WorldWideScience

Sample records for twenty human subjects

  1. The characterization of twenty sequenced human genomes.

    Directory of Open Access Journals (Sweden)

    Kimberly Pelak

    2010-09-01

    Full Text Available We present the analysis of twenty human genomes to evaluate the prospects for identifying rare functional variants that contribute to a phenotype of interest. We sequenced at high coverage ten "case" genomes from individuals with severe hemophilia A and ten "control" genomes. We summarize the number of genetic variants emerging from a study of this magnitude, and provide a proof of concept for the identification of rare and highly-penetrant functional variants by confirming that the cause of hemophilia A is easily recognizable in this data set. We also show that the number of novel single nucleotide variants (SNVs discovered per genome seems to stabilize at about 144,000 new variants per genome, after the first 15 individuals have been sequenced. Finally, we find that, on average, each genome carries 165 homozygous protein-truncating or stop loss variants in genes representing a diverse set of pathways.

  2. Human subjects research handbook: Protecting human research subjects. Second edition

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-01-30

    This handbook serves as a guide to understanding and implementing the Federal regulations and US DOE Orders established to protect human research subjects. Material in this handbook is directed towards new and continuing institutional review board (IRB) members, researchers, institutional administrators, DOE officials, and others who may be involved or interested in human subjects research. It offers comprehensive overview of the various requirements, procedures, and issues relating to human subject research today.

  3. Protecting human subjects in research.

    Science.gov (United States)

    Orticio, Lily P

    2009-01-01

    The quest for advancing scientific knowledge through human experimentations using vulnerable groups is traced back to ancient history, when Herophilus performed vivisections on prisoners. The violation of the rights of human subjects through the 20th century led to the formulation of the Nuremberg Code in 1947 and the Declaration of Helsinki in 1964. In the United States, the most infamous was the Tuskegee public health study that resulted in the enactment of the National Research Act that authorized the creation of the National Commission for the Protection of Human Subjects in Biomedical and Behavioral Research in 1974. In spite of existing federal regulations, the system of protecting human subjects is still flawed. Transparency of conflict ofinterest, clarity, and strict adherence to institutional guidelines are critical in safeguarding the rights and safety of human subjects and the integrity of research. Education on ethics and emerging complex ethical issues, global awareness, and governmental cooperation and sanctions are important steps in addressing the inadequacies in protecting the most vulnerable populations in experimentations worldwide. Investigators must always remember that the primary safeguards of protecting human life rest in their hands.

  4. Humanities: The Unexpected Success Story of the Twenty-First Century

    Science.gov (United States)

    Davis, Virginia

    2012-01-01

    Humanities within universities faced challenges in the latter half of the twentieth century as their value in the modern world was questioned. This paper argues that there is strong potential for the humanities to thrive in the twenty-first century university sector. It outlines some of the managerial implications necessary to ensure that this…

  5. Zinc balance of twenty healthy elderly subjects consuming self-selected diets

    Energy Technology Data Exchange (ETDEWEB)

    Souza, M.C.; Prather, E.S.; Rhodes, D.G. (Univ. of Maryland, College Park (United States))

    1991-03-15

    Dietary zinc (Zn) intake and balance were determined in ten male and ten female free-living, healthy, elderly subjects on self-selected diets over a period of seven consecutive days. Zn content in the diet, fecal and urine composites for each subject was determined by atomic absorption spectrophotometry. Mean age for the 20 participants was 73.9 years. Mean Zn intakes were 8.9 and 23.3 mg/day for females and males, respectively. Female dietary intakes ranged from 8.2 to 26.8 mg Zn/day. However, three of the males took Zn supplements which extended the total intake range to 64.9 mg/day. Mean Zn balances were +0.1 and +5.1 mg/day for females and males, respectively; ranges for females were {minus}0.1 to +4.3 mg/day and for males were {minus}7.3 to +15.1 mg/day. The 1989 RDAs are 15 mg for males and 12 mg for females. Only three females consumed more than 12 mg Zn/day. Only 2 males consumed more than 15 mg/day from their diet; two other males consumed more than 15 mg due to Zn supplements. Total dietary phytate (TDP) and total dietary fiber (TDF) were calculated from the 7-day weighed food records. Mean TDP intake for females was 1,159 mg/day; mean TDP for the males was 1,661 mg/day. Mean TDF intake for females was 19 g/day; mean TDF for males was 30 g/day.

  6. Effects of Twenty Days of the Ketogenic Diet on Metabolic and Respiratory Parameters in Healthy Subjects.

    Science.gov (United States)

    Alessandro, Rubini; Gerardo, Bosco; Alessandra, Lodi; Lorenzo, Cenci; Andrea, Parmagnani; Keith, Grimaldi; Yang, Zhongjin; Antonio, Paoli

    2015-12-01

    The effects of the ketogenic diet (KD) on weight loss, metabolic, and respiratory parameters were investigated in healthy subjects. Thirty-two healthy subjects were randomized into two groups. The KD group followed a ketogenic diet for 20 days (KD t 0-t 20), then switched to a low-carbohydrate, no-ketogenic diet for 20 days (KD t 20-t 40), and finally was on a Mediterranean diet (MD) for 2 more months (KD t 40-t 2m). The MD group followed a MD for 20 days (MD t 0-t 20), then followed a MD of 1400 kcal over the next 20 days (MD t 20-t 40), and completed the study with the MD for 2 months (MD t 40-t 2m). Body weight, body fat, respiratory rate, and respiratory gas parameters (including respiratory exchange ratio (RER) and carbon dioxide end-tidal partial pressure (PETCO2), oxygen uptake (VO2), carbon dioxide production (VCO2), and resting energy expenditure (REE)) were measured at each point. A significant decrease (p < 0.05) in RER was observed after 20 and 40 days in the KD group, but not in the MD group. In the KD group, significant reductions were observed for both carbon dioxide output and PETCO2, however, there was no significant change in VO2, VCO2, and REE. While both diets significantly decreased body fat mass, the KD diet overall proved to have a higher percentage of fat loss versus the MD diet. The KD may significantly decrease carbon dioxide body stores, which may theoretically be beneficial for patients with increased carbon dioxide arterial partial pressure due to respiratory insufficiency or failure.

  7. Human subjects protection in the African context

    Directory of Open Access Journals (Sweden)

    Embry Howell

    2016-06-01

    Full Text Available Research and evaluation are growing in Africa. All evaluators have an ethical responsibility to protect their research subjects from harm that could occur if sensitive data are revealed. In this article, we use a literature and document review to provide an overview of the protection of human subjects internationally and in Africa; we then use interviews with evaluators working in Africa to place human subjects protection principles and practice in an African context. We conclude that human subjects protection must be supported by improved guidelines tailored to the African context and local conditions; improved infrastructure for implementing and enforcing the guidelines; and increased training in awareness of human subjects principles and approaches. These efforts could stimulate increased research and evaluation and more confidence in results in the communities where research is conducted.

  8. Human Subjects Issues in AIDS Research.

    Science.gov (United States)

    Bayer, Ronald, Ed.

    1990-01-01

    Six articles are presented on the use of human subjects in research on acquired immune deficiency syndrome (AIDS). Topics include the ethics of human experimentation, female and pediatric AIDS patients, Human Immunodeficiency Virus (HIV) infection and AIDS among correctional inmates, community-based AIDS research, and clinical trials of HIV…

  9. Human Resource Subjects Allocation and Students' Academic ...

    African Journals Online (AJOL)

    Human Resource Subjects Allocation and Students' Academic Performance in ... AFRICAN JOURNALS ONLINE (AJOL) · Journals · Advanced Search · USING AJOL ... while the dependent variables were students' academic performance.

  10. Subjective Quantitative Studies of Human Agency

    Science.gov (United States)

    Alkire, Sabina

    2005-01-01

    Amartya Sen's writings have articulated the importance of human agency, and identified the need for information on agency freedom to inform our evaluation of social arrangements. Many approaches to poverty reduction stress the need for empowerment. This paper reviews "subjective quantitative measures of human agency at the individual level." It…

  11. Human Subjects Research and the Physics Classroom

    Science.gov (United States)

    Kubitskey, Beth W.; Thomsen, Marshall

    2012-01-01

    Physics Education Research is a form of social science research in that it uses human subjects. As physicists we need to be aware of the ethical and legal ramifications of performing this research, taking into account the fundamental differences between working with substances and working with people. For several decades, the federal government…

  12. subjective approach to subjective approach to human physiological ...

    African Journals Online (AJOL)

    eobe

    approach on human physiology and this focuses on the skin temperature which is the primary ... digital anemometer (Lutron Electronics Enterprise co. Ltd, Taiwan). .... that on the warm side of the comfort zone the relative humidity should not ...

  13. [Comparison of 51 element contents in normal human lung tissue over twenty years].

    Science.gov (United States)

    Zeng, Jing; Ouyang, Li; Wang, Xiao-Yan; Liu, Ya-Qiong; Xie, Qing; Chu, Hong-Da; Wu, Quan; Fan, Ti-Qiang; Wang, Jing-Yu

    2008-05-01

    Changes in content and distribution of elements in human tissues may reflect changes in environmental backgrounds, and are closely related to human health. To investigate the change in element background in normal lung tissue in different stage, we used ICP-MS, ICP-AES and GFAAS to determine 51 element contents in normal human lung samples of 1982-83 year (n = 7) and compare with those of 2004-05 year (n = 16). Samples were from healthy male adults who died suddenly, and were treated with microwave digestion and wet digestion method. The results show that the contents of 23 elements (Na, Mg, P, K, As, Mo, Ag, Ba, Bi, Y, La, Ce, Pr, Nd, Sm, Gd, Tb, Dy, Ho, Er, Tm, Yb and Lu) are significantly higher, and 6 elements (Zn, Ga, Ge, Se, Au and Zr) are significantly lower in the 2004-05 samples than those in the 1982-83 samples. This difference would be related to the changes in environmental backgrounds and people's living habit during twenty years. The distinctive decrease in contents of the 2004-05 samples for most measured rare earth elements (REEs) may be due to more rational usage of REEs in present, while were the soil and corps were largely abused in 1980s in China. The significant increase in contents of some useful micro-elements (Zn and Se ) in the present samples maybe because of the increased intake of these elements as people own more health consciousness. Besides, the increased contents of heavy metal Pb, Cd, Cr and Ni in the present samples may be related to the deterioration of air quality as industrialization course. More than half of measured elements have been significantly changed over twenty years, indicating that some normal value ranges of element contents should be adjusted according to the difference.

  14. Environmental Health Research Involving Human Subjects: Ethical Issues

    Directory of Open Access Journals (Sweden)

    David B. Resnik

    2008-01-01

    Full Text Available This article reviews some of the ethical issues that arise in environmental health research with human subjects, such as minimizing risks to subjects, balancing benefits and risks in research, intentional exposure studies with human subjects, protecting third parties in research, informing subjects about environmental hazards, communicating health information to subjects, and protecting privacy and confidentiality.

  15. Protections for Subjects in Human Research with Pesticides

    Science.gov (United States)

    All pesticide research using human subjects must meet our strict protective standards before we would consider using them in evaluating pesticides. EPA's regulation “Protections for Subjects in Human Research” was promulgated in 2006 and amended in 2013.

  16. Braille character discrimination in blindfolded human subjects.

    Science.gov (United States)

    Kauffman, Thomas; Théoret, Hugo; Pascual-Leone, Alvaro

    2002-04-16

    Visual deprivation may lead to enhanced performance in other sensory modalities. Whether this is the case in the tactile modality is controversial and may depend upon specific training and experience. We compared the performance of sighted subjects on a Braille character discrimination task to that of normal individuals blindfolded for a period of five days. Some participants in each group (blindfolded and sighted) received intensive Braille training to offset the effects of experience. Blindfolded subjects performed better than sighted subjects in the Braille discrimination task, irrespective of tactile training. For the left index finger, which had not been used in the formal Braille classes, blindfolding had no effect on performance while subjects who underwent tactile training outperformed non-stimulated participants. These results suggest that visual deprivation speeds up Braille learning and may be associated with behaviorally relevant neuroplastic changes.

  17. 42 CFR 86.19 - Human subjects; animal welfare.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Human subjects; animal welfare. 86.19 Section 86.19... Occupational Safety and Health Training Grants § 86.19 Human subjects; animal welfare. No grant award may be... concerning animal welfare. 2 The Department Grants Administration Manual is available for inspection at...

  18. 42 CFR 86.33 - Human subjects; animal welfare.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Human subjects; animal welfare. 86.33 Section 86.33... Occupational Safety and Health Direct Traineeships § 86.33 Human subjects; animal welfare. Where the...) Chapter 1-43 of the Department Grants Administration Manual 2 068 concerning animal welfare. 2...

  19. Lifeboat habitability and effects on human subjects

    Energy Technology Data Exchange (ETDEWEB)

    Power, Jonathan T.; Simoes Re, Antonio J. [National Research Council of Canada: Institute for Ocean Technology, St. John' s, Newfoundland and Labrador (Canada)], email: Jonathan.power@nrc.ca, email: Antonio.simoesre@nrc.ca

    2010-07-01

    When an accident occurs offshore, lifeboats are the principal means used to evacuate shipping and offshore industries. However, in the International Maritime Organization Lifesaving Appliances code, no criteria are established as to habitability and the effects on human of those evacuation craft. The aim of this project was to study the impact of prolonged occupancy on the human body. This study was carried out in a SOLAS lifeboat in Conception Bay with 2 persons on-board wearing immersion suit systems; measurements of their skin temperature, deep body temperature and heart rate while doing their tasks were conducted. Results showed that when the lifeboat is sealed, the thermal comfort is quickly reduced with occupants sweating. This study highlighted that hatches and immersions suits should be kept open when possible to reduce the thermal strain on the occupants and that properly designed ventilation systems should be installed in lifeboats.

  20. Human subject research for engineers a practical guide

    CERN Document Server

    de Winter, Joost C F

    2017-01-01

    This Brief introduces engineers to the main principles in ethics, research design, statistics, and publishing of human subject research. In recent years, engineering has become strongly connected to disciplines such as biology, medicine, and psychology. Often, engineers (and engineering students) are expected to perform human subject research. Typical human subject research topics conducted by engineers include human-computer interaction (e.g., evaluating the usability of software), exoskeletons, virtual reality, teleoperation, modelling of human behaviour and decision making (often within the framework of ‘big data’ research), product evaluation, biometrics, behavioural tracking (e.g., of work and travel patterns, or mobile phone use), transport and planning (e.g., an analysis of flows or safety issues), etc. Thus, it can be said that knowledge on how to do human subject research is indispensable for a substantial portion of engineers. Engineers are generally well trained in calculus and mechanics, but m...

  1. The Humanities Are Not a Luxury: A Manifesto for the Twenty-First Century

    Science.gov (United States)

    Smith, Martha Nell

    2011-01-01

    The humanities are at the heart of knowing about the human condition; they are not a luxury. The erosion of support for the humanities and the perennial anxiety about the state of the humanities are systemic. The author contends that until people acknowledge this fact, they will keep lurching from one point to another, unable to recognize the…

  2. Human brain : biochemical lateralization in normal subjects.

    Directory of Open Access Journals (Sweden)

    Jayasundar R

    2002-07-01

    Full Text Available Chemical asymmetries in normal human brain were studied using the non-invasive technique of volume localized proton magnetic resonance spectroscopy (MRS. The technique of STEAM was used to acquire water-suppressed proton spectra from 8 ml voxels placed in bilaterally symmetrical positions in the two hemispheres of the brain. One hundred and sixty eight right-handed male volunteers were studied for six different regions in the brain (n=28, for each region. Parietal, occipital, temporal, frontal, thalamus and cerebellum regions were studied. The focus was on metabolites such as N-acetyl aspartate (NAA, creatine/phosphocreatine (Cr/PCr and choline (Cho containing compounds. Ratios of the peak areas were calculated for them. Quantitation of the metabolites were carried for data on 18 volunteers. Significant interhemispheric differences in the distribution of metabolites were observed for all the regions studied. There were statistically significant differences on right and left side for the metabolite ratios in all the regions studied. The study has shown the existence of significant lateralization in the distribution of proton MR visible metabolites for all the regions studied.

  3. Palestine Refugees Today. Human Rights Day: Twenty-Fifth Anniversary. Newsletter Number 76.

    Science.gov (United States)

    United Nations Relief and Works Agency, New York, NY.

    A special issue of the United Nations Relief and Works Agency (UNRWA) newsletter relates the ideals of human rights as carried out for the Palestine refugees. An overview of the publication and its contents is followed by a copy of the Universal Declaration of Human Rights. Three articles--The Right to Education, An Adequate Standard of Living,…

  4. Twenty six cases of human Fasciola gigantica infection in Dali,Yunnan province

    Institute of Scientific and Technical Information of China (English)

    陈木新

    2013-01-01

    Objective To investigate the epidemic situation,clinical symptom,diagnosis and epidemiological characteristics of human Fasciola gigantica infection in Dali,Yunnan province. It will also provide a scientific basis for fasciolosis control and prevention. Methods Epidemic

  5. Subjective dimension in the analysis of human development

    Directory of Open Access Journals (Sweden)

    LÓPEZ NOVAL, Borja

    2012-06-01

    Full Text Available In recent years subjective evaluations about own quality of life, resumed in levels of life satisfactionor happiness, are gaining importance as indicators of development. Some authors state that subjectivewell-being is a necessary and sufficient condition for human development. In this work the arguments ofthese authors are explained and it is discussed the role subjective evaluations must play on developmentstudies. The main conclusion is that although it is necessary to integrate subjective well-being into humandevelopment studies we cannot identify subjective well-being and development.

  6. Challenging research on human subjects: justice and uncompensated harms.

    Science.gov (United States)

    Napier, Stephen

    2013-02-01

    Ethical challenges to certain aspects of research on human subjects are not uncommon; examples include challenges to first-in-human trials (Chapman in J Clin Res Bioethics 2(4):1-8, 2011), certain placebo controlled trials (Anderson in J Med Philos 31:65-81, 2006; Anderson and Kimmelman in Kennedy Inst Ethics J 20(1):75-98, 2010) and "sham" surgery (Macklin in N Engl J Med 341:992-996, 1999). To date, however, there are few challenges to research when the subjects are competent and the research is more than minimal risk with no promise of direct benefit. The principal reason given for allowing research that is more than minimal risk without benefit is that we should respect the autonomy of competent subjects. I argue that though the moral intuitions informing respect for autonomy are sound, there is another set of intuitions regarding what we take to be just treatment of another when one agent knowingly causes or allows suffering on another agent. I argue that concerns generated by commutative justice serve as limitations on permissible research. I highlight our intuitions informing this notion of justice by appealing to work done on theodicy; what counts as a morally sufficient reason for God to allow suffering in humans is applicable also to the researcher-subject relationship. I conclude that all human subjects who are exposed to more than minimal risk research should enjoy the same actual protections (e.g., subpart D) as those given subjects who cannot consent.

  7. Twenty-year summary of surveillance for human hantavirus infections, United States.

    Science.gov (United States)

    Knust, Barbara; Rollin, Pierre E

    2013-12-01

    In the past 20 years of surveillance for hantavirus in humans in the United States, 624 cases of hantavirus pulmonary syndrome (HPS) have been reported, 96% of which occurred in states west of the Mississippi River. Most hantavirus infections are caused by Sin Nombre virus, but cases of HPS caused by Bayou, Black Creek Canal, Monongahela, and New York viruses have been reported, and cases of domestically acquired hemorrhagic fever and renal syndrome caused by Seoul virus have also occurred. Rarely, hantavirus infections result in mild illness that does not progress to HPS. Continued testing and surveillance of clinical cases in humans will improve our understanding of the etiologic agents involved and the spectrum of diseases.

  8. Twenty years of human immunodeficiency virus care at the Mayo Clinic: Past, present and future

    Science.gov (United States)

    Cummins, Nathan W; Badley, Andrew D; Kasten, Mary J; Sampath, Rahul; Temesgen, Zelalem; Whitaker, Jennifer A; Wilson, John W; Yao, Joseph D; Zeuli, John; Rizza, Stacey A

    2016-01-01

    The Mayo human immunodeficiency virus (HIV) Clinic has been providing patient centered care for persons living with HIV in Minnesota and beyond for the past 20 years. Through multidisciplinary engagement, vital clinical outcomes such as retention in care, initiation of antiretroviral therapy and virologic suppression are maximized. In this commentary, we describe the history of the Mayo HIV Clinic and its best practices, providing a “Mayo Model” of HIV care that exceeds national outcomes and may be applicable in other settings. PMID:27175350

  9. Genetic diversity and evolution of human metapneumovirus fusion protein over twenty years

    Directory of Open Access Journals (Sweden)

    Liem Alexis

    2009-09-01

    Full Text Available Abstract Background Human metapneumovirus (HMPV is an important cause of acute respiratory illness in children. We examined the diversity and molecular evolution of HMPV using 85 full-length F (fusion gene sequences collected over a 20-year period. Results The F gene sequences fell into two major groups, each with two subgroups, which exhibited a mean of 96% identity by predicted amino acid sequences. Amino acid identity within and between subgroups was higher than nucleotide identity, suggesting structural or functional constraints on F protein diversity. There was minimal progressive drift over time, and the genetic lineages were stable over the 20-year period. Several canonical amino acid differences discriminated between major subgroups, and polymorphic variations tended to cluster in discrete regions. The estimated rate of mutation was 7.12 × 10-4 substitutions/site/year and the estimated time to most recent common HMPV ancestor was 97 years (95% likelihood range 66-194 years. Analysis suggested that HMPV diverged from avian metapneumovirus type C (AMPV-C 269 years ago (95% likelihood range 106-382 years. Conclusion HMPV F protein remains conserved over decades. HMPV appears to have diverged from AMPV-C fairly recently.

  10. Can Human Subject Pool Participation Benefit Sociology Students?

    Science.gov (United States)

    Chin, Lynn Gencianeo; Gibbs Stayte, Patricia

    2015-01-01

    Instructors at non-research institutions are less able to expose their students to research firsthand. Utilizing human subject pools (HSPs) in class may be a solution. Given that HSPs tend to be used in introduction to psychology classes at research institutions, we examine a community college HSP to answer three questions: (1) Do community…

  11. Can Human Subject Pool Participation Benefit Sociology Students?

    Science.gov (United States)

    Chin, Lynn Gencianeo; Gibbs Stayte, Patricia

    2015-01-01

    Instructors at non-research institutions are less able to expose their students to research firsthand. Utilizing human subject pools (HSPs) in class may be a solution. Given that HSPs tend to be used in introduction to psychology classes at research institutions, we examine a community college HSP to answer three questions: (1) Do community…

  12. Demystifying the IRB: Human Subjects Research in Academic Libraries

    Science.gov (United States)

    Smale, Maura A.

    2010-01-01

    Many academic librarians are interested in pursuing research studies that involve students, faculty, and other library patrons; these projects must be approved by an institutional review board (IRB). This article reviews federal requirements and regulations for human subjects research and explains the IRB application process. The author discusses…

  13. ETHICS IN HEALTH CARE: INDUCEMENT AND HUMAN SUBJECTS

    Directory of Open Access Journals (Sweden)

    MUNIR HOSSAIN TALUKDER

    2011-05-01

    Full Text Available Currently, most health researchers or donor organizations considerinducement as a vital part in promoting research. They propose benefits, such as post research free medical treatment, food, insurance facilities, or even cash, in order to meet sufficient number of subjects. So, inducement may influence one to participate in a research. Is it ethical to offer inducement to human subjects? What are the risks in such practice? What will happen if the donor agencies use subjects by hiding possible risks from them? When an inducement can satisfy ethical criteria? The CIOMS, FDA, and other ethical guidelines hold that inducement is unethical because it involves enough risk for voluntary informed consent. Supporting this position, a group of ethicists has argued that inducement undermines voluntariness especially when subjects are poor and vulnerable, and thus, unethical. In contrast to them, others argue that inducement contributes to discover new knowledge which can improve miserable condition of the poor. In their view, an inducement maintains all ethical criteria including subject’s autonomy, and therefore, morally permissible. The paper focuses this debate and analyzes both types ofargument. It examines whether inducement invalidate informed consent.Even if inducement may not violate the basic components of informedconsent, the paper concludes, subjects may claim a prima facie right to enjoy research outcomes.

  14. Animal models of human cerebellar ataxias: a cornerstone for the therapies of the twenty-first century.

    Science.gov (United States)

    Manto, Mario; Marmolino, Daniele

    2009-09-01

    Cerebellar ataxias represent a group of disabling neurological disorders. Our understanding of the pathogenesis of cerebellar ataxias is continuously expanding. A considerable number of laboratory animals with neurological mutations have been reported and numerous relevant animal models mimicking the phenotype of cerebellar ataxias are becoming available. These models greatly help dissecting the numerous mechanisms of cerebellar dysfunction, a major step for the assessment of therapeutics targeting a given deleterious pathway and for the screening of old or newly synthesized chemical compounds. Nevertheless, differences between animal models and human disorders should not be overlooked and difficulties in terms of characterization should not be occulted. The identification of the mutations of many hereditary ataxias, the development of valuable animal models, and the recent identifications of the molecular mechanisms underlying cerebellar disorders represent a combination of key factors for the development of anti-ataxic innovative therapies. It is anticipated that the twenty-first century will be the century of effective therapies in the field of cerebellar ataxias. The animal models are a cornerstone to reach this goal.

  15. Human development I: twenty fundamental problems of biology, medicine, and neuro-psychology related to biological information.

    Science.gov (United States)

    Hermansen, Tyge Dahl; Ventegodt, Søren; Rald, Erik; Clausen, Birgitte; Nielsen, Maj Lyck; Merrick, Joav

    2006-07-06

    In a new series of papers, we address a number of unsolved problems in biology today. First of all, the unsolved enigma concerning how the differentiation from a single zygote to an adult individual happens has been object for severe research for decades. By uncovering a new holistic biological paradigm that introduces an energetic-informational interpretation of reality as a new way to experience biology, these papers will try to solve the problems connected with the events of biological ontogenesis involving a fractal hierarchy, from a single cell to the function of the human brain. The problems discussed are interpreted within the frames of a universe of roomy fractal structures containing energetic patterns that are able to deliver biological information. We think biological organization is guided by energetic changes on the level of quantum mechanics, interacting with the intention that again guides the energetic conformation of the fractal structures to gain disorders or healthiness. Furthermore, we introduce two new concepts: "metamorphous top down" evolution and "adult human metamorphosis". The first is a new evolutionary theory involving metamorphosis as a main concept of evolution. The last is tightly linked to the evolutionary principle and explains how human self-recovery is governed. Other subjects of special interest that we shall look deeper into are the immunological self-nonself discrimination, the structure and function of the human brain, the etiology and salutogenesis of mental and somatic diseases, and the structure of the consciousness of a human being. We shall criticize Szentagothai's model for the modulated structure of the human cerebral cortex and Jerne's theory of the immunological regulatory anti-idiotypic network.

  16. Human development I: Twenty Fundamental Problems of Biology, Medicine, and Neuro-Psychology Related to Biological Information

    Directory of Open Access Journals (Sweden)

    Tyge Dahl Hermansen

    2006-01-01

    Full Text Available In a new series of papers, we address a number of unsolved problems in biology today. First of all, the unsolved enigma concerning how the differentiation from a single zygote to an adult individual happens has been object for severe research for decades. By uncovering a new holistic biological paradigm that introduces an energetic-informational interpretation of reality as a new way to experience biology, these papers will try to solve the problems connected with the events of biological ontogenesis involving a fractal hierarchy, from a single cell to the function of the human brain. The problems discussed are interpreted within the frames of a universe of roomy fractal structures containing energetic patterns that are able to deliver biological information. We think biological organization is guided by energetic changes on the level of quantum mechanics, interacting with the intention that again guides the energetic conformation of the fractal structures to gain disorders or healthiness. Furthermore, we introduce two new concepts: “metamorphous top down” evolution and “adult human metamorphosis”. The first is a new evolutionary theory involving metamorphosis as a main concept of evolution. The last is tightly linked to the evolutionary principle and explains how human self-recovery is governed. Other subjects of special interest that we shall look deeper into are the immunological self-nonself discrimination, the structure and function of the human brain, the etiology and salutogenesis of mental and somatic diseases, and the structure of the consciousness of a human being. We shall criticize Szentagothai’s model for the modulated structure of the human cerebral cortex and Jerne’s theory of the immunological regulatory anti-idiotypic network.

  17. Gastroprotection induced by capsaicin in healthy human subjects

    Institute of Scientific and Technical Information of China (English)

    Gyula Mózsik; János Szolcsányi; István Rácz

    2005-01-01

    AIM: To evaluate the gastro-protective effect of capsaicin against the ethanol- and indomethacin (IND)-induced gastric mucosal damage in healthy human subjects.METHODS: The effects of small doses (1-8 μg/mL,100 mL) of capsaicin on the gastric acid secretion basal acid output (BAO) and its electrolyte concentration,gastric transmucosal potential difference (GTPD),ethanol- (5 mL 300 mL/L i.g.) and IND- (3x25 mg/d)induced gastric mucosal damage were tested in a randomized, prospective study of 84 healthy human subjects. The possible role of desensitization of capsaicin-sensitive afferents was tested by repeated exposures and during a prolonged treatment.RESULTS: Intragastric application of capsaicin decreased the BAO and enhanced "non-parietal" component, GTPD in a dose-dependent manner. The decrease of GTPD evoked by ethanol was inhibited by the capsaicin application,which was reproducible. Gastric microbleeding induced by IND was inhibited by co-administration with capsaicin,but was not influenced by two weeks pretreatment with a daily capsaicin dose of 3x400 μg i.g.CONCLUSION: Capsaicin in low concentration range protects against gastric injuries induced by ethanol or IND, which is attributed to stimulation of the sensory nerve endings.

  18. Human subjects protection issues in QUERI implementation research: QUERI Series

    Directory of Open Access Journals (Sweden)

    Ritchie Mona

    2008-02-01

    Full Text Available Abstract Background Human Subjects protections approaches, specifically those relating to research review board oversight, vary throughout the world. While all are designed to protect participants involved in research, the structure and specifics of these institutional review boards (IRBs can and do differ. This variation affects all types of research, particularly implementation research. Methods In 2001, we began a series of inter-related studies on implementing evidence-based collaborative care for depression in Veterans Health Administration primary care. We have submitted more than 100 IRB applications, amendments, and renewals, and in doing so, we have interacted with 13 VA and University IRBs across the United States (U.S.. We present four overarching IRB-related themes encountered throughout the implementation of our projects, and within each theme, identify key challenges and suggest approaches that have proved useful. Where applicable, we showcase process aids developed to assist in resolving a particular IRB challenge. Results There are issues unique to implementation research, as this type of research may not fit within the traditional Human Subjects paradigm used to assess clinical trials. Risks in implementation research are generally related to breaches of confidentiality, rather than health risks associated with traditional clinical trials. The implementation-specific challenges discussed are: external validity considerations, Plan-Do-Study-Act cycles, risk-benefit issues, the multiple roles of researchers and subjects, and system-level unit of analysis. Discussion Specific aspects of implementation research interact with variations in knowledge, procedures, and regulatory interpretations across IRBs to affect the implementation and study of best methods to increase evidence-based practice. Through lack of unambiguous guidelines and local liability concerns, IRBs are often at risk of applying both variable and inappropriate or

  19. 40 CFR 26.118 - Applications and proposals lacking definite plans for involvement of human subjects.

    Science.gov (United States)

    2010-07-01

    ... definite plans for involvement of human subjects. 26.118 Section 26.118 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL PROTECTION OF HUMAN SUBJECTS Basic EPA Policy for Protection of Subjects... plans for involvement of human subjects. Certain types of applications for grants,...

  20. 16 CFR 1028.118 - Applications and proposals lacking definite plans for involvement of human subjects.

    Science.gov (United States)

    2010-01-01

    ... plans for involvement of human subjects. 1028.118 Section 1028.118 Commercial Practices CONSUMER PRODUCT... definite plans for involvement of human subjects. Certain types of applications for grants, cooperative... subjects remain to be selected; and projects in which human subjects' involvement will depend...

  1. Twenty-four-hour plasma tryptophan concentrations and ratios are below normal in obese subjects and are not normalized by substantial weight reduction

    DEFF Research Database (Denmark)

    Breum, Leif; Rasmussen, Michael H; Hilsted, Jannik

    2003-01-01

    subjects. Blood samples were drawn frequently throughout the 24-h period. An insulin tolerance test was also used to determine whether weight loss altered the ability of insulin to modify plasma concentrations of tryptophan and of the other large neutral amino acids. RESULTS: Plasma tryptophan......BACKGROUND: Plasma tryptophan concentrations and the ratio of tryptophan to other large neutral amino acids (plasma tryptophan ratio) are reportedly low in obese subjects. The plasma tryptophan ratio predicts brain tryptophan uptake and serotonin production. If this ratio is low in obese subjects...... concentrations and ratios in obese subjects were low at all times; these effects persisted after weight reduction. Plasma concentrations of all the large neutral amino acids decreased during insulin infusion in all the groups. CONCLUSIONS: The low 24-h plasma tryptophan ratios in obese and formerly obese...

  2. Ethical fundamentals in human subjects research : On equipoise and human dignity

    NARCIS (Netherlands)

    van der Graaf - Verhave, R.|info:eu-repo/dai/nl/304821373

    2010-01-01

    In her PhD thesis Rieke van der Graaf has studied how we can ethically justify human subjects research. In particular she has studied two ethical fundamentals that play a key role in the justification process, that of equipoise and human dignity. Equipoise is often taken to mean that

  3. Ethical fundamentals in human subjects research : On equipoise and human dignity

    NARCIS (Netherlands)

    van der Graaf - Verhave, R.

    2010-01-01

    In her PhD thesis Rieke van der Graaf has studied how we can ethically justify human subjects research. In particular she has studied two ethical fundamentals that play a key role in the justification process, that of equipoise and human dignity. Equipoise is often taken to mean that physician-resea

  4. Prebiotic Effects of Xylooligosaccharides on the Improvement of Microbiota Balance in Human Subjects

    Directory of Open Access Journals (Sweden)

    Shyh-Hsiang Lin

    2016-01-01

    Full Text Available It has been indicated that probiotics can be nourished by consuming prebiotics in order to function more efficiently, allowing the bacteria to stay within a healthy balance. In this study, we investigated the effects of xylooligosaccharides- (XOS- enriched rice porridge consumption on the ecosystem in the intestinal tract of human subjects. Twenty healthy subjects participated in this 6-week trial, in which 10 subjects received XOS-enriched rice porridge while the others received placebo rice porridge. Fecal samples were collected at the end of weeks 0, 1, 3, 4, 6, and 7 for microorganism examination. The results showed that 6-week daily ingestion of the XOS-enriched rice porridge induced significant increases in fecal bacterial counts of Lactobacillus spp. and Bifidobacterium spp., as well as decreases in Clostridium perfringens without changing the total anaerobic bacterial counts, compared to that of placebo rice porridge. However, fluctuations in the counts of coliforms were observed in both groups during the 6-week intervention. In conclusion, the intestinal microbiota balance was improved after daily consumption of 150 g of rice porridge containing XOS for 6 weeks, demonstrating the prebiotic potential of XOS incorporated into foods. This also indicates the effectiveness of XOS as a functional ingredient in relation to its role as a prebiotic compound.

  5. Prebiotic Effects of Xylooligosaccharides on the Improvement of Microbiota Balance in Human Subjects.

    Science.gov (United States)

    Lin, Shyh-Hsiang; Chou, Liang-Mao; Chien, Yi-Wen; Chang, Jung-Su; Lin, Ching-I

    2016-01-01

    It has been indicated that probiotics can be nourished by consuming prebiotics in order to function more efficiently, allowing the bacteria to stay within a healthy balance. In this study, we investigated the effects of xylooligosaccharides- (XOS-) enriched rice porridge consumption on the ecosystem in the intestinal tract of human subjects. Twenty healthy subjects participated in this 6-week trial, in which 10 subjects received XOS-enriched rice porridge while the others received placebo rice porridge. Fecal samples were collected at the end of weeks 0, 1, 3, 4, 6, and 7 for microorganism examination. The results showed that 6-week daily ingestion of the XOS-enriched rice porridge induced significant increases in fecal bacterial counts of Lactobacillus spp. and Bifidobacterium spp., as well as decreases in Clostridium perfringens without changing the total anaerobic bacterial counts, compared to that of placebo rice porridge. However, fluctuations in the counts of coliforms were observed in both groups during the 6-week intervention. In conclusion, the intestinal microbiota balance was improved after daily consumption of 150 g of rice porridge containing XOS for 6 weeks, demonstrating the prebiotic potential of XOS incorporated into foods. This also indicates the effectiveness of XOS as a functional ingredient in relation to its role as a prebiotic compound.

  6. Toxicokinetics of inhaled bromotrifluoromethane (Halon 1301) in human subjects

    Science.gov (United States)

    Lam, C. W.; Weir, F. W.; Williams-Cavender, K.; Tan, M. N.; Galen, T. J.; Pierson, D. L.

    1993-01-01

    Bromotrifluoromethane (Halon 1301, CBrF3), is used as a fire extinguishant in the Space Shuttle, where several scenarios, such as a fire or a faulty alarm, could lead to its discharge resulting in a Halon 1301 concentration of up to 1 percent in the cabin atmosphere. The effect of Halon 1301 on mental performance and physiologic function was investigated in a NASA-sponsored human inhalation study in which four pairs of male subjects were each exposed in a double-blind fashion for 24 hr to 1 percent Halon 1301 and to air in two exposures about 1 week apart. Blood and breath samples from the exposed subjects were collected to provide dosimetric and toxicokinetic information. Halon 1301 blood levels increased rapidly and approached a steady state within 2 hr of the beginning the exposure; the steady-state concentration was approximately 3-4.5 microg/ml. Breath samples collected during exposures closely reflected chamber concentrations. Analysis of postexposure blood samples revealed that Halon 1301 was eliminated biphasically with an average t(1/2) alpha and t(1/2) beta of 4.5 min and 200 min, respectively.

  7. Diclofenac delays micropore closure following microneedle treatment in human subjects.

    Science.gov (United States)

    Brogden, Nicole K; Milewski, Mikolaj; Ghosh, Priyanka; Hardi, Lucia; Crofford, Leslie J; Stinchcomb, Audra L

    2012-10-28

    Drugs absorbed poorly through the skin are commonly delivered via injection with a hypodermic needle, which is painful and increases the risk of transmitting infectious diseases. Microneedles (MNs) selectively and painlessly permeabilize the outermost skin layer, allowing otherwise skin-impermeable drugs to cross the skin through micron-sized pores and reach therapeutic concentrations. However, rapid healing of the micropores prevents further drug delivery, blunting the clinical utility of this unique transdermal technique. We present the first human study demonstrating that micropore lifetime can be extended following MN treatment. Subjects received one-time MN treatment and daily topical application of diclofenac sodium. Micropore closure was measured with impedance spectroscopy, and area under the admittance-time curve (AUC) was calculated. AUC was significantly higher at MN+diclofenac sodium sites vs. placebo, suggesting slower rates of micropore healing. Colorimetry measurements confirmed the absence of local erythema and irritation. This mechanistic human proof-of-concept study demonstrates that micropore lifetime can be prolonged with simple topical administration of a non-specific cyclooxygenase inhibitor, suggesting the involvement of subclinical inflammation in micropore healing. These results will allow for longer patch wear time with MN-enhanced delivery, thus increasing patient compliance and expanding the transdermal field to a wider variety of clinical conditions. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. 22 CFR 225.118 - Applications and proposals lacking definite plans for involvement of human subjects.

    Science.gov (United States)

    2010-04-01

    ... plans for involvement of human subjects. 225.118 Section 225.118 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT PROTECTION OF HUMAN SUBJECTS § 225.118 Applications and proposals lacking definite plans for involvement of human subjects. Certain types of applications for grants,...

  9. 15 CFR 27.118 - Applications and proposals lacking definite plans for involvement of human subjects.

    Science.gov (United States)

    2010-01-01

    ... definite plans for involvement of human subjects. 27.118 Section 27.118 Commerce and Foreign Trade Office of the Secretary of Commerce PROTECTION OF HUMAN SUBJECTS § 27.118 Applications and proposals lacking definite plans for involvement of human subjects. Certain types of applications for grants,...

  10. 28 CFR 46.118 - Applications and proposals lacking definite plans for involvement of human subjects.

    Science.gov (United States)

    2010-07-01

    ... definite plans for involvement of human subjects. 46.118 Section 46.118 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) PROTECTION OF HUMAN SUBJECTS § 46.118 Applications and proposals lacking definite plans for involvement of human subjects. Certain types of applications for grants,...

  11. 14 CFR 1230.118 - Applications and proposals lacking definite plans for involvement of human subjects.

    Science.gov (United States)

    2010-01-01

    ... plans for involvement of human subjects. 1230.118 Section 1230.118 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION PROTECTION OF HUMAN SUBJECTS § 1230.118 Applications and proposals lacking definite plans for involvement of human subjects. Certain types of applications for...

  12. Me acuerdo… ¿Te acuerdas?: Memory, Space and the Individualizing Transformation of the Subject in Twenty-First-Century Mexican Fiction

    Directory of Open Access Journals (Sweden)

    Elsa Treviño Ramírez

    2014-12-01

    Full Text Available During the second half of the twentieth-century, Mexican fictions operated under a revisionist historical logic that employed national spaces to allegorize the relationship between the individual, society and the nation. Countering this trend, since the mid-nineties, Mexican literature has witnessed a departure from an interest in collectivizing discourses of identity, displaying instead a growing faith in individualism as a means to resist state-driven cultural visions. To analyze this emphasis in individual personal emergence, this paper proposes a comparative reading of subject-formation in Álvaro Enrigue's Vidas perpendiculares (2008, and in José Emilio Pacheco’s canonical novella Las batallas en el desierto (1981. The publication of Vidas and Las batallas coincides with two moments of crisis and transformation in Mexico. Consequently, these novels of formation reflect the reconceptualization of the multiple relations between individuals, communities, and the state prompted by such changes. These coming-of-age fictions use the personal recollections of their protagonists to articulate the narration of their characters’ emergence into adulthood. Vidas and Las batallas present two highly divergent visions of the subject and her or his relationship to the social body, where in the case of Vidas the individual takes primacy over the community. Following Ulrich Beck’s insights regarding individualization in industrial societies, and informed by theories of memory and nostalgia, this study explores how literary understandings of identity have transformed to reflect the experience of late modernity in Mexico. This paper argues that in recent Mexican fiction history is spatialized as a way of examining individual subjectivity outside the framework that views history in literature as a discourse directly linked to collective, often national, identity.

  13. 48 CFR 1352.235-70 - Protection of human subjects.

    Science.gov (United States)

    2010-10-01

    ... subjects research involves pregnant women, prisoners, or children, the contractor is also required to... subjects research protocol, all questionnaires, surveys, advertisements, and informed consent forms..., questionnaires, surveys, advertisements, and informed consent forms by the cognizant IRB; (3) Documentation...

  14. 78 FR 10538 - Protections for Subjects in Human Research Involving Pesticides

    Science.gov (United States)

    2013-02-14

    ... AGENCY 40 CFR Part 26 RIN 2070-AJ76 Protections for Subjects in Human Research Involving Pesticides... human subjects and to persons who submit the results of human research with pesticides to EPA. The amendments broaden the applicability of the rules to cover human testing with pesticides submitted to EPA...

  15. 38 CFR 16.118 - Applications and proposals lacking definite plans for involvement of human subjects.

    Science.gov (United States)

    2010-07-01

    ... proposals lacking definite plans for involvement of human subjects. 16.118 Section 16.118 Pensions, Bonuses... and proposals lacking definite plans for involvement of human subjects. Certain types of applications... knowledge that subjects may be involved within the period of support, but definite plans would not...

  16. 32 CFR 219.118 - Applications and proposals lacking definite plans for involvement of human subjects.

    Science.gov (United States)

    2010-07-01

    ... plans for involvement of human subjects. 219.118 Section 219.118 National Defense Department of Defense....118 Applications and proposals lacking definite plans for involvement of human subjects. Certain types... agencies with the knowledge that subjects may be involved within the period of support, but definite...

  17. Cerebral circulation and metabolism in the patients with higher brain dysfunction caused by chronic minor traumatic brain injury. A study by the positron emission tomography in twenty subjects with normal MRI findings

    Energy Technology Data Exchange (ETDEWEB)

    Kabasawa, Hidehiro; Ogawa, Tetsuo; Iida, Akihiko; Matsubara, Michitaka [Nagoya City Rehabilitation and Sports Center (Japan)

    2002-06-01

    Many individuals are affected on their higher brain functions, such as intelligence, memory, and attention, even after minor traumatic brain injury (MTBI). Although higher brain dysfunction is based on impairment of the cerebral circulation and metabolism, the precise relationship between them remains unknown. This study was undertaken to investigate the relationship between the cerebral circulation or cerebral metabolism and higher brain dysfunction. Twenty subjects with higher brain dysfunction caused by chronic MTBI were studied. They had no abnormal MRI findings. The full-scale intelligence quotient (FIQ) were quantitatively evaluated by the Wechsler Adult Intelligence Scale-Revised (WAIS-R), and the subjects were classified into the normal group and the impaired group. Concurrent with the evaluation of FIQ, positron emission tomography (PET) was performed by the steady state method with {sup 15}O gases inhalation. Regional cerebral blood flow (rCBF), oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO{sub 2}) were calculated in the bilateral frontal, parietal, temporal, and occipital lobe. First, of all twenty subjects, we investigated rCBF, OEF and CMRO{sub 2} in all regions. Then we compared rCBF, OEF, and CMRO{sub 2} between the normal group and the impaired group based on FIQ score. We also studied the change of FIQ score of 13 subjects 9.3 months after the first evaluation. In addition, we investigated the change of rCBF, OEF and CMRO{sub 2} along with the improvement of FIQ score. Although rCBF and OEF of all subjects were within the normal range in all regions, CMRO{sub 2} of more than half of subjects was under the lower normal limit in all regions except in the right occipital lobe, showing the presence of ''relative luxury perfusion''. Comparison of rCBF, OEF and CMRO{sub 2} between normal group and impaired group revealed that CMRO{sub 2} of the impaired group was significantly lower than that of the

  18. Disulfiram enhances subjective effects of dextroamphetamine in humans

    Science.gov (United States)

    Sofuoglu, Mehmet; Poling, James; Waters, Andrew; Sewell, Andrew; Hill, Kevin; Kosten, Thomas

    2008-01-01

    Disulfiram has shown promise in several clinical trials for cocaine addiction, but its potential utility in the treatment of amphetamine addiction has not been examined. The goal of this study was to determine the effects of disulfiram on acute physiological and subjective responses to dextroamphetamine in healthy volunteers. Five male and 5 female subjects participated in an outpatient double-blind, placebo-controlled, crossover study. Subjects were randomly assigned to a sequence of disulfiram (250 mg/day) or placebo treatments each lasting for 4 days. Day four of each treatment period was the experimental session, in which subjects orally ingested a single dose of dextroamphetamine (20 mg/70 kg). Outcome measures included heart rate, blood pressure, plasma cortisol and prolactin, subjective and performance on the Sustained Attention to Response Test (SART). Disulfiram did not affect dextroamphetamine-induced increases in heart rate, blood pressure, cortisol, or prolactin. Disulfiram did enhance some of the subjective effects of dextroamphetamine including ratings of “high,” “anxious,” “bad drug effects,” “want more drug” and “drug liking” and was also associated with decreased performance in the SART test. How these enhanced subjective amphetamine responses affect cocaine use behavior remains to be determined in future clinical trials. PMID:18474395

  19. From the Philosophy of Consciousness to the Philosophy of Difference: The Subject for Education after Humanism

    Science.gov (United States)

    Zhao, Guoping

    2015-01-01

    Biesta has suggested that education after humanism should be interested in existence, not essence, in what the subject can do, not in what the subject is--the truth about the subject--and this is the way inspired by Foucault and Levinas. In this article, I analyze Foucault's alleged deconstruction and reconfiguration of the subject and Levinas'…

  20. From the Philosophy of Consciousness to the Philosophy of Difference: The Subject for Education after Humanism

    Science.gov (United States)

    Zhao, Guoping

    2015-01-01

    Biesta has suggested that education after humanism should be interested in existence, not essence, in what the subject can do, not in what the subject is--the truth about the subject--and this is the way inspired by Foucault and Levinas. In this article, I analyze Foucault's alleged deconstruction and reconfiguration of the subject and Levinas'…

  1. No Effect of Cathodal Transcranial Direct Current Stimulation on Fear Memory in Healthy Human Subjects

    Directory of Open Access Journals (Sweden)

    Aditya Mungee

    2016-11-01

    Full Text Available Background: Studies have demonstrated that fear memories can be modified using non-invasive methods. Recently, we demonstrated that anodal transcranial direct current stimulation (tDCS of the right dorsolateral prefrontal cortex is capable of enhancing fear memories. Here, we examined the effects of cathodal tDCS of the right dorsolateral prefrontal cortex during fear reconsolidation in humans. Methods: Seventeen young, healthy subjects were randomly assigned to two groups, which underwent fear conditioning with mild electric stimuli paired with a visual stimulus. Twenty-four hours later, both groups were shown a reminder of the conditioned fearful stimulus. Shortly thereafter, they received either tDCS (right prefrontal—cathodal, left supraorbital—anodal for 20 min at 1 mA, or sham stimulation. A day later, fear responses of both groups were compared. Results: On Day 3, during fear response assessment, there were no significant differences between the tDCS and sham group (p > 0.05. Conclusion: We conclude that cathodal tDCS of the right dorsolateral prefrontal cortex (right prefrontal—cathodal, left supraorbital—anodal did not influence fear memories.

  2. 10 CFR 745.118 - Applications and proposals lacking definite plans for involvement of human subjects.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Applications and proposals lacking definite plans for involvement of human subjects. 745.118 Section 745.118 Energy DEPARTMENT OF ENERGY PROTECTION OF HUMAN SUBJECTS § 745.118 Applications and proposals lacking definite plans for involvement of human...

  3. Salivary Alpha Amylase Activity in Human Beings of Different Age Groups Subjected to Psychological Stress

    National Research Council Canada - National Science Library

    Sahu, Gopal K; Upadhyay, Seema; Panna, Shradha M

    2014-01-01

    ... in different age groups is least studied. This article reports the activity of sAA in human subjects of different age groups subjected to psychological stress induced through stressful video clip...

  4. Dose estimation for repeated phosphorus-32 ingestion in human subjects

    Energy Technology Data Exchange (ETDEWEB)

    Chao, J.H.; Tseng, C.L.; Hsieh, W.A.; Hung, D.Z.; Chang, W.P. E-mail: wpc94@mailsrv.ym.edu.tw

    2001-01-15

    Dose estimation was conducted for internal phosphorus-32 exposure in one young male subject from repeated oral mis-ingestion for >1 year. Since disclosure for previous continuous contamination, a series of urine samples were collected from this individual weekly for a period of >2 months. P-32 radioactivity in urine samples were measured by the acid precipitation method. Estimation for retrospective total effective dose equivalent received by this subject was conducted for cumulative internal dose estimation. A minimum of 9.4 mSv was estimated for an assumed single ingestion. As this was a rare case in radiation protection and internal radiation dosimetry, its implications were of considerable significance.

  5. Dietary guidelines to nourish humanity and the planet in the twenty-first century. A blueprint from Brazil.

    Science.gov (United States)

    Monteiro, Carlos Augusto; Cannon, Geoffrey; Moubarac, Jean-Claude; Martins, Ana Paula Bortoletto; Martins, Carla Adriano; Garzillo, Josefa; Canella, Daniela Silva; Baraldi, Larissa Galastri; Barciotte, Maluh; Louzada, Maria Laura da Costa; Levy, Renata Bertazzi; Claro, Rafael Moreira; Jaime, Patrícia Constante

    2015-09-01

    To present and discuss the dietary guidelines issued by the Brazilian government in 2014. The present paper describes the aims of the guidelines, their shaping principles and the approach used in the development of recommendations. The main recommendations are outlined, their significance for the cultural, socio-economic and environmental aspects of sustainability is discussed, and their application to other countries is considered. Brazil in the twenty-first century. All people in Brazil, now and in future. The food- and meal-based Brazilian Dietary Guidelines address dietary patterns as a whole and so are different from nutrient-based guidelines, even those with some recommendations on specific foods or food groups. The guidelines are based on explicit principles. They take mental and emotional well-being into account, as well as physical health and disease prevention. They identify diet as having cultural, socio-economic and environmental as well as biological and behavioural dimensions. They emphasize the benefits of dietary patterns based on a variety of natural or minimally processed foods, mostly plants, and freshly prepared meals eaten in company, for health, well-being and all relevant aspects of sustainability, as well as the multiple negative effects of ready-to-consume ultra-processed food and drink products. The guidelines' recommendations are designed to be sustainable personally, culturally, socially, economically and environmentally, and thus fit to face this century. They are for foods, meals and dietary patterns of types that are already established in Brazil, which can be adapted to suit the climate, terrain and customs of all countries.

  6. Human rhinovirus infections in symptomatic and asymptomatic subjects

    Directory of Open Access Journals (Sweden)

    C.N. Camargo

    2012-12-01

    Full Text Available The role of rhinovirus asymptomatic infections in the transmission among close contacts subjects is unknown. We tested health care workers, a pair of one child and a family member and immunocompromised patients (n =191. HRV were detected on 22.9% symptomatic and 3.6% asymptomatic cases suggesting lower transmission among contacts.

  7. Human Biology teaching portfolio for education subject Biology

    OpenAIRE

    Hlasová, Zuzana

    2011-01-01

    The aim of the thesis is to create a teaching portfolio with special attention to the educational content of Human Biology. Instructional manuals are created for teaching natural science at primary school and are focused on selected systems in Biology of the human being, which are: muscle system, breathing system, circulation system, digest system, sensuous system, and a chapter about nourishment. Regarding the present?day School educational programmes the teachers themselves choose the year ...

  8. Subject,Object and Target Systems of Rural Human Resource Development

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    From subject,object and target subsystems,we analyze the rural human resource development system.The subject system includes government,education and training organizations,society,and rural human resource itself.Different development subject bears different responsibility.Object system includes farmers engaged in farming,farmer workers,rural unemployed people,rural students,rural left-behind people,and other people in rural areas.Different development object has different features.Development target system includes raising quality of rural human resource,keeping reasonable population size,optimizing structure of rural human resource,and improving vitality of rural human resource,etc.

  9. Hallucinogenic drugs attenuate the subjective response to alcohol in humans.

    Science.gov (United States)

    Barrett, Sean P; Archambault, Jennifer; Engelberg, Marla J; Pihl, Robert O

    2000-10-01

    This study investigated possible interactions between alcohol and hallucinogens in 22 lysergic acid diethylamide (LSD) and/or psilocybin users through retrospective structured interviews. Of those who had used LSD with alcohol, 86;7 per cent reported a complete blockade of subjective alcohol effects, while the remaining cases reported a diminished response. In addition, 60 per cent of respondents who had used alcohol and psilocybin together reported a partial antagonism of subjective alcohol effects.T-test analyses revealed that LSD's antagonism of alcohol effects were significantly greater than those associated with psilocybin. It is proposed that LSD's effect on alcohol intoxication may involve interactions with various serotonergic and/or dopaminergic receptor systems. Copyright 2000 John Wiley & Sons, Ltd.

  10. Biologic effect of a hybrid preparation of human chorionic gonadotropin in human subjects.

    Science.gov (United States)

    Rosemberg, E

    1982-01-01

    Alpha and beta-hCG subunits were recombined generating a hybrid hCG preparation (AB1ER-CR-2XY) which met the required specifications of a pharmaceutical product. The biologic activity contained in each vial of AB1ER-CR-2XY was equivalent to 10 000IU of hCG-IS. This preparation was given as a single dose of 10 000IU by the i.m. route to four female subjects presenting unexplained infertility. The hCG hybrid was demonstrated to effect gonadal stimulation in humans.

  11. 48 CFR 1352.235-73 - Research involving human subjects-after initial contract award.

    Science.gov (United States)

    2010-10-01

    ... women, prisoners, or children, the contractor is also required to follow the guidelines set forth at 45... documentation may include: (1) Copies of the human subjects research protocol, advertisements, recruitment... human subjects research protocol, advertisements, recruitment material, and informed consent forms...

  12. 7 CFR 1c.118 - Applications and proposals lacking definite plans for involvement of human subjects.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Applications and proposals lacking definite plans for involvement of human subjects. 1c.118 Section 1c.118 Agriculture Office of the Secretary of Agriculture PROTECTION OF HUMAN SUBJECTS § 1c.118 Applications and proposals lacking definite plans for involvement...

  13. 45 CFR 46.118 - Applications and proposals lacking definite plans for involvement of human subjects.

    Science.gov (United States)

    2010-10-01

    ... Research Subjects § 46.118 Applications and proposals lacking definite plans for involvement of human... 45 Public Welfare 1 2010-10-01 2010-10-01 false Applications and proposals lacking definite plans for involvement of human subjects. 46.118 Section 46.118 Public Welfare DEPARTMENT OF HEALTH AND...

  14. 49 CFR 11.118 - Applications and proposals lacking definite plans for involvement of human subjects.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Applications and proposals lacking definite plans for involvement of human subjects. 11.118 Section 11.118 Transportation Office of the Secretary of Transportation PROTECTION OF HUMAN SUBJECTS § 11.118 Applications and proposals lacking definite plans...

  15. 34 CFR 97.118 - Applications and proposals lacking definite plans for involvement of human subjects.

    Science.gov (United States)

    2010-07-01

    ... for Protection of Human Research Subjects) § 97.118 Applications and proposals lacking definite plans... 34 Education 1 2010-07-01 2010-07-01 false Applications and proposals lacking definite plans for involvement of human subjects. 97.118 Section 97.118 Education Office of the Secretary, Department...

  16. HEW Proposed Policy on the Protection of Human Subjects: Experimentation and the Institutionalized Mentally Disabled

    Science.gov (United States)

    Washington University Law Quarterly, 1975

    1975-01-01

    Underlying bases for federal interest in experimentation on human subjects, including abuses of investigative processes and efforts at regulation, are explored. Focus is on recent HEW rules on the protection of human subjects, which will have a significant impact on many research institutions. (LBH)

  17. Computer science security research and human subjects: emerging considerations for research ethics boards.

    Science.gov (United States)

    Buchanan, Elizabeth; Aycock, John; Dexter, Scott; Dittrich, David; Hvizdak, Erin

    2011-06-01

    This paper explores the growing concerns with computer science research, and in particular, computer security research and its relationship with the committees that review human subjects research. It offers cases that review boards are likely to confront, and provides a context for appropriate consideration of such research, as issues of bots, clouds, and worms enter the discourse of human subjects review.

  18. The research subject advocate at minority Clinical Research Centers: an added resource for protection of human subjects.

    Science.gov (United States)

    Easa, David; Norris, Keith; Hammatt, Zoë; Kim, Kari; Hernandez, Esther; Kato, Kambrie; Balaraman, Venkataraman; Ho, Tammy; Shomaker, Samuel

    2005-01-01

    In early 2001, the National Institutes of Health (NIH) created the research subject advocate (RSA) position as an additional resource for human subjects protection at NIH-funded Clinical Research Centers (CRCs) to enhance the protection of human participants in clinical research studies. We describe the RSA position in the context of clinical research, with a particular emphasis on the role of the RSA in two of the five CRCs funded by the NIH Research Centers in Minority Institutions (RCMI) program. Through participation in protocol development, informed consent procedures, study implementation and follow-up with adverse events, the RSA works closely with research investigators and their staff to protect study participants. The RSA also conducts workshops, training and education sessions, and consultation with investigators to foster enhanced communication and adherence to ethical standards and safety regulations. Although we cannot yet provide substantive evidence of positive outcomes, this article illuminates the value of the RSA position in ensuring that safety of research participants is accorded the highest priority at CRCs. On the basis of initial results, we conclude that the RSA is an effective mechanism for achieving the NIH goal of maintaining the utmost scrutiny of protocols involving human subjects.

  19. Diurnal and twenty-four hour patterning of human diseases: acute and chronic common and uncommon medical conditions.

    Science.gov (United States)

    Smolensky, Michael H; Portaluppi, Francesco; Manfredini, Roberto; Hermida, Ramon C; Tiseo, Ruana; Sackett-Lundeen, Linda L; Haus, Erhard L

    2015-06-01

    The symptom intensity and mortality of human diseases, conditions, and syndromes exhibit diurnal or 24 h patterning, e.g., skin: atopic dermatitis, urticaria, psoriasis, and palmar hyperhidrosis; gastrointestinal: esophageal reflux, peptic ulcer (including perforation and hemorrhage), cyclic vomiting syndrome, biliary colic, hepatic variceal hemorrhage, and proctalgia fugax; infection: susceptibility, fever, and mortality; neural: frontal, parietal, temporal, and occipital lobe seizures, Parkinson's and Alzheimer's disease, hereditary progressive dystonia, and pain (cancer, post-surgical, diabetic neuropathic and foot ulcer, tooth caries, burning mouth and temporomandibular syndromes, fibromyalgia, sciatica, intervertebral vacuum phenomenon, multiple sclerosis muscle spasm, and migraine, tension, cluster, hypnic, and paroxysmal hemicranial headache); renal: colic and nocturnal enuresis and polyuria; ocular: bulbar conjunctival redness, keratoconjunctivitis sicca, intraocular pressure and anterior ischemic optic neuropathy, and recurrent corneal erosion syndrome; psychiatric/behavioral: major and seasonal affective depressive disorders, bipolar disorder, parasuicide and suicide, dementia-associated agitation, and addictive alcohol, tobacco, and heroin cravings and withdrawal phenomena; plus autoimmune and musculoskeletal: rheumatoid arthritis, osteoarthritis, axial spondylarthritis, gout, Sjögren's syndrome, and systemic lupus erythematosus. Knowledge of these and other 24 h patterns of human pathophysiology informs research of their underlying circadian and other endogenous mechanisms, external temporal triggers, and more effective patient care entailing clinical chronopreventive and chronotherapeutic strategies.

  20. Refined localization of twenty-one genes in subregion p13.1 of human chromosome 1.

    Science.gov (United States)

    Chelala, C; Imbeaud, S; Devignes, M D; Zoorob, R; Auffray, C

    2001-01-01

    In this report, we describe a refinement of the human transcript map of chromosome 1p13.1, a subregion undergoing many aberrations in various types of human cancers. Publicly available genetic linkage, radiation hybrid and physical maps, as well as cytogenetic and sequence data were used to establish the relative order and orientation of ten known intragenic markers. The complete sequence of genomic clones of the region, available at the Sanger Centre, provided the tool for further studies performed by BLAST analysis against all cDNA sequences registered in the Genexpress Index2. This allowed us to assign to subband 1p13.1 nine of the ten known genes, an additional member of the gene family of one of these genes and eleven new transcripts. The remaining known gene and one additional new transcript map at the 1p13.1 and 1p13.2 boundary. The corresponding genes may be responsible for disorders related to this region. The resulting transcript map of 1p13.1 is presented in the printed article with additional data available on a dedicated Web site at the address http://idefix.upr420.vjf.cnrs.fr/CARTO.

  1. Capturing the angel in "angel dust": twenty years of translational neuroscience studies of NMDA receptor antagonists in animals and humans.

    Science.gov (United States)

    Moghaddam, Bita; Krystal, John H

    2012-09-01

    Here, we describe our collaborative efforts to use N-methyl-d-aspartate (NMDA) receptor antagonists as a translational tool to advance our understanding of the pathophysiology of schizophrenia and identify potential new targets for treatment of schizophrenia. We began these efforts in the late 1980s with a keen sense that, in both human and animal studies, we needed to move beyond the dopamine hypothesis of schizophrenia; if the dopamine hypothesis were correct, the existing dopamine antagonists should have cured the disease but they have not. We used NMDA receptor antagonists, not to produce schizophrenia, but as a tool to provide insights into effects of disturbances in glutamate synaptic function in schizophrenia. Our work has provided insights into potential mechanisms that may contribute to disrupted cortical function in schizophrenia and has helped identify potential treatment targets for the disorder. The translational nature of this study made the clinical testing of the first of these targets feasible. Advances in systems neuroscience approaches in animals and humans make new types of translational research possible; however, our concern is that the current obstacles facing translational research funding and academia-industry collaborations threaten the future progress in this field.

  2. Robot Tracking of Human Subjects in Field Environments

    Science.gov (United States)

    Graham, Jeffrey; Shillcutt, Kimberly

    2003-01-01

    Future planetary exploration will involve both humans and robots. Understanding and improving their interaction is a main focus of research in the Intelligent Systems Branch at NASA's Johnson Space Center. By teaming intelligent robots with astronauts on surface extra-vehicular activities (EVAs), safety and productivity can be improved. The EVA Robotic Assistant (ERA) project was established to study the issues of human-robot teams, to develop a testbed robot to assist space-suited humans in exploration tasks, and to experimentally determine the effectiveness of an EVA assistant robot. A companion paper discusses the ERA project in general, its history starting with ASRO (Astronaut-Rover project), and the results of recent field tests in Arizona. This paper focuses on one aspect of the research, robot tracking, in greater detail: the software architecture and algorithms. The ERA robot is capable of moving towards and/or continuously following mobile or stationary targets or sequences of targets. The contributions made by this research include how the low-level pose data is assembled, normalized and communicated, how the tracking algorithm was generalized and implemented, and qualitative performance reports from recent field tests.

  3. Influence of diet on flatus volume in human subjects

    Science.gov (United States)

    Davies, P. J.

    1971-01-01

    Ten flatulent but otherwise healthy subjects were studied while consuming two or three different diets. Flatus collections showed that a bean-containing, high crude-fibre diet produced more flatus (mean 49·4 ml/hr) than either a diet with a restricted crude-fibre content (mean 26·7 ml/hr) or a liquid chemically defined diet (mean 10·9 ml/hr). There was a close correlation between the crude-fibre content of the diet and the production of flatus. The results are consistent with the conclusion that flatus is not the result of swallowing air, but arises mainly from bacterial fermentation of indigestible carbohydrate, eg, cellulose, passing into the colon. PMID:5098326

  4. OKN asymmetry in human subjects: a literature review.

    Science.gov (United States)

    Knapp, Christopher M; Proudlock, Frank A; Gottlob, Irene

    2013-03-01

    Optokinetic nystagmus (OKN) is a reflex eye movement induced by motion of the whole or a large proportion of the visual field. It can be horizontal, vertical, and torsional in direction and consists of two basic components, a slow tracking movement and a rapid recovery saccade. Two forms of OKN exist: "look" and "stare" OKN. There is strong evidence that horizontal OKN is symmetrical in normal healthy adults and that the OKN gains can be influenced by a variety of different factors including target size, shape, contrast, and velocity. Vertical OKN on the other hand is less well understood, although there is a belief that vertical OKN is asymmetrical with an upward preference. Recent publications contradict this assertion. In this article a comprehensive literature review was carried out to determine whether a vertical OKN asymmetry exists in healthy subjects and to explain any anomalous findings.

  5. Gastrointestinal Physiology During Head Down Tilt Bedrest in Human Subjects

    Science.gov (United States)

    Vaksman, Z.; Guthienz, J.; Putcha, L.

    2008-01-01

    Introduction: Gastrointestinal (GI) motility plays a key role in the physiology and function of the GI tract. It directly affects absorption of medications and nutrients taken by mouth, in addition to indirectly altering GI physiology by way of changes in the microfloral composition and biochemistry of the GI tract. Astronauts have reported nausea, loss of appetite and constipation during space flight all of which indicate a reduction in GI motility and function similar to the one seen in chronic bed rest patients. The purpose of this study is to determine GI motility and bacterial proliferation during -6 degree head down tilt bed rest (HTD). Methods: Healthy male and female subjects between the ages of 25-40 participated in a 60 day HTD study protocol. GI transit time (GITT) was determined using lactulose breath hydrogen test and bacterial overgrowth was measured using glucose breath hydrogen test. H. Pylori colonization was determined using C13-urea breath test (UBIT#). All three tests were conducted on 9 days before HDT, and repeated on HDT days 2, 28, 58, and again on day 7 after HDT. Results: GITT increased during HTD compared to the respective ambulatory control values; GITT was significantly lower on day 7 after HTD. A concomitant increase in bacterial colonization was also noticed during HDT starting after approximately 28 days of HDT. However, H. Pylori proliferation was not recorded during HDT as indicated by UBIT#. Conclusion: GITT significantly decreased during HDT with a concomitant increase in the proliferation of GI bacterial flora but not H. pylori.

  6. Can ropinirole modulate reinforcing subjective effects of cocaine in humans?

    Directory of Open Access Journals (Sweden)

    Angelo Giovanni Icro eMaremmani

    2011-08-01

    Full Text Available In this study we evaluated, by means of the Cocaine Rush Visual Analogue Scale (CRVAS, the impact of ropinirole on the expected rush induced by cocaine in a group of heroin addicts abusing cocaine; the self-reported reaction to the rush blockade (if any on cocaine consumption, and the correlations between this self-reported reaction and individual, clinical and therapeutic parameters. Nineteen cocaine abuser heroin-dependent patients entered the study. Their experienced cocaine rush was 61.31±32.1% of the maximum effect previously experienced. Compared with their previous rush intensity 16 patients experienced significantly lower intensity, three the same intensity and none a higher intensity. In particular, two patients experienced a complete blockade of rush and reported a reduced use of cocaine. Fourteen patients experienced a partial blockade of cocaine rush; of these, nine reported they had reduced their use of cocaine. Ropinirole does diminish the subjective intensity of an expected cocaine rush, so interfering with the dynamics of reward, while supporting its possible use in the treatment of cocaine dependence.

  7. 77 FR 25533 - Agency Requests for Approval of a New Information Collection(s): Human Subjects Experiments...

    Science.gov (United States)

    2012-04-30

    ...(s): Human Subjects Experiments Related to Keyless Ignition Controls, Gear Selection Controls, and....gov . SUPPLEMENTARY INFORMATION: OMB Control Number: 2127-New. Title: Human Subjects Experiments... available at www.regulations.gov . Human factors observational experiments are proposed to examine...

  8. Hans Jonas' Thought on The Ethics of Research on Human Subjects

    African Journals Online (AJOL)

    Dr Olaleye

    Subjects: Implications for Contemporary Medical Research in. Nigeria. Ebeh J.I1 and ... Keywords: Human Research ethics, Nigeria, Hans Jonas. *Author for corresp .... 1998) reported a case of over sixty embryos that were transplanted into ...

  9. Using genetic algorithms with subjective input from human subjects: implications for fitting hearing aids and cochlear implants.

    Science.gov (United States)

    Başkent, Deniz; Eiler, Cheryl L; Edwards, Brent

    2007-06-01

    To present a comprehensive analysis of the feasibility of genetic algorithms (GA) for finding the best fit of hearing aids or cochlear implants for individual users in clinical or research settings, where the algorithm is solely driven by subjective human input. Due to varying pathology, the best settings of an auditory device differ for each user. It is also likely that listening preferences vary at the same time. The settings of a device customized for a particular user can only be evaluated by the user. When optimization algorithms are used for fitting purposes, this situation poses a difficulty for a systematic and quantitative evaluation of the suitability of the fitting parameters produced by the algorithm. In the present study, an artificial listening environment was generated by distorting speech using a noiseband vocoder. The settings produced by the GA for this listening problem could objectively be evaluated by measuring speech recognition and comparing the performance to the best vocoder condition where speech was least distorted. Nine normal-hearing subjects participated in the study. The parameters to be optimized were the number of vocoder channels, the shift between the input frequency range and the synthesis frequency range, and the compression-expansion of the input frequency range over the synthesis frequency range. The subjects listened to pairs of sentences processed with the vocoder, and entered a preference for the sentence with better intelligibility. The GA modified the solutions iteratively according to the subject preferences. The program converged when the user ranked the same set of parameters as the best in three consecutive steps. The results produced by the GA were analyzed for quality by measuring speech intelligibility, for test-retest reliability by running the GA three times with each subject, and for convergence properties. Speech recognition scores averaged across subjects were similar for the best vocoder solution and for the

  10. Experimentation with human subjects: a critique of the views of Hans Jonas.

    OpenAIRE

    Schafer, A.

    1983-01-01

    The ethics of experimentation on human subjects has become the subject of much debate among medical scientists and philosophers. Ethical problems and conflicts of interest become especially serious when research subjects are recruited from the class of patients. Are patients who are ill and suffering in a position to give voluntary and informed consent? Are there inevitable conflicts of interest and moral obligation when a personal physician recruits his own patients for an experiment designe...

  11. 45 CFR 690.118 - Applications and proposals lacking definite plans for involvement of human subjects.

    Science.gov (United States)

    2010-10-01

    ... Applications and proposals lacking definite plans for involvement of human subjects. Certain types of... knowledge that subjects may be involved within the period of support, but definite plans would not normally... 45 Public Welfare 3 2010-10-01 2010-10-01 false Applications and proposals lacking definite...

  12. Endurance training enhances skeletal muscle interleukin-15 in human male subjects

    DEFF Research Database (Denmark)

    Rinnov, Anders; Yfanti, Christina; Nielsen, Søren

    2014-01-01

    endurance running. With the present study we aimed to determine if muscular IL-15 production would increase in human male subjects following 12 weeks of endurance training. In two different studies we obtained plasma and muscle biopsies from young healthy subjects performing: (1) 12 weeks of ergometer...

  13. Swinging on the pendulum. Shifting views of justice in human subjects research.

    Science.gov (United States)

    Mastroianni, A; Kahn, J

    2001-01-01

    Federal policies on human subjects research have performed a near-about face. In the 1970s, policies were motivated chiefly by a belief that subjects needed protection from the harms and risks of research. Now the driving concern is that patients, and the populations they represent, need access to the benefits of research.

  14. Effects of growth hormone on glucose and fat metabolism in human subjects

    DEFF Research Database (Denmark)

    Jørgensen, Jens O L; Møller, Louise; Krag, Morten Brøgger

    2007-01-01

    This article focuses on in vivo data from tests performed in normal subjects and in patients who had abnormal growth hormone (GH) status. Experimental data in human subjects demonstrate that GH acutely inhibits glucose disposal in skeletal muscle. At the same time GH stimulates the turnover...

  15. Paying human subjects in research: where are we, how did we get here, and now what?

    Science.gov (United States)

    VanderWalde, Ari; Kurzban, Seth

    2011-01-01

    Both international and federal regulations exist to ensure that scientists perform research on human subjects in an environment free of coercion and in which the benefits of the research are commensurate with the risks involved. Ensuring that these conditions hold is difficult, and perhaps even more so when protocols include the issue of monetary compensation of research subjects. The morality of paying human research subjects has been hotly debated for over 40 years, and the grounds for this debate have ranged from discussion of legal rights, economic rights, philosophical principles of vulnerability and altruism to bioethical concepts of consent, best-interest determination, and justice theory. However, the thought surrounding these issues has evolved over time, and the way we think about the role of the human research subject today is markedly different than the way we thought in the past. Society first thought of the research subject as an altruist, necessarily giving of his time to benefit society as a whole. As time progressed, many suggested that the subject should not need to sacrifice himself for research: if something goes wrong, someone should compensate the subject for injuries. The concept of redress evolved into a system in which subjects were offered money as an inducement to participate in research, sometimes merely to offset the monetary costs of participation, but sometimes even to mitigate the risks of the study. This article examines ethical and legal conversations regarding compensation from the 1960s through today, examining theories of the ethics of compensation both comparatively and critically. In conclusion, we put forward an ethical framework for treating paid research subjects, with an attempt to use this framework as a means of resolving some of the more difficult problems with paying human subjects in research.

  16. Re-emergent human adenovirus genome type 7d caused an acute respiratory disease outbreak in Southern China after a twenty-one year absence.

    Science.gov (United States)

    Zhao, Suhui; Wan, Chengsong; Ke, Changwen; Seto, Jason; Dehghan, Shoaleh; Zou, Lirong; Zhou, Jie; Cheng, Zetao; Jing, Shuping; Zeng, Zhiwei; Zhang, Jing; Wan, Xuan; Wu, Xianbo; Zhao, Wei; Zhu, Li; Seto, Donald; Zhang, Qiwei

    2014-12-08

    Human adenoviruses (HAdVs) are highly contagious pathogens causing acute respiratory disease (ARD), among other illnesses. Of the ARD genotypes, HAdV-7 presents with more severe morbidity and higher mortality than the others. We report the isolation and identification of a genome type HAdV-7d (DG01_2011) from a recent outbreak in Southern China. Genome sequencing, phylogenetic analysis, and restriction endonuclease analysis (REA) comparisons with past pathogens indicate HAdV-7d has re-emerged in Southern China after an absence of twenty-one years. Recombination analysis reveals this genome differs from the 1950s-era prototype and vaccine strains by a lateral gene transfer, substituting the coding region for the L1 52/55 kDa DNA packaging protein from HAdV-16. DG01_2011 descends from both a strain circulating in Southwestern China (2010) and a strain from Shaanxi causing a fatality and outbreak (Northwestern China; 2009). Due to the higher morbidity and mortality rates associated with HAdV-7, the surveillance, identification, and characterization of these strains in population-dense China by REA and/or whole genome sequencing are strongly indicated. With these accurate identifications of specific HAdV types and an epidemiological database of regional HAdV pathogens, along with the HAdV genome stability noted across time and space, the development, availability, and deployment of appropriate vaccines are needed.

  17. 10 CFR 35.604 - Surveys of patients and human research subjects treated with a remote afterloader unit.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Surveys of patients and human research subjects treated... Stereotactic Radiosurgery Units § 35.604 Surveys of patients and human research subjects treated with a remote... shall survey the patient or the human research subject and the remote afterloader unit with a...

  18. 40 CFR 26.1203 - Prohibition of research involving intentional exposure of any human subject who is a pregnant...

    Science.gov (United States)

    2010-07-01

    ... intentional exposure of any human subject who is a pregnant woman (and therefore her fetus), a nursing woman... Exposure of Human Subjects who are Children or Pregnant or Nursing Women § 26.1203 Prohibition of research involving intentional exposure of any human subject who is a pregnant woman (and therefore her fetus),...

  19. Subjective thermal sensation and human body exergy consumption rate: analysis and correlation

    DEFF Research Database (Denmark)

    Simone, Angela; Dovjak, M.; Kolarik, Jakub

    2011-01-01

    The exergy approach to design and operation of climate conditioning systems is relatively well established, while its exploitation in connection to human perception of the indoor environment is relatively rare. As a building should provide healthy and comfortable environment for its occupants......, it is reasonable to consider both the exergy flows in building and those within the human body. There is a need to verify the human-body exergy model with the Thermal-Sensation (TS) response of subjects exposed to different combinations of indoor climate parameters (temperature, humidity, etc.). First results...... available on the relation between human-body exergy consumption rates and subjectively assessed thermal sensation showed that the minimum human body exergy consumption rate is associated with thermal sensation votes close to thermal neutrality, tending to slightly cool side of thermal sensation. By applying...

  20. Subjective thermal sensation and human body exergy consumption rate: analysis and correlation

    DEFF Research Database (Denmark)

    Simone, Angela; Dovjak, M.; Kolarik, Jakub

    2011-01-01

    The exergy approach to design and operation of climate conditioning systems is relatively well established, while its exploitation in connection to human perception of the indoor environment is relatively rare. As a building should provide healthy and comfortable environment for its occupants......, it is reasonable to consider both the exergy flows in building and those within the human body. There is a need to verify the human-body exergy model with the Thermal-Sensation (TS) response of subjects exposed to different combinations of indoor climate parameters (temperature, humidity, etc.). First results...... available on the relation between human-body exergy consumption rates and subjectively assessed thermal sensation showed that the minimum human body exergy consumption rate is associated with thermal sensation votes close to thermal neutrality, tending to slightly cool side of thermal sensation. By applying...

  1. Deliberate Microbial Infection Research Reveals Limitations to Current Safety Protections of Healthy Human Subjects.

    Science.gov (United States)

    Evers, David L; Fowler, Carol B; Mason, Jeffrey T; Mimnall, Rebecca K

    2015-08-01

    Here we identify approximately 40,000 healthy human volunteers who were intentionally exposed to infectious pathogens in clinical research studies dating from late World War II to the early 2000s. Microbial challenge experiments continue today under contemporary human subject research requirements. In fact, we estimated 4,000 additional volunteers who were experimentally infected between 2010 and the present day. We examine the risks and benefits of these experiments and present areas for improvement in protections of participants with respect to safety. These are the absence of maximum limits to risk and the potential for institutional review boards to include questionable benefits to subjects and society when weighing the risks and benefits of research protocols. The lack of a duty of medical care by physician-investigators to research subjects is likewise of concern. The transparency of microbial challenge experiments and the safety concerns raised in this work may stimulate further dialogue on the risks to participants of human experimentation.

  2. A Method for Remotely Sensing Vital Signs of Human Subjects Outdoors

    Directory of Open Access Journals (Sweden)

    Chuantao Li

    2015-06-01

    Full Text Available After chemical or nuclear leakage or explosions, finding survivors is a huge challenge. Although human bodies can be found by smart vehicles and drones equipped with cameras, it is difficult to verify if the person is alive or dead this way. This paper describes a continuous wave radar sensor for remotely sensing the vital signs of human subjects. Firstly, a compact and portable 24 GHz Doppler radar system is designed to conduct non-contact detection of respiration signal. Secondly, in order to improve the quality of the respiration signals, the self-correlation and adaptive line enhancer (ALE methods are proposed to minimize the interferences of any moving objects around the human subject. Finally, the detection capabilities of the radar system and the signal processing method are verified through experiments which show that human respiration signals can be extracted when the subject is 7 m away outdoors. The method provided in this paper will be a promising way to search for human subjects outdoors.

  3. A Method for Remotely Sensing Vital Signs of Human Subjects Outdoors

    Science.gov (United States)

    Li, Chuantao; Chen, Fuming; Jin, Jingxi; Lv, Hao; Li, Sheng; Lu, Guohua; Wang, Jianqi

    2015-01-01

    After chemical or nuclear leakage or explosions, finding survivors is a huge challenge. Although human bodies can be found by smart vehicles and drones equipped with cameras, it is difficult to verify if the person is alive or dead this way. This paper describes a continuous wave radar sensor for remotely sensing the vital signs of human subjects. Firstly, a compact and portable 24 GHz Doppler radar system is designed to conduct non-contact detection of respiration signal. Secondly, in order to improve the quality of the respiration signals, the self-correlation and adaptive line enhancer (ALE) methods are proposed to minimize the interferences of any moving objects around the human subject. Finally, the detection capabilities of the radar system and the signal processing method are verified through experiments which show that human respiration signals can be extracted when the subject is 7 m away outdoors. The method provided in this paper will be a promising way to search for human subjects outdoors. PMID:26115454

  4. Olfactory Sensitivity for Six Predator Odorants in CD-1 Mice, Human Subjects, and Spider Monkeys

    Science.gov (United States)

    Sarrafchi, Amir; Odhammer, Anna M. E.; Hernandez Salazar, Laura Teresa; Laska, Matthias

    2013-01-01

    Using a conditioning paradigm, we assessed the olfactory sensitivity of six CD-1 mice (Mus musculus) for six sulfur-containing odorants known to be components of the odors of natural predators of the mouse. With all six odorants, the mice discriminated concentrations <0.1 ppm (parts per million) from the solvent, and with five of the six odorants the best-scoring animals were even able to detect concentrations <1 ppt (parts per trillion). Four female spider monkeys (Ateles geoffroyi) and twelve human subjects (Homo sapiens) tested in parallel were found to detect the same six odorants at concentrations <0.01 ppm, and with four of the six odorants the best-scoring animals and subjects even detected concentrations <10 ppt. With all three species, the threshold values obtained here are generally lower than (or in the lower range of) those reported for other chemical classes tested previously, suggesting that sulfur-containing odorants may play a special role in olfaction. Across-species comparisons showed that the mice were significantly more sensitive than the human subjects and the spider monkeys with four of the six predator odorants. However, the human subjects were significantly more sensitive than the mice with the remaining two odorants. Human subjects and spider monkeys significantly differed in their sensitivity with only two of the six odorants. These comparisons lend further support to the notion that the number of functional olfactory receptor genes or the relative or absolute size of the olfactory bulbs are poor predictors of a species’ olfactory sensitivity. Analysis of odor structure–activity relationships showed that in both mice and human subjects the type of alkyl rest attached to a thietane and the type of oxygen moiety attached to a thiol significantly affected olfactory sensitivity. PMID:24278296

  5. Acute ozone exposure increases plasma prostaglandin F2 alpha in ozone-sensitive human subjects

    Energy Technology Data Exchange (ETDEWEB)

    Schelegle, E.S.; Adams, W.C.; Giri, S.N.; Siefkin, A.D.

    1989-07-01

    Twenty O/sub 3/-sensitive and /sup 2/O O/sub 3/-nonsensitive subjects participated in a study to investigate the effects of disparate O/sub 3/ sensitivity on plasma prostaglandin F2 alpha responses consequent to exposure to ambient O3 concentrations. Subjects were selected from a pool of 75 normal healthy college-aged males who had been previously exposed to 0.35 ppm O3 for 1 h at an exercising VE of 60 L/min. The selection criterion used was the observed decrement in FEV1 after the O/sub 3/ exposure: O/sub 3/-sensitive, FEV1 decrement greater than 24%; O/sub 3/-nonsensitive, FEV1 decrement less than 11%. Each subject was exposed to filtered air and to 0.20 and 0.35 ppm O/sub 3/ for 80 min while exercising at a VE of 50 L/min. These experimental protocols were divided into two 40-min sessions separated by a period of 4 to 10 min. PGF2 alpha, FVC, FEV1, and FEF25-75 were evaluated before, during, and after each protocol. SGaw and Vtg were measured before and after each protocol. Plasma PGF2 alpha was significantly increased in the O/sub 3/-sensitive group during and after the 0.35-ppm O/sub 3/ exposure.

  6. Dose and effect of inhaled ozone in resting versus exercising human subjects: comparison with resting rats

    Science.gov (United States)

    Dose and effect of inhaled ozone in resting versus exercising human subjects: comparison with resting rats Authors: Gary E. Hatch, John McKee, James Brown, Bill McDonnell, Elston Seal, Joleen Soukup, Ralph Slade, Kay Crissman and Robert Devlin, National Health and Environmental...

  7. Ethics in action: Approving and improving medical research with human subjects

    NARCIS (Netherlands)

    J.P. de Jong

    2013-01-01

    In this thesis, Jean Philippe de Jong presents a new understanding of ethical oversight on medical research with human subjects and proposes that two philosophies for ethical oversight exist: '(dis)approving' and 'improving'. Systems for ethical oversight on medical research have been in place for m

  8. Ethical and Legal Considerations in Dental Caries Research Using Human Subjects: Conference Summary.

    Science.gov (United States)

    Jenny, Joanna

    1980-01-01

    Guidelines of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research are discussed. It is concluded that dentistry must not uncritically accept guidelines meant for a broader class of research, that guidelines can be misapplied, and that researchers must educate themselves on the Commission…

  9. Education and the Labour Market: Subjective Aspects of Human Capital Investment.

    Science.gov (United States)

    Killeen, John; Turton, Richard; Diamond, Wayne; Dosnon, Odile; Wach, Monique

    1999-01-01

    Explores subjective aspects of human-capital investment decisions in education. Explores connections that 11th- and 13th-year British students perceive between their education and the labor market, and between qualifications mechanisms and life chances. Most students believe education plays a market-signaling role and a marginal role in raising…

  10. 48 CFR 1352.235-71 - Protection of human subjects-exemption.

    Science.gov (United States)

    2010-10-01

    ...). (f) In the event the human subjects research involves pregnant women, prisoners, or children..., all questionnaires, surveys, advertisements, and informed consent forms approved by the cognizant IRB..., advertisements, and informed consent forms by the cognizant IRB; (3) Documentation of continuing IRB approval...

  11. Validity of animal models for the cholesterol-raising effects of coffee diterpenes in human subjects

    NARCIS (Netherlands)

    Roos, de B.; Sawyer, J.K.; Katan, M.B.; Rudel, L.L.

    1999-01-01

    Cafestol and kahweol, coffee lipids present in unfiltered coffee brews, potently increase LDL-cholesterol concentration in human subjects. We searched for an animal species in which cafestol similarly increases LDL-cholesterol. Such an animal model could be used subsequently as a model to study the

  12. Synchronization of lower limb motor unit activity during walking in human subjects

    DEFF Research Database (Denmark)

    Hansen, Naja L; Hansen, S; Christensen, L. O. D.

    2001-01-01

    Synchronization of motor unit activity was investigated during treadmill walking (speed: 3-4 km/h) in 25 healthy human subjects. Recordings were made by pairs of wire electrodes inserted into the tibialis anterior (TA) muscle and by pairs of surface electrodes placed over this muscle and a number...

  13. Nocturnal variations in subcutaneous blood flow rate in lower leg of normal human subjects

    DEFF Research Database (Denmark)

    Sindrup, J H; Kastrup, J; Jørgensen, B;

    1991-01-01

    Subcutaneous adipose tissue blood flow rate was measured in the lower leg of 22 normal human subjects over 12- to 20-h ambulatory conditions. The 133Xe washout technique, portable CdTe(Cl) detectors, and a portable data storage unit were used. The tracer depot was applied on the medial aspect...

  14. A Pilot Study of Phase-Evoked Acoustic Responses From the Ears of Human Subjects

    DEFF Research Database (Denmark)

    Christensen, Anders Tornvig; Dewey, James; Dhar, Sumitrajit

    2015-01-01

    cochlear excitation revealing properties of the nonlinearity responsible for OAE generation. To explore the temporal properties of OAEs further, we studied acoustic responses from the ears of nine young, normal-hearing human subjects to abrupt changes in the phase of pure tones. The measurement paradigm...

  15. Overcoming Deformations of the Legal Consciousness of Teenagers through the Medium of Teaching Humanities Subjects

    OpenAIRE

    2014-01-01

    This article proposes a model for teaching humanities subjects, which is oriented towards overcoming deformations of the legal consciousness of teenagers. The author provides a description of the model’s aims, content, stages, and procedural characteristics. The author views the learning process as the opportunity to forestall illicit behavior by the underage.

  16. Overcoming Deformations of the Legal Consciousness of Teenagers through the Medium of Teaching Humanities Subjects

    Directory of Open Access Journals (Sweden)

    Elena N. Katysheva

    2014-09-01

    Full Text Available This article proposes a model for teaching humanities subjects, which is oriented towards overcoming deformations of the legal consciousness of teenagers. The author provides a description of the model’s aims, content, stages, and procedural characteristics. The author views the learning process as the opportunity to forestall illicit behavior by the underage.

  17. Biomarkers of mitochondrial content in skeletal muscle of healthy young human subjects

    DEFF Research Database (Denmark)

    Larsen, Steen; Nielsen, Joachim; Neigaard Nielsen, Christina

    2012-01-01

    closely associated these commonly used biochemical measures are to muscle mitochondrial content and muscle oxidative capacity (OXPHOS).Sixteen young healthy male subjects were recruited for this study. Subjects completed a graded exercise test to determine maximal oxygen uptake (VO(2peak)) and muscle......Skeletal muscle mitochondrial content varies extensively between human subjects. Biochemical measures of mitochondrial proteins, enzyme activities and lipids are often used as markers of mitochondrial content and muscle oxidative capacity (OXPHOS). The purpose of this study was to determine how...... to muscle oxidative capacity followed by complex II activity.We conclude that cardiolipin content, CS and complex I activity are the biomarkers that exhibit the strongest association to mitochondrial content, while complex IV activity is strongly associated with OXPHOS capacity in human skeletal muscle....

  18. An adaptive breath sampler for use with human subjects with an impaired respiratory function.

    Science.gov (United States)

    Basanta, M; Koimtzis, T; Singh, D; Wilson, I; Thomas, C L P

    2007-02-01

    An adaptive sampler for collecting 2.5 dm(3) samples of exhaled air from human subjects with an impaired respiratory function is described. Pressure in the upper respiratory tract is continuously monitored and the data used to control an automated system to collect select portions of the expired breathing cycle onto a mixed bed Tenax(trade mark) and Carbotrap(trade mark) adsorbent trap for analysis by GC-MS. The sampling approach is intended for use in metabolomic profiling of volatiles in human breath at concentrations greater than microg m(-3). The importance of experimental reproducibility in metabolomic data is emphasised and consequently a high purity air supply is used to maintain a stable exogenous volatile organic compound profile at concentrations in the range 5 to 30 microg m(-3). The results of a 90 day stability study showed that exogenous VOCs were maintained at significantly lower levels (40 times lower for isopropyl alcohol) and with significantly higher reproducibility (80 times lower standard deviation for isopropyl alcohol) than would have been be the case if ambient air had been used. The sampling system was evaluated with healthy controls alongside subjects with chronic obstructive pulmonary disease. Subjects were able to breathe normally with control subjects observed to breathe at a rate of 9 to 17 breaths per minute, compared to 16 to 30 breaths per minute for subjects with COPD. This study presents, for the first time, observations and estimates of intra-subject breath sample reproducibility from human subjects. These reproducibility studies indicated that VOCs in exhaled breath exhibit a variety of dynamic behaviours, with some species recovered with a RSD <30%, while other species were observed to have significantly more variable concentrations, 30 to 130% RSD. The approach was also demonstrated to reliably differentiate the differences in the VOC profiles between alveolar and dead space air.

  19. Cold sore susceptibility gene-1 genotypes affect the expression of herpes labialis in unrelated human subjects.

    Science.gov (United States)

    Kriesel, John D; Bhatia, Amiteshwar; Thomas, Alun

    2014-01-01

    Our group has recently described a gene on human chromosome 21, the Cold Sore Susceptibility Gene-1 (CSSG-1, also known as C21orf91), which may confer susceptibility to frequent cold sores in humans. We present here a genotype-phenotype analysis of CSSG-1 in a new, unrelated human population. Seven hundred fifty-eight human subjects were enrolled in a case/control Cold Sore Study. CSSG-1 genotyping, herpes simplex virus 1 (HSV1) serotyping, demographic and phenotypic data was available from 622 analyzed subjects. Six major alleles (H1-H6) were tested for associations with each of the self-reported phenotypes. The statistical analysis was adjusted for age, sex and ethnicity. Genotype-phenotype associations were analyzed from 388 HSV1-seropositive subjects. There were significant CSSG-1 haplotype effects on annual cold sore outbreaks (P=0.006), lifetime cold sores (P=0.012) and perceived cold sore severity (P=0.012). There were relatively consistent trends toward protection from frequent and severe cold sores among those with the H3 or H5/6 haplotypes, whereas those with H1, H2, and H4 haplotypes tended to have more frequent and more severe episodes. Different alleles of the newly described gene CSSG-1 affect the expression of cold sore phenotypes in this new, unrelated human population, confirming the findings of the previous family-based study.

  20. Reporting of ethical protection in recent oral and maxillofacial surgery research involving human subjects.

    Science.gov (United States)

    Pitak-Arnnop, P; Sader, R; Hervé, C; Dhanuthai, K; Bertrand, J-Ch; Hemprich, A

    2009-07-01

    This retrospective observational study investigated the frequency of reporting ethical approval and informed consent in recently published oral and maxillofacial surgery (OMS) research involving human subjects. All research involving human subjects published in the International Journal of Oral and Maxillofacial Surgery, Journal of Oral and Maxillofacial Surgery, British Journal of Oral and Maxillofacial Surgery, and Journal of Cranio-Maxillofacial Surgery during January to June 2005-2007 were analysed for disclosure of ethical approval by a local ethical committee and obtaining informed consent from the subjects. 534 articles were identified; ethical approval was documented in 118 (22%) and individual patient consent in 135 (25%). 355 reports (67%) did not include a statement on ethical approval or informed consent and only 74 reports (14%) disclosed statements of both. Ethical documentation in retrospective and observational studies was scant; 12% of randomised controlled trials and 38% of non-random trials did not report both of ethical protections. Most recent OMS publications involving humans failed to mention ethical review or subjects' consent. Authors must adhere to the international research ethics guidelines and journal instructions, while editors should play a gatekeeper role to protect research participants, uphold scientific integrity and maintain public trust in the experimental process and OMS profession.

  1. Informed consent in human subject research: a comparison of current international and Nigerian guidelines.

    Science.gov (United States)

    Fadare, Joseph O; Porteri, Corinna

    2010-03-01

    Informed consent is a basic requirement for the conduct of ethical research involving human subjects. Currently, the Helsinki Declaration of the World Medical Association and the International Ethical Guidelines for Biomedical Research of the Council for International Organizations of Medical Sciences (CIOMS) are widely accepted as international codes regulating human subject research and the informed consent sections of these documents are quite important. Debates on the applicability of these guidelines in different socio-cultural settings are ongoing and many workers have advocated the need for national or regional guidelines. Nigeria, a developing country, has recently adopted its national guideline regulating human subject research: the National Health Research Ethics Committee (NHREC) code. A content analysis of the three guidelines was done to see if the Nigerian guidelines confer any additional protection for research subjects. The concept of a Community Advisory Committee in the Nigerian guideline is a novel one that emphasizes research as a community burden and should promote a form of "research friendship" to foster the welfare of research participants. There is also the need for a regular update of the NHREC code so as to address some issues that were not considered in its current version.

  2. Comparison of pharmacokinetics of two fenofibrate tablet formulations in healthy human subjects.

    Science.gov (United States)

    Chachad, Siddharth S; Gole, Milind; Malhotra, Geena; Naidu, Raghu

    2014-06-01

    Fenofibrate is a serum lipid-lowering agent used as an adjunct to diet in patients with hypercholesterolemia and hypertriglyceridemia. The new fenofibrate tablet formulation was developed as a pharmaceutical equivalent to the marketed tablet formulation containing 145 mg. The objective of this study was to compare the pharmacokinetics and safety of 2 tablet formulations containing 145 mg of fenofibrate (CAS number 49562-28-9) in healthy human subjects. The study was a randomized, 2-treatment, 3-period, 3-sequence, single-dose, 3-way crossover, partial replicate bioequivalence study in healthy human subjects under fasting conditions. Eligible subjects received each treatment in a crossover manner according to the randomization schedule. Replicate dosing was conducted for the reference formulation to determine its intrasubject variability. The predose blood sample was taken within 1 hour before dosing, and serial blood sampling was performed up to 72.0 hours' postdose. The analysis of plasma samples for concentrations of fenofibric acid, the active metabolite of fenofibrate, was conducted by using a validated LC-MS/MS method. Bioequivalence was to be concluded if the 90% CIs as constructed were within the range of 80% to 125% for Cmax, AUC0-t, and AUC0-∞ for fenofibric acid. Subjects were monitored for safety and tolerability throughout the study. 15 healthy human subjects between 18 and 45 years of age and having body mass index between 18.5 and 30 kg/m(2) were recruited into the study. The 90% CIs for the test/reference mean ratios of the ln-transformed pharmacokinetic variables Cmax, AUC0-t, and AUC0-∞ were within the conventional bioequivalence range of 80% to 125%. Both formulations were well tolerated after a single oral dose in these healthy male subjects. Both fenofibrate tablet formulations demonstrated equivalent rates and extent of systemic absorption, and hence were considered bioequivalent. Copyright © 2014 Elsevier HS Journals, Inc. All rights

  3. Losses of Humanity in Times of War: The Actions of Alternative Subjects of Justice

    Directory of Open Access Journals (Sweden)

    Julia Estela Monárrez

    2014-12-01

    Full Text Available This article discusses loss of humanity due to violence in Ciudad Juarez (2008–2014 and the actions of alternative subjects of justice – the organized civil society – seeking to address it. This paper resonates with theoretical currents of feminism and humanism, both of which have created a critical apparatus for thinking about social inequality in the context of life, death, and injustice. The discussion draws on the theoretical concepts of discourse societies, necropolitics, private government and actions. With this theoretical structure, the paper seeks to understand the political actions of eight civil society organizations aiming to recover the right to the body, to space and to be a political subject for a community shattered by violence. The paper argues that, through these actions, they helped to prevent crime, enhance public safety and stabilise a society suffering from continued violence due in large part to the war on drugs.

  4. Rapid Evolution from the First Episode of Acute Pancreatitis to Chronic Pancreatitis in Human Subjects

    OpenAIRE

    Elie Aoun; Adam Slivka; Papachristou, Dionysios J.; Whitcomb, David C.; Gleeson, Ferga C; Papachristou, Georgios I

    2007-01-01

    Context Growing evidence suggests that recurrent acute pancreatitis leads to chronic pancreatitis, but this sequence is seldom reported in human subjects. The sentinel acute pancreatitis event hypothesis suggests that an initial episode of acute pancreatitis is the first step in a complicated series of events ultimately leading to chronic pancreatitis. Objective To identify patients who evolved from recurrent acute pancreatitis to chronic pancreatitis. Setting The Severity of Acute Pancreatit...

  5. Effects of air pollutants on the carbon dioxide (CO2) emission rate of human subjects

    DEFF Research Database (Denmark)

    Bako-Biro, Zsolt; Wargocki, Pawel; Wyon, David

    2004-01-01

    Several laboratory studies have shown the negative effects of emissions from typical indoor pollution sources on perceived air quality, SBS symptoms and the performance of office work. The subjects performed typical office tasks at their own pace while they were exposed for several hours...... to different air quality conditions. A re-analysis of the CO2 measurements obtained in two independent studies showed that human CO2 emission rates were affected by air quality (P...

  6. Cholesterol-lowering potential in human subjects of fat from pigs fed rapeseed oil.

    Science.gov (United States)

    Sandström, B; Bügel, S; Lauridsen, C; Nielsen, F; Jensen, C; Skibsted, L H

    2000-08-01

    The possibility of achieving blood-lipid-lowering characteristics of pig fat by increasing the content of unsaturated fat in pig feed was evaluated. Three pig feeding regimens were applied: basal feed (no added fat or vitamin E), basal feed + rapeseed oil (60 g/kg feed), and basal feed + rapeseed oil (60 g/kg) + vitamin E (200 mg/kg). Meat and meat products from the three pig groups were incorporated into diets providing 86 g pig fat/10 MJ. The diets were served to twelve healthy human male subjects for 3 weeks each in a randomised crossover design. The diets prepared from pigs fed rapeseed oil had a lower content of saturated fatty acids (approximately 9 v. 11% of energy) and a higher content of polyunsaturated fatty acids (approximately 6 v. 4% of energy) than the diet prepared from pigs fed the basal feed. Diets based on fat from pigs fed the rapeseed oil resulted in significantly lower (approximately 4%, P = 0.019) total serum cholesterol concentration compared with the diet from pigs fed the basal feed. No differences were observed in LDL-, HDL- or VLDL-cholesterol, or in triacylglycerol or VLDL-triacylglycerol concentrations. Addition of vitamin E to the pig feed resulted in only a minor increase in vitamin E content in the human subjects' diet and the vitamin E content was low in all three pig diets. Plasma vitamin E concentration in the human subjects at the end of the period with diets from pigs fed rapeseed oil without vitamin E was significantly lower (P = 0.04) than in the other two diet periods. In conclusion, an increased content of rapeseed oil in pig feed changes the fatty acid composition of the pig fat in a way that has a potential to reduce blood cholesterol concentrations in human subjects. However, intake of pig fat with a higher content of unsaturated fatty acids needs to be matched by a higher dietary intake of vitamin E.

  7. Thermal Injury in Human Subjects Due to 94-GHz Radio Frequency Radiation Exposures

    Science.gov (United States)

    2016-02-24

    AFRL-RH-FS-TR-2016-0001 Thermal Injury in Human Subjects Due to 94-GHz Radio Frequency Radiation Exposures James E. Parker General...them. This report was cleared for public release by the 88th ABW Public Affairs Office and is available to the general public, including foreign ...This report is published in the interest of scientific and technical information exchange , and its

  8. Simultaneous transdermal extraction of glucose and lactate from human subjects by reverse iontophoresis

    OpenAIRE

    Connolly,Patricia

    2008-01-01

    Tak S Ching1, Patricia Connolly21Asia University, Taiwan; 2Bioengineering Unit, University of Strathclyde, Glasgow, Scotland, UKAbstract: This study investigated the possibility of simultaneously extracting glucose and lactate from human subjects, at the same skin location, using transdermal reverse iontophoresis. Transdermal monitoring using iontophoresis is made possible by the skin’s permeability to small molecules and the nanoporous and microporous nature of the structure of ski...

  9. Ethical review of research on human subjects at Unilever: reflections on governance.

    Science.gov (United States)

    Sheehan, Mark; Marti, Vernon; Roberts, Tony

    2014-07-01

    This article considers the process of ethical review of research on human subjects at a very large multinational consumer products company. The commercial context of this research throws up unique challenges and opportunities that make the ethics of the process of oversight distinct from mainstream medical research. Reflection on the justification of governance processes sheds important, contrasting light on the ethics of governance of other forms and context of research. © 2013 John Wiley & Sons Ltd.

  10. Oral sensitivity to fatty acids, food consumption and BMI in human subjects.

    Science.gov (United States)

    Stewart, Jessica E; Feinle-Bisset, Christine; Golding, Matthew; Delahunty, Conor; Clifton, Peter M; Keast, Russell S J

    2010-07-01

    Fatty acids are the chemical moieties that are thought to stimulate oral nutrient sensors, which detect the fat content of foods. In animals, oral hypersensitivity to fatty acids is associated with decreased fat intake and body weight. The aims of the present study were to investigate oral fatty acid sensitivity, food selection and BMI in human subjects. The study included two parts; study 1 established in thirty-one subjects (29 (sem 1.4) years, 22.8 (sem 0.5) kg/m2) taste thresholds using 3-AFC (3-Alternate Forced Choice Methodology) for oleic, linoleic and lauric acids, and quantified oral lipase activity. During study 2, fifty-four subjects (20 (sem 0.3) years, 21.5 (sem 0.4) kg/m2) were screened for oral fatty acid sensitivity using oleic acid (1.4 mm), and they were defined as hypo- or hypersensitive via triplicate triangle tests. Habitual energy and macronutrient intakes were quantified from 2 d diet records, and BMI was calculated from height and weight. Subjects also completed a fat ranking task using custard containing varying amounts (0, 2, 6 and 10 %) of fat. Study 1 reported median lipase activity as 2 mumol fatty acids/min per l, and detection thresholds for oleic, linoleic and lauric acids were 2.2 (sem 0.1), 1.5 (sem 0.1) and 2.6 (sem 0.3) mm. Study 2 identified twelve hypersensitive subjects, and hypersensitivity was associated with lower energy and fat intakes, lower BMI (P acid was correlated to performance in the fat ranking task (r 0.4, P fatty acid hypersensitivity is associated with lower energy and fat intakes and BMI, and it may serve as a factor that influences fat consumption in human subjects.

  11. Mechanical work as an indirect measure of subjective costs influencing human movement.

    Science.gov (United States)

    Zelik, Karl E; Kuo, Arthur D

    2012-01-01

    To descend a flight of stairs, would you rather walk or fall? Falling seems to have some obvious disadvantages such as the risk of pain or injury. But the preferred strategy of walking also entails a cost for the use of active muscles to perform negative work. The amount and distribution of work a person chooses to perform may, therefore, reflect a subjective valuation of the trade-offs between active muscle effort and other costs, such as pain. Here we use a simple jump landing experiment to quantify the work humans prefer to perform to dissipate the energy of landing. We found that healthy normal subjects (N = 8) preferred a strategy that involved performing 37% more negative work than minimally necessary (Pheights. This then required additional positive work to return to standing rest posture, highlighting the cost of this preference. Subjects were also able to modulate the amount of landing work, and its distribution between active and passive tissues. When instructed to land softly, they performed 76% more work than necessary (Pwork, with more of it performed passively through soft tissue deformations (at least 30% in stiff landings vs. 16% preferred). During jump landings, humans appear not to minimize muscle work, but instead choose to perform a consistent amount of extra work, presumably to avoid other subjective costs. The degree to which work is not minimized may indirectly quantify the relative valuation of costs that are otherwise difficult to measure.

  12. Twenty lectures on thermodynamics

    CERN Document Server

    Buchdahl, H A

    2013-01-01

    Twenty Lectures on Thermodynamics is a course of lectures, parts of which the author has given various times over the last few years. The book gives the readers a bird's eye view of phenomenological and statistical thermodynamics. The book covers many areas in thermodynamics such as states and transition; adiabatic isolation; irreversibility; the first, second, third and Zeroth laws of thermodynamics; entropy and entropy law; the idea of the application of thermodynamics; pseudo-states; the quantum-static al canonical and grand canonical ensembles; and semi-classical gaseous systems. The text

  13. Vestibular implantation and longitudinal electrical stimulation of the semicircular canal afferents in human subjects.

    Science.gov (United States)

    Phillips, James O; Ling, Leo; Nie, Kaibao; Jameyson, Elyse; Phillips, Christopher M; Nowack, Amy L; Golub, Justin S; Rubinstein, Jay T

    2015-06-01

    Animal experiments and limited data in humans suggest that electrical stimulation of the vestibular end organs could be used to treat loss of vestibular function. In this paper we demonstrate that canal-specific two-dimensionally (2D) measured eye velocities are elicited from intermittent brief 2 s biphasic pulse electrical stimulation in four human subjects implanted with a vestibular prosthesis. The 2D measured direction of the slow phase eye movements changed with the canal stimulated. Increasing pulse current over a 0-400 μA range typically produced a monotonic increase in slow phase eye velocity. The responses decremented or in some cases fluctuated over time in most implanted canals but could be partially restored by changing the return path of the stimulation current. Implantation of the device in Meniere's patients produced hearing and vestibular loss in the implanted ear. Electrical stimulation was well tolerated, producing no sensation of pain, nausea, or auditory percept with stimulation that elicited robust eye movements. There were changes in slow phase eye velocity with current and over time, and changes in electrically evoked compound action potentials produced by stimulation and recorded with the implanted device. Perceived rotation in subjects was consistent with the slow phase eye movements in direction and scaled with stimulation current in magnitude. These results suggest that electrical stimulation of the vestibular end organ in human subjects provided controlled vestibular inputs over time, but in Meniere's patients this apparently came at the cost of hearing and vestibular function in the implanted ear.

  14. Physiological and subjective evaluation of a human-robot object hand-over task.

    Science.gov (United States)

    Dehais, Frédéric; Sisbot, Emrah Akin; Alami, Rachid; Causse, Mickaël

    2011-11-01

    In the context of task sharing between a robot companion and its human partners, the notions of safe and compliant hardware are not enough. It is necessary to guarantee ergonomic robot motions. Therefore, we have developed Human Aware Manipulation Planner (Sisbot et al., 2010), a motion planner specifically designed for human-robot object transfer by explicitly taking into account the legibility, the safety and the physical comfort of robot motions. The main objective of this research was to define precise subjective metrics to assess our planner when a human interacts with a robot in an object hand-over task. A second objective was to obtain quantitative data to evaluate the effect of this interaction. Given the short duration, the "relative ease" of the object hand-over task and its qualitative component, classical behavioral measures based on accuracy or reaction time were unsuitable to compare our gestures. In this perspective, we selected three measurements based on the galvanic skin conductance response, the deltoid muscle activity and the ocular activity. To test our assumptions and validate our planner, an experimental set-up involving Jido, a mobile manipulator robot, and a seated human was proposed. For the purpose of the experiment, we have defined three motions that combine different levels of legibility, safety and physical comfort values. After each robot gesture the participants were asked to rate them on a three dimensional subjective scale. It has appeared that the subjective data were in favor of our reference motion. Eventually the three motions elicited different physiological and ocular responses that could be used to partially discriminate them. Copyright © 2011 Elsevier Ltd and the Ergonomics Society. All rights reserved.

  15. A Single Human Papillomavirus Vaccine Dose Improves B Cell Memory in Previously Infected Subjects

    Directory of Open Access Journals (Sweden)

    Erin M. Scherer

    2016-08-01

    Full Text Available Although licensed human papillomavirus (HPV vaccines are most efficacious in persons never infected with HPV, they also reduce infection and disease in previously infected subjects, indicating natural immunity is not entirely protective against HPV re-infection. The aim of this exploratory study was to examine the B cell memory elicited by HPV infection and evaluate whether vaccination merely boosts antibody (Ab levels in previously infected subjects or also improves the quality of B cell memory. Toward this end, the memory B cells (Bmem of five unvaccinated, HPV-seropositive subjects were isolated and characterized, and subject recall responses to a single HPV vaccine dose were analyzed. Vaccination boosted Ab levels 24- to 930-fold (median 77-fold and Bmem numbers 3- to 27-fold (median 6-fold. In addition, Abs cloned from naturally elicited Bmem were generally non-neutralizing, whereas all those isolated following vaccination were neutralizing. Moreover, Ab and plasmablast responses indicative of memory recall responses were only observed in two subjects. These results suggest HPV vaccination augments both the magnitude and quality of natural immunity and demonstrate that sexually active persons could also benefit from HPV vaccination. This study may have important public policy implications, especially for the older ‘catch-up’ group within the vaccine's target population.

  16. The Belmont Report. Ethical principles and guidelines for the protection of human subjects of research.

    Science.gov (United States)

    2014-01-01

    On July 12, 1974, the National Research Act (Pub. L. 93-348) was signed into law, thereby creating the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. One of the charges to the Commission was to identify the basic ethical principles that should underlie the conduct of biomedical and behavioral research involving human subjects and to develop guidelines which should be followed to assure that such research is conducted in accordance with those principles. In carrying out the above, the Commission was directed to consider: (a) the boundaries between biomedical and behavioral research and the accepted and routine practice of medicine, (b) the role of assessment of risk-benefit criteria in the determination of the appropriateness of research involving human subjects, (c) appropriate guidelines for the selection of human subjects for participation in such research and (d) the nature and definition of informed consent in various research settings. The Belmont Report attempts to summarize the basic ethical principles identified by the Commission in the course of its deliberations. It is the outgrowth of an intensive four-day period of discussions that were held in February 1976 at the Smithsonian Institution's Belmont Conference Center supplemented by the monthly deliberations of the Commission that were held over a period of nearly four years. It is a statement of basic ethical principles and guidelines that should assist in resolving the ethical problems that surround the conduct of research with human subjects. By publishing the Report in the Federal Register, and providing reprints upon request, the Secretary intends that it may be made readily available to scientists, members of Institutional Review Boards, and Federal employees. The two-volume Appendix, containing the lengthy reports of experts and specialists who assisted the Commission in fulfilling this part of its charge, is available as DHEW Publication No. (OS

  17. A relation between calculated human body exergy consumption rate and subjectively assessed thermal sensation

    DEFF Research Database (Denmark)

    Simone, Angela; Kolarik, Jakub; Iwamatsu, Toshiya

    2011-01-01

    . Generally, the relationship between air temperature and the exergy consumption rate, as a first approximation, shows an increasing trend. Taking account of both convective and radiative heat exchange between the human body and the surrounding environment by using the calculated operative temperature, exergy...... consumption rates increase as the operative temperature increases above 24 ◦C or decreases below 22 ◦C. With the data available so far, a second-order polynomial relationship between thermal sensation and the exergy consumption rate was established....... occupants, it is reasonable to consider both the exergy flows in building and those within the human body. Until now, no data have been available on the relation between human-body exergy consumption rates and subjectively assessed thermal sensation. The objective of the present work was to relate thermal...

  18. Mechanical work as an indirect measure of subjective costs influencing human movement.

    Directory of Open Access Journals (Sweden)

    Karl E Zelik

    Full Text Available To descend a flight of stairs, would you rather walk or fall? Falling seems to have some obvious disadvantages such as the risk of pain or injury. But the preferred strategy of walking also entails a cost for the use of active muscles to perform negative work. The amount and distribution of work a person chooses to perform may, therefore, reflect a subjective valuation of the trade-offs between active muscle effort and other costs, such as pain. Here we use a simple jump landing experiment to quantify the work humans prefer to perform to dissipate the energy of landing. We found that healthy normal subjects (N = 8 preferred a strategy that involved performing 37% more negative work than minimally necessary (P<0.001 across a range of landing heights. This then required additional positive work to return to standing rest posture, highlighting the cost of this preference. Subjects were also able to modulate the amount of landing work, and its distribution between active and passive tissues. When instructed to land softly, they performed 76% more work than necessary (P<0.001, with a higher proportion from active muscles (89% vs. 84%, P<0.001. Stiff-legged landings, performed by one subject for demonstration, exhibited close to the minimum of work, with more of it performed passively through soft tissue deformations (at least 30% in stiff landings vs. 16% preferred. During jump landings, humans appear not to minimize muscle work, but instead choose to perform a consistent amount of extra work, presumably to avoid other subjective costs. The degree to which work is not minimized may indirectly quantify the relative valuation of costs that are otherwise difficult to measure.

  19. Quantifying human subjective experience and social interaction using the eXperience Induction Machine.

    Science.gov (United States)

    Bernardet, Ulysses; Väljamäe, Aleksander; Inderbitzin, Martin; Wierenga, Sytse; Mura, Anna; Verschure, Paul F M J

    2011-06-30

    With the advance of novel brain imaging technology more correlations between complex human properties and the neuronal substrate can be assessed. However, thus far, not many well-validated paradigms exist that would allow for a systematic and quantitative exploration of these phenomena. For instance, despite the rapid technological advances in the domain of mixed and virtual reality systems, a fundamental issue remains how we can define and quantify "presence". A standard approach has been to use questionnaires and self-report measures. However, it has been well established that humans' capabilities to access and externalize their internal states are limited. Hence, we have investigated the question whether other less subjective measures can be devised that can corroborate subjective self-reports on presence. In particular, we have developed a quantitative recollection task that assesses the ability of human subjects (N=40) to recollect the factual structure and organization of a structured and fully controlled experience in a human accessible mixed reality space, the eXperience Induction Machine (XIM). In this structured experience - referred to as the "Autodemo"--a virtual guide explains the key elements and properties of XIM while the user is able to freely move around in the space. To evaluate the users' experience and the amount of factual information retained about the Autodemo, we used the ITC-SOPI questionnaire and a recall test specifically designed for the Autodemo. We found significant correlations between spatial presence and engagement factors of ITC-SOPI and recall performance. Moreover we observed an interaction with the participants' gender. Our results show that we can assess correlates of "presence" by focusing on other dependent measures such as those related to memory and performance. Additionally, our work exemplifies how virtual and mixed reality systems provide new ways to address fundamental questions in psychology and cognitive neuroscience

  20. Twenty Years of KSHV

    Directory of Open Access Journals (Sweden)

    Yuan Chang

    2014-11-01

    Full Text Available Twenty years ago, Kaposi’s sarcoma (KS was the oncologic counterpart to Winston Churchill’s Russia: a riddle, wrapped in a mystery, inside an enigma. First described by Moritz Kaposi in 1872, who reported it to be an aggressive skin tumor, KS became known over the next century as a slow-growing tumor of elderly men—in fact, most KS patients were expected to die with the tumor rather than from it. Nevertheless, the course and manifestations of the disease varied widely in different clinical contexts. The puzzle of KS came to the forefront as a harbinger of the AIDS epidemic. The articles in this issue of Viruses recount progress made in understanding Kaposi’s sarcoma herpesvirus (KSHV since its initial description in 1994.

  1. Digital music exposure reliably induces temporary threshold shift (TTS) in normal hearing human subjects

    Science.gov (United States)

    Le Prell, C. G.; Dell, S.; Hensley, B.; Hall, J. W.; Campbell, K. C. M.; Antonelli, P. J.; Green, G. E.; Miller, J. M.; Guire, K.

    2012-01-01

    Objectives One of the challenges for evaluating new otoprotective agents for potential benefit in human populations is availability of an established clinical paradigm with real world relevance. These studies were explicitly designed to develop a real-world digital music exposure that reliably induces temporary threshold shift (TTS) in normal hearing human subjects. Design Thirty-three subjects participated in studies that measured effects of digital music player use on hearing. Subjects selected either rock or pop music, which was then presented at 93–95 (n=10), 98–100 (n=11), or 100–102 (n=12) dBA in-ear exposure level for a period of four hours. Audiograms and distortion product otoacoustic emissions (DPOAEs) were measured prior to and after music exposure. Post-music tests were initiated 15 min, 1 hr 15 min, 2 hr 15 min, and 3 hr 15 min after the exposure ended. Additional tests were conducted the following day and one week later. Results Changes in thresholds after the lowest level exposure were difficult to distinguish from test-retest variability; however, TTS was reliably detected after higher levels of sound exposure. Changes in audiometric thresholds had a “notch” configuration, with the largest changes observed at 4 kHz (mean=6.3±3.9dB; range=0–13 dB). Recovery was largely complete within the first 4 hours post-exposure, and all subjects showed complete recovery of both thresholds and DPOAE measures when tested 1-week post-exposure. Conclusions These data provide insight into the variability of TTS induced by music player use in a healthy, normal-hearing, young adult population, with music playlist, level, and duration carefully controlled. These data confirm the likelihood of temporary changes in auditory function following digital music player use. Such data are essential for the development of a human clinical trial protocol that provides a highly powered design for evaluating novel therapeutics in human clinical trials. Care must be

  2. Digital music exposure reliably induces temporary threshold shift in normal-hearing human subjects.

    Science.gov (United States)

    Le Prell, Colleen G; Dell, Shawna; Hensley, Brittany; Hall, James W; Campbell, Kathleen C M; Antonelli, Patrick J; Green, Glenn E; Miller, James M; Guire, Kenneth

    2012-01-01

    One of the challenges for evaluating new otoprotective agents for potential benefit in human populations is the availability of an established clinical paradigm with real-world relevance. These studies were explicitly designed to develop a real-world digital music exposure that reliably induces temporary threshold shift (TTS) in normal-hearing human subjects. Thirty-three subjects participated in studies that measured effects of digital music player use on hearing. Subjects selected either rock or pop music, which was then presented at 93 to 95 (n = 10), 98 to 100 (n = 11), or 100 to 102 (n = 12) dBA in-ear exposure level for a period of 4 hr. Audiograms and distortion product otoacoustic emissions (DPOAEs) were measured before and after music exposure. Postmusic tests were initiated 15 min, 1 hr 15 min, 2 hr 15 min, and 3 hr 15 min after the exposure ended. Additional tests were conducted the following day and 1 week later. Changes in thresholds after the lowest-level exposure were difficult to distinguish from test-retest variability; however, TTS was reliably detected after higher levels of sound exposure. Changes in audiometric thresholds had a "notch" configuration, with the largest changes observed at 4 kHz (mean = 6.3 ± 3.9 dB; range = 0-14 dB). Recovery was largely complete within the first 4 hr postexposure, and all subjects showed complete recovery of both thresholds and DPOAE measures when tested 1 week postexposure. These data provide insight into the variability of TTS induced by music-player use in a healthy, normal-hearing, young adult population, with music playlist, level, and duration carefully controlled. These data confirm the likelihood of temporary changes in auditory function after digital music-player use. Such data are essential for the development of a human clinical trial protocol that provides a highly powered design for evaluating novel therapeutics in human clinical trials. Care must be taken to fully inform potential subjects in

  3. Development and validation of a biomarker for diarrhea-predominant irritable bowel syndrome in human subjects.

    Directory of Open Access Journals (Sweden)

    Mark Pimentel

    Full Text Available Diarrhea-predominant irritable bowel syndrome (IBS is diagnosed through clinical criteria after excluding "organic" conditions, and can be precipitated by acute gastroenteritis. Cytolethal distending toxin B (CdtB is produced by bacteria that cause acute gastroenteritis, and a post-infectious animal model demonstrates that host antibodies to CdtB cross-react with vinculin in the host gut, producing an IBS-like phenotype. Therefore, we assessed circulating anti-CdtB and anti-vinculin antibodies as biomarkers for D-IBS in human subjects. Subjects with D-IBS based on Rome criteria (n=2375 were recruited from a large-scale multicenter clinical trial for D-IBS (TARGET 3. Subjects with inflammatory bowel disease (IBD (n=142, subjects with celiac disease (n=121, and healthy controls (n=43 were obtained for comparison. Subjects with IBD and celiac disease were recruited based on the presence of intestinal complaints and histologic confirmation of chronic inflammatory changes in the colon or small intestine. Subjects with celiac disease were also required to have an elevated tTG and biopsy. All subjects were aged between 18 and 65 years. Plasma levels of anti-CdtB and anti-vinculin antibodies were determined by ELISA, and compared between groups. Anti-CdtB titers were significantly higher in D-IBS subjects compared to IBD, healthy controls and celiac disease (P<0.001. Anti-vinculin titers were also significantly higher in IBS (P<0.001 compared to the other groups. The area-under-the-receiver operating curves (AUCs were 0.81 and 0.62 for diagnosis of D-IBS against IBD for anti-CdtB and anti-vinculin, respectively. Both tests were less specific in differentiating IBS from celiac disease. Optimization demonstrated that for anti-CdtB (optical density≥2.80 the specificity, sensitivity and likelihood ratio were 91.6%, 43.7 and 5.2, respectively, and for anti-vinculin (OD≥1.68 were 83.8%, 32.6 and 2.0, respectively. These results confirm that anti-CdtB and

  4. Assessing the abuse potential of methylphenidate in nonhuman and human subjects: a review.

    Science.gov (United States)

    Kollins, S H; MacDonald, E K; Rush, C R

    2001-03-01

    Methylphenidate (MPH) is widely used for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in children, adolescents, and adults. Methylphenidate is clearly effective for the treatment of ADHD, but there is controversy as to whether it has significant abuse potential like other psychostimulants (e.g., D-amphetamine and cocaine). In general, the drug is believed to be abused at rates much lower than those for other stimulants. The present review examines studies that investigated the behavioral pharmacological profile of methylphenidate and discusses how results from these studies address its abuse liability. Using MEDLINE search terms methylphenidate, drug discrimination, reinforcement, self-administration, subjective effects, subject-rated effects, abuse potential, and abuse liability, along with a review of the references from identified articles, 60 studies were located in which the reinforcing, discriminative-stimulus, or subjective effects of methylphenidate were directly assessed in nonhumans or humans. Forty-eight (80.0%) of the studies reviewed indicate that methylphenidate either functions in a manner similar to D-amphetamine or cocaine (e.g., functions as a reinforcer, substitutes fully in drug discrimination experiments), or produces a pattern of subjective effects suggestive of abuse potential. The results are discussed as they pertain to factors that may account for the apparent discrepancy in abuse rates between methylphenidate and other stimulants, including characterization of actual abuse rates, defining abuse and misuse, pharmacokinetic factors, and validity of abuse liability assays.

  5. Dopamine D3 receptor-preferring agonist enhances the subjective effects of cocaine in humans.

    Science.gov (United States)

    Newton, Thomas F; Haile, Colin N; Mahoney, James J; Shah, Ravi; Verrico, Christopher D; De La Garza, Richard; Kosten, Thomas R

    2015-11-30

    Pramipexole is a D3 dopamine receptor-preferring agonist indicated for the treatment of Parkinson disease. Studies associate pramipexole with pathological gambling and impulse control disorders suggesting a role for D3 receptors in reinforcement processes. Clinical studies showed pramipexole decreased cocaine craving and reversed central deficits in individuals with cocaine use disorder. Preclinical studies have shown acute administration of pramipexole increases cocaine's reinforcing effects whereas other reports suggest chronic pramipexole produces tolerance to cocaine. In a randomized, double-blind, placebo-controlled study we examined the impact of pramipexole treatment on the subjective effects produced by cocaine in volunteers with cocaine use disorder. Volunteers received pramipexole titrated up to 3.0mg/d or placebo over 15 days. Participants then received intravenous cocaine (0, 20 and 40mg) on day 15. Cardiovascular and subjective effects were obtained with visual analog scales at time points across the session. Pramipexole alone increased peak heart rate following saline and diastolic blood pressure following cocaine. Pramipexole produced upwards of two-fold increases in positive subjective effects ratings following cocaine. These results indicate that chronic D3 receptor activation increases the subjective effects of cocaine in humans. Caution should be used when prescribing pramipexole to patients that may also use cocaine.

  6. Simultaneous transdermal extraction of glucose and lactate from human subjects by reverse iontophoresis.

    Science.gov (United States)

    Ching, Tak S; Connolly, Patricia

    2008-01-01

    This study investigated the possibility of simultaneously extracting glucose and lactate from human subjects, at the same skin location, using transdermal reverse iontophoresis. Transdermal monitoring using iontophoresis is made possible by the skin's permeability to small molecules and the nanoporous and microporous nature of the structure of skin. The study was intended to provide information which could be used to develop a full, biosensor-based, monitoring system for multiple parameters from transdermal extraction. As a precursor to the human study, in vitro reverse iontophoresis experiments were performed in an artificial skin system to establish the optimum current waveforms to be applied during iontophoresis. In the human study, a bipolar DC current waveform (with reversal of the electrode current direction every 15 minutes) was applied to ten healthy volunteers via skin electrodes and utilized for simultaneous glucose and lactate transdermal extraction at an applied current density of 300 microA/cm2. Glucose and lactate were successfully extracted through each subject's skin into the conducting gel that formed part of each iontophoresis electrode. The results suggest that it will be possible to noninvasively and simultaneously monitor glucose and lactate levels in patients using this approach and this could have future applications in diagnostic monitoring for a variety of medical conditions.

  7. Photoacoustic physio-chemical analysis of liver conditions in animal and human subjects

    Science.gov (United States)

    Wang, Xueding; Xu, Guan; Tian, Chao; Wan, Shanshan; Welling, Theodore H.; Lok, Anna S. F.; Rubin, Jonathan M.

    2016-03-01

    Non-alcoholic fatty liver disease (NAFLD) is a common liver disease affecting 30% of the population in the United States. Biopsy is the gold standard for diagnosing NAFLD. Liver histology assesses the amount of fat, and determines type and extent of cell injury, inflammation and fibrosis. However, liver biopsy is invasive and is limited by sampling error. Current radiological diagnostic modalities can evaluate the 'physical' morphology in liver by quantifying the backscattered US signals, but cannot interrogate the 'histochemical' components forming these backscatterers. For example, ultrasound (US) imaging can detect the presence of fat but cannot differentiate steatosis alone from steatohepatitis. Our previous study of photoacoustic physiochemical analysis (PAPCA) has demonstrated that this method can characterize the histological changes in livers during the progression of NAFLD in animal models. In this study, we will further validate PAPCA with human livers. Ex vivo human liver samples with steatosis, fibrosis and cirrhosis will be scanned using optical illumination at wavelengths of 680-1700 nm and compared to histology results. In vivo study on human subjects with confirmed steatosis is planned using our PA-ultrasound (US) parallel imaging system based on Verasonic US imaging flatform with an L7-4 probe. 10 mJ/cm2 per pulse optical energy at 755 nm will be delivered to the skin surface, which is under the safety limit of American National Standard Institute. Preliminary study with ex vivo human tissue has demonstrated the potential of the proposed approach in differentiating human liver conditions.

  8. Adaptive correction of human-eye aberrations in a subjective feedback loop.

    Science.gov (United States)

    Vdovin, G; Loktev, M; Simonov, A; Kijko, V; Volkov, S

    2005-04-01

    An adaptive optical system with a subjective feedback loop is used to improve the visual acuity and to determine the aberrations of the human eye. Corrections of as many as 12 low-order aberration modes were made, based on the perceived sharpness of the test object observed through the adaptive optical system. The acuity of vision was improved by adjustment of the weights of the orthogonal modes produced by a deformable mirror. Objective measurements of the correcting aspherical figures, obtained in independent subjective correction cycles for one person, demonstrated good repeatability. Participants in the study with strong ocular aberrations reported moderate to significant improvement of their visual acuity, estimated with the U.S. Air Force 1951 acuity chart.

  9. The motor cortex drives the muscles during walking in human subjects

    DEFF Research Database (Denmark)

    Petersen, Tue Hvass; Willerslev-Olsen, Maria; Conway, B A;

    2012-01-01

    to address if activity arising in the motor cortex contributes to the muscle activity during gait. Nine healthy human subjects walked on a treadmill at a speed of 3.5–4 km h(-1). Seven of the subjects in addition walked at a speed of 1 km h(-1). Significant coupling between EEG recordings over the leg motor...... area and EMG from the anterior tibial muscle was found in the frequency band 24–40 Hz prior to heel strike during the swing phase of walking. This signifies that rhythmic cortical activity in the 24–40 Hz frequency band is transmitted via the corticospinal tract to the active muscles during walking...

  10. Pregnant woman and road safety: experimental crash test with post mortem human subject.

    Science.gov (United States)

    Delotte, Jerome; Behr, Michel; Thollon, Lionel; Arnoux, Pierre-Jean; Baque, Patrick; Bongain, Andre; Brunet, Christian

    2008-05-01

    Trauma affect between 3 and 7% of all pregnancies in industrialized countries, and the leading cause of these traumas is car crashes. The difficulty to appreciate physiologic and anatomic changes occurring during pregnancy explain that majority of studies were not based on anatomical data. We present a protocol to create a realistic anatomical model of pregnant woman using a post mortem human subject (PMHS). We inserted a physical model of the gravid uterus into the pelvis of a PMHS. 3D acceleration sensors were placed on the subject to measure the acceleration on different body segments. We simulated three frontal impact situations at 20 km/h between two average European cars. Two main kinematics events were identified as possible causes of injuries: lap belt loading and backrest impact. Cadaver experiments provide one interesting complementary approach to study injury mechanisms related to road accidents involving pregnant women. This anatomical accuracy makes it possible to progress in the field of safety devices.

  11. Effects of air pollutants on the carbon dioxide (CO2) emission rate of human subjects

    DEFF Research Database (Denmark)

    Bako-Biro, Zsolt; Wargocki, Pawel; Wyon, David

    2004-01-01

    Several laboratory studies have shown the negative effects of emissions from typical indoor pollution sources on perceived air quality, SBS symptoms and the performance of office work. The subjects performed typical office tasks at their own pace while they were exposed for several hours to diffe......Several laboratory studies have shown the negative effects of emissions from typical indoor pollution sources on perceived air quality, SBS symptoms and the performance of office work. The subjects performed typical office tasks at their own pace while they were exposed for several hours...... to different air quality conditions. A re-analysis of the CO2 measurements obtained in two independent studies showed that human CO2 emission rates were affected by air quality (P...

  12. Where are human subjects in Big Data research? The emerging ethics divide

    Directory of Open Access Journals (Sweden)

    Jacob Metcalf

    2016-06-01

    Full Text Available There are growing discontinuities between the research practices of data science and established tools of research ethics regulation. Some of the core commitments of existing research ethics regulations, such as the distinction between research and practice, cannot be cleanly exported from biomedical research to data science research. Such discontinuities have led some data science practitioners and researchers to move toward rejecting ethics regulations outright. These shifts occur at the same time as a proposal for major revisions to the Common Rule—the primary regulation governing human-subjects research in the USA—is under consideration for the first time in decades. We contextualize these revisions in long-running complaints about regulation of social science research and argue data science should be understood as continuous with social sciences in this regard. The proposed regulations are more flexible and scalable to the methods of non-biomedical research, yet problematically largely exclude data science methods from human-subjects regulation, particularly uses of public datasets. The ethical frameworks for Big Data research are highly contested and in flux, and the potential harms of data science research are unpredictable. We examine several contentious cases of research harms in data science, including the 2014 Facebook emotional contagion study and the 2016 use of geographical data techniques to identify the pseudonymous artist Banksy. To address disputes about application of human-subjects research ethics in data science, critical data studies should offer a historically nuanced theory of “data subjectivity” responsive to the epistemic methods, harms and benefits of data science and commerce.

  13. Where are human subjects in Big Data research? The emerging ethics divide

    Directory of Open Access Journals (Sweden)

    Jacob Metcalf

    2016-06-01

    Full Text Available There are growing discontinuities between the research practices of data science and established tools of research ethics regulation. Some of the core commitments of existing research ethics regulations, such as the distinction between research and practice, cannot be cleanly exported from biomedical research to data science research. Such discontinuities have led some data science practitioners and researchers to move toward rejecting ethics regulations outright. These shifts occur at the same time as a proposal for major revisions to the Common Rule—the primary regulation governing human-subjects research in the USA—is under consideration for the first time in decades. We contextualize these revisions in long-running complaints about regulation of social science research and argue data science should be understood as continuous with social sciences in this regard. The proposed regulations are more flexible and scalable to the methods of non-biomedical research, yet problematically largely exclude data science methods from human-subjects regulation, particularly uses of public datasets. The ethical frameworks for Big Data research are highly contested and in flux, and the potential harms of data science research are unpredictable. We examine several contentious cases of research harms in data science, including the 2014 Facebook emotional contagion study and the 2016 use of geographical data techniques to identify the pseudonymous artist Banksy. To address disputes about application of human-subjects research ethics in data science, critical data studies should offer a historically nuanced theory of “data subjectivity” responsive to the epistemic methods, harms and benefits of data science and commerce.

  14. Sumatriptan does not affect arteriovenous oxygen differences in jugular and cubital veins in normal human subjects

    DEFF Research Database (Denmark)

    Wienecke, T.; Hansen, J.M.; Petersen, J.;

    2008-01-01

    Arteriovenous anastomoses (AVAs) may open up during migraine attacks. In studies with anaesthetized and bilaterally vagosympatectomized pigs, triptans reduce AVA blood flow and increase the arteriovenous O-2 difference (AVDO(2)). To investigate whether subcutaneous sumatriptan 6 mg could induce...... changes in the AVDO(2), we measured the AVDO(2) in the external jugular vein in healthy subjects. We also measured the AVDO(2) in the internal jugular and cubital veins. There were no changes in AVDO(2) after subcutaneous sumatriptan, probably because AVA blood flow is limited in humans with an intact...

  15. Plutonium stories. [Stories of subjects of Department of Energy human experimentation

    Energy Technology Data Exchange (ETDEWEB)

    Presented here are thumbnail sketches of six people who received injections of plutonium in an Atomic Energy Commission experiment, presumably designed to assess the biological effects of radiation on the human body. The information was drawn from a copyrighted series in the Albuquerque Tribune, a newspaper that counts Los Alamos within its circulation area. Eighteen subjects were involved in this plutonium experiment. They received their injections at the Manhattan Project hospital in Oak Ridge, Tennessee and at prestigious teaching hospitals--the University of California Hospital in San Francisco, Billings Hospital at the University of Chicago, and Strong Memorial Hospital at the University of Rochester.

  16. Chapter Twenty Six

    African Journals Online (AJOL)

    User

    wisdom, that is, the results of human efforts to understand life and the ... Some of the characteristics of Hebrew poetry include parallelism, figurative language, .... each line in these 3 verses is really saying the same thing in a repetitive fashion.

  17. The effect of feeding frequency on insulin and ghrelin responses in human subjects

    DEFF Research Database (Denmark)

    Solomon, Thomas; Chambers, Edward S; Jeukendrup, Asker E

    2008-01-01

    Recent work shows that increased meal frequency reduces ghrelin responses in sheep. Human research suggests there is an interaction between insulin and ghrelin. The effect of meal frequency on this interaction is unknown. Therefore, we investigated the effect of feeding frequency on insulin...... and ghrelin responses in human subjects. Five healthy male volunteers were recruited from the general population: age 24 (SEM 2)years, body mass 75.7 (SEM 3.2) kg and BMI 23.8 (SEM 0.8) kg/m(2). Volunteers underwent three 8-h feeding regimens: fasting (FAST); low-frequency(two) meal ingestion (LOFREQ(MEAL......)); high-frequency (twelve) meal ingestion (HIFREQ(MEAL)). Meals were equi-energetic within trials,consisting of 64% carbohydrate, 23% fat and 13% protein. Total energy intake was equal between feeding trials. Total area under the curve for serum insulin and plasma ghrelin responses did not differ between...

  18. Top at Twenty

    CERN Document Server

    2015-01-01

    The "Top at Twenty" workshop is dedicated to the celebration of 20 years since the top quark discovery at Fermilab in 1995. Speakers from all experiments capable of studying top quark, ATLAS, CDF, CMS and DZero, will present the most recent results of the top quark studies based on Run II of the Tevatron and Run I of the LHC. Reviews of such fundamental measurements as mass of the top quark, its spin, charge and production properties are planned with some of them orders of magnitude better in precision in comparison with original CDF and DZero papers announcing the top quark discovery. Measurements of top quark production and decay that illuminate the nature of the Higgs boson and seek new phenomena will be presented. Theoretical talks on how the top quark fits into the Standard Model and its potential extensions will also be presented. This workshop will complement the yearly Top Workshop which is held in September and will benefit from many new results expected to be presented at winter conferences in 2015...

  19. Vaccination of healthy subjects and autoantibodies: from mice through dogs to humans.

    Science.gov (United States)

    Toplak, N; Avcin, T

    2009-11-01

    Vaccination against pathogenic microorganisms is one of the major achievements of modern medicine, but due to an increasing number of reports of adverse reactions the vaccination procedure has induced also considerable debate. It is well known that certain infections are involved in triggering the production of autoantibodies, which could lead to autoimmune adverse reactions in genetically predisposed subjects. Based on these findings it was assumed that vaccinations might induce similar autoimmune reactions. At present there is no clear-cut evidence that vaccinations are associated with overt autoimmune diseases but it has been demonstrated that in genetically predisposed persons vaccination can trigger the production of autoantibodies and autoimmune adverse reactions. The first studies investigating the production of autoantibodies following vaccination were done in dogs and mice. Several studies investigated the production of autoantibodies following vaccination in patients with autoimmune diseases, but there are only limited data on the autoimmune responses after vaccinations in apparently healthy humans. This review summarizes current evidence on the vaccination-induced autoantibodies in apparently healthy subjects including studies in animals and humans.

  20. Human Subjects Protection and Technology in Prevention Science: Selected Opportunities and Challenges.

    Science.gov (United States)

    Pisani, Anthony R; Wyman, Peter A; Mohr, David C; Perrino, Tatiana; Gallo, Carlos; Villamar, Juan; Kendziora, Kimberly; Howe, George W; Sloboda, Zili; Brown, C Hendricks

    2016-08-01

    Internet-connected devices are changing the way people live, work, and relate to one another. For prevention scientists, technological advances create opportunities to promote the welfare of human subjects and society. The challenge is to obtain the benefits while minimizing risks. In this article, we use the guiding principles for ethical human subjects research and proposed changes to the Common Rule regulations, as a basis for discussing selected opportunities and challenges that new technologies present for prevention science. The benefits of conducting research with new populations, and at new levels of integration into participants' daily lives, are presented along with five challenges along with technological and other solutions to strengthen the protections that we provide: (1) achieving adequate informed consent with procedures that are acceptable to participants in a digital age; (2) balancing opportunities for rapid development and broad reach, with gaining adequate understanding of population needs; (3) integrating data collection and intervention into participants' lives while minimizing intrusiveness and fatigue; (4) setting appropriate expectations for responding to safety and suicide concerns; and (5) safeguarding newly available streams of sensitive data. Our goal is to promote collaboration between prevention scientists, institutional review boards, and community members to safely and ethically harness advancing technologies to strengthen impact of prevention science.

  1. Research monitoring by US medical institutions to protect human subjects: compliance or quality improvement?

    Science.gov (United States)

    de Jong, Jean Philippe; van Zwieten, Myra C B; Willems, Dick L

    2013-04-01

    In recent years, to protect the rights and welfare of human subjects, institutions in the USA have begun to set up programmes to monitor ongoing medical research. These programmes provide routine, onsite oversight, and thus go beyond existing oversight such as investigating suspected misconduct or reviewing paperwork provided by investigators. However, because of a lack of guidelines and evidence, institutions have had little guidance in setting up their programmes. To help institutions make the right choices, we used interviews and document analysis to study how and why 11 US institutions have set up their monitoring programmes. Although these programmes varied considerably, we were able to distinguish two general types. 'Compliance' programmes on the one hand were part of the institutional review board office and set up to ensure compliance with regulations. Investigators' participation was mandatory. Monitors focused on documentation. Investigators could be disciplined, and could be obliged to take corrective actions. 'Quality-improvement' programmes on the other hand were part of a separate office. Investigators requested to be monitored. Monitors focused more on actual research conduct. Investigators and other parties received feedback on how to improve the research process. Although both types of programmes have their drawbacks and advantages, we argue that if institutions want to set up monitoring programmes, quality improvement is the better choice: it can help foster an atmosphere of trust between investigators and the institutional review board, and can help raise the standards for the protection of human subjects.

  2. Liver Afferents Contribute to Water Drinking-Induced Sympathetic Activation in Human Subjects: A Clinical Trial

    Science.gov (United States)

    May, Marcus; Gueler, Faikah; Barg-Hock, Hannelore; Heiringhoff, Karl-Heinz; Engeli, Stefan; Heusser, Karsten; Diedrich, André; Brandt, André; Strassburg, Christian P.; Tank, Jens; Sweep, Fred C. G. J.; Jordan, Jens

    2011-01-01

    Water drinking acutely increases sympathetic activity in human subjects. In animals, the response appears to be mediated through transient receptor potential channel TRPV4 activation on osmosensitive hepatic spinal afferents, described as osmopressor response. We hypothesized that hepatic denervation attenuates water drinking-induced sympathetic activation. We studied 20 liver transplant recipients (44±2.6 years, 1.2±0.1 years post transplant) as model of hepatic denervation and 20 kidney transplant recipients (43±2.6 years, 0.8±0.1 years post transplant) as immunosuppressive drug matched control group. Before and after 500 ml water ingestion, we obtained venous blood samples for catecholamine analysis. We also monitored brachial and finger blood pressure, ECG, and thoracic bioimpedance. Plasma norepinephrine concentration had changed by 0.01±0.07 nmol/l in liver and by 0.21±0.07 nmol/l in kidney transplant recipients (pwater drinking. While blood pressure and systemic vascular resistance increased in both groups, the responses tended to be attenuated in liver transplant recipients. Our findings support the idea that osmosensitive hepatic afferents are involved in water drinking-induced sympathetic activation in human subjects. Trial Registration ClinicalTrials.gov NCT01237431 PMID:22016786

  3. The Role of Intuition in Risk/Benefit Decision-Making in Human Subjects Research.

    Science.gov (United States)

    Resnik, David B

    2017-01-01

    One of the key principles of ethical research involving human subjects is that the risks of research to should be acceptable in relation to expected benefits. Institutional review board (IRB) members often rely on intuition to make risk/benefit decisions concerning proposed human studies. Some have objected to using intuition to make these decisions because intuition is unreliable and biased and lacks transparency. In this article, I examine the role of intuition in IRB risk/benefit decision-making and argue that there are practical and philosophical limits to our ability to reduce our reliance on intuition in this process. The fact that IRB risk/benefit decision-making involves intuition need not imply that it is hopelessly subjective or biased, however, since there are strategies that IRBs can employ to improve their decisions, such as using empirical data to estimate the probability of potential harms and benefits, developing classification systems to guide the evaluation of harms and benefits, and engaging in moral reasoning concerning the acceptability of risks.

  4. [Encountering the subject in the health field: a human care theory based on lived experience].

    Science.gov (United States)

    Vonarx, Nicolas; Desgroseilliers, Valérie

    2013-09-01

    Dominated by a bio-mechanistic paradigm, Western health systems are suffering from numerous problems. One such problem is the lack of consideration for lived experiences and the complexity and depth of meaning that characterize them. We accordingly emphasize in this text the importance of talking a deep look at the experiences of the cared-for Subject and changing the viewpoint on his or her problems. We defend this viewpoint with the help of a few ideas borrowed from Georges Canguilhem. We then refer to a socio-phenomenological approach inspired by the work of Alfred Schütz which allows us to better grasp people's lived experiences. We thus rehabilitate the Subject by proposing a human care theory that focuses on its' relationship(s) with the body, others, time and space, as well as on self-referent identity labels that give meaning to one's existence. This study is a theoretical reflection on human care that considers professional collaboration and interdisciplinarity, and that does not ignore the concrete practices of stakeholders and professionals.

  5. Liver afferents contribute to water drinking-induced sympathetic activation in human subjects: a clinical trial.

    Directory of Open Access Journals (Sweden)

    Marcus May

    Full Text Available UNLABELLED: Water drinking acutely increases sympathetic activity in human subjects. In animals, the response appears to be mediated through transient receptor potential channel TRPV4 activation on osmosensitive hepatic spinal afferents, described as osmopressor response. We hypothesized that hepatic denervation attenuates water drinking-induced sympathetic activation. We studied 20 liver transplant recipients (44±2.6 years, 1.2±0.1 years post transplant as model of hepatic denervation and 20 kidney transplant recipients (43±2.6 years, 0.8±0.1 years post transplant as immunosuppressive drug matched control group. Before and after 500 ml water ingestion, we obtained venous blood samples for catecholamine analysis. We also monitored brachial and finger blood pressure, ECG, and thoracic bioimpedance. Plasma norepinephrine concentration had changed by 0.01±0.07 nmol/l in liver and by 0.21±0.07 nmol/l in kidney transplant recipients (p<0.05 between groups after 30-40 minutes of water drinking. While blood pressure and systemic vascular resistance increased in both groups, the responses tended to be attenuated in liver transplant recipients. Our findings support the idea that osmosensitive hepatic afferents are involved in water drinking-induced sympathetic activation in human subjects. TRIAL REGISTRATION: ClinicalTrials.gov NCT01237431.

  6. Human preferences for symmetry: subjective experience, cognitive conflict and cortical brain activity.

    Directory of Open Access Journals (Sweden)

    David W Evans

    Full Text Available This study examines the links between human perceptions, cognitive biases and neural processing of symmetrical stimuli. While preferences for symmetry have largely been examined in the context of disorders such as obsessive-compulsive disorder and autism spectrum disorders, we examine various these phenomena in non-clinical subjects and suggest that such preferences are distributed throughout the typical population as part of our cognitive and neural architecture. In Experiment 1, 82 young adults reported on the frequency of their obsessive-compulsive spectrum behaviors. Subjects also performed an emotional Stroop or variant of an Implicit Association Task (the OC-CIT developed to assess cognitive biases for symmetry. Data not only reveal that subjects evidence a cognitive conflict when asked to match images of positive affect with asymmetrical stimuli, and disgust with symmetry, but also that their slowed reaction times when asked to do so were predicted by reports of OC behavior, particularly checking behavior. In Experiment 2, 26 participants were administered an oddball Event-Related Potential task specifically designed to assess sensitivity to symmetry as well as the OC-CIT. These data revealed that reaction times on the OC-CIT were strongly predicted by frontal electrode sites indicating faster processing of an asymmetrical stimulus (unparallel lines relative to a symmetrical stimulus (parallel lines. The results point to an overall cognitive bias linking disgust with asymmetry and suggest that such cognitive biases are reflected in neural responses to symmetrical/asymmetrical stimuli.

  7. A phase response curve to single bright light pulses in human subjects

    Science.gov (United States)

    Khalsa, Sat Bir S.; Jewett, Megan E.; Cajochen, Christian; Czeisler, Charles A.

    2003-01-01

    The circadian pacemaker is differentially sensitive to the resetting effects of retinal light exposure, depending upon the circadian phase at which the light exposure occurs. Previously reported human phase response curves (PRCs) to single bright light exposures have employed small sample sizes, and were often based on relatively imprecise estimates of circadian phase and phase resetting. In the present study, 21 healthy, entrained subjects underwent pre- and post-stimulus constant routines (CRs) in dim light (approximately 2-7 lx) with maintained wakefulness in a semi-recumbent posture. The 6.7 h bright light exposure stimulus consisted of alternating 6 min fixed gaze (approximately 10 000 lx) and free gaze (approximately 5000-9000 lx) exposures. Light exposures were scheduled across the circadian cycle in different subjects so as to derive a PRC. Plasma melatonin was used to determine the phase of the onset, offset, and midpoint of the melatonin profiles during the CRs. Phase shifts were calculated as the difference in phase between the pre- and post-stimulus CRs. The resultant PRC of the midpoint of the melatonin rhythm revealed a characteristic type 1 PRC with a significant peak-to-trough amplitude of 5.02 h. Phase delays occurred when the light stimulus was centred prior to the critical phase at the core body temperature minimum, phase advances occurred when the light stimulus was centred after the critical phase, and no phase shift occurred at the critical phase. During the subjective day, no prolonged 'dead zone' of photic insensitivity was apparent. Phase shifts derived using the melatonin onsets showed larger magnitudes than those derived from the melatonin offsets. These data provide a comprehensive characterization of the human PRC under highly controlled laboratory conditions.

  8. The effect of low light intensity on the maintenance of circadian synchrony in human subjects

    Science.gov (United States)

    Winget, C. M.; Lyman, J.; Beljan, J. R.

    1977-01-01

    The light-intensity threshold for humans is not known. In past space flights owing to power restrictions, light intensities have been minimal and reported to be as low as 15 ft. c. This study was conducted to determine whether the light (L)/dark (D) environment of 16L : 8D at the relatively low light intensity of 15 ft. c. was adequate for the maintenance of circadian synchrony in human subjects. Six healthy male subjects aged 20-23 years were exposed for 21 days to a 16L : 8D photoperiod. During the first 7 days the light intensity was 100 ft. c.; it was reduced to 15 ft. c. during the next 7 days and increased again to 100 ft. c. during the last 7 days of the study. Rectal temperature (RT) and heart rate (HR) were recorded continuously throughout the 21 days of the study. In the 100 ft. c. 16L : 8D the RT and HR rhythms remained stable and circadian throughout. When the light intensity was decreased to 15 ft. c. the periodicity of the HR rhythm was significantly decreased and this rhythm showed marked instability. In contrast the period of the RT rhythm did not change but a consistent phase delay occurred due to a delay in the lights-on associated rise in RT. These divergent effects on these two rhythms in internal desynchronization and performance decrement during the 15 ft. c. exposure. The data emphasize the need for establishing accurately the minimal lighting requirements for the maintenance of circadian rhythms of humans in confined environments.

  9. Simultaneous transdermal extraction of glucose and lactate from human subjects by reverse iontophoresis

    Directory of Open Access Journals (Sweden)

    Tak S Ching

    2008-06-01

    Full Text Available Tak S Ching1, Patricia Connolly21Asia University, Taiwan; 2Bioengineering Unit, University of Strathclyde, Glasgow, Scotland, UKAbstract: This study investigated the possibility of simultaneously extracting glucose and lactate from human subjects, at the same skin location, using transdermal reverse iontophoresis. Transdermal monitoring using iontophoresis is made possible by the skin’s permeability to small molecules and the nanoporous and microporous nature of the structure of skin. The study was intended to provide information which could be used to develop a full, biosensor-based, monitoring system for multiple parameters from transdermal extraction. As a precursor to the human study, in vitro reverse iontophoresis experiments were performed in an artificial skin system to establish the optimum current waveforms to be applied during iontophoresis. In the human study, a bipolar DC current waveform (with reversal of the electrode current direction every 15 minutes was applied to ten healthy volunteers via skin electrodes and utilized for simultaneous glucose and lactate transdermal extraction at an applied current density of 300 µA/cm2. Glucose and lactate were successfully extracted through each subject’s skin into the conducting gel that formed part of each iontophoresis electrode. The results suggest that it will be possible to noninvasively and simultaneously monitor glucose and lactate levels in patients using this approach and this could have future applications in diagnostic monitoring for a variety of medical conditions.Keywords: transdermal, iontophoresis, glucose, lactate, diagnostic monitoring

  10. Human Body as Subjectivity in Edith Stein. A Discussion on Anthropological Monism

    Directory of Open Access Journals (Sweden)

    Diego I. Rosales Meana

    2014-11-01

    Full Text Available This text aims to explain why «anthropological monism» is the most adequate perspective in order to understand human reality, and that this ‘monism’ must not be necessarily considered as materialist. I will divide my work in four sections. First, I will explain briefly the Cartesian paradigm and what I consider some of its ontological mistakes. Then, I will try to build a phenomenology of the self with Edith Stein’s anthropology as its base, in order to reunite the two realities separated by Descartes: body and subjectivity. Third, I will talk about the concept of ‘form’ as the inseparable vital principle of living beings and, finally, I will talk about empathy as the phenomenon by which we constitute the idea of ‘I’ and the notion of ‘human being’. This way, monism will be presented as the best option to explain human reality and its activity.

  11. Robust adaptive control modeling of human arm movements subject to altered gravity and mechanical loads

    Science.gov (United States)

    Tryfonidis, Michail

    It has been observed that during orbital spaceflight the absence of gravitation related sensory inputs causes incongruence between the expected and the actual sensory feedback resulting from voluntary movements. This incongruence results in a reinterpretation or neglect of gravity-induced sensory input signals. Over time, new internal models develop, gradually compensating for the loss of spatial reference. The study of adaptation of goal-directed movements is the main focus of this thesis. The hypothesis is that during the adaptive learning process the neural connections behave in ways that can be described by an adaptive control method. The investigation presented in this thesis includes two different sets of experiments. A series of dart throwing experiments took place onboard the space station Mir. Experiments also took place at the Biomechanics lab at MIT, where the subjects performed a series of continuous trajectory tracking movements while a planar robotic manipulandum exerted external torques on the subjects' moving arms. The experimental hypothesis for both experiments is that during the first few trials the subjects will perform poorly trying to follow a prescribed trajectory, or trying to hit a target. A theoretical framework is developed that is a modification of the sliding control method used in robotics. The new control framework is an attempt to explain the adaptive behavior of the subjects. Numerical simulations of the proposed framework are compared with experimental results and predictions from competitive models. The proposed control methodology extends the results of the sliding mode theory to human motor control. The resulting adaptive control model of the motor system is robust to external dynamics, even those of negative gain, uses only position and velocity feedback, and achieves bounded steady-state error without explicit knowledge of the system's nonlinearities. In addition, the experimental and modeling results demonstrate that

  12. An Evaluation of Twenty Years of EU Framework Programme-funded Immune-mediated Inflammatory Translational Research in Non-human Primates

    Directory of Open Access Journals (Sweden)

    Krista Geraldine Haanstra

    2016-11-01

    Full Text Available Ageing western societies are facing an increasing prevalence of chronic inflammatory and degenerative diseases for which often no effective treatments exist, resulting in increasing health care expenditure. Despite high investments in drug development, the number of promising new drug candidates decreases. We propose that preclinical research in non-human primate can help to bridge the gap between drug discovery and drug prescription.Translational research covers various stages of drug development of which pre-clinical efficacy tests in valid animal models is usually the last stage. Pre-clinical research in non-human primates may be essential in the evaluation of new drugs or therapies when a relevant rodent model is not available. Non-human primate models for life-threatening or severely debilitating diseases in humans are available at the Biomedical Primate Research Centre (BPRC. These have been instrumental in translational research for several decades.In order to stimulate European health research and innovation from bench to bedside, the European Commission (EC has invested heavily in access to non-human primate research for more than 20 years. BPRC has hosted European users in a series of transnational access programs covering a wide range of research areas with the common theme being immune-mediated inflammatory disorders. We present an overview of the results and give an account of the studies performed as part of European Union Framework Programme (EU FP-funded translational non-human primate research performed at the BPRC. The data illustrate value of translational non-human primate research for the development of new therapies and emphasize the importance of EU FP funding

  13. Higher prevalence and abundance of Bdellovibrio bacteriovorus in the human gut of healthy subjects.

    Directory of Open Access Journals (Sweden)

    Valerio Iebba

    Full Text Available INTRODUCTION: Members of the human intestinal microbiota are key players in maintaining human health. Alterations in the composition of gut microbial community (dysbiosis have been linked with important human diseases. Understanding the underlying processes that control community structure, including the bacterial interactions within the microbiota itself, is essential. Bdellovibrio bacteriovorus is a gram-negative bacterium that preys other gram-negative species for survival, acting as a population-balancer. It was found in terrestrial/aquatic ecosystems, and in animal intestines, postulating its presence also in the human gut. METHODS: The present study was aimed to evaluate, by end-point PCR and qPCR, the presence of B. bacteriovorus in intestinal and faecal biopsy specimens from 92 paediatric healthy subjects and patients, suffering from Inflammatory Bowel Diseases (IBD, Celiac disease and Cystic fibrosis (CF. RESULTS: i B. bacteriovorus was present and abundant only in healthy individuals, while it was heavily reduced in patients, as in the case of IBD and Celiac, while in CF patients and relative controls we observed comparable results; ii B. bacteriovorus seemed to be mucosa-associated, because all IBD and Celiac biopsies (and related controls were treated with mucus-removing agents, leaving only the mucosa-attached microflora; iii B. bacteriovorus abundance was district-dependent, with a major preponderance in duodenum, and gradually decreasing up to rectum; iv B. bacteriovorus levels significantly dropped in disease status, in duodenum and ileum. CONCLUSIONS: Results obtained in this study could represent the first step for new therapeutic strategies aimed to restore a balance in the intestinal ecosystem, utilizing Bdellovibrio as a probiotic.

  14. Striatal μ-opioid receptor availability predicts cold pressor pain threshold in healthy human subjects

    DEFF Research Database (Denmark)

    Hagelberg, Nora; Aalto, Sargo; Tuominen, Lauri;

    2012-01-01

    Previous PET studies in healthy humans have shown that brain μ-opioid receptor activation during experimental pain is associated with reductions in the sensory and affective ratings of the individual pain experience. The aim of this study was to find out whether brain μ-opioid receptor binding...... at the resting state, in absence of painful stimulation, can be a long-term predictor of experimental pain sensitivity. We measured μ-opioid receptor binding potential (BP(ND)) with μ-opioid receptor selective radiotracer [(11)C]carfentanil and positron emission tomography (PET) in 12 healthy male subjects...... the potential associations between μ-opioid receptor BP(ND) and psychophysical measures. The results show that striatal μ-opioid receptor BP(ND) predicts cold pressor pain threshold, but not cold pressor pain tolerance or tactile sensitivity. This finding suggests that striatal μ-opioid receptor density...

  15. In vivo applications of X-ray fluorescence in human subjects

    Indian Academy of Sciences (India)

    D R Chettle

    2011-02-01

    X-ray fluorescence has been used to measure several elements noninvasively within living human subjects. Some description is given of the constraints imposed by this rather unusual form of analysis together with a brief listing indicating the range of elements for which such analyses have been developed. Measurements of two elements are then presented in more detail. Lead is measured in bone and has become a well-established tool in continuing research into the long term effects of lead. Strontium is also measured in bone and, although presently not in widespread use, offers the potential for essential information in the study of the reported benefits of strontium supplementation.

  16. Documentation of ethical conduct of human subject research published in Saudi medical journals.

    Science.gov (United States)

    Al-Gaai, E A; Hammami, M M; Al Eidan, M

    2012-07-01

    We evaluated the documentation of ethical conduct (obtaining institutional review board approval and consent and following ethical guidelines) of human subject research studies published in Saudi Arabian medical journals between 1979 and 2007. Studies were classified as retrospective, prospective noninterventional, interventional or survey/interview. Of 1838 studies published in 286 journal issues of 11 Saudi Arabian medical journals, only 0.9% documented the ethical guidelines followed, with a significantly higher rate for studies published after year 2000 (1.7%). Of 821 studies requiring institutional review board approval, 8.6% documented obtaining the approval and informed consent, with a significantly higher rate for interventional studies (19.4%), post-year 2000 studies (19.7%) and studies performed outside Saudi Arabia (15.9%). The low documentation rate suggests editor's lack of rigor and/or investigators' ignorance of guidelines. The higher documentation rate after year 2000 suggests an ongoing improvement.

  17. Suppression of EMG activity by transcranial magnetic stimulation in human subjects during walking

    DEFF Research Database (Denmark)

    Petersen, Nicolas Caesar; Butler, Jane E; Marchand-Pauvert, Veronique

    2001-01-01

    1. The involvement of the motor cortex during human walking was evaluated using transcranial magnetic stimulation (TMS) of the motor cortex at a variety of intensities. Recordings of EMG activity in tibialis anterior (TA) and soleus muscles during walking were rectified and averaged. 2. TMS of low...... intensity (below threshold for a motor-evoked potential, MEP) produced a suppression of ongoing EMG activity during walking. The average latency for this suppression was 40.0 +/- 1.0 ms. At slightly higher intensities of stimulation there was a facilitation of the EMG activity with an average latency of 29.......5 +/- 1.0 ms. As the intensity of the stimulation was increased the facilitation increased in size and eventually a MEP was clear in individual sweeps. 3. In three subjects TMS was replaced by electrical stimulation over the motor cortex. Just below MEP threshold there was a clear facilitation at short...

  18. Interaction of transcranial magnetic stimulation and electrical transmastoid stimulation in human subjects

    DEFF Research Database (Denmark)

    Taylor, Janet L; Petersen, Nicolas Caesar; Butler, Jane E

    2002-01-01

    Transcranial magnetic stimulation activates corticospinal neurones directly and transsynaptically and hence, activates motoneurones and results in a response in the muscle. Transmastoid stimulation results in a similar muscle response through activation of axons in the spinal cord. This study...... was designed to determine whether the two stimuli activate the same descending axons. Responses to transcranial magnetic stimuli paired with electrical transmastoid stimuli were examined in biceps brachii in human subjects. Twelve interstimulus intervals (ISIs) from -6 ms (magnet before transmastoid) to 5 ms......-wave, facilitation still occurred at ISIs of -6 and -5 ms and depression of the paired response at ISIs of 0, 1, 4 and 5 ms. The interaction of the response to transmastoid stimulation with the multiple descending volleys elicited by magnetic stimulation of the cortex is complex. However, depression of the response...

  19. Recommendations for nanomedicine human subjects research oversight: an evolutionary approach for an emerging field.

    Science.gov (United States)

    Fatehi, Leili; Wolf, Susan M; McCullough, Jeffrey; Hall, Ralph; Lawrenz, Frances; Kahn, Jeffrey P; Jones, Cortney; Campbell, Stephen A; Dresser, Rebecca S; Erdman, Arthur G; Haynes, Christy L; Hoerr, Robert A; Hogle, Linda F; Keane, Moira A; Khushf, George; King, Nancy M P; Kokkoli, Efrosini; Marchant, Gary; Maynard, Andrew D; Philbert, Martin; Ramachandran, Gurumurthy; Siegel, Ronald A; Wickline, Samuel

    2012-01-01

    The nanomedicine field is fast evolving toward complex, "active," and interactive formulations. Like many emerging technologies, nanomedicine raises questions of how human subjects research (HSR) should be conducted and the adequacy of current oversight, as well as how to integrate concerns over occupational, bystander, and environmental exposures. The history of oversight for HSR investigating emerging technologies is a patchwork quilt without systematic justification of when ordinary oversight for HSR is enough versus when added oversight is warranted. Nanomedicine HSR provides an occasion to think systematically about appropriate oversight, especially early in the evolution of a technology, when hazard and risk information may remain incomplete. This paper presents the consensus recommendations of a multidisciplinary, NIH-funded project group, to ensure a science-based and ethically informed approach to HSR issues in nanomedicine, and to integrate HSR analysis with analysis of occupational, bystander, and environmental concerns. We recommend creating two bodies, an interagency Human Subjects Research in Nanomedicine (HSR/N) Working Group and a Secretary's Advisory Committee on Nanomedicine (SAC/N). HSR/N and SAC/N should perform 3 primary functions: (1) analysis of the attributes and subsets of nanomedicine interventions that raise HSR challenges and current gaps in oversight; (2) providing advice to relevant agencies and institutional bodies on the HSR issues, as well as federal and federal-institutional coordination; and (3) gathering and analyzing information on HSR issues as they emerge in nanomedicine. HSR/N and SAC/N will create a home for HSR analysis and coordination in DHHS (the key agency for relevant HSR oversight), optimize federal and institutional approaches, and allow HSR review to evolve with greater knowledge about nanomedicine interventions and greater clarity about attributes of concern.

  20. Comparison of techniques for morphologic evaluation of glycerol-preserved human skim subjected to gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Bringel, Fabiana de A. [Faculty of Humanities, Economic and Health Sciences of Araguaina ITPAC (FAHESA/ITPAC/TO) Araguaina, TO (Brazil); Isaac, Cesar [Faculty of Medicine, University of Sao Paulo (FMUSP/SP) Sao Paulo, SP (Brazil); Herson, Marisa R., E-mail: marisah@vifm.org [Tissue Bank of Victoria, Victoria (Australia); Freitas, Anderson Z. de; Martinho Junior, Antonio C.; Mathor, Monica B., E-mail: azanardi@ipen.br, E-mail: mathor@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Radiation Technology Centre; Oliveira, Sergio F. de [Institute of Biomedical Sciences, University of Sao Paulo (ICB-USP/SP), SP (Brazil)

    2011-07-01

    Extensive skin lesions expose the body to damaging agents, which makes spontaneous regeneration difficult and, in many cases, leads patient to death. In such cases, if there are no donating areas for auto graft, allografts can be used. In this type of graft, tissue is processed in tissue banks, where it can be subjected to radiosterilization. According to in vitro studies, gamma radiation, in doses higher than 25 kGy, causes breakdown of collagen I fibrils in the skin preserved in glycerol at 85% and this change influences fibroblast migration and deposition of new collagen. In order to assess if the alterations observed in vitro, would compromise in vivo use, transplants of human tissue, irradiated or not, were performed in Nude mice. After the surgery the skins of the mice was subjected to macroscopic analysis on the 3{sup rd}, 7{sup th}, 21{sup st} and 90{sup th} days; optical coherence tomography on the 90{sup th} day and histological assay on the 3{sup rd}, 7{sup th}, 21{sup st} days to compare the results of the repair process among the techniques, considering that the OCT allows in vivo and not destructive morphological analysis. According to the results obtained through OCT it was possible to observe a more organized repair process in the animals which received irradiated grafts (25 and 50 kGy) if compared to unirradiated grafts. It was not possible to observe such phenomena through macroscopic or histological evaluation. (author)

  1. Immune response to acetaldehyde-human serum albumin adduct among healthy subjects related to alcohol intake.

    Science.gov (United States)

    Romanazzi, Valeria; Schilirò, Tiziana; Carraro, Elisabetta; Gilli, Giorgio

    2013-09-01

    Acetaldehyde (AA) is the main metabolic product in ethanol metabolism, although it can also derive from sources of airborne pollution. As a typical aldehyde, AA is able to react with a variety of molecular targets, including DNA and protein. This property justifies the hypothesis of a immune reaction against this kind of adduct, to be studied by a seroprevalence screening approach. In this study, the correlation between drinking habits and the amount of circulating AA-human serum albumin adduct (AA-HSA) was evaluated in a group of healthy subjects, non alcohol-addicted. Daily ethanol intake (grams) was inferred for each subject using the information collected through a questionnaire, and AA-HSA antibodies (AA-HSA ab) analyses were performed using the Displacement Assay on whole blood samples. The findings showed a correlation between ethanol intake and immune response to molecular adduct. These results underscore the evaluation of AA-HSA ab amount as a suitable molecular marker for alcohol intake that can be applied in future investigations on a large scale for prevention screening.

  2. Airflow in a Multiscale Subject-Specific Breathing Human Lung Model

    CERN Document Server

    Choi, Jiwoong; Hoffman, Eric A; Tawhai, Merryn H; Lin, Ching-Long

    2013-01-01

    The airflow in a subject-specific breathing human lung is simulated with a multiscale computational fluid dynamics (CFD) lung model. The three-dimensional (3D) airway geometry beginning from the mouth to about 7 generations of airways is reconstructed from the multi-detector row computed tomography (MDCT) image at the total lung capacity (TLC). Along with the segmented lobe surfaces, we can build an anatomically-consistent one-dimensional (1D) airway tree spanning over more than 20 generations down to the terminal bronchioles, which is specific to the CT resolved airways and lobes (J Biomech 43(11): 2159-2163, 2010). We then register two lung images at TLC and the functional residual capacity (FRC) to specify subject-specific CFD flow boundary conditions and deform the airway surface mesh for a breathing lung simulation (J Comput Phys 244:168-192, 2013). The 1D airway tree bridges the 3D CT-resolved airways and the registration-derived regional ventilation in the lung parenchyma, thus a multiscale model. Larg...

  3. Effect of Grewia asiatica fruit on glycemic index and phagocytosis tested in healthy human subjects.

    Science.gov (United States)

    Mesaik, Muhammad Ahmed; Ahmed, Asif; Khalid, Ahmed Shukralla; Jan, Saleem; Siddiqui, Afaq Ahmed; Perveen, Shahida; Azim, Muhammad Kamran

    2013-01-01

    The Grewia asiatica (commonly known as Phalsa or Fasla) is a shrub or small tree found in southern Asia. It produces purple to black color fruit when ripe. In folk medicine the edible Grewia asiatica fruit is used in a number of pathological conditions. The current study described the effects of Grewia asiatica fruit on glycemic index (GI) and phagocytosis in healthy non-diabetic human subjects. The results showed that Grewia asiatica fruit has low GI value of 5.34 with modest hypoglycemic activity. Luminol-enhanced chemiluminescence assay was carried out to determine the production of reactive oxygen species (ROS) in the oxidative burst activity of whole blood. ROS production was found to be significantly affected, having the 78.3, 58.6 and 30.8% when the subjects were fed with D-glucose, mixture of D-glucose and Grewia asiatica fruit and Grewia asiatica fruit alone respectively as compared to the control. The aqueous, methanolic and butanolic extracts of Grewia asiatica fruits were found to produce a stimulatory effect on ROS production however; the chloroform, hexane and ethanol-acetate extracted exerted significant inhibitory effect. These results demonstrated that Grewia asiatica fruit has desirable effects on blood glucose metabolism manifested as low glycemic response and modulation of ROS production.

  4. Mechanical Characterization of the Human Lumbar Intervertebral Disc Subjected to Impact Loading Conditions

    Science.gov (United States)

    Jamison, David, IV

    Low back pain is a large and costly problem in the United States. Several working populations, such as miners, construction workers, forklift operators, and military personnel, have an increased risk and prevalence of low back pain compared to the general population. This is due to exposure to repeated, transient impact shocks, particularly while operating vehicles or other machinery. These shocks typically do not cause acute injury, but rather lead to pain and injury over time. The major focus in low back pain is often the intervertebral disc, due to its role as the major primary load-bearing component along the spinal column. The formation of a reliable standard for human lumbar disc exposure to repeated transient shock could potentially reduce injury risk for these working populations. The objective of this project, therefore, is to characterize the mechanical response of the lumbar intervertebral disc subjected to sub-traumatic impact loading conditions using both cadaveric and computational models, and to investigate the possible implications of this type of loading environment for low back pain. Axial, compressive impact loading events on Naval high speed boats were simulated in the laboratory and applied to human cadaveric specimen. Disc stiffness was higher and hysteresis was lower than quasi-static loading conditions. This indicates a shift in mechanical response when the disc is under impact loads and this behavior could be contributing to long-term back pain. Interstitial fluid loss and disc height changes were shown to affect disc impact mechanics in a creep study. Neutral zone increased, while energy dissipation and low-strain region stiffness decreased. This suggests that the disc has greater clinical instability during impact loading with progressive creep and fluid loss, indicating that time of day should be considered for working populations subjected to impact loads. A finite element model was developed and validated against cadaver specimen

  5. The Effect of Drinking on Plasma Vasopressin and Renin in Dehydrated Human Subjects

    Science.gov (United States)

    Geelen, G.; Keil, L. C.; Kravik, S. E.; Wade, C. E.; Thrasher, T. N.; Barnes, P. R.; Pyka, G.; Nesvig, C.; Greenleaf, J. E.

    1996-01-01

    Oropharyngeal mechanisms activated by drinking have been shown to induce a rapid decline in plasma vasopressin which preceeds postabsorptive changes in plasma composition in the dehydrated dog. The present study was undertaken to determine what factor(s) inhibit(s) vasopressin secretion after rehydration in water deprived human subjects. Hematocrit (Hct) and hemoglobin (Hb) were determined on the day of the experiment, together with electrolytes and osmolalities which were measured on freshly separated serum. Plasma was immediately frozen and further analyzed by radioimmunoassay for renin activity (PRA), vasopressin (AVP), and aldosterone. The data were analyzed using an analysis of variance for repeated measurements and significant differences between the dehydrated control period and various time points after the start of rehydration were determined using a multiple-range test. began and reached water replete levels 15 minutes after drinking in the absence of any detectable decline in serum sodium or osmolality, we conclude that 427 oropharyngeal factors, alone or combined with gastric distension account for the extremely rapid inhibition of AVP secretion after drinking in the water-deprived human, as has been shown to be the case in dogs. Our findings are also in agreement wiht the recent demonstration that at the onset of drinking in the dehydrated monkey, there is an abrupt fall in plasma AVP concentration associated with a considerable decrease in the firing rate of the supraoptic neurosecretory neurons.

  6. Kinetics of Beta-14[14C] Carotene in a Human Subject Using Accelerator Mass Spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Dueker, S.R.; Lin, Y.; Follett, J.R.; Clifford, A.J.; Buchholz, B.A.

    2000-01-31

    {beta}-Carotene is a tetraterpenoid distributed widely throughout the plant kingdom. It is a member of a group of pigments referred to as carotenoids that have the distinction of serving as metabolic precursors to vitamin A in humans and many animals [1,2]. We used Accelerator Mass Spectrometry (AMS) [3] to determine the metabolic behavior of a physiologic oral dose of {beta}-[{sup 14}C]carotene (200 nanoCuries; 0.57 {micro}mol) in a healthy human subject. Serial blood specimens were collected for 210-d and complete urine and feces were collected for 17 and 10-d, respectively. Balance data indicated that the dose was 42% bioavailable. The absorbed {beta}-carotene was lost slowly via urine in accord with the slow body turnover of {beta}-carotene and vitamin A [4]. HPLC fractionation of plasma taken at early time points (0-24-h) showed the label was distributed between {beta}-carotene and retinyl esters (vitamin A) derived from intestinal metabolism.

  7. Population of 224 realistic human subject-based computational breast phantoms

    Energy Technology Data Exchange (ETDEWEB)

    Erickson, David W. [Carl E. Ravin Advanced Imaging Laboratories, Duke University Medical Center, Durham, North Carolina 27705 and Medical Physics Graduate Program, Duke University, Durham, North Carolina 27705 (United States); Wells, Jered R., E-mail: jered.wells@duke.edu [Clinical Imaging Physics Group and Carl E. Ravin Advanced Imaging Laboratories, Duke University Medical Center, Durham, North Carolina 27705 and Medical Physics Graduate Program, Duke University, Durham, North Carolina 27705 (United States); Sturgeon, Gregory M. [Carl E. Ravin Advanced Imaging Laboratories, Duke University Medical Center, Durham, North Carolina 27705 (United States); Samei, Ehsan [Department of Radiology and Carl E. Ravin Advanced Imaging Laboratories, Duke University Medical Center, Durham, North Carolina 27705 and Departments of Physics, Electrical and Computer Engineering, and Biomedical Engineering, and Medical Physics Graduate Program, Duke University, Durham, North Carolina 27705 (United States); Dobbins, James T. [Department of Radiology and Carl E. Ravin Advanced Imaging Laboratories, Duke University Medical Center, Durham, North Carolina 27705 and Departments of Physics and Biomedical Engineering and Medical Physics Graduate Program, Duke University, Durham, North Carolina 27705 (United States); Segars, W. Paul [Department of Radiology and Carl E. Ravin Advanced Imaging Laboratories, Duke University Medical Center, Durham, North Carolina 27705 and Medical Physics Graduate Program, Duke University, Durham, North Carolina 27705 (United States); Lo, Joseph Y. [Department of Radiology and Carl E. Ravin Advanced Imaging Laboratories, Duke University Medical Center, Durham, North Carolina 27705 and Departments of Electrical and Computer Engineering and Biomedical Engineering and Medical Physics Graduate Program, Duke University, Durham, North Carolina 27705 (United States)

    2016-01-15

    Purpose: To create a database of highly realistic and anatomically variable 3D virtual breast phantoms based on dedicated breast computed tomography (bCT) data. Methods: A tissue classification and segmentation algorithm was used to create realistic and detailed 3D computational breast phantoms based on 230 + dedicated bCT datasets from normal human subjects. The breast volume was identified using a coarse three-class fuzzy C-means segmentation algorithm which accounted for and removed motion blur at the breast periphery. Noise in the bCT data was reduced through application of a postreconstruction 3D bilateral filter. A 3D adipose nonuniformity (bias field) correction was then applied followed by glandular segmentation using a 3D bias-corrected fuzzy C-means algorithm. Multiple tissue classes were defined including skin, adipose, and several fractional glandular densities. Following segmentation, a skin mask was produced which preserved the interdigitated skin, adipose, and glandular boundaries of the skin interior. Finally, surface modeling was used to produce digital phantoms with methods complementary to the XCAT suite of digital human phantoms. Results: After rejecting some datasets due to artifacts, 224 virtual breast phantoms were created which emulate the complex breast parenchyma of actual human subjects. The volume breast density (with skin) ranged from 5.5% to 66.3% with a mean value of 25.3% ± 13.2%. Breast volumes ranged from 25.0 to 2099.6 ml with a mean value of 716.3 ± 386.5 ml. Three breast phantoms were selected for imaging with digital compression (using finite element modeling) and simple ray-tracing, and the results show promise in their potential to produce realistic simulated mammograms. Conclusions: This work provides a new population of 224 breast phantoms based on in vivo bCT data for imaging research. Compared to previous studies based on only a few prototype cases, this dataset provides a rich source of new cases spanning a wide range

  8. True or False, Process or Procedure: Parrhesia and a Consideration of Humanism, Subjectivity, and Ethics within Educational Research

    Science.gov (United States)

    Roof, David; Polush, Elena

    2016-01-01

    This paper seeks to examine ethics, humanism, and the concept of "parrhesia" ("pa???s?a") in the context of educational research. More specifically, it surveys Foucault's lectures on ethics to explore a framework for educational research that disrupts subjectivity and traditional forms of humanism while retaining a relational…

  9. Lateral neck injury assessments in side impact using post mortem human subject tests.

    Science.gov (United States)

    Yoganandan, Narayan; Humm, John; Pintar, Frank A; Wolfla, Christopher E; Maiman, Dennis J

    2011-01-01

    Current neck injury criteria are based on matching upper cervical spine injuries from piglet tests to airbag deployment loads and pairing kinematics from child dummies. These "child-based" scaled data together with adult human cadaver tolerances in axial loading are used to specify neck injury thresholds in axial compression and tension, and flexion and extension moment about the occipital condyles; no thresholds are specified for any other force or moment including lateral bending. The objective of this study was to develop a testing methodology and to determine the lateral bending moment injury threshold under coronal loading. Post mortem human subjects (PMHS) were used. Specimens consisted of whole body and isolated head-neck complexes with intact musculature. Intact specimen positioning included: sitting PMHS upright on a rigid seat, supporting the torso by a plate, maintaining Frankfurt plane horizontal. Isolated head-neck complexes were fixed at T1 with the occiput connected via a custom apparatus to a testing device to induce lateral bending motion. Head angular and linear accelerations and angular velocities were computed using a pyramid nine accelerometer package on the head; specimen-specific physical properties including center of gravity and moments of inertia in the three-dimensions; and equations of equilibrium. These data were used to determine neck loads at the occipital condyles. No specimens sustained injuries, identified by palpation, x-rays, CT, and autopsy. Results from 24 tests indicated that PMHS head-neck complexes can tolerate 75 Nm of coronal moment at low axial load without failure, and this level may be used as an initial estimate of the injury reference value under lateral loading to the human head-neck complex.

  10. Outlook: The Next Twenty Years

    Energy Technology Data Exchange (ETDEWEB)

    Murayama, Hitoshi

    2003-12-07

    I present an outlook for the next twenty years in particle physics. I start with the big questions in our field, broken down into four categories: horizontal, vertical, heaven, and hell. Then I discuss how we attack the bigquestions in each category during the next twenty years. I argue for a synergy between many different approaches taken in our field.

  11. In vitro evaluation of a passive radio frequency identification microchip implanted in human molars subjected to compression forces, for forensic purposes of human identification

    National Research Council Canada - National Science Library

    Moreno, Freddy; Vallejo, Diego; Garzón, Herney; Moreno, Sandra

    2013-01-01

    To evaluate the in vitro behavior of a passive Radio Frequency Identification (RFID) microchip implanted in human molars subjected to compression forces to determine its technical and clinical viability...

  12. Are research subjects adequately protected? A review and discussion of studies conducted by the Advisory Committee on Human Radiation Experiments.

    Science.gov (United States)

    Kass, Nancy E; Sugarman, Jeremy

    1996-09-01

    In light of information uncovered about human radiation experiments conducted during the Cold War, an important charge for the Advisory Committee on Human Radiation Experiments was to assess the current state of protections for human research subjects. This assessment was designed to enhance the Committee's ability to make informed recommendations for the improvement of future policies and practices for the protection of research subjects. The Committee's examination of current protections revealed great improvement over those from the past, yet some problems remain. Although the data collected by the Committee highlight specific areas in need of attention, the Committee's work should be viewed in part as the beginning of a series of ongoing assessments of the adequacy and effectiveness of the protections afforded to human subjects.

  13. Development of realistic physical breast phantoms matched to virtual breast phantoms based on human subject data.

    Science.gov (United States)

    Kiarashi, Nooshin; Nolte, Adam C; Sturgeon, Gregory M; Segars, William P; Ghate, Sujata V; Nolte, Loren W; Samei, Ehsan; Lo, Joseph Y

    2015-07-01

    Physical phantoms are essential for the development, optimization, and evaluation of x-ray breast imaging systems. Recognizing the major effect of anatomy on image quality and clinical performance, such phantoms should ideally reflect the three-dimensional structure of the human breast. Currently, there is no commercially available three-dimensional physical breast phantom that is anthropomorphic. The authors present the development of a new suite of physical breast phantoms based on human data. The phantoms were designed to match the extended cardiac-torso virtual breast phantoms that were based on dedicated breast computed tomography images of human subjects. The phantoms were fabricated by high-resolution multimaterial additive manufacturing (3D printing) technology. The glandular equivalency of the photopolymer materials was measured relative to breast tissue-equivalent plastic materials. Based on the current state-of-the-art in the technology and available materials, two variations were fabricated. The first was a dual-material phantom, the Doublet. Fibroglandular tissue and skin were represented by the most radiographically dense material available; adipose tissue was represented by the least radiographically dense material. The second variation, the Singlet, was fabricated with a single material to represent fibroglandular tissue and skin. It was subsequently filled with adipose-equivalent materials including oil, beeswax, and permanent urethane-based polymer. Simulated microcalcification clusters were further included in the phantoms via crushed eggshells. The phantoms were imaged and characterized visually and quantitatively. The mammographic projections and tomosynthesis reconstructed images of the fabricated phantoms yielded realistic breast background. The mammograms of the phantoms demonstrated close correlation with simulated mammographic projection images of the corresponding virtual phantoms. Furthermore, power-law descriptions of the phantom images

  14. Development of realistic physical breast phantoms matched to virtual breast phantoms based on human subject data

    Energy Technology Data Exchange (ETDEWEB)

    Kiarashi, Nooshin [Carl E. Ravin Advanced Imaging Laboratories, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710 and Department of Electrical and Computer Engineering, Duke University, Durham, North Carolina 27708 (United States); Nolte, Adam C. [Carl E. Ravin Advanced Imaging Laboratories, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710 and Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708 (United States); Sturgeon, Gregory M.; Ghate, Sujata V. [Carl E. Ravin Advanced Imaging Laboratories, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710 (United States); Segars, William P. [Carl E. Ravin Advanced Imaging Laboratories, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710 and Medical Physics Graduate Program, Duke University, Durham, North Carolina 27708 (United States); Nolte, Loren W. [Department of Electrical and Computer Engineering, Duke University, Durham, North Carolina 27708 and Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708 (United States); Samei, Ehsan [Carl E. Ravin Advanced Imaging Laboratories, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710 (United States); Department of Electrical and Computer Engineering, Duke University, Durham, North Carolina 27708 (United States); Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708 (United States); Medical Physics Graduate Program, Duke University, Durham, North Carolina 27708 (United States); Department of Physics, Duke University, Durham, North Carolina 27708 (United States); and others

    2015-07-15

    Purpose: Physical phantoms are essential for the development, optimization, and evaluation of x-ray breast imaging systems. Recognizing the major effect of anatomy on image quality and clinical performance, such phantoms should ideally reflect the three-dimensional structure of the human breast. Currently, there is no commercially available three-dimensional physical breast phantom that is anthropomorphic. The authors present the development of a new suite of physical breast phantoms based on human data. Methods: The phantoms were designed to match the extended cardiac-torso virtual breast phantoms that were based on dedicated breast computed tomography images of human subjects. The phantoms were fabricated by high-resolution multimaterial additive manufacturing (3D printing) technology. The glandular equivalency of the photopolymer materials was measured relative to breast tissue-equivalent plastic materials. Based on the current state-of-the-art in the technology and available materials, two variations were fabricated. The first was a dual-material phantom, the Doublet. Fibroglandular tissue and skin were represented by the most radiographically dense material available; adipose tissue was represented by the least radiographically dense material. The second variation, the Singlet, was fabricated with a single material to represent fibroglandular tissue and skin. It was subsequently filled with adipose-equivalent materials including oil, beeswax, and permanent urethane-based polymer. Simulated microcalcification clusters were further included in the phantoms via crushed eggshells. The phantoms were imaged and characterized visually and quantitatively. Results: The mammographic projections and tomosynthesis reconstructed images of the fabricated phantoms yielded realistic breast background. The mammograms of the phantoms demonstrated close correlation with simulated mammographic projection images of the corresponding virtual phantoms. Furthermore, power

  15. Highly immunoreactive IgG antibodies directed against a set of twenty human proteins in the sera of patients with amyotrophic lateral sclerosis identified by protein array.

    Directory of Open Access Journals (Sweden)

    Caroline May

    Full Text Available Amyotrophic lateral sclerosis (ALS, the most common adult-onset motor neuron disorder, is characterized by the progressive and selective loss of upper and lower motor neurons. Diagnosis of this disorder is based on clinical assessment, and the average survival time is less than 3 years. Injections of IgG from ALS patients into mice are known to specifically mark motor neurons. Moreover, IgG has been found in upper and lower motor neurons in ALS patients. These results led us to perform a case-control study using human protein microarrays to identify the antibody profiles of serum samples from 20 ALS patients and 20 healthy controls. We demonstrated high levels of 20 IgG antibodies that distinguished the patients from the controls. These findings suggest that a panel of antibodies may serve as a potential diagnostic biomarker for ALS.

  16. Vinegar lacks antiglycemic action on enteral carbohydrate absorption in human subjects.

    Science.gov (United States)

    Salbe, Arline D; Johnston, Carol S; Buyukbese, M Akif; Tsitouras, Panayiotis D; Harman, S Mitchell

    2009-12-01

    The antiglycemic effects of vinegar have been known for more than a century and have been demonstrated in animal as well as human studies. Although the exact mechanism of vinegar action is not known, several possibilities have been proposed including suppression of disaccharidase activity, delayed gastric emptying, enhanced glucose uptake in the periphery and conversion to glycogen, and increased satiety. We hypothesized that by suppressing endogenous insulin secretion, we could estimate the glucose absorption rate from an oral carbohydrate load and determine the effects of vinegar ingestion on this rate. To do so, 5 subjects had 4 studies at 1-week intervals, randomly receiving placebo twice (60 mL water) and vinegar twice (20 mL apple cider vinegar, 40 mL water), followed 2 minutes later by a meal of mashed potatoes (0.75 g carbohydrate per kilogram body weight) that was consumed over 20 minutes. At the beginning of the meal, an oral octreotide/insulin suppression test (25-microg bolus octreotide; 180 minute infusion 5 mU/m(2) body surface area per minute regular human insulin, and 0.5 microg/min octreotide) was begun. Blood samples for insulin and glucose were drawn at 20-minute intervals. The oral octreotide/insulin suppression test suppressed endogenous insulin secretion for the first 100 minutes of the study. During this time, the rate of rise of glucose was modestly but significantly (P = .01) greater after vinegar ingestion compared to placebo, suggesting that vinegar does not act to decrease glycemia by interference with enteral carbohydrate absorption.

  17. A dynamic network of transcription in LPS-treated human subjects

    Directory of Open Access Journals (Sweden)

    Moldawer Lyle L

    2009-07-01

    Full Text Available Abstract Background Understanding the transcriptional regulatory networks that map out the coordinated dynamic responses of signaling proteins, transcription factors and target genes over time would represent a significant advance in the application of genome wide expression analysis. The primary challenge is monitoring transcription factor activities over time, which is not yet available at the large scale. Instead, there have been several developments to estimate activities computationally. For example, Network Component Analysis (NCA is an approach that can predict transcription factor activities over time as well as the relative regulatory influence of factors on each target gene. Results In this study, we analyzed a gene expression data set in blood leukocytes from human subjects administered with lipopolysaccharide (LPS, a prototypical inflammatory challenge, in the context of a reconstructed regulatory network including 10 transcription factors, 99 target genes and 149 regulatory interactions. We found that the computationally estimated activities were well correlated to their coordinated action. Furthermore, we found that clustering the genes in the context of regulatory influences greatly facilitated interpretation of the expression data, as clusters of gene expression corresponded to the activity of specific factors or more interestingly, factor combinations which suggest coordinated regulation of gene expression. The resulting clusters were therefore more biologically meaningful, and also led to identification of additional genes under the same regulation. Conclusion Using NCA, we were able to build a network that accounted for between 8–11% genes in the known transcriptional response to LPS in humans. The dynamic network illustrated changes of transcription factor activities and gene expressions as well as interactions of signaling proteins, transcription factors and target genes.

  18. From 'human being' to 'social subject': "unfreezing" ergonomics and the implications for understanding and intervening health-disease process.

    Science.gov (United States)

    Morales, Karen Lange; García-Acosta, Gabriel

    2012-01-01

    Ergonomics has been successful in increasing productivity and comfort in the work arena. It has also contributed to reducing occupational accidents. Despite this, ergonomics is frequently limited to understanding the health-disease process related to human-technology interactions, as this process is more complex than what can be understood from an ergonomic evaluation. Recognising this limit, this work ontologically and epistemologically contrasts the notions of 'human being' and 'social subject', and concludes that the study object of ergonomics, or human-technology interaction, greatly depends on social aspects that nowadays are not tackled explicitly: route (history), project, structure, agency, motivations and power. It also analyses how participatory ergonomics tacitly includes many of these aspects, including some implications that the change of notion, from 'human being' to 'social subject', brings to the understanding of the health-disease process and the reduction of associated risks during human activities.

  19. Association between amebic liver abscess and Human Immunodeficiency Virus infection in Taiwanese subjects

    Directory of Open Access Journals (Sweden)

    Chen Mao-Yuan

    2008-04-01

    Full Text Available Abstract Purpose Invasive amebiasis is an emerging parasitic disorder in Taiwan, especially in patients diagnosed with human immunodeficiency virus (HIV infection. Thirty-three Taiwanese subjects with amebic liver abscess (ALA were examined and a possible correlation between ALA and HIV infection was investigated. Results Among ALA patients, the proportion of HIV-positive individuals increased during the study period. ALA was the first major clinical presentation in 54% of HIV patients with ALA. Overall, 58% (14/24 of HIV-infected patients had a CD4+ count > 200 cells/μL and 82.1% (23/28 had no concurrent opportunistic infection or other evidence of HIV infection. There was no marked difference in clinical characteristics between HIV-positive and HIV-negative ALA patients except the level of leukocytosis. Conclusion While the clinical characteristics described herein cannot be used to determine whether ALA patients have HIV infection, routine HIV testing is recommended in patients with ALA, even in the absence of HIV symptoms.

  20. Large eddy simulation of LDL surface concentration in a subject specific human aorta.

    Science.gov (United States)

    Lantz, Jonas; Karlsson, Matts

    2012-02-02

    The development of atherosclerosis is correlated to the accumulation of lipids in the arterial wall, which, in turn, may be caused by the build-up of low-density lipoproteins (LDL) on the arterial surface. The goal of this study was to model blood flow within a subject specific human aorta, and to study how the LDL surface concentration changed during a cardiac cycle. With measured velocity profiles as boundary conditions, a scale-resolving technique (large eddy simulation, LES) was used to compute the pulsatile blood flow that was in the transitional regime. The relationship between wall shear stress (WSS) and LDL surface concentration was investigated, and it was found that the accumulation of LDL correlated well with WSS. In general, regions of low WSS corresponded to regions of increased LDL concentration and vice versa. The instantaneous LDL values changed significantly during a cardiac cycle; during systole the surface concentration was low due to increased convective fluid transport, while in diastole there was an increased accumulation of LDL on the surface. Therefore, the near-wall velocity was investigated at four representative locations, and it was concluded that in regions with disturbed flow the LDL concentration had significant temporal changes, indicating that LDL accumulation is sensitive to not only the WSS but also near-wall flow.

  1. Quantifying turbulent wall shear stress in a subject specific human aorta using large eddy simulation.

    Science.gov (United States)

    Lantz, Jonas; Gårdhagen, Roland; Karlsson, Matts

    2012-10-01

    In this study, large-eddy simulation (LES) is employed to calculate the disturbed flow field and the wall shear stress (WSS) in a subject specific human aorta. Velocity and geometry measurements using magnetic resonance imaging (MRI) are taken as input to the model to provide accurate boundary conditions and to assure the physiological relevance. In total, 50 consecutive cardiac cycles were simulated from which a phase average was computed to get a statistically reliable result. A decomposition similar to Reynolds decomposition is introduced, where the WSS signal is divided into a pulsating part (due to the mass flow rate) and a fluctuating part (originating from the disturbed flow). Oscillatory shear index (OSI) is plotted against time-averaged WSS in a novel way, and locations on the aortic wall where elevated values existed could easily be found. In general, high and oscillating WSS values were found in the vicinity of the branches in the aortic arch, while low and oscillating WSS were present in the inner curvature of the descending aorta. The decomposition of WSS into a pulsating and a fluctuating part increases the understanding of how WSS affects the aortic wall, which enables both qualitative and quantitative comparisons.

  2. Nonlinear dynamics in pulsatile secretion of parathyroid hormone in normal human subjects

    Science.gov (United States)

    Prank, Klaus; Harms, Heio; Brabant, Georg; Hesch, Rolf-Dieter; Dämmig, Matthias; Mitschke, Fedor

    1995-03-01

    In many biological systems, information is transferred by hormonal ligands, and it is assumed that these hormonal signals encode developmental and regulatory programs in mammalian organisms. In contrast to the dogma of endocrine homeostasis, it could be shown that the biological information in hormonal networks is not only present as a constant hormone concentration in the circulation pool. Recently, it has become apparent that hormone pulses contribute to this hormonal pool, which modulates the responsiveness of receptors within the cell membrane by regulation of the receptor synthesis, movement within the membrane layer, coupling to signal transduction proteins and internalization. Phase space analysis of dynamic parathyroid hormone (PTH) secretion allowed the definition of a (in comparison to normal subjects) relatively quiet ``low dynamic'' secretory pattern in osteoporosis, and a ``high dynamic'' state in hyperparathyroidism. We now investigate whether this pulsatile secretion of PTH in healthy men exhibits characteristics of nonlinear determinism. Our findings suggest that this is conceivable, although on the basis of presently available data and techniques, no proof can be established. Nevertheless, pulsatile secretion of PTH might be a first example of nonlinear deterministic dynamics in an apparently irregular hormonal rhythm in human physiology.

  3. Phenolic acid metabolites as biomarkers for tea- and coffee-derived polyphenol exposure in human subjects.

    Science.gov (United States)

    Hodgson, Jonathan M; Chan, Shin Yee; Puddey, Ian B; Devine, Amanda; Wattanapenpaiboon, Naiyana; Wahlqvist, Mark L; Lukito, Widjaja; Burke, Valerie; Ward, Natalie C; Prince, Richard L; Croft, Kevin D

    2004-02-01

    Tea and coffee are rich in polyphenols with a variety of biological activities. Many of the demonstrated activities are consistent with favourable effects on the risk of chronic diseases. 4-O-methylgallic acid (4OMGA) and isoferulic acid are potential biomarkers of exposure to polyphenols derived from tea and coffee respectively. 4OMGA is derived from gallic acid in tea, and isoferulic acid is derived from chlorogenic acid in coffee. Our major objective was to explore the relationships of tea and coffee intake with 24 h urinary excretion of 4OMGA and isoferulic acid in human subjects. The relationships of long-term usual (111 participants) and contemporaneously recorded current (344 participants) tea and coffee intake with 24 h urinary excretion of 4OMGA and isoferulic acid were assessed in two populations. 4OMGA was related to usual (r 0.50, Pcoffee intake. Overall, our present results are consistent with the proposal that 4OMGA is a good biomarker for black tea-derived polyphenol exposure, but isoferulic acid may be of limited usefulness as a biomarker for coffee-derived polyphenol exposure.

  4. Near-infrared spectroscopy and polysomnography during all-night sleep in human subjects

    Science.gov (United States)

    Fantini, Sergio; Aggarwal, Payal; Chen, Kathleen; Franceschini, Maria Angela; Ehrenberg, Bruce L.

    2003-10-01

    We have performed cerebral near-infrared spectroscopy (NIRS) and polysomnography (electro-encephalography, electro-oculography, electro-myography, pulse oximetry, and respiratory monitoring) during all-night sleep in five human subjects. Polysomnography data were used for sleep staging, while NIRS data were used to measure the concentration and the oxygen saturation of hemoglobin in the frontal brain region. Immediately after sleep onset we observed a decrease in the cerebral concentration of oxy-hemoglobin ([HbO2]) and an increase in the concentration of deoxy-hemoglobin ([Hb]), consistent with a decrease in the cerebral blood flow velocity or an increase in cerebral metabolic rate of oxygen. An opposite trend (increase in [HbO2] and decrease in [Hb]) was usually observed after transition to deep sleep (stages III and IV). During rapid eye movement (REM) sleep, we observed an increase in [HbO2] and decrease in [Hb], consistent with an increase in the cerebral blood flow that overcompensates the increase in the metabolic rate of oxygen associated with REM sleep.

  5. A second generation of physical anthropomorphic 3D breast phantoms based on human subject data

    Science.gov (United States)

    Nolte, Adam; Kiarashi, Nooshin; Samei, Ehsan; Segars, W. P.; Lo, Joseph Y.

    2014-03-01

    Previous fabrication of anthropomorphic breast phantoms has demonstrated their viability as a model for 2D (mammography) and 3D (tomosynthesis) breast imaging systems. Further development of these models will be essential for the evaluation of breast x-ray systems. There is also the potential to use them as the ground truth in virtual clinical trials. The first generation of phantoms was segmented from human subject dedicated breast computed tomography data and fabricated into physical models using highresolution 3D printing. Two variations were made. The first was a multi-material model (doublet) printed with two photopolymers to represent glandular and adipose tissues with the greatest physical contrast available, mimicking 75% and 35% glandular tissue. The second model was printed with a single 75% glandular equivalent photopolymer (singlet) to represent glandular tissue, which can be filled independently with an adipose-equivalent material such as oil. For this study, we have focused on improving the latter, the singlet phantom. First, the temporary oil filler has been replaced with a permanent adipose-equivalent urethane-based polymer. This offers more realistic contrast as compared to the multi-material approach at the expense of air bubbles and pockets that form during the filling process. Second, microcalcification clusters have been included in the singlet model via crushed eggshells, which have very similar chemical composition to calcifications in vivo. The results from these new prototypes demonstrate significant improvement over the first generation of anthropomorphic physical phantoms.

  6. Indomethacin pretreatment reduces ozone-induced pulmonary function decrements in human subjects

    Energy Technology Data Exchange (ETDEWEB)

    Schelegle, E.S.; Adams, W.C.; Siefkin, A.D.

    1987-12-01

    We studied whether O/sub 3/-induced pulmonary function decrements could be inhibited by the prostaglandin synthetase inhibitor, indomethacin, in healthy human subjects. Fourteen college-age males completed six 1-h exposure protocols consisting of no drug, placebo, and indomethacin (Indocin SR 75 mg every 12 h for 5 days) pretreatments, with filtered air and O/sub 3/ (0.35 ppm) exposures within each pretreatment. Pretreatments were delivered weekly in random order in a double-blind fashion. Ozone and filtered air exposures, separated by 72 h, were delivered in random order in a single-blind fashion. Exposures consisted of 1-h exercise on a bicycle ergometer with work loads set to elicit a mean minute ventilation of 60 L/min. Statistical analysis revealed significant (p less than 0.05) across pretreatment effects for FVC and FEV1, with no drug versus indomethacin and placebo versus indomethacin comparisons being significant. These findings suggest that cyclooxygenase products of arachidonic acid, which are sensitive to indomethacin inhibition, play a prominent role in the development of pulmonary function decrements consequent to acute O/sub 3/ exposure.

  7. Optimized lower leg injury probability curves from postmortem human subject tests under axial impacts.

    Science.gov (United States)

    Yoganandan, Narayan; Arun, Mike W J; Pintar, Frank A; Szabo, Aniko

    2014-01-01

    Derive optimum injury probability curves to describe human tolerance of the lower leg using parametric survival analysis. The study reexamined lower leg postmortem human subjects (PMHS) data from a large group of specimens. Briefly, axial loading experiments were conducted by impacting the plantar surface of the foot. Both injury and noninjury tests were included in the testing process. They were identified by pre- and posttest radiographic images and detailed dissection following the impact test. Fractures included injuries to the calcaneus and distal tibia-fibula complex (including pylon), representing severities at the Abbreviated Injury Score (AIS) level 2+. For the statistical analysis, peak force was chosen as the main explanatory variable and the age was chosen as the covariable. Censoring statuses depended on experimental outcomes. Parameters from the parametric survival analysis were estimated using the maximum likelihood approach and the dfbetas statistic was used to identify overly influential samples. The best fit from the Weibull, log-normal, and log-logistic distributions was based on the Akaike information criterion. Plus and minus 95% confidence intervals were obtained for the optimum injury probability distribution. The relative sizes of the interval were determined at predetermined risk levels. Quality indices were described at each of the selected probability levels. The mean age, stature, and weight were 58.2±15.1 years, 1.74±0.08 m, and 74.9±13.8 kg, respectively. Excluding all overly influential tests resulted in the tightest confidence intervals. The Weibull distribution was the most optimum function compared to the other 2 distributions. A majority of quality indices were in the good category for this optimum distribution when results were extracted for 25-, 45- and 65-year-olds at 5, 25, and 50% risk levels age groups for lower leg fracture. For 25, 45, and 65 years, peak forces were 8.1, 6.5, and 5.1 kN at 5% risk; 9.6, 7.7, and 6.1 k

  8. Detection and quantitation of twenty-seven cytokines, chemokines and growth factors pre- and post-high abundance protein depletion in human plasma

    Directory of Open Access Journals (Sweden)

    Seong-Beom Ahn

    2014-06-01

    Full Text Available Cytokines, chemokines and growth factors (CCGFs in human plasma are analyzed for identification of biomarkers. However concentrations of CCGFs are very low; it is difficult to identify and quantify low abundance proteins in the presence of the high abundance proteins (HAPs unless HAPs are removed prior to analysis. However, there is a concern that the low abundance proteins such as CCGFs may also be removed during the HAP depletion process. In this study, we have examined whether or not depletion of the HAPs enhances detection of the CCGFs by immuno-assays. Top 14 HAPs were depleted from 10 healthy volunteers’ plasma using MARS-14 immuno-depletion column and a total of 27 CCGFs were analyzed by bead-based multiplexed immuno-assay. All 27 CCGFs were detected in neat plasma (NP, 25 were detected in flow through fraction (FT and 21 were detected in bound protein (BP fraction. Concentrations of 22 CCGFs were significantly higher in NP compared to FT and BP. Only one CCGF had higher concentration in FT compared to NP. The remaining 2 CCGFs were not different between NP and FT. It was counter-productive for the detection of 24 CCGFs after HAP removal, primarily due to post-depletion protein precipitation and/or re-suspension of pellets.

  9. The exodus of health professionals from sub-Saharan Africa: balancing human rights and societal needs in the twenty-first century.

    Science.gov (United States)

    Ogilvie, Linda; Mill, Judy E; Astle, Barbara; Fanning, Anne; Opare, Mary

    2007-06-01

    Increased international migration of health professionals is weakening healthcare systems in low-income countries, particularly those in sub-Saharan Africa. The migration of nurses, physicians and other health professionals from countries in sub-Saharan Africa poses a major threat to the achievement of health equity in this region. As nurses form the backbone of healthcare systems in many of the affected countries, it is the accelerating migration of nurses that will be most critical over the next few years. In this paper we present a comprehensive analysis of the literature and argue that, from a human rights perspective, there are competing rights in the international migration of health professionals: the right to leave one's country to seek a better life; the right to health of populations in the source and destination countries; labour rights; the right to education; and the right to non-discrimination and equality. Creative policy approaches are required to balance these rights and to ensure that the individual rights of health professionals do not compromise the societal right to health.

  10. Dynamic transcriptional signatures and network responses for clinical symptoms in influenza-infected human subjects using systems biology approaches.

    Science.gov (United States)

    Linel, Patrice; Wu, Shuang; Deng, Nan; Wu, Hulin

    2014-10-01

    Recent studies demonstrate that human blood transcriptional signatures may be used to support diagnosis and clinical decisions for acute respiratory viral infections such as influenza. In this article, we propose to use a newly developed systems biology approach for time course gene expression data to identify significant dynamically response genes and dynamic gene network responses to viral infection. We illustrate the methodological pipeline by reanalyzing the time course gene expression data from a study with healthy human subjects challenged by live influenza virus. We observed clear differences in the number of significant dynamic response genes (DRGs) between the symptomatic and asymptomatic subjects and also identified DRG signatures for symptomatic subjects with influenza infection. The 505 common DRGs shared by the symptomatic subjects have high consistency with the signature genes for predicting viral infection identified in previous works. The temporal response patterns and network response features were carefully analyzed and investigated.

  11. Investigation of dynamic SPECT measurements of the arterial input function in human subjects using simulation, phantom and human studies

    Science.gov (United States)

    Winant, Celeste D.; Aparici, Carina Mari; Zelnik, Yuval R.; Reutter, Bryan W.; Sitek, Arkadiusz; Bacharach, Stephen L.; Gullberg, Grant T.

    2012-01-01

    Computer simulations, a phantom study and a human study were performed to determine whether a slowly rotating single-photon computed emission tomography (SPECT) system could provide accurate arterial input functions for quantification of myocardial perfusion imaging using kinetic models. The errors induced by data inconsistency associated with imaging with slow camera rotation during tracer injection were evaluated with an approach called SPECT/P (dynamic SPECT from positron emission tomography (PET)) and SPECT/D (dynamic SPECT from database of SPECT phantom projections). SPECT/P simulated SPECT-like dynamic projections using reprojections of reconstructed dynamic 94Tc-methoxyisobutylisonitrile (94Tc-MIBI) PET images acquired in three human subjects (1 min infusion). This approach was used to evaluate the accuracy of estimating myocardial wash-in rate parameters K1 for rotation speeds providing 180° of projection data every 27 or 54 s. Blood input and myocardium tissue time-activity curves (TACs) were estimated using spatiotemporal splines. These were fit to a one-compartment perfusion model to obtain wash-in rate parameters K1. For the second method (SPECT/D), an anthropomorphic cardiac torso phantom was used to create real SPECT dynamic projection data of a tracer distribution derived from 94Tc-MIBI PET scans in the blood pool, myocardium, liver and background. This method introduced attenuation, collimation and scatter into the modeling of dynamic SPECT projections. Both approaches were used to evaluate the accuracy of estimating myocardial wash-in parameters for rotation speeds providing 180° of projection data every 27 and 54 s. Dynamic cardiac SPECT was also performed in a human subject at rest using a hybrid SPECT/CT scanner. Dynamic measurements of 99mTc-tetrofosmin in the myocardium were obtained using an infusion time of 2 min. Blood input, myocardium tissue and liver TACs were estimated using the same spatiotemporal splines. The spatiotemporal maximum

  12. Investigation of dynamic SPECT measurements of the arterial input function in human subjects using simulation, phantom and human studies.

    Science.gov (United States)

    Winant, Celeste D; Aparici, Carina Mari; Zelnik, Yuval R; Reutter, Bryan W; Sitek, Arkadiusz; Bacharach, Stephen L; Gullberg, Grant T

    2012-01-21

    Computer simulations, a phantom study and a human study were performed to determine whether a slowly rotating single-photon computed emission tomography (SPECT) system could provide accurate arterial input functions for quantification of myocardial perfusion imaging using kinetic models. The errors induced by data inconsistency associated with imaging with slow camera rotation during tracer injection were evaluated with an approach called SPECT/P (dynamic SPECT from positron emission tomography (PET)) and SPECT/D (dynamic SPECT from database of SPECT phantom projections). SPECT/P simulated SPECT-like dynamic projections using reprojections of reconstructed dynamic (94)Tc-methoxyisobutylisonitrile ((94)Tc-MIBI) PET images acquired in three human subjects (1 min infusion). This approach was used to evaluate the accuracy of estimating myocardial wash-in rate parameters K(1) for rotation speeds providing 180° of projection data every 27 or 54 s. Blood input and myocardium tissue time-activity curves (TACs) were estimated using spatiotemporal splines. These were fit to a one-compartment perfusion model to obtain wash-in rate parameters K(1). For the second method (SPECT/D), an anthropomorphic cardiac torso phantom was used to create real SPECT dynamic projection data of a tracer distribution derived from (94)Tc-MIBI PET scans in the blood pool, myocardium, liver and background. This method introduced attenuation, collimation and scatter into the modeling of dynamic SPECT projections. Both approaches were used to evaluate the accuracy of estimating myocardial wash-in parameters for rotation speeds providing 180° of projection data every 27 and 54 s. Dynamic cardiac SPECT was also performed in a human subject at rest using a hybrid SPECT/CT scanner. Dynamic measurements of (99m)Tc-tetrofosmin in the myocardium were obtained using an infusion time of 2 min. Blood input, myocardium tissue and liver TACs were estimated using the same spatiotemporal splines. The

  13. From the ideal market to the ideal clinic: constructing a normative standard of fairness for human subjects research.

    Science.gov (United States)

    Phillips, Trisha

    2011-02-01

    Preventing exploitation in human subjects research requires a benchmark of fairness against which to judge the distribution of the benefits and burdens of a trial. This paper proposes the ideal market and its fair market price as a criterion of fairness. The ideal market approach is not new to discussions about exploitation, so this paper reviews Wertheimer's inchoate presentation of the ideal market as a principle of fairness, attempt of Emanuel and colleagues to apply the ideal market to human subjects research, and Ballantyne's criticisms of both the ideal market and the resulting benchmark of fairness. It argues that the criticism of this particular benchmark is on point, but the rejection of the ideal market is mistaken. After presenting a complete account of the ideal market, this paper proposes a new method for applying the ideal market to human subjects research and illustrates the proposal by considering a sample case.

  14. Development, characterization, and epitope mapping of a panel of twenty-four monoclonal antibodies specific for human inducible nitric oxide synthase.

    Science.gov (United States)

    Webber, Robert J; Rodriguez, John G; Webber, Douglas S; Dunnebacke, Thelma H

    2005-02-01

    A panel of monoclonal antibodies (MAbs) to human inducible nitric oxide synthase (hiNOS) has been developed. By isotype analysis of the MAbs cloned from the 24 different positive hybridomas, 13 were determined to be mouse IgG1, two were mouse IgG2a, two were mouse IgG2b, and the seven others were mouse IgM antibodies: all contained kappa light chains. The anti-hiNOS MAbs were initially characterized by ELISA, RIA, Western blot, and immunocytochemistry, and then they were epitope mapped using synthetic peptides and a three-step mapping procedure. In the first step, each of the 24 MAbs was tested by indirect ELISA for binding to 96 overlapping 18-amino acid-long peptides that span the entire 1153-amino acid length of hiNOS. Eight IgG class anti-hiNOS MAbs were found to bind to one of five different peptides. In the second step, a series of amino terminal and carboxyl terminal truncated peptides were synthesized for each of the five peptides to which one or more of the MAbs bound. Each of the eight anti-hiNOS MAbs was found to bind to the truncated peptides with a unique specificity that identified the amino acid segment involved in binding. The third step in the epitope mapping process utilized three series of overlapping 5-, 6-, 7-, 8-, and 9-amino acid-long peptides for each of these segments and identified the exact amino acids of hiNOS involved in antibody binding. Anti-hiNOS MAbs 2A1-F8, 2D2-B2, 21C10-1D10, and 24B10-2C7 were found to be especially useful in different immunoassays.

  15. Subjective valuation of cushioning in a human drop landing task as quantified by trade-offs in mechanical work.

    Science.gov (United States)

    Skinner, Nathaniel E; Zelik, Karl E; Kuo, Arthur D

    2015-07-16

    Humans can perform motor tasks in a variety of ways, yet often favor a particular strategy. Some factors governing the preferred strategy may be objective and quantifiable, (e.g. metabolic energy or mechanical work) while others may be more subjective and less measurable, (e.g. discomfort, pain, or mental effort). Subjectivity can make it challenging to explain or predict preferred movement strategies. We propose that subjective factors might nevertheless be characterized indirectly by their trade-offs against more objective measures such as work. Here we investigated whether subjective costs that influence human movement during drop landings could be indirectly assessed by quantifying mechanical work performed. When landing on rigid ground, humans typically absorb much of the collision actively by bending their knees, perhaps to avoid the discomfort of stiff-legged landings. We measured how work performed by healthy adults (N=8) changed as a function of surface cushioning for drop landings (fixed at about 0.4m) onto varying amounts of foam. Landing on more foam dissipated more energy passively in the surface, thus reducing the net dissipation required of subjects, due to relatively fixed landing energy. However, subjects actually performed even less work in the dissipative collision, as well as in the subsequent active, positive work to return to upright stance (approximately linear decrease of about 1.52 J per 1 cm of foam thickness). As foam thickness increased, there was also a corresponding reduction in center-of-mass vertical displacement after initial impact by up to 43%. Humans appear to subjectively value cushioning, revealed by the extra work they perform landing without it. Cushioning is thus worth more than the energy it dissipates, in an amount that indicates the subjective discomfort of stiff landings.

  16. Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies.

    Science.gov (United States)

    Studerus, Erich; Kometer, Michael; Hasler, Felix; Vollenweider, Franz X

    2011-11-01

    Psilocybin and related hallucinogenic compounds are increasingly used in human research. However, due to limited information about potential subjective side effects, the controlled medical use of these compounds has remained controversial. We therefore analysed acute, short- and long-term subjective effects of psilocybin in healthy humans by pooling raw data from eight double-blind placebo-controlled experimental studies conducted between 1999 and 2008. The analysis included 110 healthy subjects who had received 1-4 oral doses of psilocybin (45-315 µg/kg body weight). Although psilocybin dose-dependently induced profound changes in mood, perception, thought and self-experience, most subjects described the experience as pleasurable, enriching and non-threatening. Acute adverse drug reactions, characterized by strong dysphoria and/or anxiety/panic, occurred only in the two highest dose conditions in a relatively small proportion of subjects. All acute adverse drug reactions were successfully managed by providing interpersonal support and did not need psychopharmacological intervention. Follow-up questionnaires indicated no subsequent drug abuse, persisting perception disorders, prolonged psychosis or other long-term impairment of functioning in any of our subjects. The results suggest that the administration of moderate doses of psilocybin to healthy, high-functioning and well-prepared subjects in the context of a carefully monitored research environment is associated with an acceptable level of risk.

  17. Unsteady-state human-body exergy consumption rate and its relation to subjective assessment of dynamic thermal environments

    DEFF Research Database (Denmark)

    Schweiker, Marcel; Kolarik, Jakub; Dovjak, Mateja

    2016-01-01

    Few examples studied applicability of exergy analysis on human thermal comfort. These examples relate the human-body exergy consumption rate with subjectively obtained thermal sensation votes and had been based on steady-state calculation methods. However, humans are rarely exposed to steady......-state thermal environments. Therefore, the first objective of the current paper was to compare a recently introduced unsteady-state model with previously used steady-state model using data obtained under both constant and transient temperature conditions. The second objective was to explore a relationship...... between the human-body exergy consumption rate and subjective assessment of thermal environment represented by thermal sensation as well as to extend the investigation towards thermal acceptability votes. Comparison of steady-state and unsteady-state model showed that results from both models were...

  18. The response of endocrine system to stress loads during space flight in human subject.

    Science.gov (United States)

    Macho, L; Koska, J; Ksinantova, L; Pacak, K; Hoff, T; Noskov, V B; Grigoriev, A I; Vigas, M; Kvetnansky, R

    2003-01-01

    The responses of endocrine system to the exposure to stress-work load and hormonal changes during oral glucose tolerance tests were studied in the Slovak astronaut before (three weeks before flight), during (on the 4th and the 6th days of space flight), and after space flight (1-3 days and 15-17 days after space flight) on board of space station MIR. Blood samples during the tests were collected via cannula inserted into cubital vein, centrifuged in the special appliance Plasma-03, frozen in Kryogem-03, and at the end of the 8-day space flight transferred to Earth in special container for hormonal analysis. Preflight workload produced an increase of plasma norepinephrine and a moderate elevation of epinephrine levels. Plasma levels of insulin, growth hormone, prolactin and cortisol were not markedly changed immediately or 10 min after the end of work load. The higher increases of plasma growth hormone, prolactin and catecholamine levels were noted after workload during space flight as compared to preflight response. The higher plasma glucose and insulin levels were noted during the oral glucose tolerance test in space flight and also in the post flight period. Plasma epinephrine levels were slightly decreasing during glucose tolerance test; however, plasma norepinephrine levels were not changed. The similar patterns of catecholamine levels during glucose tolerance test were found when compared the preflight, in-flight and post flight values. These data demonstrate the changes of the dynamic responses of endocrine system to stress-work and metabolic loads during space flight in human subject.

  19. Brain neuronal CB2 cannabinoid receptors in drug abuse and depression: from mice to human subjects.

    Directory of Open Access Journals (Sweden)

    Emmanuel S Onaivi

    Full Text Available BACKGROUND: Addiction and major depression are mental health problems associated with stressful events in life with high relapse and reoccurrence even after treatment. Many laboratories were not able to detect the presence of cannabinoid CB2 receptors (CB2-Rs in healthy brains, but there has been demonstration of CB2-R expression in rat microglial cells and other brain associated cells during inflammation. Therefore, neuronal expression of CB2-Rs had been ambiguous and controversial and its role in depression and substance abuse is unknown. METHODOLOGY/PRINCIPAL FINDINGS: In this study we tested the hypothesis that genetic variants of CB2 gene might be associated with depression in a human population and that alteration in CB2 gene expression may be involved in the effects of abused substances including opiates, cocaine and ethanol in rodents. Here we demonstrate that a high incidence of (Q63R but not (H316Y polymorphism in the CB2 gene was found in Japanese depressed subjects. CB2-Rs and their gene transcripts are expressed in the brains of naïve mice and are modulated following exposure to stressors and administration of abused drugs. Mice that developed alcohol preference had reduced CB2 gene expression and chronic treatment with JWH015 a putative CB2-R agonist, enhanced alcohol consumption in stressed but not in control mice. The direct intracerebroventricular microinjection of CB2 anti-sense oligonucleotide into the mouse brain reduced mouse aversions in the plus-maze test, indicating the functional presence of CB2-Rs in the brain that modifies behavior. We report for the using electron microscopy the sub cellular localization of CB2-Rs that are mainly on post-synaptic elements in rodent brain. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate the functional expression of CB2-Rs in brain that may provide novel targets for the effects of cannabinoids in depression and substance abuse disorders beyond neuro-immunocannabinoid activity.

  20. The response of endocrine system to stress loads during space flight in human subject

    Science.gov (United States)

    Macho, L.; Koška, J.; Kšinantová, L.; Pacak, K.; Hoff, T.; Noskov, V. B.; Grigoriev, A. I.; Vigaš, M.; Kvetňanský, R.

    The responses of endocrine system to the exposure to stress-work load and hormonal changes during oral glucose tolerance tests were studied in the Slovak astronaut before (three weeks before flight), during (on the 4th and the 6th days of space flight), and after space flight (1-3 days and 15-17 days after space flight) on board of space station MIR. Blood samples during the tests were collected via cannula inserted into cubital vein, centrifuged in the special appliance Plasma-03, frozen in Kryogem-03, and at the end of the 8-day space flight transforred to Earth in special container for hormonal analysis. Preflight workload produced an increase of plasma norepinephrine and a moderate elevation of epinephrine levels. Plasma levels of insulin, growth hormone, prolactin and cortisol were not markedly changed immediately or 10 min after the end of work load. The higher increases of plasma growth hormone, prolactin and catecholamine levels were noted after workload during space flight as compared to preflight response. The higher plasma glucose and insulin levels were noted during the oral glucose tolerance test in space flight and also in the post flight period. Plasma epinephrine levels were slightly decreasing during glucose tolerance test; however, plasma norepinephrine levels were not changed. The similar patterns of catecholamine levels during glucose tolerance test were found when compared the preflight, in-flight and post flight values. These data demonstrate the changes of the dynamic responses of endocrine system to stress-work and metabolic loads during space flight in human subject.

  1. Investigation of Pelvic Injuries on Eighteen Post Mortem Human Subjects Submitted to Oblique Lateral Impacts.

    Science.gov (United States)

    Lebarbé, Matthieu; Baudrit, Pascal; Potier, Pascal; Petit, Philippe; Trosseille, Xavier; Compigne, Sabine; Masuda, Mitsutoshi; Fujii, Takumi; Douard, Richard

    2016-11-01

    The aim of this study was to investigate the sacroiliac joint injury mechanism. Two test configurations were selected from full scale car crashes conducted with the WorldSID 50(th) dummy resulting in high sacroiliac joint loads and low pubic symphysis force, i.e. severe conditions for the sacroiliac joint. The two test conditions were reproduced in laboratory using a 150-155 kg guided probe propelled respectively at 8 m/s and 7.5 m/s and with different shapes and orientations for the plate impacting the pelvis. Nine Post Mortem Human Subject (PMHS) were tested in each of the two configurations (eighteen PMHS in total). In order to get information on the time of fracture, eleven strain gauges were glued on the pelvic bone of each PMHS. Results - In the first configuration, five PMHS out of nine sustained AIS2+ pelvic injuries. All five presented sacroiliac joint injuries associated with pubic area injuries. In the second configuration, four specimens out of nine sustained AIS2+ pelvic injuries. Two of them presented sacroiliac joint fractures associated with pubic area injuries. The other two presented injuries at the pubic area and acetabulum only. The strain gauges signals suggested that the pubic fractures occurred before the sacroiliac joint fractures in the great majority of the cases (five cases out of seven). Conclusions - Even in the oblique impact conditions of the present study, the pubic symphysis area was observed to be the weakest zone of the pelvis and its failure the predominant cause of sacroiliac joint injuries. It was hypothesized that the failure of the pubic rami allowed the hemi-pelvis to rotate inward, and that this closing-book motion induced the failure of the sacroiliac joint.

  2. Analysis of the Chaotic Characteristics of Human Colonic Activities and Comparison of Healthy Participants to Costive Subjects.

    Science.gov (United States)

    Lu, Li; Yan, Guozheng; Zhao, Kai; Xu, Fei

    2016-01-01

    Constipation is a common yet distressing disease that has high rates of morbidity and impacts patients' quality of life. However, there is no perfect method to distinguish costive patients from healthy subjects. Is there chaos in human colonic activities? Are there any differences for the chaos indicators of colonic activities between healthy and costive subjects? Can these indicators distinguish patients with constipation from healthy subjects? To answer these questions, colonic pressure data from 16 healthy subjects and 48 patients with constipation were analyzed using the chaos theory. Three chaotic indicators [i.e., the largest Lyapunov exponent (LyE), correlation dimension (CorDim), and Kolmogorov entropy (KoEn)] were calculated and compared between groups with the Wilcoxon rank sum test. As a result, the LyE was greater than zero and the CorDim was fractioned, which showed that human colonic activities have clear chaotic characteristics. Statistically significant differences were observed between groups for CorDim (p chaotic indicator of CorDim was able to differentiate between patients with constipation and healthy subjects. The chaos theory provides a new method for learning the nonlinear dynamics of human gastrointestinal activities.

  3. Pharmacokinetic evaluation of the tau PET radiotracer [18F]T807 ([18F]AV-1451) in human subjects.

    Science.gov (United States)

    Wooten, Dustin; Guehl, Nicolas J; Verwer, Eline E; Shoup, Timothy M; Yokell, Daniel L; Zubcevik, Nevena; Vasdev, Neil; Zafonte, Ross D; Johnson, Keith A; El Fakhri, Georges; Normandin, Marc David

    2016-09-22

    [(18)F]T807 is a PET radiotracer developed for imaging tau protein aggregates, which are implicated in neurological disorders including Alzheimer's disease (AD) and traumatic brain injury (TBI). The current study characterizes [(18)F]T807 pharmacokinetics in human subjects using dynamic PET imaging and metabolite-corrected arterial input functions.

  4. Comparisons of synthetic 1-18 ACTH (Organon 2001) and 1-39 ACTH of animal origin in human subjects.

    Science.gov (United States)

    Danowski, T S; Fisher, E R; Robinson, S M

    The studies in human subjects herein reported provide data on the relative effects of 1-18 ACTH (Organon 2001) and commercial 1-39 ACTH of animal origin on plasma cortisol, serum non-esterified fatty acids, and certain urinary steroids.

  5. Role of the vestibular system in the arterial pressure response to parabolic-flight-induced gravitational changes in human subjects.

    Science.gov (United States)

    Iwata, Chihiro; Abe, Chikara; Tanaka, Kunihiko; Morita, Hironobu

    2011-05-16

    Arterial pressure (AP) is known to fluctuate during parabolic-flight-induced gravitational changes in human subjects, increasing during hypergravity and decreasing during microgravity. In this study, we examined whether the vestibular system participates in the AP response to the gravitational changes induced by parabolic flight in human subjects. Eight subjects performed parabolic flights in a supine position as their AP was measured. Their vestibular inputs during the gravitational changes were reversibly masked by artificial electrical stimulation (galvanic vestibular stimulation, GVS). The AP responses during the parabolas were then compared between the GVS-off and GVS-on conditions. AP increased during hypergravity and decreased during microgravity. The AP responses at the onset of hypergravity and microgravity were abolished by GVS. These results indicate that the vestibular system elicits pressor and depressor responses during parabolic-flight-induced hypergravity and microgravity, respectively. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  6. 76 FR 5735 - Revisions to EPA's Rule on Protections for Subjects in Human Research Involving Pesticides

    Science.gov (United States)

    2011-02-02

    ... requirement that human studies be ``designed and based on the results of animal experimentation.'' Finally... the principles of the Nuremberg Code with respect to human experimentation; and shall establish an... Nuremberg Code pertaining to human experimentation. Petitioners argued that the 2006 rule was...

  7. Near-surface structural examination of human tooth enamel subject to in vitro demineralization and remineralization

    Science.gov (United States)

    Gaines, Carmen Veronica

    The early stages of chemical tooth decay are governed by dynamic processes of demineralization and remineralization of dental enamel that initiates along the surface of the tooth. Conventional diagnostic techniques lack the spatial resolution required to analyze near-surface structural changes in enamel at the submicron level. In this study, slabs of highly-polished, decay-free human enamel were subjected to 0.12M EDTA and buffered lactic acid demineralizing agents and MI Paste(TM) and calcifying (0.1 ppm F) remineralizing treatments in vitro. Grazing incidence x-ray diffraction (GIXD), a technique typically used for thin film analysis, provided depth profiles of crystallinity changes in surface enamel with a resolution better than 100 nm. In conjunction with nanoindentation, a technique gaining acceptance as a means of examining the mechanical properties of sound enamel, these results were corroborated with well-established microscopy and Raman techniques to assess the nanohardness, morphologies and chemical nature of treated enamel. Interestingly, the average crystallite size of surface enamel along its c-axis dimension increased by nearly 40% after a 60 min EDTA treatment as detected by GIXD. This result was in direct contrast to the obvious surface degradation observed by microscopic and confocal Raman imaging. A decrease in nanohardness from 4.86 +/- 0.44 GPa to 0.28 +/- 0.10 GPa was observed. Collective results suggest that mineral dissolution characteristics evident on the micron scale may not be fully translated to the nanoscale in assessing the integrity of chemically-modified tooth enamel. While an intuitive decrease in enamel crystallinity was observed with buffered lactic acid-treated samples, demineralization was too slow to adequately quantify the enamel property changes seen. MI Paste(TM) treatment of EDTA-demineralized enamel showed preferential growth along the a-axis direction. Calcifying solution treatments of both demineralized sample types

  8. Generation of a suite of 3D computer-generated breast phantoms from a limited set of human subject data

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, Christina M. L. [Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708 and Carl E. Ravin Advanced Imaging Laboratories, Duke University Medical Center, Durham, North Carolina 27705 (United States); Palmeri, Mark L. [Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708 (United States); Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina 27710 (United States); Segars, W. Paul [Carl E. Ravin Advanced Imaging Laboratories, Duke University Medical Center, Durham, North Carolina 27705 (United States); Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710 (United States); Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708 (United States); Medical Physics Graduate Program, Duke University, Durham, North Carolina 27705 (United States); Veress, Alexander I. [Department of Mechanical Engineering, University of Washington, Seattle, Washington 98195 (United States); Dobbins, James T. III [Carl E. Ravin Advanced Imaging Laboratories, Duke University Medical Center, Durham, North Carolina 27705 (United States); Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710 (United States); Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708 (United States); Medical Physics Graduate Program, Duke University, Durham, North Carolina 27705 (United States); Department of Physics, Duke University, Durham, North Carolina 27708 (United States)

    2013-04-15

    Purpose: The authors previously reported on a three-dimensional computer-generated breast phantom, based on empirical human image data, including a realistic finite-element based compression model that was capable of simulating multimodality imaging data. The computerized breast phantoms are a hybrid of two phantom generation techniques, combining empirical breast CT (bCT) data with flexible computer graphics techniques. However, to date, these phantoms have been based on single human subjects. In this paper, the authors report on a new method to generate multiple phantoms, simulating additional subjects from the limited set of original dedicated breast CT data. The authors developed an image morphing technique to construct new phantoms by gradually transitioning between two human subject datasets, with the potential to generate hundreds of additional pseudoindependent phantoms from the limited bCT cases. The authors conducted a preliminary subjective assessment with a limited number of observers (n= 4) to illustrate how realistic the simulated images generated with the pseudoindependent phantoms appeared. Methods: Several mesh-based geometric transformations were developed to generate distorted breast datasets from the original human subject data. Segmented bCT data from two different human subjects were used as the 'base' and 'target' for morphing. Several combinations of transformations were applied to morph between the 'base' and 'target' datasets such as changing the breast shape, rotating the glandular data, and changing the distribution of the glandular tissue. Following the morphing, regions of skin and fat were assigned to the morphed dataset in order to appropriately assign mechanical properties during the compression simulation. The resulting morphed breast was compressed using a finite element algorithm and simulated mammograms were generated using techniques described previously. Sixty-two simulated mammograms

  9. The musical brain: brain waves reveal the neurophysiological basis of musicality in human subjects.

    Science.gov (United States)

    Tervaniemi, M; Ilvonen, T; Karma, K; Alho, K; Näätänen, R

    1997-04-18

    To reveal neurophysiological prerequisites of musicality, auditory event-related potentials (ERPs) were recorded from musical and non-musical subjects, musicality being here defined as the ability to temporally structure auditory information. Instructed to read a book and to ignore sounds, subjects were presented with a repetitive sound pattern with occasional changes in its temporal structure. The mismatch negativity (MMN) component of ERPs, indexing the cortical preattentive detection of change in these stimulus patterns, was larger in amplitude in musical than non-musical subjects. This amplitude enhancement, indicating more accurate sensory memory function in musical subjects, suggests that even the cognitive component of musicality, traditionally regarded as depending on attention-related brain processes, in fact, is based on neural mechanisms present already at the preattentive level.

  10. THE DEVELOPMENT OF PROFESSIONAL SUBJECTIVE POSITION OF MANAGEMENT HUMAN RESOURCES FOR HEALTH

    Directory of Open Access Journals (Sweden)

    Ol'ga L. Zadvornaya

    2016-01-01

    Full Text Available The article is devoted to the problem of development of professional-subjective position of managerial staff of health care in the system of continuous professional education in the conditions of optimization of activities of the health system. Professional and subject position reflects the position of individual managers in a professional environment, its relationship to the quality of professional activity, to himself, to patients and colleagues to level their skills.Purpose/objectives: analysis of core competencies, forming the professional and subject position of heads of medical organizations; identify possible ways of development of professional-subjective position of managerial staff of the public health based on the use of modern technologies and active methods of training in system of continuous professional education. Methodology. In conducting the present study used data from official sources, literature review, scientific methods of analysis and synthesis, comparative analysis and modeling. The results of the study indicate the necessity of actualization of the subject position of heads of medical organizations. Conclusions /Significance. The necessity of formation and development of professional subjective position of the heads due to the needs of society and the health care system with modern requirements for quality management training of health. Professional and subject position is a characteristic feature of a highly qualified specialist in the area of governance, reflecting its active attitude toward self and professional activity, factor of efficiency of activity of medical organizations. The real practice of activity of medical organizations requires improved approaches in the preparation of healthcare managers. Most of the leaders are having difficulties, associated not only with necessity of development of universal and professional competences, but also the necessity of development of professional-subjective position

  11. Genotyping of Giardia duodenalis isolates from human subjects in Zabul, using PCR-RFLP

    Directory of Open Access Journals (Sweden)

    Maryam Abedi

    2016-09-01

    Full Text Available Objective: To uncover the molecular prevalence of Giardia duodenalis by PCR-restriction fragment length polymorphism (RFLP in Zabul city, Iran. Methods: Twenty-four stool samples were collected from 215 patients with suspected giardiasis by microscopic examination. To increase the sensitivity of the PCR, the total genomic DNA from isolates was extracted by applying glass beads and the QIAamp Kit. A one-step PCRRFLP method, targeting the glutamate dehydrogenase gene, was utilized to differentiate the assemblages A and B among isolates. Results: The PCR fragment was determined from 30 isolates, RFLP assay of 24 isolates showed 24 (100 isolates as Genotype B group BIII. Conclusions: The results with the glutamate dehydrogenase gene assay demonstrated that the predominant subtype of Giardia duodenalis in the area is BIII, which showed animals are the main reservoir of the isolates in this area.

  12. Effects of cake made from whole soy powder on postprandial blood glucose and insulin levels in human subjects.

    Science.gov (United States)

    Oku, Tsuneyuki; Nakamura, Mariko; Takasugi, Ayako; Hashiguchi-Ishiguro, Michiru; Tanabe, Kenichi; Nakamura, Sadako

    2009-01-01

    We investigated the glycemic index (GI) and the insulinemic index (II) of cake made from whole soy powder (SBC) and the suppressive effects of SBC on the postprandial blood glucose and insulin by other carbohydrate foods. Furthermore, breath hydrogen excretion was simultaneously investigated. Twenty subjects were given 114 g SBC, 144 g cooked paddy-rice, and 60 g SBC with 144 g cooked paddy-rice in random order using a within-subject, repeated-measures design. Blood and end-expiratory gas were collected at the indicated periods after ingestion. The GI and the II of SBC were 22+/-6 and 48+/-29, respectively. The elevation of blood glucose by cooked paddy-rice was significantly suppressed by the addition of 60 g SBC, although the insulin secretion did not decrease. Breath hydrogen excretion by the addition of SBC to 144 g cooked paddy-rice was not significantly increased in comparison with cooked paddy-rice alone. SBC was of low GI and low II, but the postprandial insulin secretion in response to cooked paddy-rice was not suppressed.

  13. Indirect detection of an epitope-specific response to HIV-1 gp120 immunization in human subjects.

    Directory of Open Access Journals (Sweden)

    Evgeny Shmelkov

    Full Text Available A specific response of human serum neutralizing antibodies (nAb to a conformational epitope as a result of vaccination of human subjects with the surface envelope glycoprotein (gp120 of HIV-1 has not previously been documented. Here, we used computational analysis to assess the epitope-specific responses of human subjects, which were immunized with recombinant gp120 immunogens in the VAX003 and VAX004 clinical trials. Our computational methodology--a variation of sieve analysis--compares the occurrence of specific nAb targeted conformational 3D epitopes on viruses from infected individuals who received vaccination to the occurrence of matched epitopes in the viruses infecting placebo subjects. We specifically studied seven crystallographically defined nAb targeted conformational epitopes in the V3 loop, an immunogenic region of gp120. Of the six epitopes present in the immunogens and targeted by known monoclonal neutralizing antibodies, only the one targeted by the anti-V3 nAb 2219 exhibited a significant reduction in occurrence in vaccinated subjects compared to the placebo group. This difference occurred only in the VAX003 Thailand cohort. No difference was seen between vaccinated and placebo groups for the occurrence of an epitope that was not present in the immunogen. Thus, it can be theorized that a specific 2219-like human neutralizing antibody immune response to AIDSVAX immunization occurred in the VAX003 cohort, and that this response protected subjects from a narrow subset of HIV-1 viruses circulating in Thailand in the 1990s and bearing the conformational epitope targeted by the neutralizing antibody 2219.

  14. Antibody responses to bacteriophage phi X-174 in human subjects exposed to the antarctic winter-over model of spaceflight

    Science.gov (United States)

    Shearer, W. T.; Lugg, D. J.; Rosenblatt, H. M.; Nickolls, P. M.; Sharp, R. M.; Reuben, J. M.; Ochs, H. D.

    2001-01-01

    BACKGROUND: It has been proposed that exposure to long-term spaceflight conditions (stress, isolation, sleep disruption, containment, microbial contamination, and solar radiation) or to ground-based models of spaceflight will alter human immune responses, but specific antibody responses have not been fully evaluated. OBJECTIVE: We sought to determine whether exposure to the 8-month Antarctic winter-over model of spaceflight would alter human antibody responses. METHODS: During the 1999 Australian National Antarctic Research Expeditions, 11 adult study subjects at Casey, Antarctica, and 7 control subjects at Macquarie Island, sub-Antarctica, received primary and secondary immunizations with the T cell-dependent neoantigen bacteriophage phi X-174. Periodic plasma samples were analyzed for specific antibody function. RESULTS: All of the subjects from Casey, Antarctica, cleared bacteriophage phi X-174 normally by 1 week after primary immunization, and all had normal primary and secondary antibody responses, including immunologic memory amplification and switch from IgM to IgG antibody production. One subject showed a high normal pattern, and one subject had a low normal pattern. The control subjects from Macquarie Island also had normal immune responses to bacteriophage phi X-174. CONCLUSIONS: These data do not support the hypothesis that de novo specific antibody responses of subjects become defective during the conditions of the Antarctic winter-over. Because the Antarctic winter-over model of spaceflight lacks the important factors of microgravity and solar radiation, caution must be used in interpreting these data to anticipate normal antibody responses in long-term spaceflight.

  15. Airflow in the Human Nasal Passage and Sinuses of Chronic Rhinosinusitis Subjects.

    Directory of Open Access Journals (Sweden)

    Haribalan Kumar

    Full Text Available Endoscopic surgery is performed on patients with chronic inflammatory disease of the paranasal sinuses to improve sinus ventilation. Little is known about how sinus surgery affects sinonasal airflow. In this study nasal passage geometry was reconstructed from computed tomographic imaging from healthy normal, pre-operative, and post-operative subjects. Transient air flow through the nasal passage during calm breathing was simulated. Subject-specific differences in ventilation of the nasal passage were observed. Velocity magnitude at ostium was different between left and right airway. In FESS, airflow in post-surgical subjects, airflow at the maxillary sinus ostium was upto ten times higher during inspiration. In a Lothrop procedure, airflow at the frontal sinus ostium can be upto four times higher during inspiration. In both post-operative subjects, airflow at ostium was not quasi-steady. The subject-specific effect (of surgery on sinonasal interaction evaluated through airflow simulations may have important consequences for pre- and post-surgical assessment and surgical planning, and design for improvement of the delivery efficiency of nasal therapeutics.

  16. A phase 1 study evaluating the pharmacokinetics, safety and tolerability of repeat dosing with a human IL-13 antibody (CAT-354 in subjects with asthma

    Directory of Open Access Journals (Sweden)

    Roskos Lorin

    2010-01-01

    Full Text Available Abstract Background IL-13 has been implicated in the development of airway inflammation and hyperresponsiveness. This study investigated the multiple-dose pharmacokinetics and safety profile of human anti-IL-13 antibody (CAT-354 in adults with asthma. Methods This was a multiple-dose, randomised, double-blind, placebo-controlled phase 1 study in asthmatics (forced expiratory volume in 1 second [FEV1] ≥ 80% predicted. Subjects were randomised to receive three intravenous infusions of CAT-354 (1 mg/kg, 5 mg/kg or 10 mg/kg or placebo at 28-day intervals. Blood samples were taken for pharmacokinetic measurements. Safety was assessed by adverse events, vital signs, ECGs, laboratory and pulmonary function parameters. Results Twenty-three subjects (aged 21-60 years, FEV1 88-95% predicted received ≥ 1 dose of study medication. The half-life of CAT-354 was 12-17 days and was dose-independent. The maximum serum concentration and area under the curve were dose-dependent. Clearance (2.2-2.6 mL/day/kg and volume of distribution (44-57 mL/kg were both low and dose-independent. The observed maximum serum concentration after each dose increased slightly from dose 1 through dose 3 at all dose levels, consistent with an accumulation ratio of 1.4 to 1.7 for area under the curve. Most adverse events were deemed mild to moderate and unrelated to study medication. One SAE was reported and deemed unrelated to study drug. There were no effects of clinical concern for vital signs, ECG, laboratory or pulmonary parameters. Conclusions CAT-354 exhibited linear pharmacokinetics and an acceptable safety profile. These findings suggest that at the doses tested, CAT-354 can be safely administered in multiple doses to patients with asthma. Trial registration NCT00974675.

  17. EFFECT OF ANTIOXIDANT SUPPLEMENTATION ON OZONE-INDUCED LUNG INJURY IN HUMAN SUBJECTS

    Science.gov (United States)

    Epidemiological, in vitro and animal studies suggest that dietary antioxidants can modulate the cellular and physiologic effects of ozone (O3) inhalation in humans. To determine whether antioxidants can influence human susceptibility to O3-induced changes in lung function and a...

  18. Generalization Gradients in Human Predictive Learning: Effects of Discrimination Training and within-Subjects Testing

    Science.gov (United States)

    Vervliet, Bram; Iberico, Carlos; Vervoort, Ellen; Baeyens, Frank

    2011-01-01

    Generalization gradients have been investigated widely in animal conditioning experiments, but much less so in human predictive learning tasks. Here, we apply the experimental design of a recent study on conditioned fear generalization in humans (Lissek et al., 2008) to a predictive learning task, and examine the effects of a number of relevant…

  19. Attempting to train a digital human model to reproduce human subject reach capabilities in an ejection seat aircraft

    NARCIS (Netherlands)

    Zehner, G.F.; Hudson, J.A.; Oudenhuijzen, A.

    2006-01-01

    From 1997 through 2002, the Air Force Research Lab and TNO Defence, Security and Safety (Business Unit Human Factors) were involved in a series of tests to quantify the accuracy of five Human Modeling Systems (HMSs) in determining accommodation limits of ejection seat aircraft. The results of these

  20. Abnormal epigenetic changes during differentiation of human skeletal muscle stem cells from obese subjects

    DEFF Research Database (Denmark)

    Davegårdh, Cajsa; Broholm, Christa; Perfilyev, Alexander

    2017-01-01

    is associated with low relative muscle mass and diminished metabolism. Epigenetic alterations taking place during myogenesis might contribute to these defects. METHODS: We used Infinium HumanMethylation450 BeadChip Kit (Illumina) and HumanHT-12 Expression BeadChip (Illumina) to analyze genome-wide DNA......BACKGROUND: Human skeletal muscle stem cells are important for muscle regeneration. However, the combined genome-wide DNA methylation and expression changes taking place during adult myogenesis have not been described in detail and novel myogenic factors may be discovered. Additionally, obesity...... methylation and transcription before versus after differentiation of primary human myoblasts from 14 non-obese and 14 obese individuals. Functional follow-up experiments were performed using siRNA mediated gene silencing in primary human myoblasts and a transgenic mouse model. RESULTS: We observed genome...

  1. Effects of varied doses of psilocybin on time interval reproduction in human subjects.

    Science.gov (United States)

    Wackermann, Jirí; Wittmann, Marc; Hasler, Felix; Vollenweider, Franz X

    2008-04-11

    Action of a hallucinogenic substance, psilocybin, on internal time representation was investigated in two double-blind, placebo-controlled studies: Experiment 1 with 12 subjects and graded doses, and Experiment 2 with 9 subjects and a very low dose. The task consisted in repeated reproductions of time intervals in the range from 1.5 to 5s. The effects were assessed by parameter kappa of the 'dual klepsydra' model of internal time representation, fitted to individual response data and intra-individually normalized with respect to initial values. The estimates kappa were in the same order of magnitude as in earlier studies. In both experiments, kappa was significantly increased by psilocybin at 90 min from the drug intake, indicating a higher loss rate of the internal duration representation. These findings are tentatively linked to qualitative alterations of subjective time in altered states of consciousness.

  2. Growth hormone signaling in muscle and adipose tissue of obese human subjects: associations with measures of body composition and interaction with resveratrol treatment.

    Science.gov (United States)

    Clasen, Berthil F; Poulsen, Morten M; Escande, Carlos; Pedersen, Steen B; Møller, Niels; Chini, Eduardo N; Jessen, Niels; Jørgensen, Jens O L

    2014-12-01

    Growth hormone (GH) secretion is reduced in obesity, despite normal serum insulin-like growth factor I (IGF-1) levels, but the association between obesity and the GH signaling is unknown. Furthermore, SIRT1, an nicotinamide adenine dinucleotide-dependent protein deacetylase, reduces hepatic IGF-1 production in mice via blunting of GH-induced STAT5 signaling. To study GH signaling in muscle and fat in obese subjects and the interaction with concomitant administration of the putative SIRT1 activator resveratrol, and to assess the effects of inhibiting or knocking down SIRT1 on GH regulated genes in vitro. Twenty-four obese males were examined in a randomized, double blinded, parallel-group study with resveratrol or placebo treatment for 5 weeks followed by a GH bolus. Muscle and fat biopsies were collected before and after GH. Body composition was assessed by DEXA and MRI. (1) Effect of body composition and age on GH-stimulated STAT5b phosphorylation and IGF-1, SOCS2, and CISH mRNA in muscle and fat. (2) The impact of resveratrol treatment on GH activity. (3) Impact of inhibiting or knocking down SIRT1 on effects of GH in vitro. Significant GH-induced STAT5b phosphorylation in muscle and fat in obese subjects was recorded together with increased CISH and SOCS2 mRNA. GH-induced STAT5b phosphorylation in muscle correlated positively with age [r = 0.53, p < 0.01], but not with body composition. Resveratrol administration had no impact on body composition, serum IGF-1, or GH signaling in vivo, and SIRT1 knock down or inhibition did not affect GH signaling in vitro. (1) GH induced STAT5b phosphorylation is detectable in muscle and fat in adult males with simple obesity, but is not determined by body composition. (2) Resveratrol supplementation does not impact circulating IGF-1 levels or GH signaling in human muscle and fat. (3) Our data speak against a major impact of SIRT1on GH action in human subjects.

  3. Evaluating variation in human gut microbiota profiles due to DNA extraction method and inter-subject differences

    Directory of Open Access Journals (Sweden)

    Brett eWagner Mackenzie

    2015-02-01

    Full Text Available The human gut contains dense and diverse microbial communities which have profound influences on human health. Gaining meaningful insights into these communities requires provision of high quality microbial nucleic acids from human fecal samples, as well as an understanding of the sources of variation and their impacts on the experimental model. We present here a systematic analysis of commonly used microbial DNA extraction methods, and identify significant sources of variation. Five extraction methods (Human Microbiome Project protocol, MoBio PowerSoil DNA Isolation Kit, QIAamp DNA Stool Mini Kit, ZR Fecal DNA MiniPrep, phenol:chloroform-based DNA isolation were evaluated based on the following criteria: DNA yield, quality and integrity, and microbial community structure based on Illumina amplicon sequencing of the V4 region of bacterial and archaeal 16S rRNA genes. Our results indicate that the largest portion of variation within the model was attributed to differences between subjects (biological variation, with a smaller proportion of variation associated with DNA extraction method (technical variation and intra-subject variation. A comprehensive understanding of the potential impact of technical variation on the human gut microbiota will help limit preventable bias, enabling more accurate diversity estimates.

  4. 38 CFR 17.85 - Treatment of research-related injuries to human subjects.

    Science.gov (United States)

    2010-07-01

    ... OF VETERANS AFFAIRS MEDICAL Research-Related Injuries § 17.85 Treatment of research-related injuries... apply to: (1) Treatment for injuries due to noncompliance by a subject with study procedures, or (2... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Treatment of...

  5. Effect of carbohydrate ingestion on brain exchange of amino acids during sustained exercise in human subjects

    DEFF Research Database (Denmark)

    Blomstrand, Eva; Møller, Kirsten; Secher, Niels Henry

    2005-01-01

    AIM: This study investigated the effect of prolonged exercise with and without carbohydrate intake on the brain exchange of amino acids, especially focussing on tryptophan and branched-chain amino acids (BCAA). METHODS: Five male subjects exercised for 3 h on a cycle ergometer at 200 +/- 7 W on t...

  6. Inter-subject alignment of human cortical anatomy using functional connectivity

    OpenAIRE

    Conroy, Bryan R.; Singer, Benjamin D.; Guntupalli, J. Swaroop; Ramadge, Peter J.; Haxby, James V.

    2013-01-01

    Inter-subject alignment of functional MRI (fMRI) data is necessary for group analyses. The standard approach to this problem matches anatomical features of the brain, such as major anatomical landmarks or cortical curvature. Precise alignment of functional cortical topographies, however, cannot be derived using only anatomical features.

  7. His majesty's subjects: from laboratory to human experiment in pneumatic chemistry.

    Science.gov (United States)

    Stewart, Larry

    2009-09-20

    Experiments in pneumatic chemistry paved the way for medical innovation in the last quarter of the eighteenth century. Thomas Beddoes and James Watt were instrumental in the spread of the use of new gas chemistry in pneumatic therapy, but they were far from alone. There was no shortage of experimental subjects, as the practice was quickly taken up by medics throughout Britain.

  8. Does an onion-enriched diet beneficially affect the microbiotal composition in healthy human subjects?

    DEFF Research Database (Denmark)

    Bergström, Anders; Borg, Birgitte; Marin, Eduvigis Roldán

    are considered to have beneficial effects on the intestinal environment. The aim of the present study was to analyze the effects of onion consumption on the gut microbiotal profile. In this project, five male and five female subjects were randomized to two 14 days intervention periods including one onion...

  9. 75 FR 62738 - Revisions to EPA's Rule on Protections for Subjects in Human Research Involving Pesticides...

    Science.gov (United States)

    2010-10-13

    ... as a result of a settlement agreement resolving a judicial challenge to the promulgation of these... considerations to be addressed in EPA science and ethics reviews of proposed and completed human research...

  10. [THE LEGAL STATUS OF ELEMENTS AND PRODUCTS OF THE HUMAN BODY: OBJECT OR SUBJECT OF LAW?].

    Science.gov (United States)

    De Lameigné, Anaïs Gayte-Papon

    2015-07-01

    The 2004 Act on bioethics has amended the 1994 Act regarding the donation and the use of elements and products of the human body, medically assisted procreation and prenatal diagnosis. The very purpose of these laws led the legislature not to attempt the summa divisio order distinguishing the object to the person. The analysis of bioethical laws reveals the consecration of the non-commercialization of the human body at the expense of its unavailability. Bioethical laws appear to be catalysts of biological scientific advances releasing the status of the components and the products of the human body while framing it. By limiting scientific opportunities, they prevent human beings from trying to play the sorcerer's apprentice.

  11. A randomised, double- blind, cross-over study investigating the prebiotic effect of agave fructans in healthy human subjects

    OpenAIRE

    Ramnani, Priya; Costabile, Adele; Bustillo, A. G. R.; Gibson, Glenn R.

    2015-01-01

    This placebo-controlled, randomised, double-blind, cross-over human feeding study aimed to determine the prebiotic effect of agave fructans. A total of thirty-eight volunteers completed this trial. The treatment consisted of 3 weeks' supplementation with 5 g/d of prebiotic agave fructan (Predilife) or equivalent placebo (maltodextrin), followed by a 2-week washout period following which subjects were crossed over to alternate the treatment arm for 3 weeks followed by a 2-week washout. Faecal ...

  12. Using Human Panels for Subjective Evaluation of Emissions from Indoor Activities and Materials: Principles and State of Technology

    OpenAIRE

    Cometto-Muñiz, J E

    1995-01-01

    This report addresses the topic of sensory evaluation of indoor air through the use of human subjects. It begins by discussing the chemical senses involved in such evaluation, specifically the senses of smell (olfaction) and chemical sensory irritation (common chemical sense, CCS, now called chemesthesis). An analysis of similarities and differences between these two sensory modalities regarding key measurements and issues follows. Later, the report discusses the quantification of sensory rea...

  13. Time to Separate the Men From the Beasts: Symbolic Anticipation as the Typically Human Subjective Dimension

    Science.gov (United States)

    De Grave, Dieter

    2004-08-01

    In this paper it is argued that the dividing line that runs between the human psyche as opposed to any other complex system is made up by symbolic anticipation. The functionality of the human mind as an anticipatory system is entirely caught up in the crucial role that finiteness, shortage or lack plays for human beings. Anticipation for us is the way by which this negative finiteness or lack is translated into a positive longing, want or desire. We take a look at the three dimensional view of Jacques Lacan regarding these matters in a sophistical example and we illustrate how anticipation as a Symbolic phenomenon is distinct from the Imaginary or the Real register. As Lacan points out anticipation creates a symbolic social link which binds two or more interacting humans together in an anticipatory relationship. Beliefs, expectations and convictions are the typically human social links which ground human interaction and set it apart from other forms of social interaction we can observe in other complex biological entities.

  14. Ethical Standards of Scientific Research Involving Human Subjects in Brazil: Perspectives Concerning Psychology

    Directory of Open Access Journals (Sweden)

    Selma Leitão

    2015-01-01

    Full Text Available AbstractBrazilian associations for research in human, social and applied social sciences have long sought ethical aspects regulation compatible with the epistemological, theoretical and methodological specificities of these sciences. Consequently, the Brazilian regulatory system (Research Ethics Committees/CEPs of the National Research Ethics Commission/CONEP is currently undergoing an important review process. This article presents the positions taken by the National Association of Research and Postgraduate Studies in Psychology - ANPEPP. The article: (1 highlights the origins of the current ethics review model, based on biomedical research; (2 summarizes criticisms recurrent to this model; (3 identifies the directions required for the improvement of the system; and (4 lists the challenges to be overcome in the current process of creating specific regulations for the human and social sciences. The considerations presented highlight two crucial points that challenge the construction of a specific resolution for research ethics in the human and social sciences: (1 the clear characterization of what is meant by 'research in the human and social sciences' - and that would, therefore, have its ethical review regulated from the perspective of the specific resolution for the human and social sciences; and (2 the definition of parameters from which different risk levels in studies can be identified.

  15. Ethylphenidate formation in human subjects after the administration of a single dose of methylphenidate and ethanol.

    Science.gov (United States)

    Markowitz, J S; DeVane, C L; Boulton, D W; Nahas, Z; Risch, S C; Diamond, F; Patrick, K S

    2000-06-01

    Ethylphenidate was recently reported as a novel drug metabolite in two overdose fatalities where there was evidence of methylphenidate and ethanol coingestion. This study explores the pharmacokinetics of ethylphenidate relative to methylphenidate and the major metabolite ritalinic acid, in six healthy subjects who received methylphenidate and ethanol under controlled conditions. Subjects (three males, three females) received a single oral dose of methylphenidate (20 mg; two 10-mg tablets) followed by consumption of ethanol (0.6 g/kg) 30 min later. Methylphenidate, ritalinic acid, and ethylphenidate were quantified using liquid chromatography-tandem mass spectrometry. Ethylphenidate was detectable in the plasma and urine of all subjects after ethanol ingestion. The mean (+/-S.D.) area under the concentration versus time curve for ethylphenidate was 1.2 +/- 0.7 ng/ml/h, representing 2.3 +/- 1.3% that of methylphenidate (48 +/- 12 ng/ml/h). A significant correlation was observed between the area under the concentration versus time curve of methylphenidate and that of ethylphenidate. In view of the known dopaminergic activity of racemic ethylphenidate, it remains possible that under certain circumstances of higher level dosing, e.g., in the abuse of methylphenidate and ethanol, the metabolite ethylphenidate may contribute to drug effects.

  16. Substrate Metabolism and Insulin Sensitivity During Fasting in Obese Human Subjects: Impact of GH Blockade.

    Science.gov (United States)

    Pedersen, Morten Høgild; Svart, Mads Vandsted; Lebeck, Janne; Bidlingmaier, Martin; Stødkilde-Jørgensen, Hans; Pedersen, Steen Bønløkke; Møller, Niels; Jessen, Niels; Jørgensen, Jens O L

    2017-04-01

    Insulin resistance and metabolic inflexibility are features of obesity and are amplified by fasting. Growth hormone (GH) secretion increases during fasting and GH causes insulin resistance. To study the metabolic effects of GH blockade during fasting in obese subjects. Nine obese males were studied thrice in a randomized design: (1) after an overnight fast (control), (2) after 72 hour fasting (fasting), and (3) after 72 hour fasting with GH blockade (pegvisomant) [fasting plus GH antagonist (GHA)]. Each study day consisted of a 4-hour basal period followed by a 2-hour hyperinsulinemic, euglycemic clamp combined with indirect calorimetry, assessment of glucose and palmitate turnover, and muscle and fat biopsies. GH levels increased with fasting (P fasting-induced reduction of serum insulin-like growth factor I was enhanced by GHA (P Fasting increased lipolysis and lipid oxidation independent of GHA, but fasting plus GHA caused a more pronounced suppression of lipid intermediates in response to hyperinsulinemic, euglycemic clamp. Fasting-induced insulin resistance was abrogated by GHA (P Fasting plus GHA also caused elevated glycerol levels and reduced levels of counterregulatory hormones. Fasting significantly reduced the expression of antilipolytic signals in adipose tissue independent of GHA. Suppression of GH activity during fasting in obese subjects reverses insulin resistance and amplifies insulin-stimulated suppression of lipid intermediates, indicating that GH is an important regulator of substrate metabolism, insulin sensitivity, and metabolic flexibility also in obese subjects.

  17. Gastric inhibitory polypeptide (GIP) dose-dependently stimulates glucagon secretion in healthy human subjects at euglycaemia

    DEFF Research Database (Denmark)

    Meier, J J; Gallwitz, B; Siepmann, N

    2003-01-01

    secretion under normoglycaemic conditions. METHODS: Ten healthy subjects (9 men, 1 woman; age 33+/-11; BMI 26.8+/-2.2 kg/m(2)) received three different doses of intravenous GIP (7, 20, and 60 pmol/kg body weight) and placebo. Venous blood samples were drawn over 30 min for glucagon and GIP concentrations...... (specific radioimmunoassays). In addition, 31 healthy subjects (16 men, 15 women; 42+/-11 years; BMI 24.4+/-2.7 kg/m(2)) were studied with 20 pmol GIP/kg. Statistics were done with RM-ANOVA and Duncan's post hoc tests. RESULTS: Gastric inhibitory polypeptide dose-dependently stimulated glucagon secretion...... ( p=0.019) with a maximal increment after 10 min. Incremental glucagon concentrations (Delta(10-0 min)) were 0.1+/-0.7, 1.4+/-0.5, 2.4+/-0.5, and 3.4+/-0.8 pmol/l (for placebo and for 7, 20, and 60 pmol GIP/kg, respectively; p=0.017). After the injection of 20 pmol GIP/kg b.w. in 31 healthy subjects...

  18. Frequency of null allele of Human Leukocyte Antigen-G (HLA-G) locus in subjects to recurrent miscarriage

    Science.gov (United States)

    Alizadeh, Nazila; Mosaferi, Elnaz; Farzadi, Laya; Majidi, Jafar; Monfaredan, Amir; Yousefi, Bahman; Baradaran, Behzad

    2016-01-01

    Background: Human leukocyte antigen-G (HLA-G) is a non-classical class I molecule highly expressed by extravillous cytotrophoblast cells. Due to a single base pair deletion, its function can be compensated by other isoforms. Investigating the frequency of null allele in Recurrent Miscarriage (RM) subjects could be useful in understanding the relationship between frequency of this allele and RM in a given population. Objective: This study aimed to determine the frequency of HLA-G*0105N null allele and its potential association with down-regulation of HLA-G in subjects with RM. Materials and Methods: Western blotting was used to assess the level of HLA-G protein expression. For investigating the frequency of HLA-G*0105N null allele in RM subjects, PCR-RFLP method was used. Exon 3 of HLA-G gene was amplified by polymerase chain reaction (PCR). Subsequently, PpuM-1 enzyme was employed to digest the PCR products and fragments were analyzed using gel electrophoresis. Results: Digestion using restriction enzyme showed the presence of heterozygous HLA-G*0105N null allele in 10% of the test population. Western blotting results confirmed the decrease in expression of HLA-G in the placental tissue of subjects with RM compared to subjects who could give normal birth. Conclusion: The frequency of heterozygous HLA-G*0105N null allele was high to some extent in subjects with RM. The mutation rate in subjects suggested that there is a significant association between RM and frequency of mutations in this allele. PMID:27525330

  19. Human Adipose Tissue Conditioned Media from Lean Subjects Is Protective against H2O2 Induced Neurotoxicity in Human SH-SY5Y Neuronal Cells

    Directory of Open Access Journals (Sweden)

    Zhongxiao Wan

    2015-01-01

    Full Text Available Adipose tissue secretes numerous hormone-like factors, which are known as adipokines. Adipokine receptors have been identified in the central nervous system but the potential role of adipokine signaling in neuroprotection is unclear. The aim of this study is to determine (1 Whether adipokines secreted from cultured adipose tissue of lean humans is protective against oxidative stress-induced neurotoxicity in human SH-SY5Y neuronal cells; and (2 To explore potential signaling pathways involved in these processes. Adipose tissue conditioned media (ATCM from healthy lean subjects completely prevented H2O2 induced neurotoxicity, while this effect is lost after heating ATCM. ATCM activated the phosphorylation of ERK1/2, JNK and Akt at serine 308 in SH-SY5Y cells. PD98059 (25 µM, SP600125 (5 µM and LY29400 (20 µM partially blocked the protective effects of ATCM against H2O2 induced neurotoxicity. Findings demonstrate that heat-sensitive factors secreted from human adipose tissue of lean subjects are protective against H2O2 induced neurotoxicity and ERK1/2, JNK, and PI3K signaling pathways are involved in these processes. In conclusion, this study demonstrates preliminary but encouraging data to further support that adipose tissue secreted factors from lean human subjects might possess neuroprotective properties and unravel the specific roles of ERK1/2, JNK and PI3K in these processes.

  20. Serum vitamin D levels are not altered after controlled diesel exhaust exposures in healthy human subjects

    Science.gov (United States)

    Past research has suggested that exposure to urban air pollution may be associated with vitamin D deficiency in human populations. Vitamin D is widely known for its importance in bone growth/remodeling, muscle metabolism, and its ability to promote calcium absorption in the gut; ...

  1. Keys to an open lock : Subject specific biomechanical modelling of luxations of the human temporomandibular joint

    NARCIS (Netherlands)

    Tuijt, M.

    2017-01-01

    In this thesis, the aims are to: • increase the understanding of the interplay of morphological aspects, such as joint shape and muscle orientation, in open locks of the human temporomandibular joint. • increase the understanding of the biomechanics behind open locks of the temporomandibular joint.

  2. Postmortem succession of gut microbial communities in deceased human subjects

    Directory of Open Access Journals (Sweden)

    Jennifer M. DeBruyn

    2017-06-01

    Full Text Available The human microbiome has demonstrated an importance for the health and functioning in living individuals. However, the fate of the microbiome after death is less understood. In addition to a better understanding of microbe-mediated decomposition processes, postmortem succession of human-associated microbial communities has been suggested as a possible forensic tool for estimating time since death, or postmortem interval (PMI. The objective of our study was to document postmortem changes in human gut bacterial communities. Gut microflora were repeatedly sampled from the caeca of cadavers as they decayed under natural environmental conditions. 16S rRNA gene amplicon sequencing revealed that over time, bacterial richness significantly increased (rs = 0.449 while diversity decreased (rs =  − 0.701. The composition of gut bacterial communities changed in a similar manner over time towards a common decay community. OTUs belonging to Bacteroidales (Bacteroides, Parabacteroides significantly declined while Clostridiales (Clostridium, Anaerosphaera and the fly-associated Gammaproteobacteria Ignatzschineria and Wohlfahrtiimonas increased. Our examination of human caeca microflora in decomposing cadavers adds to the growing literature on postmortem microbial communities, which will ultimately contribute to a better understanding of decomposition processes.

  3. Distortion-Product Otoacoustic Emission Measured Below 300 Hz in Normal-Hearing Human Subjects

    DEFF Research Database (Denmark)

    Christensen, Anders Tornvig; Ordoñez Pizarro, Rodrigo Eduardo; Hammershøi, Dorte

    2017-01-01

    Physiological noise levels in the human ear canal often exceed naturally low levels of otoacoustic emissions (OAEs) near the threshold of hearing. Low-frequency noise, and electronic filtering to cope with it, has effectively limited the study of OAE to frequencies above about 500 Hz. Presently, ...

  4. The subject matters: the ICJ and human rights, rights of shareholders, and the Diallo case

    NARCIS (Netherlands)

    A. Vermeer-Künzli

    2011-01-01

    On 30 November 2010, the International Court of Justice issued its decision in the merits phase of the Ahmadou Sadio Diallo case. This decision turned on the questions of whether the DRC had violated Mr Diallo's human rights and his rights as a shareholder and manager in two corporations he owned in

  5. Human pharmacology of ayahuasca: subjective and cardiovascular effects, monoamine metabolite excretion, and pharmacokinetics.

    Science.gov (United States)

    Riba, Jordi; Valle, Marta; Urbano, Gloria; Yritia, Mercedes; Morte, Adelaida; Barbanoj, Manel J

    2003-07-01

    The effects of the South American psychotropic beverage ayahuasca on subjective and cardiovascular variables and urine monoamine metabolite excretion were evaluated, together with the drug's pharmacokinetic profile, in a double-blind placebo-controlled clinical trial. This pharmacologically complex tea, commonly obtained from Banisteriopsis caapi and Psychotria viridis, combines N,N-dimethyltryptamine (DMT), an orally labile psychedelic agent showing 5-hydroxytryptamine2A agonist activity, with monoamine oxidase (MAO)-inhibiting beta-carboline alkaloids (harmine, harmaline, and tetrahydroharmine). Eighteen volunteers with prior experience in the use of psychedelics received single oral doses of encapsulated freeze-dried ayahuasca (0.6 and 0.85 mg of DMT/kg of body weight) and placebo. Ayahuasca produced significant subjective effects, peaking between 1.5 and 2 h, involving perceptual modifications and increases in ratings of positive mood and activation. Diastolic blood pressure showed a significant increase at the high dose (9 mm Hg at 75 min), whereas systolic blood pressure and heart rate were moderately and nonsignificantly increased. Cmax values for DMT after the low and high ayahuasca doses were 12.14 ng/ml and 17.44 ng/ml, respectively. Tmax (median) was observed at 1.5 h after both doses. The Tmax for DMT coincided with the peak of subjective effects. Drug administration increased urinary normetanephrine excretion, but, contrary to the typical MAO-inhibitor effect profile, deaminated monoamine metabolite levels were not decreased. This and the negligible harmine plasma levels found suggest a predominantly peripheral (gastrointestinal and liver) site of action for harmine. MAO inhibition at this level would suffice to prevent first-pass metabolism of DMT and allow its access to systemic circulation and the central nervous system.

  6. Oxidised fish oil does not influence established markers of oxidative stress in healthy human subjects

    DEFF Research Database (Denmark)

    Ottestad, Inger; Vogt, Gjermund; Retterstøl, Kjetil

    2012-01-01

    8-iso-PGF2a; plasma levels of 4-hydroxy-2-hexenal, 4-hydroxy-2-nonenal and a-tocopherol; serum high sensitive C-reactive protein; or activity of antioxidant enzymes in erythrocytes. A significant increase in plasma level of EPA þ DHA was observed in both fish oil groups, but no significant...... markers of oxidative stress, lipid peroxidation and inflammation, and the level of plasma n-3 FA after intake of oxidised fish oil. In a double-blinded randomised controlled study, healthy subjects (aged 18–50 years, n 54) were assigned into one of three groups receiving capsules containing either 8 g...

  7. Resistant starches types 2 and 4 have differential effects on the composition of the fecal microbiota in human subjects.

    Directory of Open Access Journals (Sweden)

    Inés Martínez

    Full Text Available BACKGROUND: To systematically develop dietary strategies based on resistant starch (RS that modulate the human gut microbiome, detailed in vivo studies that evaluate the effects of different forms of RS on the community structure and population dynamics of the gut microbiota are necessary. The aim of the present study was to gain a community wide perspective of the effects of RS types 2 (RS2 and 4 (RS4 on the fecal microbiota in human individuals. METHODS AND FINDINGS: Ten human subjects consumed crackers for three weeks each containing either RS2, RS4, or native starch in a double-blind, crossover design. Multiplex sequencing of 16S rRNA tags revealed that both types of RS induced several significant compositional alterations in the fecal microbial populations, with differential effects on community structure. RS4 but not RS2 induced phylum-level changes, significantly increasing Actinobacteria and Bacteroidetes while decreasing Firmicutes. At the species level, the changes evoked by RS4 were increases in Bifidobacterium adolescentis and Parabacteroides distasonis, while RS2 significantly raised the proportions of Ruminococcus bromii and Eubacterium rectale when compared to RS4. The population shifts caused by RS4 were numerically substantial for several taxa, leading for example, to a ten-fold increase in bifidobacteria in three of the subjects, enriching them to 18-30% of the fecal microbial community. The responses to RS and their magnitudes varied between individuals, and they were reversible and tightly associated with the consumption of RS. CONCLUSION: Our results demonstrate that RS2 and RS4 show functional differences in their effect on human fecal microbiota composition, indicating that the chemical structure of RS determines its accessibility by groups of colonic bacteria. The findings imply that specific bacterial populations could be selectively targeted by well designed functional carbohydrates, but the inter-subject variations in

  8. Effects of dietary salt levels on monocytic cells and immune responses in healthy human subjects: a longitudinal study.

    Science.gov (United States)

    Yi, Buqing; Titze, Jens; Rykova, Marina; Feuerecker, Matthias; Vassilieva, Galina; Nichiporuk, Igor; Schelling, Gustav; Morukov, Boris; Choukèr, Alexander

    2015-07-01

    Increasing evidence indicated that excess salt consumption can impose risks on human health and a reduction in daily salt intake from the current average of approximately 12 g/d to 5-6 g/d was suggested by public health authorities. The studies on mice have revealed that sodium chloride plays a role in the modulation of the immune system and a high-salt diet can promote tissue inflammation and autoimmune disease. However, translational evidence of dietary salt on human immunity is scarce. We used an experimental approach of fixing salt intake of healthy human subjects at 12, 9, and 6 g/d for months and examined the relationship between salt-intake levels and changes in the immune system. Blood samples were taken from the end point of each salt intake period. Immune phenotype changes were monitored through peripheral leukocyte phenotype analysis. We assessed immune function changes through the characterization of cytokine profiles in response to mitogen stimulation. The results showed that subjects on the high-salt diet of 12 g/d displayed a significantly higher number of immune cell monocytes compared with the same subjects on a lower-salt diet, and correlation test revealed a strong positive association between salt-intake levels and monocyte numbers. The decrease in salt intake was accompanied by reduced production of proinflammatory cytokines interleukin (IL)-6 and IL-23, along with enhanced producing ability of anti-inflammatory cytokine IL-10. These results suggest that in healthy humans high-salt diet has a potential to bring about excessive immune response, which can be damaging to immune homeostasis, and a reduction in habitual dietary salt intake may induce potentially beneficial immune alterations.

  9. Molecular identification of bacteria by total sequence screening: determining the cause of death in ancient human subjects.

    Directory of Open Access Journals (Sweden)

    Catherine Thèves

    Full Text Available Research of ancient pathogens in ancient human skeletons has been mainly carried out on the basis of one essential historical or archaeological observation, permitting specific pathogens to be targeted. Detection of ancient human pathogens without such evidence is more difficult, since the quantity and quality of ancient DNA, as well as the environmental bacteria potentially present in the sample, limit the analyses possible. Using human lung tissue and/or teeth samples from burials in eastern Siberia, dating from the end of 17(th to the 19(th century, we propose a methodology that includes the: 1 amplification of all 16S rDNA gene sequences present in each sample; 2 identification of all bacterial DNA sequences with a degree of identity ≥ 95%, according to quality criteria; 3 identification and confirmation of bacterial pathogens by the amplification of the rpoB gene; and 4 establishment of authenticity criteria for ancient DNA. This study demonstrates that from teeth samples originating from ancient human subjects, we can realise: 1 the correct identification of bacterial molecular sequence signatures by quality criteria; 2 the separation of environmental and pathogenic bacterial 16S rDNA sequences; 3 the distribution of bacterial species for each subject and for each burial; and 4 the characterisation of bacteria specific to the permafrost. Moreover, we identified three pathogens in different teeth samples by 16S rDNA sequence amplification: Bordetella sp., Streptococcus pneumoniae and Shigella dysenteriae. We tested for the presence of these pathogens by amplifying the rpoB gene. For the first time, we confirmed sequences from Bordetella pertussis in the lungs of an ancient male Siberian subject, whose grave dated from the end of the 17(th century to the early 18(th century.

  10. Twenty-Seventh Symposium (International) on Combustion. Volume 1

    Science.gov (United States)

    1998-01-01

    pollutant emissions on human driving the development of highly efficient low- health range from respiratory diseases (e.g., child- emission combustion...Systems (N. 101. Stein, S. E., Walker, J. A., Suryan, M. M., and Fahr , Peters and B. Rogg, eds.), Lecture Notes in Physics, A., in Twenty-Third Symposium...M. M., and Fahr , A., and Kawano, H., Int. j. Chem. Kinet. 21:643-666 in Twenty-Third Symposium (International) on Com- (1989). bustion, The

  11. Arachidonic acid metabolism in the platelets and neutrophils of diabetic rabbit and human subjects

    Energy Technology Data Exchange (ETDEWEB)

    Greco, N.J.

    1985-01-01

    An alteration of arachidonic acid metabolism to prostaglandins and leukotrienes from platelets and polymorphonuclear leukocytes respectively is evident in subjects with diabetes mellitus. There is evidence of altered platelet/vascular wall interactions in diabetes mellitus and evidence that polymorphonuclear leukocytes influence the vascular walls. Theories on the pathogenesis of atherosclerosis include both blood cells. Platelet hypersensitivity is evident in those platelets from the alloxan-induced diabetic rabbit either suspended in plasma or buffer. Arachidonic acid- and collagen-induced platelet aggregation, release of /sup 14/serotonin, and T x B/sub 2/ and 12-HETE production is enhanced when responses of diabetic platelets are compared to control platelets. Control rabbit neutrophils produce more LTB/sub 4/, LTB/sub 4/ isomers and 5-HETE than diabetic rabbits neutrophils. Decreased synthesis from diabetic rabbit neutrophils is not explained by increased catabolism of LTB/sub 4/, reesterification of 5-HETE, or increased eicosanoid formation. These experiments demonstrate both platelet and neutrophil dysfunction in diabetic subjects. Because of the involvement of these cells in regulating circulatory homeostatis, abnormal behavior could aggravate the atherosclerotic process. Platelet and neutrophil dysfunctions are noted before macroscopic vascular lesions are apparent suggesting an important role in the pathogenesis of atherosclerosis.

  12. Alteration of cyclic nucleotides levels and oxidative stress in saliva of human subjects with periodontitis.

    Science.gov (United States)

    Mashayekhi, Fereshteh; Aghahoseini, Farzaneh; Rezaie, Ali; Zamani, Mohammad J; Khorasani, Reza; Abdollahi, Mohammad

    2005-11-15

    Experimental findings suggest a protective role for cyclic nucleotides against induction of oxidative stress in saliva. Oxidative stress is a major contributor to the pathogenesis of inflammatory diseases. This study was conducted to evaluate salivary oxidative stress along with cGMP and cAMP levels in periodontitis subjects. cAMP and cGMP are second messengers that have important roles in salivary gland functions. Unstimulated whole saliva samples were obtained from periodontitis patients and age- and sex-matched healthy individuals. Saliva samples were analyzed for thiobarbituric reactive substances (TBARS) as a marker of lipid peroxidation, ferric reducing ability (total antioxidant power, TAP), and levels of cAMP and cGMP. Concentrations of cAMP and cGMP were reduced in the saliva of patients with moderate and severe periodontitis. Saliva of patients with severe periodontitis had higher TBARS and lower TAP than control subjects. The presence of oxidative stress and lower levels of salivary cGMP and cAMP in periodontitis are in association with disease severity.

  13. Short-term sertraline treatment suppresses sympathetic nervous system activity in healthy human subjects.

    Science.gov (United States)

    Shores, M M; Pascualy, M; Lewis, N L; Flatness, D; Veith, R C

    2001-05-01

    Increased sympathetic nervous system (SNS) activity has been associated with stress, major depression, aging, and several medical conditions. This study assessed the effect of the selective serotonin reuptake inhibitor (SSRI), sertraline, on sympathetic nervous system (SNS) activity in healthy subjects. Twelve healthy volunteers participated in a double-blind, placebo-controlled, norepinephrine (NE) kinetic study, in which the effects of sertraline on SNS activity were ascertained by determining NE plasma concentrations and NE plasma appearance rates and clearance rates in sertraline or placebo conditions. Subjects received 50 mg of sertraline or placebo for two days and then one week later underwent the same protocol with the other drug. By single compartmental analysis, plasma NE appearance rates were significantly lower in the sertraline compared to the placebo condition (0.26+/-0.10 vs 0.40+/-0.23 microg/m(2)/min; P=0.04). Our study found that the net effect of short-term SSRI treatment is an apparent suppression of SNS activity as indicated by a decreased plasma NE appearance rate in the sertraline condition. If this preliminary finding can be extended to long-term treatment of patients, this could have significant therapeutic relevance for treating depression in elderly patients or those with cardiac disease, in which elevated SNS activity may exacerbate underlying medical conditions.

  14. Growth Hormone signaling in skeletal muscle and adipose tissue in healthy human subjects

    DEFF Research Database (Denmark)

    Vestergaard, Poul Frølund; Vendelbo, Mikkel Holm; Pedersen, Steen Bønnelykke

    2014-01-01

    '>60 years (5F/5M)) were studied after: i) an i.v. GH bolus (0.5 mg) and ii) saline. METHODS: Muscle and fat biopsies were obtained after 30 and 120 min. Total and phosphorylated STAT5B proteins, gene expression of IGF1, SOCS1, SOCS2, SOCS3 and CISH, body composition, VO2max, and muscle strength were...... measured. RESULTS: In the GH-unstimulated state, women displayed significantly elevated levels of CISH mRNA in muscle (P=0.002) and fat (P=0.05) and reduced levels of IGF1 mRNA in fat. Phosphorylated STAT5B (pSTAT5b) was maximally increased in all subjects 30 min after GH exposure and more pronounced...... in women when compared with men (P=0.01). IGF1, SOCS1, SOCS2, SOCS3, and CISH mRNA expression increased significantly in muscle after 120 min in all subjects with no impact of age and gender. GH-induced pSTAT5b correlated inversely with lean body mass (LBM; r=-0.56, P=0.01) and positively with the CISH m...

  15. Congenital candidiasis as a subject of research in medicine and human ecology.

    Science.gov (United States)

    Skoczylas, Michał M; Walat, Anna; Kordek, Agnieszka; Loniewska, Beata; Rudnicki, Jacek; Maleszka, Romuald; Torbé, Andrzej

    2014-01-01

    Congenital candidiasis is a severe complication of candidal vulvovaginitis. It occurs in two forms,congenital mucocutaneous candidiasis and congenital systemic candidiasis. Also newborns are in age group the most vulnerable to invasive candidiasis. Congenital candidiasis should be considered as an interdisciplinary problem including maternal and fetal condition (including antibiotic therapy during pregnancy), birth age and rare genetic predispositions as severe combined immunodeficiency or neutrophil-specific granule deficiency. Environmental factors are no less important to investigate in diagnosing, treatment and prevention. External factors (e.g., food) and microenvironment of human organism (microflora of the mouth, intestine and genitalia) are important for solving clinical problems connected to congenital candidiasis. Physician knowledge about microorganisms in a specific compartments of the microenvironment of human organism and in the course of defined disorders of homeostasis makes it easier to predict the course of the disease and allows the development of procedures that can be extremely helpful in individualized diagnostic and therapeutic process.

  16. Correlation of Respirator Fit Measured on Human Subjects and a Static Advanced Headform

    Science.gov (United States)

    2016-04-19

    Ziqing Zhuang1, Brian K. Heimbuch2, Ronald E. Shaffer1, Melanie Choe3, and Joseph D. Wander4 1National Personal Protective Technology Laboratory...FF and MFF values to assess the relationship between the values obtained from humans and the StAH. This is the first study to report a positive...correlation between FF and MFF. For all respirators the geometric mean (GM) FF values were consistently higher than those of the GM MFF. For 50% of

  17. The surface area of human V1 predicts the subjective experience of object size

    OpenAIRE

    Schwarzkopf, Dietrich Samuel; Song, Chen; Rees, Geraint

    2010-01-01

    Abstract The surface area of human primary visual cortex (V1) varies substantially between individuals for unknown reasons. Here, we show that this variability is strongly and negatively correlated with the magnitude of two common visual illusions, where two physically identical objects appear different in size due to their context. Because such illusions dissociate conscious perception from physical stimulation, our findings indicate that the surface area of V1 predicts variabilit...

  18. Human herpesvirus 8 DNA load in leukocytes of human immunodeficiency virus-infected subjects: correlation with the presence of Kaposi's sarcoma and response to anticytomegalovirus therapy.

    Science.gov (United States)

    Boivin, G; Gaudreau, A; Toma, E; Lalonde, R; Routy, J P; Murray, G; Handfield, J; Bergeron, M G

    1999-02-01

    Specific human herpesvirus 8 (HHV-8) DNA sequences were found in leukocytes of 12 of 29 (41.4%) AIDS subjects with Kaposi's sarcoma (KS), whereas they were found in 4 of 43 (9.3%) AIDS subjects without KS (P = 0.003), although the peak HHV-8 DNA load in PCR-positive subjects with KS (mean, 425 copies per 0.2 microgram of DNA) did not significantly differ from the one found in PCR-positive patients without KS (mean, 218 copies). The use of intravenous ganciclovir or foscarnet therapy to treat cytomegalovirus disease did not affect the HHV-8 DNA load in seven patients for whom serial samples were analyzed.

  19. Human Herpesvirus 8 DNA Load in Leukocytes of Human Immunodeficiency Virus-Infected Subjects: Correlation with the Presence of Kaposi’s Sarcoma and Response to Anticytomegalovirus Therapy

    Science.gov (United States)

    Boivin, Guy; Gaudreau, Annie; Toma, Emil; Lalonde, Richard; Routy, Jean-Pierre; Murray, Gilles; Handfield, Julie; Bergeron, Michel G.

    1999-01-01

    Specific human herpesvirus 8 (HHV-8) DNA sequences were found in leukocytes of 12 of 29 (41.4%) AIDS subjects with Kaposi’s sarcoma (KS), whereas they were found in 4 of 43 (9.3%) AIDS subjects without KS (P = 0.003), although the peak HHV-8 DNA load in PCR-positive subjects with KS (mean, 425 copies per 0.2 μg of DNA) did not significantly differ from the one found in PCR-positive patients without KS (mean, 218 copies). The use of intravenous ganciclovir or foscarnet therapy to treat cytomegalovirus disease did not affect the HHV-8 DNA load in seven patients for whom serial samples were analyzed. PMID:9925538

  20. Hysteresis of haptic vertical and straight ahead in healthy human subjects

    Directory of Open Access Journals (Sweden)

    Tarnutzer Alexander A

    2012-09-01

    Full Text Available Abstract Background The subjective haptic vertical (SHV task requires subjects to adjust the roll orientation of an object, mostly in the roll plane, in such a way that it is parallel to perceived direction of gravity. Previously we found a tendency for clockwise rod rotations to deviate counter-clockwise and vice versa, indicating hysteresis. However, the contributing factors remained unclear. To clarify this we characterized the SHV in terms of handedness, hand used, direction of hand rotation, type of grasping (wrap vs. precision grip and gender, and compared findings with perceived straight-ahead (PSA. Healthy subjects repetitively performed adjustments along SHV (n = 21 and PSA (n = 10 in complete darkness. Results For both SHV and PSA significant effects of the hand used and the direction of rod/plate rotation were found. The latter effect was similar for SHV and PSA, leading to significantly larger counter-clockwise shifts (relative to true earth-vertical and objective straight-ahead for clockwise rotations compared to counter-clockwise rotations irrespective of the handedness and the type of grip. The effect of hand used, however, was opposite in the two tasks: while the SHV showed a counter-clockwise bias when the right hand was used and no bias for the left hand, in the PSA a counter-clockwise bias was obtained for the left hand without a bias for the right hand. No effects of grip and handedness (studied for SHV only on accuracy were observed, however, SHV precision was significantly (p  Conclusions Unimanual haptic tasks require control for the hand used and the type of grip as these factors significantly affect task performance. Furthermore, aligning objects with the SHV and PSA resulted in systematic direction-dependent deviations that could not be attributed to handedness, the hand used, or the type of grip. These deviations are consistent with hysteresis and are likely not related to gravitational pull, as they were

  1. Effect of carbohydrate ingestion on brain exchange of amino acids during sustained exercise in human subjects

    DEFF Research Database (Denmark)

    Blomstrand, E.; Møller, K.; Secher, Niels Henry

    2005-01-01

    AIM: This study investigated the effect of prolonged exercise with and without carbohydrate intake on the brain exchange of amino acids, especially focussing on tryptophan and branched-chain amino acids (BCAA). METHODS: Five male subjects exercised for 3 h on a cycle ergometer at 200 +/- 7 W on two...... occasions; either supplemented with a 6% carbohydrate solution or with flavoured water (placebo). Catheters were inserted into the right internal jugular vein and the radial artery of the non-dominant arm. The brain exchange of amino acids during exercise was calculated from the arterial-jugular venous...... concentration difference multiplied by plasma flow. RESULTS: About 106 micromol (22 mg) of tryptophan was taken up by the brain during exercise in the placebo trial, whereas no significant uptake was observed in the carbohydrate trial. In accordance, the arterial concentration of free tryptophan increased from...

  2. Unprecedented high insulin secretion in a healthy human subject after intravenous glucagon-like peptide-1

    DEFF Research Database (Denmark)

    Knop, Filip K; Lund, Asger; Madsbad, Sten

    2014-01-01

    to as one of the most insulinotropic substances known. CASE PRESENTATION: Plasma insulin and C-peptide concentrations were measured in a healthy Caucasian male (age: 53 years; body mass index: 28.6 kg/m2; fasting plasma glucose: 5.7 mM; 2 h plasma glucose value following 75 g-oral glucose tolerance test: 3...... insulin and C-peptide responses were observed during meal test (peak concentrations: 300 and 3,278 pM) and glucagon test (peak concentrations: 250 and 2,483 pM). During the hyperglycaemic clamp with continuous intravenous infusion of GLP-1 the subject exhibited plasma insulin and C-peptide concentrations...

  3. Power assessment for genetic association study of human longevity using offspring of long-lived subjects

    DEFF Research Database (Denmark)

    Tan, Qihua; Zhao, Jing Hua; Li, Shuxia

    2010-01-01

    Recently, an indirect genetic association approach that compares genotype frequencies in offspring of long-lived subjects and offspring from random families has been introduced to study gene-longevity associations. Although the indirect genetic association has certain advantages over the direct...... association approach that compares genotype frequency between centenarians and young controls, the power has been of concern. This paper reports a power study performed on the indirect approach using computer simulation. We perform our simulation study by introducing the current Danish population life table...... and the proportional hazard model for generating individual lifespan. Family genotype data is generated using a genetic linkage program for given SNP allele frequency. Power is estimated by setting the type I error rate at 0.05 and by calculating the Armitage's chi-squared test statistic for 200 replicate samples...

  4. Effects of Lactobacillus acidophilus NCFM on insulin sensitivity and the systemic inflammatory response in human subjects

    DEFF Research Database (Denmark)

    Andreasen, Anne Sofie; Larsen, Nadja; Pedersen-Skovsgaard, Theis

    2010-01-01

    According to animal studies, intake of probiotic bacteria may improve glucose homeostasis. We hypothesised that probiotic bacteria improve insulin sensitivity by attenuating systemic inflammation. Therefore, the effects of oral supplementation with the probiotic bacterium Lactobacillus acidophilus...... course with either L. acidophilus NCFM or placebo. L. acidophilus was detected in stool samples by denaturating gradient gel electrophoresis and real-time PCR. Separated by the 4-week intervention period, two hyperinsulinaemic-euglycaemic clamps were performed to estimate insulin sensitivity. Furthermore......, the systemic inflammatory response was evaluated by subjecting the participants to Escherichia coli lipopolysaccharide injection (0·3 ng/kg) before and after the treatment course. L. acidophilus NCFM was detected in 75 % of the faecal samples after treatment with the probiotic bacterium. Insulin sensitivity...

  5. Power assessment for genetic association study of human longevity using offspring of long-lived subjects

    DEFF Research Database (Denmark)

    Tan, Qihua; Zhao, Jing Hua; Li, Shuxia;

    2010-01-01

    Recently, an indirect genetic association approach that compares genotype frequencies in offspring of long-lived subjects and offspring from random families has been introduced to study gene-longevity associations. Although the indirect genetic association has certain advantages over the direct...... and the proportional hazard model for generating individual lifespan. Family genotype data is generated using a genetic linkage program for given SNP allele frequency. Power is estimated by setting the type I error rate at 0.05 and by calculating the Armitage's chi-squared test statistic for 200 replicate samples...... for each setting of the specified allele risk and frequency parameters under different modes of inheritance and for different sample sizes. The indirect genetic association analysis is a valid approach for studying gene-longevity association, but the sample size requirement is about 3-4 time larger than...

  6. State-dependent variations in brainstem auditory evoked responses in human subjects.

    Science.gov (United States)

    Sersen, E A; Majkowski, J; Clausen, J; Heaney, G M

    1984-12-01

    BAERs from 16 subjects during 3 sessions varied in the latency or amplitude of some components depending upon level of arousal as indicated by EEG patterns. There was a general tendency for activation to produce the fastest responses with the largest amplitudes and for drowsiness to produce the slowest responses with the smallest amplitudes. The latency of P2 was significantly prolonged during drowsiness, relative to those during relaxation or activation. For right-ear stimulation, P5 latency was longest during drowsiness, and shortest during activation while for left-ear stimulation the shortest latency occurred during relaxation. The amplitudes of Wave II and Wave VII were significantly smaller during drowsiness than during activation. Although the differences were below the level of clinical significance, the data indicate a modification in the characteristics of brainstem transmission as a function of concurrent activity in other brain areas.

  7. Effects of blue pulsed light on human physiological functions and subjective evaluation

    Directory of Open Access Journals (Sweden)

    Katsuura Tetsuo

    2012-09-01

    Full Text Available Abstract Background It has been assumed that light with a higher irradiance of pulsed blue light has a much greater influence than that of light with a lower irradiance of steady blue light, although they have the same multiplication value of irradiance and duration. We examined the non-visual physiological effects of blue pulsed light, and determined whether it is sensed visually as being blue. Findings Seven young male volunteers participated in the study. We placed a circular screen (diameter 500 mm in front of the participants and irradiated it using blue and/or white light-emitting diodes (LEDs, and we used halogen lamps as a standard illuminant. We applied three steady light conditions of white LED (F0, blue LED + white LED (F10, and blue LED (F100, and a blue pulsed light condition of a 100-μs pulse width with a 10% duty ratio (P10. The irradiance of all four conditions at the participant's eye level was almost the same, at around 12 μW/cm2. We measured their pupil diameter, recorded electroencephalogram readings and Kwansei Gakuin Sleepiness Scale score, and collected subjective evaluations. The subjective bluish score under the F100 condition was significantly higher than those under other conditions. Even under the P10 condition with a 10% duty ratio of blue pulsed light and the F10 condition, the participant did not perceive the light as bluish. Pupillary light response under the P10 pulsed light condition was significantly greater than under the F10 condition, even though the two conditions had equal blue light components. Conclusions The pupil constricted under the blue pulsed light condition, indicating a non-visual effect of the lighting, even though the participants did not perceive the light as bluish.

  8. Sensory stimulation (TENS): effects of parameter manipulation on mechanical pain thresholds in healthy human subjects.

    Science.gov (United States)

    Chesterton, Linda S; Barlas, Panos; Foster, Nadine E; Lundeberg, Thomas; Wright, Christine C; Baxter, G David

    2002-09-01

    Transcutaneous electrical nerve stimulation (TENS) is a popular form of electrostimulation. Despite an extensive research base, there remains no consensus regarding the parameter selection required to achieve maximal hypoalgesic effects. The aim of this double blind, sham-controlled study was to investigate the relative hypoalgesic effects of different TENS parameters (frequency, intensity and stimulation site) upon experimentally induced mechanical pain. Two hundred and forty participants were recruited in order to provide statistical analysis with 80% power at alpha = 0.05. Subjects were randomised to one of the six TENS groups, a control, and a sham TENS group (n = 30, 15 males, 15 females, per group). TENS groups differed in their combinations of stimulation; frequency (4 or 110 Hz), intensity ('to tolerance' or 'strong but comfortable') and stimulation site (segmental--over the distribution of the radial nerve or, extrasegmental--over acupuncture point 'gall bladder 34', or a combination of both segmental and extrasegmental). Pulse duration was fixed at 200 micros. Stimulation was delivered for 30 min and subjects were then monitored for a further 30 min. Mechanical pain threshold (MPT) was measured using a pressure algometer and taken from the first dorsal interosseous muscle of the dominant hand, ipsilateral to the stimulation site. MPT measures were taken, at baseline, and at 10-min intervals for 60 min. Difference scores were analysed using repeated measures and one-way ANOVA and relevant post hoc tests. Low frequency, high intensity, extrasegmental stimulation produced a rapid onset hypoalgesic effect, which increased during the stimulation period (P < 0.0005 control and sham) and was sustained for 30 min post-stimulation (P < 0.0005(control), P = 0.024(sham)). Whilst high frequency, 'strong but comfortable' intensity, segmental stimulation produced comparable hypoalgesic levels during stimulation, this effect was not sustained post

  9. Quantification of airport community noise impact in terms of noise levels, population density, and human subjective response

    Science.gov (United States)

    Deloach, R.

    1981-01-01

    The Fraction Impact Method (FIM), developed by the National Research Council (NRC) for assessing the amount and physiological effect of noise, is described. Here, the number of people exposed to a given level of noise is multiplied by a weighting factor that depends on noise level. It is pointed out that the Aircraft-noise Levels and Annoyance MOdel (ALAMO), recently developed at NASA Langley Research Center, can perform the NRC fractional impact calculations for given modes of operation at any U.S. airport. The sensitivity of these calculations to errors in estimates of population, noise level, and human subjective response is discussed. It is found that a change in source noise causes a substantially smaller change in contour area than would be predicted simply on the basis of inverse square law considerations. Another finding is that the impact calculations are generally less sensitive to source noise errors than to systematic errors in population or subjective response.

  10. Francesco Bonatelli: A Critical (Experience-grounded Approach to Consciousness and Human Subject between Spiritualism and Positivism

    Directory of Open Access Journals (Sweden)

    Davide Poggi

    2016-08-01

    Full Text Available In the context of nineteenth-century philosophical reflection, Francesco Bonatelli (1830-1911 set himself the following goal: to defend the pillars of Spiritualism (the existence of a human subject with intellectual or supra-sensitive cognitive functions and ontology (the notions of esse and substantia through an careful examination of psychic contents and consciousness, while closely contesting both the psychology and the psychophysiology of Positivism (without rejecting its results in toto and Spiritualism itself (with all its uncritical assumptions and unnecessary metaphysical speculations. In works such as Pensiero e conoscenza (1864, La coscienza e il meccanesimo interiore (1872 and Percezione e pensiero (1892-1895 Bonatelli puts forward his “critical experience-grounded philosophy” and proposes an original solution to the problem of the nature of the subject, (self-consciousness and its unity, using an analysis of “sentiments” to reveal the inseparable tangle of the cognitive and ontological dimensions of the self.

  11. The development and validation of a digital peak respiratory pressure monitor and its characteristics in healthy human subjects.

    Science.gov (United States)

    Maruthy, K N; Vaz, M

    1999-04-01

    A digital peak respiratory pressure (DPRP) monitor for determining maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP) was developed using a pressure transducer and an analog to digital converter. It was calibrated using a mercury manometer. Human studies were conducted in healthy young adults in order to determine within-subject and inter-individual variability, as well as diurnal variations and gender differences in maximal respiratory pressures. The calibration studies for the instrument indicated that the instrument recorded accurate pressures, with little temporal drift. Within-subject variability was generally low while inter-individual variability was higher and significant. Gender differences were similar to those recorded in literature for other racial groups. The DPRP monitor described is inexpensive, accurate and portable, making it ideal for use at the patient's bedside.

  12. Reductions in circulating endocannabinoid 2-arachidonoylglycerol levels in healthy human subjects exposed to chronic stressors.

    Science.gov (United States)

    Yi, Buqing; Nichiporuk, Igor; Nicolas, Michel; Schneider, Stefan; Feuerecker, Matthias; Vassilieva, Galina; Thieme, Detlef; Schelling, Gustav; Choukèr, Alexander

    2016-06-01

    Increasing evidence indicates that chronic stress, such as social isolation, plays an important role in the development of a variety of psychiatric and somatic disorders. Meanwhile, chronic stress imposed by prolonged isolation and confinement in the spacecraft is also one of the major concerns for the health of future interplanetary space travelers. Preclinical studies suggest that the peripheral endocannabinoid (eCB) system is involved in the regulation of the stress response and eCB signaling is implicated in the pathogenesis of stress-related diseases. However, there are only few human studies addressing this topic, of which most focusing on patients who have already developed a certain type of disorder. It remains unknown whether chronic stress may affect eCB signaling in healthy humans. A 520-d isolation and confinement study simulating a flight to Mars provided an extraordinary chance to study the effects of prolonged stress in healthy humans. During the study period, the participants lived in confinement and could not meet their families, friends, or strangers for more than 500 days. We examined the impact of chronic exposure to isolation and confinement through monitoring their psychological state, brain cortical activity, sympathetic adrenal-medullary system response and eCB signaling response. We observed reduced positive emotion ratings, decreased brain cortical activities and high levels of catecholamine release, indicating that prolonged exposure to isolation and confinement stressors may bring about changes both psychologically and physiologically. Importantly, for eCB signaling response, blood concentrations of eCB 2-arachidonoylglycerol (2-AG), but not anandamide (AEA), were significantly reduced (p<0.001), suggesting that dysregulation of 2-AG signaling might be specifically implicated in the response to chronic stressors.

  13. IL-6, but not TNF-α, increases plasma YKL-40 in human subjects

    DEFF Research Database (Denmark)

    Nielsen, Anders R; Plomgaard, Peter; Krabbe, Karen S

    2011-01-01

    Plasma levels of YKL-40 are elevated in patients with systemic infection, inflammatory disorders and cancer. Both monocytes/macrophages, neutrophils, and cancer cells have the capacity to produce YKL-40, but the regulation during the inflammatory response is unknown. To study the possible role...... of interleukin-6 (IL-6) and tumor necrosis factor (TNF)-a in the regulation of YKL-40 plasma levels, we included healthy men, who received either recombinant human (rh)IL-6 (n=6), rhTNF-a (n=8) or vehicle (n=7) for 3h. The plasma levels of IL-6 and TNF-a reached ~ 150 and ~ 18 pg/ml, respectively, during...

  14. Measurement of Vibration Detection Threshold and Tactile Spatial Acuity in Human Subjects.

    Science.gov (United States)

    Moshourab, Rabih; Frenzel, Henning; Lechner, Stefan; Haseleu, Julia; Bégay, Valérie; Omerbašić, Damir; Lewin, Gary R

    2016-09-01

    Tests that allow the precise determination of psychophysical thresholds for vibration and grating orientation provide valuable information about mechanosensory function that are relevant for clinical diagnosis as well as for basic research. Here, we describe two psychophysical tests designed to determine the vibration detection threshold (automated system) and tactile spatial acuity (handheld device). Both procedures implement a two-interval forced-choice and a transformed-rule up and down experimental paradigm. These tests have been used to obtain mechanosensory profiles for individuals from distinct human cohorts such as twins or people with sensorineural deafness.

  15. Differential representation of liver proteins in obese human subjects suggests novel biomarkers and promising targets for drug development in obesity.

    Science.gov (United States)

    Caira, Simonetta; Iannelli, Antonio; Sciarrillo, Rosaria; Picariello, Gianluca; Renzone, Giovanni; Scaloni, Andrea; Addeo, Pietro

    2017-12-01

    The proteome of liver biopsies from human obese (O) subjects has been compared to those of nonobese (NO) subjects using two-dimensional gel electrophoresis (2-DE). Differentially represented proteins were identified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS)-based peptide mass fingerprinting (PMF) and nanoflow-liquid chromatography coupled to electrospray-tandem mass spectrometry (nLC-ESI-MS/MS). Overall, 61 gene products common to all of the liver biopsies were identified within 65 spots, among which 25 ones were differently represented between O and NO subjects. In particular, over-representation of short-chain acyl-CoA dehydrogenase, Δ(3,5)-Δ(2,4)dienoyl-CoA isomerase, acetyl-CoA acetyltransferase, glyoxylate reductase/hydroxypyruvate reductase, fructose-biphosphate aldolase B, peroxiredoxin I, protein DJ-1, catalase, α- and β-hemoglobin subunits, 3-mercaptopyruvate S-transferase, calreticulin, aminoacylase 1, phenazine biosynthesis-like domain-containing protein and a form of fatty acid-binding protein, together with downrepresentation of glutamate dehydrogenase, glutathione S-transferase A1, S-adenosylmethionine synthase 1A and a form of apolipoprotein A-I, was associated with the obesity condition. Some of these metabolic enzymes and antioxidant proteins have already been identified as putative diagnostic markers of liver dysfunction in animal models of steatosis or obesity, suggesting additional investigations on their role in these syndromes. Their differential representation in human liver was suggestive of their consideration as obesity human biomarkers and for the development of novel antiobesity drugs.

  16. A History of In Vivo Neutron Activation Analysis in Measurement of Aluminum in Human Subjects.

    Science.gov (United States)

    Mohseni, Hedieh K; Chettle, David R

    2016-01-01

    Aluminum, as an abundant metal, has gained widespread use in human life, entering the body predominantly as an additive to various foods and drinking water. Other major sources of exposure to aluminum include medical, cosmetic, and occupational routes. As a common environmental toxin, with well-known roles in several medical conditions such as dialysis encephalopathy, aluminum is considered a potential candidate in the causality of Alzheimer's disease. Aluminum mostly accumulates in the bone, which makes bone an indicator of the body burden of aluminum and an ideal organ as a proxy for the brain. Most of the techniques developed for measuring aluminum include bone biopsy, which requires invasive measures, causing inconvenience for the patients. There has been a considerable effort in developing non-invasive approaches, which allow for monitoring aluminum levels for medical and occupational purposes in larger populations. In vivo neutron activation analysis, a method based on nuclear activation of isotopes of elements in the body and their subsequent detection, has proven to be an invaluable tool for this purpose. There are definite challenges in developing in vivo non-invasive techniques capable of detecting low levels of aluminum in healthy individuals and aluminum-exposed populations. The following review examines the method of in vivo neutron activation analysis in the context of aluminum measurement in humans focusing on different neutron sources, interference from other activation products, and the improvements made in minimum detectable limits and patient dose over the past few decades.

  17. Significant association between glycemic status and increased estimated postglomerular resistance in nondiabetic subjects - study of inulin and para-aminohippuric acid clearance in humans.

    Science.gov (United States)

    Yasumoto, Mari; Tsuda, Akihiro; Ishimura, Eiji; Uedono, Hideki; Ohno, Yoshiteru; Ichii, Mitsuru; Ochi, Akinobu; Nakatani, Shinya; Mori, Katsuhito; Uchida, Junji; Emoto, Masanori; Nakatani, Tatsuya; Inaba, Masaaki

    2015-03-01

    We investigated whether glomerular hemodynamic parameters in nondiabetic subjects, including healthy subjects, are associated with glycemic status indices, by simultaneous measurement of inulin (Cin) and para-aminohippuric acid (CPHA) clearance. Twenty-six subjects (age 49.5 ± 13.3 years; 13 men and 13 women; 14 healthy subjects and 12 subjects with mild proteinuria) were enrolled. Cin and CPAH were measured simultaneously. All 26 subjects were nondiabetics. Estimated preglomerular resistance, estimated postglomerular resistance, and estimated glomerular hydrostatic pressure (Pglo) were calculated according to Gomez' formula. Pglo correlated significantly and positively with hemoglobin A1c (HbA1c) in both healthy subjects (r = 0.532, P = 0.0498) and subjects with mild proteinuria (r = 0.681, P = 0.015). While there was no significant correlation between estimated preglomerular resistance and HbA1c, estimated postglomerular resistance correlated significantly and positively with HbA1c both in healthy subjects (r = 0.643, P = 0.013) and subjects with mild proteinuria (r = 0.589, P = 0.044). Glomerular filtration fraction, estimated Pglo and estimated postglomerular resistance in total subjects were associated significantly with HbA1c after adjustment for age, gender, and body mass index. These results demonstrate that, even in nondiabetic subjects, glycemic status is associated with estimated postglomerular resistance, but not estimated preglomerular resistance. It is suggested that increased estimated postglomerular resistance associated with higher HbA1c levels, even within the normal range, causes increased estimated Pglo, leading to increased FF. Thus, hemodynamic abnormalities associated with higher HbA1c levels may be related to glomerular hypertension, even in nondiabetic subjects.

  18. Determination of material emission signatures by PTR-MS and their correlations with odor assessments by human subjects

    DEFF Research Database (Denmark)

    K H, Han; J S, Zhang; Wargocki, Pawel;

    2010-01-01

    with the PTR-MS emission signatures. The data on the acceptability of air quality assessed by human subjects were obtained from a previous experimental study in which the emissions from the same batch of materials were determined under the same area-specific ventilation rates as in the case of the measurements...... with PTR-MS. Results show that PTR-MS can be an effective tool for establishing VOC emission signatures of material types and that there were reasonable correlations between the PTR-MS measurements and the acceptability of air quality for the nine materials tested when the sum of selected major individual...

  19. Current outlook of ethics in research with human subjects Panorama atual da ética em pesquisa em seres humanos

    Directory of Open Access Journals (Sweden)

    Marystella Tomoe Takahashi

    2011-04-01

    Full Text Available In the last decades, medical care has been increasingly permeated by the concept of evidence-based-medicine, in which clinical research plays a crucial role in establishing diagnostic and treatment. Following the improvements in clinical research, we have a growing concern and understanding that some ethical issues must be respected when the subjects are human beings. Research with human subjects relies on the principles of autonomy, beneficence, no maleficence and justice. Ordinance 196/96 from the National Health Board adds to the Brazilian legislation such renowned bioethical principles. AIM: Discuss the main ethical aspects involved in research with human subjects. MATERIALS AND METHODS: Critical analysis of Ordinance 196/96 and related literature. CONCLUSION: Ordinance 196/96 rules research with human subjects; nevertheless, it requires more in-depth discussions regarding the informed consent, use of placebo, research with vulnerable populations and research in developing countries.Nas últimas décadas, a medicina tem sido cada vez mais permeada pelo conceito de medicina baseada em evidências, na qual a pesquisa clínica possui papel crucial no estabelecimento de diretrizes diagnósticas e terapêuticas. Com o avanço da pesquisa clínica, surgiu a preocupação e o entendimento que certos padrões éticos devam ser obedecidos quando o objeto de estudo é o ser humano. A pesquisa em seres humanos baseia-se nos princípios da autonomia, beneficência, não maleficência e justiça. A Resolução 196/96 do Conselho Nacional de Saúde incorpora à legislação brasileira tais princípios bioéticos consagrados. OBJETIVO: Discutir os principais aspectos éticos envolvidos na pesquisa em seres humanos. MATERIAL E MÉTODO: Análise crítica da Resolução 196/96 do CNS e literatura correlata. CONCLUSÃO: A Resolução 196/96 do Conselho Nacional de Saúde regulamenta a experimentação em seres humanos, no entanto necessita de discussões mais

  20. Ethics and experimentation on human subjects in mid-nineteenth-century France: the story of the 1859 syphilis experiments.

    Science.gov (United States)

    Dracobly, Alex

    2003-01-01

    This article examines a series of experiments involving the deliberate infection of human subjects with syphilis that were performed in Paris in 1859 by Dr. Camille Gibert and Dr. Joseph Alexandre Auzias-Turenne. Using the scientific literature on syphilis, the contemporary reaction in the French medical press to Gibert's and Auzias-Turenne's experiments, and the private papers of Auzias-Turenne, this paper places these experiments within a context of scientific and professional rivalry, and seeks to show how both moral and scientific concerns shaped and limited experimental practices in mid-nineteenth-century France.

  1. Absorption, conjugation and excretion of the flavanones, naringenin and hesperetin from alpha-rhamnosidase-treated orange juice in human subjects

    DEFF Research Database (Denmark)

    Bredsdorff, Lea; Nielsen, I.L.F.; Rasmussen, S.E.

    2010-01-01

    We have determined the absorption, conjugation and excretion of naringenin-7-O-rutinosicle (narirutin) compared to the corresponding glucoside in an orange juice matrix in human subjects. Healthy volunteers (eight men and eight women), in a double blind, randomised, crossover study, consumed orange......-rhamnosidase-treated orange juice was increased about 4-fold (P...... juice with (1) natural content of naringenin-7-O-rutinoside; (2) alpha-rhamnosidase-treated to yield naringenin-7-O-glucoside. Blood was sampled at twelve time points and three fractions of urine were collected over 24 h. The area under the plasma-time curve of naringenin from (2) alpha...

  2. Kinetics of the human thyroid trap: experience in normal subjects and in thyroid disease

    Energy Technology Data Exchange (ETDEWEB)

    Hays, M.T.

    1979-03-01

    Kinetics of the thyroid pertechnetate trap were assessed in 39 normal subjects, five untreated patients with Graves' disease (two before and after treatment), two hypothyroid patients, and in one patient each with Hashimoto's thyroiditis of recent onset, subacute thyroiditis, and massive anaplastic carcinoma. In normal subjects, the effects of sex, time of day, and order of experimental sessions were studied. A three-compartment model was assumed for all studies. Data on thyroidal and neck-background pertechnetate were collected with a multicrystal camera during 40 min after iv injection. The two thyroidal compartments in the model - the follicular cell, v/sub 2/, and the colloidal plasma-equivalent space, V/sub 3/ - is a multi-exponential function of plasma radioactivity, V/sub 1/. None of the model parameters was systematically affected by sex and order of session did not consistently alter any parameter, except for V/sub 3/, which was greater in session 2 than in session 1. That increase was not consistent and is believed to be spurious. Time of day affected only the exit rate constant from the colloid ..lambda../sub 23/, which was increased later in the day (P < 0.02). Distribution of the normal parameters was more log-normal than normal. After 5% were excluded at the high end and at the low end, the range for a parameter, p, was found empirically to be: antiln (mean ln p - 1.7 s.d. ln p), and antiln (mean ln p + 1.5 s.d. ln p). In Graves' disease, V/sub 2/ is increased (P < 0.02), but the increases in V/sub 3/ and in ..lambda../sub 21/ (the clearance into the thyroid from serum) are more dramatic (P < 10/sup -8/). After treatment, V/sub 3/ and ..lambda../sub 21/ fell toward normal. The hypothyroid patients showed no trap activity, and the trap was normal in the patient with early Hashimoto's thyroiditis. The patients with subacute thyroiditis and anaplastic carcinoma had increases in V/sub 2/, V/sub 3/, and ..lambda../sub 21/, but the

  3. Twenty-first century vaccines

    Science.gov (United States)

    Rappuoli, Rino

    2011-01-01

    In the twentieth century, vaccination has been possibly the greatest revolution in health. Together with hygiene and antibiotics, vaccination led to the elimination of many childhood infectious diseases and contributed to the increase in disability-free life expectancy that in Western societies rose from 50 to 78–85 years (Crimmins, E. M. & Finch, C. E. 2006 Proc. Natl Acad. Sci. USA 103, 498–503; Kirkwood, T. B. 2008 Nat. Med 10, 1177–1185). In the twenty-first century, vaccination will be expected to eliminate the remaining childhood infectious diseases, such as meningococcal meningitis, respiratory syncytial virus, group A streptococcus, and will address the health challenges of this century such as those associated with ageing, antibiotic resistance, emerging infectious diseases and poverty. However, for this to happen, we need to increase the public trust in vaccination so that vaccines can be perceived as the best insurance against most diseases across all ages. PMID:21893537

  4. Deqi Induction by HT7 Acupuncture Alters Theta and Alpha Band Coherence in Human Healthy Subjects.

    Science.gov (United States)

    Lee, Go-Eun; Yun, Jong-Min; Yang, Seung-Bum; Kang, Yeonseok; Kang, Hyung-Won; Choi, Kwang-Ho; Kim, Junbeom; Kwon, O Sang; Park, Ji-Eun; Kim, Jae-Hyo

    2017-01-01

    The aim of this preliminary study is to investigate the changes in phase synchronization in the theta and alpha bands before and during the performance of classical acupuncture on the Sinmun (HT7). The electroencephalogram (EEG) signals from nine healthy young subjects were recorded before and during acupuncture in the "closed-eye" state. The EEG signals were acquired from 19 surface scalp electrodes (FP1, FP2, F7, F3, Fz F4, F8, T3, C3, Cz, C4, T4, T5, P3, Pz, P4, T6, O1, and O2). Needles were inserted into the HT7 bilaterally and were then manipulated to induce deqi and retained for 15 minutes. Phase synchronization was measured by phase coherence. In the theta band, coherence significantly increased between the temporal (T5, T6) and occipital areas (O1, O2) during the acupuncture stimulation. In the alpha band, coherence significantly increased between the left temporal area (T5) and other areas (frontal, parietal, and occipital). Phase coherence in the theta and alpha bands tended to increase during the retention of the acupuncture needles after deqi. Therefore, it can be concluded that acupuncture stimulation with deqi is clinically effective via the central nervous system (CNS).

  5. Deqi Induction by HT7 Acupuncture Alters Theta and Alpha Band Coherence in Human Healthy Subjects

    Directory of Open Access Journals (Sweden)

    Go-Eun Lee

    2017-01-01

    Full Text Available The aim of this preliminary study is to investigate the changes in phase synchronization in the theta and alpha bands before and during the performance of classical acupuncture on the Sinmun (HT7. The electroencephalogram (EEG signals from nine healthy young subjects were recorded before and during acupuncture in the “closed-eye” state. The EEG signals were acquired from 19 surface scalp electrodes (FP1, FP2, F7, F3, Fz F4, F8, T3, C3, Cz, C4, T4, T5, P3, Pz, P4, T6, O1, and O2. Needles were inserted into the HT7 bilaterally and were then manipulated to induce deqi and retained for 15 minutes. Phase synchronization was measured by phase coherence. In the theta band, coherence significantly increased between the temporal (T5, T6 and occipital areas (O1, O2 during the acupuncture stimulation. In the alpha band, coherence significantly increased between the left temporal area (T5 and other areas (frontal, parietal, and occipital. Phase coherence in the theta and alpha bands tended to increase during the retention of the acupuncture needles after deqi. Therefore, it can be concluded that acupuncture stimulation with deqi is clinically effective via the central nervous system (CNS.

  6. Power assessment for genetic association study of human longevity using offspring of long-lived subjects.

    Science.gov (United States)

    Tan, Qihua; Zhao, Jing Hua; Li, Shuxia; Kruse, Torben A; Christensen, Kaare

    2010-07-01

    Recently, an indirect genetic association approach that compares genotype frequencies in offspring of long-lived subjects and offspring from random families has been introduced to study gene-longevity associations. Although the indirect genetic association has certain advantages over the direct association approach that compares genotype frequency between centenarians and young controls, the power has been of concern. This paper reports a power study performed on the indirect approach using computer simulation. We perform our simulation study by introducing the current Danish population life table and the proportional hazard model for generating individual lifespan. Family genotype data is generated using a genetic linkage program for given SNP allele frequency. Power is estimated by setting the type I error rate at 0.05 and by calculating the Armitage's chi-squared test statistic for 200 replicate samples for each setting of the specified allele risk and frequency parameters under different modes of inheritance and for different sample sizes. The indirect genetic association analysis is a valid approach for studying gene-longevity association, but the sample size requirement is about 3-4 time larger than the direct approach. It also has low power in detecting non-additive effect genes. Indirect genetic association using offspring from families with both parents as nonagenarians is nearly as powerful as using offspring from families with one centenarian parent. In conclusion, the indirect design can be a good choice for studying longevity in comparison with other alternatives, when relatively large sample size is available.

  7. Lung deposition of salbutamol in healthy human subjects from the MAGhaler dry powder inhaler.

    Science.gov (United States)

    Newman, S; Malik, S; Hirst, R; Pitcairn, G; Heide, A; Pabst, J; Dinkelaker, A; Fleischer, W

    2002-12-01

    The MAGhaler (Mundipharma GmbH) is a multidose dry powder inhaler (DPI) containing a novel formulation of drug and lactose compacted by an isostatic pressing technique (GGU GmbH). On actuation, a precise dose is metered from a compacted ring-shaped drug tablet. In this study, the lung deposition of salbutamol from this device has been assessed. Ten healthy non-smoking subjects completed a two-way cross-over study assessing the pulmonary deposition of salbutamol (200 microg) from the MAGhaler at high (60 l/min) and low (30 l/min) peak inhaled flow rates (PIFRs), representing maximal and sub-maximal inspiratory efforts. The formulation was radiolabelled with 99mTc, and lung and oropharyngeal depositions were quantified by gamma scintigraphyThe mean (SD)% ofthe delivered dose deposited in the lungs was 26.4 (4.3)% at 60 l/min and 21.1 (5.1)% at 30 l/min (P < 0.05), corresponding to mean lung depositions of 52.8 and 42.2 microg salbutamol, respectively. The distribution of drug within different lung regions did not vary significantly with inhaled flow rate. The data provided proof of concept for the novel inhaler device and the innovative drug formulation. In comparison with previous deposition data obtained with other DPIs, the lung deposition was relatively high, relatively reproducible (coefficient of variation 16% at 60 l/min) and relatively insensitive to the change in peak inhaled flow rate.

  8. Magnesium absorption in human subjects from leafy vegetables, intrinsically labeled with stable /sup 26/Mg

    Energy Technology Data Exchange (ETDEWEB)

    Schwartz, R.; Spencer, H.; Welsh, J.J.

    1984-04-01

    Collards, turnip greens, leaf lettuce, and spinach, grown in nutrient solution so that their Mg content was 80 to 90% /sup 26/Mg, were tested in ambulant male volunteers stabilized on a constant metabolic diet. The freeze-dried vegetables were incorporated in bran muffins in which the vegetables replaced part of the bran. Bran muffins without vegetables were consumed for breakfast each day. They were also used as a standard test meal to which the vegetable muffins were compared. All subjects participated in three consecutive isotope absorption tests: one of the standard test meal and two of the vegetables. The standard test was carried out after at least 30 days on the controlled diet. Subsequent tests of vegetables followed at 4-wk intervals. Each test meal contained 30 microCi /sup 28/MgCl2 and 50 mg stable /sup 26/Mg, the latter either as the intrinsic label of a test vegetable or as /sup 26/MgCl/sub 2/ in solution taken with the standard bran muffins. Net absorption of both isotopes was measured to establish exchangeability and to determine relative Mg absorption from the vegetables. Exchangeability was 90% or higher from all meals tested. Relative Mg absorption was highest from collards and least from the standard test meal. Net absorption values ranged from 40 to 60%.

  9. Application of dermal microdialysis for the determination of bioavailability of clobetasol propionate applied to the skin of human subjects

    DEFF Research Database (Denmark)

    Au, W L; Skinner, M F; Benfeldt, E

    2012-01-01

    Dermal microdialysis was used to assess the bioavailability of a topical corticosteroid, clobetasol propionate, following application onto the skin of human subjects. The penetration of clobetasol propionate from a 4% m/v ethanolic solution applied onto 4 sites on one forearm of healthy human...... drug of interest. Furthermore, the study clearly demonstrated the application of dermal microdialysis as a valuable tool to assess the bioavailability/bioequivalence of clobetasol propionate penetration into the skin following topical application....... volunteers was studied. A lipid emulsion, Intralipid®, was used as the perfusate and linear microdialysis probes with a 2-kDa cutoff were inserted intradermally at the designated sites. The results indicated that Intralipid could be used as a suitable perfusate for in vivo microdialysis of this lipophilic...

  10. [Defining trials of medicinal products according to the revised Dutch Medical Research in Human Subjects Act (WMO)].

    Science.gov (United States)

    Vos, E J; Huitema, A D R

    2006-09-23

    The revised Dutch Medical Research in Human Subjects Act (WMO), which implements the European directive regarding 'good clinical practice in the conduct of clinical trials on medicinal products for human use' (2001/20/EC), became effective on March 1, 2006. The revision places additional requirements on trials of medicinal products. Whether a trial should be regarded as a trial of a medicinal product is therefore an important question. The law does not provide adequate guidance for the classification of trials in which biological samples are collected, e.g. for genomic, proteomic or pharmacokinetic studies, while a medicinal product is given for a registered indication. Classifying these types of trials as trials of medicinal products does not enhance the safety of the participants. Therefore, these studies should not be considered as trials of medicinal products to avoid the increased administrative burden required by the revised WMO.

  11. IL-6, but not TNF-α, increases plasma YKL-40 in human subjects

    DEFF Research Database (Denmark)

    Nielsen, Anders R; Plomgaard, Peter; Krabbe, Karen S

    2011-01-01

    Plasma levels of YKL-40 are elevated in patients with systemic infection, inflammatory disorders and cancer. Both monocytes/macrophages, neutrophils, and cancer cells have the capacity to produce YKL-40, but the regulation during the inflammatory response is unknown. To study the possible role...... of interleukin-6 (IL-6) and tumor necrosis factor (TNF)-α in the regulation of YKL-40 plasma levels, we included healthy men, who received either recombinant human (rh)IL-6 (n=6), rhTNF-α (n=8) or vehicle (n=7) for 3h. The plasma levels of IL-6 and TNF-α reached ∼ 150 and ∼ 18 pg/ml, respectively, during...

  12. Atypical evening cortisol profile induces visual recognition memory deficit in healthy human subjects

    Directory of Open Access Journals (Sweden)

    Gilpin Heather

    2008-08-01

    Full Text Available Abstract Background Diurnal rhythm-mediated endogenous cortisol levels in humans are characterised by a peak in secretion after awakening that declines throughout the day to an evening trough. However, a significant proportion of the population exhibits an atypical cycle of diurnal cortisol due to shift work, jet-lag, aging, and mental illness. Results The present study has demonstrated a correlation between elevation of cortisol in the evening and deterioration of visual object recognition memory. However, high evening cortisol levels have no effect on spatial memory. Conclusion This study suggests that atypical evening salivary cortisol levels have an important role in the early deterioration of recognition memory. The loss of recognition memory, which is vital for everyday life, is a major symptom of the amnesic syndrome and early stages of Alzheimer's disease. Therefore, this study will promote a potential physiologic marker of early deterioration of recognition memory and a possible diagnostic strategy for Alzheimer's disease.

  13. Nitinol Stent Fatigue in a Peripheral Human Artery Subjected to Pulsatile and Articulation Loading

    Science.gov (United States)

    Harvey, Sean Michael

    2011-07-01

    Nitinol self-expanding stents are used to treat peripheral occluded vessels such as the superficial femoral artery or the carotid. The complex vessel articulation requires a stent device that is flexible and kink resistant yet durable. The present study shows how the latest advances in commercially available engineering software tools permit engineering simulations of the many aspects of the Nitinol stent design and analysis. Two stent geometries are evaluated: a helical type stent design, and a more traditional straight strut, with multiple crowns design. The fatigue performance of the two stents is compared. The results show that advanced nonlinear finite element simulations and fatigue predictions of the Nitinol stent are possible today inside realistic simulated human arteries. The finite element analysis software used in this study is SimXpert, Marc, and Mentat (MSC Software, Santa Ana, CA).

  14. Immunomodulatory effects of a standardized Lycium barbarum fruit juice in Chinese older healthy human subjects.

    Science.gov (United States)

    Amagase, Harunobu; Sun, Bixuang; Nance, Dwight M

    2009-10-01

    Lycium barbarum has been traditionally used in combination with several herbs for medicinal properties, but systematic modern clinical evaluation as a single herb has not been reported. To examine the systematic effects of L. barbarum on immune function, general well-being, and safety, we tested the effects of a standardized L. barbarum fruit juice (GoChi, FreeLife International, Phoenix, AZ, USA) at 120 mL/day, equivalent to at least 150 g of fresh fruit, the amount traditionally used, or placebo for 30 days in a randomized, double-blind, placebo-controlled clinical study in 60 older healthy adults (55-72 years old). The GoChi group showed a statistically significant increase in the number of lymphocytes and levels of interleukin-2 and immunoglobulin G compared to pre-intervention and the placebo group, whereas the number of CD4, CD8, and natural killer cells or levels of interleukin-4 and immunoglobulin A were not significantly altered. The placebo group showed no significant changes in any immune measures. Whereas the GoChi group showed a significant increase in general feelings of well-being, such as fatigue and sleep, and showed a tendency for increased short-term memory and focus between pre- and post-intervention, the placebo group showed no significant positive changes in these measures. No adverse reactions, abnormal symptoms, or changes in body weight, blood pressure, pulse, visual acuity, urine, stool, or blood biochemistry were seen in either group. In conclusion, daily consumption of GoChi significantly increased several immunological responses and subjective feelings of general well-being without any adverse reactions.

  15. Hormonal and Dietary Characteristics in Obese Human Subjects with and without Food Addiction

    Directory of Open Access Journals (Sweden)

    Pardis Pedram

    2014-12-01

    Full Text Available The concept of food addiction (FA is a potentially important contributing factor to the development of obesity in the general population; however, little is known about the hormonal and dietary differences between obesity with and without FA. Therefore, the aim of our study was to explore potential biomarkers, including various hormones and neuropeptides, which regulate appetite and metabolism, and dietary components that could potentially differentiate obesity with and without FA. Of the 737 adults recruited from the general Newfoundland population, 58 food-addicted and non-food-addicted overweight/obese individuals (FAO, NFO matched for age, sex, BMI and physical activity were selected. A total of 34 neuropeptides, gut hormones, pituitary polypeptide hormones and adipokines were measured in fasting serum. We found that the FAO group had lower levels of TSH, TNF-α and amylin, but higher levels of prolactin, as compared to NFO group. The total calorie intake (per kg body weight, the dietary intake of fat (per g/kg body weight, per BMI and per percentage of trunk fat and the percent calorie intake from fat and carbohydrates (g/kg was higher in the FAO group compared to the NFO group. The FAO subjects consumed more sugar, minerals (including sodium, potassium, calcium and selenium, fat and its components (such as saturated, monounsaturated and trans fat, omega 3 and 6, vitamin D and gamma-tocopherol compared to the NFO group. To our knowledge, this is the first study indicating possible differences in hormonal levels and micro-nutrient intakes between obese individuals classified with and without food addiction. The findings provide insights into the mechanisms by which FA could contribute to obesity.

  16. Hormonal and dietary characteristics in obese human subjects with and without food addiction.

    Science.gov (United States)

    Pedram, Pardis; Sun, Guang

    2014-12-31

    The concept of food addiction (FA) is a potentially important contributing factor to the development of obesity in the general population; however, little is known about the hormonal and dietary differences between obesity with and without FA. Therefore, the aim of our study was to explore potential biomarkers, including various hormones and neuropeptides, which regulate appetite and metabolism, and dietary components that could potentially differentiate obesity with and without FA. Of the 737 adults recruited from the general Newfoundland population, 58 food-addicted and non-food-addicted overweight/obese individuals (FAO, NFO) matched for age, sex, BMI and physical activity were selected. A total of 34 neuropeptides, gut hormones, pituitary polypeptide hormones and adipokines were measured in fasting serum. We found that the FAO group had lower levels of TSH, TNF-α and amylin, but higher levels of prolactin, as compared to NFO group. The total calorie intake (per kg body weight), the dietary intake of fat (per g/kg body weight, per BMI and per percentage of trunk fat) and the percent calorie intake from fat and carbohydrates (g/kg) was higher in the FAO group compared to the NFO group. The FAO subjects consumed more sugar, minerals (including sodium, potassium, calcium and selenium), fat and its components (such as saturated, monounsaturated and trans fat), omega 3 and 6, vitamin D and gamma-tocopherol compared to the NFO group. To our knowledge, this is the first study indicating possible differences in hormonal levels and micro-nutrient intakes between obese individuals classified with and without food addiction. The findings provide insights into the mechanisms by which FA could contribute to obesity.

  17. Measurement of vascular water transport in human subjects using time-resolved pulsed arterial spin labelling.

    Science.gov (United States)

    Bibic, Adnan; Knutsson, Linda; Schmidt, Anders; Henningsson, Erik; Månsson, Sven; Abul-Kasim, Kasim; Åkeson, Jonas; Gunther, Matthias; Ståhlberg, Freddy; Wirestam, Ronnie

    2015-08-01

    Most approaches to arterial spin labelling (ASL) data analysis aim to provide a quantitative measure of the cerebral blood flow (CBF). This study, however, focuses on the measurement of the transfer time of blood water through the capillaries to the parenchyma (referred to as the capillary transfer time, CTT) as an alternative parameter to characterise the haemodynamics of the system. The method employed is based on a non-compartmental model, and no measurements need to be added to a common time-resolved ASL experiment. Brownian motion of labelled spins in a potential was described by a one-dimensional general Langevin equation as the starting point, and as a Fokker-Planck differential equation for the averaged distribution of labelled spins at the end point, which takes into account the effects of flow and dispersion of labelled water by the pseudorandom nature of the microvasculature and the transcapillary permeability. Multi-inversion time (multi-TI) ASL data were acquired in 14 healthy subjects on two occasions in a test-retest design, using a pulsed ASL sequence and three-dimensional gradient and spin echo (3D-GRASE) readout. Based on an error analysis to predict the size of a region of interest (ROI) required to obtain reasonably precise parameter estimates, data were analysed in two relatively large ROIs, i.e. the occipital lobe (OC) and the insular cortex (IC). The average values of CTT in OC were 260 ± 60 ms in the first experiment and 270 ± 60 ms in the second experiment. The corresponding IC values were 460 ± 130 ms and 420 ± 139 ms, respectively. Information related to the water transfer time may be important for diagnostics and follow-up of cerebral conditions or diseases characterised by a disrupted blood-brain barrier or disturbed capillary blood flow.

  18. Plasma appearance and correlation between coffee and green tea metabolites in human subjects.

    Science.gov (United States)

    Renouf, Mathieu; Guy, Philippe; Marmet, Cynthia; Longet, Karin; Fraering, Anne-Lise; Moulin, Julie; Barron, Denis; Dionisi, Fabiola; Cavin, Christophe; Steiling, Heike; Williamson, Gary

    2010-12-01

    Coffee and green tea are two of the most widely consumed hot beverages in the world. Their respective bioavailability has been studied separately, but absorption of their respective bioactive phenolics has not been compared. In a randomised cross-over design, nine healthy subjects drank instant coffee and green tea. Blood samples were collected over 12 h and at 24 h to assess return to baseline. After green tea consumption, (-)-epigallocatechin (EGC) was the major catechin, appearing rapidly in the plasma; (-)-EGC gallate (EGCg) and (-)-epicatechin (EC) were also present, but (-)-EC gallate and C were not detected. Dihydroferulic acid and dihydrocaffeic acid were the major metabolites that appeared after coffee consumption with a long time needed to reach maximum plasma concentration, suggesting metabolism and absorption in the colon. Other phenolic acid equivalents (caffeic acid (CA), ferulic acid (FA) and isoferulic acid (iFA)) were detected earlier, and they peaked at lower concentrations. Summations of the plasma area under the curves (AUC) for the measured metabolites showed 1.7-fold more coffee-derived phenolic acids than green tea-derived catechins (P = 0.0014). Furthermore, we found a significant correlation between coffee metabolites based on AUC. Inter-individual differences were observed, but individuals with a high level of CA also showed a correspondingly high level of FA. However, no such correlation was observed between the tea catechins and coffee phenolic acids. Correlation between AUC and maximum plasma concentration was also significant for CA, FA and iFA and for EGCg. This implies that the mechanisms of absorption for these two classes of compounds are different, and that a high absorber of phenolic acids is not necessarily a high absorber of catechins.

  19. Tissue gas and blood analyses of human subjects breathing 80% argon and 20% oxygen

    Science.gov (United States)

    Horrigan, D. J.; Wells, C. H.; Guest, M. M.; Hart, G. B.; Goodpasture, J. E.

    1979-01-01

    Eight human volunteers, individually studied in a hyperbaric chamber, breathed: (1) air at 1 ATA; (2) 80% argon and 20% oxygen at 1 ATA for 30 min; (3) air at 1 ATA for 30 min; (4) 100% O2 at 1 ATA for 30 min; (5) air at 1 ATA for 30 min; (6) 100% O2 at 2 ATA for 60 min; and (7) 80% argon and 20% oxygen at 1 ATA for 30 min. Oxygen, carbon dioxide, nitrogen, and argon tensions were measured in muscle and subcutaneous tissue by mass spectroscopic analyses. Venous blood obtained at regular intervals was analyzed for coagulation and fibrinolytic factors. Inert gas narcosis was not observed. After breathing argon for 30 min, muscle argon tensions were almost three times the subcutaneous tensions. Argon wash-in mirrored nitrogen wash-out. Argon wash-in and wash-out had no effect on tissue PO2 or PCO2. Coagulation and fibrinolytic changes usually associated with vascular bubbles were absent.

  20. Magneto encephalography (MEG: perspectives of speech areas functional mapping in human subjects

    Directory of Open Access Journals (Sweden)

    Butorina A. V.

    2012-06-01

    Full Text Available One of the main problems in clinical practice and academic research is how to localize speech zones in the human brain. Two speech areas (Broca and Wernicke areas that are responsible for language production and for understanding of written and spoken language have been known since the past century. Their location and even hemispheric lateralization have a substantial inter-individual variability, especially in neurosurgery patients. Wada test is one of the most frequently used invasive methodology for speech hemispheric lateralization in neurosurgery patients. However, besides relatively high-risk of Wada test for patient's health, it has its own limitation, e. g. low reliability of Wada-based evidence of verbal memory brain lateralization. Therefore, there is an urgent need for non-invasive, reliable methods of speech zones mapping.The current review summarizes the recent experimental evidence from magnitoencephalographic (MEG research suggesting that speech areas are included in the speech processing within the first 200 ms after the word onset. The electro-magnetic response to deviant word, mismatch negativity wave with latency of 100—200 ms, can be recorded from auditory cortex within the oddball-paradigm. We provide the arguments that basic features of this brain response, such as its automatic, pre-attentive nature, high signal to noise ratio, source localization at superior temporal sulcus, make it a promising vehicle for non-invasive MEG-based speech areas mapping in neurosurgery.

  1. Synaptic dysfunction in human immunodeficiency virus type-1-positive subjects: inflammation or impaired neuronal plasticity?

    Science.gov (United States)

    Avdoshina, Valeriya; Bachis, Alessia; Mocchetti, Italo

    2013-01-01

    Many people infected with the human immunodeficiency virus type-1 (HIV) exhibit mild or severe neurological problems, termed HIV-associated neurocognitive disorder (HAND), even when receiving antiretroviral therapy. Thus, novel adjunctive therapies must be developed to overcome the neurotoxic effect of HIV. New therapies require a better understanding of the molecular and cellular mechanisms of HIV-induced neurotoxicity and the risk factors that, besides inflammation and T cell depletion and drugs of abuse, render the central nervous system (CNS) a target of HIV-induced neurotoxicity. HIV appears to impair neuronal plasticity, which refers to the innate ability of the CNS to respond to injury and promote recovery of function. The availability of brain-derived neurotrophic factor (BDNF), a potent neurotrophic factor that is present in abundance in the adult brain, is essential for neuronal plasticity. BDNF acts through a receptor system composed of Trk and p75NTR. Here we present experimental evidence that some of the clinical features of HIV-mediated neurological impairment could result from altered BDNF/TrkB/p75NTR regulation and function. PMID:23600400

  2. Tissue gas and blood analyses of human subjects breathing 80% argon and 20% oxygen

    Science.gov (United States)

    Horrigan, D. J.; Wells, C. H.; Guest, M. M.; Hart, G. B.; Goodpasture, J. E.

    1979-01-01

    Eight human volunteers, individually studied in a hyperbaric chamber, breathed: (1) air at 1 ATA; (2) 80% argon and 20% oxygen at 1 ATA for 30 min; (3) air at 1 ATA for 30 min; (4) 100% O2 at 1 ATA for 30 min; (5) air at 1 ATA for 30 min; (6) 100% O2 at 2 ATA for 60 min; and (7) 80% argon and 20% oxygen at 1 ATA for 30 min. Oxygen, carbon dioxide, nitrogen, and argon tensions were measured in muscle and subcutaneous tissue by mass spectroscopic analyses. Venous blood obtained at regular intervals was analyzed for coagulation and fibrinolytic factors. Inert gas narcosis was not observed. After breathing argon for 30 min, muscle argon tensions were almost three times the subcutaneous tensions. Argon wash-in mirrored nitrogen wash-out. Argon wash-in and wash-out had no effect on tissue PO2 or PCO2. Coagulation and fibrinolytic changes usually associated with vascular bubbles were absent.

  3. Are quantum dots ready for in vivo imaging in human subjects?

    Directory of Open Access Journals (Sweden)

    Cai Weibo

    2007-01-01

    Full Text Available AbstractNanotechnology has the potential to profoundly transform the nature of cancer diagnosis and cancer patient management in the future. Over the past decade, quantum dots (QDs have become one of the fastest growing areas of research in nanotechnology. QDs are fluorescent semiconductor nanoparticles suitable for multiplexed in vitro and in vivo imaging. Numerous studies on QDs have resulted in major advancements in QD surface modification, coating, biocompatibility, sensitivity, multiplexing, targeting specificity, as well as important findings regarding toxicity and applicability. For in vitro applications, QDs can be used in place of traditional organic fluorescent dyes in virtually any system, outperforming organic dyes in the majority of cases. In vivo targeted tumor imaging with biocompatible QDs has recently become possible in mouse models. With new advances in QD technology such as bioluminescence resonance energy transfer, synthesis of smaller size non-Cd based QDs, improved surface coating and conjugation, and multifunctional probes for multimodality imaging, it is likely that human applications of QDs will soon be possible in a clinical setting.

  4. Impact of Open Data Policies on Consent to Participate in Human Subjects Research: Discrepancies between Participant Action and Reported Concerns.

    Science.gov (United States)

    Cummings, Jorden A; Zagrodney, Jessica M; Day, T Eugene

    2015-01-01

    Research outlets are increasingly adopting open data policies as a requisite for publication, including studies with human subjects data. We investigated whether open data policies influence participants' rate of consent by randomly assigning participants to view consent forms with and without discussion of open data policies. No participants declined to participate, regardless of condition, nor did rates of drop-out vs. completion vary between conditions. Furthermore, no significant change in potential consent rates was reported when participants were openly asked about the influence of open data policies on their likelihood of consent. However, follow-up analyses indicated possible poor attention to consent forms, consistent with previous research. Moreover, thematic analysis of participants' considerations of open data policy indicated multiple considerations such as concerns regarding confidentiality, anonymity, data security, and study sensitivity. The impact of open data policies on participation raises complex issues at the intersection of ethics and scientific innovation. We conclude by encouraging researchers to consider participants as stakeholders in open data policy and by providing recommendations for open data policies in human subjects research.

  5. Envelope statistics of self-motion signals experienced by human subjects during everyday activities: Implications for vestibular processing.

    Science.gov (United States)

    Carriot, Jérome; Jamali, Mohsen; Cullen, Kathleen E; Chacron, Maurice J

    2017-01-01

    There is accumulating evidence that the brain's neural coding strategies are constrained by natural stimulus statistics. Here we investigated the statistics of the time varying envelope (i.e. a second-order stimulus attribute that is related to variance) of rotational and translational self-motion signals experienced by human subjects during everyday activities. We found that envelopes can reach large values across all six motion dimensions (~450 deg/s for rotations and ~4 G for translations). Unlike results obtained in other sensory modalities, the spectral power of envelope signals decreased slowly for low (2 Hz) temporal frequencies and thus was not well-fit by a power law. We next compared the spectral properties of envelope signals resulting from active and passive self-motion, as well as those resulting from signals obtained when the subject is absent (i.e. external stimuli). Our data suggest that different mechanisms underlie deviation from scale invariance in rotational and translational self-motion envelopes. Specifically, active self-motion and filtering by the human body cause deviation from scale invariance primarily for translational and rotational envelope signals, respectively. Finally, we used well-established models in order to predict the responses of peripheral vestibular afferents to natural envelope stimuli. We found that irregular afferents responded more strongly to envelopes than their regular counterparts. Our findings have important consequences for understanding the coding strategies used by the vestibular system to process natural second-order self-motion signals.

  6. Dose-related Behavioral, Subjective, Endocrine and Psychophysiological Effects Of the Kappa Opioid Agonist Salvinorin A in Humans

    Science.gov (United States)

    Ranganathan, Mohini; Schnakenberg, Ashley; Skosnik, Patrick D.; Cohen, Bruce; Pittman, Brian; Sewell, R. Andrew; D’Souza, Deepak Cyril

    2012-01-01

    Background Salvia divinorum (Salvia) is an increasingly popular recreational drug amongst adolescents and young adults. Its primary active ingredient, Salvinorin A (SA), a highly selective agonist at the kappa opiate receptor (KOR), is believed to be one of the most potent naturally occurring hallucinogens. However, there is little experimental data on the effects of SA in humans. Methods In a 3-day, double-blind, randomized, crossover, counterbalanced study, the behavioral, subjective, cognitive, psychophysiological and endocrine effects of 0 mg, 8 mg and 12 mg of inhaled SA were characterized in 10 healthy individuals who had previously used Salvia. Results SA produced psychotomimetic effects and perceptual alterations including dissociative and somaesthetic effects, increased plasma cortisol and prolactin and reduced resting EEG spectral power. SA administration was associated with a rapid increase of its levels in the blood. SA did not produce euphoria, cognitive deficits or changes in vital signs. The effects were transient and not dose-related. SA administration was very well tolerated without acute or delayed adverse effects. Conclusions SA produced a wide range of transient effects in healthy subjects. The perceptual altering effects and lack of euphoric effects would explain its intermittent use pattern. Such a profile would also suggest a low addictive potential similar to other hallucinogens and consistent with KOR agonism. Further work is warranted to carefully characterize a full spectrum of its effects in humans, to elucidate the underlying mechanisms involved and to explore the basis for individual variability in its effects. PMID:22817868

  7. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects.

    Science.gov (United States)

    2014-01-01

    Published research in English-language journals are increasingly required to carry a statement that the study has been approved and monitored by an Institutional Review Board in conformance with 45 CFR 46 standards if the study was conducted in the United States. Alternative language attesting conformity with the Helsinki Declaration is often included when the research was conducted in Europe or elsewhere. The Helsinki Declaration was created by the World Medical Association in 1964 (ten years before the Belmont Report) and has been amended several times. The Helsinki Declaration differs from its American version in several respects, the most significant of which is that it was developed by and for physicians. The term "patient" appears in many places where we would expect to see "subject." It is stated in several places that physicians must either conduct or have supervisory control of the research. The dual role of the physician-researcher is acknowledged, but it is made clear that the role of healer takes precedence over that of scientist. In the United States, the federal government developed and enforces regulations on researcher; in the rest of the world, the profession, or a significant part of it, took the initiative in defining and promoting good research practice, and governments in many countries have worked to harmonize their standards along these lines. The Helsinki Declaration is based less on key philosophical principles and more on prescriptive statements. Although there is significant overlap between the Belmont and the Helsinki guidelines, the latter extends much further into research design and publication. Elements in a research protocol, use of placebos, and obligation to enroll trials in public registries (to ensure that negative findings are not buried), and requirements to share findings with the research and professional communities are included in the Helsinki Declaration. As a practical matter, these are often part of the work of American

  8. Quantification of etodolac in human plasma for pharmacokinetics and bioequivalence studies in 27 Korean subjects.

    Science.gov (United States)

    Song, Il-Dong; Kang, Je-Seop; Kim, Hyun-Jin; Kim, Se-Mi; Zhao, Dong-Xu; Kim, Shin-Hee; Chun, Min-Young; Lee, Kyuhyun

    2017-01-16

    We developed a simple and validated liquid chromatography tandem mass spectrometry(LC-MS/MS) for quantification of etodolac using pioglitazone as an internal standard (IS) to assess pharmacokinetics and to appraise bioequivalence of two formulations of etodolac (reference and tested) in 27 healthy Korean subjects. Isocratic mobile phase consisted of 10 mM ammonium formate and acetonitrile were used to separate the analytes on a Gemini C18 column. Also, analytes were analyzed by MS/MS in multiple reaction monitoring (MRM) mode using the transitions of (M+H)+ ions, m/z 288.2→172.3 and m/z 357.1→134.2 for quantification of etodolac and IS each. The standard calibration curves displayed significant linearity within the range of 0.2-30.0 μg/mL (r2=0.9956, 1/x2 weighting) with LLOQ of 0.1 μg/mL. The retention times of etodolac and the IS were 0.77 min and 0.57 min each, indicating the high-throughput potential of the proposed method. The pharmacokinetic parameters were calculated from the plasma samples and data form the reference and test drugs were represented as follows; Area under plasma concentration-time curve (AUCt) (78.03 vs. 84.00 μg×h/mL), AUC∞ (86.67 vs. 93.92 μg×h/mL), maximal plasma concentration (Cmax) (19.49 vs. 18.94 μg/mL), time for maximal concentrations (Tmax) (2.13 vs. 2.26 h), Plasma elimination half-life (T1/2) (8.12 vs. 8.47 h), elimination rate constant (λz) (0.0853 vs. 0.0818 h-1). Pharmacokinetic parameters with 90% confidence interval fall within the bioequivalence range of 80-125%. Thus, the new testified method was successfully applied for the pharmacokinetic and bioequivalence studies for two etodolac formulations.

  9. Evaluation of the AMPLICOR cytomegalovirus test with specimens from human immunodeficiency virus-infected subjects.

    Science.gov (United States)

    Boivin, G; Handfield, J; Toma, E; Murray, G; Lalonde, R; Tevere, V J; Sun, R; Bergeron, M G

    1998-09-01

    The AMPLICOR cytomegalovirus (CMV) test, a new qualitative assay for the detection of CMV DNA in plasma, was compared to conventional methods and quantitative PCR (Q-PCR) assays by using leukocytes and plasma from 179 blood samples from subjects with AIDS. For the diagnosis of CMV disease, cell-based assays such as a Q-PCR with polymorphonuclear leukocytes (Q-PCR-PMNL) and a pp65 antigenemia assay had the highest sensitivities but suffered from a lack of specificity. The best agreement between the results of the Q-PCR-PMNL assay and those of the AMPLICOR test was found when a threshold diagnostic value of 690 copies per 10(5) cells was selected for the Q-PCR-PMNL assay. In that context, the AMPLICOR CMV test had a sensitivity of 96.4% and a specificity of 95.3% when results were compared to results of the cell-based PCR assay. This threshold was close to the one described as associated with the best sensitivity and specificity for the diagnosis of CMV disease in a recently published study (4). Blood samples that tested positive by the Q-PCR-PMNL assay but negative by the AMPLICOR CMV test were associated with viral loads (mean, 785 copies, median, 96 copies per 10(5) leukocytes) lower than the viral loads of blood samples that tested positive by both assays (mean, 21,452 copies; median, 9,784 copies per 10(5) leukocytes) (P = 0.003). The AMPLICOR CMV test gave positive results at least 48 days before the development of symptomatic CMV disease in a longitudinal analysis of a limited subset of patients (n = 6) from whom sequential specimens were available for testing. In conclusion, the AMPLICOR CMV test is a very convenient assay combining rapidity, simplicity, and the possibility of batch testing. A positive result by this test seems particularly important since this implies, in most instances, the presence or the imminence of CMV disease, although a negative test result does not rule out disease.

  10. Detection of human papillomavirus in normal oral cavity in a group of Pakistani subjects using real-time PCR.

    Science.gov (United States)

    Gichki, Abdul Samad; Buajeeb, Waranun; Doungudomdacha, Sombhun; Khovidhunkit, Siribang-on Pibooniyom

    2012-01-01

    Since there is evidence that human papillomavirus (HPV) may play some role in oral carcinogenesis, we investigated the presence of HPV in a group of Pakistani subjects with normal oral cavity using real-time PCR analysis. Two-hundred patients attending the Dental Department, Sandaman Provincial Hospital, Balochistan, Pakistan, were recruited. After interview, oral epithelial cells were collected by scraping and subjected to DNA extraction. The HPV-positive DNA samples were further analyzed using primer sets specific for HPV-16 and -18. It was found that out of 200 DNA samples, 192 were PCR-positive for the β-globin gene and these were subsequently examined for the presence of HPV DNA. Among these, 47 (24.5%) were HPV-positive with the virus copy number ranged between 0.43-32 copies per 1 μg of total DNA (9-99 copies per PCR reaction). There were 4 and 11 samples containing HPV-16 and -18, respectively. Additionally, one sample harbored both types of HPV. Among the investigated clinical parameters, smoking habit was associated with the presence of HPV (p=0.001) while others indicated no significant association. The prevalence of HPV in normal oral cavity in our Pakistani subjects appears to be comparable to other studies. However, the association between the presence of HPV and smoking warrants further investigations whether both of these factors can cooperate in inducing oral cancer in this group of patients.

  11. An Anthropometric-Based Subject-Specific Finite Element Model of the Human Breast for Predicting Large Deformations

    Science.gov (United States)

    Pianigiani, Silvia; Ruggiero, Leonardo; Innocenti, Bernardo

    2015-01-01

    The large deformation of the human breast threatens proper nodules tracking when the subject mammograms are used as pre-planning data for biopsy. However, techniques capable of accurately supporting the surgeons during biopsy are missing. Finite element (FE) models are at the basis of currently investigated methodologies to track nodules displacement. Nonetheless, the impact of breast material modeling on the mechanical response of its tissues (e.g., tumors) is not clear. This study proposes a subject-specific FE model of the breast, obtained by anthropometric measurements, to predict breast large deformation. A healthy breast subject-specific FE parametric model was developed and validated by Cranio-caudal (CC) and Medio-Lateral Oblique (MLO) mammograms. The model was successively modified, including nodules, and utilized to investigate the effect of nodules size, typology, and material modeling on nodules shift under the effect of CC, MLO, and gravity loads. Results show that a Mooney–Rivlin material model can estimate healthy breast large deformation. For a pathological breast, under CC compression, the nodules displacement is very close to zero when a linear elastic material model is used. Finally, when nodules are modeled, including tumor material properties, under CC, or MLO or gravity loads, nodules shift shows ~15% average relative difference. PMID:26734604

  12. Haplotype-based case-control study of the human AGTR1 gene and essential hypertension in Han Chinese subjects.

    Science.gov (United States)

    Nie, Sheng-jie; Wen-ru, Tang; Bi-feng, Chen; Jin, Li; Wen, Zhang; Sheng-jun, Luo; Wei-wei, Li; Hai-jing, Yu; Chun-jie, Xiao

    2010-02-01

    Essential hypertension is considered to be a multifactorial trait resulting from the combined influence of environmental and genetic determinants. The aim of the study is to assess the association between the human AGTR1 gene and essential hypertension (EH) using a haplotype-based case-control study in Han Chinese subjects. Seven tag SNPs and the A1166C polymorphism of the AGTR1 gene were genotyped in 510 hypertension subjects and 510 normotensive subjects using PCR-RFLP method. Single SNP analyses indicated that the rs12695895 was significantly associated with hypertension, adjusted for covariates. Compared with the other haplotypes, Hap4 (AGGACTT) which carry the susceptible rs12695895 A allele was found to significantly increase the risk of EH with odds ratios equal to 1.84 (p=0.0002). The present results indicate that rs12695895 might be a genetic marker for EH and Hap4 (AGGACTT) was associated with hypertension in Han Chinese population. (c) 2009 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  13. Human Bronchial Epithelial Cell-Derived Factors from Severe Asthmatic Subjects Stimulate Eosinophil Differentiation.

    Science.gov (United States)

    Salter, Brittany M A; Smith, Steven G; Mukherjee, Manali; Plante, Sophie; Krisna, Sakktee; Nusca, Graeme; Oliveria, John Paul; Irshad, Anam; Gauvreau, Gail M; Chakir, Jamila; Nair, Parameswaran; Sehmi, Roma

    2017-08-30

    Activated bronchial epithelial cells release alarmins, including thymic stromal lymphopoietin (TSLP) that drive type 2 inflammatory responses. We hypothesize that bronchial epithelial-derived factors enhance in situ eosinophil differentiation and maturation from myeloid precursors, a process that is driven by an IL-5 rich micro-environment within asthma airways. To assess the eosinophilopoietic potential of epithelial-derived factors, eosinophil/basophil colony forming units (Eo/B-CFU) were enumerated in 14-day methylcellulose cultures of blood-derived mononuclear cells (NAMNCs) incubated with bronchial epithelial cell supernatants (BECSN) from healthy non-atopic controls (NC; n = 8), mild atopic asthmatics (MA; n = 9) and severe asthmatics (SA; n = 5). Receptor blocking antibodies were used to evaluate the contribution of alarmins. Modulation of mRNA expression of transcription factors crucial for eosinophil differentiation was evaluated. BECSN stimulated the clonogenic expansion of eosinophil progenitors, in vitro. In the presence of IL-5, Eo/B-CFU growth was significantly greater in co-cultures of BESCN from SA, compared to MA and NC. This effect was attenuated by a TSLP receptor blocking antibody but not by an ST2 antibody. Recombinant human TSLP (optimal at 100 pg/ml) stimulated significant Eo/B-CFU growth, which was significantly enhanced in presence of IL-5 (1 ng/ml). Overnight culture of CD34+ cells with IL-5 and TSLP synergistically increased GATA-2 and CEBP-alpha mRNA expression. The eosinophilopoietic potential of factors derived from bronchial epithelial cells is increased in severe asthma. Our data suggest that TSLP is a key alarmin produced by bronchial epithelial cells, which promotes in situ eosinophilopoiesis in a type 2 rich microenvironment.

  14. An In Vitro Evaluation of Human Enamel Surfaces Subjected to Erosive Challenge After Bleaching.

    Science.gov (United States)

    de Fátima Carvalho Vasconcelos, Maria; Fonseca-Gonçalves, Andréa; de França, Adílis Kalina Alexandria; de Medeiros, Urubatan Vieira; Maia, Lucianne Cople; Queiroz, Celso Silva

    2017-04-01

    This study aimed to evaluate whether tooth enamel bleached with hydrogen peroxide (H2 O2 ) is more susceptible to erosion when compared with unbleached tooth enamel; and whether the presence of calcium (Ca) in the bleaching gel influenced this process. Enamel blocks were prepared from human molars, and submitted to surface microhardness analysis (baseline). Blocks were prepared and randomly divided into four treatment groups (n = 20): G1 and G2-bleached with 7.5% H2 O2 , with and without Ca, respectively; G3 and G4-bleached with 35% H2 O2 , with and without Ca, respectively. After bleaching, these groups were submitted to an erosive challenge with 1% citric acid. G5 and G6 (n = 20, each) were the negative (without bleaching) and positive controls (without bleaching, but with erosion), respectively. The percentage of surface hardness loss (%SHL), the 3D non-contact profilometry and Scanning Electron Microscopy (SEM) analyses were performed. G2 showed the highest %SHL after bleaching. G1 presented the lowest %SHL in comparison with G2, G3, G4, and G6 after erosion (p < 0.05), which was confirmed only by the SEM analysis. It is suggested that low concentration of H2 O2 with calcium can be recommended for at-home bleaching agents, which may avoid the mineral loss of bleached enamel after an erosive challenge. Low concentration of H2 02 with calcium can be recommended for at-home bleaching agents, which may avoid the mineral loss of bleached enamel after an erosive challenge. (J Esthet Restor Dent 29:128-136, 2017). © 2016 Wiley Periodicals, Inc.

  15. Ozone-induced inflammation in the lower airways of human subjects

    Energy Technology Data Exchange (ETDEWEB)

    Koren, H.S.; Devlin, R.B.; Graham, D.E.; Mann, R.; McGee, M.P.; Horstman, D.H.; Kozumbo, W.J.; Becker, S.; House, D.E.; McDonnell, W.F.

    1989-02-01

    Although ozone (O3) has been shown to induce inflammation in the lungs of animals, very little is known about its inflammatory effects on humans. In this study, 11 healthy nonsmoking men, 18 to 35 yr of age (mean, 25.4 +/- 3.5), were exposed once to 0.4 ppm O3 and once to filtered air for 2 h with intermittent exercise. Eighteen hours later, bronchoalveolar lavage (BAL) was performed and the cells and fluid were analyzed for various indicators of inflammation. There was an 8.2-fold increase in the percentage of polymorphonuclear leukocytes (PMN) in the total cell population, and a small but significant decrease in the percentage of macrophages after exposure to O3. Immunoreactive neutrophil elastase often associated with inflammation and lung damage increased by 3.8-fold in the fluid while its activity increased 20.6-fold in the lavaged cells. A 2-fold increase in the levels of protein, albumin, and IgG suggested increased vascular permeability of the lung. Several biochemical markers that could act as chemotactic or regulatory factors in an inflammatory response were examined in the BAL fluid (BALF). The level of complement fragment C3 alpha was increased by 1.7-fold. The chemotactic leukotriene B4 was unchanged while prostaglandin E2 increased 2-fold. In contrast, three enzyme systems of phagocytes with potentially damaging effects on tissues and microbes, namely, NADPH-oxidase and the lysosomal enzymes acid phosphatase and beta-glucuronidase, were increased neither in the lavaged fluid nor cells. In addition, the amounts of fibrogenic-related molecules were assessed in BALF.

  16. Biotransformation and toxicokinetics of the insect repellent IR3535® in male and female human subjects after dermal exposure.

    Science.gov (United States)

    Broschard, Thomas H; Bohlmann, Anja M; Konietzny, Stefan; Schauer, Ute M D; Dekant, Wolfgang

    2013-04-26

    The absorption and excretion of the insect repellent IR3535(®) was studied in human subjects (five males and five females) after dermal application of approx. 3g of a formulation containing 20% IR3535(®), i.e. the amounts of IR3535(®) applied were between 1.94 and 3.4 mmol/person (418-731 mg/person). Blood and urinary concentrations of IR3535(®) and its only metabolite, IR3535(®)-free acid, were determined over time. In plasma, concentrations of the parent compound IR3535(®) were at or below the limit of quantification (0.037 μmol/L). IR3535(®)-free acid peaked in plasma samples 2-6h after dermal application. Cmax mean values were 5.7 μmol/L in males, 3.0 μmol/L in females and 4.2 μmol/L in all volunteers. Mean AUC values were 41.6, 24.5 and 33.9 μmolL(-1)h in males, females and all subjects, respectively. In urine samples from all human subjects, both IR3535(®) and IR3535(®)-free acid were detectable, however, only very small amounts of IR3535(®) were found. Concentrations of IR3535(®)-free acid were several thousand-fold higher than the parent compound and peaked at the first two sampling points (4h and 8h after dermal application). Overall, IR3535(®) and IR3535(®)-free acid excreted with urine over 48 h representing 13.3 ± 3.05% of the dose applied. Since IR3535(®) is rapidly and extensively metabolized, and IR3535(®)-free acid has a low molecular weight and high water solubility, it is expected that urinary excretion of IR3535(®)-free acid and IR3535(®) represents the total extent of absorption of IR3535(®) in humans. Based on the results of this study, the skin penetration rate of IR3535(®) is 13.3% in humans after dermal application.

  17. Effect of Curcuma longa on CYP2D6- and CYP3A4-mediated metabolism of dextromethorphan in human liver microsomes and healthy human subjects.

    Science.gov (United States)

    Al-Jenoobi, Fahad Ibrahim; Al-Thukair, Areej A; Alam, Mohd Aftab; Abbas, Fawkeya A; Al-Mohizea, Abdullah M; Alkharfy, Khalid M; Al-Suwayeh, Saleh A

    2015-03-01

    Effect of Curcuma longa rhizome powder and its ethanolic extract on CYP2D6 and CYP3A4 metabolic activity was investigated in vitro using human liver microsomes and clinically in healthy human subjects. Dextromethorphan (DEX) was used as common probe for CYP2D6 and CYP3A4 enzymes. Metabolic activity of CYP2D6 and CYP3A4 was evaluated through in vitro study; where microsomes were incubated with NADPH in presence and absence of Curcuma extract. In clinical study phase-I, six healthy human subjects received a single dose (30 mg) of DEX syrup, and in phase-II DEX syrup was administered with Curcuma powder. The enzyme CYP2D6 and CYP3A4 mediated O- and N-demethylation of dextromethorphan into dextrorphan (DOR) and 3-methoxymorphinan (3-MM), respectively. Curcuma extract significantly inhibited the formation of DOR and 3-MM, in a dose-dependent and linear fashion. The 100 μg/ml dose of curcuma extract produced highest inhibition, which was about 70 % for DOR and 80 % for 3-MM. Curcuma significantly increases the urine metabolic ratio of DEX/DOR but the change in DEX/3-MM ratio was statistically insignificant. Present findings suggested that curcuma significantly inhibits the activity of CYP2D6 in in vitro as well as in vivo; which indicates that curcuma has potential to interact with CYP2D6 substrates.

  18. Cardiac lipid levels show diurnal changes and long-term variations in healthy human subjects.

    Science.gov (United States)

    Ith, Michael; Stettler, Christoph; Xu, Jian; Boesch, Chris; Kreis, Roland

    2014-11-01

    (1) H-MRS is regularly applied to determine lipid content in ectopic tissue - mostly skeletal muscle and liver - to investigate physiological and/or pathologic conditions, e.g. insulin resistance. Technical developments also allow non-invasive in vivo assessment of cardiac lipids; however, basic data about methodological reliability (repeatability) and physiological variations are scarce. The aim of the presented work was to determine potential diurnal changes of cardiac lipid stores in humans, and to put the results in relation to methodological repeatability and normal physiological day-to-day variations. Optimized cardiac- and respiratory-gated (1) H-MRS was used for non-invasive quantification of intracardiomyocellular lipids (ICCL), creatine, trimethyl-ammonium compounds (TMA), and taurine in nine healthy young men at three time points per day on two days separated by one week. This design allowed determination of (a) diurnal changes, (b) physiological variation over one week and (c) methodological repeatability of the ICCL levels. Comparison of fasted morning to post-absorptive evening measurements revealed a significant 37 ± 19% decrease of ICCL during the day (p = 0.0001). There was a significant linear correlation between ICCL levels in the morning and their decrease during the day (p = 0.015). Methodological repeatability for the ICCL/creatine ratio was excellent, with a coefficient of variance of ~5%, whereas physiological variation was found to be considerably higher (22%) in spite of a standardized physiological preparation protocol. In contrast, TMA levels remained stable over this time period. The proposed (1) H-MRS technique provides a robust way to investigate relevant physiological changes in cardiac metabolites, in particular ICCL. The present results suggest that ICCL reveal a diurnal course, with higher levels in the morning as compared to evening. In addition, a considerable long-term variation of ICCL levels, in both the morning and evening

  19. Influence of lower body negative pressure release on soleus H reflex, respiratory sensations and reflexes in human subjects.

    Science.gov (United States)

    Anand, Ashima; Raj, Hans; Gupta, Uday A; Srivastava, Niraj

    2010-09-30

    Using a physiological model of acutely increasing venous return into the lungs, i.e. by applying and then releasing lower body negative pressure (LBNP) to mimic the natural stimulus of juxtapulmonary capillary (J) or pulmonary C fibre receptors, produced an immediate and significant reduction in the amplitude of the Hoffman (H) reflex by 81±4% (P=0.001) in a majority of subjects 70% (n=5). Accompanying this was a notable change in the respiratory pattern with tidal volume (V(T)) increasing in all subjects from (mean) 0.462±.038 to 0.777±.061l/min (P=0.001) and the respiratory rate (F(R)) in 40% from 14±1 to 24±0.8 breaths/min. A feeling of pressure in throat, upper chest was reported by all and a shortness of breath-by 70% of the subjects. These were similar in nature to the respiratory sensations felt with threshold doses of intravenous lobeline, a well-established chemical stimulant of J receptors. All effects lasted for 15-20s and within a minute the parameters resumed their earlier control values. In animals, respiratory augmentation and locomotion inhibition are well-established reflexes of J receptors - this simultaneous though transitory reduction in H reflex amplitude reflecting change in the excitability of the motoneurone pool and appearance of respiratory effects, is the first demonstration in human subjects of the two reflexes appearing in response to a sudden increase in pulmonary blood flow that mimics the natural stimulus of these receptors. Copyright 2010 Elsevier B.V. All rights reserved.

  20. Naltrexone but Not Ketanserin Antagonizes the Subjective, Cardiovascular, and Neuroendocrine Effects of Salvinorin-A in Humans

    Science.gov (United States)

    Maqueda, Ana Elda; Valle, Marta; Addy, Peter H.; Antonijoan, Rosa Maria; Puntes, Montserrat; Coimbra, Jimena; Ballester, Maria Rosa; Garrido, Maite; González, Mireia; Claramunt, Judit; Barker, Steven; Lomnicka, Izabela; Waguespack, Marian; Johnson, Matthew W.; Griffiths, Roland R.

    2016-01-01

    Background: Salvinorin-A is a terpene found in the leaves of the plant Salvia divinorum. When administered to humans, salvinorin-A induces an intense but short-lasting modified state of awareness, sharing features with those induced by the classical serotonin-2A receptor agonist psychedelics. However, unlike substances such as psilocybin or mescaline, salvinorin-A shows agonist activity at the kappa-opioid receptor rather than at the serotonin-2A receptor. Here, we assessed the involvement of kappa-opioid receptor and serotonin-2A agonism in the subjective, cardiovascular, and neuroendocrine effects of salvinorin-A in humans. Methods: We conducted a placebo-controlled, randomized, double-blind study with 2 groups of 12 healthy volunteers with experience with psychedelic drugs. There were 4 experimental sessions. In group 1, participants received the following treatment combinations: placebo+placebo, placebo+salvinorin-A, naltrexone+placebo, and naltrexone+salvinorin-A. Naltrexone, a nonspecific opioid receptor antagonist, was administered at a dose of 50mg orally. In group 2, participants received the treatment combinations: placebo+placebo, placebo+salvinorin-A, ketanserin+placebo, and ketanserin+salvinorin-A. Ketanserin, a selective serotonin-2A antagonist, was administered at a dose of 40mg orally. Results: Inhalation of 1mg of vaporized salvinorin-A led to maximum plasma concentrations at 1 and 2 minutes after dosing. When administered alone, salvinorin-A severely reduced external sensory perception and induced intense visual and auditory modifications, increased systolic blood pressure, and cortisol and prolactin release. These effects were effectively blocked by naltrexone, but not by ketanserin. Conclusions: Results support kappa opioid receptor agonism as the mechanism of action underlying the subjective and physiological effects of salvinorin-A in humans and rule out the involvement of a serotonin-2A-mediated mechanism. PMID:26874330

  1. The Worldwide Significance of Chinese Aesthetics in the Twenty-First Century

    Institute of Scientific and Technical Information of China (English)

    Liu Qingping

    2006-01-01

    Through comparisons between traditional Chinese and Western aesthetics,this article tries to explain the worldwide significance of Chinese aesthetic tradition in the twentyfirst century.In contrast to cognitive-rational spirit and the tendency to distinguish the subjectives and objectives of traditional Western aesthetics,traditional Chinese aesthetics shows a distinctive practical-emotional spirit and a tendency to harmoniously unite human beings with nature,and believes that beauty is,first and foremost,a free state or way (Dao) of human life;the most important thing for human beings is how to make their own lives and existence beautiful.Therefore,it puts forward some persuasive and valuable insights into beauty and art,thus playing an independent and constructive role in intercultural aesthetic dialogues of the twenty-first century.

  2. An evaluation of the influence of a magnetic field on a human subject with the use of bio-impedance

    Energy Technology Data Exchange (ETDEWEB)

    Papezova, S [Faculty of Mechanical Engineering, CTU in Prague, Technicka 4, 166 07 Prague (Czech Republic); Papez, V, E-mail: stanislava.papezova@fs.cvut.c, E-mail: papez@feld.cvut.c [Faculty of Electrical Engineering, CTU in Prague, Technicka 2, 166 27 Prague (Czech Republic)

    2010-01-01

    The influence of a magnetic field on a living human organism was monitored using a bio-impedance evaluation of vasodilatation effects. A quantitative evaluation of the influence of a magnetic field on a human being was implemented by means of a quantitative evaluation of changes in the bio-impedance of the tissue. The pulse of the magnetic field was controlled by a pseudo-random impulse signal using a power switch that controlled the current of the applicator coil. The peak magnetic field flux density was approximately 60 mT. The bio-impedance was measured by a four-electrode method by means of a radiofrequency narrow band vector bioimpedance meter. Experiments were performed on the magnetic exposure of the forearm of an exposed human subject. During exposure to a magnetic field, the bio-impedance change signal level increases above the normal level, and reaches the maximum level after about 10 minutes. The maximum value is approximately 50 % higher than the normal level.

  3. Activation of coagulation by administration of recombinant factor VIIa elicits interleukin 6 (IL-6) and IL-8 release in healthy human subjects

    National Research Council Canada - National Science Library

    Jonge, de, E; Friederich, P.W; Vlasuk, G.P; Rote, W; Vroom, M.B; Levi, M.M; Poll, van der, T

    2003-01-01

    .... Here we report that the activation of coagulation in healthy human subjects by the administration of recombinant factor VIIa also elicits a small but significant increase in the concentrations of interleukin 6 (IL-6) and IL-8 in plasma...

  4. Auditory streaming by phase relations between components of harmonic complexes: a comparative study of human subjects and bird forebrain neurons.

    Science.gov (United States)

    Dolležal, Lena-Vanessa; Itatani, Naoya; Günther, Stefanie; Klump, Georg M

    2012-12-01

    Auditory streaming describes a percept in which a sequential series of sounds either is segregated into different streams or is integrated into one stream based on differences in their spectral or temporal characteristics. This phenomenon has been analyzed in human subjects (psychophysics) and European starlings (neurophysiology), presenting harmonic complex (HC) stimuli with different phase relations between their frequency components. Such stimuli allow evaluating streaming by temporal cues, as these stimuli only vary in the temporal waveform but have identical amplitude spectra. The present study applied the commonly used ABA- paradigm (van Noorden, 1975) and matched stimulus sets in psychophysics and neurophysiology to evaluate the effects of fundamental frequency (f₀), frequency range (f(LowCutoff)), tone duration (TD), and tone repetition time (TRT) on streaming by phase relations of the HC stimuli. By comparing the percept of humans with rate or temporal responses of avian forebrain neurons, a neuronal correlate of perceptual streaming of HC stimuli is described. The differences in the pattern of the neurons' spike rate responses provide for a better explanation for the percept observed in humans than the differences in the temporal responses (i.e., the representation of the periodicity in the timing of the action potentials). Especially for HC stimuli with a short 40-ms duration, the differences in the pattern of the neurons' temporal responses failed to represent the patterns of human perception, whereas the neurons' rate responses showed a good match. These results suggest that differential rate responses are a better predictor for auditory streaming by phase relations than temporal responses.

  5. Differential tolerance to biological and subjective effects of four closely spaced doses of N,N-dimethyltryptamine in humans.

    Science.gov (United States)

    Strassman, R J; Qualls, C R; Berg, L M

    1996-05-01

    Tolerance of the behavioral effects of the short-acting, endogenous hallucinogen, N,N-dimethyltryptamine (DMT) is seen inconsistently in animals, and has not been produced in humans. The nature and time course of responses to repetitive, closely spaced administrations of an hallucinogenic dose of DMT were characterized. Thirteen experienced hallucinogen users received intravenous 0.3 mg/kg DMT fumarate, or saline placebo, four times, at 30 min intervals, on 2 separate days, in a randomized, double-blind, design. Tolerance to "psychedelic" subjective effects did not occur according to either clinical interview or Hallucinogen Rating Scale scores. Adrenocorticotropic hormone (ACTH), prolactin, cortisol, and heart rate responses decreased with repeated DMT administration, although blood pressure did not. These data demonstrate the unique properties of DMT relative to other hallucinogens and underscore the differential regulation of the multiple processes mediating the effects of DMT.

  6. Italy-Japan international project-based learning for developing human resources using design of welfare equipment as a subject.

    Science.gov (United States)

    Hanafusa, A; Komeda, T; Ito, K; Zobel, P Beomonte

    2015-08-01

    Project-based learning (PBL) is effective for developing human resources of young students. The design of welfare equipment, such as wheelchairs and gait assistive devices, is taken as the subject in this study because these devices must be fit to their environment, users, and method of use; students must consider the circumstances of each country concerned. The program commenced in 2012 at L'Aquila, Italy, and the Shibaura Institute of Technology, Japan and has been continuing for three years. Students were divided into four groups and discussions were held on how to adapt the equipment to the user and environment. After discussion, they designed and simulated a model of the equipment using CAD. Finally, they presented their designs to each other. Through the program, students had fruitful discussions, exchanged ideas from different cultures, and learned from each other. Furthermore, friendships among the students were nurtured. It is believed that the objective of the program was satisfactorily accomplished.

  7. Effects of ritanserin on the behavioral, neuroendocrine, and cardiovascular responses to meta-chlorophenylpiperazine in healthy human subjects.

    Science.gov (United States)

    Seibyl, J P; Krystal, J H; Price, L H; Woods, S W; D'Amico, C; Heninger, G R; Charney, D S

    1991-09-01

    Ten healthy male subjects were administered i.v. meta-chlorophenylpiperazine (MCPP) (0.1 mg/kg) after oral ritanserin (5-10 mg), a putative 5HT1c/5HT2 (serotonin) antagonist, or placebo. Behavioral responses, cardiovascular effects, and neuroendocrine responses (cortisol, growth hormone, and prolactin) were measured serially for 4 hours after MCPP infusion. Premedication with ritanserin attenuated the MCPP-induced increases in self-rated anxiety and prolactin, and completely antagonized MCPP cortisol elevations. In contrast, ritanserin did not significantly alter growth hormone response to MCPP. These findings suggest a role for 5-HT1c/5-HT2 receptors in the endocrine and behavioral responses to the mixed serotonin agonist MCPP in humans.

  8. The effect of polyamines on the binding of anti-DNA antibodies from patients with SLE and normal human subjects.

    Science.gov (United States)

    Wang, Xiao; Stearns, Nancy A; Li, Xingfu; Pisetsky, David S

    2014-07-01

    Antibodies to DNA (anti-DNA) are the serological hallmark of systemic lupus erythematosus (SLE). To elucidate specificity further, the effect of polyamines on the binding of anti-DNA antibodies from patients with lupus was tested by ELISA to calf thymus (CT) DNA; we also assessed the binding of plasmas of patients and normal human subjects (NHS) to Micrococcus luteus (MC) DNA. As these studies showed, spermine can dose-dependently inhibit SLE anti-DNA binding to CT DNA and can promote dissociation of preformed immune complexes. With MC DNA as antigen, spermine failed to inhibit the NHS anti-DNA binding. Studies using plasmas adsorbed to a CT DNA cellulose affinity indicated that SLE plasmas are mixtures of anti-DNA that differ in inhibition by spermine and binding to conserved and non-conserved determinants. Together, these studies demonstrate that spermine can influence the binding of anti-DNA autoantibodies and may contribute to the antigenicity of DNA.

  9. Bioavailability of anthocyanins and ellagitannins following consumption of raspberries by healthy humans and subjects with an ileostomy.

    Science.gov (United States)

    González-Barrio, Rocío; Borges, Gina; Mullen, William; Crozier, Alan

    2010-04-14

    The fate of anthocyanins, ellagic acid, and ellagitannins was studied following the consumption of 300 g of raspberries by healthy human volunteers and subjects with an ileostomy. Postingestion plasma and urine from the former and ileal fluid and urine from the latter group were collected and analyzed by HPLC-PDA-MS(2). Plasma from the healthy volunteers did not contain detectable quantities of either the native raspberry polyphenolics or their metabolites. The three main raspberry anthocyanins were excreted in urine in both healthy and ileostomy volunteers 0-7 h after ingestion, in quantities corresponding to urolithin A-O-glucuronide, two of its isomers, and urolithin B-O-glucuronide in urine collected 7-48 h after raspberry consumption. There was marked variation in the urolithin profile of individual volunteers, indicating differences in the colonic microflora responsible for ellagitannin degradation.

  10. Hypoxia imaging endoscopy equipped with laser light source from preclinical live animal study to first-in-human subject research.

    Directory of Open Access Journals (Sweden)

    Kazuhiro Kaneko

    Full Text Available A goal in next-generation endoscopy is to develop functional imaging techniques to open up new opportunities for cancer diagnosis. Although spatial and temporal information on hypoxia is crucial for understanding cancer physiology and expected to be useful for cancer diagnosis, existing techniques using fluorescent indicators have limitations due to low spatial resolution and invasive administration. To overcome these problems, we developed an imaging technology based on hemoglobin oxygen saturation in both the tumor and surrounding mucosa using a laser endoscope system, and conducted the first human subject research for patients with aero-digestive tract cancer. The oxygen saturation map overlapped the images of cancerous lesions and indicated highly heterogeneous features of oxygen supply in the tumor. The hypoxic region of the tumor surface was found in both early cancer and cancer precursors. This technology illustrates a novel aspect of cancer biology as a potential biomarker and can be widely utilized in cancer diagnosis.

  11. Peripheral erythrocytes decrease upon specific respiratory challenge with grass pollen allergen in sensitized mice and in human subjects.

    Directory of Open Access Journals (Sweden)

    Galateja Jordakieva

    Full Text Available BACKGROUND AND AIMS: Specific hyper-responsiveness towards an allergen and non-specific airway hyperreactivity both impair quality of life in patients with respiratory allergic diseases. We aimed to investigate cellular responses following specific and non-specific airway challenges locally and systemically in i sensitized BALB/c mice challenged with grass pollen allergen Phl p 5, and in ii grass pollen sensitized allergic rhinitis subjects undergoing specific airway challenge in the Vienna Challenge Chamber (VCC. METHODS AND RESULTS: BALB/c mice (n = 20 were intraperitoneally immunized with grass pollen allergen Phl p 5 and afterwards aerosol challenged with either the specific allergen Phl p 5 (n = 10 or the non-specific antigen ovalbumin (OVA (n = 10. A protocol for inducing allergic asthma as well as allergic rhinitis, according to the united airway concept, was used. Both groups of exposed mice showed significantly reduced physical activity after airway challenge. Specific airway challenge further resulted in goblet cell hyperplasia, enhanced mucous secretion, intrapulmonary leukocyte infiltration and lymphoid follicle formation, associated with significant expression of IL-4, IL-5 and IL-13 in splenocytes and also partially in lung tissue. Concerning circulating blood cell dynamics, we observed a significant drop of erythrocyte counts, hemoglobin and hematocrit levels in both mouse groups, challenged with allergen or OVA. A significant decrease in circulating erythrocytes and hematocrit levels after airway challenges with grass pollen allergen was also found in grass pollen sensitized human rhinitis subjects (n = 42 at the VCC. The effects on peripheral leukocyte counts in mice and humans however were opposed, possibly due to the different primary inflammation sites. CONCLUSION: Our data revealed that, besides significant leukocyte dynamics, particularly erythrocytes are involved in acute hypersensitivity reactions to respiratory allergens

  12. A randomised, double- blind, cross-over study investigating the prebiotic effect of agave fructans in healthy human subjects.

    Science.gov (United States)

    Ramnani, P; Costabile, A; Bustillo, A G R; Gibson, G R

    2015-01-01

    This placebo-controlled, randomised, double-blind, cross-over human feeding study aimed to determine the prebiotic effect of agave fructans. A total of thirty-eight volunteers completed this trial. The treatment consisted of 3 weeks' supplementation with 5 g/d of prebiotic agave fructan (Predilife) or equivalent placebo (maltodextrin), followed by a 2-week washout period following which subjects were crossed over to alternate the treatment arm for 3 weeks followed by a 2-week washout. Faecal samples were collected at baseline, on the last day of treatment (days 22 and 58) and washout (days 36 and 72), respectively. Changes in faecal bacterial populations, SCFA and secretory IgA were assessed using fluorescent in situ hybridisation, GC and ELISA, respectively. Bowel movements, stool consistencies, abdominal comfort and mood changes were evaluated by a recorded daily questionnaire. In parallel, the effect of agave fructans on different regions of the colon using a three-stage continuous culture simulator was studied. Predilife significantly increased faecal bifidobacteria (log10 9·6 (sd 0·4)) and lactobacilli (log10 7·7 (sd 0·8)) compared with placebo (log10 9·2 (sd 0·4); P = 0·00) (log10 7·4 (sd 0·7); P = 0·000), respectively. No change was observed for other bacterial groups tested, SCFA, secretory IgA, and PGE2 concentrations between the treatment and placebo. Denaturing gradient gel electrophoresis analysis indicated that bacterial communities were randomly dispersed and no significant differences were observed between Predilife and placebo treatments. The in vitro models showed similar increases in bifidobacterial and lactobacilli populations to that observed with the in vivo trial. To conclude, agave fructans are well tolerated in healthy human subjects and increased bifidobacteria and lactobacilli numbers in vitro and in vivo but did not influence other products of fermentation.

  13. Early suppression of NFkappaB and IL-8 in bronchial epithelium after ozone exposure in healthy human subjects.

    Science.gov (United States)

    Bosson, Jenny; Blomberg, Anders; Pourazar, Jamshid; Mudway, Ian S; Frew, Anthony J; Kelly, Frank J; Sandström, Thomas

    2009-09-01

    Exposure to elevated concentrations of ozone, a common air pollutant, has been associated with numerous adverse health effects. We have previously reported the time-course of ozone-induced airway inflammation, demonstrating an early up-regulation of vascular endothelial adhesion molecules in bronchial mucosa at 1.5 hours, followed by a neutrophilic infiltration 6 hours after exposure to 0.2 ppm ozone. We hypothesized that the neutrophilic infiltration in the bronchial mucosa would reflect an early increase in bronchial epithelial expression of redox-sensitive transcription factors and kinases regulating neutrophil chemoattractant expression. To test this hypothesis, endobronchial biopsies were obtained from healthy human subjects (n = 11) 1.5 hours after 0.2 ppm of ozone and filtered air exposures (lasting for 2 hours) and stained for mitogen-activated protein kinases (MAPKs), transcription factors, and neutrophil chemoattractants. Total epithelial staining was quantified, as well as the extent of nuclear translocation. Contrary to expectation, ozone significantly suppressed total and nuclear expression of nuclear factor kappaB (NFkappaB) in bronchial epithelial cells (p = 0.02 and p = 0.003 respectively). Similarly, the total staining for phosphorylated C-jun was suppressed (p = 0.021). Expression of interleukin 8 (IL-8) in the bronchial epithelium was likewise decreased after ozone (p = 0.018), while GRO-alpha, ENA-78, C-fos, p-p38, p-JNK, and p-ERK stainings were unchanged. These data suggest that the redox-sensitive NFkappaB and activator protein 1 (AP-1) pathways within the human bronchial epithelium do not seem to be involved in the early inflammatory cell recruitment pathways in healthy subjects exposed to ozone.

  14. Global metabolomic analysis of human saliva and plasma from healthy and diabetic subjects, with and without periodontal disease.

    Science.gov (United States)

    Barnes, Virginia M; Kennedy, Adam D; Panagakos, Fotinos; Devizio, William; Trivedi, Harsh M; Jönsson, Thomas; Guo, Lining; Cervi, Shannon; Scannapieco, Frank A

    2014-01-01

    Recent studies suggest that periodontal disease and type 2 diabetes mellitus are bi-directionally associated. Identification of a molecular signature for periodontitis using unbiased metabolic profiling could allow identification of biomarkers to assist in the diagnosis and monitoring of both diabetes and periodontal disease. This cross-sectional study identified plasma and salivary metabolic products associated with periodontitis and/or diabetes in order to discover biomarkers that may differentiate or demonstrate an interaction of these diseases. Saliva and plasma samples were analyzed from 161 diabetic and non-diabetic human subjects with a healthy periodontium, gingivitis and periodontitis. Metabolite profiling was performed using Metabolon's platform technology. A total of 772 metabolites were found in plasma and 475 in saliva. Diabetics had significantly higher levels of glucose and α-hydroxybutyrate, the established markers of diabetes, for all periodontal groups of subjects. Comparison of healthy, gingivitis and periodontitis saliva samples within the non-diabetic group confirmed findings from previous studies that included increased levels of markers of cellular energetic stress, increased purine degradation and glutathione metabolism through increased levels of oxidized glutathione and cysteine-glutathione disulfide, markers of oxidative stress, including increased purine degradation metabolites (e.g. guanosine and inosine), increased amino acid levels suggesting protein degradation, and increased ω-3 (docosapentaenoate) and ω-6 fatty acid (linoleate and arachidonate) signatures. Differences in saliva between diabetic and non-diabetic cohorts showed altered signatures of carbohydrate, lipid and oxidative stress exist in the diabetic samples. Global untargeted metabolic profiling of human saliva in diabetics replicated the metabolite signature of periodontal disease progression in non-diabetic patients and revealed unique metabolic signatures associated

  15. Simultaneous ingestion of high-methoxy pectin from apple can enhance absorption of quercetin in human subjects.

    Science.gov (United States)

    Nishijima, Tomohiko; Takida, Yoshiki; Saito, Yasuo; Ikeda, Takayuki; Iwai, Kunihisa

    2015-05-28

    Chronic ingestion of apple pectin has been shown to increase the absorption of quercetin in rats. The present study was designed to elucidate whether the simultaneous ingestion of quercetin with apple pectin could enhance the absorption of quercetin in humans, and the effects of dose dependency and degree of pectin methylation on quercetin absorption were also investigated. Healthy volunteers (n 19) received 200 ml of 0.5 mg/ml of quercetin drinks with or without 10 mg/ml of pectin each in a randomised cross-over design study with over 1-week intervals; urine samples from all the subjects were collected within 24 h after ingestion of the test drinks, and urinary deconjugated quercetin and its metabolites were determined using HPLC. The sum of urinary quercetin and its metabolites excreted was increased by 2.5-fold by the simultaneous ingestion of pectin. The metabolism of methylated quercetin (isorhamnetin and tamarixetin) was not affected by pectin ingestion. In six volunteers, who received quercetin drinks containing 0, 3 and 10 mg/ml of pectin, the sum of urinary quercetin and its metabolites excreted also increased in a pectin dose-dependent manner. Furthermore, the simultaneous ingestion of quercetin with low-methoxy and high-methoxy pectin, respectively, increased the sum of urinary excretion of quercetin and its metabolites by 1.69-fold and significantly by 2.13-fold compared with the ingestion of quercetin without pectin. These results elucidated that apple pectin immediately enhanced quercetin absorption in human subjects, and that its enhancing effect was dependent on the dose and degree of pectin methylation. The results also suggested that the viscosity of pectin may play a role in the enhancement of quercetin absorption.

  16. Global metabolomic analysis of human saliva and plasma from healthy and diabetic subjects, with and without periodontal disease.

    Directory of Open Access Journals (Sweden)

    Virginia M Barnes

    Full Text Available Recent studies suggest that periodontal disease and type 2 diabetes mellitus are bi-directionally associated. Identification of a molecular signature for periodontitis using unbiased metabolic profiling could allow identification of biomarkers to assist in the diagnosis and monitoring of both diabetes and periodontal disease. This cross-sectional study identified plasma and salivary metabolic products associated with periodontitis and/or diabetes in order to discover biomarkers that may differentiate or demonstrate an interaction of these diseases. Saliva and plasma samples were analyzed from 161 diabetic and non-diabetic human subjects with a healthy periodontium, gingivitis and periodontitis. Metabolite profiling was performed using Metabolon's platform technology. A total of 772 metabolites were found in plasma and 475 in saliva. Diabetics had significantly higher levels of glucose and α-hydroxybutyrate, the established markers of diabetes, for all periodontal groups of subjects. Comparison of healthy, gingivitis and periodontitis saliva samples within the non-diabetic group confirmed findings from previous studies that included increased levels of markers of cellular energetic stress, increased purine degradation and glutathione metabolism through increased levels of oxidized glutathione and cysteine-glutathione disulfide, markers of oxidative stress, including increased purine degradation metabolites (e.g. guanosine and inosine, increased amino acid levels suggesting protein degradation, and increased ω-3 (docosapentaenoate and ω-6 fatty acid (linoleate and arachidonate signatures. Differences in saliva between diabetic and non-diabetic cohorts showed altered signatures of carbohydrate, lipid and oxidative stress exist in the diabetic samples. Global untargeted metabolic profiling of human saliva in diabetics replicated the metabolite signature of periodontal disease progression in non-diabetic patients and revealed unique metabolic

  17. The number and distribution of blood dendritic cells in the epidermis and dermis of healthy human subjects.

    Science.gov (United States)

    Narbutt, Joanna; Lesiak, Aleksandra; Sysa-Jedrzejowska, Anna; Smolewski, Piotr; Robak, Tadeusz; Zalewska, Anna

    2006-01-01

    Human blood dendritic cells (BDC) can be divided into three subsets: plasmacytoid DC (PDC) and two myeloid subsets--MDC1 and MDC2. Several studies revealed the presence of both MDC and PDC in blood of healthy subjects, however no precise literature data exist on the number and distribution of BDC in the skin. The aim of our study was to assess the number and distribution of BDC and their subtypes in the healthy skin. The-study included 30 healthy volunteers (age 18-51). Punch biopsies were taken from the buttock skin from each subject, and immunofluorescent staining was performed using monoclonal mouse IgG1 antibodies directed against BDCA-1, BDCA-2, BDCA-3 and BDC-4. The BDC were present both in the epidermis and dermis. PDC were detected mainly in the dermis (mean 1.2 cells per field). Myeloid subtypes were observed mainly in the middle layers of the epidermis and in the upper part of the dermis (mean 1.8 cells per field). The detection of blood dendritic cells in the skin proves their role in immune cutaneous surveillance.

  18. Comparative evaluation of the cytomegalovirus DNA load in polymorphonuclear leukocytes and plasma of human immunodeficiency virus-infected subjects.

    Science.gov (United States)

    Boivin, G; Handfield, J; Toma, E; Murray, G; Lalonde, R; Bergeron, M G

    1998-02-01

    The cytomegalovirus (CMV) DNA load was determined in polymorphonuclear leukocytes (PMNL) and plasma samples from 106 human immunodeficiency virus-infected subjects at risk of developing CMV disease (group 1) and from 27 AIDS patients with documented CMV disease (group 2). For both groups, the number of CMV copies in PMNL was significantly higher than in plasma when results were derived from an equivalent blood volume (P < .001, PMNL vs. plasma). Additionally, group 2 (symptomatic) patients had a greater viral DNA load than group 1 (asymptomatic) subjects (P < .001 for both PMNL and plasma). The sensitivity, specificity, and positive and negative predictive values of qualitative polymerase chain reaction using PMNL (PCR-PMNL) for the presence of CMV disease were 100%, 58%, 38%, and 100%, respectively, compared with 70%, 93%, 74%, and 92% for qualitative PCR-plasma and 93%, 92%, 76%, and 98% for quantitative PCR-PMNL using a cutoff of 16,000 copies/mL. Thus, the best strategy for diagnosing CMV disease in these individuals relies on quantitative assessment of the viral DNA load in PMNL.

  19. The twenty-first century in space

    CERN Document Server

    Evans, Ben

    2015-01-01

    This final entry in the History of Human Space Exploration mini-series by Ben Evans continues with an in-depth look at the latter part of the 20th century and the start of the new millennium. Picking up where Partnership in Space left off, the story commemorating the evolution of manned space exploration unfolds in further detail. More than fifty years after Yuri Gagarin’s pioneering journey into space, Evans extends his overview of how that momentous voyage continued through the decades which followed. The Twenty-first Century in Space, the sixth book in the series, explores how the fledgling partnership between the United States and Russia in the 1990s gradually bore fruit and laid the groundwork for today’s International Space Station. The narrative follows the convergence of the Shuttle and Mir programs, together with standalone missions, including servicing the Hubble Space Telescope, many of whose technical and human lessons enabled the first efforts to build the ISS in orbit. The book also looks to...

  20. Nonlinear population receptive field changes in human area V5/MT+ of healthy subjects with simulated visual field scotomas.

    Science.gov (United States)

    Papanikolaou, Amalia; Keliris, Georgios A; Lee, Sangkyun; Logothetis, Nikos K; Smirnakis, Stelios M

    2015-10-15

    There is extensive controversy over whether the adult visual cortex is able to reorganize following visual field loss (scotoma) as a result of retinal or cortical lesions. Functional magnetic resonance imaging (fMRI) methods provide a useful tool to study the aggregate receptive field properties and assess the capacity of the human visual cortex to reorganize following injury. However, these methods are prone to biases near the boundaries of the scotoma. Retinotopic changes resembling reorganization have been observed in the early visual cortex of normal subjects when the visual stimulus is masked to simulate retinal or cortical scotomas. It is not known how the receptive fields of higher visual areas, like hV5/MT+, are affected by partial stimulus deprivation. We measured population receptive field (pRF) responses in human area V5/MT+ of 5 healthy participants under full stimulation and compared them with responses obtained from the same area while masking the left superior quadrant of the visual field ("artificial scotoma" or AS). We found that pRF estimations in area hV5/MT+ are nonlinearly affected by the AS. Specifically, pRF centers shift towards the AS, while the pRF amplitude increases and the pRF size decreases near the AS border. The observed pRF changes do not reflect reorganization but reveal important properties of normal visual processing under different test-stimulus conditions.

  1. Effects of diazepam and levodopa single doses on motor cortex plasticity modulation in healthy human subjects: A TMS study

    Directory of Open Access Journals (Sweden)

    Ilić Nela V.

    2012-01-01

    Full Text Available Introduction. Administration of pharmacological agents with specific actions on neurotransmitter systems is a powerful driver of functional cortical reorganization. Plastic reorganization of the motor cortex in humans studies by the use of non-invasive stimulation protocols, which mimic the Hebbian model of associative plasticity. Objective. Aiming to explore pharmacological modulation on human motor cortex plasticity, we tested healthy subjects after each dosage of diazepam, levodopa i placebo administration, using paired associative stimulation protocol (PAS that induce fenomena similar to a long-term potentiation and depression, as defined on the synaptic level. Methods. We analyzed effects of benzodiazepines (10 mg, levodopa (200 mg and placebo on PAS protocol in 14 healthy volunteers, using a double-blind placebo-controlled study design. PAS consisted of electrical stimuli pairs at n.medianus and magnetic pulses over the scalp (transcranial magnetic stimulation in precisely defined intervals (ISI was 10 and 25 ms for a total of about 15 minutes (200 pairs. MEP amplitudes before and after (0, 10, 20 and 30 minutes later interventional protocols were compared. Results. When protocols were applied with placebo depending on ISI (10 ms - inhibitory, 25 ms - facilitatory effects, MEP amplitudes decreased or increased, while values in the postinterventional period (0, 10, 20 and 30 min were compared with initial values before the use of SAS. The use of benzodiazepines caused the occlusion of LTP-like effect, in contrast to amplification effects recorded after the administration of levodopa. With respect to the LTD-like protocol, the reverse was true (ANOVA for repeat measurements p<0.001. Conclusion. Administration of GABA-ergic agonist diazepam interferes with the induction of associative plasticity in the motor cortex of healthy individuals, as opposed to the use of levodopa, which stimulates these processes. The observed effects point at a

  2. The Affective Core of the Self: A Neuro-Archetypical Perspective on the Foundations of Human (and Animal Subjectivity

    Directory of Open Access Journals (Sweden)

    Antonio Alcaro

    2017-09-01

    Full Text Available Psychologists usually considered the “Self” as an object of experience appearing when the individual perceives its existence within the conscious field. In accordance with such a view, the self-representing capacity of the human mind has been related to corticolimbic learning processes taking place within individual development. On the other hand, Carl Gustav Jung considered the Self as the core of our personality, in its conscious and unconscious aspects, as well as in its actual and potential forms. According to Jung, the Self originates from an inborn dynamic structure integrating the essential drives of our “brain–mind,” and leading both to instinctual behavioral actions and to archetypal psychological experiences. Interestingly, recent neuroethological studies indicate that our subjective identity rests on ancient neuropsychic processes that humans share with other animals as part of their inborn constitutional repertoire. Indeed, brain activity within subcortical midline structures (SCMSs is intrinsically related to the emergence of prototypical affective states, that not only influence our behavior in a flexible way, but alter our conscious field, giving rise to specific feelings or moods, which constitute the first form of self-orientation in the world. Moreover, such affective dynamics play a central role in the organization of individual personality and in the evolution of all other (more sophisticated psychological functions. Therefore, on the base of the convergence between contemporary cutting-edge scientific research and some psychological intuitions of Jung, we intend here to explore the first neuroevolutional layer of human mind, that we call the affective core of the Self.

  3. In vitro evaluation of a passive radio frequency identification microchip implanted in human molars subjected to compression forces, for forensic purposes of human identification

    Directory of Open Access Journals (Sweden)

    Freddy Moreno

    2013-01-01

    Full Text Available Objective: To evaluate the in vitro behavior of a passive Radio Frequency Identification (RFID microchip implanted in human molars subjected to compression forces to determine its technical and clinical viability. Materials and Methods: I n vitro experimental study to evaluate the physical behavior of a passive RFID microchip (VeriChip™ implanted in human molars through resin restoration (Filtek P90™ Silorane 3M-ESPE ® to determine the clinical and technical possibilities of the implant and the viability to withstand compression forces exerted by the stomatognathic system during mastication. Results: Through the ANOVA test, it was found that the teeth on which a microchip was implanted show great resistance to compressive forces. It was also evident that teeth with microchips implanted in Class V cavities are more resistant than those implanted in Class I cavities. Conclusions: Although microchip dimensions are big, requiring a sufficiently large cavity, from the biomechanical point of view it is plausible to implant a microchip in a Class V cavity employing restoration material based on resin for forensic purposes of human identification.

  4. Oral glucosamine sulfate supplementation does not induce endoplasmic reticulum stress or activate the unfolded protein response in circulating leukocytes of human subjects.

    Science.gov (United States)

    McAlpine, Cameron S; Beriault, Daniel R; Behdinan, Tina; Shi, Yuanyuan; Werstuck, Geoff H

    2014-04-01

    Glucosamine sulfate is a dietary supplement that is marketed as a treatment for osteoarthritis. Recent evidence from animal and cell culture models have suggested that glucosamine treatment can promote the misfolding of proteins and the activation of the unfolded protein response (UPR). We investigated whether glucosamine sulfate supplementation activates the UPR in circulating leukocytes of human subjects. Cultured Thp1 human monocytes were exposed to increasing concentrations of glucosamine (0, 0.25, 1.0, 4.0 mmol · L(-1)) for 18 h. We observed a dose-dependent increase in intracellular glucosamine levels as well as the activation of UPR. To test the effect of glucosamine sulfate supplementation in humans, 14 healthy human subjects took 1500 mg · day(-1) glucosamine sulfate for 14 days. Metabolic parameters and blood samples were collected before and after supplementation. In humans, glucosamine sulfate supplementation did not alter metabolic parameters including lipid levels and glucose tolerance. Further, glucosamine sulfate supplementation did not affect intracellular glucosamine levels or activate the UPR in the leukocytes of human subjects. Our results indicate that in healthy human subjects, the recommended dose of glucosamine sulfate (1500 mg · day(-1)) for 14 days does not significantly alter intracellular glucosamine levels and does not activate the UPR in circulating leukocytes.

  5. Knowledge on the subject of human physiology among Polish high school students--a cross-sectional study.

    Science.gov (United States)

    Zwinczewska, Helena; Rozwadowska, Joanna; Traczyk, Anna; Majda, Szymon; Wysocki, Michał; Grabowski, Kamil; Kopeć, Sylwia; Głowacki, Roman; Węgrzyn, Katarzyna; Tomaszewski, Krzysztof A; Walocha, Jerzy A

    2014-01-01

    In most cases the only knowledge an individual will receive with regards to their own body and its proper functioning is during their high school education. The aim of this study was to evaluate high school students' knowledge about basic physiology. The research was carried out in five, randomly chosen high schools in Krakow, Poland. Young people in the age of 17-19 years were asked to fill in the questionnaire designed by the authors. The first part of the survey included personal data. The second part contained 20 close-ended questions assessing students' knowledge about the basics of human physiology. Question difficulty varied from easy through average, and up to difficult. The maximum number of points to achieve was 20. One-thousand-and eighty-three (out of 1179 invited--91.86%) Polish high school students (63.25% female) filled in a 20-item questionnaire constructed by the authors regarding basic human physiology. The mean age of the group was 17.66 ± 0.80 years. The mean score among the surveyed was 10.15 ± 3.48 (range 0-20). Only 26.04% of students achieved a grade of 60% or more, and only one person obtained the highest possible score. Females achieved significantly better scores than males (10.49 ± 3.38 vs. 9.56 ± 3.56; p students did not know that mature red blood cells do not have cell nuclei and a similar number of them answered that humans have 500,000 erythrocytes in 1 mm3 of blood. Over 32% believed that plasma does not participate in the transport of respiratory gases, and 31% believed that endocrine glands secrete hormones within their immediate vicinity and into the blood. Our research has shown that young people, especially men, often lack basic physiological knowledge needed to make conscious and responsible decisions regarding their health. Our results suggest that more emphasis should be put on properly teaching human physiology in high school, especially to those students who do not plan a career in medicine-related fields. This study

  6. Elevation of Fasting Ghrelin in Healthy Human Subjects Consuming a High-Salt Diet: A Novel Mechanism of Obesity?

    Directory of Open Access Journals (Sweden)

    Yong Zhang

    2016-05-01

    Full Text Available Overweight/obesity is a chronic disease that carries an increased risk of hypertension, diabetes mellitus, and premature death. Several epidemiological studies have demonstrated a clear relationship between salt intake and obesity, but the pathophysiologic mechanisms remain unknown. We hypothesized that ghrelin, which regulates appetite, food intake, and fat deposition, becomes elevated when one consumes a high-salt diet, contributing to the progression of obesity. We, therefore, investigated fasting ghrelin concentrations during a high-salt diet. Thirty-eight non-obese and normotensive subjects (aged 25 to 50 years were selected from a rural community in Northern China. They were sequentially maintained on a normal diet for three days at baseline, a low-salt diet for seven days (3 g/day, NaCl, then a high-salt diet for seven days (18 g/day. The concentration of plasma ghrelin was measured using an immunoenzyme method (ELISA. High-salt intake significantly increased fasting ghrelin levels, which were higher during the high-salt diet (320.7 ± 30.6 pg/mL than during the low-salt diet (172.9 ± 8.9 pg/mL. The comparison of ghrelin levels between the different salt diets was statistically-significantly different (p < 0.01. A positive correlation between 24-h urinary sodium excretion and fasting ghrelin levels was demonstrated. Our data indicate that a high-salt diet elevates fasting ghrelin in healthy human subjects, which may be a novel underlying mechanism of obesity.

  7. B-cell depletion is protective against anti-AAV capsid immune response: a human subject case study

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    M Corti

    2014-01-01

    Full Text Available Gene therapy strategies for congenital myopathies may require repeat administration of adeno-associated viral (AAV vectors due to aspects of the clinical application, such as: (i administration of doses below therapeutic efficacy in patients enrolled in early phase clinical trials; (ii progressive reduction of the therapeutic gene expression over time as a result of increasing muscle mass in patients treated at a young age; and (iii a possibly faster depletion of pathogenic myofibers in this patient population. Immune response triggered by the first vector administration, and to subsequent doses, represents a major obstacle for successful gene transfer in young patients. Anti-capsid and anti-transgene product related humoral and cell-mediated responses have been previously observed in all preclinical models and human subjects who received gene therapy or enzyme replacement therapy (ERT for congenital myopathies. Immune responses may result in reduced efficacy of the gene transfer over time and/or may preclude for the possibility of re-administration of the same vector. In this study, we evaluated the immune response of a Pompe patient dosed with an AAV1-GAA vector after receiving Rituximab and Sirolimus to modulate reactions against ERT. A key finding of this single subject case report is the observation that B-cell ablation with rituximab prior to AAV vector exposure results in non-responsiveness to both capsid and transgene, therefore allowing the possibility of repeat administration in the future. This observation is significant for future gene therapy studies and establishes a clinically relevant approach to blocking immune responses to AAV vectors.

  8. Effect of propofol on the medial temporal lobe emotional memory system: a functional magnetic resonance imaging study in human subjects

    Science.gov (United States)

    Pryor, K. O.; Root, J. C.; Mehta, M.; Stern, E.; Pan, H.; Veselis, R. A.; Silbersweig, D. A.

    2015-01-01

    Background Subclinical doses of propofol produce anterograde amnesia, characterized by an early failure of memory consolidation. It is unknown how propofol affects the amygdala-dependent emotional memory system, which modulates consolidation in the hippocampus in response to emotional arousal and neurohumoral stress. We present an event-related functional magnetic resonance imaging study of the effects of propofol on the emotional memory system in human subjects. Methods Thirty-five healthy subjects were randomized to receive propofol, at an estimated brain concentration of 0.90 μg ml−1, or placebo. During drug infusion, emotionally arousing and neutral images were presented in a continuous recognition task, while blood-oxygen-level-dependent activation responses were acquired. After a drug-free interval of 2 h, subsequent memory for successfully encoded items was assessed. Imaging analysis was performed using statistical parametric mapping and behavioural analysis using signal detection models. Results Propofol had no effect on the stereotypical amygdalar response to emotional arousal, but caused marked suppression of the hippocampal response. Propofol caused memory performance to become uncoupled from amygdalar activation, but it remained correlated with activation in the posterior hippocampus, which decreased in proportion to amnesia. Conclusions Propofol is relatively ineffective at suppressing amygdalar activation at sedative doses, but abolishes emotional modulation and causes amnesia via mechanisms that commonly involve hyporesponsiveness of the hippocampus. These findings raise the possibility that amygdala-dependent fear systems may remain intact even when a patient has diminished memory of events. This may be of clinical importance in the perioperative development of fear-based psychopathologies, such as post-traumatic stress disorder. Clinical trial registration NCT00504894. PMID:26174294

  9. Elevated Levels of Plasma Mitochondrial DNA DAMPs Are Linked to Clinical Outcome in Severely Injured Human Subjects

    Science.gov (United States)

    Simmon, Jon D.; Lee, Yann-Leei; Mulekar, Sujata; Kuck, Jamie L.; Brevard, Sidney B.; Gonzalez, Richard P.; Gillespie, Mark N.; Richards, William O.

    2014-01-01

    Objective Our objective was to execute a prospective cohort study to determine relationships between plasma mtDNA DAMP levels and the occurrence of systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), and mortality. Background Mitochondrial DNA damage-associated molecular patterns (DAMPs) accumulate in the circulation after severe injury. Observations in animal models demonstrate that mtDNA DAMPs contribute to organ dys-function; however, the link between plasma mtDNA DAMPs and outcome in severely injured human subjects has not been established. Methods DNA was isolated from plasma samples taken from severely injured patients at hospital days 0, 1, and 2. Real-time PCR was used to quantify selected ≈200 base pair sequences of mtDNA within the COX1, ND1, and ND6 genes, as well as from the D-Loop transcriptional regulatory region. MODS was defined as a Denver Multiple Organ Failure score of 4 or greater. Results MtDNA DAMPs were quantified as PCR threshold cycle number. Lower threshold cycles indicate increased mtDNA DAMP content. Patients with SIRS had significantly increased mtDNA DAMP levels in all 4 sequences examined (32.14 ± 0.90 vs 29.00 ± 1.15 for COX1, 31.90 ± 0.47 vs 30.16 ± 1.42 for ND1, 32.40 ± 0.61 vs 28.94 ± 1.13 for ND6, and 33.12 ± 0.83 vs 28.30 ± 1.14 for D-Loop). Patients who developed MODS also had elevated mtDNA DAMP levels compared with those who did not (32.57 ± 0.74 vs 27.12 ± 0.66 for COX1, 32.45 ± 0.65 vs 28.20 ± 0.73 for ND1, 32.52 ± 0.56 vs 27.60 ± 0.79 for ND6, and 32.85 ± 0.75 vs 27.86 ± 1.27 for D-Loop). Patients with above-median mtDNA DAMP levels had a significantly elevated relative risk for mortality. Four patients died secondary to severe MODS. Conclusions These findings comprise the first observational evidence that plasma mtDNA DAMPs is associated with the evolution of SIRS, MODS, and mortality in severely injured human subjects. PMID:23979273

  10. Proton transfer reaction mass spectrometry and time intensity perceptual measurement of flavor release from lipid emulsions using trained human subjects.

    Science.gov (United States)

    Frank, Damian; Appelqvist, Ingrid; Piyasiri, Udayasika; Wooster, Tim J; Delahunty, Conor

    2011-05-11

    The effect of the fat component of liquid emulsions on dynamic "in-nose" flavor release was examined using a panel of trained human subjects (n = 6), proton transfer reaction mass spectrometry (PTR-MS), and time intensity (TI) sensory evaluation. A rigorous breathing and consumption protocol was developed, which synchronized subjects' breathing cycles and also the timing of sample introduction. Temporal changes in volatile release were measured in exhaled nostril breath by real-time PTR-MS. Corresponding changes in the perceived odor intensity could also be simultaneously measured using a push button TI device. The method facilitated accurate examination of both "preswallow" and "postswallow" phases of volatile release and perception. Volatile flavor compounds spanning a range of octanol/water partition coefficient (K(o/w)) values (1-1380) were spiked into water (0% fat) or lipid emulsions with various fat contents (2, 5, 10, and 20% fat). Replicate samples for each fat level were consumed according to the consumption protocol by six subjects. Statistical comparisons were made at the individual level and across the group for the effects of changes in the food matrix, such as fat content, on both pre- and postswallow volatile release. Significant group differences in volatile release parameters including area under the concentration curve (AUC) and maximum concentration (I(max)) were measured according to the lipid content of emulsions and volatile K(o/w). In a second experiment, using single compounds (2-heptanone, ethyl butanoate, and ethyl hexanoate), significant decreases in both in-nose volatile release and corresponding perceived odor intensities were measured with increasing fat addition. Overall, the effect of fat on in vivo release conformed to theory; fat had little effect on compounds with low K(o/w) values, but increased for volatiles with higher lipophilicity. In addition, significant pre- and postswallow differences were observed in AUC and I(max), as

  11. GLP-1 and Calcitonin Concentration in Humans: Lack of Evidence of Calcitonin Release from Sequential Screening in over 5000 Subjects with Type 2 Diabetes or Nondiabetic Obese Subjects Treated with the Human GLP-1 Analog, Liraglutide

    DEFF Research Database (Denmark)

    Hegedüs, Laszlo; Moses, Alan C; Zdravkovic, Milan

    2011-01-01

    to the GLP-1 receptor agonist liraglutide in subjects with type 2 diabetes mellitus or nondiabetic obese subjects. Methods: Unstimulated serum CT concentrations were measured at 3-month intervals for no more than 2 yr in a series of trials in over 5000 subjects receiving liraglutide or control therapy...

  12. Deficiency of caspase recruitment domain family, member 11 (CARD11), causes profound combined immunodeficiency in human subjects.

    Science.gov (United States)

    Stepensky, Polina; Keller, Baerbel; Buchta, Mary; Kienzler, Anne-Kathrin; Elpeleg, Orly; Somech, Raz; Cohen, Sivan; Shachar, Idit; Miosge, Lisa A; Schlesier, Michael; Fuchs, Ilka; Enders, Anselm; Eibel, Hermann; Grimbacher, Bodo; Warnatz, Klaus

    2013-02-01

    in human subjects. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  13. Twenty Questions Games Always End With Yes

    CERN Document Server

    Gill, John T

    2010-01-01

    Huffman coding is often presented as the optimal solution to Twenty Questions. However, a caveat is that Twenty Questions games always end with a reply of "Yes," whereas Huffman codewords need not obey this constraint. We bring resolution to this issue, and prove that the average number of questions still lies between H(X) and H(X)+1.

  14. Capital in the Twenty-First Century

    DEFF Research Database (Denmark)

    Hansen, Per H.

    2014-01-01

    Review essay on: Capital in the Twenty-First Century. By Thomas Piketty . Translated by Arthur Goldhammer . Cambridge, Mass.: The Belknap Press of Harvard University Press, 2014. viii + 685 pp......Review essay on: Capital in the Twenty-First Century. By Thomas Piketty . Translated by Arthur Goldhammer . Cambridge, Mass.: The Belknap Press of Harvard University Press, 2014. viii + 685 pp...

  15. Dosimetry of intravenously administered oxygen-15 labelled water in man: a model based on experimental human data from 21 subjects.

    Science.gov (United States)

    Smith, T; Tong, C; Lammertsma, A A; Butler, K R; Schnorr, L; Watson, J D; Ramsay, S; Clark, J C; Jones, T

    1994-10-01

    Models based on uniform distribution of tracer in total body water underestimate the absorbed dose from H2(15)O because of the short half-life (2.04 min) of 15O, which leads to non-uniform distribution of absorbed dose and also complicates the direct measurement of organ retention curves. However, organ absorbed doses can be predicted by the present kinetic model based on the convolution technique. The measured time course of arterial H2(15)O concentration following intravenous administration represents the input function to organs. The impulse response of a given organ is its transit time function determined by blood flow and the partition of water between tissue and blood. Values of these two parameters were taken from the literature. Integrals of the arterial input function and organ transit time functions were used to derive integrals of organ retention functions (organ residence times). The latter were used with absorbed dose calculation software (MIRDOSE-2) to obtain estimates for 24 organs. From the mean values of organ absorbed doses, the effective dose equivalent (EDE) and effective dose (ED) were calculated. From measurements on 21 subjects, the average value for both EDE and ED was calculated to be 1.2 microSv.MBq-1 compared with a value of about 0.5 microSv.MBq-1 predicted by uniform water distribution models. Based on the human data, a method of approximating H2(15)O absorbed dose values from body surface area is described.

  16. Application of a tracer gas challenge with a human subject to investigate factors affecting the performance of laboratory fume hoods.

    Science.gov (United States)

    Altemose, B A; Flynn, M R; Sprankle, J

    1998-05-01

    The results of a "user" tracer gas test were applied to investigate the effects of various parameters on hood containment ability and to evaluate accepted methods to classify hood performance. This user tracer gas test was performed with a human subject standing in front of the hood. Based on the data collected, face velocity, its variability, and cross drafts are important in determining hood leakage. Results indicate that the temporal variability of face velocity may deserve as much consideration as its spatial variability, a parameter more traditionally recognized as being important. The data collected indicate that hoods with horizontally sliding sash doors perform better with the doors positioned to provide a center opening rather than when all of the doors are pushed to one side. The observed smoke patterns suggest that this trend is caused by the location and instability of vortices formed along the perimeter edge when all doors are pushed to one side. The results of manikin tracer gas tests and the user tracer gas test are inconsistent, suggesting that more research is needed to determine how best to evaluate whether a hood protects its users.

  17. Maternal nutritional status, C(1) metabolism and offspring DNA methylation: a review of current evidence in human subjects.

    Science.gov (United States)

    Dominguez-Salas, Paula; Cox, Sharon E; Prentice, Andrew M; Hennig, Branwen J; Moore, Sophie E

    2012-02-01

    Evidence is growing for the long-term effects of environmental factors during early-life on later disease susceptibility. It is believed that epigenetic mechanisms (changes in gene function not mediated by DNA sequence alteration), particularly DNA methylation, play a role in these processes. This paper reviews the current state of knowledge of the involvement of C1 metabolism and methyl donors and cofactors in maternal diet-induced DNA methylation changes in utero as an epigenetic mechanism. Methyl groups for DNA methylation are mostly derived from the diet and supplied through C1 metabolism by way of choline, betaine, methionine or folate, with involvement of riboflavin and vitamins B6 and B12 as cofactors. Mouse models have shown that epigenetic features, for example DNA methylation, can be altered by periconceptional nutritional interventions such as folate supplementation, thereby changing offspring phenotype. Evidence of early nutrient-induced epigenetic change in human subjects is scant, but it is known that during pregnancy C1 metabolism has to cope with high fetal demands for folate and choline needed for neural tube closure and normal development. Retrospective studies investigating the effect of famine or season during pregnancy indicate that variation in early environmental exposure in utero leads to differences in DNA methylation of offspring. This may affect gene expression in the offspring. Further research is needed to examine the real impact of maternal nutrient availability on DNA methylation in the developing fetus.

  18. Subject-specific estimation of central aortic blood pressure via system identification: preliminary in-human experimental study.

    Science.gov (United States)

    Fazeli, Nima; Kim, Chang-Sei; Rashedi, Mohammad; Chappell, Alyssa; Wang, Shaohua; MacArthur, Roderick; McMurtry, M Sean; Finegan, Barry; Hahn, Jin-Oh

    2014-10-01

    This paper demonstrates preliminary in-human validity of a novel subject-specific approach to estimation of central aortic blood pressure (CABP) from peripheral circulatory waveforms. In this "Individualized Transfer Function" (ITF) approach, CABP is estimated in two steps. First, the circulatory dynamics of the cardiovascular system are determined via model-based system identification, in which an arterial tree model is characterized based on the circulatory waveform signals measured at the body's extremity locations. Second, CABP waveform is estimated by de-convolving peripheral circulatory waveforms from the arterial tree model. The validity of the ITF approach was demonstrated using experimental data collected from 13 cardiac surgery patients. Compared with the invasive peripheral blood pressure (BP) measurements, the ITF approach yielded significant reduction in errors associated with the estimation of CABP, including 1.9-2.6 mmHg (34-42 %) reduction in BP waveform errors (p < 0.05) as well as 5.8-9.1 mmHg (67-76 %) and 6.0-9.7 mmHg (78-85 %) reductions in systolic and pulse pressure (SP and PP) errors (p < 0.05). It also showed modest but significant improvement over the generalized transfer function approach, including 0.1 mmHg (2.6 %) reduction in BP waveform errors as well as 0.7 (20 %) and 5.0 mmHg (75 %) reductions in SP and PP errors (p < 0.05).

  19. Epigallocatechin-3-gallate prevents oxidative phosphorylation deficit and promotes mitochondrial biogenesis in human cells from subjects with Down's syndrome.

    Science.gov (United States)

    Valenti, Daniela; De Rasmo, Domenico; Signorile, Anna; Rossi, Leonardo; de Bari, Lidia; Scala, Iris; Granese, Barbara; Papa, Sergio; Vacca, Rosa Anna

    2013-04-01

    A critical role for mitochondrial dysfunction has been proposed in the pathogenesis of Down's syndrome (DS), a human multifactorial disorder caused by trisomy of chromosome 21, associated with mental retardation and early neurodegeneration. Previous studies from our group demonstrated in DS cells a decreased capacity of the mitochondrial ATP production system and overproduction of reactive oxygen species (ROS) in mitochondria. In this study we have tested the potential of epigallocatechin-3-gallate (EGCG) - a natural polyphenol component of green tea - to counteract the mitochondrial energy deficit found in DS cells. We found that EGCG, incubated with cultured lymphoblasts and fibroblasts from DS subjects, rescued mitochondrial complex I and ATP synthase catalytic activities, restored oxidative phosphorylation efficiency and counteracted oxidative stress. These effects were associated with EGCG-induced promotion of PKA activity, related to increased cellular levels of cAMP and PKA-dependent phosphorylation of the NDUFS4 subunit of complex I. In addition, EGCG strongly promoted mitochondrial biogenesis in DS cells, as associated with increase in Sirt1-dependent PGC-1α deacetylation, NRF-1 and T-FAM protein levels and mitochondrial DNA content. In conclusion, this study shows that EGCG is a promoting effector of oxidative phosphorylation and mitochondrial biogenesis in DS cells, acting through modulation of the cAMP/PKA- and sirtuin-dependent pathways. EGCG treatment promises thus to be a therapeutic approach to counteract mitochondrial energy deficit and oxidative stress in DS.

  20. Antioxidant Activity and Cytotoxicity Effect of Cocoa Beans Subjected to Different Processing Conditions in Human Lung Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Deborah Bauer

    2016-01-01

    Full Text Available Lung cancer is a common malignancy in men and the second leading cause of cancer-related mortality in men in the western world. Phenolic cocoa ingredients have a strong antioxidative activity and the potential to have a protective effect against cancer. In the present study, we have evaluated the influence of cocoa beans subjected to different processing conditions on cell viability and apoptosis of human lung cancer cells (A549. We measured the viability of lung cells treated with cocoa beans, unroasted slates (US, roasted slates (RS, unroasted well fermented (UWF cocoa, and roasted well fermented (RWF cocoa for 24 h. Using an MTT assay, we observed a decrease in the viability of A549 cells after treatment with cocoa bean extracts. Flow cytometer analysis revealed that cocoa beans increased the percentage of cells in sub-G1 phase and promoted up to twofold increase of apoptotic cells when compared to the control group. Taken together, the present study suggests that cocoa beans may have a protective effect against lung cancer.

  1. Antioxidant Activity and Cytotoxicity Effect of Cocoa Beans Subjected to Different Processing Conditions in Human Lung Carcinoma Cells

    Science.gov (United States)

    Bauer, Deborah; de Abreu, Joel Pimentel; Oliveira, Hilana Salete Silva; Goes-Neto, Aristoteles; Koblitz, Maria Gabriela Bello

    2016-01-01

    Lung cancer is a common malignancy in men and the second leading cause of cancer-related mortality in men in the western world. Phenolic cocoa ingredients have a strong antioxidative activity and the potential to have a protective effect against cancer. In the present study, we have evaluated the influence of cocoa beans subjected to different processing conditions on cell viability and apoptosis of human lung cancer cells (A549). We measured the viability of lung cells treated with cocoa beans, unroasted slates (US), roasted slates (RS), unroasted well fermented (UWF) cocoa, and roasted well fermented (RWF) cocoa for 24 h. Using an MTT assay, we observed a decrease in the viability of A549 cells after treatment with cocoa bean extracts. Flow cytometer analysis revealed that cocoa beans increased the percentage of cells in sub-G1 phase and promoted up to twofold increase of apoptotic cells when compared to the control group. Taken together, the present study suggests that cocoa beans may have a protective effect against lung cancer. PMID:27034742

  2. Atlasing location, asymmetry and inter-subject variability of white matter tracts in the human brain with MR diffusion tractography.

    Science.gov (United States)

    Thiebaut de Schotten, Michel; Ffytche, Dominic H; Bizzi, Alberto; Dell'Acqua, Flavio; Allin, Matthew; Walshe, Muriel; Murray, Robin; Williams, Steven C; Murphy, Declan G M; Catani, Marco

    2011-01-01

    The purpose of this study is to create a white matter atlas of the human brain using diffusion tensor imaging (DTI) tractography and to describe the constant and variable features of the major pathways. DTI was acquired from 40 healthy right-handed adults and reconstructed tracts mapped within a common reference space (MNI). Group effect maps of each tract defined constant anatomical features while overlap maps were generated to study inter-subject variability and to compare DTI derived anatomy with a histological atlas. Two patients were studied to assess the localizing validity of the atlas. The DTI-derived maps are overall consistent with a previously published histological atlas. A statistically significant leftward asymmetry was found for the volume and number of streamlines of the cortico-spinal tract and the direct connections between Broca's and Wernicke's territories (long segment). A statistically significant rightward asymmetry was found for the inferior fronto-occipital fasciculus and the fronto-parietal connections (anterior segment) of the arcuate fasciculus. Furthermore, males showed a left lateralization of the fronto-temporal segment of the arcuate fasciculus (long segment), while females had a more bilateral distribution. In two patients with brain lesions, DTI was acquired and tractography used to show that the tracts affected by the lesions were correctly identified by the atlas. This study suggests that DTI-derived maps can be used together with a previous histological atlas to establish the relationship of focal lesions with nearby tracts and improve clinico-anatomical correlation.

  3. Biodistribution and radiation dosimetry for the tau tracer (18)F-THK-5351 in healthy human subjects.

    Science.gov (United States)

    Hsiao, Ing-Tsung; Lin, Kun-Ju; Huang, Kuo-Lun; Huang, Chin-Chang; Chen, Han-Shiuan; Wey, Shiaw-Pyng; Yen, Tzu-Chen; Okamura, Nobuyuki; Hsu, Jung-Lung

    2017-03-23

    (18)F-THK-5351 is a novel radiotracer that demonstrates high binding selectivity and affinity for tau pathology and exhibits better pharmacokinetics in the living brain than previous THK tau probes. The aim of the present study was to estimate the radiation dose of (18)F-THK-5351 in humans and to compare the clinical radiation dosimetry results to estimations published previously with preclinical data. Methods: Serial whole-body positron emission tomography/computed tomography (PET/CT) imaging was performed for 240 min on 12 healthy volunteers after injecting (18)F-THK-5351 (mean administered activity: 377.8 ± 14.0 MBq, range: 340-397 MBq). The bladder and gallbladder were delineated on PET images, while the other organs were delineated on CT images. Voided urine activity was recorded. The decay-corrected and normalized (18)F-THK-5351 activity of 15 source organ regions as a function of time was entered into the OLINDA/EXM software to calculate the effective dose for each subject following the medical internal radiation dosimetry schema. Results: Overall, the (18)F-THK-5351 injection was well tolerated. The highest mean initial uptakes at 10 min post-injection were measured in the liver (11.4 ± 2.0%), lung (5.7 ± 2.1%), intestine (3.4 ± 0.8%), and kidney (1.4 ± 0.3%). The highest mean absorbed doses of radiation were in the gallbladder wall (242.2 ± 105.2 µGy/MBq), upper large intestine (90.0 ± 15.8 µGy/MBq), small intestine (79.5 ± 13.8 µGy/MBq), and liver (55.8 ± 6.1 µGy/MBq). The resultant whole-body effective dose was 22.7 ± 1.3 µSv/MBq. Conclusion: Our results suggest that a routine injection of 370 MBq of (18)F-THK-5351 would lead to an estimated effective dose of 8.4 mSv; hence, (18)F-THK-5351 shows similar radiation burdens to other commonly used clinical tracers. Our findings in humans were compatible with recently published preclinical dosimetry data extrapolated from mice.

  4. A Population Pharmacokinetic Model for Disposition in Plasma, Saliva and Urine of Scopolamine after Intranasal Administration to Healthy Human Subjects

    Science.gov (United States)

    Wu, L.; Tam, V. H.; Chow, D. S. L.; Putcha, L.

    2014-01-01

    An intranasal gel formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness. The bioavailability and pharmacokinetics (PK) were evaluated under the Food and Drug Administration guidelines for clinical trials with an Investigative New Drug (IND) protocol. The aim of this project was to develop a PK model that can predict the relationship between plasma, saliva and urinary scopolamine concentrations using data collected from the IND clinical trials with INSCOP. Methods: Twelve healthy human subjects were administered three dose levels (0.1, 0.2 and 0.4 mg) of INSCOP. Serial blood, saliva and urine samples were collected between 5 min and 24 h after dosing and scopolamine concentrations were measured by using a validated LC-MS-MS assay. Pharmacokinetic Compartmental models, using actual dosing and sampling times, were built using Phoenix (version 1.2). Model selection was based on the likelihood ratio test on the difference of criteria (-2LL) and comparison of the quality of fit plots. Results: The best structural model for INSCOP (minimal -2LL= 502.8) was established. It consisted of one compartment each for plasma, saliva and urine, respectively, which were connected with linear transport processes except the nonlinear PK process from plasma to saliva compartment. The best-fit estimates of PK parameters from individual PK compartmental analysis and Population PK model analysis were shown in Tables 1 and 2, respectively. Conclusion: A population PK model that could predict population and individual PK of scopolamine in plasma, saliva and urine after dosing was developed and validated. Incorporating a non-linear transfer from plasma to saliva compartments resulted in a significantly improved model fitting. The model could be used to predict scopolamine plasma concentrations from salivary and urinary drug levels, allowing non-invasive therapeutic monitoring of scopolamine in space and other remote environments.

  5. Mallaby’s car: colonial subjects, imperial actors, and the representation of human suffering in postcolonial exhibitions

    Directory of Open Access Journals (Sweden)

    Susan Legêne

    2014-10-01

    Full Text Available The iconic photograph of Mallaby’s car shows the wreckage of the vehicle of British brigadier A.S. Mallaby, which was destroyed in Surabaya in Indonesia on 30 October 1945 during the Indonesian uprising against the restoration of Dutch colonial rule. The streets show military vehicles, in control of the situation; however the billboard with ‘Once and forever – The Indonesia Republic’ indicate that the nationalists did not give up their political aspirations. The photograph is iconic in the fragile balance it depicts; a balance between violence and negotiations with many stakeholders, symbolised in the balancing car, with its front wheels, hood and left front door up and open. This photograph triggered my investigation into the impact of decolonisation on the representation of colonial subjects and ‘imperial actors’ in museums in Indonesia and the Netherlands. The image of the car appears in a recorded interview with the two sons of Mallaby, who in minute detail recount the events that resulted in their father’s death. The car points at a history of decolonisation that thoroughly changed the strong or weak citizenship entitlements of everyone involved. What role could they play, at the time, and how is this diverging agency now represented in historical or ethnographic displays? This theme is explored with close reference to the scholarly models provided by Asma Abbas in Liberalism and Human Suffering (2010, specifically the notion of re-presentation as ‘making present again’. I argue that distinct national frames, within which common histories of colonialism and decolonisation today are represented, create notions of ‘historical citizenship’ that discipline the victims of decolonisation, and refrain from challenging the legacies of the ethnographic categorisation in colonial museum displays.

  6. Dosimetry of intravenously administered oxygen-15 labelled water in man: a model based on experimental human data from 21 subjects

    Energy Technology Data Exchange (ETDEWEB)

    Smith, T. (Section of Medical Physics, Clinical Research Centre, Harrow (United Kingdom)); Tong, C. (MRC Cyclotron Unit, Hammersmith Hospital, London (United Kingdom)); Lammertsma, A.A. (MRC Cyclotron Unit, Hammersmith Hospital, London (United Kingdom)); Butler, K.R. (MRC Cyclotron Unit, Hammersmith Hospital, London (United Kingdom)); Schnorr, L. (MRC Cyclotron Unit, Hammersmith Hospital, London (United Kingdom)); Watson, J.D.G. (MRC Cyclotron Unit, Hammersmith Hospital, London (United Kingdom)); Ramsay, S. (MRC Cyclotron Unit, Hammersmith Hospital, London (United Kingdom)); Clark, J.C. (MRC Cyclotron Unit, Hammersmith Hospital, London (United Kingdom)); Jones, T. (MRC Cyclotron Unit, Hammersmith Hospital, London (United Kingdom))

    1994-10-01

    Models based on uniform distribution of tracer in total body water underestimate the absorbed dose from H[sub 2][sup 15]O because of the short half-life (2.04 min) of [sup 15]O, which leads to non-uniform distribution of absorbed dose and also complicates the direct measurement of organ retention curves. However, organ absorbed doses can be predicted by the present kinetic model based on the convolution technique. The measured time course of arterial H[sub 2][sup 15]O concentration following intravenous administration represents the input function to organs. The impulse response of a given organ is its transit time function determined by blood flow and the partition of water between tissue and blood. Values of these two parameters were taken from the literature. Integrals of the arterial input function and organ transit time functions were used to derive integrals of organ retention functions (organ residence times). The latter were used with absorbed dose calculation software (MIRDOSE-2) to obtain estimates for 24 organs. From the mean values of organ absorbed doses, the effective dose equivalent (EDE) and effective dose (ED) were calculated. From measurements on 21 subjects, the average value for both EDE and ED was calculated to be 1.2 [mu]Sv.MBq[sup -1] compared with a value of about 0.5 [mu]Sv.MBq[sup -1] predicted by uniform water distribution models. Based on the human data, a method of approximating H[sub 2][sup 15]O absorbed dose values from body surface area is described. (orig.)

  7. Identification of direct and indirect social network effects in the pathophysiology of insulin resistance in obese human subjects.

    Directory of Open Access Journals (Sweden)

    Christian H C A Henning

    Full Text Available OBJECTIVE: The aim of the present study was to examine to what extent different social network mechanisms are involved in the pathogenesis of obesity and insulin-resistance. DESIGN: We used nonparametric and parametric regression models to analyse whether individual BMI and HOMA-IR are determined by social network characteristics. SUBJECTS AND METHODS: A total of 677 probands (EGO and 3033 social network partners (ALTER were included in the study. Data gathered from the probands include anthropometric measures, HOMA-IR index, health attitudes, behavioural and socio-economic variables and social network data. RESULTS: We found significant treatment effects for ALTERs frequent dieting (p<0.001 and ALTERs health oriented nutritional attitudes (p<0.001 on EGO's BMI, establishing a significant indirect network effect also on EGO's insulin resistance. Most importantly, we also found significant direct social network effects on EGO's insulin resistance, evidenced by an effect of ALTERs frequent dieting (p = 0.033 and ALTERs sport activities (p = 0.041 to decrease EGO's HOMA-IR index independently of EGO's BMI. CONCLUSIONS: Social network phenomena appear not only to be relevant for the spread of obesity, but also for the spread of insulin resistance as the basis for type 2 diabetes. Attitudes and behaviour of peer groups influence EGO's health status not only via social mechanisms, but also via socio-biological mechanisms, i.e. higher brain areas might be influenced not only by biological signals from the own organism, but also by behaviour and knowledge from different human individuals. Our approach allows the identification of peer group influence controlling for potential homophily even when using cross-sectional observational data.

  8. Assessment of Potential Long Term Health Effects on Army Human Test Subjects of Relevant Biological and Chemical Agents, Drugs, Medications and Substances

    Science.gov (United States)

    2016-02-29

    cardiovascular effects disappeared in most subjects after 24 hours. Decreased body temperature , dryness of the mouth and throat, nasal stuffiness, apathy...or ingestion into the human body readily results in its metabolism to malaoxon, which is substan- tially more toxic. In studies of the effects of...from the Pre- cursors of Human Muscle Regeneration." Am J Physiol Regul Integr Comp Physiol 291, no. 6 (2006): R1651-6. 42. Yamasue, H, O. Abe, K

  9. THE HUMAN SUBJECTIVITY BETWEEN THE SUPERIOR AND INFERIOR TYPES A SUBJETIVIDADE HUMANA ENTRE OS TIPOS SUPERIORES E INFERIORES

    Directory of Open Access Journals (Sweden)

    Vagner Silva

    2011-12-01

    Full Text Available This article attempts to solve the following contradiction of Nietzsche's thought: man has a subjective drive constitution, these drives, however, are individuals, and its being (the being of the drives, is constituted for more power fight (the will to power. Nietzsche's superior man (educated and cultivated man is that one, in which there is harmony in the drives, who can give greater freedom to its most terrible drives, without, however, loses the control over them. That is the contradiction: if man has to control the drives, they are not harmonics. There is incompatibility between harmony and control. In other words, the superior man is indeed the man of culture and cultivated man of Nietzsche? If the answer to this question is yes, then, in this man, reigns the drives harmony. If, on the other hand, the answer is no, then, for this man does not become a barbarian destroyer, dangerous to himself and to others it is necessary that a drive dominates the others. However it is not possible to escape the contradiction: either there is harmony in human drive or control.Este artigo busca resolver a seguinte contradição do pensamento de Nietzsche: o homem possui uma constituição subjetiva pulsional, estas pulsões, porém, são individuais, e o seu ser, o das pulsões, constitui-se da luta por mais poder (vontade de poder. O homem superior de Nietzsche (homem culto e cultivado é aquele no qual há harmonia nas pulsões, aquele que pode dar mais liberdade às suas mais terríveis pulsões, sem, no entanto, perder o controle sobre elas. Eis a contradição: se o homem superior exerce controle sobre as pulsões então elas não são harmônicas. Há, aqui, a incompatibilidade entre harmonia e controle. Em outros termos: o homem superior é de fato o homem culto e cultivado de Nietzsche? Se a resposta para esta pergunta for sim, então neste homem reina a harmonia pulsional. Se, por outro lado, a resposta for não, então, para que este homem n

  10. Conflictos en ética de investigación con seres humanos Ethical conflicts in research with human subjects

    Directory of Open Access Journals (Sweden)

    Miguel H. Kottow

    2005-06-01

    Full Text Available Desde la Declaración de Helsinki 2000, se intensificó y amplió un conflictivo debate que ha cuestionado muchos aspectos de la ética de investigación con seres humanos. La polémica incluye el uso de placebos, la aplicación del concepto de equiponderación, la distinción entre ética de investigación y ética clínica, así como la diferencia entre ensayos terapéuticos y no terapéuticos. El presente artículo insiste en fortalecer todos los argumentos, parámetros y estrategias de investigación que sean necesarios para proteger a los paciente-probandos, ante todo el mantenimiento de la mejor terapia existente, el rechazo del uso de placebos, la aplicación de la equiponderación, la preservación de requerimientos terapéuticos más allá del estudio y la compensación a comunidades-huésped en la medida que ellas hayan facilitado y apoyado la investigación. La propuesta de establecer un doble estándar de ética de investigación en seres humanos, una de máximos para países desarrollados y otra de mínimos pragmáticos a aplicar en países de desarrollo precario, debe ser rechazada por contravenir las intenciones de universalizabilidad de toda prescripción ética.The Declaration of Helsinki (2000 helped trigger a major debate on many ethical aspects of research with human subjects. Topics under discussion include the use of placebos, the application of equipoise, the distinction between research ethics and clinical ethics, and the difference between therapeutic and non-therapeutic trials. This article supports tenets that serve to protect patients involved in research, especially in those aspects concerning maintenance of best existing therapy, the rejection of using placebos, support of equipoise, the assurance that required medication shall be available beyond the termination of the research project, and that appropriate compensation will obtain to host communities inasmuch as they may have facilitated and supported the project

  11. Investigation on occupant ejection in high severity rear impact based on post mortem human subject sled tests.

    Science.gov (United States)

    Petit, Philippe; Luet, Carole; Potier, Pascal; Vallancien, Guy

    2011-11-01

    Occupant protection in rear impact involves two competing challenges. On one hand, allowing a deformation of the seat would act as an energy absorber in low severity impacts and would consequently decrease the risk of neck injuries. However, on the other hand, large deformations of the seat may increase the likelihood of occupant ejection in high severity cases. Green et al. 1987 analyzed a total of 919 accidents in Great Britain. They found that occupant ejection resulted in a risk of severe injuries and fatalities between 3.6 and 4.5 times higher than those cases where no ejection was observed. The sample included single front, side and rear impacts as well as multiple impacts and rollover. The rate of belt use in the sample was 50%. While this analysis included all forms of impact scenarios, nevertheless, it highlights the relative injury severity of occupant ejection. Extensive literature search has found no full-scale rear impact tests involving Post Mortem Human Subjects (PMHS) conducted in a laboratory environment and resulting in ejection. This paper describes a total of 10 sled tests conducted on 3 belted PMHS using a simplified seat design composed of rigid plates assembled such that the angular and linear stiffness of the seatback (including the foam) was modeled. The initial angular position and the range of motion of the seatback, the size of the PMHS, the slack length of the seatbelt, the angular stiffness of the seatback, and the use of headrest were varied in the test matrix while the pulse was kept constant (triangular acceleration with a peak of 17 G at 30 ms and a duration of 95 ms). In the test series, the tests were not run randomly but the likelihood of occupant ejection was increased systematically until ejection occurred. PMHS seat ejection was observed only for the 95th percentile, initially positioned with a seatback angle relative to the vertical equal to 22°, a range of seatback angular motion equal to 44° and no headrest. Repeating

  12. A 15-Year Review of Trends in Representation of Female Subjects in Islamic Bioethics Research.

    Science.gov (United States)

    Hussain, Zeenat; Kuzian, Edyta; Hussain, Naveed

    2017-02-01

    Gender representation in Islamic bioethics research in the twenty-first century has not been studied. To study temporal trends in representation of female subjects in Islamic bioethics research, PubMed-listed publications on Islamic bioethics from years 2000 to 2014 were reviewed for gender participation in human subjects' research. There were temporal trends of increasing publications of Islamic bioethics-related human subjects' research (64 papers over 15 years; R (2) = 0.72; p women from Muslim-majority countries even in non-gender-focused studies over the past 15 years.

  13. Experience with magnetic resonance imaging of human subjects with passive implants and tattoos at 7 T: a retrospective study.

    Science.gov (United States)

    Noureddine, Yacine; Bitz, Andreas K; Ladd, Mark E; Thürling, Markus; Ladd, Susanne C; Schaefers, Gregor; Kraff, Oliver

    2015-12-01

    Over the last decade, the number of clinical MRI studies at 7 T has increased dramatically. Since only limited information about the safety of implants/tattoos is available at 7 T, many centers either conservatively exclude all subjects with implants/tattoos or have started to perform dedicated tests for selected implants. This work presents our experience in imaging volunteers with implants/tattoos at 7 T over the last seven and a half years. 1796 questionnaires were analyzed retrospectively to identify subjects with implants/tattoos imaged at 7 T. For a total of 230 subjects, the type of local transmit/receive RF coil used for examination, imaging sequences, acquisition time, and the type of implants/tattoos and their location with respect to the field of view were documented. These subjects had undergone examination after careful consideration by an internal safety panel consisting of three experts in MR safety and physics. None of the subjects reported sensations of heat or force before, during, or after the examination. None expressed any discomfort related to implants/tattoos. Artifacts were reported in 52% of subjects with dental implants; all artifacts were restricted to the mouth area and did not affect image quality in the brain parenchyma. Our initial experience at 7 T indicates that a strict rejection of subjects with tattoos and/or implants is not justified. Imaging can be conditionally performed in carefully selected subjects after collection of substantial safety information and evaluation of the detailed exposure scenario (RF coil/type and position of implant). Among the assessed subjects with tattoos, no side effects from the exposure to 7 T MRI were reported.

  14. A whey-protein supplement increases fat loss and spares lean muscle in obese subjects: a randomized human clinical study

    Directory of Open Access Journals (Sweden)

    Ward Loren S

    2008-03-01

    Full Text Available Abstract Background This study evaluated a specialized whey fraction (Prolibra™, high in leucine, bioactive peptides and milk calcium for use as a dietary supplement to enhance weight loss. Methods This was a randomized, double-blind, parallel-arm, 12-week study. Caloric intake was reduced 500 calories per day. Subjects consumed Prolibra or an isocaloric ready-to-mix beverage 20 minutes before breakfast and 20 minutes before dinner. Body fat and lean muscle tissue were measured by dual-energy x-ray absorptiometry (DEXA. Body weight and anthropometric measurements were recorded every 4 weeks. Blood samples were taken at the beginning and end of the study. Statistical analyses were performed on all subjects that completed (completer analysis and all subjects that lost at least 2.25 kg of body weight (responder analysis. Within group significance was determined at P Results Both groups lost a significant amount of weight and the Prolibra group tended to lose more weight than the control group; however the amount of weight loss was not significantly different between groups after 12 weeks. Prolibra subjects lost significantly more body fat compared to control subjects for both the completer (2.81 vs. 1.62 kg P = 0.03 and responder (3.63 vs. 2.11 kg, P = 0.01 groups. Prolibra subjects lost significantly less lean muscle mass in the responder group (1.07 vs. 2.41 kg, P = 0.02. The ratio of fat to lean loss (kg fat lost/kg lean lost was much larger for Prolibra subjects for both completer (3.75 vs. 1.05 and responder (3.39 vs. 0.88 groups. Conclusion Subjects in both the control and treatment group lost a significant amount of weight with a 500 calorie reduced diet. Subjects taking Prolibra lost significantly more body fat and showed a greater preservation of lean muscle compared to subjects consuming the control beverage. Because subjects taking Prolibra lost 6.1% of their body fat mass, and because a 5% reduction of body fat mass has been shown to

  15. ANTIBIOTICS SUSCEPTIBILITY AND RESISTANCE PATTERNS OF CAMPYLOBACTER OBTAINED FROM HUMANS AND CHICKENS IN OSOGBO

    OpenAIRE

    O.C Adekunle

    2012-01-01

    Occurrence of gastroenteritis due to Campylobacter species has been established in both humans and chickens Osogbo. This study was done to compare antibiotic susceptibility and resistance patterns in both humans and chickens. Twenty three Campylobacter isolates were obtained from humans and twenty isolates from chickens. The isolates were also subjected to the antimicrobial sensitivity testing. All the isolates exhibited varying degree of sensivity to the antimicrobial agents with ciprofloxac...

  16. Effects of dietary supplementation with a combination of fish oil, bilberry extract, and lutein on subjective symptoms of asthenopia in humans.

    Science.gov (United States)

    Kawabata, Fuminori; Tsuji, Tomoko

    2011-12-01

    The aim of this study was to determine the effects of dietary supplementation with a combination of fish oil, bilberry extract, and lutein on subjective symptoms of asthenopia in humans by a double- blind, randomized, parallel-group, and placebo-controlled trial. In the Active group, eleven subjects ingested a supplement containing omega-3 fatty acid-rich fish oil (docosahexaenoic acid 783 mg/day, eicosapentaenoic acid 162 mg/day), bilberry extract (anthocyanidin 59 mg/day), and lutein (17.5 mg/day) in soft gel capsule form, every day for 4 weeks. In the Placebo group, nine subjects ingested placebo capsules. Before and after supplementation, subjects completed a questionnaire to determine their asthenopia symptoms and were also assessed for mental fatigue symptom by the visual analog scale (VAS) test. Asthenopia symptoms such as "stiff shoulder, low back pain", "frustration", "dry-eye", and "stuffy head" were improved in the Active group. Furthermore, a score of mental fatigue was improved after 4 weeks of supplementation, and no side effects were observed after the 4-week supplementation and a 2-week washout period in the Active group. These results suggest that dietary supplementation with the combination of omega-3 fatty acid-rich fish oil, bilberry extract, and lutein may safely improve subjective symptoms of asthenopia and mental fatigue in humans.

  17. Equine and human mutual welfare: a whole subject? Critical aspects and possible strategies in equine-assisted activities and therapies

    OpenAIRE

    Li Destri Nicosia, Dora

    2011-01-01

    General aim of the study is equine welfare, particularly concerning different husbandry methodic and inter-specific relational factors. Specific aim is the evaluation of possible mutual (to humans and to equines) benefits and the analysis of critical factors/strength points, of human-horse relationship within Therapeutic Riding context (TR). The peculiarities of human-horse relationship (compared to the bond with “Pet”) are analyzed, concerning their socio-anthropological, psychological, p...

  18. 谈生命伦理学在医学人体试验中应用的特殊性%Discussion on bioethical uniqueness in human subjects research

    Institute of Scientific and Technical Information of China (English)

    陈玲; 刘延; 刘珺; 孙玮

    2011-01-01

    To demonstrate the application and specification of bioethical uniqueness in human subjects research. Analysis was made with regard to the ethics of clinical blind trial to display the bioethical uniqueness in human subjects research. Autonomy was one of the most important factors, which was different from the informed consent in medical treatment. Em -phasis was laid on the subjects' free decision rather than being provided with sufficient information. The research was in -tended to promote the medical development social progress. Social welfare could be achieved in bioethics in the human subjects research. So combinaion of autonomy and social welfare is the real reflection of bioethical uniqueness in human subjects research.%为探讨生命伦理学在医学人体试验中的具体应用有其特殊性,说明不能照搬医疗中的自主性原则.本文对临床盲试伦理进行具体分析,发现医学人体试验中的自主性原则应注重受试者的自主决定权而不是知情权;同时,鉴于医学人体试验旨在促进医学发展和社会进步,社会利益也是医学人体试验伦理应考虑的重要因素.因此,自主性原则与社会利益的兼顾才真正符合医学人体试验的伦理道德.

  19. Early twenty-first-century droughts during the warmest climate

    Directory of Open Access Journals (Sweden)

    Felix Kogan

    2016-01-01

    Full Text Available The first 13 years of the twenty-first century have begun with a series of widespread, long and intensive droughts around the world. Extreme and severe-to-extreme intensity droughts covered 2%–6% and 7%–16% of the world land, respectively, affecting environment, economies and humans. These droughts reduced agricultural production, leading to food shortages, human health deterioration, poverty, regional disturbances, population migration and death. This feature article is a travelogue of the twenty-first-century global and regional droughts during the warmest years of the past 100 years. These droughts were identified and monitored with the National Oceanic and Atmospheric Administration operational space technology, called vegetation health (VH, which has the longest period of observation and provides good data quality. The VH method was used for assessment of vegetation condition or health, including drought early detection and monitoring. The VH method is based on operational satellites data estimating both land surface greenness (NDVI and thermal conditions. The twenty-first-century droughts in the USA, Russia, Australia and Horn of Africa were intensive, long, covered large areas and caused huge losses in agricultural production, which affected food security and led to food riots in some countries. This research also investigates drought dynamics presenting no definite conclusion about drought intensification or/and expansion during the time of the warmest globe.

  20. A Controlled Challenge Study on Di(2-ethylhexyl) Phthalate (DEHP) in House Dust and the Immune Response in Human Nasal Mucosa of Allergic Subjects

    OpenAIRE

    Deutschle, Tom; Reiter, Rudolf; Butte, Werner; Heinzow, Birger; Keck, Tilman; Riechelmann, Herbert

    2008-01-01

    Background Few studies have yet addressed the effects of di(2-ethylhexyl) phthalate (DEHP) in house dust on human nasal mucosa. Objectives We investigated the effects of house dust containing DEHP on nasal mucosa of healthy and house dust mite (HDM)–allergic subjects in a short-term exposure setting. Methods We challenged 16 healthy and 16 HDM-allergic subjects for 3 hr with house dust at a concentration of 300 μg/m3 containing either low (0.41 mg/g) or high (2.09 mg/g) levels of DEHP. Exposu...

  1. Human resource management practices aimed at seeking the commitment of employees on financial and non-financial (subjective performance in spanish firms: an empirical contribution

    Directory of Open Access Journals (Sweden)

    Rafael Triguero

    2012-06-01

    Full Text Available The purpose of this paper is to assess the relationship between Human Resource Management (HRM practices and organizational performance in Spanish firms from a financial and non-financial perspective (subjective. The empirical study was conducted with a sample of 102 firms in the region of Andalucía (Spain. The results of statistical analysis have shown the fundamental role of establishing HRM practices aimed at seeking the employees’ commitment and its positive influence on organizational performance. Results also showed that the subjective measures for organizational performance better explained this phenomenon of study.

  2. Vitamin K absorption and kinetics in human subjects after consumption of 13C-labelled phylloquinone from kale.

    Science.gov (United States)

    Novotny, Janet A; Kurilich, Anne C; Britz, Steven J; Baer, David J; Clevidence, Beverly A

    2010-09-01

    The absorption and plasma disappearance of vitamin K were investigated by uniformly labelling phylloquinone in kale with carbon-13, and by feeding the kale to study subjects. Seven healthy volunteers ingested a single 400 g serving of kale with 30 g vegetable oil. The kale provided 156 nmol of phylloquinone. Serial plasma samples were collected and analysed for the appearance of 13C-phylloquinone by HPLC-MS. Six of the subjects showed significant amounts of labelled phylloquinone in plasma, though one subject's plasma was not consistently enriched above the detection limit, and this subject's baseline plasma phylloquinone level was the lowest in the group. After ingestion of the labelled kale, plasma 13C-phylloquinone concentration increased rapidly to a peak between 6 and 10 h, and then rapidly decreased. Average peak plasma concentration for the six subjects with detectable 13C-phylloquinone was 2.1 nmol/l. Plasma concentration-time data were analysed by compartmental modelling. Modelling results demonstrated a mean (n 6) bioavailability of phylloquinone from kale to be 4.7%. Plasma and tissue half-times for phylloquinone were found to be 8.8 and 215 h, respectively.

  3. Male and female WorldSID and post mortem human subject responses in full-scale vehicle tests.

    Science.gov (United States)

    Yoganandan, Narayan; Humm, John; Pintar, Frank; Rhule, Heather; Moorhouse, Kevin; Suntay, Brian; Stricklin, Jim; Rudd, Rodney; Craig, Matthew

    2017-05-29

    This study compares the responses of male and female WorldSID dummies with post mortem human subject (PMHS) responses in full-scale vehicle tests. Tests were conducted according to the FMVSS-214 protocols and using the U.S. Side Impact New Car Assessment Program change in velocity to match PMHS experiments, published earlier. Moving deformable barrier (MDB) tests were conducted with the male and female surrogates in the left front and left rear seats. Pole tests were performed with the male surrogate in the left front seat. Three-point belt restraints were used. Sedan-type vehicles were used from the same manufacturer with side airbags. The PMHS head was instrumented with a pyramid-shaped nine-axis accelerometer package, with angular velocity transducers on the head. Accelerometers and angular velocity transducers were secured to T1, T6, and T12 spinous processes and sacrum. Three chest bands were secured around the upper, middle, and lower thoraces. Dummy instrumentation included five infrared telescoping rods for assessment of chest compression (IR-TRACC) and a chest band at the first abdomen rib, head angular velocity transducer, and head, T1, T4, T12, and pelvis accelerometers. Morphological responses of the kinematics of the head, thoracic spine, and pelvis matched in both surrogates for each pair. The peak magnitudes of the torso accelerations were lower for the dummy than for the biological surrogate. The brain rotational injury criterion (BrIC) response was the highest in the male dummy for the MDB test and PMHS. The probability of AIS3+ injuries, based on the head injury criterion, ranged from 3% to 13% for the PMHS and from 3% to 21% for the dummy from all tests. The BrIC-based metrics ranged from 0 to 21% for the biological and 0 to 48% for the dummy surrogates. The deflection profiles from the IR-TRACC sensors were unimodal. The maximum deflections from the chest band placed on the first abdominal rib were 31.7 mm and 25.4 mm for the male and female

  4. Simulated flight path control of fighter pilots and novice subjects at +3 Gz in a human centrifuge.

    Science.gov (United States)

    Dalecki, Marc; Bock, Otmar; Guardiera, Simon

    2010-05-01

    We have previously shown that subjects produce exaggerated manual forces in +3 Gz. When subjects execute discrete flight path changes in a flight simulator, their performance is less stable in +3 Gz than in +1 Gz. Here we explore whether Gz-related deficits are found with continuous flight path changes. Novice subjects and fighter pilots sat in a high-fidelity flight simulator equipped with the reproduction of the Eurofighter 2000 cockpit, including the realistic flight stick, and pursued continuous altitude changes of a target airplane in +1 Gz and +3 Gz. Subjects also produced verbal responses in a Stroop task. Pursuit and Stroop tasks were administered alone and concurrently. Flight instability increased in +3 Gz compared to +1 Gz in novices (+46%), but not in pilots (+3%), and even there only during the first minute. Flight performance improved after the first minute in both subject groups. Stroop reaction time was higher in novices (+5.27%) than in pilots (+3.77%) at +3 Gz. Dual-task costs did not differ between groups or Gz levels. Deficits of force production in high Gz are largely compensated for when subjects apply forces to produce a continuously changing flight path. This compensation seems not to require additional cognitive resources and may be achieved by using visual feedback. Force production deficits in high Gz seem to have no appreciable effects on flight performance and cognitive load of experienced pilots using a force-plus-displacement stick in +3 Gz. It remains to be shown whether this conclusion extends to purely isometric sticks and to higher Gz levels.

  5. Twenty-Channel Voice Response System.

    Science.gov (United States)

    1981-06-01

    programs and vocabulary. 0 Telephone Company (TELCO) Switched Lines - provides access to VRS using telephones. * Bell 407C Data Sets - Converts the Touch...from the twenty 407C units. 0 DLII-E - Asynchronous interface to the 11/34 unibus for the VOTRAX unit. * 20 Channel ADPCM Decoder - a specially designed

  6. Educating the Ablest: Twenty Years Later

    Science.gov (United States)

    Culross, Rita R.

    2015-01-01

    This study examines the current lives of thirty-five individuals who participated in high school gifted programs twenty years ago. The research specifically looked at educational attainment and career goals in terms of expressed aspirations in high school, using social media and other Internet sources. Results indicated continued support for the…

  7. Pro-inflammatory wnt5a and anti-inflammatory sFRP5 are differentially regulated by nutritional factors in obese human subjects.

    Directory of Open Access Journals (Sweden)

    Dominik M Schulte

    Full Text Available BACKGROUND: Obesity is associated with macrophage infiltration of adipose tissue. These inflammatory cells affect adipocytes not only by classical cytokines but also by the secreted glycopeptide wnt5a. Healthy adipocytes are able to release the wnt5a inhibitor sFRP5. This protective effect, however, was found to be diminished in obesity. The aim of the present study was to examine (1 whether obese human subjects exhibit increased serum concentrations of wnt5a and (2 whether wnt5a and/or sFRP5 serum concentrations in obese subjects can be influenced by caloric restriction. METHODOLOGY: 23 obese human subjects (BMI 44.1 ± 1.1 kg/m(2 and 12 age- and sex-matched lean controls (BMI 22.3 ± 0.4 kg/m(2 were included in the study. Obese subjects were treated with a very low-calorie diet (approximately 800 kcal/d for 12 weeks. Body composition was assessed by impedance analysis, insulin sensitivity was estimated by HOMA-IR and the leptin-to-adiponectin ratio and wnt5a and sFRP5 serum concentrations were measured by ELISA. sFRP5 expression in human adipose tissue biopsies was further determined on protein level by immunohistology. PRINCIPAL FINDINGS: Pro-inflammatory wnt5a was not measurable in any serum sample of lean control subjects. In patients with obesity, however, wnt5a became significantly detectable consistent with low grade inflammation in such subjects. Caloric restriction resulted in a weight loss from 131.9 ± 4.0 to 112.3 ± 3.2 kg in the obese patients group. This was accompanied by a significant decrease of HOMA-IR and leptin-to-adiponectin ratio, indicating improved insulin sensitivity. Interestingly, these metabolic improvements were associated with a significant increase in serum concentrations of the anti-inflammatory factor and wnt5a-inhibitor sFRP5. CONCLUSIONS/SIGNIFICANCE: Obesity is associated with elevated serum levels of pro-inflammatory wnt5a in humans. Furthermore, caloric restriction beneficially affects serum concentrations

  8. Using CHAINS, a QuickBASIC 4.5 Program, to Teach Single-Subject Experimentation with Humans

    Science.gov (United States)

    Dermer, Marshall Lev

    2004-01-01

    Students enrolled in a single-subject design course studied the repeated acquisition of response sequences by using CHAINS, a QuickBASIC 4.5 program, which runs in DOS or Windows. For about 2 months, students examined the learning of such sequences as a function of various treatments. Each week students graphed their data, discussed their…

  9. Pronounced between-subject and circadian variability in thymidylate synthase and dihydropyrimidine dehydrogenase enzyme activity in human volunteers

    NARCIS (Netherlands)

    Jacobs, Bart A W; Deenen, Maarten J; Pluim, Dick; van Hasselt, J G Coen; Krähenbühl, Martin D; van Geel, Robin M J M; de Vries, Niels; Rosing, Hilde; Meulendijks, Didier; Burylo, Artur M; Cats, Annemieke; Beijnen, Jos H; Huitema, Alwin D R; Schellens, Jan H M

    2016-01-01

    AIMS: The enzymatic activity of dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS) are important for the tolerability and efficacy of the fluoropyrimidine drugs. In the present study, we explored between-subject variability (BSV) and circadian rhythmicity in DPD and TS activity in h

  10. Human Pharmacokinetics of High Dose Oral Curcumin and Its Effect on Heme Oxygenase-1 Expression in Healthy Male Subjects

    Directory of Open Access Journals (Sweden)

    Uros Klickovic

    2014-01-01

    Full Text Available Purpose. Heme oxygenase-1 (HO-1 has been proposed to exert pharmacological benefits by its antioxidative and anti-inflammatory effects. HO-1 expression may be affected by the GT length polymorphism in the promoter region of the HO-1 gene. We investigated the inducibility of HO-1 by orally administered curcumin in healthy male subjects and its correlation with the GT length polymorphism. Methods. In an open label uncontrolled phase-1 pilot study, ten male subjects received 12 g of oral curcumin. To investigate the effects of the GT length polymorphism on the inducibility of HO-1, five subjects with homozygous short and five with homozygous long GT genotypes were studied. Plasma concentrations of curcumin, bilirubin, HO-1 mRNA, and protein expression in peripheral blood mononuclear cells (PBMCs were analyzed over 48 hours. Results. At a detection limit of 1 µg/mL curcumin could not be detected in plasma of any subject. Compared to baseline, HO-1 mRNA and protein levels were not induced in PBMCs at any time point up to 48 hours. There was no correlation between any of the parameters and GT length polymorphism. Conclusions. Oral curcumin administration has low bioavailability and does not induce HO-1 on mRNA or protein level in PBMCs.

  11. Vitamin K absorption and kinetics in human subjects after consumption of 13C-labeled phylloquinone from kale

    Science.gov (United States)

    The absorption and plasma elimination of vitamin K was investigated by uniformly labeling phylloquinone in kale with carbon-13 and feeding the kale to study subjects. Seven healthy volunteers ingested a single 400 g serving of kale with 30 g vegetable oil. The kale provided 156 nmol of phylloquino...

  12. Clinical study on the combined effect of capsaicin, green tea extract and essence of chicken on body fat content in human subjects.

    Science.gov (United States)

    Tsi, Daniel; Nah, Agatha Khow Hui; Kiso, Yoshinobu; Moritani, Toshio; Ono, Hiroyuki

    2003-12-01

    This study was conducted to assess the body fat content of free-living healthy human subjects taking a health supplement containing 0.4 mg capsaicin, 625 mg green tea extract (125 mg catechins and 50 mg caffeine) and 800 mg essence of chicken (CGTE). Subjects were advised to maintain their regular dietary habits and routine physical activity throughout study duration. Their body fat content was measured before and throughout the trial duration using a hand-grip body fat monitor. After 2 wk of supplementation with CGTE, the mean body fat percentage of males and female subjects was significantly less than the initial value (p essence of chicken could translate to a positive clinical effect by reducing approximately 460 g of body fat, following 2 wk of supplementation and the application of this natural health supplement for excess fat regulation, should be considered.

  13. Elevated aspartic proteinase secretion and experimental pathogenicity of Candida albicans isolates from oral cavities of subjects infected with human immunodeficiency virus.

    OpenAIRE

    De Bernardis, F; Chiani, P; Ciccozzi, M; Pellegrini, G; Ceddia, T; D'Offizzi, G; Quinti, I; Sullivan, P A; Cassone, A

    1996-01-01

    Isolates of Candida albicans from the oral cavities of subjects at different stages of human immunodeficiency virus (HIV) infection or uninfected controls were examined for (i) production of aspartic proteinase(s), a putative virulence-associated factor(s); (ii) the presence in the fungal genome of two major genes (SAP1 and SAP2) of the aspartic proteinase family; and (iii) experimental pathogenicity in a murine model of systemic infection. It was found that the fungal isolates from symptomat...

  14. DEVELOPING ‘STANDARD NOVEL ‘VAD’ TECHNIQUE’ AND ‘NOISE FREE SIGNALS’ FOR SPEECH AUDITORY BRAINSTEM RESPONSES FOR HUMAN SUBJECTS

    OpenAIRE

    Ranganadh Narayanam*

    2016-01-01

    In this research as a first step we have concentrated on collecting non-intra cortical EEG data of Brainstem Speech Evoked Potentials from human subjects in an Audiology Lab in University of Ottawa. The problems we have considered are the most advanced and most essential problems of interest in Auditory Neural Signal Processing area in the world: The first problem is the Voice Activity Detection (VAD) in Speech Auditory Brainstem Responses (ABR); The second problem is to identify the best De-...

  15. Subjective Response to Alcohol and Associated Craving in Heavy Drinkers vs. Alcohol Dependents: An Examination of Koob's Allostatic Model in Humans*

    OpenAIRE

    Bujarski, S; Ray, LA

    2014-01-01

    Background: Koob's allostatic model of addiction emphasizes the transition from positive reinforcement to negative reinforcement as dependence develops. This study seeks to extend this well-established neurobiological model to humans by examining subjective response to alcohol (SR) as a biobehavioral marker of alcohol reinforcement. Specifically, this study examines (a) differential SR in heavy drinkers (HDs) vs. alcohol dependent individuals (ADs) and (b) whether HDs and ADs differ in terms ...

  16. Delta Inulin Adjuvant Enhances Plasmablast Generation, Expression of Activation-Induced Cytidine Deaminase and B-Cell Affinity Maturation in Human Subjects Receiving Seasonal Influenza Vaccine.

    Directory of Open Access Journals (Sweden)

    Lei Li

    Full Text Available There is a major need for new adjuvants to improve the efficacy of seasonal and pandemic influenza vaccines. Advax is a novel polysaccharide adjuvant based on delta inulin that has been shown to enhance the immunogenicity of influenza vaccine in animal models and human clinical trials. To better understand the mechanism for this enhancement, we sought to assess its effect on the plasmablast response in human subjects. This pilot study utilised cryopreserved 7 day post-vaccination (7dpv peripheral blood mononuclear cell samples obtained from a subset of 25 adult subjects from the FLU006-12 trial who had been immunized intramuscularly with a standard dose of 2012 trivalent inactivated influenza vaccine (TIV alone (n=9 subjects or combined with 5mg (n=8 or 10mg (n=8 of Advax adjuvant. Subjects receiving Advax adjuvant had increased 7dpv plasmablasts, which in turn exhibited a 2-3 fold higher rate of non-silent mutations in the B-cell receptor CDR3 region associated with higher expression of activation-induced cytidine deaminase (AID, the major enzyme controlling BCR affinity maturation. Together, these data suggest that Advax adjuvant enhances influenza immunity in immunized subjects via multiple mechanisms including increased plasmablast generation, AID expression and CDR3 mutagenesis resulting in enhanced BCR affinity maturation and increased production of high avidity antibody. How Advax adjuvant achieves these beneficial effects on plasmablasts remains the subject of ongoing investigation.Australia New Zealand Clinical Trials Register ACTRN12612000709842 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=362709.

  17. Human bone hardness seems to depend on tissue type but not on anatomical site in the long bones of an old subject.

    Science.gov (United States)

    Ohman, Caroline; Zwierzak, Iwona; Baleani, Massimiliano; Viceconti, Marco

    2013-02-01

    It has been hypothesised that among different human subjects, the bone tissue quality varies as a function of the bone segment morphology. The aim of this study was to assess and compare the quality, evaluated in terms of hardness of packages of lamellae, of cortical and trabecular bones, at different anatomical sites within the human skeleton. The contralateral six long bones of an old human subject were indented at different levels along the diaphysis and at both epiphyses of each bone. Hardness value, which is correlated to the degree of mineralisation, of both cortical and trabecular bone tissues was calculated for each indentation location. It was found that the cortical bone tissue was harder (+18%) than the trabecular one. In general, the bone hardness was found to be locally highly heterogeneous. In fact, considering one single slice obtained for a bone segment, the coefficient of variation of the hardness values was up to 12% for cortical bone and up to 17% for trabecular bone. However, the tissue hardness was on average quite homogeneous within and among the long bones of the studied donor, although differences up to 9% among levels and up to 7% among bone segments were found. These findings seem not to support the mentioned hypothesis, at least not for the long bones of an old subject.

  18. Analysis of twenty phenolic compounds in human urine: hydrochloric acid hydrolysis, solid-phase extraction based on K2CO 3-treated silica, and gas chromatography tandem mass spectrometry.

    Science.gov (United States)

    Lu, Dasheng; Feng, Chao; Wang, Dongli; Lin, Yuanjie; Ip, Ho Sai Simon; She, Jianwen; Xu, Qian; Wu, Chunhua; Wang, Guoquan; Zhou, Zhijun

    2015-05-01

    This study developed a new method for the analysis of 20 phenolic compounds in human urine. The urine samples were prepared by hydrochloric acid (HCl) hydrolysis, liquid-liquid extraction (LLE), and solid-phase extraction (SPE) cleanup. We found that HCl hydrolysis is of similar effectiveness to, and much cheaper than, the traditional enzymatic method. Vanillic acid was co-eluted with butyl paraben and interfered with the determination of butyl paraben in urine. K2CO3-treated-silica-gel SPE was designed to efficiently eliminate interference from the endogenous organic acids (especially vanillic acid) in urine. After derivatization, the samples were analyzed by large-volume-injection gas chromatography-tandem mass spectrometry (LVI-GC-MS-MS). Good linearity (R (2) ≥ 0.996) was established in the range 0.1-100 ng mL(-1) for all analytes. Method detection limits (MDLs) were 0.7-9.8 pg mL(-1). Intraday (n = 5) and interday (n = 5 days) validation was performed, with satisfactory accuracy (recovery: 70-126 % and 73-107 %, respectively) and precision (RSD ≤ 19 %) at two levels (low: 0.1 and 0.5 ng mL(-1); high: 5 and 10 ng mL(-1)). The method was used in a population study and achieved more than 85 % detection for most analytes; mean analyte concentrations were in the range 0.01-185 ng mL(-1). The method is suitable for the analysis of multiple phenolic metabolites in human urine.

  19. Visual feedback of the moving arm allows complete adaptation of pointing movements to centrifugal and Coriolis forces in human subjects.

    Science.gov (United States)

    Bourdin, C; Gauthier, G; Blouin, J; Vercher, J L

    2001-03-23

    A classical visuo-manual adaptation protocol carried out on a rotating platform was used to test the ability of subjects to adapt to centrifugal and Coriolis forces when visual feedback of the arm is manipulated. Three main results emerge: (a) an early modification of the initial trajectory of the movements takes place even without visual feedback of the arm; (b) despite the change in the initial trajectory, the new external force decreases the accuracy of the pointing movements when vision is precluded; (c) a visual adaptive phase allows complete adaptation of the pointing movements performed in a modified gravitoinertial field. Therefore vision would be essential for subjects to completely adapt to centrifugal and Coriolis forces. However, other sensory signals (i.e. vestibular and proprioceptive) may constitute the basis for early but partial correction of the pointing movements.

  20. Objective confirmation of subjective measures of human well-being: evidence from the U.S.A.

    Science.gov (United States)

    Oswald, Andrew J; Wu, Stephen

    2010-01-29

    A huge research literature, across the behavioral and social sciences, uses information on individuals' subjective well-being. These are responses to questions--asked by survey interviewers or medical personnel--such as, "How happy do you feel on a scale from 1 to 4?" Yet there is little scientific evidence that such data are meaningful. This study examines a 2005-2008 Behavioral Risk Factor Surveillance System random sample of 1.3 million U.S. citizens. Life satisfaction in each U.S. state is measured. Across America, people's answers trace out the same pattern of quality of life as previously estimated, from solely nonsubjective data, in one branch of economics (so-called "compensating differentials" neoclassical theory, originally from Adam Smith). There is a state-by-state match (r = 0.6, P < 0.001) between subjective and objective well-being. This result has some potential to help to unify disciplines.

  1. Effect of rye bran on excretion of bile acids, cholesterol, nitrogen, and fat in human subjects with ileostomies.

    Science.gov (United States)

    Zhang, J X; Lundin, E; Hallmans, G; Adlercreutz, H; Andersson, H; Bosaeus, I; Aman, P; Stenling, R; Dahlgren, S

    1994-02-01

    The excretion of bile acids, cholesterol, dry matter, nitrogen, fat, and energy in ileostomy effluent, and plasma lipid concentrations were studied in eight subjects with ileostomies. The subjects consumed a wheat bread-based, low-fiber diet (LFD) for 3 wk and a rye bran bread-based, high-fiber diet (HFD) for 3 wk. The ileal excretion of dry matter, nitrogen, fat, and energy was higher during the HFD period. The daily excretion and the percentage of conjugated bile acids were significantly higher and the percentage of free bile acids lower in the ileostomy effluents during the HFD as compared with the LFD period. No significant difference in the excretion of cholesterol, net cholesterol, sterol, or net sterol was noted between the HFD and LFD periods. No significant differences in plasma concentrations of HDL-, LDL-, and total cholesterol, and apolipoprotein A-I and B were observed between the two 3-wk dietary periods.

  2. Identification of Direct and Indirect Social Network Effects in the Pathophysiology of Insulin Resistance in Obese Human Subjects

    OpenAIRE

    Henning, Christian H.C.A.; Nana Zarnekow; Johannes Hedtrich; Sascha Stark; Kathrin Türk; Matthias Laudes

    2014-01-01

    OBJECTIVE: The aim of the present study was to examine to what extent different social network mechanisms are involved in the pathogenesis of obesity and insulin-resistance. DESIGN: We used nonparametric and parametric regression models to analyse whether individual BMI and HOMA-IR are determined by social network characteristics. SUBJECTS AND METHODS: A total of 677 probands (EGO) and 3033 social network partners (ALTER) were included in the study. Data gathered from the probands include ant...

  3. "Thin" property and controversial subject matter: Yanner v. Eaton and property rights in human tissue and embryos.

    Science.gov (United States)

    Moses, Lyria Bennett; Gollan, Nicola

    2013-12-01

    This article examines the definitions of "property" offered by the majority of the High Court of Australia in the case of Yanner v Eaton (1999) 201 CLR 351, which involved a statute giving the Crown "property" in fauna. It argues that the majority judges in that case endorsed a flexible or "thin" conception of property that is consistent with recognition of property in "things" such as excised human tissue and in vitro human embryos, despite the many differences between such "things" and ordinary chattels. A similar flexible conception of property was also an important factor in the United Kingdom case of Yearworth v North Bristol NHS Trust[2010] QB 1.

  4. Twenty Practices of an Entrepreneurial University

    DEFF Research Database (Denmark)

    Gjerding, Allan Næs; Wilderom, Celeste P.M.; Cameron, Shona P.B.;

    2006-01-01

    similarities; especially that entrepreneurship within universities has to be welcomed and facilitated top-down, but organically occurs and develops bottom-up. Implementing entrepreneurship at universities is thus about stimulating a culture of organic intrapreneurship and we provide practical recommendations...... studies twenty organisational practices against which a University's entrepreneurship can be measured. These twenty practices or factors in effect formed the basis for an entrepreneurship audit. During a series of interviews, the extent to which the universities are seen as entrepreneurial...... by the interviewees was surveyed. We showed that the practices have been implemented only to various degrees and rather unsystematically. There are important differences among the universities, to some extent depending on the level of ambition that each university has regarding each practice. There are also important...

  5. 40 CFR 26.1703 - Prohibition of reliance on research involving intentional exposure of human subjects who are...

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Prohibition of reliance on research...), nursing women, or children. 26.1703 Section 26.1703 Protection of Environment ENVIRONMENTAL PROTECTION... Results of Human Research in EPA Actions § 26.1703 Prohibition of reliance on research...

  6. A Comparison of National Policies on Research Involving Human Subjects to Facilitate Review and Approval of Collaborative Research

    Science.gov (United States)

    2008-11-26

    procedures, undergoing acceptable, occupational training techniques (e.g. military pilots taking centrifuge training). However, experiments on...mean: 20 a living individual about whom an investigator (whether professional or student ) conducting research obtains (1) data through...which may arise from work activities. Human Tissue Act 2004 A licence is required for removal of tissue and for retention and use of tissue

  7. Intelligence in the Twenty-First Century

    OpenAIRE

    2000-01-01

    The author concludes that the world will most probably remain rife with conflict even in the twenty first century and that the traditional role of intelligence will not only continue but will increase in importance. He characterizes the international situation as being "more of the same historically"; that is, the existence of several different centers of power and mutual conflicts based solely on national interests. In order to protect and promote one's national interests, sovereign states w...

  8. Servicing the twenty-first century

    Energy Technology Data Exchange (ETDEWEB)

    Fisk, D. [DTLR, London (United Kingdom)

    2002-04-01

    Twentieth century governments have committed themselves to the principle of sustainable development. Efforts to fulfil this goal offer an insight into changes in building services provision in the opening decades of the new century. Sustainable development indicators are used to identify possible trends. The analysis also forms the basis for some speculative conjectures as a basis for a research agenda for the twenty-first century. (Author)

  9. Twenty-first century learning in afterschool.

    Science.gov (United States)

    Schwarz, Eric; Stolow, David

    2006-01-01

    Twenty-first century skills increasingly represent the ticket to the middle class. Yet, the authors argue, in-school learning is simply not enough to help students develop these skills. The authors make the case that after-school (or out-of-school) learning programs are emerging as one of the nation's most promising strategies for preparing young people for the workforce and civic life. Most school systems have significant limitations for teaching twenty-first century skills. They have the limits of time: with only six hours per day there is barely enough time to teach even the basic skills, especially for those students starting already behind. They have the limits of structure: typical school buildings and classrooms are not physically set up for innovative learning. They have the limits of inertia and bureaucracy: school systems are notoriously resistant to change. And perhaps most important, they have the limits of priorities: especially with the onset of the No Child Left Behind Act, schools are laserlike in their focus on teaching the basics and therefore have less incentive to incorporate twenty-first century skills. Meanwhile, the authors argue that after-school programs are an untapped resource with three competitive advantages. First, they enable students to work collaboratively in small groups, a setup on which the modern economy will increasingly rely. Second, they are well suited to project-based learning and the development of mastery. Third, they allow students to learn in the real-world contexts that make sense. Yet the after-school sector is fraught with challenges. It lacks focus-Is it child care, public safety, homework tutoring? And it lacks rigorous results. The authors argue that the teaching of twenty-first century skills should become the new organizing principle for afterschool that will propel the field forward and more effectively bridge in-school and out-of-school learning.

  10. Characterization of human myotubes from type 2 diabetic and non-diabetic subjects using complementary quantitative mass spectrometric methods

    DEFF Research Database (Denmark)

    Thingholm, Tine E; Bak, Steffen; Beck-Nielsen, Henning

    2011-01-01

    2 diabetes. Several abnormalities have been identified in skeletal muscle from type 2 diabetic subjects, however, the exact molecular mechanisms leading to the diabetic phenotype has still not been found. Here we present a large-scale study in which we combine a quantitative proteomic discovery....... Twelve proteins were, however, differentially expressed between the three different groups. Thirty-six proteins were chosen for further analysis and validation using SRM based on the regulation identified in the iTRAQ discovery study. The abundance of adenosine deaminase was considerably down...

  11. The Total Antioxidant Power of Semen and Its Correlation with the Fertility Potential of Human Male Subjects

    Science.gov (United States)

    Pahune, Pranjali Prabhakarrao; Choudhari, Ajay Rajeshwar; Muley, Parikshit Ashok

    2013-01-01

    Background: There are growing evidences that the damage which is caused to the spermatozoa by the Reactive Oxygen Species (ROS) plays a key role in the male infertility. The seminal plasma is endowed with many enzymatic and nonenzymatic antioxidants which protect the spermatozoa against oxidative stress.The present study was undertaken by using a simple, colourimetric, ferric reducing, antioxidant power for assessing the total antioxidant power rather than the individual antioxidants. The measurement of the individual antioxidants in the seminal plasma, such as Superoxide Dismutase, Vitamin E, etc. is time consuming, which often requires sophisticated and expensive techniques and these measurements may not correlate with the quality of semen. Aim: To evaluate the total antioxidant capacity of seminal plasma by estimating the Ferric Reducing Antioxidant Power (FRAP) of semen in different groups of subjects and to correlate it with the different seminogram parameters. Material and Methods: The semen samples were obtained from 150 male partners of infertile couples who attended the Reproductive Biology Unit (Infertility Clinic) of the Department of Physiology, MGIMS, Sevagram, who were aged 20-58 years and they were analyzed for the routine seminogram parameters. All the subjects were categorized into two main groups, A. The subjects with abnormal ejaculates, who were further sub classified into the following groups i) Asthenoteratozoospermics (n=25) ii) Oligoasthenoteratozoospermics (n=26) and iii) Azoospermics (n=19) and B. The subjects with normal ejaculates (n=80). The total antioxidant power was measured spectrophotometrically by using the Ferric Reducing Antioxidant Power (FRAP) assay. Results: The Total Antioxidant Capacity (TAC) was found to be significantly lower in the abnormal ejaculates than in the normal ejaculates. A statistically significant positive correlation was observed between the TAC and all the seminogram parameters such as the sperm

  12. Reinforcing, subject-rated, performance and physiological effects of methylphenidate and d-amphetamine in stimulant abusing humans.

    Science.gov (United States)

    Stoops, William W; Glaser, Paul E A; Fillmore, Mark T; Rush, Craig R

    2004-12-01

    Methylphenidate has potential for abuse because it produces behavioural effects similar to those observed with other abused stimulants, such as d-amphetamine and cocaine. The aim of this study was to further characterize the abuse potential of oral methylphenidate relative to oral d-amphetamine. Ten drug-abusing volunteers were recruited to participate in this study, which consisted of seven dose conditions: methylphenidate (16, 32 and 48 mg), d-amphetamine (8, 16 and 24 mg) and placebo. The reinforcing effects of these drugs were assessed during a self-administration session (preceded by a sampling session for each condition) with a modified progressive-ratio procedure. Subject-rated, performance and physiological effects were assessed concurrently during both the sampling and self-administration sessions. The intermediate dose of methylphenidate and d-amphetamine increased responding significantly above placebo levels. Both methylphenidate and d-amphetamine produced dose-dependent increases in stimulant-like subject ratings (e.g. Active, Alert, or Energetic and High), but the effects of these drugs were not isomorphic. These findings are consistent with epidemiological data and previous findings from laboratory studies that suggest methylphenidate has at least some abuse potential.

  13. Effect of different curcuminoid supplement dosages on total in vivo antioxidant capacity and cholesterol levels of healthy human subjects.

    Science.gov (United States)

    Pungcharoenkul, Kanit; Thongnopnua, Phensri

    2011-11-01

    The impact of consuming curcuminoids containing curcumin at 500 mg/day and 6 g/day for 7 days on plasma antioxidant capacity and serum cholesterol level were determined by using vitamin E 200 IU/day consumption as a comparison. Group A and group B subjects consumed 500 mg and 6 g curcumin, respectively, but group C subjects consumed vitamin E 200 IU. By using the oxygen radical absorbance capacity (ORAC) assay, it was found that plasma antioxidant capacity of group A rose from a baseline of 13% to 24% on day 1 and day 7, as against a 19-20% increase for group B. Serum cholesterol and triglyceride levels were significantly decreased after curcumin treatment at 500 mg/day. By consuming vitamin E, both ORAC values and plasma α-tocopherol concentrations were significantly increased, but only very slight responses on serum cholesterol or triglyceride levels were observed. It is therefore suggested that curcumin supplement would not be appropriate for healthy people except for reducing serum cholesterol or triglyceride levels. The dosage of a daily curcumin supplement at 500 mg is more effective than 6 g, although vitamin E is also considered to be an effective antioxidant supplement.

  14. A yang-promoting Chinese herbal suppository preparation enhances the antioxidant status of red cells in male human subjects.

    Science.gov (United States)

    Mak, D H F; Chiu, P Y; Poon, M K T; Ng, T T L; Chung, Y K; Lam, B Y H; Du, Y; Ko, K M

    2004-07-01

    In the 16-week pilot study, the effect of a Yang-promoting Chinese herbal suppository preparation (VI-28) on the red cell antioxidant status was examined in 31 healthy male subjects aged 41-66 years old. VI-28 treatment for 12 weeks (one suppository (0.3 g) daily for week 1-4; one every 2 days for week 5-8; one every 3 days for week 9-12) produced a time/dose-dependent alteration in red cell antioxidant status. The VI-28-induced change is characterized by a slight depletion in cellular reduced glutathione (GSH) level and a decrease in susceptibility to peroxide-induced lipid peroxidation as well as increases in catalase (CAT) and Cu-Zn-superoxide dismutase (SOD) activities. While a reversal trend of change was observed in cellular GSH level, the susceptibility to lipid peroxidation as well as the CAT activity after the cessation of treatment for 4 weeks, the SOD activity exhibited a protracted increase. The results indicate that VI-28 treatment enhances red cell antioxidant status in male subjects. The beneficial effect of VI-28 treatment on red cells may re fl ect a corresponding change in antioxidant status of peripheral tissues.

  15. GH receptor signaling in skeletal muscle and adipose tissue in human subjects following exposure to an intravenous GH bolus

    DEFF Research Database (Denmark)

    Jørgensen, Jens O L; Jessen, Niels; Pedersen, Steen Bønløkke

    2006-01-01

    Growth hormone (GH) regulates muscle and fat metabolism, which impacts on body composition and insulin sensitivity, but the underlying GH signaling pathways have not been studied in vivo in humans. We investigated GH signaling in biopsies from muscle and abdominal fat obtained 30 (n = 3) or 60 (n...... in vivo model may be used to study the mechanisms subserving the actions of GH on substrate metabolism and insulin sensitivity in muscle and fat....

  16. Cosmology and Particle Physics/Human evolution and infectious disease/Cognitive evolution (1 page - 3 subjects)

    CERN Multimedia

    Carroll, Sean; Hauser, Marc D

    2007-01-01

    "On the theoretical side, particle phenomenologists will continue to develop physics beyond the Standard Model; string theorists are connecting ore strongly to cosmology and astrophysics/With the recent advent of whole-genome sequencing and increasingly complete surveys of genetic variation, we are now routinely studying 500 thousand variations at a time, enabling complete genome wide surveys in many human populations and in specific disease populations./The most exciting developments today sit at the intersection between science and philosophy.

  17. Occupancy of Nociceptin/Orphanin FQ Peptide Receptors by the Antagonist LY2940094 in Rats and Healthy Human Subjects.

    Science.gov (United States)

    Raddad, Eyas; Chappell, Amy; Meyer, Jeffery; Wilson, Alan; Ruegg, Charles E; Tauscher, Johannes; Statnick, Michael A; Barth, Vanessa; Zhang, Xin; Verfaille, Steven J

    2016-09-01

    Therapeutic benefits from nociceptin opioid peptide receptor (NOP) antagonism were proposed for obesity, eating disorders, and depression. LY2940094 ([2-[4-[(2-chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-3-methyl-pyrazol-1-yl]-3-pyridyl]methanol) is a novel, orally bioavailable, potent, and selective NOP antagonist. We studied NOP receptor occupancy (RO) after single oral LY2940094 doses in rat hypothalamus and human brain by use of liquid chromatography with tandem mass spectrometry (LC-MS/MS) (LSN2810397) and positron emission tomography (PET) ([(11)C]NOP-1A) tracers, respectively. A bolus plus constant infusion tracer protocol with PET was employed in humans at 2.5 and 26.5 hours after administration of the LY2940094 dose. The RO was calculated from the change in regional distributional volume (VT) corrected for nondisplaceable volume using Lasson plots. The RO followed a simple Emax relationship to plasma LY2940094 concentration, reaching near complete occupancy in both species. For rat hypothalamus, the plasma concentration at half-maximum RO (EC50) was 5.8 ng/ml. In humans, LY2940094 was well tolerated and safe over the 4-40 mg dose range, and it peaked in plasma at 2 to 6 hours after a 1- to 2-hour lag, with approximate dose-proportional exposure. After 4-40 mg doses, NOP RO was similar across the prefrontal cortex, occipital cortex, putamen, and thalamus, with EC50 of 2.94 to 3.46 ng/ml, less than 2-fold lower than in rats. Over 4-40 mg doses, LY2940094 mean plasma levels at peak and 24 hours were 7.93-102 and 1.17-14.1 ng/ml, corresponding to the cross-region average NOP RO of 73%-97% and 28%-82%, respectively. The rat EC50 translates well to humans. LY2940094 readily penetrates the human brain, and a once-daily oral dose of 40 mg achieves sustainably high (>80%) NOP RO levels suitable for testing clinical efficacy.

  18. Kinetic Modeling of the Tau PET Tracer (18)F-AV-1451 in Human Healthy Volunteers and Alzheimer Disease Subjects.

    Science.gov (United States)

    Barret, Olivier; Alagille, David; Sanabria, Sandra; Comley, Robert A; Weimer, Robby M; Borroni, Edilio; Mintun, Mark; Seneca, Nicholas; Papin, Caroline; Morley, Thomas; Marek, Ken; Seibyl, John P; Tamagnan, Gilles D; Jennings, Danna

    2017-07-01

    (18)F-AV-1451 is currently the most widely used of several experimental tau PET tracers. The objective of this study was to evaluate (18)F-AV-1451 binding with full kinetic analysis using a metabolite-corrected arterial input function and to compare parameters derived from kinetic analysis with SUV ratio (SUVR) calculated over different imaging time intervals. Methods:(18)F-AV-1451 PET brain imaging was completed in 16 subjects: 4 young healthy volunteers (YHV), 4 aged healthy volunteers (AHV), and 8 Alzheimer disease (AD) subjects. Subjects were imaged for 3.5 h, with arterial blood samples obtained throughout. PET data were analyzed using plasma and reference tissue-based methods to estimate the distribution volume, binding potential (BPND), and SUVR. BPND and SUVR were calculated using the cerebellar cortex as a reference region and were compared across the different methods and across the 3 groups (YHV, AHV, and AD). Results: AD demonstrated increased (18)F-AV-1451 retention compared with YHV and AHV based on both invasive and noninvasive analyses in cortical regions in which paired helical filament tau accumulation is expected in AD. A correlation of R(2) > 0.93 was found between BPND (130 min) and SUVR-1 at all time intervals. Cortical SUVR curves reached a relative plateau around 1.0-1.2 for YHV and AHV by approximately 50 min, but increased in AD by up to approximately 20% at 110-130 min and approximately 30% at 160-180 min relative to 80-100 min. Distribution volume (130 min) was lower by 30%-35% in the YHV than AHV. Conclusion: Our data suggest that although (18)F-AV-1451 SUVR curves do not reach a plateau and are still increasing in AD, an SUVR calculated over an imaging window of 80-100 min (as currently used in clinical studies) provides estimates of paired helical filament tau burden in good correlation with BPND, whereas SUVR sensitivity to regional cerebral blood changes needs further investigation. © 2017 by the Society of Nuclear Medicine and

  19. Quantitative determination of caffeine and alcohol in energy drinks and the potential to produce positive transdermal alcohol concentrations in human subjects.

    Science.gov (United States)

    Ayala, Jessica; Simons, Kelsie; Kerrigan, Sarah

    2009-01-01

    The purpose of this study was to determine whether non-alcoholic energy drinks could result in positive "alcohol alerts" based on transdermal alcohol concentration (TAC) using a commercially available electrochemical monitoring device. Eleven energy drinks were quantitatively assayed for both ethanol and caffeine. Ethanol concentrations for all of the non-alcoholic energy drinks ranged in concentration from 0.03 to 0.230% (w/v) and caffeine content per 8-oz serving ranged from 65 to 126 mg. A total of 15 human subjects participated in the study. Subjects consumed between 6 and 8 energy drinks over an 8-h period. The SCRAM II monitoring device was used to determine TACs every 30 min before, during, and after the study. None of the subjects produced TAC readings that resulted in positive "alcohol alerts". TAC measurements for all subjects before, during and after the energy drink study period (16 h total) were energy drink that greatly exceeds what would be considered typical. Based on these results, it appears that energy drink consumption is an unlikely explanation for elevated TACs that might be identified as potential drinking episodes or "alcohol alerts" using this device.

  20. [Sulfonamide-research on human subjects in Nazi concentration camps: a critical re-evaluation of the epistemological and ethical dimension].

    Science.gov (United States)

    Roelcke, Volker

    2009-01-01

    Existing scholarship on the experiments performed in concentration camps beginning in 1942 on the value of sulfonamides in treatment of wound infections, in which inmates were used as experimental subjects, maintains that not only were the experiments ethically and legally completely reprehensible and unacceptable, but that they were also bad science in the sense that they were investigating questions that had already been resolved by valid medical research. In contrast to this, the paper argues on the basis of contemporary publications that the value of sulfonamides in the treatment of wound infections, including gas gangrene infections, was not yet established, that is, that the questions pursued by the experiments had not been resolved. It also argues that regarding their "design" and methodical principles, the experiments directly followed the rationality of contemporary clinical trials and animal experiments. However, for the step from animal to the human experiment, the experimental "objects" were only in regard to their body, but not to their individuality and subjectivity regarded as "human". In a concluding section, the paper lines out some implications for an adequate historical reconstruction of medical research on humans, in particular the importance of a combined focus on the scientific rationality as well as explicit or implicit value hierarchies. Further, the article points to the potential impact of such a revised image of the sulfonamide experiments for present day debates on the ethics of medical research.

  1. Evaluation through in vivo reflectance confocal microscopy of the cutaneous neurogenic inflammatory reaction induced by capsaicin in human subjects

    Science.gov (United States)

    Căruntu, Constantin; Boda, Daniel

    2012-08-01

    We perform an in vivo analysis of the effects of capsaicin on cutaneous microvascularization. A total of 29 healthy subjects are administered a solution of capsaicin (CAP group) or a vehicle solution (nonCAP group) on the dorsal side of the nondominant hand. The evaluation is performed using in vivo reflectance confocal microscopy (RCM). Ten minutes after administration, the area of the section, the perimeter, and the Feret's diameter of the capillaries in the dermal papillae become significantly larger in the CAP group as against the nonCAP group, and this difference is maintained until the conclusion of the experiment. In vivo RCM allows the investigation of cutaneous vascular reactions induced by capsaicin. As such, this method may constitute an useful technique both for research and clinical practice.

  2. Human Cumulative Irritation Tests of Common Preservatives Used in Personal Care Products: A Retrospective Analysis of Over 45 000 Subjects.

    Science.gov (United States)

    Walters, Russel M; Khanna, Preeya; Hamilton, Matthew; Mays, David A; Telofski, Lorena

    2015-11-01

    The cumulative irritation test (CIT) is an accepted method used to evaluate the skin irritation potential and safety of individual ingredients and formulas of leave-on skin care and cosmetic compounds. Here, we report the results of CITs collected by JOHNSON & JOHNSON Consumer Companies, Inc. (Skillman, NJ), part of an extensive tiered program to evaluate product safety. In the CIT, test formulations were applied to the skin of adults (18-70 years) with no known skin disease or allergies, 3 times per week for 2 weeks using semi-occlusive clinical patches. Preservatives were 1 of up to 16 components of test formulas, and included ethylenediaminetetraacetic acid, diazolidinyl urea, 1,3-Bis(hydroxymethyl)-5,5-dimethylimidazolidine-2,4-dione, parabens, isothiazolinone, phenoxyethanol, sorbates, or benzoates. Skin sites were scored after each patch removal using a 5-point scale, with 0 = no visible reaction and 4 = erythema, marked edema, or substantial vesiculation. Scores were reported as percentage of maximal irritation score. Data were analyzed from 1363 CIT studies (over 45 000 subjects). There were no significant differences in percentage of maximal scores between formulas grouped by preservative types (p > .1). Median score across the entire dataset was 0.44, with most formulas showing none or mild irritation. Although seasonal variations were observed, no correlation was noted between score and preservative concentration. In conclusion, in a large, normal subject dataset, preservatives at typical in-use concentrations did not appear to contribute to skin irritation. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. A factorial study of fat and fibre changes and sodium restriction on blood pressure of human hypertensive subjects.

    Science.gov (United States)

    Sciarrone, S E; Rouse, I L; Rogers, P; Beilin, L J

    1990-03-01

    1. Diets used to reduce sodium intake often involve changes in fats and fibre which might themselves affect blood pressure and/or lipid metabolism. To evaluate the relative importance of these dietary changes for the management of hypertension we have studied the independent and additive effects of sodium restriction (less than 60 mmol/day) and a low fat (30% energy), high P/S ratio (1.0), high fibre (30-50 g/day) 'cholesterol lowering' diet. 2. Ninety-five hypertensives entered a four group parallel study with a factorial design. Following 5 weeks familiarization subjects [BP range 109/66-168/105 mmHg] were randomly assigned to either a 'low sodium, cholesterol lowering' diet or a 'low sodium, cholesterol maintaining' diet. Half the subjects in each group were then assigned to 100 mmol/day NaCl supplement and the remainder to placebo. These diets were continued for 8 weeks. Seventy-nine of the 91 hypertensives who completed the study were on antihypertensive therapy throughout. 3. Mean urinary sodium excretion decreased from 137 (54 mmol/day (n = 43) at baseline (B) to 52 (32) mmol/day (n = 45, P = 0.0001) during intervention (I) in the low sodium groups and remained unchanged in the groups which received slow sodium (B = 129 [46], n = 43; I = 134 [29], n = 42). Diet record and plasma fatty acid analysis confirmed that the dietary aims of the study were achieved. 4. Sodium restriction reduced supine and standing systolic BP by a mean (+/- s.e.m.) of 6 +/- 2 and 6 +/- 4 mmHg, respectively (P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

  4. [The Gulf War Syndrome twenty years on].

    Science.gov (United States)

    Auxéméry, Y

    2013-10-01

    After Operation Desert Storm which took place in Iraq from August 1990 to July 1991 involving a coalition of 35 countries and a 700,000 strong contingent of mainly American men, some associations of war veterans, the media and researchers described a new diagnostic entity: the Gulf War Syndrome (GWS). GWS seems to be a new disorder which associates a litany of functional symptoms integrating the musculoskeletal, digestive, tegumentary and neurosensory systems. The symptoms presented do not allow a syndrome already known to be considered and the aetiology of the clinical picture remains unexplained, an increasing cause for concern resulting from the extent of the phenomenon and its media coverage. It quickly appears that there is no consensus amongst the scientific community concerning a nosographic description of GWS: where can all these functional complaints arise from? Different aetiopathogenic hypotheses have been studied by the American administration who is attempting to incriminate exposure to multiple risks such as vaccines and their adjuvants, organophosphorous compounds, pyridostigmine (given to the troops for the preventive treatment of the former), impoverished uranium, and the toxic emanations from oil well fires. But despite extremely in-depth scientific investigations, 10 years after the end of the war, no objective marker of physical suffering has been retained to account for the disorders presented. It would appear that the former soldiers are in even better objective health than the civil population whereas their subjective level of health remains low. Within this symptomatic population, some authors have begun to notice that the psychological disorders appear and persist associating: asthenia, fatigability, mood decline, sleep disorders, cognitive disorders and post-traumatic stress disorder (PTSD). Within the nosological framework, does GWS cause functional disorders or somatisation? Finally, 20 years after the end of the fighting, only PTSD has

  5. 云南省大理州大片形吸虫群体感染26例分析%Twenty six cases of human Fasciola gigantica infection in Dali, Yunnan province

    Institute of Scientific and Technical Information of China (English)

    陈木新; 罗家军; 陈家旭; 艾琳; 许学年; 吕山; 焦建明; 苏慧勇; 臧伟; 诸廷俊; 蔡玉春

    2012-01-01

    预防控制部门应加强对当地居民健康教育,了解生食水生植物的潜在危害,预防本病的发生.%Objective The aim of the study was to investigate the epidemic situation,clinical symptom,diagnosis and epidemiological characteristics of human Fasciola gigantica infection in Dali,Yunnan province.It will also provide a scientific basis for fasciolosis control and prevention.Methods Epidemic data were collected and patient's clinical signs and symptoms were studied.Serum soluble antigen of Fasciola gigantica of patients and part of family members and health people in the same village was detected using enzyme-linked immunosorbent assay (ELISA) and the eggs of Fasciola gigantica in stool were observed under microscope.Sequencing and PCR amplification of Fasciola gigantica eggs had been done.Sequencing results were analyzed using basic local alignment search tool (BLAST) program of the U.S.National Center for Biotechnology Information (NCBI) and the similarity of the two in the sequence of nucleic acid was compared.Furthermore,patients were experimentally given orally therapeutic doses of Triclabendazole 10 mg·kg-1·d-1 daily for 2 days,and kept in the hospital for observation for one week.Moreover,host and vector were investigated in the surrounding ditches of Dali prefecture and Limnaea peregra snail samples were collected.All the snails were squashed by glass sheet in order to detect the cercarie.Cow dung and sheep manure was collected in the Limnaea peregra distribution environment,and the eggs in the feces were checked by microscope after washing and precipitation.Results All the 26 patients had a continued hyperpyrexia with distinct alimentary system symptoms of nausea,vomiting,stomachache,abdominal distension as well as hepatomegaly,sensitive to percussion,different levels of liver damage detected by CT.All the patients had an eaten history of raw Herba Houttuyniae and other aquatic plants,and the course of the disease was similar,with the

  6. Non-AIDS definings malignancies among human immunodeficiency virus-positive subjects: Epidemiology and outcome after two decades of HAART era

    Science.gov (United States)

    Brugnaro, Pierluigi; Morelli, Erika; Cattelan, Francesca; Petrucci, Andrea; Panese, Sandro; Eseme, Franklyn; Cavinato, Francesca; Barelli, Andrea; Raise, Enzo

    2015-01-01

    Highly active antiretroviral therapy (HAART) for human immunodeficiency virus (HIV) infection has been widely available in industrialized countries since 1996; its widespread use determined a dramatic decline in acquired immunodeficiency syndrome (AIDS)-related mortality, and consequently, a significant decrease of AIDS-defining cancers. However the increased mean age of HIV-infected patients, prolonged exposure to environmental and lifestyle cancer risk factors, and coinfection with oncogenic viruses contributed to the emergence of other malignancies that are considered non-AIDS-defining cancers (NADCs) as a relevant fraction of morbidity and mortality among HIV-infected people twenty years after HAART introduction. The role of immunosuppression in the pathogenesis of NADCs is not well defined, and future researches should investigate the etiology of NADCs. In the last years there is a growing evidence that intensive chemotherapy regimens and radiotherapy could be safely administrated to HIV-positive patients while continuing HAART. This requires a multidisciplinary approach and a close co-operation of oncologists and HIV-physicians in order to best manage compliance of patients to treatment and to face drug-related side effects. Here we review the main epidemiological features, risk factors and clinical behavior of the more common NADCs, such as lung cancer, hepatocellular carcinoma, colorectal cancer and anal cancer, Hodgkin’s lymphoma and some cutaneous malignancies, focusing also on the current therapeutic approaches and preventive screening strategies. PMID:26279983

  7. Activated human neonatal CD8+ T cells are subject to immunomodulation by direct TLR2 or TLR5 stimulation.

    LENUS (Irish Health Repository)

    McCarron, Mark

    2012-02-01

    In conditions of optimal priming, the neonate possesses competency to mount quantitatively adult-like responses. Vaccine formulations containing sufficiently potent adjuvants may overcome the neonate\\'s natural tendency for immunosuppression and provoke a similarly robust immune response. TLR expression on T cells represents the possibility of directly enhancing T cell immunity. We examined the ex vivo responsiveness of highly purified human cord blood-derived CD8(+) T cells to direct TLR ligation by a repertoire of TLR agonists. In concert with TCR stimulation, only Pam(3)Cys (palmitoyl-3-Cys-Ser-(Lys)(4)) and flagellin monomers significantly enhanced proliferation, CD25(+) expression, IL-2, IFN-gamma, TNF-alpha, and intracellular granzyme B expression. TLR2 and TLR5 mRNA was detected in the CD8(+) T cells. Blocking studies confirmed that the increase in IFN-gamma production was by the direct triggering of surface TLR2 or TLR5. The simultaneous exposure of CD8(+) T cells to both TLR agonists had an additive effect on IFN-gamma production. These data suggest that a combination of the two TLR ligands would be a potent T cell adjuvant. This may represent a new approach to TLR agonist-based adjuvant design for future human neonatal vaccination strategies requiring a CD8(+) component.

  8. Safety analysis of a Russian phage cocktail: From MetaGenomic analysis to oral application in healthy human subjects

    Energy Technology Data Exchange (ETDEWEB)

    McCallin, Shawna, E-mail: semccallin@yahoo.com [Nestlé Research Centre, Nestec Ltd, Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland); Alam Sarker, Shafiqul, E-mail: sasarker@icddrb.org [International Centre for Diarrhoeal Diseases Research, Bangladesh (icddr,b), 68 Shaheed Tajuddin Ahmed Sharani, Mohakhali, Dhaka 1212 (Bangladesh); Barretto, Caroline, E-mail: Caroline.Barretto@rdls.nestle.com [Nestlé Research Centre, Nestec Ltd, Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland); Sultana, Shamima, E-mail: shamima@icddrb.org [International Centre for Diarrhoeal Diseases Research, Bangladesh (icddr,b), 68 Shaheed Tajuddin Ahmed Sharani, Mohakhali, Dhaka 1212 (Bangladesh); Berger, Bernard, E-mail: bernard.berger@rdls.nestle.com [Nestlé Research Centre, Nestec Ltd, Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland); Huq, Sayeda, E-mail: sayeeda@mail.icddrb.org [International Centre for Diarrhoeal Diseases Research, Bangladesh (icddr,b), 68 Shaheed Tajuddin Ahmed Sharani, Mohakhali, Dhaka 1212 (Bangladesh); Krause, Lutz, E-mail: ltz.krause@gmail.com [Nestlé Research Centre, Nestec Ltd, Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland); Bibiloni, Rodrigo, E-mail: Rodrigo.Bibiloni@agresearch.co.nz [Nestlé Research Centre, Nestec Ltd, Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland); Schmitt, Bertrand, E-mail: bertrand.schmitt@rdls.nestle.com [Nestlé Research Centre, Nestec Ltd, Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland); Reuteler, Gloria, E-mail: gloria.reuteler@rdls.nestle.com [Nestlé Research Centre, Nestec Ltd, Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland); Brüssow, Harald, E-mail: harald.bruessow@rdls.nestle.com [Nestlé Research Centre, Nestec Ltd, Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland)

    2013-09-01

    Phage therapy has a long tradition in Eastern Europe, where preparations are comprised of complex phage cocktails whose compositions have not been described. We investigated the composition of a phage cocktail from the Russian pharmaceutical company Microgen targeting Escherichia coli/Proteus infections. Electron microscopy identified six phage types, with numerically T7-like phages dominating over T4-like phages. A metagenomic approach using taxonomical classification, reference mapping and de novo assembly identified 18 distinct phage types, including 7 genera of Podoviridae, 2 established and 2 proposed genera of Myoviridae, and 2 genera of Siphoviridae. De novo assembly yielded 7 contigs greater than 30 kb, including a 147-kb Myovirus genome and a 42-kb genome of a potentially new phage. Bioinformatic analysis did not reveal undesired genes and a small human volunteer trial did not associate adverse effects with oral phage exposure. - Highlights: • We analyzed the composition of a commercial Russian phage cocktail. • The cocktail consists of at least 10 different phage genera. • No undesired genes were detected. • No adverse effects were seen upon oral application in a small human clinical trial.

  9. Dose-response study of N,N-dimethyltryptamine in humans. II. Subjective effects and preliminary results of a new rating scale.

    Science.gov (United States)

    Strassman, R J; Qualls, C R; Uhlenhuth, E H; Kellner, R

    1994-02-01

    Validation of animal models of hallucinogenic drugs' subjective effects requires human data. Previous human studies used varied groups of subjects and assessment methods. Rating scales for hallucinogen effects emphasized psychodynamic principles or the drugs' dysphoric properties. We describe the subjective effects of graded doses of N,N-dimethyltryptamine (DMT), an endogenous hallucinogen and drug of abuse, in a group of experienced hallucinogen users. We also present preliminary data from a new rating scale for these effects. Twelve highly motivated volunteers received two doses (0.04 and 0.4 mg/kg) of intravenous (IV) dimethyltryptamine fumarate "nonblind," before entering a double-blind, saline placebo-controlled, randomized study using four doses of IV DMT. Subjects were carefully interviewed after resolution of drug effects, providing thorough and systematic descriptions of DMT's effects. They also were administered a new instrument, the Hallucinogen Rating Scale (HRS). The HRS was drafted from interviews obtained from an independent sample of 19 experienced DMT users, and modified during early stages of the study. Psychological effects of IV DMT began almost immediately after administration, peaked at 90 to 120 seconds, and were almost completely resolved by 30 minutes. This time course paralleled DMT blood levels previously described. Hallucinogenic effects were seen after 0.2 and 0.4 mg/kg of dimethyltryptamine fumarate, and included a rapidly moving, brightly colored visual display of images. Auditory effects were less common. "Loss of control," associated with a brief, but overwhelming "rush," led to a dissociated state, where euphoria alternated or coexisted with anxiety. These effects completely replaced subjects' previously ongoing mental experience and were more vivid and compelling than dreams or waking awareness. Lower doses, 0.1 and 0.05 mg/kg, were primarily affective and somaesthetic, while 0.1 mg/kg elicited the least desirable effects

  10. On using the Microsoft Kinect$^{\\rm TM}$ sensors to determine the lengths of the arm and leg bones of a human subject in motion

    CERN Document Server

    Malinowski, M J

    2015-01-01

    The present study is part of a broader programme, exploring the possibility of involving the Microsoft Kinect$^{\\rm TM}$ sensor in the analysis of human motion. We examine the output obtained from the two available versions of this sensor in relation to the variability of the estimates of the lengths of eight bones belonging to the subject's extremities: of the humerus (upper arm), ulna (lower arm, forearm), femur (upper leg), and tibia (lower leg, shank). Large systematic effects in the output of the two sensors have been observed.

  11. Study of air pollution: Effects of ozone on neuropeptide-mediated responses in human subjects. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Boushey, H.A.

    1991-11-01

    The study examined the hypothesis that ozone inactivates the enzyme, neutral endopeptidase, responsible for limiting the effects of neuropeptides released from afferent nerve endings. Cough response of capsaicin solution delivered from a nebulizer at 2 min. intervals until two or more coughs were produced. Other endpoints measured included irritative symptoms as rated by the subjects on a nonparametric scale, spirometry, of each concentration of ozone were compared to those of filtered air in a single-blind randomized sequence. The results indicate that a 2 h. exposure to 0.4 ppm of ozone with intermittent light exercise alters the sensitivity of airway nerves that mediate the cough response to inhaled materials. This dose of ozone also caused a change in FEV1. A lower level of ozone, 0.02 ppm, caused a change in neither cough threshold nor FEV1, even when the duration of exposure was extended to three hours. The findings are consistent with the author's hypothesis that ozone may sensitize nerve endings in the airways by inactivating neutral endopeptidase, an enzyme that regulates their activity, but they do not demonstrate that directly examining an effect directly mediated by airway nerves allows detection of effects of ozone at doses below those causing effects detected by standard tests of pulmonary function.

  12. Effects of experimental weight perturbation on skeletal muscle work efficiency, fuel utilization, and biochemistry in human subjects.

    Science.gov (United States)

    Goldsmith, Rochelle; Joanisse, Denis R; Gallagher, Dympna; Pavlovich, Katherine; Shamoon, Elisabeth; Leibel, Rudolph L; Rosenbaum, Michael

    2010-01-01

    Maintenance of a body weight 10% above or below that "customary" for lean or obese individuals results in respective increases or decreases in the energy expended in low levels of physical activity (nonresting energy expenditure, NREE). These changes are greater than can be accounted for by the altered body weight or composition and are due mainly to altered skeletal muscle work efficiency at low levels of power generation. We performed biochemical analysis of vastus lateralis muscle needle biopsy samples to determine whether maintenance of an altered body weight was associated with changes in skeletal muscle histomorphology. We found that the maintenance of a 10% reduced body weight was associated with significant declines in glycolytic (phosphofructokinase, PFK) enzyme activity and, in particular, in the ratio of glycolytic to oxidative (cytochrome c oxidase, COX) enzyme activity without significant changes in the activities of enzymes relevant to mitochondrial density, respiratory chain activity, or fuel transport; or in skeletal muscle fiber type or glycogen stores. The fractional change in the ratio of PFK/COX activity in subjects following weight loss was significantly correlated with changes in the systemic respiratory exchange ratio (RER) and measures of mechanical efficiency of skeletal muscle at low workloads (pedaling a bicycle to generate 10 or 25 W of power). Thus, predictable changes in systemic skeletal muscle biochemistry accompany the maintenance of an altered body weight and account for a significant portion of the variance in skeletal muscle work efficiency and fuel utilization at reduced body weight.

  13. Carica papaya increases regulatory T cells and reduces IFN-γ+ CD4+ T cells in healthy human subjects.

    Science.gov (United States)

    Abdullah, Maha; Chai, Pei-Shin; Loh, Chiew-Yee; Chong, Mun-Yee; Quay, Huai-Wei; Vidyadaran, Sharmili; Seman, Zainina; Kandiah, Mirnalini; Seow, Heng-Fong

    2011-05-01

    Fruit and vegetables have therapeutic potential as they dampen inflammation, have no known side-effects and as whole foods have prospective additive and synergistic benefits. Th1 (IFN-γ(+) CD4(+))/Th2 (IL-4(+)CD4(+)) T cells play a vital role in mediating inflammatory responses and may be regulated by regulatory T cells (Tregs). Effects of Carica papaya on cells of healthy individuals were determined using flow cytometry methods. Significant down-regulation of IFN-γ(+) CD4(+) (p=0.03, n=13), up-regulation of IL-4(+) CD4(+) (p=0.04, n=13) T cells and up-regulation of CD3(+) CD4(+) CD25(+) CD127(-) (p=0.001, n=15) Tregs were observed after papaya consumption. In vitro cultures showed up-regulation of Tregs in male subjects and was significantly associated with levels of IL-1β in culture supernatants (R(2) =0.608, p=0.04, n=12). Other inflammatory cytokines were significantly suppressed. Papaya consumption may exert an anti-inflammatory response mediated through Tregs and have potential in alleviating inflammatory conditions. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. An analysis of the dependence of saccadic latency on target position and target characteristics in human subjects

    Directory of Open Access Journals (Sweden)

    Rosenberg Jay R

    2001-09-01

    Full Text Available Abstract Background Predictions from conduction velocity data for primate retinal ganglion cell axons indicate that the conduction time to the lateral geniculate nucleus for stimulation of peripheral retina should be no longer than for stimulation of central retina. On this basis, the latency of saccadic eye movements should not increase for more peripherally located targets. However, previous studies have reported relatively very large increases, which has the implication of a very considerable increase in central processing time for the saccade-generating system. Results In order to resolve this paradox, we have undertaken an extended series of experiments in which saccadic eye movements were recorded by electro-oculography in response to targets presented in the horizontal meridian in normal young subjects. For stationary or moving targets of either normal beam intensity or reduced red intensity, with the direction of gaze either straight ahead with respect to the head or directed eccentrically, the saccadic latency was shown to remain invariant with respect to a wide range of target angular displacements. Conclusions These results indicate that, irrespective of the angular displacement of the target, the direction of gaze or the target intensity, the saccade-generating system operates with a constant generation time.

  15. Subjective well-being and human welfare around the world as reflected in the Gallup World Poll.

    Science.gov (United States)

    Diener, Ed; Tay, Louis

    2015-03-01

    We present data on well-being and quality of life in the world, including material quality of life such as not going hungry, physical health quality of life such as longevity, social quality of life such as social support, environmental health such as clean water, equality in income and life satisfaction, and levels of subjective well-being (SWB). There are large differences between nations in SWB, and these are predicted not only by economic development, but also by environmental health, equality and freedom in nations. Improving trends in SWB are seen in many countries, but declining SWB is evident in a few. Besides average differences in SWB between nations, there are also large disparities within many countries. We discuss the policy opportunities provided by national accounts of SWB, which are increasingly being adopted by many societies. They provide the opportunity to inform policy deliberations with well-being information that reflects not only economic development, but also other facets of quality of life as well. National accounts of SWB reflect the quality of life in areas such as health, social relationships and the natural environment, and therefore capture a broader view of societal well-being than afforded by measures of economic progress alone.

  16. Role of Pro-Inflammatory Cytokines and Biochemical Markers in the Pathogenesis of Type 1 Diabetes: Correlation with Age and Glycemic Condition in Diabetic Human Subjects

    Science.gov (United States)

    Zubair, Swaleha; Ajmal, Mohd; Siddiqui, Sheelu Shafiq; Moin, Shagufta; Owais, Mohammad

    2016-01-01

    Background Type 1 diabetes mellitus is a chronic inflammatory disease involving insulin producing β-cells destroyed by the conjoined action of auto reactive T-cells, inflammatory cytokines and monocytic cells. The aim of this study was to elucidate the status of pro-inflammatory cytokines and biochemical markers and possible correlation of these factors towards outcome of the disease. Methods The study was carried out on 29 T1D subjects and 20 healthy subjects. Plasma levels of oxidative stress markers, enzymatic and non-enzymatic antioxidants were estimated employing biochemical assays. The levels of pro-inflammatory cytokines such as by IL-1β & IL-17 in the serum were determined by ELISA, while the expression of TNF-α, IL-23 & IFN-γ was ascertained by qRT-PCR. Results The onset of T1D disease was accompanied with elevation in levels of Plasma malondialdehyde, protein carbonyl content and nitric oxide while plasma vitamin C, reduced glutathione and erythrocyte sulfhydryl groups were found to be significantly decreased in T1D patients as compared to healthy control subjects. Activity of antioxidant enzymes, superoxide dismutase, catalase, glutathione reductase and glutathione-s-transferase showed a significant suppression in the erythrocytes of T1D patients as compared to healthy subjects. Nevertheless, the levels of pro-inflammatory cytokines IL-1β and IL-17A were significantly augmented (***p≤.001) on one hand, while expression of T cell based cytokines IFN-γ, TNF-α and IL-23 was also up-regulated (*p≤.05) as compared to healthy human subjects. Conclusion The level of pro-inflammatory cytokines and specific biochemical markers in the serum of the patient can be exploited as potential markers for type 1 diabetes pathogenesis. The study suggests that level of inflammatory markers is up-regulated in T1D patients in an age dependent manner. PMID:27575603

  17. Expanding subjectivities

    DEFF Research Database (Denmark)

    Lundgaard Andersen, Linda; Soldz, Stephen

    2012-01-01

    A major theme in recent psychoanalytic thinking concerns the use of therapist subjectivity, especially “countertransference,” in understanding patients. This thinking converges with and expands developments in qualitative research regarding the use of researcher subjectivity as a tool to understa...

  18. Safety analysis of a Russian phage cocktail: from metagenomic analysis to oral application in healthy human subjects.

    Science.gov (United States)

    McCallin, Shawna; Alam Sarker, Shafiqul; Barretto, Caroline; Sultana, Shamima; Berger, Bernard; Huq, Sayeda; Krause, Lutz; Bibiloni, Rodrigo; Schmitt, Bertrand; Reuteler, Gloria; Brüssow, Harald

    2013-09-01

    Phage therapy has a long tradition in Eastern Europe, where preparations are comprised of complex phage cocktails whose compositions have not been described. We investigated the composition of a phage cocktail from the Russian pharmaceutical company Microgen targeting Escherichia coli/Proteus infections. Electron microscopy identified six phage types, with numerically T7-like phages dominating over T4-like phages. A metagenomic approach using taxonomical classification, reference mapping and de novo assembly identified 18 distinct phage types, including 7 genera of Podoviridae, 2 established and 2 proposed genera of Myoviridae, and 2 genera of Siphoviridae. De novo assembly yielded 7 contigs greater than 30 kb, including a 147-kb Myovirus genome and a 42-kb genome of a potentially new phage. Bioinformatic analysis did not reveal undesired genes and a small human volunteer trial did not associate adverse effects with oral phage exposure.

  19. Linking Electrical Stimulation of Human Primary Visual Cortex, Size of Affected Cortical Area, Neuronal Responses, and Subjective Experience.

    Science.gov (United States)

    Winawer, Jonathan; Parvizi, Josef

    2016-12-21

    Electrical brain stimulation (EBS) complements neural measurements by probing the causal relationship between brain and perception, cognition, and action. Many fundamental questions about EBS remain unanswered, including the spatial extent of cortex responsive to stimulation, and the relationship between the circuitry engaged by EBS and the types of neural responses elicited by sensory stimulation. Here, we measured neural responses and the effects of EBS in primary visual cortex in four patients implanted with intracranial electrodes. Using stimulation, behavior, and retinotopic mapping, we show the relationship between the size of affected cortical area and the magnitude of electrical charge. Furthermore, we show that the spatial location of electrically induced visual sensations is matched to the receptive field of the cortical site measured with broadband field potentials, and less so with event related potentials. Together, these findings broaden our knowledge about the mechanism of EBS and the neuromodulation of the human brain. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Clinical performance of a dermal filler containing natural glycolic Acid and a polylactic Acid polymer: results of a clinical trial in human immunodeficiency virus subjects with facial lipoatrophy.

    Science.gov (United States)

    Tagle, Jorge M; Macchetto, Pedro Cervantes; Durán Páramo, Rosa Margarita

    2010-02-01

    Lipoatrophy is a condition that affects certain individuals, most commonly those who are infected with the human immunodeficiency virus.(1-3) Injectable fillers are used for the treatment of these dermal contour deformities to smooth dermal depressions formed by the loss of volume. These dermal fillers (also known as soft tissue augmentation devices) can correct contour deformities caused by lipoatrophy in patients who are human immunodeficiency virus positive or negative. The product used in this study is a patented, second-generation, injectable, dermal collagen stimulator that combines glycolic acid and polylactic acid. The glycolic acid used is not a polymer, but rather an acid derived from sugar cane. Its chemical structure corresponds to that of an alpha-hydroxy acid. Glycolic acid is a well-characterized agent that is present in a number of cosmetic products. Polylactic acid is a synthetic, biocompatible, biodegradable, inert, synthetic polymer from the poly a-hydroxy-acid family that is believed to stimulate fibroblasts to produce more collagen, thus increasing facial volume. Together, polylactic acid and glycolic acid act in concert to 1) stimulate collagen production and 2) hydrate the outer layers of the skin. A multicenter, clinical investigation authorized by the Mexican Secretariat of Health was conducted between September 20, 2002, and September 19, 2004. This clinical study was conducted in male patients between 32 and 60 years of age with lipoatrophy as a result of highly active antiretroviral therapy for human immunodeficiency virus infection. The study objective was to measure the improvement of contour deformities after the injection of a dermal collagen stimulator containing glycolic acid and polylactic acid. In addition to safety, this dermal filler was assessed when used to correct volume deformities caused by lipoatrophy in subjects who are human immunodeficiency virus positive. Thirty male subjects participated and were treated as follows

  1. Psychomotor performance in relation to acute oral administration of Delta9-tetrahydrocannabinol and standardized cannabis extract in healthy human subjects.

    Science.gov (United States)

    Roser, Patrik; Gallinat, Jürgen; Weinberg, Gordon; Juckel, Georg; Gorynia, Inge; Stadelmann, Andreas M

    2009-08-01

    Abnormalities in psychomotor performance are a consistent finding in schizophrenic patients as well as in chronic cannabis users. The high levels of central cannabinoid (CB(1)) receptors in the basal ganglia, the cerebral cortex and the cerebellum indicate their implication in the regulation of motor activity. Based on the close relationship between cannabis use, the endogenous cannabinoid system and motor disturbances found in schizophrenia, we expected that administration of cannabinoids may change pattern of psychomotor activity like in schizophrenic patients. This prospective, double-blind, placebo-controlled cross-over study investigated the acute effects of cannabinoids on psychomotor performance in 24 healthy right-handed volunteers (age 27.9 +/- 2.9 years, 12 male) by comparing Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and standardized cannabis extract containing Delta(9)-THC and cannabidiol. Psychomotor performance was assessed by using a finger tapping test series. Cannabis extract, but not Delta(9)-THC, revealed a significant reduction of right-hand tapping frequencies that was also found in schizophrenia. As to the pure Delta(9)-THC condition, left-hand tapping frequencies were correlated with the plasma concentrations of the Delta(9)-THC metabolite 11-OH-THC. These effects are thought to be related to cannabinoid actions on CB(1) receptors in the basal ganglia, the cerebral cortex and the cerebellum. Our data further demonstrate that acute CB(1) receptor activation under the cannabis extract condition may also affect intermanual coordination (IMC) as an index of interhemispheric transfer. AIR-Scale scores as a measure of subjective perception of intoxication were dose-dependently related to IMC which was shown by an inverted U-curve. This result may be due to functional changes involving GABAergic and glutamatergic neurotransmission within the corpus callosum.

  2. Gastric digestion of α-lactalbumin in adult human subjects using capsule endoscopy and nasogastric tube sampling.

    Science.gov (United States)

    Sullivan, Louise M; Kehoe, Joseph J; Barry, Lillian; Buckley, Martin J M; Shanahan, Fergus; Mok, K H; Brodkorb, André

    2014-08-28

    In the present study, structural changes in the milk protein α-lactalbumin (α-LA) and its proteolysis were investigated for the potential formation of protein-fatty acid complexes during in vivo gastric digestion. Capsule endoscopy allowed visualisation of the digestion of the test drinks, with nasogastric tubes allowing sampling of the gastric contents. A total of ten healthy volunteers had nasogastric tubes inserted into the stomach and ingested test drinks containing 50 g/l of sucrose and 25 g/l of α-LA with and without 4 g/l of oleic acid (OA). The samples of gastric contents were collected for analysis at 3 min intervals. The results revealed a rapid decrease in the pH of the stomach of the subjects. The fasting pH of 2·31 (SD 1·19) increased to a pH maxima of pH 6·54 (SD 0·29) after ingestion, with a subsequent decrease to pH 2·22 (SD 1·91) after 21 min (n 8). Fluorescence spectroscopy and Fourier transform IR spectroscopy revealed partial protein unfolding, coinciding with the decrease in pH below the isoelectric point of α-LA. The activity of pepsin in the fasting state was found to be 39 (SD 12) units/ml of gastric juice. Rapid digestion of the protein occurred: after 15 min, no native protein was detected using SDS-PAGE; HPLC revealed the presence of small amounts of native protein after 24 min of gastric digestion. Mirocam® capsule endoscopy imaging and video clips (see the online supplementary material) revealed that gastric peristalsis resulted in a heterogeneous mixture during gastric digestion. Unfolding of α-LA was observed during gastric transit; however, there was no evidence of a cytotoxic complex being formed between α-LA and OA.

  3. Effect of sucrose in different commonly used pediatric medicines upon plaque pH in human subjects

    Directory of Open Access Journals (Sweden)

    Arun Sharma

    2011-01-01

    Full Text Available Introduction: This study was conducted with the aim to investigate the acidogenic potential of three commonly used pediatric medicines (benadryl syrup, crocin syrup, and novamox dry syrup upon plaque pH. Materials and Methods: The protocol used in the study followed the guidelines laid down at Scientific Consensus Conferences on methods for assessment of cariogenic potential of food, San Antonio, Texas. Ten young healthy adult volunteers were selected for the study. Subjects were refrained from brushing their teeth for 48 h and did not eat or drink for at least 2 ΍ h prior to each appointment. pH measurements were taken at baseline to determine resting plaque pH and at time interval of 5, 10, 15, 20, 25, and 30 min following a 1 min rinse with each medication. A pooled sample of plaque was removed from buccal / lingual surfaces, thoroughly mixed with 0.6 ml of double distilled deionized water and plaque pH was determined using a glass combination electrode. Data were compared with plaque pH changes after rinsing with control solution of 10 % sucrose and 10 % sorbitol. Analysis of minimum pH, maximum pH drop, and area under the baseline pH was computed for each medicine and for each case and the test of significance was conducted through the unpaired Student ′t′ test. Results: There was no significant difference between the benadryl syrup, crocin syrup, and sucrose solution as the medicines behaving essentially same as ten percent sucrose solution with respect to their potential to generate acids.

  4. Rethinking the humanities in twenty-first century Africa

    African Journals Online (AJOL)

    Ngwira's paper examines how the female body is portrayed in selected ... Mapatidwe – with the objective of illustrating how this daring representation ... film and on the phenomenon of witchcraft, from theological and philosophical perspectives ...

  5. Inactivation of the Haemophilus ducreyi luxS gene affects the virulence of this pathogen in human subjects.

    Science.gov (United States)

    Labandeira-Rey, Maria; Janowicz, Diane M; Blick, Robert J; Fortney, Kate R; Zwickl, Beth; Katz, Barry P; Spinola, Stanley M; Hansen, Eric J

    2009-08-01

    Haemophilus ducreyi 35000HP contains a homologue of the luxS gene, which encodes an enzyme that synthesizes autoinducer 2 (AI-2) in other gram-negative bacteria. H. ducreyi 35000HP produced AI-2 that functioned in a Vibrio harveyi-based reporter system. A H. ducreyi luxS mutant was constructed by insertional inactivation of the luxS gene and lost the ability to produce AI-2. Provision of the H. ducreyi luxS gene in trans partially restored AI-2 production by the mutant. The luxS mutant was compared with its parent for virulence in the human challenge model of experimental chancroid. The pustule-formation rate in 5 volunteers was 93.3% (95% confidence interval, 81.7%-99.9%) at 15 parent sites and 60.0% (95% confidence interval, 48.3%-71.7%) at 15 mutant sites (1-tailed P < .001). Thus, the luxS mutant was partially attenuated for virulence. This is the first report of AI-2 production contributing to the pathogenesis of a genital ulcer disease.

  6. Perioperative release of pro-regenerative biochemical signals from human renal allografts subjected to ischemia-reperfusion injury.

    Science.gov (United States)

    Błogowski, Wojciech; Dolegowska, Barbara; Budkowska, Marta; Sałata, Daria; Domański, Leszek; Starzynska, Teresa

    2014-02-01

    Complement-derived molecules modulate the intensity of renal ischemia-reperfusion injury and may lead to the generation of biochemical signals [such as stromal-derived factor-1 (SDF-1) or sphingosine-1-phosphate (S1P)], which stimulate tissue/organ regeneration after injury. We tested the association between perioperative C5b-9/membrane attack complex (MAC) levels and intensified erythrocyte lysis, and asked whether significant changes in the levels of pro-regenerative substances occur during the early phase of renal allograft reperfusion. Seventy-five recipients were enrolled and divided into the early, slow, and delayed graft function (DGF) groups. Perioperative blood samples were collected from the renal vein during consecutive minutes of reperfusion. Extracellular hemoglobin (eHb), albumin (plasma S1P transporter), 8-iPF2α-III isoprostane, SDF-1 and S1P concentrations were measured. Throughout the reperfusion period, erythrocyte lysis intensified and was most pronounced in the DGF group. However, perioperative eHb levels did not correlate significantly with C5b-9/MAC values, but rather with the intensity of oxidative stress. No significant changes were observed in S1P, its plasma transporter (albumin) or SDF-1 levels, which were relatively low in all groups throughout the reperfusion period. Our study therefore demonstrates that no known biochemical signal for bone marrow-derived stem cell mobilization is released from human renal allografts to the periphery during the early phase of reperfusion.

  7. Relationship between mosquito (Diptera: Culicidae) landing rates on a human subject and numbers captured using CO2-baited light traps.

    Science.gov (United States)

    Barnard, D R; Knue, G J; Dickerson, C Z; Bernier, U R; Kline, D L

    2011-06-01

    Capture rates of insectary-reared female Aedes albopictus (Skuse), Anopheles quadrimaculatus Say, Culex nigripalpus Theobald, Culex quinquefasciatus Say and Aedes triseriatus (Say) in CDC-type light traps (LT) supplemented with CO2 and using the human landing (HL) collection method were observed in matched-pair experiments in outdoor screened enclosures. Mosquito responses were compared on a catch-per-unit-effort basis using regression analysis with LT and HL as the dependent and independent variables, respectively. The average number of mosquitoes captured in 1 min by LT over a 24-h period was significantly related to the average number captured in 1 min by HL only for Cx. nigripalpus and Cx. quinquefasciatus. Patterns of diel activity indicated by a comparison of the mean response to LT and HL at eight different times in a 24-h period were not superposable for any species. The capture rate efficiency of LT when compared with HL was ≤15% for all mosquitoes except Cx. quinquefasciatus (43%). Statistical models of the relationship between mosquito responses to each collection method indicate that, except for Ae. albopictus, LT and HL capture rates are significantly related only during certain times of the diel period. Estimates of mosquito activity based on observations made between sunset and sunrise were most precise in this regard for An. quadrimaculatus and Cx. nigripalpus, as were those between sunrise and sunset for Cx. quinquefasciatus and Ae. triseriatus.

  8. Scientific research on human subjects and ethics procedures at the Istituto Superiore di Sanità: a survey of the articles issued in 2001.

    Science.gov (United States)

    Rosmini, Francesco; Ferrigno, Luigina; D'Angelo, Franca; Poltronieri, Elisabetta

    2006-01-01

    Principles promoting the protection of subjects involved in biomedical research are interpreted differently within the scientific community. The purpose of this paper is to describe the attitudes of researchers working at the Istituto Superiore di Sanità (ISS) regarding the ethical implications of studies involving human beings, with particular emphasis on aspects concerning informed consent (IC) and ethics committee (EC) review. In 2001, ISS researchers published a total of 733 articles, 93 (12.7%) of which were studies involving human beings. Nearly 2/3 (60/93) were epidemiological, while the remaining 35.5% were based on laboratory data. Half (47/93) reported physical or psychological interventions or treatments on study subjects. 40.9% of articles mentioned that informed consent had been obtained and only 12.9% that approval had been given by an ethics committee. The low proportion of articles on which a protocol had been submitted the EC was due in part to the type of studies, but also to the absence of an institutional EC prior to 2001. Ethical procedures were more present in laboratory than in epidemiologic studies (IC: 69.7% vs 25.0%, p ethical awareness on the part of epidemiologists. Further efforts are needed to develop and enforce clear institutional policies regarding ethical procedures.

  9. Soothing and anti-itch effect of quercetin phytosome in human subjects: a single-blind study

    Directory of Open Access Journals (Sweden)

    Maramaldi G

    2016-02-01

    Full Text Available Giada Maramaldi,1 Stefano Togni,1 Ivan Pagin,1 Luca Giacomelli,2 Roberta Cattaneo,3 Roberto Eggenhöffner,2 Samuele E Burastero4 1Indena S.p.A, Milan, 2Department of Surgical Sciences and Integrated Diagnostics, School of Medicine, Genova University, Genoa, 3Abich Srl, Verbania, 4San Raffaele Scientific Institute, Milan, ItalyBackground: We evaluated the ability of quercetin, a natural antioxidant formulated in a specific delivery system, to reduce skin inflammation induced by a variety of stimuli, including UV radiation, stimulation with a histamine solution, or contact with chemical irritants. In particular, we tested the soothing and anti-itch effect of Quercevita®, 1% cream for external use, a formulation characterized by a phospholipids-based delivery system.Patients and methods: The study was a monocentric, single blind trial that enrolled a group of 30 healthy volunteers. The back of each subject was examined to identify four quadrants with no previous skin damage or naevi that were treated in order to induce a controlled and reversible form of skin stress. The areas were treated as follows: no product; Quercevita® 1% cream, 2 mg/cm2; placebo; positive control (a commercially available topical formulation containing 1% dexchlorpheniramine.Results: Only quercetin phospholipids 1% and dexchlorpheniramine 1% achieved a significant reduction in erythema with comparable results: (–10.05% [P=0.00329] for quercetin phospholipids 1% vs –14.05% [P=0.00046] for the positive control. Moreover, quercetin phospholipids 1% and dexchlorpheniramine 1% were both associated with a significant decrease in mean wheal diameter: (–13.25% and –12.23% for dexchlorpheniramine 1%, respectively. Similar findings were reported for the other tested parameters.Conclusion: Quercetin has a skin protective effect against damage caused by a variety of insults, including UV radiation, histamine, or contact with toxic chemical compounds. Indeed, quercetin is able

  10. DNA Methylation Profiling of Uniparental Disomy Subjects Provides a Map of Parental Epigenetic Bias in the Human Genome.

    Science.gov (United States)

    Joshi, Ricky S; Garg, Paras; Zaitlen, Noah; Lappalainen, Tuuli; Watson, Corey T; Azam, Nidha; Ho, Daniel; Li, Xin; Antonarakis, Stylianos E; Brunner, Han G; Buiting, Karin; Cheung, Sau Wai; Coffee, Bradford; Eggermann, Thomas; Francis, David; Geraedts, Joep P; Gimelli, Giorgio; Jacobson, Samuel G; Le Caignec, Cedric; de Leeuw, Nicole; Liehr, Thomas; Mackay, Deborah J; Montgomery, Stephen B; Pagnamenta, Alistair T; Papenhausen, Peter; Robinson, David O; Ruivenkamp, Claudia; Schwartz, Charles; Steiner, Bernhard; Stevenson, David A; Surti, Urvashi; Wassink, Thomas; Sharp, Andrew J

    2016-09-01

    Genomic imprinting is a mechanism in which gene expression varies depending on parental origin. Imprinting occurs through differential epigenetic marks on the two parental alleles, with most imprinted loci marked by the presence of differentially methylated regions (DMRs). To identify sites of parental epigenetic bias, here we have profiled DNA methylation patterns in a cohort of 57 individuals with uniparental disomy (UPD) for 19 different chromosomes, defining imprinted DMRs as sites where the maternal and paternal methylation levels diverge significantly from the biparental mean. Using this approach we identified 77 DMRs, including nearly all those described in previous studies, in addition to 34 DMRs not previously reported. These include a DMR at TUBGCP5 within the recurrent 15q11.2 microdeletion region, suggesting potential parent-of-origin effects associated with this genomic disorder. We also observed a modest parental bias in DNA methylation levels at every CpG analyzed across ∼1.9 Mb of the 15q11-q13 Prader-Willi/Angelman syndrome region, demonstrating that the influence of imprinting is not limited to individual regulatory elements such as CpG islands, but can extend across entire chromosomal domains. Using RNA-seq data, we detected signatures consistent with imprinted expression associated with nine novel DMRs. Finally, using a population sample of 4,004 blood methylomes, we define patterns of epigenetic variation at DMRs, identifying rare individuals with global gain or loss of methylation across multiple imprinted loci. Our data provide a detailed map of parental epigenetic bias in the human genome, providing insights into potential parent-of-origin effects.

  11. A first-in-human study of DS-1040, an inhibitor of the activated form of thrombin-activatable fibrinolysis inhibitor, in healthy subjects.

    Science.gov (United States)

    Zhou, J; Kochan, J; Yin, O; Warren, V; Zamora, C; Atiee, G; Pav, J; Orihashi, Y; Vashi, V; Dishy, V

    2017-05-01

    Essentials DS-1040 inhibits the activated form of thrombin-activatable fibrinolysis inhibitor (TAFIa). Infusion of DS-1040 was safe and well tolerated in healthy young and elderly subjects. DS-1040 substantially decreased TAFIa activity but had no impact on bleeding time. DS-1040 may provide an option of safer thrombolytic therapy. Background Current treatments for acute ischemic stroke and venous thromboembolism, such as recombinant tissue-type plasminogen activator and thrombectomy, are limited by a narrow time window and the risk of bleeding. DS-1040 is a novel low molecular weight compound that inhibits the activated form of thrombin-activatable fibrinolysis inhibitor (TAFIa), and was developed as a fibrinolysis enhancer for the treatment of thromboembolic diseases. Objectives This first-in-human, randomized, placebo-controlled, three-part, phase 1 study was conducted to evaluate the safety, pharmacokinetics and pharmacodynamics of DS-1040 in healthy subjects. Subjects/Methods Young (18-45 years) or elderly (65-75 years) subjects (N = 103) were randomized to receive single ascending doses of DS-1040 ranging from 0.1 mg to 40 mg, or placebo, administered either as a 0.5-h intravenous infusion or as a 24-h continuous infusion. Results All doses of DS-1040 were tolerated, and no serious adverse events (AEs) or discontinuations resulting from AEs occurred during the study. Bleeding time remained within the normal range for all doses tested in all subjects. Plasma exposure of DS-1040 increased proportionally with increase in dose. Elderly subjects had higher exposures to DS-1040 and prolonged elimination times, probably because of decreased renal clearance. DS-1040 caused a substantial dose-dependent and time-dependent decrease in TAFIa activity and in 50% clot lysis time. The levels of D-dimer, indicative of endogenous fibrinolysis, increased in some individuals following DS-1040 treatment. No effects of DS-1040 on coagulation parameters or platelet

  12. Twenty-One: cross-language disclosure and retrieval of multimedia documents on sustainable development

    NARCIS (Netherlands)

    Stal, ter W.G.; Beijert, J.-H.; Bruin, de G.; Gent, van J.; Jong, de F.M.G.; Kraaij, W.; Netter, K.; Smart, G.

    1998-01-01

    The Twenty-One project brings together environmental organisations, technology providers and research institutes from several European countries. The main objective of the project is to make documents on environmental issues—in particular, on the subject of sustainable development—available on CD-RO

  13. A Subjective Assessment of Alternative Mission Architecture Operations Concepts for the Human Exploration of Mars at NASA Using a Three-Dimensional Multi-Criteria Decision Making Model

    Science.gov (United States)

    Tavana, Madjid

    2003-01-01

    The primary driver for developing missions to send humans to other planets is to generate significant scientific return. NASA plans human planetary explorations with an acceptable level of risk consistent with other manned operations. Space exploration risks can not be completely eliminated. Therefore, an acceptable level of cost, technical, safety, schedule, and political risks and benefits must be established for exploratory missions. This study uses a three-dimensional multi-criteria decision making model to identify the risks and benefits associated with three alternative mission architecture operations concepts for the human exploration of Mars identified by the Mission Operations Directorate at Johnson Space Center. The three alternatives considered in this study include split, combo lander, and dual scenarios. The model considers the seven phases of the mission including: 1) Earth Vicinity/Departure; 2) Mars Transfer; 3) Mars Arrival; 4) Planetary Surface; 5) Mars Vicinity/Departure; 6) Earth Transfer; and 7) Earth Arrival. Analytic Hierarchy Process (AHP) and subjective probability estimation are used to captures the experts belief concerning the risks and benefits of the three alternative scenarios through a series of sequential, rational, and analytical processes.

  14. PERSONAL LEADERSHIP PROTECTS RESEARCH SUBJECTS

    Science.gov (United States)

    Personal leadership promotes the ethical conduct of human research activities. Leadership entails application of one’s cognitive abilities, technical skills, and emotional intelligence during the conduct of research activities, Personal leadership assures human research subject protection....

  15. Human endogenous retrovirus K(HML-2) Gag- and Env-specific T-cell responses are infrequently detected in HIV-1-infected subjects using standard peptide matrix-based screening

    NARCIS (Netherlands)

    R.B. Jones (R. Brad); V.M. John (Vivek); D.V. Hunter (Diana); E. Martin (Eric); S. Mujib (Shariq); V. Mihajlovic (Vesna); P.C. Burgers (Peter); T.M. Luider (Theo); G. Gyenes (Gabor); N.C. Sheppard (Neil); D. SenGupta (Devi); R. Tandon (Ravi); F.-Y. Yue (Feng-Yun); W.S. Benko (William); C. Kovacs (Carrie); R. Nixon; M.A. Ostrowski (Mario)

    2012-01-01

    textabstractT-cell responses to human endogenous retrovirus (HERV) K(HML-2) Gag and Env were mapped in HIV-1-infected subjects using 15mer peptides. Small peptide pools and high concentrations were used to maximize sensitivity. In the 23 subjects studied, only three bona fide HERV-K(HML-2)-specific

  16. Twenty hanging Dolls and a Lynching:

    DEFF Research Database (Denmark)

    Risør, Helene

    2010-01-01

    paradoxical entanglement with the enactments of citizenship and state-citizen relations, the article argues that people's attempts to remain safe constitute a permanent process of making visible and defacing (following Michael Taussig's notion of defacement) dangerousness and criminal subjects vis...

  17. Analysis by NASA's VESGEN Software of Retinal Blood Vessels in Human Subjects Undergoing Head-Down Tilt During 70-Day Bed Rest

    Science.gov (United States)

    Vyas, Ruchi J.; Murray, Matthew C.; Predovic, Marina; Lim, Shiyin; Askin, Kayleigh N.; Vizzeri, Gianmarco; Taibbi, Giovanni; Mason, Sara Stroble; Zanello, Susana B.; Young, Millenia; hide

    2017-01-01

    Significant risks for visual impairment associated with increased intracranial pressure (VIIP) are incurred by microgravity spaceflight, especially long-duration missions [1]. We hypothesize that microgravity-induced fluid shifts result in pathological changes within blood vessels of the retina that precede development of visual and other ocular impairments. Potential contributions of retinal vascular remodeling to VIIP etiology are therefore being investigated for two studies in 30deg infrared (IR) Heidelberg Spectralis(Registered Trademark) images with NASA's innovative VESsel GENeration Analysis (VESGEN) software [2,3]. The retrospective studies include: (1) before, during and after (pre, mid and post) 6º head-down tilt (HDT) in human subjects during 70 days of bed rest, and (2) before and after missions to the International Space Station (ISS) by U.S. crew members. Results for both studies are almost complete. A preliminary example for HDT is described below.

  18. Recovery of distortion product otoacoustic emissions (DPOAE) with high time-resolution from a moderate monaural-exposure to 2-kHz in human subjects

    DEFF Research Database (Denmark)

    de Toro, Miguel Angel Aranda; Ordoñez, Rodrigo Pizarro; Reuter, Karen

    2008-01-01

    The amplitude of distortion product otoacoustic emissions (DPOAE) decreases temporarily after exposure to a sound of moderate level. These changes show similarities to the changes observed in absolute hearing thresholds after similar sound exposures. This paper presents the experimental protocol...... to study how DPOAEs in human subjects are affected after a monaural exposure of ten minutes to a pure tone of 2 kHz. The experimental protocol allows to measure fine structures of the DPOAE with high time-resolution in a limited frequency range. Thus, the results give a detailed description of the DPOAE...... recovery process and can be used to develop a mathematical model of the recovery. This is the first approximation to study the recovery of more complex exposures. [Work supported by the Danish Research Council for Technology and Production.]...

  19. Can biophysics tell us something about the weak equivalence principle vis a vis the thought experiment of Einstein involving human subjects?

    Science.gov (United States)

    Thaheld, Fred H

    2009-08-01

    Over a period of several decades it has been noticed that most astronauts, either orbiting the earth or on trips to the moon, have observed phosphenes or light flashes (LF) including streaks, spots and clouds of light when their eyes are closed or they are in a darkened cabin. Scientists suspect that two separate components of cosmic rays cause these flashes due to direct interaction with the retina. This phenomenon is not noticed on the ground because of cosmic ray interaction with the atmosphere. The argument is advanced that this effect may provide us with a new method of exploring the weak equivalence principle from the standpoint of Einstein's original thought experiment involving human subjects. This can be done, utilizing the retina only, as an animate quantum mechanical measuring device or, in conjunction with the Anomalous Long Term Effects on Astronauts (ALTEA) facility.

  20. Crank-Nicholson Scheme for the Estimation of Thermal Disturbance on the Peripheral Tissues of Human Body Subjected to Oscillatory Boundary Condition and Time Dependent Heat Source

    Science.gov (United States)

    Khanday, M. A.; Hussain, Fida

    2015-07-01

    To predict the behaviour of thermal physiology of a finite biological tissue in severe cold climatic conditions, a mathematical model has been established based on Pennes' bio-heat transfer equation with oscillatory boundary condition and time dependent heat source term. Crank-Nicholson scheme has been employed to obtain the solution of the boundary value problem to understand the change in stable temperature profiles at the peripheral tissues of human body subjected to forced convection due to cold. Thermal stress at these regions with respect to different input parameters has been computed under extreme environmental conditions using MATLAB Software. The results have shown a relative significance and provide a reasonable outcome in terms of variable metabolic heat generation and oscillatory heat source. The oscillations of the temperature profiles from the mean temperatures were computed in relation with tissue medium and other physiological parameters.

  1. Down-regulation of human leukocyte antigens class I on peripheral T lymphocytes and NK cells from subjects in region of high-incidence gastrointestinal tumor

    Institute of Scientific and Technical Information of China (English)

    ZHANG Zhi-mian; LI Ying-jie; GUAN Xiao; YANG Xiao-yun; GAO Xi-mei; YANG Xiao-jing; WANG Li-shui; ZOU Xiong

    2011-01-01

    Background Many types of human tumors can suppress the immune system to enhance their survival. Loss or down-regulation of human leukocyte antigens (HLA) class I on tumors is considered to be a major mechanism of tumor immune escape. Our previous studies found that HLA class I on peripheral-blood mononuclear cells was significantly lower in gastric cancer patients. The present study made an analysis of HLA class I expression on peripheral-blood T lymphocytes and NK cells from subjects of Lijiadian village, a village with high-incidence gastrointestinal tumor. Methods A total of 181 villagers from Lijiadian village and 153 normal controls from the Department of Health Examination Center were enrolled in this study. Using a multi-tumor markers detection system, these villagers were divided into two groups: high-risk group (tumor markers positive group) and low-risk group (tumor markers negative group). The percentage of T lymphocytes and NK cells and levels of HLA class I on their surface were determined in these subjects by flow cytometry.Results Percentages of T lymphocytes and NK cells in peripheral-blood mononuclear cells did not vary with age. The expression level of HLA class I on peripheral T lymphocytes and NK cells was not affected by age or gender, but was significantly down-regulated in Lijiadian villagers (P<0.05), especially on the surface of NK cells (P<0.01). Compared with the low-risk group, there was a significant reduction of HLA class I on peripheral T lymphocytes (P <0.05) and NK cells (P <0.05) in the high-risk group.Conclusions HLA class I on peripheral T lymphocytes and NK cells may be involved in tumorigenesis and development of gastrointestinal tumor, and understanding their changes in expression may provide new insights into the mechanism of tumor immunity.

  2. Studies on immunoproteasome in human liver. Part I: Absence in fetuses, presence in normal subjects, and increased levels in chronic active hepatitis and cirrhosis

    Energy Technology Data Exchange (ETDEWEB)

    Vasuri, Francesco; Capizzi, Elisa [Pathology Unit of the ' F. Addarii' Institute of Oncology, S.Orsola-Malpighi Hospital, Bologna University (Italy); Bellavista, Elena [Department of Experimental Pathology, Bologna University (Italy); Interdepartmental Center for Studies on Biophysics, Bioinformatics and Biocomplexity ' L. Galvani' (CIG), Bologna University (Italy); Mishto, Michele [Department of Experimental Pathology, Bologna University (Italy); Interdepartmental Center for Studies on Biophysics, Bioinformatics and Biocomplexity ' L. Galvani' (CIG), Bologna University (Italy); Institute of Biochemistry, Medical Faculty Charite, Berlin (Germany); Santoro, Aurelia [Department of Experimental Pathology, Bologna University (Italy); Interdepartmental Center for Studies on Biophysics, Bioinformatics and Biocomplexity ' L. Galvani' (CIG), Bologna University (Italy); Fiorentino, Michelangelo [Pathology Unit of the ' F. Addarii' Institute of Oncology, S.Orsola-Malpighi Hospital, Bologna University (Italy); Capri, Miriam [Department of Experimental Pathology, Bologna University (Italy); Interdepartmental Center for Studies on Biophysics, Bioinformatics and Biocomplexity ' L. Galvani' (CIG), Bologna University (Italy); Cescon, Matteo; Grazi, Gian Luca [Unit of General and Transplantation Surgery, S.Orsola-Malpighi Hospital, Bologna University (Italy); Grigioni, Walter Franco; D' Errico-Grigioni, Antonia [Pathology Unit of the ' F. Addarii' Institute of Oncology, S.Orsola-Malpighi Hospital, Bologna University (Italy); Franceschi, Claudio, E-mail: claudio.franceschi@unibo.it [Department of Experimental Pathology, Bologna University (Italy); Interdepartmental Center for Studies on Biophysics, Bioinformatics and Biocomplexity ' L. Galvani' (CIG), Bologna University (Italy)

    2010-06-25

    Despite the central role of proteasomes in relevant physiological pathways and pathological processes, this topic is unexpectedly largely unexplored in human liver. Here we present data on the presence of proteasome and immunoproteasome in human livers from normal adults, fetuses and patients affected by major hepatic diseases such as cirrhosis and chronic active hepatitis. Immunohistochemistry for constitutive ({alpha}4 and {beta}1) and inducible (LMP2 and LMP7) proteasome subunits, and for the PA28{alpha}{beta} regulator, was performed in liver samples from 38 normal subjects, 6 fetuses, 2 pediatric cases, and 19 pathological cases (10 chronic active hepatitis and 9 cirrhosis). The immunohistochemical data have been validated and quantified by Western blotting analysis. The most striking result we found was the concomitant presence in hepatocyte cytoplasm of all healthy subjects, including the pediatric cases, of constitutive proteasome and immunoproteasome subunits, as well as PA28{alpha}{beta}. At variance, immunoproteasome was not present in hepatocytes from fetuses, while a strong cytoplasmic and nuclear positivity for LMP2 and LMP7 was found in pathological samples, directly correlated to the histopathological grade of inflammation. At variance from other organs such as the brain, immunoproteasome is present in livers from normal adult and pediatric cases, in apparent absence of pathological processes, suggesting the presence of a peculiar regulation of the proteasome/immunoproteasome system, likely related to the physiological stimuli derived from the gut microbiota after birth. Other inflammatory stimuli contribute in inducing high levels of immunoproteasome in pathological conditions, where its role deserve further attention.

  3. Twenty Years After: Armenian Research Libraries Today

    Directory of Open Access Journals (Sweden)

    D. Aram Donabedian

    2012-05-01

    Full Text Available Since achieving statehood in 1991, Armenia has faced major economic and political obstacles which have significantly affected the nation’s research libraries. This research paper will quantitatively and qualitatively examine the challenges facing Armenian research libraries just over twenty years after the collapse of the Soviet Union. Specifically, the authors analyze their interviews with five library administrators at five major institutions, respectively. These include Yerevan State University Library, the National Library of Armenia, the Fundamental Scientific Library of the National Academy of Sciences of Armenia, the Republican Scientific-Medical Library of Armenia, and the Papazian Library of the American University of Armenia. The instrument for the interviews consists of 73 questions based on the 2004 Association of College and Research Libraries Standards for Libraries in Higher Education and evaluates the following factors:• The library’s mission, goals and objectives• Public or user services• Instruction activities at the library• Resources (print, media, or electronic and collection development• Access to the library’s resources• Outcome assessment, or evaluation of the library• Staffing issues• Facility maintenance and plans for library development• Communication and cooperation both within the library and with the user community• Administration• BudgetIn addition, we will focus on the strengths and weaknesses of these libraries and investigate the growing open access movement in Armenia. Based on our findings, the authors wish to facilitate dialogue and consider possible approaches to help these libraries meet Armenia’s pressing information needs.

  4. Divergence of canonical danger signals: The genome-level expression patterns of human mononuclear cells subjected to heat shock or lipopolysaccharide

    Directory of Open Access Journals (Sweden)

    Sakthivel Bhuvaneswari

    2008-05-01

    Full Text Available Abstract Background Peripheral blood mononuclear cells (PBMC serve a sentinel role allowing the host to efficiently sense and adapt to the presence of danger signals. Herein we have directly compared the genome-level expression patterns (microarray of a human PBMC model (THP-1 cells subjected to one of two canonical danger signals, heat shock or lipopolysaccharide (LPS. Results and Discussion Based on sequential expression and statistical filters, and in comparison to control cells, we found that 3,988 genes were differentially regulated in THP-1 cells subjected to LPS stress, and 2,921 genes were differentially regulated in THP-1 cells subjected to heat shock stress. Venn analyses demonstrated that the majority of differentially regulated genes (≥ 70% were uniquely expressed in response to one of the two danger signals. Functional analyses demonstrated that the two danger signals induced expression or repression of genes corresponding to unique pathways, molecular functions, biological processes, and gene networks. In contrast, there were 184 genes that were commonly upregulated by both stress signals, and 430 genes that were commonly downregulated by both stress signals. Interestingly, the 184 commonly upregulated genes corresponded to a gene network broadly related to inflammation, and more specifically to chemokine signaling. Conclusion These data demonstrate that the mononuclear cell responses to the canonical stress signals, heat shock and LPS, are highly divergent. However, there is a heretofore unrecognized common pattern of gene network expression corresponding to chemokine-related biology. The data also serve as a reference database for investigators in the field of stress signaling.

  5. Physiological observations validate finite element models for estimating subject-specific electric field distributions induced by transcranial magnetic stimulation of the human motor cortex.

    Science.gov (United States)

    Opitz, Alexander; Legon, Wynn; Rowlands, Abby; Bickel, Warren K; Paulus, Walter; Tyler, William J

    2013-11-01

    Recent evidence indicates subject-specific gyral folding patterns and white matter anisotropy uniquely shape electric fields generated by TMS. Current methods for predicting the brain regions influenced by TMS involve projecting the TMS coil position or center of gravity onto realistic head models derived from structural and functional imaging data. Similarly, spherical models have been used to estimate electric field distributions generated by TMS pulses delivered from a particular coil location and position. In the present paper we inspect differences between electric field computations estimated using the finite element method (FEM) and projection-based approaches described above. We then more specifically examined an approach for estimating cortical excitation volumes based on individualistic FEM simulations of electric fields. We evaluated this approach by performing neurophysiological recordings during MR-navigated motormapping experiments. We recorded motor evoked potentials (MEPs) in response to single pulse TMS using two different coil orientations (45° and 90° to midline) at 25 different locations (5×5 grid, 1cm spacing) centered on the hotspot of the right first dorsal interosseous (FDI) muscle in left motor cortex. We observed that motor excitability maps varied within and between subjects as a function of TMS coil position and orientation. For each coil position and orientation tested, simulations of the TMS-induced electric field were computed using individualistic FEM models and compared to MEP amplitudes obtained during our motormapping experiments. We found FEM simulations of electric field strength, which take into account subject-specific gyral geometry and tissue conductivity anisotropy, significantly correlated with physiologically observed MEP amplitudes (rmax=0.91, p=1.8×10(-5) rmean=0.81, p=0.01). These observations validate the implementation of individualistic FEM models to account for variations in gyral folding patterns and tissue

  6. Measurement of electric fields induced in a human subject due to natural movements in static magnetic fields or exposure to alternating magnetic field gradients.

    Science.gov (United States)

    Glover, P M; Bowtell, R

    2008-01-21

    A dual dipole electric field probe has been used to measure surface electric fields in vivo on a human subject over a frequency range of 0.1-800 Hz. The low-frequency electric fields were induced by natural body movements such as walking and turning in the fringe magnetic fields of a 3 T magnetic resonance whole-body scanner. The rate-of-change of magnetic field (dB/dt) was also recorded simultaneously by using three orthogonal search coils positioned near to the location of the electric field probe. Rates-of-change of magnetic field for natural body rotations were found to exceed 1 T s(-1) near the end of the magnet bore. Typical electric fields measured on the upper abdomen, head and across the tongue for 1 T s(-1) rate of change of magnetic field were 0.15+/-0.02, 0.077+/-0.003 and 0.015+/-0.002 V m(-1) respectively. Electric fields on the abdomen and chest were measured during an echo-planar sequence with the subject positioned within the scanner. With the scanner rate-of-change of gradient set to 10 T m(-1) s(-1) the measured rate-of-change of magnetic field was 2.2+/-0.1 T s(-1) and the peak electric field was 0.30+/-0.01 V m(-1) on the chest. The values of induced electric field can be related to dB/dt by a 'geometry factor' for a given subject and sensor position. Typical values of this factor for the abdomen or chest (for measured surface electric fields) lie in the range of 0.10-0.18 m. The measured values of electric field are consistent with currently available numerical modelling results for movement in static magnetic fields and exposure to switched magnetic field gradients.

  7. Measurement of electric fields induced in a human subject due to natural movements in static magnetic fields or exposure to alternating magnetic field gradients

    Science.gov (United States)

    Glover, P. M.; Bowtell, R.

    2008-01-01

    A dual dipole electric field probe has been used to measure surface electric fields in vivo on a human subject over a frequency range of 0.1-800 Hz. The low-frequency electric fields were induced by natural body movements such as walking and turning in the fringe magnetic fields of a 3 T magnetic resonance whole-body scanner. The rate-of-change of magnetic field (dB/dt) was also recorded simultaneously by using three orthogonal search coils positioned near to the location of the electric field probe. Rates-of-change of magnetic field for natural body rotations were found to exceed 1 T s-1 near the end of the magnet bore. Typical electric fields measured on the upper abdomen, head and across the tongue for 1 T s-1 rate of change of magnetic field were 0.15 ± 0.02, 0.077 ± 0.003 and 0.015 ± 0.002 V m-1 respectively. Electric fields on the abdomen and chest were measured during an echo-planar sequence with the subject positioned within the scanner. With the scanner rate-of-change of gradient set to 10 T m-1 s-1 the measured rate-of-change of magnetic field was 2.2 ± 0.1 T s-1 and the peak electric field was 0.30 ± 0.01 V m-1 on the chest. The values of induced electric field can be related to dB/dt by a 'geometry factor' for a given subject and sensor position. Typical values of this factor for the abdomen or chest (for measured surface electric fields) lie in the range of 0.10-0.18 m. The measured values of electric field are consistent with currently available numerical modelling results for movement in static magnetic fields and exposure to switched magnetic field gradients.

  8. Effects of alcohol on food and energy intake in human subjects: evidence for passive and active over-consumption of energy.

    Science.gov (United States)

    Yeomans, Martin R

    2004-08-01

    The effects of alcohol on food and energy intake in human subjects have been the subject of a number of controlled studies recently. Unlike the evidence for other macronutrients, there is minimal evidence for any compensatory reduction in food intake in response to energy ingested as alcohol. In contrast, all studies testing intake within 1 h of preload ingestion report a higher intake of food following alcohol relative to energy-matched controls, although this short-term stimulatory effect is not evident if the test meal is delayed beyond 1 h. This time-course suggests that short-term stimulation of appetite may be mediated by the pharmacological action of alcohol on the appetite control system, either through enhanced orosensory reward or impaired satiety. In the long term, energy ingested as alcohol is additive to energy from other sources, suggesting that moderate alcohol consumption results in long-term passive over-consumption alongside short-term active over-consumption of energy through appetite stimulation. Despite the consistency of enhanced energy intake after moderate alcohol, evidence of an association between alcohol in the diet and obesity remains contentious, although the most recent results suggest that alcohol intake correlates with BMI. Future research needs to address this issue and clarify the mechanisms underlying appetite stimulation by alcohol.

  9. Association of HLA-DR3 with human immune response to Lol p I and Lol p II allergens in allergic subjects.

    Science.gov (United States)

    Freidhoff, L R; Ehrlich-Kautzky, E; Meyers, D A; Ansari, A A; Bias, W B; Marsh, D G

    1988-04-01

    Associations between HLA type and IgE or IgG antibody (Ab) responses to two well-characterized, antigenetically non-crossreactive components of Lolium perenne (rye grass) pollen extract, Lol p I (Rye I) and Lol p II (Rye II) were studied in two groups of skin-test positive (ST+) Caucasoid adults. By both nonparametric and parametric statistical methods, significant associations were found between Ab responses to both Lol I and Lol II and the possession of HLA-DR3. In view of the well-known associations of both DR3 and B8 (which are in linkage disequilibrium) with many autoimmune diseases, differences in anti-Lol I and anti-Lol II mean log[Ab] levels between B8+, DR3- vs B8-, DR3- subjects and B8+, DR3+ vs B8-, DR3+ subjects were investigated. No differences were found. Our data, along with recent RFLP and DNA sequence studies, suggest that an Ia molecule involved in immune recognition of a similar major Ia recognition site of both the Lol molecules may consist of a DR3 alpha-beta I pair. Abbreviations used: Ab: Antibody. HLA: Human leukocyte antigen. Lol p I, Lol I: Group I allergen from Lolium perenne pollen (Rye I). Lol p II, Lol II: Group II allergen from Lolium perenne pollen (Rye II). Mr: Relative molecular mass. Rx: Immunotherapy with grass pollen extracts. ST: Skin test.

  10. Proceedings of the Twenty-First Water Reactor Safety Information Meeting: Volume 1, Plenary session; Advanced reactor research; advanced control system technology; advanced instrumentation and control hardware; human factors research; probabilistic risk assessment topics; thermal hydraulics; thermal hydraulic research for advanced passive LWRs

    Energy Technology Data Exchange (ETDEWEB)

    Monteleone, S. [Brookhaven National Lab., Upton, NY (United States)] [comp.

    1994-04-01

    This three-volume report contains 90 papers out of the 102 that were presented at the Twenty-First Water Reactor Safety Information Meeting held at the Bethesda Marriott Hotel, Bethesda, Maryland, during the week of October 25--27, 1993. The papers are printed in the order of their presentation in each session and describe progress and results of programs in nuclear safety research conducted in this country and abroad. Foreign participation in the meeting included papers presented by researchers from France, Germany, Japan, Russia, Switzerland, Taiwan, and United Kingdom. The titles of the papers and the names of the authors have been updated and may differ from those that appeared in the final program of the meeting. Individual papers have been cataloged separately. This document, Volume 1 covers the following topics: Advanced Reactor Research; Advanced Instrumentation and Control Hardware; Advanced Control System Technology; Human Factors Research; Probabilistic Risk Assessment Topics; Thermal Hydraulics; and Thermal Hydraulic Research for Advanced Passive Light Water Reactors.

  11. Education, Subject, and Human Development

    Directory of Open Access Journals (Sweden)

    GLORIA MARCIALES-VIVAS

    2008-12-01

    Full Text Available Cambios acelerados en la producción, procesamiento y distribuciónde la información; avances en la ciencia y la tecnología;reconfiguración de las estructuras de poder y de las formas deejercicio de la ciudadanía; así como crisis de diverso orden, sonsolamente algunos de los fenómenos que marcan el mundo dehoy. Este campo de tensiones interpela a la educación, la cual seve puesta en cuestión y es desafiada a transformarse y a agenciarprocesos de formación haciendo frente a criterios eficientistasque intentan imponerse, en no pocas ocasiones, sobreaquellos de tipo pedagógico orientados a la generación de condicionesde desarrollo social.

  12. Beneficial effects of metformin on energy metabolism and visceral fat volume through a possible mechanism of fatty acid oxidation in human subjects and rats.

    Science.gov (United States)

    Tokubuchi, Ichiro; Tajiri, Yuji; Iwata, Shimpei; Hara, Kento; Wada, Nobuhiko; Hashinaga, Toshihiko; Nakayama, Hitomi; Mifune, Hiroharu; Yamada, Kentaro

    2017-01-01

    Metformin is known to have a beneficial effect on body weight and body composition, although the precise mechanism has not been elucidated yet. The aim of this study is to investigate the effects of metformin on energy metabolism and anthropometric factors in both human subjects and rats. In human studies, metformin (1500mg/day) was administered to 23 healthy subjects and 18 patients with type 2 diabetes for 2 weeks. Metabolic parameters and energy metabolism were measured during a meal tolerance test in the morning before and after the treatment of metformin. In animal studies, 13 weeks old SD rats were fed 25-26 g of standard chow only during 12-hours dark phase with either treated by metformin (2.5mg/ml in drinking water) or not for 2 weeks, and metabolic parameters, anthropometric factors and energy metabolism together with expressions related to fat oxidation and adaptive thermogenesis were measured either in fasting or post-prandial state at 15 weeks old. Post-prandial plasma lactate concentration was significantly increased after the metformin treatment in both healthy subjects and diabetic patients. Although energy expenditure (EE) did not change, baseline respiratory quotient (RQ) was significantly decreased and post-prandial RQ was significantly increased vice versa following the metformin treatment in both groups. By the administration of metformin to SD rats for 2 weeks, plasma levels of lactate and pyruvate were significantly increased in both fasting and post-prandial states. RQ during a fasting state was significantly decreased in metformin-treated rats compared to controls with no effect on EE. Metformin treatment brought about a significant reduction of visceral fat mass compared to controls accompanied by an up-regulation of fat oxidation-related enzyme in the liver, UCP-1 in the brown adipose tissue and UCP-3 in the skeletal muscle. From the results obtained, beneficial effects of metformin on visceral fat reduction has been demonstrated probably

  13. Genomic research with human samples. Points of view from scientists and research subjects about disclosure of results and risks of genomic research. Ethical and empirical approach.

    Science.gov (United States)

    Valle Mansilla, José Ignacio

    2011-01-01

    Biomedical researchers often now ask subjects to donate samples to be deposited in biobanks. This is not only of interest to researchers, patients and society as a whole can benefit from the improvements in diagnosis, treatment, and prevention that the advent of genomic medicine portends. However, there is a growing debate regarding the social and ethical implications of creating biobanks and using stored human tissue samples for genomic research. Our aim was to identify factors related to both scientists and patients' preferences regarding the sort of information to convey to subjects about the results of the study and the risks related to genomic research. The method used was a survey addressed to 204 scientists and 279 donors from the U.S. and Spain. In this sample, researchers had already published genomic epidemiology studies; and research subjects had actually volunteered to donate a human sample for genomic research. Concerning the results, patients supported more frequently than scientists their right to know individual results from future genomic research. These differences were statistically significant after adjusting by the opportunity to receive genetic research results from the research they had previously participated and their perception of risks regarding genetic information compared to other clinical data. A slight majority of researchers supported informing participants about individual genomic results only if the reliability and clinical validity of the information had been established. Men were more likely than women to believe that patients should be informed of research results even if these conditions were not met. Also among patients, almost half of them would always prefer to be informed about individual results from future genomic research. The three main factors associated to a higher support of a non-limited access to individual results were: being from the US, having previously been offered individual information and considering

  14. Beneficial effects of metformin on energy metabolism and visceral fat volume through a possible mechanism of fatty acid oxidation in human subjects and rats

    Science.gov (United States)

    Tokubuchi, Ichiro; Tajiri, Yuji; Iwata, Shimpei; Hara, Kento; Wada, Nobuhiko; Hashinaga, Toshihiko; Nakayama, Hitomi; Mifune, Hiroharu; Yamada, Kentaro

    2017-01-01

    Objective Metformin is known to have a beneficial effect on body weight and body composition, although the precise mechanism has not been elucidated yet. The aim of this study is to investigate the effects of metformin on energy metabolism and anthropometric factors in both human subjects and rats. Methods In human studies, metformin (1500mg/day) was administered to 23 healthy subjects and 18 patients with type 2 diabetes for 2 weeks. Metabolic parameters and energy metabolism were measured during a meal tolerance test in the morning before and after the treatment of metformin. In animal studies, 13 weeks old SD rats were fed 25–26 g of standard chow only during 12-hours dark phase with either treated by metformin (2.5mg/ml in drinking water) or not for 2 weeks, and metabolic parameters, anthropometric factors and energy metabolism together with expressions related to fat oxidation and adaptive thermogenesis were measured either in fasting or post-prandial state at 15 weeks old. Results Post-prandial plasma lactate concentration was significantly increased after the metformin treatment in both healthy subjects and diabetic patients. Although energy expenditure (EE) did not change, baseline respiratory quotient (RQ) was significantly decreased and post-prandial RQ was significantly increased vice versa following the metformin treatment in both groups. By the administration of metformin to SD rats for 2 weeks, plasma levels of lactate and pyruvate were significantly increased in both fasting and post-prandial states. RQ during a fasting state was significantly decreased in metformin-treated rats compared to controls with no effect on EE. Metformin treatment brought about a significant reduction of visceral fat mass compared to controls accompanied by an up-regulation of fat oxidation-related enzyme in the liver, UCP-1 in the brown adipose tissue and UCP-3 in the skeletal muscle. Conclusion From the results obtained, beneficial effects of metformin on visceral fat

  15. Peak strain magnitudes and rates in the tibia exceed greatly those in the skull: An in vivo study in a human subject.

    Science.gov (United States)

    Hillam, Richard A; Goodship, Allen E; Skerry, Tim M

    2015-09-18

    Bone mass and architecture are the result of a genetically determined baseline structure, modified by the effect of internal hormonal/biochemical regulators and the effect of mechanical loading. Bone strain is thought to drive a feedback mechanism to regulate bone formation and resorption to maintain an optimal, but not excessive mass and organisation of material at each skeletal location. Because every site in the skeleton has different functions, we have measured bone strains induced by physiological and more unusual activities, at two different sites, the tibia and cranium of a young human male in vivo. During the most vigorous activities, tibial strains were shown to exceed 0.2%, when ground reaction exceeded 5 times body weight. However in the skull the highest strains recorded were during heading a heavy medicine/exercise ball where parietal strains were up to 0.0192%. Interestingly parietal strains during more physiological activities were much lower, often below 0.01%. Strains during biting were not dependent upon bite force, but could be induced by facial contortions of similar appearance without contact between the teeth. Rates of strain change in the two sites were also very different, where peak tibial strain rate exceeded rate in the parietal bone by more than 5 fold. These findings suggest that the skull and tibia are subject to quite different regulatory influences, as strains that would be normal in the human skull would be likely to lead to profound bone loss by disuse in the long bones.

  16. Impact of Gluten-Friendly Bread on the Metabolism and Function of In Vitro Gut Microbiota in Healthy Human and Coeliac Subjects

    Science.gov (United States)

    Bevilacqua, Antonio; Costabile, Adele; Bergillos-Meca, Triana; Gonzalez, Isidro; Landriscina, Loretta; Ciuffreda, Emanuela; D’Agnello, Paola; Corbo, Maria Rosaria; Sinigaglia, Milena; Lamacchia, Carmela

    2016-01-01

    The main aim of this paper was to assess the in vitro response of healthy and coeliac human faecal microbiota to gluten-friendly bread (GFB). Thus, GFB and control bread (CB) were fermented with faecal microbiota in pH-controlled batch cultures. The effects on the major groups of microbiota were monitored over 48 h incubations by fluorescence in situ hybridisation. Short-chain fatty acids (SCFAs) were measured by high-performance liquid chromatography (HPLC). Furthermore, the death kinetics of Lactobacillus acidophilus, Bifidobacterium animalis subsp. lactis, Staphylococcus aureus, and Salmonella Typhimurium in a saline solution supplemented with GFB or CB were also assessed. The experiments in saline solution pinpointed that GFB prolonged the survival of L. acidophilus and exerted an antibacterial effect towards S. aureus and S. Typhimurium. Moreover, GFB modulated the intestinal microbiota in vitro, promoting changes in lactobacilli and bifidobacteria members in coeliac subjects. A final multivariate approach combining both viable counts and metabolites suggested that GFB could beneficially modulate the coeliac gut microbiome; however, human studies are needed to prove its efficacy. PMID:27632361

  17. Brain SPECT imaging and whole-body biodistribution with [{sup 123}I]ADAM - a serotonin transporter radiotracer in healthy human subjects

    Energy Technology Data Exchange (ETDEWEB)

    Lin, K.-J. [Graduate Institute of Clinical Medical Sciences, Chang-Gung University, Tao-Yuan 333, Taiwan (China); Molecular Imaging Center, Chang-Gung Memorial Hospital, Tao-Yuan 333, Taiwan (China); Department of Nuclear Medicine, Chang-Gung Memorial Hospital, Tao-Yuan 333, Taiwan (China); Liu, C.-Y. [Neuroscience Research Center, Chang-Gung Memorial Hospital, Tao-Yuan 333, Taiwan (China); Department of Psychiatry, Chang-Gung Memorial Hospital, Tao-Yuan 333, Taiwan (China); Wey, S.-P. [Molecular Imaging Center, Chang-Gung Memorial Hospital, Tao-Yuan 333, Taiwan (China); Department of Medical Imaging and Radiological Sciences, Chang-Gung University, Tao-Yuan 333, Taiwan (China); Hsiao, I.-T. [Molecular Imaging Center, Chang-Gung Memorial Hospital, Tao-Yuan 333, Taiwan (China); Department of Medical Imaging and Radiological Sciences, Chang-Gung University, Tao-Yuan 333, Taiwan (China); Wu, Jay [Health Physics Divisions, Atomic Energy Council, Institute of Nuclear Energy Research, Tao-Yuan 325, Taiwan (China); Fu, Y.-K. [Atomic Energy Council, Institute of Nuclear Energy Research, Tao-Yuan 325, Taiwan (China); Yen, T.-C. [Molecular Imaging Center, Chang-Gung Memorial Hospital, Tao-Yuan 333, Taiwan (China) and Department of Nuclear Medicine, Chang-Gung Memorial Hospital, Tao-Yuan 333, Taiwan (China)]. E-mail: yen1110@adm.cgmh.org.tw

    2006-02-15

    Introduction: [{sup 123}I]-2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine ([{sup 123}I]ADAM), a novel radiotracer, has promising application in the imaging of the serotonin transporter (SERT) in the human brain. In this study, the optimal scanning time for acquiring brain single photon emission computed tomography (SPECT) images was determined by performing dynamic SPECT studies at intervals from 0 to 6 h postinjection of [{sup 123}I]ADAM. Additionally, radiation-absorbed doses were determined for three healthy human subjects using attenuation-corrected images. Methods: Twelve subjects were randomized into one of three study groups as follows: whole-body distribution imaging (n=3), dynamic SPECT imaging (n=3) and brain SPECT imaging (n=6). The radiation-absorbed dose was calculated using MIRDOSE 3.0 software with attenuation-corrected data. The specific binding (SB) ratio of the brain stem was measured from dynamic SPECT images to determine the optimal scanning time. Results: Dynamic SPECT images showed that the SB of the brain stem gradually increased to a maximum 4 h postinjection. Single photon emission computed tomography images at 4 h postinjection showed a high uptake of the radiotracer (SB) in the hypothalamus (1.40{+-}0.12), brain stem (1.44{+-}0.16), pons (1.13{+-}0.14) and medial temporal lobe (0.59{+-}0.10). The mean adult male value of effective dose was 3.37x10{sup -2} mSv/MBq with a 4.8-h urine-voiding interval. Initial high uptake in SERT-rich sites was demonstrated in the lung and brain. A prominent washout of the radiotracer from the lung further increased brain radioactivity that reached a peak value of 5.03% of injected dose 40 min postinjection. Conclusions: [{sup 123}I]ADAM is a promising radiotracer for SPECT imaging of SERT in humans with acceptable dosimetry and high uptake in SERT-rich regions. Brain SPECT images taken within 4 h following injection show optimal levels of radiotracer uptake in known SERT sites. However, dynamic

  18. Evaluation of calcium, magnesium, potassium and sodium in biological samples of male human immunodeficiency virus patients with tuberculosis and diarrhea compared to healthy control subjects in Pakistan.

    Science.gov (United States)

    Afridi, Hassan Imran; Kazi, Tasneem Gul; Talpur, Farah Naz; Kazi, Naveed; Naeemullah, Faheem Shah; Arain, Sadaf Sadia; Brahman, Kapil Dev

    2013-01-01

    Electrolyte deficiency has been associated with an increased risk of human immunodeficiency virus type 1 (HIV-1) disease progression and mortality. This study examined the association between low electrolyte concentrations in blood and scalp hair and the presence of opportunistic infections in patients with acquired immune deficiency syndrome (AIDS). Sixty-two male HIV positive patients (HIV-1) from various cities in Pakistan were recruited to the study. These Patients were divided into two groups according to secondary infections (tuberculosis and high fever with diarrhea), and biological samples (scalp hair, serum, blood and urine) were collected from them. As a comparative control group, 120 healthy subjects (males) of the same age group (31 - 45 years), socio-economic status, localities and dietary habits were also included in the study. The elements in the biological samples were analyzed by flame atomic absorption spectrophotometry after microwave-assisted acid digestion. Validity and accuracy of the methodology were checked using certified reference materials (CRMs) and against values obtained by a conventional wet acid digestion method on the same CRMs. The results indicated significantly lower levels of calcium, potassium, magnesium and natrium in all analyzed biological samples (blood, serum and scalp hair) of male patients with Acquired Immune Deficiency Syndrome (AIDS) in comparison to healthy controls (p < 0.01), while the levels of these elements were found to be higher in urine samples of the AIDS patients than in those of the control group. These data offer guidance to clinicians and other professionals investigating the deficiency of electrolytes in biological samples (scalp hair, serum and blood) of AIDS patients in relation to healthy subjects.

  19. HIV-1 envelope glycoprotein resistance to monoclonal antibody 2G12 is subject-specific and context-dependent in macaques and humans.

    Directory of Open Access Journals (Sweden)

    Delphine C Malherbe

    Full Text Available HIV-1 Envelope (Env protein is the sole target of neutralizing antibodies (NAbs that arise during infection to neutralize autologous variants. Under this immune pressure, HIV escape variants are continuously selected and over the course of infection Env becomes more neutralization resistant. Many common alterations are known to affect sensitivity to NAbs, including residues encoding potential N-linked glycosylation sites (PNGS. Knowledge of Env motifs associated with neutralization resistance is valuable for the design of an effective Env-based vaccine so we characterized Envs isolated longitudinally from a SHIV(SF162P4 infected macaque for sensitivity to neutralizing monoclonal antibodies (MAbs B12, 2G12, 4E10 and 2F5. The early Env, isolated from plasma at day 56 after infection, was the most sensitive and the late Env, from day 670, was the most resistant to MAbs. We identified four PNGS in these Envs that accumulated over time at positions 130, 139, 160 and 397. We determined that removal of these PNGS significantly increased neutralization sensitivity to 2G12, and conversely, we identified mutations by in silico analyses that contributed resistance to 2G12 neutralization. In order to expand our understanding of these PNGS, we analyzed Envs from clade B HIV-infected human subjects and identified additional glycan and amino acid changes that could affect neutralization by 2G12 in a context-dependent manner. Taken together, these in vitro and in silico analyses of clade B Envs revealed that 2G12 resistance is achieved by previously unrecognized PNGS substitutions in a context-dependent manner and by subject-specific pathways.

  20. Human glioblastoma stem-like cells accumulate protoporphyrin IX when subjected to exogenous 5-aminolaevulinic acid, rendering them sensitive to photodynamic treatment.

    Science.gov (United States)

    Schimanski, Adrian; Ebbert, Lara; Sabel, Michael C; Finocchiaro, Gaetano; Lamszus, Katrin; Ewelt, Christian; Etminan, Nima; Fischer, Johannes C; Sorg, Rüdiger V

    2016-10-01

    Glioblastoma (GBM) is the most frequent and lethal primary brain tumor in adults. Despite multimodal therapy combining resection, radio- and alkylating chemotherapy, disease recurrence is universal and prognosis of patients is poor. Glioblastoma stem-like cells (GSC), which can be grown as neurospheres from primary tumors in vitro, appear to be resistant to the established therapies and are suspected to be the driving force for disease recurrence. Thus, efficacy of emerging therapies may depend on targeting GSC. 5-aminolaevulinic acid-mediated photodynamic therapy (5-ALA/PDT) is a promising therapeutic approach in GBM. It utilizes the selective accumulation of the photosensitizer protoporphyrin IX (PPIX) in GBM cells after application of 5-ALA. When exposed to laser light of 635nm wavelength, PPIX initiates a photochemical reaction resulting in the generation of reactive oxygen species, which kill the tumor cells. Whether GSC accumulate PPIX and are sensitive to 5-ALA/PDT is currently unknown. Therefore, human GSC were derived from primary tumors and grown as neurospheres under serum free conditions. When subjected to exogenous 5-ALA, a dose- and time-dependent accumulation of PPIX in GSC was observed by flow cytometry, which varied between individual GSC preparations. Subsequent exposure to laser light of 635nm wavelength substantially killed GSC, whereas treatment with 5-ALA or exposure to laser light only had no effect. LD50 values differed between GSC preparations, but were negatively correlated with PPIX accumulation in GSC. In summary, we report for the first time that glioblastoma stem-like cells accumulate PPIX when subjected to 5-aminolaevulinic acid and are sensitive to 5-aminolaevulinc acid based photodynamic therapy. Copyright © 2016 Elsevier B.V. All rights reserved.