alter the liver microenvironment, favouring liver injury. In this Review, we discuss how maternal, fetal, neonatal and infant exposures provide developmental clues and mechanisms to help explain NAFLD acceleration and increased disease prevalence. Mechanisms identified in clinical and preclinical models suggest important opportunities for prevention and intervention that could slow down the growing epidemic of NAFLD in the next generation. PMID:27780972

Library collaboration with medical humanities in an american medical college in qatar.

PubMed

Birch, Sally; Magid, Amani; Weber, Alan

2013-11-01

The medical humanities, a cross-disciplinary field of practice and research that includes medicine, literature, art, history, philosophy, and sociology, is being increasingly incorporated into medical school curricula internationally. Medical humanities courses in Writing, Literature, Medical Ethics and History can teach physicians-in-training communication skills, doctor-patient relations, and medical ethics, as well as empathy and cross-cultural understanding. In addition to providing educational breadth and variety, the medical humanities can also play a practical role in teaching critical/analytical skills. These skills are utilized in differential diagnosis and problem-based learning, as well as in developing written and oral communications. Communication skills are a required medical competency for passing medical board exams in the U.S., Canada, the UK and elsewhere. The medical library is an integral part of medical humanities training efforts. This contribution provides a case study of the Distributed eLibrary at the Weill Cornell Medical College in Qatar in Doha, and its collaboration with the Writing Program in the Premedical Program to teach and develop the medical humanities. Programs and initiatives of the DeLib library include: developing an information literacy course, course guides for specific courses, the 100 Classic Books Project, collection development of 'doctors' stories' related to the practice of medicine (including medically-oriented movies and TV programs), and workshops to teach the analytical and critical thinking skills that form the basis of humanistic approaches to knowledge. This paper outlines a 'best practices' approach to developing the medical humanities in collaboration among the medical library, faculty and administrative stakeholders.

Library Collaboration with Medical Humanities in an American Medical College in Qatar

PubMed Central

Birch, Sally; Magid, Amani; Weber, Alan

2013-01-01

The medical humanities, a cross-disciplinary field of practice and research that includes medicine, literature, art, history, philosophy, and sociology, is being increasingly incorporated into medical school curricula internationally. Medical humanities courses in Writing, Literature, Medical Ethics and History can teach physicians-in-training communication skills, doctor-patient relations, and medical ethics, as well as empathy and cross-cultural understanding. In addition to providing educational breadth and variety, the medical humanities can also play a practical role in teaching critical/analytical skills. These skills are utilized in differential diagnosis and problem-based learning, as well as in developing written and oral communications. Communication skills are a required medical competency for passing medical board exams in the U.S., Canada, the UK and elsewhere. The medical library is an integral part of medical humanities training efforts. This contribution provides a case study of the Distributed eLibrary at the Weill Cornell Medical College in Qatar in Doha, and its collaboration with the Writing Program in the Premedical Program to teach and develop the medical humanities. Programs and initiatives of the DeLib library include: developing an information literacy course, course guides for specific courses, the 100 Classic Books Project, collection development of ‘doctors’ stories’ related to the practice of medicine (including medically-oriented movies and TV programs), and workshops to teach the analytical and critical thinking skills that form the basis of humanistic approaches to knowledge. This paper outlines a ‘best practices’ approach to developing the medical humanities in collaboration among the medical library, faculty and administrative stakeholders. PMID:24223240

An interdisciplinary review of current and future approaches to improving human-predator relations.

PubMed

Pooley, S; Barua, M; Beinart, W; Dickman, A; Holmes, G; Lorimer, J; Loveridge, A J; Macdonald, D W; Marvin, G; Redpath, S; Sillero-Zubiri, C; Zimmermann, A; Milner-Gulland, E J

2017-06-01

In a world of shrinking habitats and increasing competition for natural resources, potentially dangerous predators bring the challenges of coexisting with wildlife sharply into focus. Through interdisciplinary collaboration among authors trained in the humanities, social sciences, and natural sciences, we reviewed current approaches to mitigating adverse human-predator encounters and devised a vision for future approaches to understanding and mitigating such encounters. Limitations to current approaches to mitigation include too much focus on negative impacts; oversimplified equating of levels of damage with levels of conflict; and unsuccessful technical fixes resulting from failure to engage locals, address hidden costs, or understand cultural (nonscientific) explanations of the causality of attacks. An emerging interdisciplinary literature suggests that to better frame and successfully mitigate negative human-predator relations conservation professionals need to consider dispensing with conflict as the dominant framework for thinking about human-predator encounters; work out what conflicts are really about (they may be human-human conflicts); unravel the historical contexts of particular conflicts; and explore different cultural ways of thinking about animals. The idea of cosmopolitan natures may help conservation professionals think more clearly about human-predator relations in both local and global context. These new perspectives for future research practice include a recommendation for focused interdisciplinary research and the use of new approaches, including human-animal geography, multispecies ethnography, and approaches from the environmental humanities notably environmental history. Managers should think carefully about how they engage with local cultural beliefs about wildlife, work with all parties to agree on what constitutes good evidence, develop processes and methods to mitigate conflicts, and decide how to monitor and evaluate these. Demand for immediate solutions that benefit both conservation and development favors dispute resolution and technical fixes, which obscures important underlying drivers of conflicts. If these drivers are not considered, well-intentioned efforts focused on human-wildlife conflicts will fail. © 2016 The Authors. Conservation Biology published by Wiley Periodicals, Inc. on behalf of Society for Conservation Biology.

45 CFR 284.30 - What information must the State include in its assessment of the impact of the TANF program(s) in...

Code of Federal Regulations, 2014 CFR

2014-10-01

... assessment of the impact of the TANF program(s) in the State on the increase in child poverty? 284.30 Section... TANF PROGRAM § 284.30 What information must the State include in its assessment of the impact of the... PROGRAMS), ADMINISTRATION FOR CHILDREN AND FAMILIES, DEPARTMENT OF HEALTH AND HUMAN SERVICES METHODOLOGY...

45 CFR 284.30 - What information must the State include in its assessment of the impact of the TANF program(s) in...

Code of Federal Regulations, 2012 CFR

2012-10-01

... assessment of the impact of the TANF program(s) in the State on the increase in child poverty? 284.30 Section... TANF PROGRAM § 284.30 What information must the State include in its assessment of the impact of the... PROGRAMS), ADMINISTRATION FOR CHILDREN AND FAMILIES, DEPARTMENT OF HEALTH AND HUMAN SERVICES METHODOLOGY...

45 CFR 284.30 - What information must the State include in its assessment of the impact of the TANF program(s) in...

Code of Federal Regulations, 2013 CFR

2013-10-01

... assessment of the impact of the TANF program(s) in the State on the increase in child poverty? 284.30 Section... TANF PROGRAM § 284.30 What information must the State include in its assessment of the impact of the... PROGRAMS), ADMINISTRATION FOR CHILDREN AND FAMILIES, DEPARTMENT OF HEALTH AND HUMAN SERVICES METHODOLOGY...

45 CFR 284.30 - What information must the State include in its assessment of the impact of the TANF program(s) in...

Code of Federal Regulations, 2011 CFR

2011-10-01

... assessment of the impact of the TANF program(s) in the State on the increase in child poverty? 284.30 Section... TANF PROGRAM § 284.30 What information must the State include in its assessment of the impact of the... PROGRAMS), ADMINISTRATION FOR CHILDREN AND FAMILIES, DEPARTMENT OF HEALTH AND HUMAN SERVICES METHODOLOGY...

Reducing the Risk of Human Missions to Mars Through Testing

NASA Astrophysics Data System (ADS)

Drake, Bret G.

2007-07-01

The NASA Deputy Administrator charted an internal NASA planning group to develop the rationale for exploration beyond low-Earth orbit. This team, termed the Exploration Blueprint, performed architecture analyses to develop roadmaps for how to accomplish the first steps beyond Low-Earth Orbit through the human exploration of Mars. Following the results of the Exploration Blueprint study, the NASA Administrator asked for a recommendation on the next steps in human and robotic exploration. Much of the focus during this period was on integrating the results from the previous studies into more concrete implementation strategies in order to understand the relationship between NASA programs, timing, and resulting budgetary implications. This resulted in an integrated approach including lunar surface operations to retire risk of human Mars missions, maximum use of common and modular systems including what was termed the exploration transfer vehicle, Earth orbit and lunar surface demonstrations of long-life systems, collaboration of human and robotic missions to vastly increase mission return, and high-efficiency transportation systems (nuclear) for deep-space transportation and power. The data provided in this summary presentation was developed to begin to address one of the key elements of the emerging implementation strategy, namely how lunar missions help retire risk of human missions to Mars. During this process the scope of the activity broadened into the issue of how testing in general, in various venues including the moon, can help reduce the risk for Mars missions.

Characterization and pathogenesis of aerosolized eastern equine encephalitis in the common marmoset (Callithrix jacchus).

PubMed

Porter, Aimee I; Erwin-Cohen, Rebecca A; Twenhafel, Nancy; Chance, Taylor; Yee, Steven B; Kern, Steven J; Norwood, David; Hartman, Laurie J; Parker, Michael D; Glass, Pamela J; DaSilva, Luis

2017-02-07

Licensed antiviral therapeutics and vaccines to protect against eastern equine encephalitis virus (EEEV) in humans currently do not exist. Animal models that faithfully recapitulate the clinical characteristics of human EEEV encephalitic disease, including fever, drowsiness, anorexia, and neurological signs such as seizures, are needed to satisfy requirements of the Food and Drug Administration (FDA) for clinical product licensing under the Animal Rule. In an effort to meet this requirement, we estimated the median lethal dose and described the pathogenesis of aerosolized EEEV in the common marmoset (Callithrix jacchus). Five marmosets were exposed to aerosolized EEEV FL93-939 in doses ranging from 2.4 × 10 1 PFU to 7.95 × 10 5 PFU. The median lethal dose was estimated to be 2.05 × 10 2 PFU. Lethality was observed as early as day 4 post-exposure in the highest-dosed marmoset but animals at lower inhaled doses had a protracted disease course where humane study endpoint was not met until as late as day 19 post-exposure. Clinical signs were observed as early as 3 to 4 days post-exposure, including fever, ruffled fur, decreased grooming, and leukocytosis. Clinical signs increased in severity as disease progressed to include decreased body weight, subdued behavior, tremors, and lack of balance. Fever was observed as early as day 2-3 post-exposure in the highest dose groups and hypothermia was observed in several cases as animals became moribund. Infectious virus was found in several key tissues, including brain, liver, kidney, and several lymph nodes. Clinical hematology results included early neutrophilia, lymphopenia, and thrombocytopenia. Key pathological changes included meningoencephalitis and retinitis. Immunohistochemical staining for viral antigen was positive in the brain, retina, and lymph nodes. More intense and widespread IHC labeling occurred with increased aerosol dose. We have estimated the medial lethal dose of aerosolized EEEV and described the pathology of clinical disease in the marmoset model. The results demonstrate that the marmoset is an animal model suitable for emulation of human EEEV disease in the development of medical countermeasures.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Siegel, S.

An increased level of mathematical sophistication will be needed in the future to be able to handle the spectrum of information as it comes from a broad array of biological systems and other sources. Classification will be an increasingly complex and difficult issue. Several projects that are discussed are being developed by the US Department of Health and Human Services (DHHS), including a directory of risk assessment projects and a directory of exposure information resources.

Malondialdehyde-Derived Epitopes In Human Skin Result From Acute Exposure To Solar UV And Occur In Nonmelanoma Skin Cancer Tissue

PubMed Central

Williams, Joshua D.; Bermudez, Yira; Park, Sophia L.; Stratton, Steven P.; Uchida, Koji; Hurst, Craig A.; Wondrak, Georg T.

2014-01-01

Cutaneous exposure to solar ultraviolet radiation (UVR) is a causative factor in photoaging and photocarcinogenesis. In human skin, oxidative stress is widely considered a key mechanism underlying the detrimental effects of acute and chronic UVR exposure. The lipid peroxidation product malondialdehyde (MDA) accumulates in tissue under conditions of increased oxidative stress, and the occurrence of MDA-derived protein epitopes, including dihydropyridine-lysine (DHP), has recently been substantiated in human skin. Here we demonstrate for the first time that acute exposure to sub-apoptogenic doses of solar simulated UV light (SSL) causes the formation of free MDA and protein-bound MDA-derived epitopes in cultured human HaCaT keratinocytes and healthy human skin. Immunohistochemical staining revealed that acute exposure to SSL is sufficient to cause an almost twenty-fold increase in general MDA- and specific DHP-epitope content in human skin. When compared to dose-matched solar simulated UVA, complete SSL was more efficient generating both free MDA and MDA-derived epitopes. Subsequent tissue microarray (TMA) analysis revealed the prevalence of MDA- and DHP-epitopes in nonmelanoma skin cancer (NMSC). In squamous cell carcinoma tissue, both MDA- and DHP-epitopes were increased more than three-fold as compared to adjacent normal tissue. Taken together, these date demonstrate the occurrence of MDA-derived epitopes in both solar UVR-exposed healthy human skin and NMSC TMA tissue; however, the potential utility of these epitopes as novel biomarkers of cutaneous photodamage and a functional role in the process of skin photocarcinogenesis remain to be explored. PMID:24584085

Viral fitness: definitions, measurement, and current insights

USGS Publications Warehouse

Wargo, Andrew R.; Kurath, Gael

2012-01-01

Viral fitness is an active area of research, with recent work involving an expanded number of human, non-human vertebrate, invertebrate, plant, and bacterial viruses. Many publications deal with RNA viruses associated with major disease emergence events, such as HIV-1, influenza virus, and Dengue virus. Study topics include drug resistance, immune escape, viral emergence, host jumps, mutation effects, quasispecies diversity, and mathematical models of viral fitness. Important recent trends include increasing use of in vivo systems to assess vertebrate virus fitness, and a broadening of research beyond replicative fitness to also investigate transmission fitness and epidemiologic fitness. This is essential for a more integrated understanding of overall viral fitness, with implications for disease management in the future.

Oxidative stress signaling to chromatin in health and disease

PubMed Central

Kreuz, Sarah; Fischle, Wolfgang

2016-01-01

Oxidative stress has a significant impact on the development and progression of common human pathologies, including cancer, diabetes, hypertension and neurodegenerative diseases. Increasing evidence suggests that oxidative stress globally influences chromatin structure, DNA methylation, enzymatic and non-enzymatic post-translational modifications of histones and DNA-binding proteins. The effects of oxidative stress on these chromatin alterations mediate a number of cellular changes, including modulation of gene expression, cell death, cell survival and mutagenesis, which are disease-driving mechanisms in human pathologies. Targeting oxidative stress-dependent pathways is thus a promising strategy for the prevention and treatment of these diseases. We summarize recent research developments connecting oxidative stress and chromatin regulation. PMID:27319358

Human G109E-inhibitor-1 impairs cardiac function and promotes arrhythmias.

PubMed

Haghighi, Kobra; Pritchard, Tracy J; Liu, Guan-Sheng; Singh, Vivek P; Bidwell, Philip; Lam, Chi Keung; Vafiadaki, Elizabeth; Das, Parthib; Ma, Jianyong; Kunduri, Swati; Sanoudou, Despina; Florea, Stela; Vanderbilt, Erica; Wang, Hong-Shang; Rubinstein, Jack; Hajjar, Roger J; Kranias, Evangelia G

2015-12-01

A hallmark of human and experimental heart failure is deficient sarcoplasmic reticulum (SR) Ca-uptake reflecting impaired contractile function. This is at least partially attributed to dephosphorylation of phospholamban by increased protein phosphatase 1 (PP1) activity. Indeed inhibition of PP1 by transgenic overexpression or gene-transfer of constitutively active inhibitor-1 improved Ca-cycling, preserved function and decreased fibrosis in small and large animal models of heart failure, suggesting that inhibitor-1 may represent a potential therapeutic target. We recently identified a novel human polymorphism (G109E) in the inhibitor-1 gene with a frequency of 7% in either normal or heart failure patients. Transgenic mice, harboring cardiac-specific expression of G109E inhibitor-1, exhibited decreases in contractility, Ca-kinetics and SR Ca-load. These depressive effects were relieved by isoproterenol stimulation. Furthermore, stress conditions (2Hz +/- Iso) induced increases in Ca-sparks, Ca-waves (60% of G109E versus 20% in wild types) and after-contractions (76% of G109E versus 23% of wild types) in mutant cardiomyocytes. Similar findings were obtained by acute expression of the G109E variant in adult cardiomyocytes in the absence or presence of endogenous inhibitor-1. The underlying mechanisms included reduced binding of mutant inhibitor-1 to PP1, increased PP1 activity, and dephosphorylation of phospholamban at Ser16 and Thr17. However, phosphorylation of the ryanodine receptor at Ser2808 was not altered while phosphorylation at Ser2814 was increased, consistent with increased activation of Ca/calmodulin-dependent protein kinase II (CaMKII), promoting aberrant SR Ca-release. Parallel in vivo studies revealed that mutant mice developed ventricular ectopy and complex ventricular arrhythmias (including bigeminy, trigeminy and ventricular tachycardia), when challenged with isoproterenol. Inhibition of CaMKII activity by KN-93 prevented the increased propensity to arrhythmias. These findings suggest that the human G109E inhibitor-1 variant impairs SR Ca-cycling and promotes arrhythmogenesis under stress conditions, which may present an additional insult in the compromised function of heart failure carriers. Copyright © 2015 Elsevier Ltd. All rights reserved.

Human G109E-Inhibitor-1 Impairs Cardiac Function and Promotes Arrhythmias

PubMed Central

Haghighi, Kobra; Pritchard, Tracy J.; Liu, Guan-Sheng; Singh, Vivek P.; Bidwell, Philip; Lam, Chi Keung; Vafiadaki, Elizabeth; Das, Parthib; Ma, Jianyong; Kunduri, Swati; Sanoudou, Despina; Florea, Stela; Vanderbilt, Erica; Wang, Hong-Shang; Rubinstein, Jack; Hajjar, Roger J.; Kranias, Evangelia G.

2015-01-01

A hallmark of human and experimental heart failure is deficient sarcoplasmic reticulum (SR) Ca-uptake reflecting impaired contractile function. This is at least partially attributed to dephosphorylation of phospholamban by increased protein phosphatase 1 (PP1) activity. Indeed inhibition of PP1 by transgenic overexpression or gene-transfer of constitutively active inhibitor-1 improved Ca-cycling, preserved function and decreased fibrosis in small and large animal models of heart failure, suggesting that inhibitor-1 may represent a potential therapeutic target. We recently identified a novel human polymorphism (G109E) in the inhibitor-1 gene with a frequency of 7% in either normal or heart failure patients. Transgenic mice, harboring cardiac-specific expression of G109E inhibitor-1, exhibited decreases in contractility, Ca-kinetics and SR Ca-load. These depressive effects were relieved by isoproterenol stimulation. Furthermore, stress conditions (2 Hz +/− Iso) induced increases in Ca-sparks, Ca-waves (60% of G109E versus 20% in wild types) and after-contractions (76% of G109E versus 23% of wild types) in mutant cardiomyocytes. Similar findings were obtained by acute expression of the G109E variant in adult cardiomyocytes in the absence or presence of endogenous inhibitor-1. The underlying mechanisms included reduced binding of mutant inhibitor-1 to PP1, increased PP1 activity, and dephosphorylation of phospholamban at Ser16 and Thr17. However, phosphorylation of the ryanodine receptor at Ser2808 was not altered while phosphorylation at Ser2814 was increased, consistent with increased activation of Ca/calmodulin-dependent protein kinase II (CaMKII), promoting aberrant SR Ca-release. Parallel in vivo studies revealed that mutant mice developed ventricular ectopy and complex ventricular arrhythmias (including bigeminy, trigeminy and ventricular tachycardia), when challenged with isoproterenol. Inhibition of CaMKII activity by KN-93 prevented the increased propensity to arrhythmias. These findings suggest that the human G109E inhibitor-1 variant impairs SR Ca-cycling and promotes arrhythmogenesis under stress conditions, which may present an additional insult in the compromised function of heart failure carriers. PMID:26455482

Toxic Effects of Mercury on the Cardiovascular and Central Nervous Systems

PubMed Central

Fernandes Azevedo, Bruna; Barros Furieri, Lorena; Peçanha, Franck Maciel; Wiggers, Giulia Alessandra; Frizera Vassallo, Paula; Ronacher Simões, Maylla; Fiorim, Jonaina; Rossi de Batista, Priscila; Fioresi, Mirian; Rossoni, Luciana; Stefanon, Ivanita; Alonso, María Jesus; Salaices, Mercedes; Valentim Vassallo, Dalton

2012-01-01

Environmental contamination has exposed humans to various metal agents, including mercury. This exposure is more common than expected, and the health consequences of such exposure remain unclear. For many years, mercury was used in a wide variety of human activities, and now, exposure to this metal from both natural and artificial sources is significantly increasing. Many studies show that high exposure to mercury induces changes in the central nervous system, potentially resulting in irritability, fatigue, behavioral changes, tremors, headaches, hearing and cognitive loss, dysarthria, incoordination, hallucinations, and death. In the cardiovascular system, mercury induces hypertension in humans and animals that has wide-ranging consequences, including alterations in endothelial function. The results described in this paper indicate that mercury exposure, even at low doses, affects endothelial and cardiovascular function. As a result, the reference values defining the limits for the absence of danger should be reduced. PMID:22811600

Human tolerance to space flight

NASA Technical Reports Server (NTRS)

Huntoon, C. L.

1989-01-01

Medical studies of astronauts and cosmonauts before, during, and after space missions have identified several effects of weightlessness and other factors that influence the ability of humans to tolerate space flight. Weightlessness effects include space motion sickness, cardiovascular abnormalities, reduction in immune system function, loss of red blood cells, loss of bone mass, and muscle atrophy. Extravehicular activity (EVA) increases the likelihood that decompression sickness may occur. Radiation also gives reason for concern about health of crewmembers, and psychological factors are important on long-term flights. Countermeasures that have been used include sensory preadaptation, prebreathing and use of various air mixtures for EVA, loading with water and electrolytes, exercise, use of pharmacological agents and special diets, and psychological support. It appears that humans can tolerate and recover satisfactorily from at least one year of space flight, but a number of conditions must be further ameliorated before long-duration missions can be considered routine.

Brain-mapping projects using the common marmoset.

PubMed

Okano, Hideyuki; Mitra, Partha

2015-04-01

Globally, there is an increasing interest in brain-mapping projects, including the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative project in the USA, the Human Brain Project (HBP) in Europe, and the Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) project in Japan. These projects aim to map the structure and function of neuronal circuits to ultimately understand the vast complexity of the human brain. Brain/MINDS is focused on structural and functional mapping of the common marmoset (Callithrix jacchus) brain. This non-human primate has numerous advantages for brain mapping, including a well-developed frontal cortex and a compact brain size, as well as the availability of transgenic technologies. In the present review article, we discuss strategies for structural and functional mapping of the marmoset brain and the relation of the common marmoset to other animals models. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Genetic and pathogenic difference between Streptococcus agalactiae serotype Ia fish and human isolates.

PubMed

Chu, Chishih; Huang, Pei-Yu; Chen, Hung-Ming; Wang, Ying-Hsiang; Tsai, I-An; Lu, Chih-Cheng; Chen, Che-Chun

2016-08-02

Streptococcus agalactiae (GBS) is a common pathogen to infect newborn, woman, the elderly, and immuno-compromised human and fish. 37 fish isolates and 554 human isolates of the GBS in 2007-2012 were investigated in serotypes, antibiotic susceptibility, genetic difference and pathogenicity to tilapia. PCR serotyping determined serotype Ia for all fish GBS isolates and only in 3.2 % (3-4.2 %) human isolates. For fish isolates, all consisted a plasmid less than 6 kb and belonged to ST7 type, which includes mainly pulsotypes I and Ia, with a difference in a deletion at the largest DNA fragment. These fish isolates were susceptible to all antimicrobials tested in 2007 and increased in non-susceptibility to penicillin, and resistance to clindamycin and ceftriaxone in 2011. Differing in pulsotype and lacking plasmid from fish isolates, human serotype Ia isolates were separated into eight pulsotypes II-IX. Main clone ST23 included pulsotypes II and IIa (50 %) and ST483 consisted of pulsotype III. Human serotype Ia isolates were all susceptible to ceftriaxone and penicillin and few were resistant to erythromycin, azithromycin, clindamycin, levofloxacin and moxifloxacine with the resistant rate of 20 % or less. Using tilapia to analyze the pathogenesis, fish isolates could cause more severe symptoms, including hemorrhage of the pectoral fin, hemorrhage of the gill, and viscous black and common scites, and mortality (>95 % for pulsotype I) than the human isolates (<30 %); however, the fish pulostype Ia isolate 912 with deletion caused less symptoms and the lowest mortality (<50 %) than pulsotype I isolates. Genetic, pathogenic, and antimicrobial differences demonstrate diverse origin of human and fish serotype Ia isolates. The pulsotype Ia of fish serotype Ia isolates may be used as vaccine strains to prevent the GBS infection in fish.

Analyzing Human-Landscape Interactions: Tools That Integrate

NASA Astrophysics Data System (ADS)

Zvoleff, Alex; An, Li

2014-01-01

Humans have transformed much of Earth's land surface, giving rise to loss of biodiversity, climate change, and a host of other environmental issues that are affecting human and biophysical systems in unexpected ways. To confront these problems, environmental managers must consider human and landscape systems in integrated ways. This means making use of data obtained from a broad range of methods (e.g., sensors, surveys), while taking into account new findings from the social and biophysical science literatures. New integrative methods (including data fusion, simulation modeling, and participatory approaches) have emerged in recent years to address these challenges, and to allow analysts to provide information that links qualitative and quantitative elements for policymakers. This paper brings attention to these emergent tools while providing an overview of the tools currently in use for analysis of human-landscape interactions. Analysts are now faced with a staggering array of approaches in the human-landscape literature—in an attempt to bring increased clarity to the field, we identify the relative strengths of each tool, and provide guidance to analysts on the areas to which each tool is best applied. We discuss four broad categories of tools: statistical methods (including survival analysis, multi-level modeling, and Bayesian approaches), GIS and spatial analysis methods, simulation approaches (including cellular automata, agent-based modeling, and participatory modeling), and mixed-method techniques (such as alternative futures modeling and integrated assessment). For each tool, we offer an example from the literature of its application in human-landscape research. Among these tools, participatory approaches are gaining prominence for analysts to make the broadest possible array of information available to researchers, environmental managers, and policymakers. Further development of new approaches of data fusion and integration across sites or disciplines pose an important challenge for future work in integrating human and landscape components.

Biogeography of Human Infectious Diseases: A Global Historical Analysis

PubMed Central

Cashdan, Elizabeth

2014-01-01

Objectives Human pathogen richness and prevalence vary widely across the globe, yet we know little about whether global patterns found in other taxa also predict diversity in this important group of organisms. This study (a) assesses the relative importance of temperature, precipitation, habitat diversity, and population density on the global distributions of human pathogens and (b) evaluates the species-area predictions of island biogeography for human pathogen distributions on oceanic islands. Methods Historical data were used in order to minimize the influence of differential access to modern health care on pathogen prevalence. The database includes coded data (pathogen, environmental and cultural) for a worldwide sample of 186 non-industrial cultures, including 37 on islands. Prevalence levels for 10 pathogens were combined into a pathogen prevalence index, and OLS regression was used to model the environmental determinants of the prevalence index and number of pathogens. Results Pathogens (number and prevalence index) showed the expected latitudinal gradient, but predictors varied by latitude. Pathogens increased with temperature in high-latitude zones, while mean annual precipitation was a more important predictor in low-latitude zones. Other environmental factors associated with more pathogens included seasonal dry extremes, frost-free climates, and human population density outside the tropics. Islands showed the expected species-area relationship for all but the smallest islands, and the relationship was not mediated by habitat diversity. Although geographic distributions of free-living and parasitic taxa typically have different determinants, these data show that variables that influence the distribution of free-living organisms also shape the global distribution of human pathogens. Understanding the cause of these distributions is potentially important, since geographical variation in human pathogens has an important influence on global disparities in human welfare. PMID:25271730

Biogeography of human infectious diseases: a global historical analysis.

PubMed

Cashdan, Elizabeth

2014-01-01

Human pathogen richness and prevalence vary widely across the globe, yet we know little about whether global patterns found in other taxa also predict diversity in this important group of organisms. This study (a) assesses the relative importance of temperature, precipitation, habitat diversity, and population density on the global distributions of human pathogens and (b) evaluates the species-area predictions of island biogeography for human pathogen distributions on oceanic islands. Historical data were used in order to minimize the influence of differential access to modern health care on pathogen prevalence. The database includes coded data (pathogen, environmental and cultural) for a worldwide sample of 186 non-industrial cultures, including 37 on islands. Prevalence levels for 10 pathogens were combined into a pathogen prevalence index, and OLS regression was used to model the environmental determinants of the prevalence index and number of pathogens. Pathogens (number and prevalence index) showed the expected latitudinal gradient, but predictors varied by latitude. Pathogens increased with temperature in high-latitude zones, while mean annual precipitation was a more important predictor in low-latitude zones. Other environmental factors associated with more pathogens included seasonal dry extremes, frost-free climates, and human population density outside the tropics. Islands showed the expected species-area relationship for all but the smallest islands, and the relationship was not mediated by habitat diversity. Although geographic distributions of free-living and parasitic taxa typically have different determinants, these data show that variables that influence the distribution of free-living organisms also shape the global distribution of human pathogens. Understanding the cause of these distributions is potentially important, since geographical variation in human pathogens has an important influence on global disparities in human welfare.

Sudden increase in human infection with avian influenza A(H7N9) virus in China, September–December 2016

PubMed Central

Zhou, Lei; Ren, Ruiqi; Yang, Lei; Bao, Changjun; Wu, Jiabing; Wang, Dayan; Li, Chao; Xiang, Nijuan; Wang, Yali; Li, Dan; Sui, Haitian; Shu, Yuelong; Feng, Zijian; Li, Qun

2017-01-01

Since the first outbreak of avian influenza A(H7N9) virus in humans was identified in 2013, there have been five seasonal epidemics observed in China. An earlier start and a steep increase in the number of humans infected with H7N9 virus was observed between September and December 2016, raising great public concern in domestic and international societies. The epidemiological characteristics of the recently reported confirmed H7N9 cases were analysed. The results suggested that although more cases were reported recently, most cases in the fifth epidemic were still highly sporadically distributed without any epidemiology links; the main characteristics remained unchanged and the genetic characteristics of virus strains that were isolated in this epidemic remained similar to earlier epidemics. Interventions included live poultry market closures in several cities that reported more H7N9 cases recently. PMID:28409054

Identification of the five human Plasmodium species including P. knowlesi by real-time polymerase chain reaction.

PubMed

Oddoux, O; Debourgogne, A; Kantele, A; Kocken, C H; Jokiranta, T S; Vedy, S; Puyhardy, J M; Machouart, M

2011-04-01

Recently, Plasmodium knowlesi has been recognised as the fifth Plasmodium species causing malaria in humans. Hundreds of human cases infected with this originally simian Plasmodium species have been described in Asian countries and increasing numbers are reported in Europe from travellers. The growing impact of tourism and economic development in South and Southeast Asia are expected to subsequently lead to a further increase in cases both among locals and among travellers. P. knowlesi is easily misidentified in microscopy as P. malariae or P. falciparum. We developed new primers for the rapid and specific detection of this species by low-cost real-time polymerase chain reaction (PCR) and added this method to an already existing panel of primers used for the molecular identification of the other four species in one reaction. Reference laboratories should now be able to identify undisputably and rapidly P. knowlesi, as it is a potentially fatal pathogen.

Modeling infectious disease dynamics in the complex landscape of global health

PubMed Central

Heesterbeek, Hans; Anderson, Roy; Andreasen, Viggo; Bansal, Shweta; De Angelis, Daniela; Dye, Chris; Eames, Ken; Edmunds, John; Frost, Simon; Funk, Sebastian; Hollingsworth, Deirdre; House, Thomas; Isham, Valerie; Klepac, Petra; Lessler, Justin; Lloyd-Smith, James; Metcalf, Jessica; Mollison, Denis; Pellis, Lorenzo; Pulliam, Juliet; Roberts, Mick; Viboud, Cecile

2015-01-01

Despite some notable successes in the control of infectious diseases, transmissible pathogens still pose an enormous threat to human and animal health. The ecological and evolutionary dynamics of infections play out on a wide range of interconnected temporal, organizational and spatial scales, which even within a single pathogen often span hours to months, cellular to ecosystem levels, and local to pandemic spread. Some pathogens are directly transmitted between individuals of a single species, while others circulate among multiple hosts, need arthropod vectors, or can survive in environmental reservoirs. Many factors, including increasing antimicrobial resistance, increased human connectivity, and dynamic human behavior, raise prevention and control from formerly national to international issues. In the face of this complexity, mathematical models offer essential tools for synthesizing information to understand epidemiological patterns, and for developing the quantitative evidence base for decision-making in global health. PMID:25766240

Challenge theme 1: Understanding and preserving ecological resources: Chapter 3 in United States-Mexican Borderlands: Facing tomorrow's challenges through USGS science

USGS Publications Warehouse

Moring, J. Bruce; Papoulias, Diana M.; van Riper, Charles

2013-01-01

Texas Plains; and Western Gulf Coastal Plain. The unique geology and many of the distinctive geographic features and climatic conditions that have given rise to the diverse populations of plants and animals found in the Borderlands also attract human populations. The number of people living in the Borderlands has increased dramatically over recent years, from about 7 million in 1980 to almost 12 million in 2003; the population is estimated to be more than 18 million by 2020 (Peach and Williams, 2003). The human population increase and associated change in land use have contributed to habitat fragmentation and habitat loss for native species, thus threatening their survival. Some ways in which humans negatively affect plants and animals in the Borderlands include dewatering of aquatic ecosystems, water pollution, introduction and spread of invasive species, outdoor lighting, military and border enforcement activity, and energy development and transmission.

Current advances in the cognitive neuroscience of music.

PubMed

Levitin, Daniel J; Tirovolas, Anna K

2009-03-01

The study of music perception and cognition is one of the oldest topics in experimental psychology. The last 20 years have seen an increased interest in understanding the functional neuroanatomy of music processing in humans, using a variety of technologies including fMRI, PET, ERP, MEG, and lesion studies. We review current findings in the context of a rich intellectual history of research, organized by the cognitive systems underlying different aspects of human musical behavior. We pay special attention to the perception of components of musical processing, musical structure, laterality effects, cultural issues, links between music and movement, emotional processing, expertise, and the amusias. Current trends are noted, such as the increased interest in evolutionary origins of music and comparisons of music and language. The review serves to demonstrate the important role that music can play in informing broad theories of higher order cognitive processes such as music in humans.

Modeling infectious disease dynamics in the complex landscape of global health.

PubMed

Heesterbeek, Hans; Anderson, Roy M; Andreasen, Viggo; Bansal, Shweta; De Angelis, Daniela; Dye, Chris; Eames, Ken T D; Edmunds, W John; Frost, Simon D W; Funk, Sebastian; Hollingsworth, T Deirdre; House, Thomas; Isham, Valerie; Klepac, Petra; Lessler, Justin; Lloyd-Smith, James O; Metcalf, C Jessica E; Mollison, Denis; Pellis, Lorenzo; Pulliam, Juliet R C; Roberts, Mick G; Viboud, Cecile

2015-03-13

Despite some notable successes in the control of infectious diseases, transmissible pathogens still pose an enormous threat to human and animal health. The ecological and evolutionary dynamics of infections play out on a wide range of interconnected temporal, organizational, and spatial scales, which span hours to months, cells to ecosystems, and local to global spread. Moreover, some pathogens are directly transmitted between individuals of a single species, whereas others circulate among multiple hosts, need arthropod vectors, or can survive in environmental reservoirs. Many factors, including increasing antimicrobial resistance, increased human connectivity and changeable human behavior, elevate prevention and control from matters of national policy to international challenge. In the face of this complexity, mathematical models offer valuable tools for synthesizing information to understand epidemiological patterns, and for developing quantitative evidence for decision-making in global health. Copyright © 2015, American Association for the Advancement of Science.

Feedbacks in human-landscape systems

NASA Astrophysics Data System (ADS)

Chin, Anne

2015-04-01

As human interactions with Earth systems intensify in the "Anthropocene", understanding the complex relationships among human activity, landscape change, and societal responses to those changes is increasingly important. Interdisciplinary research centered on the theme of "feedbacks" in human-landscape systems serves as a promising focus for unraveling these interactions. Deciphering interacting human-landscape feedbacks extends our traditional approach of considering humans as unidirectional drivers of change. Enormous challenges exist, however, in quantifying impact-feedback loops in landscapes with significant human alterations. This paper illustrates an example of human-landscape interactions following a wildfire in Colorado (USA) that elicited feedback responses. After the 2012 Waldo Canyon Fire, concerns for heightened flood potential and debris flows associated with post-fire hydrologic changes prompted local landowners to construct tall fences at the base of a burned watershed. These actions changed the sediment transport regime and promoted further landscape change and human responses in a positive feedback cycle. The interactions ultimately increase flood and sediment hazards, rather than dampening the effects of fire. A simple agent-based model, capable of integrating social and hydro-geomorphological data, demonstrates how such interacting impacts and feedbacks could be simulated. Challenges for fully capturing human-landscape feedback interactions include the identification of diffuse and subtle feedbacks at a range of scales, the availability of data linking impact with response, the identification of multiple thresholds that trigger feedback mechanisms, and the varied metrics and data needed to represent both the physical and human systems. By collaborating with social scientists with expertise in the human causes of landscape change, as well as the human responses to those changes, geoscientists could more fully recognize and anticipate the coupled human-landscape interactions that will drive the evolution of Earth systems into the future.

THE RELATIONSHIP OF URBAN DESIGN TO HUMAN HEALTH AND CONDITION

EPA Science Inventory

The population of the United States of American is currently experiencing increased illness from dispersed and synergistic causes. Many of the acute insults of the past have receded due to centralized health care and regulatory action. However, chronic ailments including asthma...

Harnessing genomics to identify environmental determinants of heritable disease

EPA Science Inventory

De novo mutation is increasingly being recognized as the cause for a range of human genetic diseases and disorders. Important examples of this include inherited genetic disorders such as autism, schizophrenia, mental retardation, epilepsy, and a broad range of adverse reproductiv...

Critical Appraisal of Mixed Methods Studies

ERIC Educational Resources Information Center

Heyvaert, Mieke; Hannes, Karin; Maes, Bea; Onghena, Patrick

2013-01-01

In several subdomains of the social, behavioral, health, and human sciences, research questions are increasingly answered through mixed methods studies, combining qualitative and quantitative evidence and research elements. Accordingly, the importance of including those primary mixed methods research articles in systematic reviews grows. It is…

Organizational Learning: A Review of the Literature with Implications for HRD Professionals.

ERIC Educational Resources Information Center

Dixon, Nancy M.

1992-01-01

A model of organizational learning includes information acquisition, information distribution/interpretation, meaning making, organizational memory, and information retrieval. Human resource development professionals have techniques for increasing competence in individuals, but they must also do so for organizations. (SK)

Iron homeostasis in the lung following asbestos exposure

EPA Science Inventory

Human exposure to asbestos can cause a wide variety of pulmonary diseases, including pneumoconiosis (i.e., asbestosis). This lung injury is mediated by oxidant generation which increases with the concentration of iron associated with the asbestos. Iron from host sources is comple...

Interactions With Robots: The Truths We Reveal About Ourselves.

PubMed

Broadbent, Elizabeth

2017-01-03

In movies, robots are often extremely humanlike. Although these robots are not yet reality, robots are currently being used in healthcare, education, and business. Robots provide benefits such as relieving loneliness and enabling communication. Engineers are trying to build robots that look and behave like humans and thus need comprehensive knowledge not only of technology but also of human cognition, emotion, and behavior. This need is driving engineers to study human behavior toward other humans and toward robots, leading to greater understanding of how humans think, feel, and behave in these contexts, including our tendencies for mindless social behaviors, anthropomorphism, uncanny feelings toward robots, and the formation of emotional attachments. However, in considering the increased use of robots, many people have concerns about deception, privacy, job loss, safety, and the loss of human relationships. Human-robot interaction is a fascinating field and one in which psychologists have much to contribute, both to the development of robots and to the study of human behavior.

Human genetic factors in tuberculosis: an update.

PubMed

van Tong, Hoang; Velavan, Thirumalaisamy P; Thye, Thorsten; Meyer, Christian G

2017-09-01

Tuberculosis (TB) is a major threat to human health, especially in many developing countries. Human genetic variability has been recognised to be of great relevance in host responses to Mycobacterium tuberculosis infection and in regulating both the establishment and the progression of the disease. An increasing number of candidate gene and genome-wide association studies (GWAS) have focused on human genetic factors contributing to susceptibility or resistance to TB. To update previous reviews on human genetic factors in TB we searched the MEDLINE database and PubMed for articles from 1 January 2014 through 31 March 2017 and reviewed the role of human genetic variability in TB. Search terms applied in various combinations were 'tuberculosis', 'human genetics', 'candidate gene studies', 'genome-wide association studies' and 'Mycobacterium tuberculosis'. Articles in English retrieved and relevant references cited in these articles were reviewed. Abstracts and reports from meetings were also included. This review provides a recent summary of associations of polymorphisms of human genes with susceptibility/resistance to TB. © 2017 John Wiley & Sons Ltd.

A chronology for late prehistoric Madagascar.

PubMed

Burney, David A; Burney, Lida Pigott; Godfrey, Laurie R; Jungers, William L; Goodman, Steven M; Wright, Henry T; Jull, A J Timothy

2004-01-01

A database has been assembled with 278 age determinations for Madagascar. Materials 14C dated include pretreated sediments and plant macrofossils from cores and excavations throughout the island, and bones, teeth, or eggshells of most of the extinct megafaunal taxa, including the giant lemurs, hippopotami, and ratites. Additional measurements come from uranium-series dates on speleothems and thermoluminescence dating of pottery. Changes documented include late Pleistocene climatic events and, in the late Holocene, the apparently human-caused transformation of the environment. Multiple lines of evidence point to the earliest human presence at ca. 2300 14C yr BP (350 cal yr BC). A decline in megafauna, inferred from a drastic decrease in spores of the coprophilous fungus Sporormiella spp. in sediments at 1720+/-40 14C yr BP (230-410 cal yr AD), is followed by large increases in charcoal particles in sediment cores, beginning in the SW part of the island, and spreading to other coasts and the interior over the next millennium. The record of human occupation is initially sparse, but shows large human populations throughout the island by the beginning of the Second Millennium AD. Dating of the "subfossil" megafauna, including pygmy hippos, elephant birds, giant tortoises, and large lemurs, demonstrates that most if not all the extinct taxa were still present on the island when humans arrived. Many taxa overlapped chronologically with humans for a millennium or more. The extinct lemurs Hadropithecus stenognathus, Pachylemur insignis, Mesopropithecus pithecoides, and Daubentonia robusta, and the elephant birds Aepyornis spp. and Mullerornis spp., were still present near the end of the First Millennium AD. Palaeopropithecus ingens, Megaladapis edwardsi, and Archaeolemur sp. (cf. edwardsi) may have survived until the middle of the Second Millennium A.D. One specimen of Hippopotamus of unknown provenance dates to the period of European colonization.

Fifteen Years after “Wingspread”—Environmental Endocrine Disrupters and Human and Wildlife Health: Where We are Today and Where We Need to Go

PubMed Central

Hotchkiss, Andrew K.; Rider, Cynthia V.; Blystone, Chad R.; Wilson, Vickie S.; Hartig, Phillip C.; Ankley, Gerald T.; Foster, Paul M.; Gray, Clark L.; Gray, L. Earl

2008-01-01

In 1991, a group of expert scientists at a Wingspread work session on endocrine-disrupting chemicals (EDCs) concluded that “Many compounds introduced into the environment by human activity are capable of disrupting the endocrine system of animals, including fish, wildlife, and humans. Endocrine disruption can be profound because of the crucial role hormones play in controlling development.” Since that time, there have been numerous documented examples of adverse effects of EDCs in invertebrates, fish, wildlife, domestic animals, and humans. Hormonal systems can be disrupted by numerous different anthropogenic chemicals including antiandrogens, androgens, estrogens, AhR agonists, inhibitors of steroid hormone synthesis, antithyroid substances, and retinoid agonists. In addition, pathways and targets for endocrine disruption extend beyond the traditional estrogen/androgen/thyroid receptor–mediated reproductive and developmental systems. For example, scientists have expressed concern about the potential role of EDCs in increasing trends in early puberty in girls, obesity and type II diabetes in the United States and other populations. New concerns include complex endocrine alterations induced by mixtures of chemicals, an issue broadened due to the growing awareness that EDCs present in the environment include a variety of potent human and veterinary pharmaceutical products, personal care products, nutraceuticals and phytosterols. In this review we (1) address what have we learned about the effects of EDCs on fish, wildlife, and human health, (2) discuss representative animal studies on (anti)androgens, estrogens and 2,3,7,8-tetrachlorodibenzo-p-dioxin–like chemicals, and (3) evaluate regulatory proposals being considered for screening and testing these chemicals. PMID:18281716

Analysis of sex and gender-specific research reveals a common increase in publications and marked differences between disciplines

PubMed Central

2010-01-01

Background The incorporation of sex and gender-specific analysis in medical research is increasing due to pressure from public agencies, funding bodies, and the clinical and research community. However, generations of knowledge and publication trends in this discipline are currently spread over distinct specialties and are difficult to analyze comparatively. Methods Using a text-mining approach, we have analysed sex and gender aspects in research within nine clinical subspecialties - Cardiology, Pulmonology, Nephrology, Endocrinology, Gastroenterology, Haematology, Oncology, Rheumatology, Neurology - using six paradigmatic diseases in each one. Articles have been classified into five pre-determined research categories - Epidemiology, Pathophysiology, Clinical research, Management and Outcomes. Additional information has been collected on the type of study (human/animal) and the number of subjects included. Of the 8,836 articles initially retrieved, 3,466 (39%) included sex and gender-specific research and have been further analysed. Results Literature incorporating sex/gender analysis increased over time and displays a stronger trend if compared to overall publication increase. All disciplines, but cardiology (22%), demonstrated an underrepresentation of research about gender differences in management, which ranges from 3 to 14%. While the use of animal models for identification of sex differences in basic research varies greatly among disciplines, studies involving human subjects are frequently conducted in large cohorts with more than 1,000 patients (24% of all human studies). Conclusions Heterogeneity characterizes sex and gender-specific research. Although large cohorts are often analysed, sex and gender differences in clinical management are insufficiently investigated leading to potential inequalities in health provision and outcomes. PMID:21067576

Practical management of cumulative anthropogenic impacts with working marine examples.

PubMed

Wright, Andrew J; Kyhn, Line A

2015-04-01

Human pressure on the environment is expanding and intensifying, especially in coastal and offshore areas. Major contributors to this are the current push for offshore renewable energy sources, which are thought of as environmentally friendly sources of power, as well as the continued demand for petroleum. Human disturbances, including the noise almost ubiquitously associated with human activity, are likely to increase the incidence, magnitude, and duration of adverse effects on marine life, including stress responses. Stress responses have the potential to induce fitness consequences for individuals, which add to more obvious directed takes (e.g., hunting or fishing) to increase the overall population-level impact. To meet the requirements of marine spatial planning and ecosystem-based management, many efforts are ongoing to quantify the cumulative impacts of all human actions on marine species or populations. Meanwhile, regulators face the challenge of managing these accumulating and interacting impacts with limited scientific guidance. We believe there is scientific support for capping the level of impact for (at a minimum) populations in decline or with unknown statuses. This cap on impact can be facilitated through implementation of regular application cycles for project authorization or improved programmatic and aggregated impact assessments that simultaneously consider multiple projects. Cross-company collaborations and a better incorporation of uncertainty into decision making could also help limit, if not reduce, cumulative impacts of multiple human activities. These simple management steps may also form the basis of a rudimentary form of marine spatial planning and could be used in support of future ecosystem-based management efforts. © 2014 Society for Conservation Biology.

Induction of ceruloplasmin synthesis by IFN-gamma in human monocytic cells

NASA Technical Reports Server (NTRS)

Mazumder, B.; Mukhopadhyay, C. K.; Prok, A.; Cathcart, M. K.; Fox, P. L.

1997-01-01

Ceruloplasmin is a 132-kDa glycoprotein abundant in human plasma. It has multiple in vitro activities, including copper transport, lipid pro- and antioxidant activity, and oxidation of ferrous ion and aromatic amines; however, its physiologic role is uncertain. Although ceruloplasmin is synthesized primarily by the liver in adult humans, production by cells of monocytic origin has been reported. We here show that IFN-gamma is a potent inducer of ceruloplasmin synthesis by monocytic cells. Activation of human monoblastic leukemia U937 cells with IFN-gamma increased the production of ceruloplasmin by at least 20-fold. The identity of the protein was confirmed by plasmin fingerprinting. IFN-gamma also increased ceruloplasmin mRNA. Induction followed a 2- to 4-h lag and was partially blocked by cycloheximide, indicating a requirement for newly synthesized factors. Ceruloplasmin induction in monocytic cells was agonist specific, as IL-1, IL-4, IL-6, IFN-alpha, IFN-beta, TNF-alpha, and LPS were completely ineffective. The induction was also cell type specific, as IFN-gamma did not induce ceruloplasmin synthesis in endothelial or smooth muscle cells. In contrast, IFN-gamma was stimulatory in other monocytic cells, including THP-1 cells and human peripheral blood monocytes, and also in HepG2 cells. Ceruloplasmin secreted by IFN-gamma-stimulated U937 cells had ferroxidase activity and was, in fact, the only secreted protein with this activity. Monocytic cell-derived ceruloplasmin may contribute to defense responses via its ferroxidase activity, which may drive iron homeostasis in a direction unfavorable to invasive organisms.

Impact of anthropogenic climate change on wildfire across western US forests.

PubMed

Abatzoglou, John T; Williams, A Park

2016-10-18

Increased forest fire activity across the western continental United States (US) in recent decades has likely been enabled by a number of factors, including the legacy of fire suppression and human settlement, natural climate variability, and human-caused climate change. We use modeled climate projections to estimate the contribution of anthropogenic climate change to observed increases in eight fuel aridity metrics and forest fire area across the western United States. Anthropogenic increases in temperature and vapor pressure deficit significantly enhanced fuel aridity across western US forests over the past several decades and, during 2000-2015, contributed to 75% more forested area experiencing high (>1 σ) fire-season fuel aridity and an average of nine additional days per year of high fire potential. Anthropogenic climate change accounted for ∼55% of observed increases in fuel aridity from 1979 to 2015 across western US forests, highlighting both anthropogenic climate change and natural climate variability as important contributors to increased wildfire potential in recent decades. We estimate that human-caused climate change contributed to an additional 4.2 million ha of forest fire area during 1984-2015, nearly doubling the forest fire area expected in its absence. Natural climate variability will continue to alternate between modulating and compounding anthropogenic increases in fuel aridity, but anthropogenic climate change has emerged as a driver of increased forest fire activity and should continue to do so while fuels are not limiting.

Impact of anthropogenic climate change on wildfire across western US forests

NASA Astrophysics Data System (ADS)

Abatzoglou, John T.; Park Williams, A.

2016-10-01

Increased forest fire activity across the western continental United States (US) in recent decades has likely been enabled by a number of factors, including the legacy of fire suppression and human settlement, natural climate variability, and human-caused climate change. We use modeled climate projections to estimate the contribution of anthropogenic climate change to observed increases in eight fuel aridity metrics and forest fire area across the western United States. Anthropogenic increases in temperature and vapor pressure deficit significantly enhanced fuel aridity across western US forests over the past several decades and, during 2000-2015, contributed to 75% more forested area experiencing high (>1 σ) fire-season fuel aridity and an average of nine additional days per year of high fire potential. Anthropogenic climate change accounted for ˜55% of observed increases in fuel aridity from 1979 to 2015 across western US forests, highlighting both anthropogenic climate change and natural climate variability as important contributors to increased wildfire potential in recent decades. We estimate that human-caused climate change contributed to an additional 4.2 million ha of forest fire area during 1984-2015, nearly doubling the forest fire area expected in its absence. Natural climate variability will continue to alternate between modulating and compounding anthropogenic increases in fuel aridity, but anthropogenic climate change has emerged as a driver of increased forest fire activity and should continue to do so while fuels are not limiting.

Melanin and blood concentration in human skin studied by multiple regression analysis: experiments

NASA Astrophysics Data System (ADS)

Shimada, M.; Yamada, Y.; Itoh, M.; Yatagai, T.

2001-09-01

Knowledge of the mechanism of human skin colour and measurement of melanin and blood concentration in human skin are needed in the medical and cosmetic fields. The absorbance spectrum from reflectance at the visible wavelength of human skin increases under several conditions such as a sunburn or scalding. The change of the absorbance spectrum from reflectance including the scattering effect does not correspond to the molar absorption spectrum of melanin and blood. The modified Beer-Lambert law is applied to the change in the absorbance spectrum from reflectance of human skin as the change in melanin and blood is assumed to be small. The concentration of melanin and blood was estimated from the absorbance spectrum reflectance of human skin using multiple regression analysis. Estimated concentrations were compared with the measured one in a phantom experiment and this method was applied to in vivo skin.

The relationship between health and mating success in humans

PubMed Central

Rhodes, Gillian 

2017-01-01

Health has been claimed to play an important role in human sexual selection, especially in terms of mate choice. Our preferences for attractive individuals are said to represent evolved adaptations for finding high-quality, healthy mates. If this is true, then we expect health to predict mating success in humans. We tested this hypothesis using several important physiological indicators of health, including immune function, oxidative stress and semen quality, and self-reported measures of sexual behaviour that contribute to mating success. In contrast to our hypothesis, we did not find a relationship between the physiological measures of health and sexual behaviour. Our results provide little support for claims that health, at least the health measures we used, increases mating success in relatively healthy humans. PMID:28280558

Distributed Neural Activity Patterns during Human-to-Human Competition

PubMed Central

Piva, Matthew; Zhang, Xian; Noah, J. Adam; Chang, Steve W. C.; Hirsch, Joy

2017-01-01

Interpersonal interaction is the essence of human social behavior. However, conventional neuroimaging techniques have tended to focus on social cognition in single individuals rather than on dyads or groups. As a result, relatively little is understood about the neural events that underlie face-to-face interaction. We resolved some of the technical obstacles inherent in studying interaction using a novel imaging modality and aimed to identify neural mechanisms engaged both within and across brains in an ecologically valid instance of interpersonal competition. Functional near-infrared spectroscopy was utilized to simultaneously measure hemodynamic signals representing neural activity in pairs of subjects playing poker against each other (human–human condition) or against computer opponents (human–computer condition). Previous fMRI findings concerning single subjects confirm that neural areas recruited during social cognition paradigms are individually sensitive to human–human and human–computer conditions. However, it is not known whether face-to-face interactions between opponents can extend these findings. We hypothesize distributed effects due to live processing and specific variations in across-brain coherence not observable in single-subject paradigms. Angular gyrus (AG), a component of the temporal-parietal junction (TPJ) previously found to be sensitive to socially relevant cues, was selected as a seed to measure within-brain functional connectivity. Increased connectivity was confirmed between AG and bilateral dorsolateral prefrontal cortex (dlPFC) as well as a complex including the left subcentral area (SCA) and somatosensory cortex (SS) during interaction with a human opponent. These distributed findings were supported by contrast measures that indicated increased activity at the left dlPFC and frontopolar area that partially overlapped with the region showing increased functional connectivity with AG. Across-brain analyses of neural coherence between the players revealed synchrony between dlPFC and supramarginal gyrus (SMG) and SS in addition to synchrony between AG and the fusiform gyrus (FG) and SMG. These findings present the first evidence of a frontal-parietal neural complex including the TPJ, dlPFC, SCA, SS, and FG that is more active during human-to-human social cognition both within brains (functional connectivity) and across brains (across-brain coherence), supporting a model of functional integration of socially and strategically relevant information during live face-to-face competitive behaviors. PMID:29218005

Targeting C-reactive protein for the treatment of cardiovascular disease

NASA Astrophysics Data System (ADS)

Pepys, Mark B.; Hirschfield, Gideon M.; Tennent, Glenys A.; Ruth Gallimore, J.; Kahan, Melvyn C.; Bellotti, Vittorio; Hawkins, Philip N.; Myers, Rebecca M.; Smith, Martin D.; Polara, Alessandra; Cobb, Alexander J. A.; Ley, Steven V.; Andrew Aquilina, J.; Robinson, Carol V.; Sharif, Isam; Gray, Gillian A.; Sabin, Caroline A.; Jenvey, Michelle C.; Kolstoe, Simon E.; Thompson, Darren; Wood, Stephen P.

2006-04-01

Complement-mediated inflammation exacerbates the tissue injury of ischaemic necrosis in heart attacks and strokes, the most common causes of death in developed countries. Large infarct size increases immediate morbidity and mortality and, in survivors of the acute event, larger non-functional scars adversely affect long-term prognosis. There is thus an important unmet medical need for new cardioprotective and neuroprotective treatments. We have previously shown that human C-reactive protein (CRP), the classical acute-phase protein that binds to ligands exposed in damaged tissue and then activates complement, increases myocardial and cerebral infarct size in rats subjected to coronary or cerebral artery ligation, respectively. Rat CRP does not activate rat complement, whereas human CRP activates both rat and human complement. Administration of human CRP to rats is thus an excellent model for the actions of endogenous human CRP. Here we report the design, synthesis and efficacy of 1,6-bis(phosphocholine)-hexane as a specific small-molecule inhibitor of CRP. Five molecules of this palindromic compound are bound by two pentameric CRP molecules, crosslinking and occluding the ligand-binding B-face of CRP and blocking its functions. Administration of 1,6-bis(phosphocholine)-hexane to rats undergoing acute myocardial infarction abrogated the increase in infarct size and cardiac dysfunction produced by injection of human CRP. Therapeutic inhibition of CRP is thus a promising new approach to cardioprotection in acute myocardial infarction, and may also provide neuroprotection in stroke. Potential wider applications include other inflammatory, infective and tissue-damaging conditions characterized by increased CRP production, in which binding of CRP to exposed ligands in damaged cells may lead to complement-mediated exacerbation of tissue injury.

Induction of group A Streptococcus virulence by a human antimicrobial peptide.

PubMed

Gryllos, Ioannis; Tran-Winkler, Hien J; Cheng, Ming-Fang; Chung, Hachung; Bolcome, Robert; Lu, Wuyuan; Lehrer, Robert I; Wessels, Michael R

2008-10-28

Group A streptococci (Streptococcus pyogenes or GAS) freshly isolated from individuals with streptococcal sore throat or invasive ("flesh-eating") infection often grow as mucoid colonies on primary culture but lose this colony appearance after laboratory passage. The mucoid phenotype is due to abundant production of the hyaluronic acid capsular polysaccharide, a key virulence determinant associated with severe GAS infections. These observations suggest that signal(s) from the human host trigger increased production of capsule and perhaps other virulence factors during infection. Here we show that subinhibitory concentrations of the human antimicrobial cathelicidin peptide LL-37 stimulate expression of the GAS capsule synthesis operon (hasABC). Up-regulation is mediated by the CsrRS 2-component regulatory system: it requires a functional CsrS sensor protein and can be antagonized by increased extracellular Mg(2+), the other identified environmental signal for CsrS. Up-regulation was also evident for other CsrRS-regulated virulence genes, including the IL-8 protease PrtS/ScpC and the integrin-like/IgG protease Mac/IdeS, findings that suggest a coordinated GAS virulence response elicited by this antimicrobial immune effector peptide. LL-37 signaling through CsrRS led to a marked increase in GAS resistance to opsonophagocytic killing by human leukocytes, an in vitro measure of enhanced GAS virulence, consistent with increased expression of the antiphagocytic capsular polysaccharide and Mac/IdeS. We propose that the human cathelicidin LL-37 has the paradoxical effect of stimulating CsrRS-regulated virulence gene expression, thereby enhancing GAS pathogenicity during infection. The ability of GAS to sense and respond to LL-37 may explain, at least in part, the unique susceptibility of the human species to streptococcal infection.

Bats and emerging zoonoses: henipaviruses and SARS.

PubMed

Field, H E

2009-08-01

Nearly 75% of all emerging infectious diseases (EIDs) that impact or threaten human health are zoonotic. The majority have spilled from wildlife reservoirs, either directly to humans or via domestic animals. The emergence of many can be attributed to predisposing factors such as global travel, trade, agricultural expansion, deforestation/habitat fragmentation, and urbanization; such factors increase the interface and/or the rate of contact between human, domestic animal, and wildlife populations, thereby creating increased opportunities for spillover events to occur. Infectious disease emergence can be regarded as primarily an ecological process. The epidemiological investigation of EIDs associated with wildlife requires a trans-disciplinary approach that includes an understanding of the ecology of the wildlife species, and an understanding of human behaviours that increase risk of exposure. Investigations of the emergence of Nipah virus in Malaysia in 1999 and severe acute respiratory syndrome (SARS) in China in 2003 provide useful case studies. The emergence of Nipah virus was associated with the increased size and density of commercial pig farms and their encroachment into forested areas. The movement of pigs for sale and slaughter in turn led to the rapid spread of infection to southern peninsular Malaysia, where the high-density, largely urban pig populations facilitated transmission to humans. Identifying the factors associated with the emergence of SARS in southern China requires an understanding of the ecology of infection both in the natural reservoir and in secondary market reservoir species. A necessary extension of understanding the ecology of the reservoir is an understanding of the trade, and of the social and cultural context of wildlife consumption. Emerging infectious diseases originating from wildlife populations will continue to threaten public health. Mitigating and managing the risk requires an appreciation of the connectedness between human, livestock and wildlife health, and of the factors and processes that disrupt the balance.

Rhinovirus exacerbates house-dust-mite induced lung disease in adult mice.

PubMed

Phan, Jennifer A; Kicic, Anthony; Berry, Luke J; Fernandes, Lynette B; Zosky, Graeme R; Sly, Peter D; Larcombe, Alexander N

2014-01-01

Human rhinovirus is a key viral trigger for asthma exacerbations. To date, murine studies investigating rhinovirus-induced exacerbation of allergic airways disease have employed systemic sensitisation/intranasal challenge with ovalbumin. In this study, we combined human-rhinovirus infection with a clinically relevant mouse model of aero-allergen exposure using house-dust-mite in an attempt to more accurately understand the links between human-rhinovirus infection and exacerbations of asthma. Adult BALB/c mice were intranasally exposed to low-dose house-dust-mite (or vehicle) daily for 10 days. On day 9, mice were inoculated with human-rhinovirus-1B (or UV-inactivated human-rhinovirus-1B). Forty-eight hours after inoculation, we assessed bronchoalveolar cellular inflammation, levels of relevant cytokines/serum antibodies, lung function and responsiveness/sensitivity to methacholine. House-dust-mite exposure did not result in a classical TH2-driven response, but was more representative of noneosinophilic asthma. However, there were significant effects of house-dust-mite exposure on most of the parameters measured including increased cellular inflammation (primarily macrophages and neutrophils), increased total IgE and house-dust-mite-specific IgG1 and increased responsiveness/sensitivity to methacholine. There were limited effects of human-rhinovirus-1B infection alone, and the combination of the two insults resulted in additive increases in neutrophil levels and lung parenchymal responses to methacholine (tissue elastance). We conclude that acute rhinovirus infection exacerbates house-dust-mite-induced lung disease in adult mice. The similarity of our results using the naturally occurring allergen house-dust-mite, to previous studies using ovalbumin, suggests that the exacerbation of allergic airways disease by rhinovirus infection could act via multiple or conserved mechanisms.

Megafauna biomass tradeoff as a driver of Quaternary and future extinctions

PubMed Central

Barnosky, Anthony D.

2008-01-01

Earth's most recent major extinction episode, the Quaternary Megafauna Extinction, claimed two-thirds of mammal genera and one-half of species that weighed >44 kg between ≈50,000 and 3,000 years ago. Estimates of megafauna biomass (including humans as a megafauna species) for before, during, and after the extinction episode suggest that growth of human biomass largely matched the loss of non-human megafauna biomass until ≈12,000 years ago. Then, total megafauna biomass crashed, because many non-human megafauna species suddenly disappeared, whereas human biomass continued to rise. After the crash, the global ecosystem gradually recovered into a new state where megafauna biomass was concentrated around one species, humans, instead of being distributed across many species. Precrash biomass levels were finally reached just before the Industrial Revolution began, then skyrocketed above the precrash baseline as humans augmented the energy available to the global ecosystem by mining fossil fuels. Implications include (i) an increase in human biomass (with attendant hunting and other impacts) intersected with climate change to cause the Quaternary Megafauna Extinction and an ecological threshold event, after which humans became dominant in the global ecosystem; (ii) with continued growth of human biomass and today's unprecedented global warming, only extraordinary and stepped-up conservation efforts will prevent a new round of extinctions in most body-size and taxonomic spectra; and (iii) a near-future biomass crash that will unfavorably impact humans and their domesticates and other species is unavoidable unless alternative energy sources are developed to replace dwindling supplies of fossil fuels. PMID:18695222

Simultaneous measurement of adenosine triphosphate release and aggregation potentiates human platelet aggregation responses for some subjects, including persons with Quebec platelet disorder.

PubMed

Hayward, C P M; Moffat, K A; Castilloux, J-F; Liu, Y; Seecharan, J; Tasneem, S; Carlino, S; Cormier, A; Rivard, G E

2012-04-01

Platelet aggregometry and dense granule adenosine triphosphate (ATP) release assays are helpful to diagnose platelet disorders. Some laboratories simultaneously measure aggregation and ATP release using Chronolume® a commercial reagent containing D-luciferin, firefly luciferase and magnesium. Chronolume® can potentiate sub-maximal aggregation responses, normalising canine platelet disorder findings. We investigated if Chronolume® potentiates human platelet aggregation responses after observing discrepancies suspicious of potentiation. Among patients simultaneously tested by light transmission aggregometry (LTA) on two instruments, 18/43 (42%), including 14/24 (58%) with platelet disorders, showed full secondary aggregation with one or more agonists only in tests with Chronolume®. As subjects with Quebec platelet disorder (QPD) did not show the expected absent secondary aggregation responses to epinephrine in tests with Chronolume®, the reason for the discrepancy was investigated using samples from 10 QPD subjects. Like sub-threshold ADP (0.75 μM), Chronolume® significantly increased QPD LTA responses to epinephrine (p<0.0001) and it increased both initial and secondary aggregation responses, leading to dense granule release. This potentiation was not restricted to QPD and it was mimicked adding 1-2 mM magnesium, but not D-luciferin or firefly luciferase, to LTA assays. Chronolume® potentiated the ADP aggregation responses of QPD subjects with a reduced response. Furthermore, it increased whole blood aggregation responses of healthy control samples to multiple agonists, tested at concentrations used for the diagnosis of platelet disorders (p values <0.05). Laboratories should be aware that measuring ATP release with Chronolume® can potentiate LTA and whole blood aggregation responses, which alters findings for some human platelet disorders, including QPD.

Dynamic proteome profiling of individual proteins in human skeletal muscle after a high-fat diet and resistance exercise.

PubMed

Camera, Donny M; Burniston, Jatin G; Pogson, Mark A; Smiles, William J; Hawley, John A

2017-12-01

It is generally accepted that muscle adaptation to resistance exercise (REX) training is underpinned by contraction-induced, increased rates of protein synthesis and dietary protein availability. By using dynamic proteome profiling (DPP), we investigated the contribution of both synthesis and breakdown to changes in abundance on a protein-by-protein basis in human skeletal muscle. Age-matched, overweight males consumed 9 d of a high-fat, low-carbohydrate diet during which time they either undertook 3 sessions of REX or performed no exercise. Precursor enrichment and the rate of incorporation of deuterium oxide into newly synthesized muscle proteins were determined by mass spectrometry. Ninety proteins were included in the DPP, with 28 proteins exhibiting significant responses to REX. The most common pattern of response was an increase in turnover, followed by an increase in abundance with no detectable increase in protein synthesis. Here, we provide novel evidence that demonstrates that the contribution of synthesis and breakdown to changes in protein abundance induced by REX differ on a protein-by-protein basis. We also highlight the importance of the degradation of individual muscle proteins after exercise in human skeletal muscle.-Camera, D. M., Burniston, J. G., Pogson, M. A., Smiles, W. J., Hawley, J. A. Dynamic proteome profiling of individual proteins in human skeletal muscle after a high-fat diet and resistance exercise. © FASEB.

The consequences of human actions on risks for infectious diseases: a review

PubMed Central

Lindahl, Johanna F.; Grace, Delia

2015-01-01

The human population is growing, requiring more space for food production, and needing more animals to feed it. Emerging infectious diseases are increasing, causing losses in both human and animal lives, as well as large costs to society. Many factors are contributing to disease emergence, including climate change, globalization and urbanization, and most of these factors are to some extent caused by humans. Pathogens may be more or less prone to emergence in themselves, and rapidly mutating viruses are more common among the emerging pathogens. The climate-sensitive vector-borne diseases are likely to be emerging due to climate changes and environmental changes, such as increased irrigation. This review lists the factors within pathogens that make them prone to emergence, and the modes of transmission that are affected. The anthropogenic changes contributing to disease emergence are described, as well as how they directly and indirectly cause either increased numbers of susceptible or exposed individuals, or cause increased infectivity. Many actions may have multiple direct or indirect effects, and it may be difficult to assess what the consequences may be. In addition, most anthropogenic drivers are related to desired activities, such as logging, irrigation, trade, and travelling, which the society is requiring. It is important to research more about the indirect and direct effects of the different actions to understand both the benefits and the risks. PMID:26615822

Human β‐defensin 3 increases the TLR9‐dependent response to bacterial DNA

PubMed Central

McGlasson, Sarah L.; Semple, Fiona; MacPherson, Heather; Gray, Mohini; Davidson, Donald J.

2017-01-01

Human β‐defensin 3 (hBD3) is a cationic antimicrobial peptide with potent bactericidal activity in vitro. HBD3 is produced in response to pathogen challenge and can modulate immune responses. The amplified recognition of self‐DNA by human plasmacytoid dendritic cells has been previously reported, but we show here that hBD3 preferentially enhances the response to bacterial DNA in mouse Flt‐3 induced dendritic cells (FLDCs) and in human peripheral blood mononuclear cells. We show the effect is mediated through TLR9 and although hBD3 significantly increases the cellular uptake of both E. coli and self‐DNA in mouse FLDCs, only the response to bacterial DNA is enhanced. Liposome transfection also increases uptake of bacterial DNA and amplifies the TLR9‐dependent response. In contrast to hBD3, lipofection of self‐DNA enhances inflammatory signaling, but the response is predominantly TLR9‐independent. Together, these data show that hBD3 has a role in the innate immune‐mediated response to pathogen DNA, increasing inflammatory signaling and promoting activation of the adaptive immune system via antigen presenting cells including dendritic cells. Therefore, our data identify an additional immunomodulatory role for this copy‐number variable defensin, of relevance to host defence against infection and indicate a potential for the inclusion of HBD3 in pathogen DNA‐based vaccines. PMID:28102569

Consumption of selenium-enriched broccoli increases cytokine production in human peripheral blood mononuclear cells stimulated ex vivo, a preliminary human intervention study.

PubMed

Bentley-Hewitt, Kerry L; Chen, Ronan K-Y; Lill, Ross E; Hedderley, Duncan I; Herath, Thanuja D; Matich, Adam J; McKenzie, Marian J

2014-12-01

Selenium (Se) is a micronutrient essential for human health, including immune function. Previous research indicates that Se supplementation may cause a shift from T helper (Th)1- to Th2-type immune responses. We aim to test the potential health promoting effects of Se-enriched broccoli. In a human trial, 18 participants consumed control broccoli daily for 3 days. After a 3-day wash-out period, the participants were provided with Se-enriched broccoli containing 200 μg of Se per serving for 3 days. Plasma and peripheral blood mononuclear cell (PBMC) samples were collected at the start and end of each broccoli feeding period for analysis of total Se and measurement of cytokine production from PBMC stimulated with antigens ex vivo. Plasma Se content remained consistent throughout the control broccoli feeding period and the baseline of the Se-enriched broccoli period (1.22 μmol/L) and then significantly increased following 3 days of Se-enriched broccoli feeding. Interleukin (IL-2, IL-4, IL-5, IL-13, and IL-22) production from PBMC significantly increased after 3 days of Se-enriched broccoli feeding compared with baseline. This study indicates that consumption of Se-enriched broccoli may increase immune responses toward a range of immune challenges. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[A profile of the population of Indonesia: developing human resources].

PubMed

Mantra, I B

1991-01-01

Population characteristics and their implications for human resource development in Indonesia are analyzed using data from official sources, including the 1990 census. The author concludes that concurrent with some socioeconomic development have been improvements in conditions and characteristics of the population, as seen in the declines in the proportion of the dependent child population and in fertility and mortality rates. An increase in spontaneous internal migration in response to changes in local conditions is also noted. (SUMMARY IN ENG)

Human Genome Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1993-01-01

The DOE Human Genome program has grown tremendously, as shown by the marked increase in the number of genome-funded projects since the last workshop held in 1991. The abstracts in this book describe the genome research of DOE-funded grantees and contractors and invited guests, and all projects are represented at the workshop by posters. The 3-day meeting includes plenary sessions on ethical, legal, and social issues pertaining to the availability of genetic data; sequencing techniques, informatics support; and chromosome and cDNA mapping and sequencing.

Self-disseminating vaccines for emerging infectious diseases.

PubMed

Murphy, Aisling A; Redwood, Alec J; Jarvis, Michael A

2016-01-01

Modern human activity fueled by economic development is profoundly altering our relationship with microorganisms. This altered interaction with microbes is believed to be the major driving force behind the increased rate of emerging infectious diseases from animals. The spate of recent infectious disease outbreaks, including Ebola virus disease and Middle East respiratory syndrome, emphasize the need for development of new innovative tools to manage these emerging diseases. Disseminating vaccines are one such novel approach to potentially interrupt animal to human (zoonotic) transmission of these pathogens.

Pharmacological Overview of Galactogogues

PubMed Central

Penagos Tabares, Felipe; Bedoya Jaramillo, Juliana V.; Ruiz-Cortés, Zulma Tatiana

2014-01-01

Galactogogues are substances used to induce, maintain, and increase milk production, both in human clinical conditions (like noninfectious agalactias and hypogalactias) and in massification of production in the animal dairy industry. This paper aims to report the state of the art on the possible mechanisms of action, effectiveness, and side effects of galactogogues, including potential uses in veterinary and human medicine. The knowledge gaps in veterinary clinical practice use of galactogogues, especially in the standardization of the lactogenic dose in some pure drugs and herbal preparations, are reviewed. PMID:25254141

Exploring consumer pathways and patterns of use for ...

EPA Pesticide Factsheets

Background: Humans may be exposed to thousands of chemicals through contact in the workplace, home, and via air, water, food, and soil. A major challenge is estimating exposures to these chemicals, which requires understanding potential exposure routes directly related to how chemicals are used. Objectives: We aimed to assign “use categories” to a database of chemicals, including ingredients in consumer products, to help prioritize which chemicals will be given more scrutiny relative to human exposure potential and target populations. The goal was to identify (a) human activities that result in increased chemical exposure while (b) simplifying the dimensionality of hazard assessment for risk characterization. Methods: Major data sources on consumer- and industrial-process based chemical uses were compiled from multiple countries, including from regulatory agencies, manufacturers, and retailers. The resulting categorical chemical use and functional information are presented through the Chemical/Product Categories Database (CPCat). Results: CPCat contains information on 43,596 unique chemicals mapped to 833 terms categorizing their usage or function. Examples presented demonstrate potential applications of the CPCat database, including the identification of chemicals to which children may be exposed (including those that are not identified on product ingredient labels), and prioritization of chemicals for toxicity screening. The CPCat database is availabl

The microbiome of the built environment and mental health.

PubMed

Hoisington, Andrew J; Brenner, Lisa A; Kinney, Kerry A; Postolache, Teodor T; Lowry, Christopher A

2015-12-17

The microbiome of the built environment (MoBE) is a relatively new area of study. While some knowledge has been gained regarding impacts of the MoBE on the human microbiome and disease vulnerability, there is little knowledge of the impacts of the MoBE on mental health. Depending on the specific microbial species involved, the transfer of microorganisms from the built environment to occupant's cutaneous or mucosal membranes has the potential to increase or disrupt immunoregulation and/or exaggerate or suppress inflammation. Preclinical evidence highlighting the influence of the microbiota on systemic inflammation supports the assertion that microorganisms, including those originating from the built environment, have the potential to either increase or decrease the risk of inflammation-induced psychiatric conditions and their symptom severity. With advanced understanding of both the ecology of the built environment, and its influence on the human microbiome, it may be possible to develop bioinformed strategies for management of the built environment to promote mental health. Here we present a brief summary of microbiome research in both areas and highlight two interdependencies including the following: (1) effects of the MoBE on the human microbiome and (2) potential opportunities for manipulation of the MoBE in order to improve mental health. In addition, we propose future research directions including strategies for assessment of changes in the microbiome of common areas of built environments shared by multiple human occupants, and associated cohort-level changes in the mental health of those who spend time in the buildings. Overall, our understanding of the fields of both the MoBE and influence of host-associated microorganisms on mental health are advancing at a rapid pace and, if linked, could offer considerable benefit to health and wellness.

MicroRNA-30b-Mediated Regulation of Catalase Expression in Human ARPE-19 Cells

PubMed Central

Haque, Rashidul; Chun, Eugene; Howell, Jennifer C.; Sengupta, Trisha; Chen, Dan; Kim, Hana

2012-01-01

Background Oxidative injury to retinal pigment epithelium (RPE) and retinal photoreceptors has been linked to a number of retinal diseases, including age-related macular degeneration (AMD). Reactive oxygen species (ROS)-mediated gene expression has been extensively studied at transcriptional levels. Also, the post-transcriptional control of gene expression at the level of translational regulation has been recently reported. However, the microRNA (miRNA/miR)-mediated post-transcriptional regulation in human RPE cells has not been thoroughly looked at. Increasing evidence points to a potential role of miRNAs in diverse physiological processes. Methodology/Principal Findings We demonstrated for the first time in a human retinal pigment epithelial cell line (ARPE-19) that the post-transcriptional control of gene expression via miRNA modulation regulates human catalase, an important and potent component of cell's antioxidant defensive network, which detoxifies hydrogen peroxide (H2O2) radicals. Exposure to several stress-inducing agents including H2O2 has been reported to alter miRNA expression profile. Here, we demonstrated that a sublethal dose of H2O2 (200 µM) up-regulated the expression of miR-30b, a member of the miR-30 family, which inhibited the expression of endogenous catalase both at the transcript and protein levels. However, antisense (antagomirs) of miR-30b was not only found to suppress the miR-30b mimics-mediated inhibitions, but also to dramatically increase the expression of catalase even under an oxidant environment. Conclusions/Significance We propose that a microRNA antisense approach could enhance cytoprotective mechanisms against oxidative stress by increasing the antioxidant defense system. PMID:22880027

The Human Impact of Earthquakes: a Historical Review of Events 1980-2009 and Systematic Literature Review

PubMed Central

Doocy, Shannon; Daniels, Amy; Packer, Catherine; Dick, Anna; Kirsch, Thomas D.

2013-01-01

Introduction. Population growth and increasing urbanization in earthquake-prone areas suggest that earthquake impacts on human populations will increase in the coming decades. Recent large earthquakes affecting large populations in Japan, Haiti, Chile and New Zealand are evidence of this trend and also illustrate significant variations in outcomes such damage and mortality levels. The objectives of this review were to describe the impact of earthquakes on human populations in terms of mortality, injury and displacement and, to the extent possible, identify risk factors associated with these outcomes. This is one of five reviews on the human impact of natural disasters. Methods. Data on the impact of earthquakes were compiled using two methods, a historical review from 1980 to mid 2009 of earthquake events from multiple databases and a systematic literature review of publications, ending in October 2012. Analysis included descriptive statistics and bivariate tests for associations between earthquake mortality and characteristics using STATA 11. Findings. From 1980 through 2009, there were a total of 372,634 deaths (range 314,634-412,599), 995,219 injuries (range: 845,345-1,145,093), and more than 61 million people affected by earthquakes, and mortality was greatest in Asia. Inconsistent reporting across data sources suggests that the numbers injured and affected are likely underestimates. Findings from a systematic review of the literature indicate that the primary cause of earthquake-related death was trauma due to building collapse and, the very young and the elderly were at increased mortality risk, while gender was not consistently associated with mortality risk. Conclusions. Strategies to mitigate the impact of future earthquakes should include improvements to the built environment and a focus on populations most vulnerable to mortality and injury. PMID:23857161

The use of glial data in human health assessments of environmental contaminants.

PubMed

Kraft, Andrew D

2015-07-03

Central nervous system (CNS) glia (i.e., astrocytes, microglia, and oligodendrocytes) are essential for maintaining neuronal homeostasis, and they orchestrate an organized cellular response to CNS injury. In addition to their beneficial roles, studies have demonstrated that disrupted glial function can have disastrous consequences on neuronal health. While effects on neuron-supportive glia are important to consider when evaluating neurotoxicity risk, interpreting glial changes is not always straightforward, particularly when attempting to discern pro-neurotoxic phenotypes from homeostatic processes or adaptive responses. To better understand how glia have been characterized and used in human health assessments of environmental contaminants (e.g., chemicals), an evaluation of all finalized assessments conducted by the U.S. Environmental Protection Agency's influential Integrated Risk Information System (IRIS) program between 1987 and 2013 was performed. Human health assessments to date have placed a clear emphasis on the neuronal cell response to potential toxicants, although more recent assessments increasingly include descriptions of glial changes. However, these descriptions are generally brief and non-specific, and they primarily consist of documenting gliosis following overt neuronal injury. As research interest in this topic continues to increase, methods for evaluating changes in glia continue to be expanded and refined, and assessors' confidence in the reliability of these data is likely to rise. Thus, glial data are anticipated to have an increasingly influential impact on the interpretation of neurotoxicity risk and underlying mechanisms. As our understanding of the complex roles these cells play grows, this knowledge is expected to support the inclusion of more extensive and specific descriptions of glial changes, including informed interpretations of the potential impact on CNS health, in future human health assessments. Published by Elsevier Ireland Ltd.

Update on Powassan virus: emergence of a North American tick-borne flavivirus.

PubMed

Ebel, Gregory D

2010-01-01

Powassan virus (POW) (Flaviviridae: Flavivirus) is the cause of rare but severe neuroinvasive disease in North America and Russia. The virus is transmitted among small- and medium-sized mammals by ixodid ticks. Human infections occur via spillover from the main transmission cycle(s). Since the late 1990s, the incidence of human disease seems to be increasing. In addition, POW constitutes a genetically diverse group of virus genotypes, including Deer tick virus, that are maintained in distinct enzootic transmission cycles. This review highlights recent research into POW, focusing on virus genetics and ecology and human disease. Important directions for future research are also discussed.

Are recent hurricane (Harvey, Irma, Maria) disasters natural?

NASA Astrophysics Data System (ADS)

Trenberth, K. E.; Lijing, C.; Jacobs, P.; Abraham, J. P.

2017-12-01

Yes and no! Hurricanes are certainly natural, but human-caused climate change is supersizing them, and unbridled growth is exacerbating risk of major damages. The addition of heat-trapping gases to the atmosphere has led to observed increases in upper ocean heat content (OHC). This human-caused increase in OHC supports higher sea surface temperatures (SSTs) and atmospheric moisture. These elevated temperatures and increased moisture availability fuel tropical storms, allowing them to grow larger, longer lasting, and more intense, and with widespread heavy rainfalls. Our preliminary analysis of OHC through the August of 2017 shows not only was it by far the highest on record globally, but it was also the highest on record in the Gulf of Mexico prior to hurricane Harvey occurring. The human influence on the climate is also evident in rising sea levels, which increases risks from storm surges. These climatic changes are taking place against a background of growing habitation along coasts, which further increases the risk storms pose to life and property. This combination of planning choice and climatic change illustrates the tragedy of global warming, as evidenced by Harvey in Houston, Irma in the Caribbean and Florida, and Maria in Puerto Rico. However, future damages and loss of life can be mitigated, by stopping or slowing human-caused climate change, and through proactive planning (e.g., better building codes, increased-capacity drainage systems, shelters, and evacuation plans). We discuss the climatic and planning contexts of the unnatural disasters of the 2017 Atlantic Hurricane season, including novel indices of climate-hurricane influence.

Trehalose upregulates progranulin expression in human and mouse models of GRN haploinsufficiency: a novel therapeutic lead to treat frontotemporal dementia.

PubMed

Holler, Christopher J; Taylor, Georgia; McEachin, Zachary T; Deng, Qiudong; Watkins, William J; Hudson, Kathryn; Easley, Charles A; Hu, William T; Hales, Chadwick M; Rossoll, Wilfried; Bassell, Gary J; Kukar, Thomas

2016-06-24

Progranulin (PGRN) is a secreted growth factor important for neuronal survival and may do so, in part, by regulating lysosome homeostasis. Mutations in the PGRN gene (GRN) are a common cause of frontotemporal lobar degeneration (FTLD) and lead to disease through PGRN haploinsufficiency. Additionally, complete loss of PGRN in humans leads to neuronal ceroid lipofuscinosis (NCL), a lysosomal storage disease. Importantly, Grn-/- mouse models recapitulate pathogenic lysosomal features of NCL. Further, GRN variants that decrease PGRN expression increase the risk of developing Alzheimer's disease (AD) and Parkinson's disease (PD). Together these findings demonstrate that insufficient PGRN predisposes neurons to degeneration. Therefore, compounds that increase PGRN levels are potential therapeutics for multiple neurodegenerative diseases. Here, we performed a cell-based screen of a library of known autophagy-lysosome modulators and identified multiple novel activators of a human GRN promoter reporter including several common mTOR inhibitors and an mTOR-independent activator of autophagy, trehalose. Secondary cellular screens identified trehalose, a natural disaccharide, as the most promising lead compound because it increased endogenous PGRN in all cell lines tested and has multiple reported neuroprotective properties. Trehalose dose-dependently increased GRN mRNA as well as intracellular and secreted PGRN in both mouse and human cell lines and this effect was independent of the transcription factor EB (TFEB). Moreover, trehalose rescued PGRN deficiency in human fibroblasts and neurons derived from induced pluripotent stem cells (iPSCs) generated from GRN mutation carriers. Finally, oral administration of trehalose to Grn haploinsufficient mice significantly increased PGRN expression in the brain. This work reports several novel autophagy-lysosome modulators that enhance PGRN expression and identifies trehalose as a promising therapeutic for raising PGRN levels to treat multiple neurodegenerative diseases.

Nature's role in sustaining economic development

PubMed Central

Dasgupta, Partha

2010-01-01

In this paper, I formalize the idea of sustainable development in terms of intergenerational well-being. I then sketch an argument that has recently been put forward formally to demonstrate that intergenerational well-being increases over time if and only if a comprehensive measure of wealth per capita increases. The measure of wealth includes not only manufactured capital, knowledge and human capital (education and health), but also natural capital (e.g. ecosystems). I show that a country's comprehensive wealth per capita can decline even while gross domestic product (GDP) per capita increases and the UN Human Development Index records an improvement. I then use some rough and ready data from the world's poorest countries and regions to show that during the period 1970–2000 wealth per capita declined in South Asia and sub-Saharan Africa, even though the Human Development Index (HDI) showed an improvement everywhere and GDP per capita increased in all places (except in sub-Saharan Africa, where there was a slight decline). I conclude that, as none of the development indicators currently in use is able to reveal whether development has been, or is expected to be, sustainable, national statistical offices and international organizations should now routinely estimate the (comprehensive) wealth of nations. PMID:20008380

Human endogenous retrovirus W env increases nitric oxide production and enhances the migration ability of microglia by regulating the expression of inducible nitric oxide synthase.

PubMed

Xiao, Ran; Li, Shan; Cao, Qian; Wang, Xiuling; Yan, Qiujin; Tu, Xiaoning; Zhu, Ying; Zhu, Fan

2017-06-01

Human endogenous retrovirus W env (HERV-W env) plays a critical role in many neuropsychological diseases such as schizophrenia and multiple sclerosis (MS). These diseases are accompanied by immunological reactions in the central nervous system (CNS). Microglia are important immunocytes in brain inflammation that can produce a gasotransmitter-nitric oxide (NO). NO not only plays a role in the function of neuronal cells but also participates in the pathogenesis of various neuropsychological diseases. In this study, we reported increased NO production in CHME-5 microglia cells after they were transfected with HERV-W env. Moreover, HERV-W env increased the expression and function of human inducible nitric oxide synthase (hiNOS) and enhanced the promoter activity of hiNOS. Microglial migration was also enhanced. These data revealed that HERV-W env might contribute to increase NO production and microglial migration ability in neuropsychological disorders by regulating the expression of inducible NOS. Results from this study might lead to the identification of novel targets for the treatment of neuropsychological diseases, including neuroinflammatory diseases, stroke, and neurodegenerative diseases.

Increasing cognitive load attenuates right arm swing in healthy human walking

NASA Astrophysics Data System (ADS)

Killeen, Tim; Easthope, Christopher S.; Filli, Linard; Lőrincz, Lilla; Schrafl-Altermatt, Miriam; Brugger, Peter; Linnebank, Michael; Curt, Armin; Zörner, Björn; Bolliger, Marc

2017-01-01

Human arm swing looks and feels highly automated, yet it is increasingly apparent that higher centres, including the cortex, are involved in many aspects of locomotor control. The addition of a cognitive task increases arm swing asymmetry during walking, but the characteristics and mechanism of this asymmetry are unclear. We hypothesized that this effect is lateralized and a Stroop word-colour naming task-primarily involving left hemisphere structures-would reduce right arm swing only. We recorded gait in 83 healthy subjects aged 18-80 walking normally on a treadmill and while performing a congruent and incongruent Stroop task. The primary measure of arm swing asymmetry-an index based on both three-dimensional wrist trajectories in which positive values indicate proportionally smaller movements on the right-increased significantly under dual-task conditions in those aged 40-59 and further still in the over-60s, driven by reduced right arm flexion. Right arm swing attenuation appears to be the norm in humans performing a locomotor-cognitive dual-task, confirming a prominent role of the brain in locomotor behaviour. Women under 60 are surprisingly resistant to this effect, revealing unexpected gender differences atop the hierarchical chain of locomotor control.

Emerging diseases and implications for Millennium Development Goals in Africa by 2015 - an overview.

PubMed

Aluwong, Tagang; Bello, Mohammed

2010-01-01

Emerging zoonotic diseases have assumed increasing fundamental importance in both public and animal health, as the last few years have seen a steady increase of new cases, each emerging from an unsuspected geographic area and causing serious problems, often leading to mortalities among animals and humans. The reasons for disease emergence or re-emergence are multiple and include certain major factors, such as expansion of the human population, climate change and globalisation of trade. Further contributing issues, such as the increased movement of animal species, microbial evolution, ecological disruption, changes in human behaviour, all imply that emerging diseases will not only continue to occur, but the rate of their emergence will also increase. These will constitute constraints for the attainment of the Millennium Development Goals by African Governments by 2015. There is no doubt that the current trend calls for more and stronger partnerships between national and international organisations, veterinary and medical communities, environmentalists, academics and policy-makers of various governments on the continent within the context of the global 'One Health' movement. This article attempts to analyse the impact of emerging diseases and the implications for the achievement of the Millennium Development Goals in Africa by the year 2015.

Nature's role in sustaining economic development.

PubMed

Dasgupta, Partha

2010-01-12

In this paper, I formalize the idea of sustainable development in terms of intergenerational well-being. I then sketch an argument that has recently been put forward formally to demonstrate that intergenerational well-being increases over time if and only if a comprehensive measure of wealth per capita increases. The measure of wealth includes not only manufactured capital, knowledge and human capital (education and health), but also natural capital (e.g. ecosystems). I show that a country's comprehensive wealth per capita can decline even while gross domestic product (GDP) per capita increases and the UN Human Development Index records an improvement. I then use some rough and ready data from the world's poorest countries and regions to show that during the period 1970-2000 wealth per capita declined in South Asia and sub-Saharan Africa, even though the Human Development Index (HDI) showed an improvement everywhere and GDP per capita increased in all places (except in sub-Saharan Africa, where there was a slight decline). I conclude that, as none of the development indicators currently in use is able to reveal whether development has been, or is expected to be, sustainable, national statistical offices and international organizations should now routinely estimate the (comprehensive) wealth of nations.

Carbon sequestration to mitigate climate change

USGS Publications Warehouse

Sundquist, Eric; Burruss, Robert; Faulkner, Stephen; Gleason, Robert; Harden, Jennifer; Kharaka, Yousif; Tieszen, Larry; Waldrop, Mark

2008-01-01

Human activities, especially the burning of fossil fuels such as coal, oil, and gas, have caused a substantial increase in the concentration of carbon dioxide (CO2) in the atmosphere. This increase in atmospheric CO2 - from about 280 to more than 380 parts per million (ppm) over the last 250 years - is causing measurable global warming. Potential adverse impacts include sea-level rise; increased frequency and intensity of wildfires, floods, droughts, and tropical storms; changes in the amount, timing, and distribution of rain, snow, and runoff; and disturbance of coastal marine and other ecosystems. Rising atmospheric CO2 is also increasing the absorption of CO2 by seawater, causing the ocean to become more acidic, with potentially disruptive effects on marine plankton and coral reefs. Technically and economically feasible strategies are needed to mitigate the consequences of increased atmospheric CO2. The United States needs scientific information to develop ways to reduce human-caused CO2 emissions and to remove CO2 from the atmosphere.

Effects of silver nanoparticles on human and rat embryonic neural stem cells

PubMed Central

Liu, Fang; Mahmood, Meena; Xu, Yang; Watanabe, Fumiya; Biris, Alexandru S.; Hansen, Deborah K.; Inselman, Amy; Casciano, Daniel; Patterson, Tucker A.; Paule, Merle G.; Slikker, William; Wang, Cheng

2015-01-01

Silver nano-particles (Ag-NPs) are becoming increasingly prevalent in consumer products as antibacterial agents. The increased use of Ag NP-enhanced products will almost certainly increase environmental silver levels, resulting in increased exposures and the potential for increased adverse reactions including neurotoxic effects. In the present study, embryonic neural stem cells (NSCs) from human and rat fetuses (gestational day-16) were used to determine whether Ag-NPs are capable of causing developmental neurotoxicity. The NSCs were cultured in serum free medium supplemented with appropriate growth factors. On the eighth day in vitro (DIV 8), the cells were exposed to Ag-NPs at concentrations of 1, 5, 10, and 20 μg/ml for 24 h. The cultured cells then were characterized by NSC markers including nestin and SOX2 and a variety of assays were utilized to determine the effects of Ag-NPs on NSC proliferation and viability and the underlying mechanisms associated with these effects. The results indicate that mitochondrial viability (MTT metabolism) was substantially attenuated and LDH release was increased significantly in a dose-dependent manner. Ag-NPs-induced neurotoxicity was further confirmed by up-regulated Bax protein expression, an increased number of TUNEL-positively stained cells, and elevated reactive oxygen species (ROS). NSC proliferation was also significantly decreased by Ag-NPs. Co-administration of acetyl-L-carnitine, an antioxidant agent, effectively blocked the adverse effects associated with Ag-NP exposure. PMID:25904840

Landscape hydrology. The hydrological legacy of deforestation on global wetlands.

PubMed

Woodward, C; Shulmeister, J; Larsen, J; Jacobsen, G E; Zawadzki, A

2014-11-14

Increased catchment erosion and nutrient loading are commonly recognized impacts of deforestation on global wetlands. In contrast, an increase in water availability in deforested catchments is well known in modern studies but is rarely considered when evaluating past human impacts. We used a Budyko water balance approach, a meta-analysis of global wetland response to deforestation, and paleoecological studies from Australasia to explore this issue. After complete deforestation, we demonstrated that water available to wetlands increases by up to 15% of annual precipitation. This can convert ephemeral swamps to permanent lakes or even create new wetlands. This effect is globally significant, with 9 to 12% of wetlands affected, including 20 to 40% of Ramsar wetlands, but is widely unrecognized because human impact studies rarely test for it. Copyright © 2014, American Association for the Advancement of Science.

Human land-use and soil change

USGS Publications Warehouse

Wills, Skye A.; Williams, Candiss O.; Duniway, Michael C.; Veenstra, Jessica; Seybold, Cathy; Pressley, DeAnn

2017-01-01

Soil change refers to the alteration of soil and soil properties over time in one location, as opposed to soil variability across space. Although soils change with pedogensis, this chapter focuses on human caused soil change. Soil change can occur with human use and management over long or short time periods and small or large scales. While change can be negative or positive; often soil change is observed when short-term or narrow goals overshadow the other soil’s ecosystem services. Many soils have been changed in their chemical, physical or biological properties through agricultural activities, including cultivation, tillage, weeding, terracing, subsoiling, deep plowing, manure and fertilizer addition, liming, draining, and irrigation. Assessing soil change depends upon the ecosystem services and soil functions being evaluated. The interaction of soil properties with the type and intensity of management and disturbance determines the changes that will be observed. Tillage of cropland disrupts aggregates and decreases soil organic carbon content which can lead to decreased infiltration, increased erosion, and reduced biological function. Improved agricultural management systems can increase soil functions including crop productivity and sustainability. Forest management is most intensive during harvesting and seedling establishment. Most active management in forests causes disturbance of the soil surface which may include loss of forest floor organic materials, increases in bulk density, and increased risk of erosion. In grazing lands, pasture management often includes periods of biological, chemical and physical disturbance in addition to the grazing management imposed on rangelands. Grazing animals have both direct and indirect impacts on soil change. Hoof action can lead to the disturbance of biological crusts and other surface features impairing the soil’s physical, biological and hydrological function. There are clear feedbacks between vegetative systems and soil properties; when vegetation is altered because of grazing or other disturbances, soil property changes often follow. Some soils are very sensitive to management and disturbance and can undergo rapid change: cropping led to massive gully formation in the southeastern USA, exposure of acid-sulfate soils led to irreversible changes in soil minerology and thawing of cold soils has created thermokarst features. These soil changes alter soil properties and functions and may impact soil ecosystem services far into the future.

What Is the Predictive Value of Animal Models for Vaccine Efficacy in Humans? Reevaluating the Potential of Mouse Models for the Human Immune System.

PubMed

Jameson, Stephen C; Masopust, David

2018-04-02

Much of what we understand about immunology, including the response to vaccines, come from studies in mice because they provide many practical advantages compared with research in higher mammals and humans. Nevertheless, modalities for preventing or treating disease do not always translate from mouse to humans, which has led to increasing scrutiny of the continued merits of mouse research. Here, we summarize the pros and cons of current laboratory mouse models for immunology research and discuss whether overreliance on nonphysiological, ultra-hygienic animal husbandry approaches has limited the ultimate translation potential of mouse-derived data to humans. Alternative approaches are discussed that may extend the use of the mouse model for preclinical studies. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

The Development of Dynamic Human Reliability Analysis Simulations for Inclusion in Risk Informed Safety Margin Characterization Frameworks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jeffrey C. Joe; Diego Mandelli; Ronald L. Boring

2015-07-01

The United States Department of Energy is sponsoring the Light Water Reactor Sustainability program, which has the overall objective of supporting the near-term and the extended operation of commercial nuclear power plants. One key research and development (R&D) area in this program is the Risk-Informed Safety Margin Characterization pathway, which combines probabilistic risk simulation with thermohydraulic simulation codes to define and manage safety margins. The R&D efforts to date, however, have not included robust simulations of human operators, and how the reliability of human performance or lack thereof (i.e., human errors) can affect risk-margins and plant performance. This paper describesmore » current and planned research efforts to address the absence of robust human reliability simulations and thereby increase the fidelity of simulated accident scenarios.« less

A modern earth narrative: What will be the fate of the biosphere?

USGS Publications Warehouse

Williams, R.S.

2000-01-01

The modern Earth Narrative is the scientific description of the natural and human history of the Earth, and it is based on two fundamental concepts: Deep (or Geologic) Time and Biological Evolution. Changes in the Earth's biosphere and geosphere are discussed from the perspective of natural variability and impacts of the rapid increase in the human population. The failure of humans to comprehend and understand the Earth Narrative, especially the place of humans in it, presages dire consequences for the Earth's biosphere. The actions humans take, individually and collectively, during the 21st century will likely determine the fate of many millions of species, including our own. It is argued that we must quickly establish an Earth System-based conservation ethic that has the objective of complete preservation of the Earth's biotic inheritance. Published by Elsevier Science Ltd.

Epigenetic therapy with inhibitors of histone methylation suppresses DNA damage signaling and increases glioma cell radiosensitivity.

PubMed

Gursoy-Yuzugullu, Ozge; Carman, Chelsea; Serafim, Rodolfo Bortolozo; Myronakis, Marios; Valente, Valeria; Price, Brendan D

2017-04-11

Radiation therapy is widely used to treat human malignancies, but many tumor types, including gliomas, exhibit significant radioresistance. Radiation therapy creates DNA double-strand breaks (DSBs), and DSB repair is linked to rapid changes in epigenetic modifications, including increased histone methylation. This increased histone methylation recruits DNA repair proteins which can then alter the local chromatin structure and promote repair. Consequently, combining inhibitors of specific histone methyltransferases with radiation therapy may increase tumor radiosensitivity, particularly in tumors with significant therapeutic resistance. Here, we demonstrate that inhibitors of the H4K20 methyltransferase SETD8 (UNC-0379) and the H3K9 methyltransferase G9a (BIX-01294) are effective radiosensitizers of human glioma cells. UNC-0379 blocked H4K20 methylation and reduced recruitment of the 53BP1 protein to DSBs, although this loss of 53BP1 caused only limited changes in radiosensitivity. In contrast, loss of H3K9 methylation through G9a inhibition with BIX-01294 increased radiosensitivity of a panel of glioma cells (SER2Gy range: 1.5 - 2.9). Further, loss of H3K9 methylation reduced DSB signaling dependent on H3K9, including reduced activation of the Tip60 acetyltransferase, loss of ATM signaling and reduced phosphorylation of the KAP-1 repressor. In addition, BIX-0194 inhibited DSB repair through both the homologous recombination and nonhomologous end-joining pathways. Inhibition of G9a and loss of H3K9 methylation is therefore an effective approach for increasing radiosensitivity of glioma cells. These results suggest that combining inhibitors of histone methyltransferases which are critical for DSB repair with radiation therapy may provide a new therapeutic route for sensitizing gliomas and other tumors to radiation therapy.

Application of Human-Autonomy Teaming to an Advanced Ground Station for Reduced Crew Operations

NASA Technical Reports Server (NTRS)

Ho, Nhut; Johnson, Walter; Panesar, Karanvir; Wakeland, Kenny; Sadler, Garrett; Wilson, Nathan; Nguyen, Bao; Lachter, Joel; Stallmann, Summer

2017-01-01

Within human factors there is burgeoning interest in the "human-autonomy teaming" (HAT) concept as a way to address the challenges of interacting with complex, increasingly autonomous systems. The HAT concept comes out of an aspiration to interact with increasingly autonomous systems as a team member, rather than simply use automation as a tool. The authors, and others, have proposed core tenets for HAT that include bi-directional communication, automation and system transparency, and advanced coordination between human and automated teammates via predefined, dynamic task sequences known as "plays." It is believed that, with proper implementation, HAT should foster appropriate teamwork, thus increasing trust and reliance on the system, which in turn will reduce workload, increase situation awareness, and improve performance. To this end, HAT has been demonstrated and/or studied in multiple applications including search and rescue operations, healthcare and medicine, autonomous vehicles, photography, and aviation. The current paper presents one such effort to apply HAT. It details the design of a HAT agent, developed by Human Automation Teaming Solutions, Inc., to facilitate teamwork between the automation and the human operator of an advanced ground dispatch station. This dispatch station was developed to support a NASA project investigating a concept called Reduced Crew Operations (RCO); consequently, we have named the agent R-HATS. Part of the RCO concept involves a ground operator providing enhanced support to a large number of aircraft with a single pilot on the flight deck. When assisted by R-HATS, operators can monitor and support or manage a large number of aircraft and use plays to respond in real-time to complicated, workload-intensive events (e.g., an airport closure). A play is a plan that encapsulates goals, tasks, and a task allocation strategy appropriate for a particular situation. In the current implementation, when a play is initiated by a user, R-HATS determines what tasks need to be completed and has the ability to autonomously execute them (e.g., determining diversion options and uplinking new routes to aircraft) when it is safe and appropriate. R-HATS has been designed to both support end users and researchers in RCO and HAT. Additionally, R-HATS and its underlying architecture were developed with generalizability in mind as a modular software applicable outside of RCO/aviation domains. This paper will also discuss future further development and testing of RHATS.

Development and Execution of Autonomous Procedures Onboard the International Space Station to Support the Next Phase of Human Space Exploration

NASA Technical Reports Server (NTRS)

Beisert, Susan; Rodriggs, Michael; Moreno, Francisco; Korth, David; Gibson, Stephen; Lee, Young H.; Eagles, Donald E.

2013-01-01

Now that major assembly of the International Space Station (ISS) is complete, NASA's focus has turned to using this high fidelity in-space research testbed to not only advance fundamental science research, but also demonstrate and mature technologies and develop operational concepts that will enable future human exploration missions beyond low Earth orbit. The ISS as a Testbed for Analog Research (ISTAR) project was established to reduce risks for manned missions to exploration destinations by utilizing ISS as a high fidelity micro-g laboratory to demonstrate technologies, operations concepts, and techniques associated with crew autonomous operations. One of these focus areas is the development and execution of ISS Testbed for Analog Research (ISTAR) autonomous flight crew procedures intended to increase crew autonomy that will be required for long duration human exploration missions. Due to increasing communications delays and reduced logistics resupply, autonomous procedures are expected to help reduce crew reliance on the ground flight control team, increase crew performance, and enable the crew to become more subject-matter experts on both the exploration space vehicle systems and the scientific investigation operations that will be conducted on a long duration human space exploration mission. These tests make use of previous or ongoing projects tested in ground analogs such as Research and Technology Studies (RATS) and NASA Extreme Environment Mission Operations (NEEMO). Since the latter half of 2012, selected non-critical ISS systems crew procedures have been used to develop techniques for building ISTAR autonomous procedures, and ISS flight crews have successfully executed them without flight controller involvement. Although the main focus has been preparing for exploration, the ISS has been a beneficiary of this synergistic effort and is considering modifying additional standard ISS procedures that may increase crew efficiency, reduce operational costs, and raise the amount of crew time available for scientific research. The next phase of autonomous procedure development is expected to include payload science and human research investigations. Additionally, ISS International Partners have expressed interest in participating in this effort. The recently approved one-year crew expedition starting in 2015, consisting of one Russian and one U.S. Operating Segment (USOS) crewmember, will be used not only for long duration human research investigations but also for the testing of exploration operations concepts, including crew autonomy.

Distribution of tick-borne diseases in China

PubMed Central

2013-01-01

As an important contributor to vector-borne diseases in China, in recent years, tick-borne diseases have attracted much attention because of their increasing incidence and consequent significant harm to livestock and human health. The most commonly observed human tick-borne diseases in China include Lyme borreliosis (known as Lyme disease in China), tick-borne encephalitis (known as Forest encephalitis in China), Crimean-Congo hemorrhagic fever (known as Xinjiang hemorrhagic fever in China), Q-fever, tularemia and North-Asia tick-borne spotted fever. In recent years, some emerging tick-borne diseases, such as human monocytic ehrlichiosis, human granulocytic anaplasmosis, and a novel bunyavirus infection, have been reported frequently in China. Other tick-borne diseases that are not as frequently reported in China include Colorado fever, oriental spotted fever and piroplasmosis. Detailed information regarding the history, characteristics, and current epidemic status of these human tick-borne diseases in China will be reviewed in this paper. It is clear that greater efforts in government management and research are required for the prevention, control, diagnosis, and treatment of tick-borne diseases, as well as for the control of ticks, in order to decrease the tick-borne disease burden in China. PMID:23617899

Studying the neurobiology of human social interaction: Making the case for ecological validity.

PubMed

Hogenelst, Koen; Schoevers, Robert A; aan het Rot, Marije

2015-01-01

With this commentary we make the case for an increased focus on the ecological validity of the measures used to assess aspects of human social functioning. Impairments in social functioning are seen in many types of psychopathology, negatively affecting the lives of psychiatric patients and those around them. Yet the neurobiology underlying abnormal social interaction remains unclear. As an example of human social neuroscience research with relevance to biological psychiatry and clinical psychopharmacology, this commentary discusses published experimental studies involving manipulation of the human brain serotonin system that included assessments of social behavior. To date, these studies have mostly been laboratory-based and included computer tasks, observations by others, or single-administration self-report measures. Most laboratory measures used so far inform about the role of serotonin in aspects of social interaction, but the relevance for real-life interaction is often unclear. Few studies have used naturalistic assessments in real life. We suggest several laboratory methods with high ecological validity as well as ecological momentary assessment, which involves intensive repeated measures in naturalistic settings. In sum, this commentary intends to stimulate experimental research on the neurobiology of human social interaction as it occurs in real life.

'Only connect': the case for public health humanities.

PubMed

Saffran, Lise

2014-12-01

Humanities in health has until now been primarily understood to mean humanities in medicine and has generally failed to include public health. I will argue in this paper that the common justifications for the former--including increased empathy among practitioners--are at least as applicable, if not more, to the latter. Growing emphasis on the social determinants of health and cultural competency in public health require public health students and professionals to develop a nuanced understanding of the influence of social context on health behaviour and to empathise with people in difficult circumstances. Literary fiction has been demonstrated to have an impact on skills related to empathy and social intelligence. Further, translating epidemiological evidence into public policy is a core task of public health and there is a growing body of research to indicate that statistical evidence is more persuasive when combined with narrative evidence. In this article I explore similarities and differences between proposed humanities in public health and programmes in humanities in medicine and highlight research gaps and possible implications of a more expansive view of humanities in health. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Extreme weather events and infectious disease outbreaks.

PubMed

McMichael, Anthony J

2015-01-01

Human-driven climatic changes will fundamentally influence patterns of human health, including infectious disease clusters and epidemics following extreme weather events. Extreme weather events are projected to increase further with the advance of human-driven climate change. Both recent and historical experiences indicate that infectious disease outbreaks very often follow extreme weather events, as microbes, vectors and reservoir animal hosts exploit the disrupted social and environmental conditions of extreme weather events. This review article examines infectious disease risks associated with extreme weather events; it draws on recent experiences including Hurricane Katrina in 2005 and the 2010 Pakistan mega-floods, and historical examples from previous centuries of epidemics and 'pestilence' associated with extreme weather disasters and climatic changes. A fuller understanding of climatic change, the precursors and triggers of extreme weather events and health consequences is needed in order to anticipate and respond to the infectious disease risks associated with human-driven climate change. Post-event risks to human health can be constrained, nonetheless, by reducing background rates of persistent infection, preparatory action such as coordinated disease surveillance and vaccination coverage, and strengthened disaster response. In the face of changing climate and weather conditions, it is critically important to think in ecological terms about the determinants of health, disease and death in human populations.

Effects of essential amino acids on lipid metabolism in mice and humans.

PubMed

Xiao, Fei; Du, Ying; Lv, Ziquan; Chen, Shanghai; Zhu, Jianmin; Sheng, Hongguang; Guo, Feifan

2016-11-01

Eight amino acids are considered essential for human nutrition, and three of them, including leucine, isoleucine and valine, are called as branched-chain amino acids (BCAAs). We recently discovered that dietary deficiency of any BCAA for 7 days rapidly reduces the abdominal fat mass in mice. The goal of this study was to investigate (1) whether dietary deficiency of the other five essential amino acids (EAAs), including phenylalanine, threonine, tryptophan, methionine and lysine, would produce similar effects and (2) whether an association between serum AAs and obesity was observed in humans in Chinese Han population. Similar to BCAAs deprivation, dietary deficiency of any of these five EAAs for 7 days significantly reduced abdominal fat mass, which is likely caused by increased energy expenditure. Expression of genes and proteins related to lipolysis, however, were differentially regulated by different EAAs. These results suggest a crucial role of EAAs deprivation on lipid metabolism in mice. Our human studies revealed that levels of four EAAs (leucine, isoleucine, valine and phenylalanine) were elevated in obese humans compared with those in lean controls in Chinese Han population. Based on the results obtained from mice, we speculate that these four EAAs might play important roles in human obesity. © 2016 Society for Endocrinology.

ON THE IMPACT OF THE HUMAN (CHILD) MICROCLIMATE ON PASSIVE AEROSOL MONITOR PERFORMANCE

EPA Science Inventory

Research into the wind microclimate and its effect on the accuracy and effectiveness of passive aerosol monitors is expanding as the importance of personal monitoring versus regional monitoring increases. The important phenomena for investigation include thermal and dynamic eff...

Wolverine conservation and management.

Treesearch

L.F. Ruggiero; K.S. McKelvey; K.B. Aubry; J.P. Copeland; D.H. Pletscher; M.G. Hornocker

2007-01-01

This Special Section includes 8 peer-reviewed papers on the wolverine (Gulo gulo) in southern North America. These papers provide new information on current and historical distribution, habitat relations at multiple spatial scales, and interaction with humans. In aggregate, these papers substantially increase our knowledge of wolverine ecology and...

Wolverine conservation and management

Treesearch

Leonard F. Ruggiero; Kevin S. Mckelvey; Keith B. Aubry; Jeffrey P. Copeland; Daniel H. Pletscher; Maurice G. Hornocker

2007-01-01

This Special Section includes 8 peer-reviewed papers on the wolverine (Gulo gulo) in southern North America. These papers provide new information on current and historical distribution, habitat relations at multiple spatial scales, and interactions with humans. In aggregate, these papers substantially increase our knowledge of wolverine ecology and...

Phosphorus recovery and reuse from waste streams

USDA-ARS?s Scientific Manuscript database

Phosphorus (P) is a macronutrient essential for all living organisms. Regrettably, it is a finite resource since phosphate rock (PR) is the main material used for production of P fertilizers. Globally, the demand for quality PR is escalating due to many factors including increasing human population....

Impact of raised without antibiotics practices on occurrences of antimicrobial resistance

USDA-ARS?s Scientific Manuscript database

Background: The increasing occurrence of antimicrobial-resistant human infections has been attributed to the use of antimicrobials in a variety of applications including food-animal production. "Raised without antibiotics" (RWA) meat production has been offered as a practice to reduce antimicrobial-...

RESPONSES OF CULTURED HUMAN AIRWAY EPITHELIAL CELLS TREATED WITH DIESEL EXHAUST EXTRACTS WILL VARY WITH THE ENGINE

EPA Science Inventory

Epidemiologic evidence suggests that increased morbidity and mortality are associated with the concentrations of ambient air particulate matter (PM). Many sources contribute to the particulate fraction of ambient pollution, including diesel exhaust particulates (DEP). Diesel ex...

A genetic network that suppresses genome rearrangements in Saccharomyces cerevisiae and contains defects in cancers

PubMed Central

Putnam, Christopher D.; Srivatsan, Anjana; Nene, Rahul V.; Martinez, Sandra L.; Clotfelter, Sarah P.; Bell, Sara N.; Somach, Steven B.; E.S. de Souza, Jorge; Fonseca, André F.; de Souza, Sandro J.; Kolodner, Richard D.

2016-01-01

Gross chromosomal rearrangements (GCRs) play an important role in human diseases, including cancer. The identity of all Genome Instability Suppressing (GIS) genes is not currently known. Here multiple Saccharomyces cerevisiae GCR assays and query mutations were crossed into arrays of mutants to identify progeny with increased GCR rates. One hundred eighty two GIS genes were identified that suppressed GCR formation. Another 438 cooperatively acting GIS genes were identified that were not GIS genes, but suppressed the increased genome instability caused by individual query mutations. Analysis of TCGA data using the human genes predicted to act in GIS pathways revealed that a minimum of 93% of ovarian and 66% of colorectal cancer cases had defects affecting one or more predicted GIS gene. These defects included loss-of-function mutations, copy-number changes associated with reduced expression, and silencing. In contrast, acute myeloid leukaemia cases did not appear to have defects affecting the predicted GIS genes. PMID:27071721

Birds and polycyclic aromatic hydrocarbons

USGS Publications Warehouse

Albers, P.H.

2006-01-01

Polycyclic aromatic hydrocarbons (PAH) are present throughout the global environment and are produced naturally and by activities of humans. Effects of PAH on birds have been determined by studies employing egg injection, egg immersion, egg shell application, single and multiple oral doses, subcutaneous injection, and chemical analysis of field-collected eggs and tissue. The four-to six-ring aromatic compounds are the most toxic to embryos, young birds, and adult birds. For embryos, effects include death, developmental abnormalities, and a variety of cellular and biochemical responses. For adult and young birds, effects include reduced egg production and hatching, increased clutch or brood abandonment, reduced growth, increased organweights, and a variety of biochemical responses. Trophic level accumulation is unlikely. Environmental exposure to PAH in areas of high human population or habitats affected by recent petroleum spills might be sufficient to adversely affect reproduction. Evidence of long-term effects of elevated concentrations of environmental PAH on bird populations is very limited and the mechanisms of effect are unclear.

Climate change, vector-borne diseases and working population.

PubMed

Vonesch, Nicoletta; D'Ovidio, Maria Concetta; Melis, Paola; Remoli, Maria Elena; Ciufolini, Maria Grazia; Tomao, Paola

2016-01-01

Risks associated with climate change are increasing worldwide and the global effects include altered weather and precipitation patterns, rising temperatures and others; human health can be affected directly and indirectly. This paper is an overview of literature regarding climate changes, their interaction with vector-borne diseases and impact on working population. Articles regarding climate changes as drivers of vector-borne diseases and evidences of occupational cases have been picked up by public databank. Technical documents were also included in the study. Evidences regarding the impact of climate changes on vector-borne diseases in Europe, provided by the analysis of the literature, are presented. Climate-sensitive vector-borne diseases are likely to be emerging due to climate modifications, with impacts on public and occupational health. However, other environmental and anthropogenic drivers such as increasing travelling and trade, deforestation and reforestation, altered land use and urbanization can influence their spread. Further studies are necessary to better understand the phenomenon and implementation of adaptation strategies to protect human health should be accelerated and strengthened.

Cybersecurity in healthcare: A narrative review of trends, threats and ways forward.

PubMed

Coventry, Lynne; Branley, Dawn

2018-07-01

Electronic healthcare technology is prevalent around the world and creates huge potential to improve clinical outcomes and transform care delivery. However, there are increasing concerns relating to the security of healthcare data and devices. Increased connectivity to existing computer networks has exposed medical devices to new cybersecurity vulnerabilities. Healthcare is an attractive target for cybercrime for two fundamental reasons: it is a rich source of valuable data and its defences are weak. Cybersecurity breaches include stealing health information and ransomware attacks on hospitals, and could include attacks on implanted medical devices. Breaches can reduce patient trust, cripple health systems and threaten human life. Ultimately, cybersecurity is critical to patient safety, yet has historically been lax. New legislation and regulations are in place to facilitate change. This requires cybersecurity to become an integral part of patient safety. Changes are required to human behaviour, technology and processes as part of a holistic solution. Copyright © 2018 Elsevier B.V. All rights reserved.

Largely Increased Nitrous Oxide Emission from Global Livestock Sector during 1860-2014: A geospatial-temporal analysis

NASA Astrophysics Data System (ADS)

Zhang, B.; Tian, H.; Xu, R.; Yang, J.; Pan, S.; Chen, G.

2017-12-01

The atmospheric concentration of nitrous oxide (N2O), one of major greenhouse gases, has increased over 121% compared with the preindustrial level, and most of the increase arises from anthropogenic activities. The shift of human diet and the ever-increasing human population pose a huge pressure on the demand of growing livestock population. Of particular interest is how changes in livestock population could alter the environmental health through emissions of greenhouse gases, especially nitrous oxide. Moreover, the quantification of livestock induced nitrous oxide emission with global coverage that characterize consecutive inter-annual variations during historical period is lacking. Thus, in this study, we tried to quantify the magnitude, temporal and spatial variations of livestock-induced nitrous oxide emission during 1860-2014. We include both direct and indirect emission of nitrous oxide from managed soils. We also further analyze the relative contribution of major livestock types on nitrous oxide emission. The results indicated that there was a significant increasing trend of livestock-induced nitrous oxide during 1860-2014. Changes in nitrous oxide emission exhibited highly spatial variability and concentrated in several hotspots during the study period. Less meat consumption is not only good for human health, but also favors for environment-friendly development.

Humans and great apes share increased neocortical neuropeptide Y innervation compared to other haplorhine primates.

PubMed

Raghanti, Mary Ann; Edler, Melissa K; Meindl, Richard S; Sudduth, Jessica; Bohush, Tatiana; Erwin, Joseph M; Stimpson, Cheryl D; Hof, Patrick R; Sherwood, Chet C

2014-01-01

Neuropeptide Y (NPY) plays a role in a variety of basic physiological functions and has also been implicated in regulating cognition, including learning and memory. A decrease in neocortical NPY has been reported for Alzheimer's disease, schizophrenia, bipolar disorder, and depression, potentially contributing to associated cognitive deficits. The goal of the present analysis was to examine variation in neocortical NPY-immunoreactive axon and varicosity density among haplorhine primates (monkeys, apes, and humans). Stereologic methods were used to measure the ratios of NPY-expressing axon length density to total neuron density (ALv/Nv) and NPY-immunoreactive varicosity density to neuron density (Vv/Nv), as well as the mean varicosity spacing in neocortical areas 10, 24, 44, and 22 (Tpt) of humans, African great apes, New World monkeys, and Old World monkeys. Humans and great apes showed increased cortical NPY innervation relative to monkey species for ALv/Nv and Vv/Nv. Furthermore, humans and great apes displayed a conserved pattern of varicosity spacing across cortical areas and layers, with no differences between cortical layers or among cortical areas. These phylogenetic differences may be related to shared life history variables and may reflect specific cognitive abilities.

Opening the black box in nursing work and management practice: the role of ward managers.

PubMed

Townsend, Keith; Wilkinson, Adrian; Kellner, Ashlea

2015-03-01

This paper aims to identify and explore key obstacles preventing ward managers from effectively performing the human resource management (HRM) responsibilities required in their role. In the context of increasing costs and the decentralisation of responsibility to ward level, the relevance of the ward manager role within the 'black box' between human resource management and firm performance is becoming increasingly pertinent. This paper presents an intensive case study including 37 interviews across all levels of a hospital where senior management attempted to shift to a high performance model of human resource management. The findings indicated that ward managers played a critical role in maintaining and improving employee performance, although they were restricted from effectively performing their responsibilities due to budget pressure and limited managerial skill development. Our findings support the contention that hospitals would benefit from focusing on the critical role of the ward manager as the central locus of influence in high performance human resource management (HPHRM) systems. Investment into high performance human resource management is discouraged if the hospital cannot adequately enable ward managers who are responsible for implementation. Introduction of managerial skills training to potential and existing ward managers is critical. © 2013 John Wiley & Sons Ltd.