WorldWideScience

Sample records for subjects include humans

  1. Verifying the attenuation of earplugs in situ: method validation on human subjects including individualized numerical simulations.

    Science.gov (United States)

    Bockstael, Annelies; Van Renterghem, Timothy; Botteldooren, Dick; D'Haenens, Wendy; Keppler, Hannah; Maes, Leen; Philips, Birgit; Swinnen, Freya; Vinck, Bart

    2009-03-01

    The microphone in real ear (MIRE) protocol allows the assessment of hearing protector's (HPD) attenuation in situ by measuring the difference between the sound pressure outside and inside the ear canal behind the HPD. Custom-made earplugs have been designed with an inner bore to insert the MIRE probe containing two microphones, the reference microphone measuring the sound pressure outside and the measurement microphone registering the sound pressure behind the HPD. Previous research on a head and torso simulator reveals a distinct difference, henceforth called transfer function, between the sound pressure at the MIRE measurement microphone and the sound pressure of interest at the eardrum. In the current study, similar measurements are carried out on humans with an extra microphone to measure the sound pressure at the eardrum. The resulting transfer functions confirm the global frequency dependency found earlier, but also show substantial variability between the ears with respect to the exact frequency and amplitude of the transfer functions' extrema. In addition, finite-difference time-domain numerical models of an ear canal with earplug are developed for each individual ear by including its specific geometrical parameters. This approach leads to a good resemblance between the simulations and their corresponding measurements.

  2. Including subjectivity in the teaching of Psychopathology

    Directory of Open Access Journals (Sweden)

    Octavio Domont de Serpa Junior

    2007-01-01

    Full Text Available Current psychopathology studies have often been presented in their descriptive dimension. This perspective is important for teaching because it helps the students to recognize and identify the symptomatology of each psychopathology case. However, subjectivity, the experience of suffering and interpersonal aspects are all lost in this perspective. Coming from another psychopathology tradition - existential anthropology - this paper presents practical psychopathology teaching experience which considers such dimensions as being relevant to the understanding of mental suffering. The features and limitations of such traditions are briefly reviewed to support this teaching experience. Two new modalities of practical teaching, used in the discipline of "Special Psychopathology I" offered by the Department of Psychiatry and Forensic Medicine at the medical school of the Federal University of Rio de Janeiro for students of psychology, will be presented according to descriptive case study methodology. With these activities we also expect to change the practice of teaching. Traditionally, interviewing of in-patients by a large group of students who observe passively what is happening is the center of this kind of education. We intend to develop a model of teaching which is closer to the proposal of the Brazilian Psychiatric Reform which views mental illness as a complex phenomenon, always involving the relationship that the subject establishes with the world.

  3. 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.

  4. Student Motivation in Science Subjects in Tanzania, Including Students' Voices

    Science.gov (United States)

    Mkimbili, Selina Thomas; Ødegaard, Marianne

    2017-12-01

    Fostering and maintaining students' interest in science is an important aspect of improving science learning. The focus of this paper is to listen to and reflect on students' voices regarding the sources of motivation for science subjects among students in community secondary schools with contextual challenges in Tanzania. We conducted a group-interview study of 46 Form 3 and Form 4 Tanzanian secondary school students. The study findings reveal that the major contextual challenges to student motivation for science in the studied schools are limited resources and students' insufficient competence in the language of instruction. Our results also reveal ways to enhance student motivation for science in schools with contextual challenges; these techniques include the use of questioning techniques and discourse, students' investigations and practical work using locally available materials, study tours, more integration of classroom science into students' daily lives and the use of real-life examples in science teaching. Also we noted that students' contemporary life, culture and familiar language can be utilised as a useful resource in facilitating meaningful learning in science in the school. Students suggested that, to make science interesting to a majority of students in a Tanzanian context, science education needs to be inclusive of students' experiences, culture and contemporary daily lives. Also, science teaching and learning in the classroom need to involve learners' voices.

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

    African Journals Online (AJOL)

    This study investigated human resource subjects' allocation and students' academic performance in Secondary Schools in Obudu, Nigeria. The relevant variables of teachers subject was used as independent variable while the dependent variables were students' academic performance. Six hundred teachers from 20 ...

  6. 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…

  7. 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...

  8. African Journals Online: Humanities (broad subject range)

    African Journals Online (AJOL)

    Items 1 - 50 of 55 ... It focuses both on conceptual or theoretical approaches and case studies or essays demonstrating how advanced information technologies further scholarly .... Global Journal of Humanities is aimed at promoting reasearch in all areas of Humanities including philosophy, languages, linguistics, literature, ...

  9. Calcitonin secretion in normal human subjects

    Energy Technology Data Exchange (ETDEWEB)

    Parthemore, J.G.; Deftos, L.J.

    1978-07-01

    A sensitive RIA for human calcitonin has been developed which can detect 1 to 2 pg hormone. This procedure permits the measurement of the low concentrations of calcitonin in the unextracted plasma of normal human subjects. In 55 normal adults, mean plasma calcitonin was 24 pg/ml with an SD of +-18 pg/ml, an SE of +-2 pg/ml, and a range of less than 10 to 75 pg/ml. There were no discernible age or sex differences in basal hormone concentration. Infusions of calcium, pentagastrin, and glucagon stimulated plasma calcitonin, whereas food and oral calcium did not. The stimulatory effect of pentagastrin was greater in males than in females. These data demonstrate that the low concentration of calcitonin in humans can be stimulated by several secretagogues and suggest that females may have decreased calcitonin reserve.

  10. subjective approach to subjective approach to human physiological

    African Journals Online (AJOL)

    eobe

    This study was based on the subjective responses of the masons that are performing physical activity of blocklaying in the outdoor condition in outdoor condition in outdoor condition in Ogun State Nigeria. A total of 204 masons were investigated on the average of seventeen. Ogun State Nigeria. A total of 204 masons were ...

  11. 48 CFR 1352.235-70 - Protection of human subjects.

    Science.gov (United States)

    2010-10-01

    ... subjects research protocol, all questionnaires, surveys, advertisements, and informed consent forms... . (f) In addition, if the contractor modifies a human subjects research protocol, questionnaire, survey... of Human Subjects (APR 2010) (a) Research involving human subjects is not permitted under this award...

  12. Reliability of Human Subject - Artificial System Interactions

    Directory of Open Access Journals (Sweden)

    M. Novák

    2002-01-01

    Full Text Available Main problems related to reliability of interaction between human subject and artificial system (namely of the transportation character are discussed. The paper consists of three mayor parts:The first one is devoted to the theoretical backgrounds of the problem from the both theory of system reliability and neurology/psychology views.Second part presents the discussion of relevant methodologies of the classification and prediction of the reliability decline. The methodology based on EEG pattern analysis is chosen as the appropriate one for the presented task. The key phenomenon of "micro-sleep" is discussed in detail.The last part presents some latest experimental results in context of presented knowledge. Proposals for the future studies are presented at the end of the presented article. The special interest should be devoted to the analysis and in-time prediction of fatal attention decreases and to the design and construction of the respective on-board applicable warning system.

  13. 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.

  14. Subjective Response to Foot-Fall Noise, Including Localization of the Source Position

    DEFF Research Database (Denmark)

    Brunskog, Jonas; Hwang, Ha Dong; Jeong, Cheol-Ho

    2011-01-01

    Although an impact noise level is objectively evaluated the same according to current standards, a lightweight floor structure is often subjectively judged more annoying than a heavy homogeneous structure. The hypothesis of the present investigation is that the subjective judgment of impact noise...

  15. 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)

  16. Measuring human wellbeing in Pakistan: objective versus subjective indicators

    OpenAIRE

    Haq, Rashida

    2009-01-01

    The concern for measuring wellbeing objectively and subjectively is found in modern political philosophy. This study explores objective indicators versus subjective perceptions of human wellbeing in ranking of survey data for districts of Pakistan. Data used for the analysis is ‘The Pakistan Social and Living Standards Measurement Survey’ for the year 2006-07. The human wellbeing is examined in four domains: education, health, living conditions and economic situation. Principal component anal...

  17. Pesticide testing on human subjects: weighing benefits and risks.

    Science.gov (United States)

    Resnik, David B; Portier, Christopher

    2005-07-01

    In the debate surrounding testing pesticides on human subjects, two distinct positions have emerged. The first position holds that pesticide experiments on human subjects should be allowed, but only under stringent scientific and ethical standards. The second position asserts that these experiments should never be allowed. In this article, we evaluate what we consider to be the strongest argument for the second position--namely, that the benefits of the experiments are not significant enough to justify the risks posed to healthy subjects. We challenge this argument by examining the benefits and risks of testing pesticides on human subjects. We argue that a study that intentionally exposes humans subjects to pesticides should be permitted if a) the knowledge gained from the study is expected to promote human health; b) the knowledge cannot be reasonably obtained by other means; c) the study is not expected to cause serious or irreversible harm to the subjects; and d) appropriate safeguards are in place to minimize harm to the subjects.

  18. Pesticide Testing on Human Subjects: Weighing Benefits and Risks

    Science.gov (United States)

    Resnik, David B.; Portier, Christopher

    2005-01-01

    In the debate surrounding testing pesticides on human subjects, two distinct positions have emerged. The first position holds that pesticide experiments on human subjects should be allowed, but only under stringent scientific and ethical standards. The second position asserts that these experiments should never be allowed. In this article, we evaluate what we consider to be the strongest argument for the second position—namely, that the benefits of the experiments are not significant enough to justify the risks posed to healthy subjects. We challenge this argument by examining the benefits and risks of testing pesticides on human subjects. We argue that a study that intentionally exposes humans subjects to pesticides should be permitted if a) the knowledge gained from the study is expected to promote human health; b) the knowledge cannot be reasonably obtained by other means; c) the study is not expected to cause serious or irreversible harm to the subjects; and d) appropriate safeguards are in place to minimize harm to the subjects. PMID:16002367

  19. Ethics of Research Involving Human Subjects in Criminal Justice

    Science.gov (United States)

    Bloomberg, Seth Allan; Wilkins, Leslie T.

    1977-01-01

    Research in criminal justice involving human subjects has increased greatly, yet we have no code of ethics to guide such research. This paper argues that the primary purpose of a code should be protection of these research subjects, who are especially susceptible to mistreatment because of their prisoner status. (Author)

  20. Parental Perspectives on a Pediatric Human Non-Subjects Biobank

    Science.gov (United States)

    Brothers, Kyle B.; Clayton, Ellen Wright

    2012-01-01

    Background Genomic biorepositories will be important tools to help unravel the effect of common genetic variants on risk for common pediatric diseases. Our objective was to explore how parents would respond to the inclusion of children in an opt-out model biobank. Methods We conducted semi-structured interviews with parents in hospital-based pediatric clinics. Participants responded to a description of a biorepository already collecting samples from adults. Two coders independently analyzed and coded interviews using framework analysis. Opt-out forms were later piloted in a clinic area. Parental opt-out choices were recorded electronically, with opt-out rates reported here. Results Parents strongly supported medical research in general and expressed a high level of trust that Vanderbilt University would keep their child’s medical information private. Parents were more likely to allow their child’s sample to be included in the biorepository than to allow their child to participate in a hypothetical study that would not help or harm their child, but might help other children. Only a minority were able to volunteer a concern raised by the description of the biobank. The opt-out rate was initially high compared with the opt-out rate in the adult biorepository, but after the first week decreased to near the baseline in adult clinics. Conclusion Parents in our study generally support an opt-out model biobank in children. Most would allow their own child’s sample to be included. Institutions seeking to build pediatric biobanks may consider the human non-subjects model as a viable alternative to traditional human-subjects biobanks. PMID:23181193

  1. 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.

  2. Oat have multifunctional uses including animal feed, human food ...

    African Journals Online (AJOL)

    Akademia Rolnicza

    2014-07-11

    Welch, 1995; Peterson,. 1998; Zhou et al., 1998). Increasing interest in oat utilization for human consumption has been stimulated by the need for soluble fibre, particularly β-glucans in diet, which have beneficial effects on ...

  3. 76 FR 44512 - Human Subjects Research Protections: Enhancing Protections for Research Subjects and Reducing...

    Science.gov (United States)

    2011-07-26

    ... organizations (CROs), data and safety monitoring committees, community-based organizations, and other entities... neuroscience has led to substantial advances in the understanding of human physiology, cognition, and behavior... subjects? What entity or organization should develop and disseminate such standardized document formats...

  4. BIOLOGY OF HUMAN MALARIA PLASMODIA INCLUDING PLASMODIUM KNOWLESI

    Directory of Open Access Journals (Sweden)

    Spinello Antinori

    2012-03-01

    Full Text Available Malaria is a vector-borne infection caused by unicellular parasite of the genus Plasmodium. Plasmodia are obligate intracellular parasites that in humans after a clinically silent replication phase in the liver are able to infect and replicate within the erythrocytes. Four species (P.falciparum, P.malariae, P.ovale and P.vivax are traditionally recognized as responsible of natural infection in human beings but the recent upsurge of P.knowlesi malaria in South-East Asia has led clinicians to consider it as the fifth human malaria parasite. Recent studies in wild-living apes in Africa have revealed that P.falciparum, the most deadly form of human malaria, is not only human-host restricted as previously believed and its phylogenetic lineage is much more complex with new species identified in gorilla, bonobo and chimpanzee. Although less impressive, new data on biology of P.malariae, P.ovale and P.vivax are also emerging and will be briefly discussed in this review.

  5. 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…

  6. Human-computer interface including haptically controlled interactions

    Science.gov (United States)

    Anderson, Thomas G.

    2005-10-11

    The present invention provides a method of human-computer interfacing that provides haptic feedback to control interface interactions such as scrolling or zooming within an application. Haptic feedback in the present method allows the user more intuitive control of the interface interactions, and allows the user's visual focus to remain on the application. The method comprises providing a control domain within which the user can control interactions. For example, a haptic boundary can be provided corresponding to scrollable or scalable portions of the application domain. The user can position a cursor near such a boundary, feeling its presence haptically (reducing the requirement for visual attention for control of scrolling of the display). The user can then apply force relative to the boundary, causing the interface to scroll the domain. The rate of scrolling can be related to the magnitude of applied force, providing the user with additional intuitive, non-visual control of scrolling.

  7. 48 CFR 1352.235-71 - Protection of human subjects-exemption.

    Science.gov (United States)

    2010-10-01

    ...; (2) Documentation of approval for the human subjects research protocol, questionnaires, surveys..., if the contractor modifies a human subjects research protocol, questionnaire, survey, advertisement... forth in solicitation #____, related to the Protection of Human Subjects in research. The Government has...

  8. Beyond human subjects: risk, ethics, and clinical development of nanomedicines.

    Science.gov (United States)

    Kimmelman, Jonathan

    2012-01-01

    Clinical testing of nanomedicines presents two challenges to prevailing, human subject-centered frameworks governing research ethics. First, some nanomedical applications may present risk to persons other than research subjects. Second, pressures encountered in testing nanomedicines may present threats to the kinds of collaborations and collective activities needed for supporting clinical translation and redeeming research risk. In this article, I describe how similar challenges were encountered and addressed in gene transfer, and sketch policy options that might be explored in the nanomedicine translation arena. © 2012 American Society of Law, Medicine & Ethics, Inc.

  9. Humanized care; the case of patients subjected to chemotherapy

    OpenAIRE

    Luz Viviana Grisales-Naranjo; María Mercedes Arias-Valencia

    2013-01-01

    Objective. Herein, we seek to know the necessities of humanized care of patients subjected to chemotherapy. Methodology. The study was carried out with patients, of both sexes, diagnosed with different types of cancer who received chemotherapy treatment in an oncology unit of the city of Medellín, Colombia during 2011. A qualitative approach was used with tools from grounded theory; 23 interviews were conducted and a field diary was kept. During the analysis, codes were extracted that were su...

  10. Intranasal oxytocin blocks alcohol withdrawal in human subjects.

    Science.gov (United States)

    Pedersen, Cort A; Smedley, Kelly L; Leserman, Jane; Jarskog, Lars Fredrik; Rau, Shane W; Kampov-Polevoi, Alexei; Casey, Robin L; Fender, Trace; Garbutt, James C

    2013-03-01

    The neuropeptide, oxytocin (OT), has been reported to block tolerance formation to alcohol and decrease withdrawal symptoms in alcohol-dependent rodents. Numerous recent studies in human subjects indicate that OT administered by the intranasal route penetrates into and exerts effects within the brain. In a randomized, double-blind clinical trial, intranasal OT (24 IU/dose, N = 7) or placebo (N = 4) was given twice daily for 3 days in alcohol-dependent subjects admitted to a research unit for medical detoxification using Clinical Institute Withdrawal Assessment for Alcohol (CIWA) score-driven PRN administration of lorazepam. Subjects rated themselves on the Alcohol Withdrawal Symptom Checklist (AWSC) each time CIWA scores were obtained. Subjects also completed the Penn Alcohol Craving Scale, an Alcohol Craving Visual Analog Scale (ACVAS) and the Profile of Mood States (POMS) on inpatient days 2 and 3. All subjects had drunk heavily each day for at least 2 weeks prior to study and had previously experienced withdrawal upon stopping/decreasing alcohol consumption. OT was superior to placebo in reducing alcohol withdrawal as evidenced by: less total lorazepam required to complete detoxification (3.4 mg [4.7, SD] vs. 16.5 [4.4], p = 0.0015), lower mean CIWA scores on admission day 1 (4.3 [2.3] vs. 11.8 [0.4], p block alcohol withdrawal in human subjects. Our results are consistent with previous findings in rodents that OT inhibits neuroadaptation to and withdrawal from alcohol. OT could have advantages over benzodiazepines in managing alcohol withdrawal because it may reverse rather than maintain sedative-hypnotic tolerance. It will be important to test whether OT treatment is effective in reducing drinking in alcohol-dependent outpatients. Copyright © 2012 by the Research Society on Alcoholism.

  11. Cardiac monitoring of human subjects exposed to the taser.

    Science.gov (United States)

    Levine, Saul D; Sloane, Christian M; Chan, Theodore C; Dunford, James V; Vilke, Gary M

    2007-08-01

    The Taser (TASER International, Scottsdale, AZ) is a high-voltage, low-amperage device used by many law enforcement agencies. Our objective in this study was to evaluate for rhythm changes utilizing cardiac monitoring during deployment of the Taser on volunteers. A prospective, observational study evaluated law enforcement personnel who had continuous electrocardiographic monitoring immediately before, during, and after having a voluntary exposure to the Taser X-26. Changes in cardiac rate, rhythm, ectopy, morphology, and conduction intervals were measured. A total of 105 subjects were evaluated. The mean shock duration was 3.0 s (range 0.9-5 s). Mean heart rate increased 15 beats/min (95% CI 12.6-18.3), from 122 beats/min before shock to 137 beats/min immediately after shock. One subject had a single premature ventricular contraction both before and after the shock, but no other subject developed ectopy or dysrhythmia. Poor inter-rater agreement prevented determination of the overall effect of shock on conduction intervals. However, several interpretable tracings demonstrated change in QT duration-either shortening or prolongation after shock. Human subjects exposed to a brief shock from the Taser developed significant increases in heart rate, but there were no cardiac dysrhythmias or morphologic changes. Alterations in the QT interval were observed in some subjects but their true incidence and clinical significance are unknown.

  12. Non-Human Primates Harbor Diverse Mammalian and Avian Astroviruses Including Those Associated with Human Infections.

    Directory of Open Access Journals (Sweden)

    Erik A Karlsson

    Full Text Available Astroviruses (AstVs are positive sense, single-stranded RNA viruses transmitted to a wide range of hosts via the fecal-oral route. The number of AstV-infected animal hosts has rapidly expanded in recent years with many more likely to be discovered because of the advances in viral surveillance and next generation sequencing. Yet no study to date has identified human AstV genotypes in animals, although diverse AstV genotypes similar to animal-origin viruses have been found in children with diarrhea and in one instance of encephalitis. Here we provide important new evidence that non-human primates (NHP can harbor a wide variety of mammalian and avian AstV genotypes, including those only associated with human infection. Serological analyses confirmed that >25% of the NHP tested had antibodies to human AstVs. Further, we identified a recombinant AstV with parental relationships to known human AstVs. Phylogenetic analysis suggests AstVs in NHP are on average evolutionarily much closer to AstVs from other animals than are AstVs from bats, a frequently proposed reservoir. Our studies not only demonstrate that human astroviruses can be detected in NHP but also suggest that NHP are unique in their ability to support diverse AstV genotypes, further challenging the paradigm that astrovirus infection is species-specific.

  13. Subjective cognitive complaints included in diagnostic evaluation of dementia helps accurate diagnosis in a mixed memory clinic cohort

    DEFF Research Database (Denmark)

    Salem, L C; Vogel, Asmus Mejling; Ebstrup, J

    2015-01-01

    functions were assessed with the Mini-mental state examination (MMSE) and Addenbrooke's cognitive examination (ACE), and symptoms of depression were rated with Major Depression Inventory (MDI). All interviews and the diagnostic conclusion were blinded to the SMC score. RESULTS: We found that young patients......OBJECTIVE: Our objective was to examine the quantity and profile of subjective cognitive complaints in young patients as compared with elderly patients referred to a memory clinic. METHODS: Patients were consecutively recruited from the Copenhagen University Hospital Memory Clinic at Rigshospitalet....... In total, 307 patients and 149 age-matched healthy controls were included. Patients were classified in 4 diagnostic groups: dementia, mild cognitive impairment, affective disorders and no cognitive impairment. Subjective memory was assessed with subjective memory complaints (SMC) scale. Global cognitive...

  14. Humanized care; the case of patients subjected to chemotherapy

    Directory of Open Access Journals (Sweden)

    Luz Viviana Grisales-Naranjo

    2013-12-01

    Full Text Available Objective. Herein, we seek to know the necessities of humanized care of patients subjected to chemotherapy. Methodology. The study was carried out with patients, of both sexes, diagnosed with different types of cancer who received chemotherapy treatment in an oncology unit of the city of Medellín, Colombia during 2011. A qualitative approach was used with tools from grounded theory; 23 interviews were conducted and a field diary was kept. During the analysis, codes were extracted that were subsequently grouped into categories that best represented the phenomenon studied. Results. Cancer patients subjected to chemotherapy have needs for humanized care. The emotional, spiritual, social, and affective necessities were highlighted as a consequence of the impact of the news of the diagnosis and the notorious physical changes confronted by these patients. The category of dehumanization of care emerged related to the information of the diagnosis and in the communication the personnel maintained with these patients. Conclusion. The cancer patient receiving chemotherapy is a seriously ill person, with necessities, who requires humanized care by the healthcare provider personnel.

  15. The Human Brain Encodes Event Frequencies While Forming Subjective Beliefs

    Science.gov (United States)

    d’Acremont, Mathieu; Schultz, Wolfram; Bossaerts, Peter

    2015-01-01

    To make adaptive choices, humans need to estimate the probability of future events. Based on a Bayesian approach, it is assumed that probabilities are inferred by combining a priori, potentially subjective, knowledge with factual observations, but the precise neurobiological mechanism remains unknown. Here, we study whether neural encoding centers on subjective posterior probabilities, and data merely lead to updates of posteriors, or whether objective data are encoded separately alongside subjective knowledge. During fMRI, young adults acquired prior knowledge regarding uncertain events, repeatedly observed evidence in the form of stimuli, and estimated event probabilities. Participants combined prior knowledge with factual evidence using Bayesian principles. Expected reward inferred from prior knowledge was encoded in striatum. BOLD response in specific nodes of the default mode network (angular gyri, posterior cingulate, and medial prefrontal cortex) encoded the actual frequency of stimuli, unaffected by prior knowledge. In this network, activity increased with frequencies and thus reflected the accumulation of evidence. In contrast, Bayesian posterior probabilities, computed from prior knowledge and stimulus frequencies, were encoded in bilateral inferior frontal gyrus. Here activity increased for improbable events and thus signaled the violation of Bayesian predictions. Thus, subjective beliefs and stimulus frequencies were encoded in separate cortical regions. The advantage of such a separation is that objective evidence can be recombined with newly acquired knowledge when a reinterpretation of the evidence is called for. Overall this study reveals the coexistence in the brain of an experience-based system of inference and a knowledge-based system of inference. PMID:23804108

  16. Subjectivity

    Directory of Open Access Journals (Sweden)

    Jesús Vega Encabo

    2015-11-01

    Full Text Available In this paper, I claim that subjectivity is a way of being that is constituted through a set of practices in which the self is subject to the dangers of fictionalizing and plotting her life and self-image. I examine some ways of becoming subject through narratives and through theatrical performance before others. Through these practices, a real and active subjectivity is revealed, capable of self-knowledge and self-transformation. 

  17. 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

  18. 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.

  19. Developing the Immunology Book for Animal and Human Physiology Subject

    Directory of Open Access Journals (Sweden)

    Zuni Mitasari

    2017-07-01

    Full Text Available he objective of the study was to develop an immunology book for Animal and Human Physiology subject. This book was developed based on the Thiagarajan development model which was modified of: Define, Design, Develop, dan Disseminate (4D. The data expert validation instrument was questionnaire using Likert scales, comments, and recommendation sheets. Expert appraisal was done by material expert and media and design learning expert. The developmental testing was conducted using questionnaire to test the readibility. The expert validation was conducted by material expert as well as design and media learning expert validator; meanwhile, the field test was done to measure the readability. The validity test results were: the material expert state that the material is valid (97.14%, as well as the design and learning media expert (84.88% and field test by students (88.17%.

  20. 15 CFR 27.119 - Research undertaken without the intention of involving human subjects.

    Science.gov (United States)

    2010-01-01

    ... intention of involving human subjects. 27.119 Section 27.119 Commerce and Foreign Trade Office of the Secretary of Commerce PROTECTION OF HUMAN SUBJECTS § 27.119 Research undertaken without the intention of involving human subjects. In the event research is undertaken without the intention of involving human...

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

    Science.gov (United States)

    Wolf, Susan M.; Jones, Cortney M.

    2011-04-01

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

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

    Science.gov (United States)

    Wolf, Susan M.; Jones, Cortney

    2012-01-01

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

  3. Human Amygdala Represents the Complete Spectrum of Subjective Valence

    Science.gov (United States)

    Jin, Jingwen; Zelano, Christina; Gottfried, Jay A.

    2015-01-01

    Although the amygdala is a major locus for hedonic processing, how it encodes valence information is poorly understood. Given the hedonic potency of odor stimuli and the amygdala's anatomical proximity to the peripheral olfactory system, we combined high-resolution fMRI with pattern-based multivariate techniques to examine how valence information is encoded in the amygdala. Ten human subjects underwent fMRI scanning while smelling 9 odorants that systematically varied in perceived valence. Representational similarity analyses showed that amygdala codes the entire dimension of valence, ranging from pleasantness to unpleasantness. This unidimensional representation significantly correlated with self-reported valence ratings but not with intensity ratings. Furthermore, within-trial valence representations evolved over time, prioritizing earlier differentiation of unpleasant stimuli. Together, these findings underscore the idea that both spatial and temporal features uniquely encode pleasant and unpleasant odor valence in the amygdala. The availability of a unidimensional valence code in the amygdala, distributed in both space and time, would create greater flexibility in determining the pleasantness or unpleasantness of stimuli, providing a mechanism by which expectation, context, attention, and learning could influence affective boundaries for guiding behavior. SIGNIFICANCE STATEMENT Our findings elucidate the mechanisms of affective processing in the amygdala by demonstrating that this brain region represents the entire valence dimension from pleasant to unpleasant. An important implication of this unidimensional valence code is that pleasant and unpleasant valence cannot coexist in the amygdale because overlap of fMRI ensemble patterns for these two valence extremes obscures their unique content. This functional architecture, whereby subjective valence maps onto a pattern continuum between pleasant and unpleasant poles, offers a robust mechanism by which context

  4. 34 CFR 97.119 - Research undertaken without the intention of involving human subjects.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Research undertaken without the intention of involving... Protection of Human Research Subjects) § 97.119 Research undertaken without the intention of involving human subjects. In the event research is undertaken without the intention of involving human subjects, but it is...

  5. 32 CFR 219.119 - Research undertaken without the intention of involving human subjects.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Research undertaken without the intention of... undertaken without the intention of involving human subjects. In the event research is undertaken without the intention of involving human subjects, but it is later proposed to involve human subjects in the research...

  6. 49 CFR 11.119 - Research undertaken without the intention of involving human subjects.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Research undertaken without the intention of... PROTECTION OF HUMAN SUBJECTS § 11.119 Research undertaken without the intention of involving human subjects. In the event research is undertaken without the intention of involving human subjects, but it is...

  7. 28 CFR 46.119 - Research undertaken without the intention of involving human subjects.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Research undertaken without the intention... (CONTINUED) PROTECTION OF HUMAN SUBJECTS § 46.119 Research undertaken without the intention of involving human subjects. In the event research is undertaken without the intention of involving human subjects...

  8. 16 CFR 1028.119 - Research undertaken without the intention of involving human subjects.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Research undertaken without the intention of... GENERAL PROTECTION OF HUMAN SUBJECTS § 1028.119 Research undertaken without the intention of involving human subjects. In the event research is undertaken without the intention of involving human subjects...

  9. 7 CFR 1c.119 - Research undertaken without the intention of involving human subjects.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Research undertaken without the intention of involving... HUMAN SUBJECTS § 1c.119 Research undertaken without the intention of involving human subjects. In the event research is undertaken without the intention of involving human subjects, but it is later proposed...

  10. 22 CFR 225.119 - Research undertaken without the intention of involving human subjects.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Research undertaken without the intention of... PROTECTION OF HUMAN SUBJECTS § 225.119 Research undertaken without the intention of involving human subjects. In the event research is undertaken without the intention of involving human subjects, but it is...

  11. 40 CFR 26.119 - Research undertaken without the intention of involving human subjects.

    Science.gov (United States)

    2010-07-01

    ... intention of involving human subjects. 26.119 Section 26.119 Protection of Environment ENVIRONMENTAL... Research Conducted or Supported by EPA § 26.119 Research undertaken without the intention of involving human subjects. In the event research is undertaken without the intention of involving human subjects...

  12. Historic Preservation An unusual way to protect human subjects in research

    Energy Technology Data Exchange (ETDEWEB)

    Prendergast, Ellen L.

    2001-09-15

    The Hanford Cultural Resources Laboratory (HCRL) at the Hanford Site interacts with human subjects in a variety of ways, some of which constitute human subjects research. A key element in this work is determining what constitutes 'research' and thus requires application of special measures to protect human subjects.

  13. 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.

  14. S5-4: Formal Modeling of Affordance in Human-Included Systems

    Directory of Open Access Journals (Sweden)

    Namhun Kim

    2012-10-01

    Full Text Available In spite of it being necessary for humans to consider modeling, analysis, and control of human-included systems, it has been considered a challenging problem because of the critical role of humans in complex systems and of humans' capability of executing unanticipated actions–both beneficial and detrimental ones. Thus, to provide systematic approaches to modeling human actions as a part of system behaviors, a formal modeling framework for human-involved systems in which humans play a controlling role based on their perceptual information is presented. The theory of affordance provides definitions of human actions and their associated properties; Finite State Automata (FSA based modeling is capable of mapping nondeterministic humans into computable components in the system representation. In this talk, we investigate the role of perception in human actions in the system operation and examine the representation of perceptual elements in affordance-based modeling formalism. The proposed framework is expected to capture the natural ways in which humans participate in the system as part of its operation. A human-machine cooperative manufacturing system control example and a human agent simulation example will be introduced for the illustrative purposes at the end of the presentation.

  15. 45 CFR 46.119 - Research undertaken without the intention of involving human subjects.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Research undertaken without the intention of... Subjects § 46.119 Research undertaken without the intention of involving human subjects. In the event research is undertaken without the intention of involving human subjects, but it is later proposed to...

  16. 10 CFR 745.119 - Research undertaken without the intention of involving human subjects.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Research undertaken without the intention of involving....119 Research undertaken without the intention of involving human subjects. In the event research is undertaken without the intention of involving human subjects, but it is later proposed to involve human...

  17. 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'…

  18. Thirst perception and drinking in euhydrate and dehydrate human subjects.

    Science.gov (United States)

    Obika, L F O; Idu, F K; George, G O; Ajayi, O I; Mowoe, R S

    2009-06-01

    Studies on how the body senses the need to correct extracellular and intracellular volumes and ionic concentration changes is relatively scanty. The present studies were designed to determine the effect of oral distilled water (DW) and saline loads, gargling with DW and DW preload on thirst perception (TP) and drinking in euhydrate and dehydrated subjects. The subjects were healthy male volunteers between the ages of 17 and 35 years. Group A subjects were given DW or various concentrations of sodium chloride [NaCl] orally. Subjects in groups B, C and D were dehydrated for 18 hours before the experiment. Group B gargled 500 ml of DW in divided volume of 50 ml at five minutes interval over a period of 50 minutes. Group C gargled with DW and different concentrations of NaCl. Group D were preloaded with four volumes of DW before ad libitum DW intake. TP was rated using the Visual Analogue Scale. Results showed that in Group A, drinking DW reduced TP, suggesting that baseline TP in normal euhydrate subjects is slightly elevated. Drinking DW reduced TP more than drinking NaCl solutions. Gargling resulted in a gradual fall in TP. The decrease in TP was statistically significant after 30 minutes of gargling. Gargling with different concentrations of NaCl solutions resulted in significant reductions in TP in all the groups. There was a significant decrease in TP in the group preloaded with 1000 ml of distilled water at 5 minutes of rehydration. At 20 minutes TP was abolished suggesting that approximately 1000 ml of water was needed for the rehydration. These results show that baseline TP in euhydrates is elevated and that TP increases in dehydrated subjects. Gargling reduces TP, but did not abolish thirst. It is suggested that a fall in plasma osmolality due to drinking may be responsible for abolishing thirst.

  19. 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.

  20. Proteomic signatures of human oral epithelial cells in HIV-infected subjects.

    Directory of Open Access Journals (Sweden)

    Elizabeth Yohannes

    Full Text Available The oral epithelium, the most abundant structural tissue lining the oral mucosa, is an important line of defense against infectious microorganisms. HIV infected subjects on highly active antiretroviral therapy (HAART are susceptible to comorbid viral, bacterial and fungal infections in the oral cavity. To provide an assessment of the molecular alterations of oral epithelia potentially associated with susceptibility to comorbid infections in such subjects, we performed various proteomic studies on over twenty HIV infected and healthy subjects. In a discovery phase two Dimensional Difference Gel Electrophoresis (2-D DIGE analyses of human oral gingival epithelial cell (HOEC lysates were carried out; this identified 61 differentially expressed proteins between HIV-infected on HAART subjects and healthy controls. Down regulated proteins in HIV-infected subjects include proteins associated with maintenance of protein folding and pro- and anti-inflammatory responses (e.g., heat-shock proteins, Cryab, Calr, IL-1RA, and Galectin-3-binding protein as well as proteins involved in redox homeostasis and detoxification (e.g., Gstp1, Prdx1, and Ero1. Up regulated proteins include: protein disulfide isomerases, proteins whose expression is negatively regulated by Hsp90 (e.g., Ndrg1, and proteins that maintain cellular integrity (e.g., Vimentin. In a verification phase, proteins identified in the protein profiling experiments and those inferred from Ingenuity Pathway Analysis were analyzed using Western blotting analysis on separate HOEC lysate samples, confirming many of the discovery findings. Additionally in HIV-infected patient samples Heat Shock Factor 1 is down regulated, which explains the reduced heat shock responses, while activation of the MAPK signal transduction cascade is observed. Overall, HAART therapy provides an incomplete immune recovery of the oral epithelial cells of the oral cavity for HIV-infected subjects, and the toxic side effects of

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

    Science.gov (United States)

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

    2009-01-01

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

  2. 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.

  3. Comorbid subjective health complaints in patients with sciatica: a prospective study including comparison with the general population.

    Science.gov (United States)

    Grøvle, Lars; Haugen, Anne J; Ihlebaek, Camilla M; Keller, Anne; Natvig, Bård; Brox, Jens I; Grotle, Margreth

    2011-06-01

    Chronic nonspecific low back pain is accompanied by high rates of comorbid mental and physical conditions. The aims of this study were to investigate if patients with specific back pain, that is, sciatica caused by lumbar herniation, report higher rates of subjective health complaints (SHCs) than the general population and if there is an association between change in sciatica symptoms and change in SHCs over a 12-month period. A multicenter cohort study of 466 sciatica patients was conducted with follow-up at 3 months and 1 year. Comorbid SHCs were measured by 27 items of the SHC inventory. Odds ratios (ORs) for each SHC were calculated with comparison to a general population sample (n=928) by logistic regression. The SHC number was calculated by summing all complaints present. At baseline, the ORs for reporting SHCs for the sciatica patients were significantly elevated in 15 of the 27 items with a mean (S.D.) SHC number of 7.5 (4.4), compared to 5.2 (4.4) in the general population (Psciatica, the SHC number was reduced to normal levels. Among those with persisting or worsening sciatica, the number increased to a level almost double that of the general population. Compared to the general population, the prevalence of subjective health complaints in sciatica is increased. During follow-up, the number of health complaints increased in patients with persisting or worsening sciatica. Copyright © 2010 Elsevier Inc. All rights reserved.

  4. Protecting the Teaching and Learning Environment: A Hybrid Model for Human Subject Research Public Policy Implementation

    Science.gov (United States)

    Hottenstein, Kristi N.

    2017-01-01

    Regulations for research involving human subjects have long been a critical issue in higher education. Federal public policy for research involving human subjects impacts institutions of higher education by requiring all federally funded research to be passed by an Institutional Review Board (IRB). Undergraduate research is no exception. Given the…

  5. 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.

  6. 45 CFR 690.119 - Research undertaken without the intention of involving human subjects.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Research undertaken without the intention of involving human subjects. 690.119 Section 690.119 Public Welfare Regulations Relating to Public Welfare... the intention of involving human subjects. In the event research is undertaken without the intention...

  7. 38 CFR 16.119 - Research undertaken without the intention of involving human subjects.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Research undertaken without the intention of involving human subjects. 16.119 Section 16.119 Pensions, Bonuses, and Veterans... the intention of involving human subjects. In the event research is undertaken without the intention...

  8. 14 CFR 1230.119 - Research undertaken without the intention of involving human subjects.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Research undertaken without the intention... SPACE ADMINISTRATION PROTECTION OF HUMAN SUBJECTS § 1230.119 Research undertaken without the intention of involving human subjects. In the event research is undertaken without the intention of involving...

  9. 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.

  10. [Characteristics of blood aggregation in human subjects of different age categories during normobaric interval hypo-oxytraining].

    Science.gov (United States)

    Subbotina, L A; Stepanov, V K; Dvornikov, M V

    2006-01-01

    Blood aggregation was studied in human subjects of different age groups given normobaric hypooxytraining. The experiment was performed with participation of two groups of volunteers: experienced human subjects well-adapted to hypoxia and young non-adapted subjects. NOT protocol included 7 min of breathing hypoxic mixture (90% N2 and 10% O2) and 3 min of breathing atmospheric air at room temperature, 6 cycles every other day during one month. Blood aggregation was assessed by 26 parameters with the use of a multifunctional diagnostic system that permitted biophysical (rheologic), biochemical (coagulative) and mathematic (systemic) diagnostics. Two groups of the human subjects displayed significantly different reactions to of blood aggregation to the extreme factor (NOT). There was a marked dependence of the blood aggregation reaction to the hypoxic factor on the body protective-adaptive potential. Our data substantiate the need to develop NOT protocols for pilots of specific ages.

  11. Pancreatic enzyme synthesis and turnover in human subjects.

    Science.gov (United States)

    O'Keefe, S J; Bennet, W M; Zinsmeister, A R; Haymond, M W

    1994-05-01

    Animal studies have shown that pancreatic enzyme secretion is independent of enzyme synthesis. To investigate this relationship in humans, we have coinfused 14C-labeled leucine tracer with cholecystokinin octapeptide in nine healthy adults for 4 h and measured the rate of appearance of secreted and newly labeled enzymes in the duodenum. Enzyme secretion was well maintained throughout, but newly labeled enzymes only appeared in juice between 75 and 101 min (median time, 86 min), indicating that initial secretion was dependent on the release of zymogen stores and that the median production time for new enzymes was 86 min. Between 85 and 225 min there was a curvilinear increase in the enrichment of secreted enzymes with newly synthesized enzymes, suggesting a median turnover rate of zymogen stores of 29%/h (range 12-47%/h). In conclusion, our results suggest that in healthy humans, postprandial pancreatic enzyme secretion is maintained by the export of a large stored pool and is not rate limited by enzyme synthesis, since it takes approximately 86 min for newly synthesized enzymes to take part in the digestive process.

  12. Physiology and biochemistry of human subjects during entrapment.

    Science.gov (United States)

    Agapiou, A; Mikedi, K; Karma, S; Giotaki, Z K; Kolostoumbis, D; Papageorgiou, C; Zorba, E; Spiliopoulou, C; Amann, A; Statheropoulos, M

    2013-03-01

    A classification of various categories of entrapped people under the ruins of collapsed buildings after earthquakes, technical failures or explosions is proposed. Type and degree of injury at the moment of building collapse and duration of entrapment are the two basic parameters in this classification. The aim is to provide sources and types of volatile organic compounds (VOCs) that can be used for establishing a new method for locating entrapped victims based on human chemical signatures. Potential target compounds, among others, are ammonia, acetone, isoprene, dimethylsulfide, dimethyldisulfide and trimethylamine. In this context, the possible neuroendocrine, metabolic and physical responses of potential victims during the different types of entrapment are correlated with the sources of VOCs such as expired air, urine, blood and sweat. The proposed classification scheme was developed as part of an integrated research project which investigates the use of combined audio, video and chemical methods for the early location of entrapped people under the ruins of collapsed buildings.

  13. 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.

  14. Research in the hospital setting on human subjects. Protecting the patient and the institution.

    Science.gov (United States)

    Scheuer, R

    1993-10-01

    A hospital's institutional review board is charged with the responsibility of fully protecting the rights of research subjects. In doing so, the board establishes that research protocols are based on sound scientific principles, that benefits to research subjects outweigh the risks, and that the subject's consent is informed and not coerced. Although it has been argued that risk management has no role in the activities of such boards, the literature indicates that risk management and quality assurance principles apply to all areas of the institution, including the activities of the board. The institution must ensure that its researchers and board members are as fully protected as possible from civil and criminal liability and that the integrity of those conducting the research is established and maintained. The institution must also provide sufficient support for the board to conduct its reviews and educate the research community and board members on current and evolving laws and regulations governing human research. Risk prevention and quality assurance strategies should recognize the rights of the research subject as paramount while protecting the institution, its researchers, and the community served.

  15. 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

  16. 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

  17. Importance to include the term superficial musculoaponeurotic system in medical subject headings and in the international anatomical nomenclature.

    Science.gov (United States)

    Ferreira, Lydia Massako; Locali, Rafael Fagionato; Lapin, Guilherme Abbud Franco; Hochman, Bernardo

    2011-06-01

    To investigate the relevance of the term superficial musculoaponeurotic system (SMAS) and demonstrate that this term is important enough to be added to the MeSH database and listed in International Anatomical Nomenclature. Terms related to SMAS were selected from original articles retrieved from the ISI Web of Science and MEDLINE (PubMed) databases. Groups of terms were created to define a search strategy with high-sensitivity and restricted to scientific periodicals devoted to plastic surgery. This study included articles between January 1996 and May 2009, whose titles, abstracts, and keywords were searched for SMAS-related terms and all occurrences were recorded. A total of 126 original articles were retrieved from the main periodicals related to plastic surgery in the referred databases. Of these articles, 51.6% had SMAS-related terms in the abstract only, and 25.4% had SMAS-related terms in both the title and abstract. The term 'superficial musculoaponeurotic system' was present as a keyword in 19.8% of the articles. The most frequent terms were 'SMAS' (71.4%) and superficial musculoaponeurotic system (62.7%). The term SMAS refers to a structure relevant enough to start a discussion about indexing it as a keyword and as an official term in Terminologia Anatomica: International Anatomical Terminology.

  18. 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.

  19. In-human subject-specific evaluation of a control-theoretic plasma volume regulation model.

    Science.gov (United States)

    Bighamian, Ramin; Kinsky, Michael; Kramer, George; Hahn, Jin-Oh

    2017-12-01

    The goal of this study was to conduct a subject-specific evaluation of a control-theoretic plasma volume regulation model in humans. We employed a set of clinical data collected from nine human subjects receiving fluid bolus with and without co-administration of an inotrope agent, including fluid infusion rate, plasma volume, and urine output. Once fitted to the data associated with each subject, the model accurately reproduced the fractional plasma volume change responses in all subjects: the error between actual versus model-reproduced fractional plasma volume change responses was only 1.4 ± 1.6% and 1.2 ± 0.3% of the average fractional plasma volume change responses in the absence and presence of inotrope co-administration. In addition, the model parameters determined by the subject-specific fitting assumed physiologically plausible values: (i) initial plasma volume was estimated to be 36 ± 11 mL/kg and 37 ± 10 mL/kg in the absence and presence of inotrope infusion, respectively, which was comparable to its actual counterpart of 37 ± 4 mL/kg and 43 ± 6 mL/kg; (ii) volume distribution ratio, specifying the ratio with which the inputted fluid is distributed in the intra- and extra-vascular spaces, was estimated to be 3.5 ± 2.4 and 1.9 ± 0.5 in the absence and presence of inotrope infusion, respectively, which accorded with the experimental observation that inotrope could enhance plasma volume expansion in response to fluid infusion. We concluded that the model was equipped with the ability to reproduce plasma volume response to fluid infusion in humans with physiologically plausible model parameters, and its validity may persist even under co-administration of inotropic agents. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Circulating ApoJ is closely associated with insulin resistance in human subjects.

    Science.gov (United States)

    Seo, Ji A; Kang, Min-Cheol; Ciaraldi, Theodore P; Kim, Sang Soo; Park, Kyong Soo; Choe, Charles; Hwang, Won Min; Lim, Dong Mee; Farr, Olivia; Mantzoros, Christos; Henry, Robert R; Kim, Young-Bum

    2018-01-01

    Insulin resistance is a major risk factor for type 2 diabetes. ApolipoproteinJ (ApoJ) has been implicated in altered pathophysiologic states including cardiovascular and Alzheimer's disease. However, the function of ApoJ in regulation of glucose homeostasis remains unclear. This study sought to determine whether serum ApoJ levels are associated with insulin resistance in human subjects and if they change after interventions that improve insulin sensitivity. Serum ApoJ levels and insulin resistance status were assessed in nondiabetic (ND) and type 2 diabetic (T2D) subjects. The impacts of rosiglitazone or metformin therapy on serum ApoJ levels and glucose disposal rate (GDR) during a hyperinsulinemic/euglycemic clamp were evaluated in a separate cohort of T2D subjects. Total ApoJ protein or that associated with the HDL and LDL fractions was measured by immunoblotting or ELISA. Fasting serum ApoJ levels were greatly elevated in T2D subjects (ND vs T2D; 100±8.3 vs. 150.6±8.5AU, Pinsulin, HOMA-IR, and BMI. ApoJ levels were significantly and independently associated with HOMA-IR, even after adjustment for age, sex, and BMI. Rosiglitazone treatment in T2D subjects resulted in a reduction in serum ApoJ levels (before vs. after treatment; 100±13.9 vs. 77±15.2AU, P=0.015), whereas metformin had no effect on ApoJ levels. The change in ApoJ levels during treatment was inversely associated with the change in GDR. Interestingly, ApoJ content in the LDL fraction was inversely associated with HOMA-IR. Serum ApoJ levels are closely correlated with the magnitude of insulin resistance regardless of obesity, and decrease along with improvement of insulin resistance in response only to rosiglitazone in type 2 diabetes. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. A review of safety, side-effects and subjective reactions to intranasal oxytocin in human research.

    Science.gov (United States)

    MacDonald, Elayne; Dadds, Mark R; Brennan, John L; Williams, Katrina; Levy, Florence; Cauchi, Avril J

    2011-09-01

    Human research investigating the impact of intranasal oxytocin on psychological processes has accelerated over the last two decades. No review of side effects, subjective reactions and safety is available. A systematic review of 38 randomised controlled trials conducted between 1990 and 2010 that investigated the central effects of intranasal oxytocin was undertaken. A systematic search for reports of adverse reactions involving intranasal oxytocin was also completed. Since 1990, research trials have reported on N=1529 (79% male) of which 8% were participants with developmental or mental health difficulties. Dosages ranged from 18 to 40 IU, mainly in single doses but ranged up to 182 administrations. Diverse methods have been used to screen and exclude participants, monitor side effects and subject reactions. Side effects are not different between oxytocin and placebo and participants are unable to accurately report on whether they have received oxytocin and placebo. Three case reports of adverse reactions due to misuse and longer-term use of intranasal oxytocin were reported. The evidence shows that intranasal oxytocin: (1) produces no detectable subjective changes in recipients, (2) produces no reliable side-effects, and (3) is not associated with adverse outcomes when delivered in doses of 18-40 IU for short term use in controlled research settings. Future research directions should include a focus on the dosage and duration of use, and application with younger age groups, vulnerable populations, and with females. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

    NARCIS (Netherlands)

    May, M.; Gueler, F.; Barg-Hock, H.; Heiringhoff, K.H.; Engeli, S.; Heusser, K.; Diedrich, A.; Brandt, A.; Strassburg, C.P.; Tank, J.; Sweep, F.C.; Jordan, J.

    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

  3. GH signaling in skeletal muscle and adipose tissue in healthy human subjects

    DEFF Research Database (Denmark)

    Vestergaard, Poul F; Vendelbo, Mikkel H; Pedersen, Steen B

    2014-01-01

    RNA response (r=0.533, P=0.05). CONCLUSION: i) GH signaling in muscle and fat after a single GH bolus in healthy human subjects is age independent, ii) we hypothesize that constitutive overexpression of CISH may contribute to the relative GH resistance in women, and iii) experimental studies on the impact...... of sex steroid administration and physical training on GH signaling in human subjects in vivo are required....

  4. 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

  5. Human Subject Effects on Torsion Pendulum Oscillations: Further Evidence of Mediation by Convection Currents.

    Science.gov (United States)

    Hammerschlag, Richard; Linda Baldwin, Ann; Schwartz, Gary E

    When a human subject sits beneath a wire mesh, hemispheric torsion pendulum (TP) a rapid-onset series of oscillations at frequencies both higher and lower than the fundamental frequency of the TP have been consistently observed. This study was designed to replicate and extend prior findings that suggest the human subject effect on TP behavior is due to subject-generated, heat-induced convection currents. Effects on pendulum behavior were tested after draping an aluminized "space blanket" over the subject and by replacing the subject with a thermal mattress pad shaped to approximate the human form. Experiments were performed in a basic science university research laboratory. Real-time recordings and Fast Fourier Transform frequency spectra of pendulum oscillatory movement. The space blanket blocked, while the mattress pad mimicked, the human subject induced complex array of pendulum oscillations. Our findings support and strengthen previous results that suggest the effects of human subjects on behavior of a torsion pendulum are mediated by body-heat-induced air convection rather than an unknown type of biofield. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. 38 CFR 17.85 - Treatment of research-related injuries to human subjects.

    Science.gov (United States)

    2010-07-01

    ...-related injuries to human subjects. 17.85 Section 17.85 Pensions, Bonuses, and Veterans' Relief DEPARTMENT 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...

  7. 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 and o......, but it is recommended that overdosing be avoided and glycemic control be monitored....

  8. Prospects for genetically modified non-human primate models, including the common marmoset.

    Science.gov (United States)

    Sasaki, Erika

    2015-04-01

    Genetically modified mice have contributed much to studies in the life sciences. In some research fields, however, mouse models are insufficient for analyzing the molecular mechanisms of pathology or as disease models. Often, genetically modified non-human primate (NHP) models are desired, as they are more similar to human physiology, morphology, and anatomy. Recent progress in studies of the reproductive biology in NHPs has enabled the introduction of exogenous genes into NHP genomes or the alteration of endogenous NHP genes. This review summarizes recent progress in the production of genetically modified NHPs, including the common marmoset, and future perspectives for realizing genetically modified NHP models for use in life sciences research. Copyright © 2015 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  9. 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......Regular onion consumption may have many beneficial effects on human health due mainly to well documented probiotic and antioxidant effects. Health effects comprise e.g. anti-inflammatory, anti-tumorigenic, cardiovascular, and gastrointestinal properties. However little is known of the specific...... mechanisms involved. Onions are rich in fructooligosaccharides (FOS), which are well acknowledged prebiotic substances. FOS consumption have previoulsy been associated with an increased level of fermenting bacterial genera e.g. Lactobacillus and Bifidobacterium. Generally, these groups of bacteria...

  10. Research ethics in Internet-enabled research: human subjects issues and methodological myopia.

    Science.gov (United States)

    Walther, Joseph B

    2002-01-01

    As Internet resources are used more frequently for research on social and psychological behavior, concerns grow about whether characteristics of such research affect human subjects protections. Early efforts to address such concerns have done more to identify potential problems than to evaluate them or to seek solutions, leaving bodies charged with human subjects oversight in a quagmire. This article critiques some of these issues in light of the US Code of Federal Regulations' policies for the Protection of Human Subjects, and argues that some of the issues have no pertinence when examined in the context of common methodological approaches that previous commentators failed to consider. By separating applicable contexts from those that are not, and by identifying cases where subjects' characteristics are irrelevant and/or impossible to provide, oversight committees may be able to consider research applications more appropriately, and investigators may be less ethically bound to ascertain and demonstrate those characteristics.

  11. 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. PMID:22105394

  12. Human and veterinary pharmaceuticals in the marine environment including fish farms in Korea.

    Science.gov (United States)

    Kim, Hee-Young; Lee, In-Seok; Oh, Jeong-Eun

    2017-02-01

    The occurrence trends and effects of 30 human and veterinary pharmaceuticals, including antibiotics, anthelmintics, anti-inflammatory drugs, and β-blockers, in the marine environment, with a focus on seawater, sediment, cultured fish, and their feed collected from coastal and fish farm areas in the southern sea of Korea, were investigated. The concentrations of total pharmaceuticals in coastal area seawater (mean: 533ng/L) were higher than those in fish farm seawater (mean: 300ng/L), while the opposite trend (coastal area: 136ng/gdrywtpharmaceuticals in fish muscle (mean: 5.08ng/gwetwt) was lower than that in organs (mean: 14.1ng/gwetwt). However, not all compounds were present at higher concentrations in organs. Characteristic distribution patterns of pharmaceuticals were observed according to sample types and sampling sites based on the predominance of various antibiotics in fish farms (including cultured fish and feed) and the predominance of pharmaceuticals of terrestrial origin (human and livestock) in coastal areas. Pharmaceuticals used as fish drugs, such as sulfadiazine, erythromycin, and trimethoprim, were commonly detected in fish farm media (seawater, sediment, and cultured fish), which might contaminate fish farm media. Copyright © 2016. Published by Elsevier B.V.

  13. 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.

  14. 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

  15. Higher Prevalence and Abundance of Bdellovibrio bacteriovorus in the Human Gut of Healthy Subjects

    Science.gov (United States)

    Iebba, Valerio; Santangelo, Floriana; Totino, Valentina; Nicoletti, Mauro; Gagliardi, Antonella; De Biase, Riccardo Valerio; Cucchiara, Salvatore; Nencioni, Lucia; Conte, Maria Pia; Schippa, Serena

    2013-01-01

    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. PMID:23613881

  16. 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.

  17. Diquafosol Tetrasodium Increases the Concentration of Mucin-like Substances in Tears of Healthy Human Subjects.

    Science.gov (United States)

    Shigeyasu, Chika; Hirano, Shinichiro; Akune, Yoko; Yamada, Masakazu

    2015-09-01

    This study was undertaken to determine the effect of topical application of diquafosol tetrasodium on proteins and mucin-like substances from tears of clinically healthy subjects. Tears were collected from both the eyes of 10 healthy volunteers. Diquafosol tetrasodium solution (3%) was applied once to the right eye and 0.9% sodium chloride solution (saline) once to the left eye. Tear samples were collected by Schirmer test strips before application and 5, 15, 30 and 60 min after application. Sialic acid, a marker of mucin-like substances, and major tear proteins including secretory IgA, lactoferrin, lipocalin-1, and lysozyme were measured by high performance liquid chromatography. Levels of total protein, sIgA and lysozyme were transiently decreased in both groups but returned to baseline levels within 15 min after application. The concentration of lactoferrin and lipocalin-1 did not change significantly in both groups. Sialic acid in tears was significantly decreased 5 min after saline application, but significantly increased 5 min after diquafosol application. No significant difference in sialic acid was seen after 15 min in both groups. Topical application of saline and diquafosol resulted in transient decrease of tear proteins possibly due to wash out or dilution effects. In contrast, diquafosol application significantly increased sialic acid, although the effect was transient. This suggests diquafosol stimulates the secretion of mucins from ocular tissues of healthy human subjects.

  18. The lifetime prevalence, health services utilization and risk of suicide of bipolar spectrum subjects, including subthreshold categories in the São Paulo ECA study.

    Science.gov (United States)

    Moreno, Doris Hupfeld; Andrade, Laura Helena

    2005-08-01

    Identifying the bipolar (BP) spectrum, including the classic Bipolar I subtype (BP-I), Bipolar II (BP-II) and subthreshold bipolar disorders not meeting DSM-IV diagnostic criteria has raised growing interest, as these softer expressions of bipolar spectrum have been underdiagnosed in spite of clinical consequences. Data are from the Sao Paulo Epidemiological Catchment Area Study (N=1464). Non-affective controls were compared to BP spectrum groups, based on DSM-IIIR and on the "clinical significance" criteria: Subsyndromal Hypomania (SSH) and Manic Symptoms (MS). The lifetime prevalence of BP subgroups was 8.3% (N=122). All BP-I and -II and around 75% of SSH and MS subjects had a lifetime depressive syndrome. Compared to controls and MS subjects, BP-I, BP-II and SSH groups searched more medical help and mental health services. SSH group displayed higher rates of clinical significance than BP-I subjects, and suicidality was higher in BP groups compared to controls. Even the softer MS group had higher rate of suicide attempts than SSH subjects. This is a cross-sectional study and interviews were conducted by lay personnel. Replication in bigger community samples using a mood spectrum approach is necessary to confirm these findings. However, our findings were very similar to those obtained by other authors. Softer expressions of BP disorders appear in 6.6% of this community sample and have serious clinical consequences, which supports the importance of including these categories in the BP spectrum.

  19. A survey of intestinal parasites including associated risk factors in humans in Panama.

    Science.gov (United States)

    Sandoval, Nidia R; Ríos, Nivia; Mena, Alberto; Fernández, Rigoberto; Perea, Milixa; Manzano-Román, Raúl; Santa-Quiteria, José A Ruiz; Hernández-Gonzalez, Ana; Siles-Lucas, Mar

    2015-07-01

    Intestinal parasitic infections are among the most common infections worldwide, leading to illness with serious and long lasting implications in children and immunocompromised people. Transmission of intestinal parasites is more frequent in tropical and sub-tropical areas where sanitation is poor and socioeconomic conditions are deficient. Panama is a country where climate and social conditions could be reflected in a high number of people infected with intestinal parasites. The presence, prevalence, and distribution of intestinal parasites in this country have been approached to date only in very restricted areas and population groups, but the impact of intestinal parasite infections at the national level is unknown. We conducted a cross-sectional survey between 2008 and 2010 to determine the prevalence of intestinal parasites across Panama. Overall, 14 municipalities in seven provinces of Panama were surveyed. The presence of eggs, cysts, and larvae was assessed by microscopy in 1123 human fecal samples using a concentration technique. A questionnaire to identify risk factors associated with the frequency of intestinal parasites in the study population was also prepared and performed. Overall, 47.4% of human samples presented parasites. Variables including community type, age group, occupation, co-presence of commensals and socioeconomic factors (use of shoes and type of sanitation) were significantly associated with intestinal parasites (pPanama, place intestinal parasitism as a major health problem in this country. Specific interventions should be planned for the indigenous population, the group most afflicted by intestinal parasites. Copyright © 2015 Elsevier B.V. All rights reserved.

  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

    , 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...... the exergy concept to the built indoor environment, additional results are going to be explored. By using the data available so far of operative temperature (to), the human body exergy consumption rates increase as to increases above 24°C or decreases below 22°C at relative humidity (RH) lower than 50...

  1. Effects of Cannabis Use on Human Behavior, Including Cognition, Motivation, and Psychosis: A Review.

    Science.gov (United States)

    Volkow, Nora D; Swanson, James M; Evins, A Eden; DeLisi, Lynn E; Meier, Madeline H; Gonzalez, Raul; Bloomfield, Michael A P; Curran, H Valerie; Baler, Ruben

    2016-03-01

    With a political debate about the potential risks and benefits of cannabis use as a backdrop, the wave of legalization and liberalization initiatives continues to spread. Four states (Colorado, Washington, Oregon, and Alaska) and the District of Columbia have passed laws that legalized cannabis for recreational use by adults, and 23 others plus the District of Columbia now regulate cannabis use for medical purposes. These policy changes could trigger a broad range of unintended consequences, with profound and lasting implications for the health and social systems in our country. Cannabis use is emerging as one among many interacting factors that can affect brain development and mental function. To inform the political discourse with scientific evidence, the literature was reviewed to identify what is known and not known about the effects of cannabis use on human behavior, including cognition, motivation, and psychosis.

  2. Metrics for the Human Proteome Project 2016: Progress on Identifying and Characterizing the Human Proteome, Including Post-Translational Modifications.

    Science.gov (United States)

    Omenn, Gilbert S; Lane, Lydie; Lundberg, Emma K; Beavis, Ronald C; Overall, Christopher M; Deutsch, Eric W

    2016-11-04

    The HUPO Human Proteome Project (HPP) has two overall goals: (1) stepwise completion of the protein parts list-the draft human proteome including confidently identifying and characterizing at least one protein product from each protein-coding gene, with increasing emphasis on sequence variants, post-translational modifications (PTMs), and splice isoforms of those proteins; and (2) making proteomics an integrated counterpart to genomics throughout the biomedical and life sciences community. PeptideAtlas and GPMDB reanalyze all major human mass spectrometry data sets available through ProteomeXchange with standardized protocols and stringent quality filters; neXtProt curates and integrates mass spectrometry and other findings to present the most up to date authorative compendium of the human proteome. The HPP Guidelines for Mass Spectrometry Data Interpretation version 2.1 were applied to manuscripts submitted for this 2016 C-HPP-led special issue [ www.thehpp.org/guidelines ]. The Human Proteome presented as neXtProt version 2016-02 has 16,518 confident protein identifications (Protein Existence [PE] Level 1), up from 13,664 at 2012-12, 15,646 at 2013-09, and 16,491 at 2014-10. There are 485 proteins that would have been PE1 under the Guidelines v1.0 from 2012 but now have insufficient evidence due to the agreed-upon more stringent Guidelines v2.0 to reduce false positives. neXtProt and PeptideAtlas now both require two non-nested, uniquely mapping (proteotypic) peptides of at least 9 aa in length. There are 2,949 missing proteins (PE2+3+4) as the baseline for submissions for this fourth annual C-HPP special issue of Journal of Proteome Research. PeptideAtlas has 14,629 canonical (plus 1187 uncertain and 1755 redundant) entries. GPMDB has 16,190 EC4 entries, and the Human Protein Atlas has 10,475 entries with supportive evidence. neXtProt, PeptideAtlas, and GPMDB are rich resources of information about post-translational modifications (PTMs), single amino acid

  3. Measurements of potential differences in human subjects induced by motion in a superconducting magnetic field.

    Science.gov (United States)

    Frinak, S; Knight, R A; Liboff, A R

    1992-01-01

    We have attempted to measure the electromotive forces (emfs) induced in human beings moving at a constant speed in a highly dense magnetic field. Experiments were initially conducted on a set of models, and then directly on human subjects. The models consisted of single circular loops of Tygon tubing (I.D., 0.635 cm; O.D., 0.9525 cm) filled with normal saline solution, with circumferences of 20, 40, 60, 80, and 100 cm. The models were connected to an amplifier via silver/silver-chloride electrodes. Each saline loop was mounted on a movable platform, with the plane of the loop perpendicular to the platform's axis; the platform was enabled to move at known constant speeds into and out of the bore of a 1.89-T magnet. The human subjects were then substituted for the saline loops, with the long axis parallel to the direction of motion, and with standard EKG electrodes placed at 180 degrees successively on the ankle, calf, lower thigh, upper thigh, chest, and head. In all cases, for human subjects and models, the peak induced voltage was directly proportional to the speed of movement and the square of the circumference of the bounded cross-sectional areas. Thus, for the saline loops, the correlation coefficient between induced voltage and circumference was .998, and for human subjects, .947. Under the loose assumption that for equal circumferences the bounded areas in human subjects were equal to those in the circular loops, the induced emfs in human subjects were consistently about 13% greater than those in the loops. At a mean speed of 1.18 m/s, the chest had a peak induced voltage of 260 mV, while the voltage at the ankle had a peak of 19.8 mV. The experimental data were used to estimate the corresponding induced-current density at the pericardium, 17 mA/m2. We conclude for a human subject moving at constant speed along the body's long axis into a magnetic field that Faraday's law is closely followed for various cross-sections of the body. Further, in those cases in

  4. Evaluation of P300 components for emotion-loaded visual event-related potential in elderly subjects, including those with dementia.

    Science.gov (United States)

    Asaumi, Yasue; Morita, Kiichiro; Nakashima, Youko; Muraoka, Akemi; Uchimura, Naohisa

    2014-07-01

    In the present study, the P300 component of the emotion-loaded visual event-related potential in response to photographs of babies crying or smiling was measured to evaluate cognitive function in elderly subjects, including those with dementia. The subjects were 48 elderly people who consulted a memory disorder clinic. The visual event-related potential was measured using oddball tasks. Brain waves were recorded from four sites. We analyzed the P300 amplitude and latency. Subjects were divided into three groups (the dementia with Alzheimer's disease group [ADG]; the intermediate group [MG], and the healthy group [HG]) based on the Revised Hasegawa Dementia Scale, Mini-mental State Examination scores and the Clinical Dementia Rating. For all subjects, there was a significant positive correlation between P300 latency and Z-score of voxel-based specific regional analysis for Alzheimer's disease for crying or smiling faces. There was a negative correlation between P300 amplitude and Z-score for the crying face. MG subjects were divided into two groups (high risk: HRMG, low risk: LRMG) based on Z-scores (HRMG ≥ 2.0). The P300 amplitude of ADG was significantly smaller than that of HG, and the P300 latency of ADG was significantly longer than those of other groups for crying or smiling faces. The P300 latency of HRMG was significantly longer than that of LRMG for the smiling face. Furthermore, the P300 latency for the crying face was significantly shorter than that for the smiling face in HG and ADG. These findings suggest that analysis of P300 components of the emotion-loaded visual event-related potential may be a useful neuropsychological index for the diagnosis of Alzheimer's disease and high-risk subjects. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

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

    OpenAIRE

    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 6...

  6. Biorepository regulatory frameworks: building parallel resources that both promote scientific investigation and protect human subjects.

    Science.gov (United States)

    Marko-Varga, György; Baker, Mark S; Boja, Emily S; Rodriguez, Henry; Fehniger, Thomas E

    2014-12-05

    Clinical samples contained in biorepositories represent an important resource for investigating the many factors that drive human biology. The biological and chemical markers contained in clinical samples provide important measures of health and disease that when combined with such medical evaluation data can aid in decision making by physicians. Nearly all disciplines in medicine and every "omic" depend upon the readouts obtained from such samples, whether the measured analyte is a gene, a protein, a lipid, or a metabolite. There are many steps in sample processing, storage, and management that need to understood by the researchers who utilize biorepositories in their own work. These include not only the preservation of the desired analytes in the sample but also good understanding of the moral and legal framework required for subject protection irrespective of where the samples have been collected. Today there is a great deal of effort in the community to align and standardize both the methodology of sample collection and storage performed in different locations and the necessary frameworks of subject protection including informed consent and institutional review of the studies being performed. There is a growing trend in developing biorepositories around the focus of large population-based studies that address both active and silent nonsymptomatic disease. Logistically these studies generate large numbers of clinical samples and practically place increasing demand upon health care systems to provide uniform sample handling, processing, storage, and documentation of both the sample and the subject as well to ensure that safeguards exist to protect the rights of the study subjects for deciding upon the fates of their samples. Currently the authority to regulate the entire scope of biorepository usage exists as national practice in law in only a few countries. Such legal protection is a necessary component within the framework of biorepositories, both now and in

  7. Salivary alpha amylase activity in human beings of different age groups subjected to psychological stress.

    Science.gov (United States)

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

    2014-10-01

    Salivary alpha-amylase (sAA) has been proposed as a sensitive non-invasive biomarker for stress-induced changes in the body that reflect the activity of the sympathetic nervous system. Though several experiments have been conducted to determine the validity of this salivary component as a reliable stress marker in human subjects, the effect of stress induced changes on sAA level 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. Differences in sAA level based on sex of different age groups under stress have also been studied. A total of 112 subjects consisting of both the male and female subjects, divided into two groups on basis of age were viewed a video clip of corneal transplant surgery as stressor. Activity of sAA from saliva samples of the stressed subjects were measured and compared with the activity of the samples collected from the subjects before viewing the clip. The age ranges of subjects were 18-25 and 40-60 years. The sAA level increased significantly in both the groups after viewing the stressful video. The increase was more pronounced in the younger subjects. The level of sAA was comparatively more in males than females in the respective groups. No significant change in sAA activity was observed after viewing the soothed video clip. Significant increase of sAA level in response to psychological stress suggests that it might act as a reliable sympathetic activity biochemical marker in different stages of human beings.

  8. 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

    2015-06-24

    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.

  9. 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.

  10. What Is Humane Education and Why It Should Be Included in Modern Education

    Science.gov (United States)

    Jacobs, G. M.

    2016-01-01

    Humane education has existed since at least the 18th century (Unti & DeRosa, 2003). This brief chapter begins with a brief definition of humane education and examples of how it can be incorporated in linguistics, cross cultural studies and foreign language education. Next, the chapter discusses why humane education constitutes an important…

  11. The Social Studies Should Include More Discussion of International Human Rights.

    Science.gov (United States)

    Torney, Judith V.

    1980-01-01

    Students need more exposure to the concept of human rights. They need to know The Universal Declaration of Human Rights and the subsequent covenants. Also, they need to know that substantial agreement exists in the international community about what constitutes human rights. (Author/KC)

  12. 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

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

    Science.gov (United States)

    Erickson, David W; Wells, Jered R; Sturgeon, Gregory M; Samei, Ehsan; Dobbins, James T; Segars, W Paul; Lo, Joseph Y

    2016-01-01

    To create a database of highly realistic and anatomically variable 3D virtual breast phantoms based on dedicated breast computed tomography (bCT) data. 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. 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. 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 of breast types, volumes, densities, and

  14. 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

  15. 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

  16. Numerous polymorphic microsatellites in the human prion gene complex (including PRNP, PRND and PRNT).

    Science.gov (United States)

    Preuss, Siegfried; Peischl, Tania; Melchinger, Elke; Geldermann, Hermann

    2004-03-31

    Microsatellite sites were analysed with DNA screening software by using about 148 kilobases (kb) of the human genomic DNA sequence GenBank accession number (acc. no.) which includes the genes PRNP, PRND and PRNT. Regarding microsatellites (MS) with at least four repeats and base replacements within the repetitive motifs<10%, 127 sites were found. Sixteen of the sites were analysed and nine of them proved to be polymorphic with up to nine alleles per site. Frequencies<0.95 of the predominant allele were observed for all polymorphic sites, and frequencies<0.4 for four sites. Some allelic DNA sequences were not only different in microsatellite repeats but also in flanking regions. Distances between microsatellite sites were in average of 1.2 kb and allow the identification of a number of further informative markers in the prion protein gene complex. The large number of polymorphic sites within a narrow chromosomal interval can be applied to study the origin of alleles as well as the association to the incidence of diseases.

  17. Neural mechanisms underlying contextual dependency of subjective values: converging evidence from monkeys and humans.

    Science.gov (United States)

    Abitbol, Raphaëlle; Lebreton, Maël; Hollard, Guillaume; Richmond, Barry J; Bouret, Sébastien; Pessiglione, Mathias

    2015-02-04

    A major challenge for decision theory is to account for the instability of expressed preferences across time and context. Such variability could arise from specific properties of the brain system used to assign subjective values. Growing evidence has identified the ventromedial prefrontal cortex (VMPFC) as a key node of the human brain valuation system. Here, we first replicate this observation with an fMRI study in humans showing that subjective values of painting pictures, as expressed in explicit pleasantness ratings, are specifically encoded in the VMPFC. We then establish a bridge with monkey electrophysiology, by comparing single-unit activity evoked by visual cues between the VMPFC and the orbitofrontal cortex. At the neural population level, expected reward magnitude was only encoded in the VMPFC, which also reflected subjective cue values, as expressed in Pavlovian appetitive responses. In addition, we demonstrate in both species that the additive effect of prestimulus activity on evoked activity has a significant impact on subjective values. In monkeys, the factor dominating prestimulus VMPFC activity was trial number, which likely indexed variations in internal dispositions related to fatigue or satiety. In humans, prestimulus VMPFC activity was externally manipulated through changes in the musical context, which induced a systematic bias in subjective values. Thus, the apparent stochasticity of preferences might relate to the VMPFC automatically aggregating the values of contextual features, which would bias subsequent valuation because of temporal autocorrelation in neural activity. Copyright © 2015 the authors 0270-6474/15/352308-13$15.00/0.

  18. Some recent developments in the international guidelines on the ethics of research involving human subjects.

    Science.gov (United States)

    Levine, R J

    2000-11-01

    We are in a period of reconsideration and revision of international ethical guidelines for the conduct of biomedical research involving human subjects. The proximate cause of much of this activity is the recent controversy over the ethics of the use of a placebo control in the clinical trials of the short-duration regimen of zidovudine for prevention of perinatal transmission of HIV infection, trials that were carried out in several so-called technologically developing countries. Critics of these trials claimed that they were in violation of Article II.3 of the Declaration of Helsinki, which states: "In any medical study, every patient--including those of a control group, if any--should be assured of the best proven diagnostic and therapeutic method. This does not exclude the use of inert placebo in studies where no proven diagnostic or therapeutic method exists." The critics claimed that since the "best proven ... method" is the 076 regimen, this is what must be provided to members of the control groups. Failure to do so, they asserted, was a serious breach of ethics. In response to this allegation, several major international and national agencies convened multidisciplinary groups to consider the ethics of multinational clinical research. The first thing they realized was that Article II.3 was in error in that it did not reflect contemporary ethical thinking. Moreover, it was routinely violated in research conducted in developed as well as in developing countries. What replaces this standard? The 1993 CIOMS International Ethical Guidelines for Biomedical Research Involving Human Subjects include several criteria for justification of research carried out in developing countries. Most importantly, the research must be responsive to the health needs and priorities of the host country. They also require that any therapeutic products developed in such research must be made "reasonably available" to residents of the host country. A new standard is emerging for

  19. Perfluorooctanesulfonate and related fluorochemicals in several organisms including humans from Italy

    Energy Technology Data Exchange (ETDEWEB)

    Corsolini, S. [Siena Univ. (Italy); Kannan, K. [New York State Univ., Albany, NY (United States)

    2004-09-15

    Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant, extremely resistant to environmental degradation and is ubiquitous in the environment. Traditional monitoring studies for persistent chemicals failed to identify this contaminant for a long time because of its unique physicochemical properties and its tendency to bind to proteins instead of accumulating in fatty tissues. PFOS is known to be toxic in laboratory animals (rats, mice, monkeys) at levels close to the range already found in organisms and people. PFOS has been commercially produced by an electrochemical fluorination process for over 40 years. Perfluorooctane sulfonylfluoride (POSF; C{sub 8}F{sub 17}SO{sub 2}F) is used as a building block for further reactions that produce several other sulfonated fluorinated compounds, including perfluorooctane sulfonate (C{sub 8}F{sub 17}SO{sub 3}{sup -}) and other precursor molecules such as n-ethyl or n-methyl perfluorooctanesulfonamidoethanol. POSF-based fluorochemicals have been used in a wide variety of industrial and consumer products, including protective coatings for carpets and apparel, paper coatings, insecticide formulations, and surfactants. These compounds repel water and oil, reduce surface tension, catalyze oligomerization and polymerization, and maintain their properties under extreme conditions. Depending upon the specific functional derivatization or the degree of polymerization, POSF-based chemicals may degrade or metabolize to PFOS, which is known to be the final metabolite of POSF-based fluorochemicals. PFOS is stable, chemically inert, and non-reactive and has the potential to bioaccumulate. It has been found in polar bears from the Arctic, albatross and other fish-eating water birds in the mid-Pacific, and aquatic organisms11 and people world-wide. PFOS and other perfluorinated chemicals such as perfluorooctanesulfonamide (PFOSA), perfluorohexanesulfonate (PFHxS), and perfluorooctanoate (PFOA) have been detected in human blood. In

  20. 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

  1. Attributes characterizing spontaneous ultra-weak photon signals of human subjects

    NARCIS (Netherlands)

    Bajpai, R.P.; Wijk, E.P.A. van; Wijk, R. van; Greef, J. van der

    2013-01-01

    Sixty visible range photon signals spontaneously emitted from the dorsal side of both hands of fifteen human subjects are analyzed with the aim of finding their attributes. The signals are of 30 min duration and detected in bins of 50 ms by two synchronized photo multipliers sensitive in the range

  2. Reflections on the Ethics of Experimentation with Human Subjects with Respect to Arrowsmith (1931

    Directory of Open Access Journals (Sweden)

    Agustín del Cañizo Fernández-Roldán

    2008-10-01

    Full Text Available The moral tension between individual rights versus common good in experimentation with human subjects has been constant throughout history. Taking as a basis the film Arrowsmith in which this problem is well reflected, an ethical analysis is made, bearing in mind the time when the film was made, some historical antecedents and, finally, establishing a comparison with the current situation.

  3. Reflections on the Ethics of Experimentation with Human Subjects with Respect to Arrowsmith (1931)

    OpenAIRE

    Agustín del Cañizo Fernández-Roldán

    2008-01-01

    The moral tension between individual rights versus common good in experimentation with human subjects has been constant throughout history. Taking as a basis the film Arrowsmith in which this problem is well reflected, an ethical analysis is made, bearing in mind the time when the film was made, some historical antecedents and, finally, establishing a comparison with the current situation.

  4. Brain-derived neurotrophic factor in human subjects with function-altering melanocortin-4 receptor variants

    Science.gov (United States)

    In rodents, hypothalamic brain-derived neurotrophic factor (BDNF) expression appears to be regulated by melanocortin-4 receptor (MC4R) activity. The impact of MC4R genetic variation on circulating BDNF in humans is unknown. The objective of this study is to compare BDNF concentrations of subjects wi...

  5. Hans Jonas' thought on the ethics of research on human subjects

    African Journals Online (AJOL)

    Dr Olaleye

    The thinking and teachings of Hans Jonas was on the need for medical research to advance beyond the use animals for research and experimentations to research on human subjects. Jonas upholds the established view that medicine is an experimental science and that most medical advances are product of trial and error ...

  6. Hans Jonas' thought on the ethics of research on human subjects ...

    African Journals Online (AJOL)

    The thinking and teachings of Hans Jonas was on the need for medical research to advance beyond the use animals for research and experimentations to research on human subjects. Jonas upholds the established view that medicine is an experimental science and that most medical advances are product of trial and error ...

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

    NARCIS (Netherlands)

    de Jong, J.P.

    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

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

    NARCIS (Netherlands)

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

    2013-01-01

    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

  9. 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...

  10. The case for evidence-based rulemaking in human subjects research.

    Science.gov (United States)

    Sachs, Benjamin

    2010-06-01

    Here I inquire into the status of the rules promulgated in the canonical pronouncements on human subjects research, such as the Declaration of Helsinki and the Belmont Report. The question is whether they are ethical rules or rules of policy. An ethical rule is supposed to accurately reflect the ethical fact (the fact that the action the rule prescribes is ethically obligatory), whereas rules of policy are implemented to achieve a goal. We should be skeptical, I argue, that the actions prescribed by the rules are ethically obligatory, and consequently we should focus our attention on how to craft the rules so as to promote the legitimate goals of human subjects research. Unfortunately, this cannot be done without evidence about the likely effects of various candidate policies-evidence we currently lack. Therefore, we should take the rules as mere starting points, subject to revision as the evidence comes in.

  11. Assessing blood brain barrier dynamics or identifying or measuring selected substances, including ethanol or toxins, in a subject by analyzing Raman spectrum signals

    Science.gov (United States)

    Lambert, James L. (Inventor); Borchert, Mark S. (Inventor)

    2008-01-01

    A non-invasive method for analyzing the blood-brain barrier includes obtaining a Raman spectrum of a selected portion of the eye and monitoring the Raman spectrum to ascertain a change to the dynamics of the blood brain barrier.Also, non-invasive methods for determining the brain or blood level of an analyte of interest, such as glucose, drugs, alcohol, poisons, and the like, comprises: generating an excitation laser beam at a selected wavelength (e.g., at a wavelength of about 400 to 900 nanometers); focusing the excitation laser beam into the anterior chamber of an eye of the subject so that aqueous humor, vitreous humor, or one or more conjunctiva vessels in the eye is illuminated; detecting (preferably confocally detecting) a Raman spectrum from the illuminated portion of the eye; and then determining the blood level or brain level (intracranial or cerebral spinal fluid level) of an analyte of interest for the subject from the Raman spectrum. In certain embodiments, the detecting step may be followed by the step of subtracting a confounding fluorescence spectrum from the Raman spectrum to produce a difference spectrum; and determining the blood level and/or brain level of the analyte of interest for the subject from that difference spectrum, preferably using linear or nonlinear multivariate analysis such as partial least squares analysis. Apparatus for carrying out the foregoing methods are also disclosed.

  12. Modal analysis of human body vibration model for Indian subjects under sitting posture.

    Science.gov (United States)

    Singh, Ishbir; Nigam, S P; Saran, V H

    2015-01-01

    Need and importance of modelling in human body vibration research studies are well established. The study of biodynamic responses of human beings can be classified into experimental and analytical methods. In the past few decades, plenty of mathematical models have been developed based on the diverse field measurements to describe the biodynamic responses of human beings. In this paper, a complete study on lumped parameter model derived from 50th percentile anthropometric data for a seated 54- kg Indian male subject without backrest support under free un-damped conditions has been carried out considering human body segments to be of ellipsoidal shape. Conventional lumped parameter modelling considers the human body as several rigid masses interconnected by springs and dampers. In this study, concept of mass of interconnecting springs has been incorporated and eigenvalues thus obtained are found to be closer to the values reported in the literature. Results obtained clearly establish decoupling of vertical and fore-and-aft oscillations. The mathematical modelling of human body vibration studies help in validating the experimental investigations for ride comfort of a sitting subject. This study clearly establishes the decoupling of vertical and fore-and-aft vibrations and helps in better understanding of possible human response to single and multi-axial excitations.

  13. Subsecond timing in primates: comparison of interval production between human subjects and rhesus monkeys.

    Science.gov (United States)

    Zarco, Wilbert; Merchant, Hugo; Prado, Luis; Mendez, Juan Carlos

    2009-12-01

    This study describes the psychometric similarities and differences in motor timing performance between 20 human subjects and three rhesus monkeys during two timing production tasks. These tasks involved tapping on a push-button to produce the same set of intervals (range of 450 to 1,000 ms), but they differed in the number of intervals produced (single vs. multiple) and the modality of the stimuli (auditory vs. visual) used to define the time intervals. The data showed that for both primate species, variability increased as a function of the length of the produced target interval across tasks, a result in accordance with the scalar property. Interestingly, the temporal performance of rhesus monkeys was equivalent to that of human subjects during both the production of single intervals and the tapping synchronization to a metronome. Overall, however, human subjects were more accurate than monkeys and showed less timing variability. This was especially true during the self-pacing phase of the multiple interval production task, a behavior that may be related to complex temporal cognition, such as speech and music execution. In addition, the well-known human bias toward auditory as opposed to visual cues for the accurate execution of time intervals was not evident in rhesus monkeys. These findings validate the rhesus monkey as an appropriate model for the study of the neural basis of time production, but also suggest that the exquisite temporal abilities of humans, which peak in speech and music performance, are not all shared with macaques.

  14. 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

    subjects. Interestingly, numerous genes implicated in metabolic diseases and epigenetic regulation showed differential methylation and expression during differentiation only in obese subjects. CONCLUSIONS: Our study identifies IL-32 as a novel myogenic regulator, provides a comprehensive map of the dynamic...... 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......-wide changes in DNA methylation and expression patterns during differentiation of primary human muscle stem cells (myoblasts). We identified epigenetic and transcriptional changes of myogenic transcription factors (MYOD1, MYOG, MYF5, MYF6, PAX7, MEF2A, MEF2C, and MEF2D), cell cycle regulators, metabolic...

  15. 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

    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...... 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......, mitochondrial DNA content, complex I-V protein content, and complex I-IV activity. Spearman correlation coefficient tests and Lin's concordance tests were applied to assess the absolute and relative association between the markers and mitochondrial content or OXPHOS.Subjects had a large range in VO(2peak...

  16. 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

    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...... sensation data, from earlier thermal comfort studies, to calculated human-body exergy consumption rates. The results show that the minimum human body exergy consumption rate is associated with thermal sensation votes close to thermal neutrality, tending to the slightly cool side of thermal sensation....... 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...

  17. Pharmacokinetics and safety of the anti-human cytomegalovirus drug letermovir in subjects with hepatic impairment.

    Science.gov (United States)

    Kropeit, Dirk; McCormick, David; Erb-Zohar, Katharina; Moiseev, Valentin S; Kobalava, Zhanna D; Stobernack, Hans-Peter; Zimmermann, Holger; Rübsamen-Schaeff, Helga

    2017-07-18

    Human cytomegalovirus constitutes a prevalent and serious threat to immunocompromised individuals and requires new treatments. Letermovir is a novel viral-terminase inhibitor that has demonstrated prophylactic/pre-emptive activity against human cytomegalovirus in Phase 2 and 3 transplant trials. As unchanged letermovir is primarily excreted via the liver by bile, this trial aimed to assess the effect of hepatic impairment on letermovir pharmacokinetics. Phase 1, open-label, parallel-group pharmacokinetic and safety comparison of multiple once-daily oral letermovir in female subjects with hepatic impairment and healthy matched controls. For 8 days, subjects with moderate hepatic impairment (n = 8) and their matched healthy controls (n = 9) received 60 mg letermovir/day and those with severe hepatic impairment (n = 8) and their matched healthy controls (n = 8) received 30 mg letermovir/day. Pharmacokinetic parameters were determined from blood samples. For subjects with moderate hepatic impairment, maximal observed concentration at steady state (Css,max ) and the area under the concentration vs. time curve over a dosing interval at steady state (AUCτ,ss ) for total letermovir were 1.37-fold (90% confidence interval: 0.87, 2.17) and 1.59-fold (0.98, 2.57) higher, respectively, than in healthy subjects. For subjects with severe hepatic impairment, Css,max and AUCτ,ss values of total letermovir were 2.34-fold (1.91, 2.88) and 3.82-fold (2.94, 4.97) higher, respectively, compared with healthy subjects. Moderate hepatic impairment increased exposure to letermovir letermovir exposure approximately 4-fold as compared with healthy subjects. Letermovir 60/30 mg/day was generally well-tolerated in subjects with hepatic impairment. © 2017 The British Pharmacological Society.

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

    Science.gov (United States)

    Hsu, Christina M L; Palmeri, Mark L; Segars, W Paul; Veress, Alexander I; Dobbins, James T

    2013-04-01

    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. 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, generated from morphing three human subject datasets, were

  19. Dietary pyrroloquinoline quinone (PQQ) alters indicators of inflammation and mitochondrial-related metabolism in human subjects.

    Science.gov (United States)

    Harris, Calliandra B; Chowanadisai, Winyoo; Mishchuk, Darya O; Satre, Mike A; Slupsky, Carolyn M; Rucker, Robert B

    2013-12-01

    Pyrroloquinoline quinone (PQQ) influences energy-related metabolism and neurologic functions in animals. The mechanism of action involves interactions with cell signaling pathways and mitochondrial function. However, little is known about the response to PQQ in humans. Using a crossover study design, 10 subjects (5 females, 5 males) ingested PQQ added to a fruit-flavored drink in two separate studies. In study 1, PQQ was given in a single dose (0.2 mg PQQ/kg). Multiple measurements of plasma and urine PQQ levels and changes in antioxidant potential [based on total peroxyl radical-trapping potential and thiobarbituric acid reactive product (TBAR) assays] were made throughout the period of 48 h. In study 2, PQQ was administered as a daily dose (0.3 mg PQQ/kg). After 76 h, measurements included indices of inflammation [plasma C-reactive protein, interleukin (IL)-6 levels], standard clinical indices (e.g., cholesterol, glucose, high-density lipoprotein, low-density lipoprotein, triglycerides, etc.) and (1)H-nuclear magnetic resonance estimates of urinary metabolites related in part to oxidative metabolism. The standard clinical indices were normal and not altered by PQQ supplementation. However, dietary PQQ exposure (Study 1) resulted in apparent changes in antioxidant potential based on malonaldehyde-related TBAR assessments. In Study 2, PQQ supplementation resulted in significant decreases in the levels of plasma C-reactive protein, IL-6 and urinary methylated amines such as trimethylamine N-oxide, and changes in urinary metabolites consistent with enhanced mitochondria-related functions. The data are among the first to link systemic effects of PQQ in animals to corresponding effects in humans. © 2013.

  20. 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.

  1. 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...... weeks of regular endurance training induced a 40% increase in basal skeletal muscle IL-15 protein content (p......Regular endurance exercise promotes metabolic and oxidative changes in skeletal muscle. Overexpression of interleukin-15 (IL-15) in mice exerts similar metabolic changes in muscle as seen with endurance exercise. Muscular IL-15 production has been shown to increase in mice after weeks of regular...

  2. Coupled modeling of land hydrology–regional climate including human carbon emission and water exploitation

    Directory of Open Access Journals (Sweden)

    Zheng-Hui Xie

    2017-06-01

    Full Text Available Carbon emissions and water use are two major kinds of human activities. To reveal whether these two activities can modify the hydrological cycle and climate system in China, we conducted two sets of numerical experiments using regional climate model RegCM4. In the first experiment used to study the climatic responses to human carbon emissions, the model were configured over entire China because the impacts of carbon emissions can be detected across the whole country. Results from the first experiment revealed that near-surface air temperature may significantly increase from 2007 to 2059 at a rate exceeding 0.1 °C per decade in most areas across the country; southwestern and southeastern China also showed increasing trends in summer precipitation, with rates exceeding 10 mm per decade over the same period. In summer, only northern China showed an increasing trend of evapotranspiration, with increase rates ranging from 1 to 5 mm per decade; in winter, increase rates ranging from 1 to 5 mm per decade were observed in most regions. These effects are believed to be caused by global warming from human carbon emissions. In the second experiment used to study the effects of human water use, the model were configured over a limited region—Haihe River Basin in the northern China, because compared with the human carbon emissions, the effects of human water use are much more local and regional, and the Haihe River Basin is the most typical region in China that suffers from both intensive human groundwater exploitation and surface water diversion. We incorporated a scheme of human water regulation into RegCM4 and conducted the second experiment. Model outputs showed that the groundwater table severely declined by ∼10 m in 1971–2000 through human groundwater over-exploitation in the basin; in fact, current conditions are so extreme that even reducing the pumping rate by half cannot eliminate the groundwater depletion cones observed in the area

  3. “An Environment Built to Include Rather than Exclude Me”: Creating Inclusive Environments for Human Well-Being

    Directory of Open Access Journals (Sweden)

    Natasha A. Layton

    2015-09-01

    Full Text Available Contemporary discourses which challenge the notion of health as the “absence of disease” are prompting changes in health policy and practice. People with disability have been influential in progressing our understanding of the impact of contextual factors in individual and population health, highlighting the impact of environmental factors on functioning and inclusion. The World Health Organization’s (WHO more holistic definition of health as “wellbeing” is now applied in frameworks and legislation, and has long been understood in occupational therapy theory. In practice, however, occupational therapists and other professionals often address only local and individual environmental factors to promote wellbeing, within systems and societies that limit equity in population health and restrict inclusion in communities. This paper presents an in-depth analysis of the supports and accommodations identified by a cohort of individuals (n-100 living with disability. A range of environmental facilitators and barriers were identified in peoples’ experience of “inclusive community environs” and found to influence inclusion and wellbeing. The roles and responsibilities of individuals, professionals, and society to enact change in environments are discussed in light of these findings. Recommendations include a focus on the subjective experience of environments, and application of theory from human rights and inclusive economics to address the multiple dimensions and levels of environments in working towards inclusion and wellbeing.

  4. "An Environment Built to Include Rather than Exclude Me": Creating Inclusive Environments for Human Well-Being.

    Science.gov (United States)

    Layton, Natasha A; Steel, Emily J

    2015-09-08

    Contemporary discourses which challenge the notion of health as the "absence of disease" are prompting changes in health policy and practice. People with disability have been influential in progressing our understanding of the impact of contextual factors in individual and population health, highlighting the impact of environmental factors on functioning and inclusion. The World Health Organization's (WHO) more holistic definition of health as "wellbeing" is now applied in frameworks and legislation, and has long been understood in occupational therapy theory. In practice, however, occupational therapists and other professionals often address only local and individual environmental factors to promote wellbeing, within systems and societies that limit equity in population health and restrict inclusion in communities. This paper presents an in-depth analysis of the supports and accommodations identified by a cohort of individuals (n-100) living with disability. A range of environmental facilitators and barriers were identified in peoples' experience of "inclusive community environs" and found to influence inclusion and wellbeing. The roles and responsibilities of individuals, professionals, and society to enact change in environments are discussed in light of these findings. Recommendations include a focus on the subjective experience of environments, and application of theory from human rights and inclusive economics to address the multiple dimensions and levels of environments in working towards inclusion and wellbeing.

  5. Detection of bacterial pathogens including potential new species in human head lice from Mali.

    Science.gov (United States)

    Amanzougaghene, Nadia; Fenollar, Florence; Sangaré, Abdoul Karim; Sissoko, Mahamadou S; Doumbo, Ogobara K; Raoult, Didier; Mediannikov, Oleg

    2017-01-01

    In poor African countries, where no medical and biological facilities are available, the identification of potential emerging pathogens of concern at an early stage is challenging. Head lice, Pediculus humanus capitis, have a short life, feed only on human blood and do not transmit pathogens to their progeny. They are, therefore, a perfect tool for the xenodiagnosis of current or recent human infection. This study assessed the occurrence of bacterial pathogens from head lice collected in two rural villages from Mali, where a high frequency of head lice infestation had previously been reported, using molecular methods. Results show that all 600 head lice, collected from 117 individuals, belonged to clade E, specific to West Africa. Bartonella quintana, the causative agent of trench fever, was identified in three of the 600 (0.5%) head lice studied. Our study also shows, for the first time, the presence of the DNA of two pathogenic bacteria, namely Coxiella burnetii (5.1%) and Rickettsia aeschlimannii (0.6%), detected in human head lice, as well as the DNA of potential new species from the Anaplasma and Ehrlichia genera of unknown pathogenicity. The finding of several Malian head lice infected with B. quintana, C. burnetii, R. aeschlimannii, Anaplasma and Ehrlichia is alarming and highlights the need for active survey programs to define the public health consequences of the detection of these emerging bacterial pathogens in human head lice.

  6. Specifics of Educational Texts Selection for Schoolchildren Doing the Humanities Subjects

    Directory of Open Access Journals (Sweden)

    T. V. Oblasova

    2015-02-01

    Full Text Available The paper proposes the new approach to educational text selection for the humanities teaching. Its specifics is based on the wide interpretation of educational texts, as the culture texts involved in cognitive learning activity and fulfilling the multiple tasks of the related subjects and personal development. The educational text is taken as a generalized model, its content and structure determining the scheme of a speech cognitive activity, as well as the meaning formation mechanism responsible for understanding and personal development. The texts and tasks selection is oriented on schoolchildren’s understanding with the reference to the psycholinguistic, psychological and hermeneutic approaches; information extraction and interpretation level related to the author’s and student’s context. The given approach could provide the basis for developing and structuring the textbooks content for the humanities subjects

  7. Specifics of Educational Texts Selection for Schoolchildren Doing the Humanities Subjects

    Directory of Open Access Journals (Sweden)

    T. V. Oblasova

    2012-01-01

    Full Text Available The paper proposes the new approach to educational text selection for the humanities teaching. Its specifics is based on the wide interpretation of educational texts, as the culture texts involved in cognitive learning activity and fulfilling the multiple tasks of the related subjects and personal development. The educational text is taken as a generalized model, its content and structure determining the scheme of a speech cognitive activity, as well as the meaning formation mechanism responsible for understanding and personal development. The texts and tasks selection is oriented on schoolchildren’s understanding with the reference to the psycholinguistic, psychological and hermeneutic approaches; information extraction and interpretation level related to the author’s and student’s context. The given approach could provide the basis for developing and structuring the textbooks content for the humanities subjects

  8. 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.

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

    OpenAIRE

    de Jong, J.P.

    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 many years, with Research Ethics Committees as their cornerstone. Although these oversight systems aim to ensure that the ethical quality of research is in order, they have been criticized for imped...

  10. Effect of the artificial sweetener, sucralose, on small intestinal glucose absorption in healthy human subjects.

    Science.gov (United States)

    Ma, Jing; Chang, Jessica; Checklin, Helen L; Young, Richard L; Jones, Karen L; Horowitz, Michael; Rayner, Christopher K

    2010-09-01

    It has been reported that the artificial sweetener, sucralose, stimulates glucose absorption in rodents by enhancing apical availability of the transporter GLUT2. We evaluated whether exposure of the proximal small intestine to sucralose affects glucose absorption and/or the glycaemic response to an intraduodenal (ID) glucose infusion in healthy human subjects. Ten healthy subjects were studied on two separate occasions in a single-blind, randomised order. Each subject received an ID infusion of sucralose (4 mM in 0.9% saline) or control (0.9% saline) at 4 ml/min for 150 min (T = - 30 to 120 min). After 30 min (T = 0), glucose (25 %) and its non-metabolised analogue, 3-O-methylglucose (3-OMG; 2.5 %), were co-infused intraduodenally (T = 0-120 min; 4.2 kJ/min (1 kcal/min)). Blood was sampled at frequent intervals. Blood glucose, plasma glucagon-like peptide-1 (GLP-1) and serum 3-OMG concentrations increased during ID glucose/3-OMG infusion (P sucralose and control infusions. In conclusion, sucralose does not appear to modify the rate of glucose absorption or the glycaemic or incretin response to ID glucose infusion when given acutely in healthy human subjects.

  11. The Patient-Worker: A Model for Human Research Subjects and Gestational Surrogates.

    Science.gov (United States)

    Ryman, Emma; Fulfer, Katy

    2017-01-13

    We propose the 'patient-worker' as a theoretical construct that responds to moral problems that arise with the globalization of healthcare and medical research. The patient-worker model recognizes that some participants in global medical industries are workers and are owed worker's rights. Further, these participants are patient-like insofar as they are beneficiaries of fiduciary relationships with healthcare professionals. We apply the patient-worker model to human subjects research and commercial gestational surrogacy. In human subjects research, subjects are usually characterized as either patients or as workers. Through questioning this dichotomy, we argue that some subject populations fit into both categories. With respect to commercial surrogacy, we enrich feminist discussions of embodied labor by describing how surrogates are beneficiaries of fiduciary obligations. They are not just workers, but patient-workers. Through these applications, the patient-worker model offers a helpful normative framework for exploring what globalized medical industries owe to the individuals who bear the bodily burdens of medical innovation. © 2017 John Wiley & Sons Ltd.

  12. Microsatellite polymorphisms associated with human behavioural and psychological phenotypes including a gene-environment interaction

    OpenAIRE

    Bagshaw, Andrew T.M.; Horwood, L. John; Fergusson, David M; Gemmell, Neil J.; Martin A Kennedy

    2017-01-01

    Background The genetic and environmental influences on human personality and behaviour are a complex matter of ongoing debate. Accumulating evidence indicates that short tandem repeats (STRs) in regulatory regions are good candidates to explain heritability not accessed by genome-wide association studies. Methods We tested for associations between the genotypes of four selected repeats and 18 traits relating to personality, behaviour, cognitive ability and mental health in a well-studied long...

  13. A controlled laboratory comparison of 4 topical skin creams moisturizing capability on human subjects.

    Science.gov (United States)

    Young, Daniel L; Chakravarthy, Debashish

    2014-01-01

    This study compares human skin capacitance (moisture) readings after the application of 4 different, commercially available, topical skin creams. Twenty-one subjects (15 women and 6 men) aged 49.38 ± 11.02) years (mean ± SD) participated. This study was conducted in a climate-controlled laboratory on healthy human subjects. Randomized experimental study comparing 4 topical skin creams for their effect on human skin capacitance (moisture). Subject forearm skin was conditioned for 7 days prior to testing by washing with a standard soap and application of no other products. Each subject was marked with 5 test sites on the forearms. Sites on the volar surface of each subject's forearms were randomly assigned for application of 1 of 4 product pairs, consisting of a cleanser and a topical skin cream or a control site. A Corneometer was used to measure skin capacitance. Each site on the arms was cleaned and dried, tested again for moisture content, subjected to topical skin cream application, and finally tested again for moisture content. Changes were measured by subtracting the capacitance readings at baseline from values measured following topical skin cream application for each test site. The mean change in capacitance was 13.9 for product 1, 10.3 for product 3, 8.7 for product 2, 1.6 for product 4, and 0.8 for the control site. The mean capacitance change in sites treated with product 1 (13.9 ± 8.0, mean ± SD) was significantly greater than all others. There was no difference between the change in capacitance of product 2 (mean = 8.7, SD = 4.9) and product 3 (10.3 ± 7.1) t(20) = 1.081, P = .293, nor between product 4 (1.6 ± 3.9) and the control site (0.3, ± 2.2) t(20) = 0.779, P = .445. The capacitance change of products 2 and 3 was greater than that of product 4 and the control site. Commercially available topical skin creams vary in their impact on human skin capacitance. In this study, sites tested with product 1 had a greater skin capacitance reading than

  14. 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.

  15. Assessment of five different guideline indication criteria for spirometry, including modified GOLD criteria, in order to detect COPD: data from 5,315 subjects in the PLATINO study.

    Science.gov (United States)

    Luize, Ana P; Menezes, Ana Maria B; Perez-Padilla, Rogelio; Muiño, Adriana; López, Maria Victorina; Valdivia, Gonzalo; Lisboa, Carmem; Montes de Oca, Maria; Tálamo, Carlos; Celli, Bartolomé; Nascimento, Oliver A; Gazzotti, Mariana R; Jardim, José R

    2014-10-30

    Spirometry is the gold standard for diagnosing chronic obstructive pulmonary disease (COPD). Although there are a number of different guideline criteria for deciding who should be selected for spirometric screening, to date it is not known which criteria are the best based on sensitivity and specificity. Firstly, to evaluate the proportion of subjects in the PLATINO Study that would be recommended for spirometry testing according to Global initiative for Obstructive Lung Disease (GOLD)-modified, American College of Chest Physicians (ACCP), National Lung Health Education Program (NLHEP), GOLD and American Thoracic Society/European Respiratory Society (ATS/ERS) criteria. Secondly, we aimed to compare the sensitivity, specificity, and positive predictive and negative predictive values, of these five different criteria. Data from the PLATINO study included information on respiratory symptoms, smoking and previous spirometry testing. The GOLD-modified spirometry indication criteria are based on three positive answers out of five questions: the presence of cough, phlegm in the morning, dyspnoea, age over 40 years and smoking status. Data from 5,315 subjects were reviewed. Fewer people had an indication for spirometry (41.3%) according to the GOLD-modified criteria, and more people had an indication for spirometry (80.4%) by the GOLD and ATS/ERS criteria. A low percentage had previously had spirometry performed: GOLD-modified (14.5%); ACCP (13.2%); NLHEP (12.6%); and GOLD and ATS/ERS (12.3%). The GOLD-modified criteria showed the least sensitivity (54.9) and the highest specificity (61.0) for detecting COPD, whereas GOLD and ATS/ERS criteria showed the highest sensitivity (87.9) and the least specificity (20.8). There is a considerable difference in the indication for spirometry according to the five different guideline criteria. The GOLD-modified criteria recruit less people with the greatest sum of sensitivity and specificity.

  16. Immunomodulation in human and experimental arthritis: including vitamin D, helminths and heat-shock proteins.

    Science.gov (United States)

    Ishikawa, L L W; Shoenfeld, Y; Sartori, A

    2014-05-01

    Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that is mainly directed to the joints, affecting the synovial membrane, the cartilage and also the bone. This disease affects 1% to 2% of the world population and is associated with significant morbidity and increased mortality. RA experimental models have allowed a great deal of information to be translated to the corresponding human disease. This review summarizes some of the most relevant findings targeting immunomodulation in arthritis. Some general guidelines to choose an adequate experimental model and also our experience with arthritis are supplied.

  17. The human genome and sport, including epigenetics, gene doping, and athleticogenomics.

    Science.gov (United States)

    Sharp, N C Craig

    2010-03-01

    Hugh Montgomery's discovery of the first of more than 239 fitness genes together with rapid advances in human gene therapy have created a prospect of using genes, genetic elements, and cells that have the capacity to enhance athletic performance (to paraphrase the World Anti-Doping Agency's definition of gene doping). This brief overview covers the main areas of interface between genetics and sport, attempts to provide a context against which gene doping may be viewed, and predicts a futuristic legitimate use of genomic (and possibly epigenetic) information in sport. Copyright 2010 Elsevier Inc. All rights reserved.

  18. 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.

  19. 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

    of other lower limb muscles (soleus, gastrocnemius lateralis, gastrocnemius medialis, biceps femoris, vastus lateralis, and vastus medialis). Short-lasting synchronization (average duration: 9.6 +/- 1.1 ms) was observed between spike trains generated from multiunit electromyographic (EMG) signals recorded......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...... lateralis and medialis of quadriceps), but not or rarely for paired recordings from ankle and knee muscles. The data demonstrate that human motor units within a muscle as well as synergistic muscles acting on the same joint receive a common synaptic drive during human gait. It is speculated that the common...

  20. Human Gait Feature Extraction Including a Kinematic Analysis toward Robotic Power Assistance

    Directory of Open Access Journals (Sweden)

    Mario I. Chacon-Murguia

    2012-09-01

    Full Text Available The present work proposes a method for human gait and kinematic analysis. Gait analysis consists of the determination of hip, knee and ankle positions through video analysis. Gait kinematic for the thigh and knee is then generated from this data. Evaluations of the gait analysis method indicate an acceptable performance of 86.66% for hip and knee position estimation, and comparable findings with other reported works for gait kinematic. A coordinate systems assignment is performed according to the DH algorithm and a direct kinematic model of the legs is obtained. The legs' angles obtained from the video analysis are applied to the kinematic model in order to revise the application of this model to robotic legs in a power assisted system.

  1. Microscopic age determination of human skeletons including an unknown but calculable variable

    DEFF Research Database (Denmark)

    Wallin, Johan Albert; Tkocz, Izabella; Kristensen, Gustav

    1994-01-01

    estimation, which includes the covariance matrix of four single equation residuals, improves the accuracy of age determination. The standard deviation, however, of age prediction remains 12.58 years. An experimental split of the data was made in order to demonstrate that the use of subgroups gives a false...

  2. 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

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

    Science.gov (United States)

    Pimentel, Mark; Morales, Walter; Rezaie, Ali; Marsh, Emily; Lembo, Anthony; Mirocha, James; Leffler, Daniel A; Marsh, Zachary; Weitsman, Stacy; Chua, Kathleen S; Barlow, Gillian M; Bortey, Enoch; Forbes, William; Yu, Allen; Chang, Christopher

    2015-01-01

    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 (PIBS (PIBS 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 anti-vinculin antibodies are elevated in D-IBS compared to non-IBS subjects. These biomarkers may be especially helpful in distinguishing D-IBS from IBD in the workup of chronic diarrhea.

  4. Effect of Sweetened Dried Cranberry Consumption on Urinary Proteome and Fecal Microbiome in Healthy Human Subjects.

    Science.gov (United States)

    Bekiares, Nell; Krueger, Christian G; Meudt, Jennifer J; Shanmuganayagam, Dhanansayan; Reed, Jess D

    2018-02-01

    The relationship among diet, human health, and disease is an area of growing interest in biomarker research. Previous studies suggest that the consumption of cranberries (Vaccinium macrocarpon) could beneficially influence urinary and digestive health. The present study sought to determine if daily consumption of sweetened dried cranberries (SDC) changes the urinary proteome and fecal microbiome, as determined in a prospective sample of 10 healthy individuals. Baseline urine and fecal samples were collected from the subjects in the fasted (8-12 h) state. The subjects then consumed one serving (42 g) of SDC daily with lunch for 2 weeks. Urine and fecal samples were collected again the day after 2 weeks of SDC consumption. Orbitrap Q-Exactive mass spectrometry of urinary proteins showed that consumption of SDC resulted in changes to 22 urinary proteins. Multiplex sequencing of 16S ribosomal RNA genes in fecal samples indicated changes in relative abundance of several bacterial taxonomic units after consumption of SDC. There was a shift in the Firmicutes:Bacteroidetes ratio, increases in commensal bacteria, and decreases or the absence of bacteria associated with negative health effects. A decrease in uromodulin in all subjects and an increase in Akkermansia bacteria in most subjects were observed and warrant further investigation. Future larger clinical studies with multiomics and multitissue sampling designs are required to determine the effects of SDC consumption on nutrition and health.

  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.

    2015-01-01

    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 3.0 mg/d or placebo over 15 days. Participants then received intravenous cocaine (0, 20 and 40 mg) 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. PMID:26239766

  6. 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.

  7. 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.

  8. 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

    Intake of fish oil reduces the risk of CHD and CHD deaths. Marine n-3 fatty acids (FA) are susceptible to oxidation, but to our knowledge, the health effects of intake of oxidised fish oil have not previously been investigated in human subjects. The aim of the present study was to investigate...... 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...... difference was observed between the fish oil groups. No changes in a variety of in vivo markers of oxidative stress, lipid peroxidation or inflammation were observed after daily intake of oxidised fish oil for 3 or 7 weeks, indicating that intake of oxidised fish oil may not have unfavourable short...

  9. Modulation of Innate Host Factors by Mycobacterium avium Complex in Human Macrophages Includes Interleukin 17

    Science.gov (United States)

    Vázquez, Nancy; Rekka, Sofia; Gliozzi, Maria; Feng, Carl G.; Amarnath, Shoba; Orenstein, Jan M.; Wahl, Sharon M.

    2012-01-01

    Background. Although opportunistic infections due to Mycobacterium avium complex (MAC) have been less common since the introduction of highly active antiretroviral therapy, globally, human immunodeficiency virus-1 (HIV-1)–positive patients remain predisposed to these infections. Absence of a properly functioning acquired immune response allows MAC persistence within macrophages localized in lymph nodes coinfected with HIV and MAC. Although a deficiency in interferon γ appears to play a part in the ability of MAC to deflect the macrophage-associated antimicrobial attack, questions about this process remain. Our study examines the ability of MAC to regulate interleukin 17 (IL-17), a proinflammatory cytokine involved in host cell recruitment. Methods. Coinfected lymph nodes were examined for IL-17 by immunohistochemical analysis. In vitro, macrophages exposed to mycobacteria were evaluated for transcription activities, proteins, and signaling pathways responsible for IL-17 expression. Infected macrophages were also analyzed for expression of interleukin 21 (IL-21) and negative regulators of immune responses. Results. Infection of macrophages triggered synthesis of IL-17, correlating with IL-17 expression by macrophages in coinfected lymph nodes. Infected macrophages exposed to exogenous IL-17 expressed CXCL10, which favors recruitment of new macrophages as targets for infection. Blockade of nuclear factor κ-light-chain-enhancer of activated B cells and mitogen-activated protein kinase pathways suppressed mycobacteria-induced IL-17 expression. MAC triggered expression of IL-21, IRF4, and STAT3 genes related to IL-17 regulation, as well as expression of the negative immunoregulators CD274(PD-L1) and suppressors of cytokine signaling. Conclusions. MAC-infected macrophages can provide an alternative source for IL-17 that favors accumulation of new targets for perpetuating bacterial and viral infection while suppressing host antimicrobial immune responses. PMID

  10. Transsphenoidal meningocele: an anatomical study using human fetuses including report of a case.

    Science.gov (United States)

    Katori, Yukio; Kawamoto, Ai; Cho, Kwang Ho; Ishii, Kiyoshi; Abe, Hiroshi; Abe, Shinichi; Rodríguez-Vázquez, Jose Francisco; Murakami, Gen; Kawase, Tetsuaki

    2013-09-01

    An asymptomatic transsphenoidal meningoencephalocele was discovered incidentally by fiber laryngoscopic examination in a 62-year-old man suffering from hoarseness due to dysplasia of the vocal cord epithelium. To provide a better understanding of the pathogenesis of this anomaly, we performed histologic observations of paraffin-embedded specimens of 42 human fetal heads at 12-16 weeks of gestation. At these stages, ossification had started in the clivus but the sphenoid sinus was not developed. In contrast to the very low incidence of the intra- or trans-sphenoidal remnant of Rathke's pouch after birth, we found (1) the typical mid-line cleft of the sphenoid body in two specimens (2/42 or 4.8 %) and (2) a duct-like, sellar inferior protrusion ending in the sphenoid body in 12 specimens (12/42 or 28.6 %). The cyst-like structure in the protrusion (two specimens) seemed to be composed of obstructed veins. The intra- and trans-sphenoidal anomalies were observed more frequently in specimens without ossification of the sphenoid body than in those with ossification. However, irrespective of ossification, a cyst-like remnant of the most upper part of Rathke's pouch was always seen between the anterior and posterior lobes of the developing pituitary gland. In addition, the bursa pharyngea was seen in four specimens and we confirmed that the notochord was attached to the bursa in each case. The consistent remnant of the intrasellar Rathke's pouch appeared to explain the high incidence of Rathke's cleft cyst in adults. The relatively high incidence of intrasphenoidal anomalies in fetuses (14/42) suggested that the intra- or trans-sphenoidal remnant of Rathke's pouch was physiologically closed by ossification of the sphenoid body.

  11. 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......, a custom-built low-frequency acoustic probe was put to use in 21 normal-hearing human subjects (of 34 recruited). Distortion-product otoacoustic emission (DPOAE) was measured in the enclosed ear canal volume as the response to two simultaneously presented tones with frequencies f1 and f2. The stimulus...... known from higher frequencies. Toward low frequencies, however, the bell broadens and the optimal ratio increases proportionally to the bandwidth of an auditory filter as defined by the equivalent rectangular bandwidth. The DPOAE phase rotates monotonously as a function of the stimulus ratio, and its...

  12. 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...

  13. Lactate influx into red blood cells from trained and untrained human subjects.

    Science.gov (United States)

    Skelton, M S; Kremer, D E; Smith, E W; Gladden, L B

    1998-04-01

    The purpose of this study was to compare the fractional contributions of the three pathways of lactate transport (band 3 system, nonionic diffusion, and monocarboxylate pathway) into red blood cells (RBC) from trained and untrained humans. Blood samples were obtained from 19 male subjects: 5 untrained, 5 aerobically-trained, 5 competitive collegiate cross-country runners, and 4 competitive collegiate sprinters. The influx of lactate into the RBC was measured by a radioactive tracer technique using [14C]lactate. Discrimination of each pathway of lactate transport was achieved by using PCMBS (1 mM) to block the monocarboxylate pathway and DIDS (0.2 mM) to block the band 3 system. Nonionic diffusion was calculated as the difference between total lactate influx and the sum of band 3 and monocarboxylate lactate influx. Total lactate influx into the RBC from the more aerobic individuals (trained subjects and cross-country runners) was significantly faster at 1.6 mM lactate concentration ([La]) as compared with the influx into RBC of the untrained subjects. Total influx of lactate was significantly higher (P untrained subjects at 41 mM [La]. There were no significant differences among the four groups with regard to the total influx of lactate at 4.1, 8.1, and 20 mM [La]. In general, the percentage of total lactate influx accounted for by each of the three parallel pathways at 1.6, 8.1, and 41.0 mM [La] was not different among the four groups of subjects. Overall, the groups were more similar than different with regard to RBC lactate influx.

  14. A structural model for the in vivo human cornea including collagen-swelling interaction

    Science.gov (United States)

    Cheng, Xi; Petsche, Steven J.; Pinsky, Peter M.

    2015-01-01

    A structural model of the in vivo cornea, which accounts for tissue swelling behaviour, for the three-dimensional organization of stromal fibres and for collagen-swelling interaction, is proposed. Modelled as a binary electrolyte gel in thermodynamic equilibrium, the stromal electrostatic free energy is based on the mean-field approximation. To account for active endothelial ionic transport in the in vivo cornea, which modulates osmotic pressure and hydration, stromal mobile ions are shown to satisfy a modified Boltzmann distribution. The elasticity of the stromal collagen network is modelled based on three-dimensional collagen orientation probability distributions for every point in the stroma obtained by synthesizing X-ray diffraction data for azimuthal angle distributions and second harmonic-generated image processing for inclination angle distributions. The model is implemented in a finite-element framework and employed to predict free and confined swelling of stroma in an ionic bath. For the in vivo cornea, the model is used to predict corneal swelling due to increasing intraocular pressure (IOP) and is adapted to model swelling in Fuchs' corneal dystrophy. The biomechanical response of the in vivo cornea to a typical LASIK surgery for myopia is analysed, including tissue fluid pressure and swelling responses. The model provides a new interpretation of the corneal active hydration control (pump-leak) mechanism based on osmotic pressure modulation. The results also illustrate the structural necessity of fibre inclination in stabilizing the corneal refractive surface with respect to changes in tissue hydration and IOP. PMID:26156299

  15. Should nonalcoholic fatty liver disease be included in the definition of metabolic syndrome? A cross-sectional comparison with Adult Treatment Panel III criteria in nonobese nondiabetic subjects

    National Research Council Canada - National Science Library

    Musso, Giovanni; Gambino, Roberto; Bo, Simona; Uberti, Barbara; Biroli, Giampaolo; Pagano, Gianfranco; Cassader, Maurizio

    2008-01-01

    The ability of the Adult Treatment Panel III (ATP III) criteria of metabolic syndrome to identify insulin-resistant subjects at increased cardiovascular risk is suboptimal, especially in the absence of obesity and diabetes...

  16. A structural model for the in vivo human cornea including collagen-swelling interaction.

    Science.gov (United States)

    Cheng, Xi; Petsche, Steven J; Pinsky, Peter M

    2015-08-06

    A structural model of the in vivo cornea, which accounts for tissue swelling behaviour, for the three-dimensional organization of stromal fibres and for collagen-swelling interaction, is proposed. Modelled as a binary electrolyte gel in thermodynamic equilibrium, the stromal electrostatic free energy is based on the mean-field approximation. To account for active endothelial ionic transport in the in vivo cornea, which modulates osmotic pressure and hydration, stromal mobile ions are shown to satisfy a modified Boltzmann distribution. The elasticity of the stromal collagen network is modelled based on three-dimensional collagen orientation probability distributions for every point in the stroma obtained by synthesizing X-ray diffraction data for azimuthal angle distributions and second harmonic-generated image processing for inclination angle distributions. The model is implemented in a finite-element framework and employed to predict free and confined swelling of stroma in an ionic bath. For the in vivo cornea, the model is used to predict corneal swelling due to increasing intraocular pressure (IOP) and is adapted to model swelling in Fuchs' corneal dystrophy. The biomechanical response of the in vivo cornea to a typical LASIK surgery for myopia is analysed, including tissue fluid pressure and swelling responses. The model provides a new interpretation of the corneal active hydration control (pump-leak) mechanism based on osmotic pressure modulation. The results also illustrate the structural necessity of fibre inclination in stabilizing the corneal refractive surface with respect to changes in tissue hydration and IOP. © 2015 The Author(s).

  17. Response of Ambulatory Human Subjects to Artificial Gravity (Short Radius Centrifugation)

    Science.gov (United States)

    Paloski, William H.; Arya, Maneesh; Newby, Nathaniel; Tucker, Jon-Michael; Jarchow, Thomas; Young, Laurence

    2006-01-01

    Prolonged exposure to microgravity results in significant adaptive changes, including cardiovascular deconditioning, muscle atrophy, bone loss, and sensorimotor reorganization, that place individuals at risk for performing physical activities after return to a gravitational environment. Planned missions to Mars include unprecedented hypogravity exposures that would likely result in unacceptable risks to crews. Artificial gravity (AG) paradigms may offer multisystem protection from the untoward effects of adaptation to the microgravity of space or the hypogravity of planetary surfaces. While the most effective AG designs would employ a rotating spacecraft, perceived issues may preclude their use. The questions of whether and how intermittent AG produced by a short radius centrifuge (SRC) could be employed have therefore sprung to the forefront of operational research. In preparing for a series of intermittent AG trials in subjects deconditioned by bed rest, we have examined the responses of several healthy, ambulatory subjects to SRC exposures.

  18. An anthropometric based subject-specific finite element model of the human breast for predicting large deformations

    Directory of Open Access Journals (Sweden)

    Silvia ePianigiani

    2015-12-01

    Full Text Available 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.

  19. The tolerance and nutritional value of two microfungal foods in human subjects.

    Science.gov (United States)

    Udall, J N; Lo, C W; Young, V R; Scrimshaw, N S

    1984-08-01

    The tolerance of human subjects to two microfungal food products was studied in separate double-blind cross-over studies. As an addition to the subject's usual diets, cookies with and without 20 g of a product from Fusarium graminearium were fed to a group of 100 individuals daily. In a second study, cupcakes with and without 10 g of Paecilomyces variotii were given daily to 50 individuals. Mild rashes possibly related to one of the microfungal food products occurred in two individuals fed P variotii. Except for a decrease in serum cholesterol during the F graminearium study, no significant changes were noted in 17 serum constituents. During nutritive value studies, digestibility, biological value, and net protein utilization were calculated for the two microfungal proteins and for milk. The values for milk were 95, 85, and 80%, respectively. The values for F graminearium were 78, 84, and 65%, respectively. For P variotii corresponding figures were 81, 67, and 54%. On the basis of these results both microfungal foods may be deemed safe for human consumption at the levels tested.

  20. [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.

  1. Effect of ozone exposure on the dispersion of inhaled aerosol boluses in healthy human subjects

    Energy Technology Data Exchange (ETDEWEB)

    Keefe, M.J.; Bennett, W.D.; Dewitt, P.; Seal, E.; Strong, A.A.

    1990-12-06

    Acute exposure of humans to low levels of ozone are known to cause decreases FVC and increases sRaw. These alterations in lung function do not, however, elucidate the potential for acute small airways responses. In the study the authors employed a test of aerosol dispersion to examine the potential effects of ozone on small airways in humans. Twenty-two healthy non-smoking male volunteers were exposed to 0.4 ppm ozone for one hour while exercising at 20 l/min/m{sup 2} (BSA). Prior to and immediately following exposure, tests of spirometry (FVC, FEV1, and FEF25-75) and plethysmography (Raw and sRaw) were performed. Subjects also performed an aerosol dispersion test before and after exposure. Each test involved a subject inhaling five to seven breaths of a 300 ml bolus of a 0.5 micrometers triphenyl phosphate (TPP) aerosol injected into a 2 liters tidal volume. The bolus was injected into the tidal breath at three different depths: at depth A the bolus was injected after 1.6 liters of clean air was inhaled from FRC; at depth B after 1.2 liters; and at depth C after 1.2 liters but with inhalation beginning from RV. The primary measure of bolus dispersion was the expired half-width (HW).

  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. 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 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.ClinicalTrials.gov NCT01237431.

  4. Development and optimization of a noncontact optical device for online monitoring of jaundice in human subjects

    Science.gov (United States)

    Polley, Nabarun; Saha, Srimoyee; Singh, Soumendra; Adhikari, Aniruddha; Das, Sukhen; Choudhury, Bhaskar Roy; Pal, Samir Kumar

    2015-06-01

    Jaundice is one of the notable markers of liver malfunction in our body, revealing a significant rise in the concentration of an endogenous yellow pigment bilirubin. We have described a method for measuring the optical spectrum of our conjunctiva and derived pigment concentration by using diffused reflection measurement. The method uses no prior model and is expected to work across the races (skin color) encompassing a wide range of age groups. An optical fiber-based setup capable of measuring the conjunctival absorption spectrum from 400 to 800 nm is used to monitor the level of bilirubin and is calibrated with the value measured from blood serum of the same human subject. We have also developed software in the LabVIEW platform for use in online monitoring of bilirubin levels in human subjects by nonexperts. The results demonstrate that relative absorption at 460 and 600 nm has a distinct correlation with that of the bilirubin concentration measured from blood serum. Statistical analysis revealed that our proposed method is in agreement with the conventional biochemical method. The innovative noncontact, low-cost technique is expected to have importance in monitoring jaundice in developing/underdeveloped countries, where the inexpensive diagnosis of jaundice with minimally trained manpower is obligatory.

  5. Psilocybin links binocular rivalry switch rate to attention and subjective arousal levels in humans.

    Science.gov (United States)

    Carter, Olivia L; Hasler, Felix; Pettigrew, John D; Wallis, Guy M; Liu, Guang B; Vollenweider, Franz X

    2007-12-01

    Binocular rivalry occurs when different images are simultaneously presented to each eye. During continual viewing of this stimulus, the observer will experience repeated switches between visual awareness of the two images. Previous studies have suggested that a slow rate of perceptual switching may be associated with clinical and drug-induced psychosis. The objective of the study was to explore the proposed relationship between binocular rivalry switch rate and subjective changes in psychological state associated with 5-HT2A receptor activation. This study used psilocybin, the hallucinogen found naturally in Psilocybe mushrooms that had previously been found to induce psychosis-like symptoms via the 5-HT2A receptor. The effects of psilocybin (215 microg/kg) were considered alone and after pretreatment with the selective 5-HT2A antagonist ketanserin (50 mg) in ten healthy human subjects. Psilocybin significantly reduced the rate of binocular rivalry switching and increased the proportion of transitional/mixed percept experience. Pretreatment with ketanserin blocked the majority of psilocybin's "positive" psychosis-like hallucinogenic symptoms. However, ketanserin had no influence on either the psilocybin-induced slowing of binocular rivalry or the drug's "negative-type symptoms" associated with reduced arousal and vigilance. Together, these findings link changes in binocular rivalry switching rate to subjective levels of arousal and attention. In addition, it suggests that psilocybin's effect on binocular rivalry is unlikely to be mediated by the 5-HT2A receptor.

  6. 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.

  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. Prevention of urinary tract infections with vitamin D supplementation 20,000 IU per week for five years. Results from an RCT including 511 subjects.

    Science.gov (United States)

    Jorde, Rolf; Sollid, Stina T; Svartberg, Johan; Joakimsen, Ragnar M; Grimnes, Guri; Hutchinson, Moira Y S

    2016-01-01

    In observational studies vitamin D deficiency is associated with increased risk of infections, whereas the effect of vitamin D supplementation in randomized controlled trials is non-conclusive. Five hundred and eleven subjects with prediabetes were randomized to vitamin D3 (20,000 IU per week) versus placebo for five years. Every sixth month, a questionnaire on respiratory tract infections (RTI) (common cold, bronchitis, influenza) and urinary tract infection (UTI) was filled in. Mean baseline serum 25-hydroxyvitamin D (25(OH)D) level was 60 nmol/L. Two hundred and fifty-six subjects received vitamin D and 255 placebo. One hundred and sixteen subjects in the vitamin D and 111 in the placebo group completed the five-year study. Eighteen subjects in the vitamin D group and 34 subjects in the placebo group reported UTI during the study (p vitamin D on UTI was unrelated to baseline serum 25(OH)D level. Supplementation with vitamin D might prevent UTI, but confirmatory studies are needed.

  9. 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.

  10. Human papilloma virus and oral lesions in gutka eating subjects in Karachi.

    Science.gov (United States)

    Baig, Saeeda; Lucky, Mohammad Haris; Qamar, Areeba; Ahmad, Farah; Khan, Shaji; Ahmed, Waqas; Chughtai, Talaiha; Hassan, Wafa; Hussain, Batool Akhlaq; Khan, Azeem

    2012-03-01

    To determine the frequency of HPV in eaters of Gutka (betel, areca, lime and tobacco concoction), presenting with oral lesions. A descriptive study. Ziauddin University Research Laboratory, from February to July 2010. Subjects munching Gutka fulfilled the inclusion criteria. Samples were collected in the form of 20 - 40 ml oral rinse from 262 subjects who were habitual eaters of Gutka after an informed consent. Gentle brushings from the lesion were taken from subjects with the help of a brush at the other end of dental floss and the oral rinse was stored at 4°C until DNA extraction. DNA was extracted and PCR was performed using HPV consensus primers Gp5+/Gp6+. Oral cavity was examined for the presence of ulcer, trismus, sub-mucosal fibrosis, leukoplakia and/or warts. Out of 262 subjects, 42 were females and 220 males with an average age of 27± 10 years. HPV was positive in 47 subjects (17.9%). HPV frequency was 2.7% greater in chewers with more than 10 years of habit compared to less than 10 years. Examination of oral cavity showed 78% presenting with more than one complaint including oral ulcers (25%), rough mucosa (62%), sub-mucosal fibrosis (24%), leukoplakia (20%) and erythroplakia (10.6%). Highest frequency of HPV was observed in erythroplakia (25%). Association between presence of symptoms and HPV shows an ODDS RATIO: ad/bc= 4982/430=11.6. Oral lesions caused by constant exposure to Gutka are associated with high frequency of HPV infection, which may be a risk factor for squamous cell carcinoma of the oral cavity. People should be educated about the consequences of Gutka abuse.

  11. Should nonalcoholic fatty liver disease be included in the definition of metabolic syndrome? A cross-sectional comparison with Adult Treatment Panel III criteria in nonobese nondiabetic subjects.

    Science.gov (United States)

    Musso, Giovanni; Gambino, Roberto; Bo, Simona; Uberti, Barbara; Biroli, Giampaolo; Pagano, Gianfranco; Cassader, Maurizio

    2008-03-01

    The ability of the Adult Treatment Panel III (ATP III) criteria of metabolic syndrome to identify insulin-resistant subjects at increased cardiovascular risk is suboptimal, especially in the absence of obesity and diabetes. Nonalcoholic fatty liver disease (NAFLD) is associated with insulin resistance and is emerging as an independent cardiovascular risk factor. We compared the strength of the associations of ATP III criteria and of NAFLD to insulin resistance, oxidative stress, and endothelial dysfunction in nonobese nondiabetic subjects. Homeostasis model assessment of insulin resistance (HOMA-IR) >2, oxidative stress (nitrotyrosine), soluble adhesion molecules (intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin), and circulating adipokines (tumor necrosis factor-alpha, leptin, adiponectin, and resistin) were cross-sectionally correlated to ATP III criteria and to NAFLD in 197 unselected nonobese nondiabetic subjects. NAFLD more accurately predicted insulin resistance than ATP III criteria: sensitivity 73 vs. 38% (P = 0.0001); positive predictive value: 81 vs. 62% (P = 0.035); negative predictive value 87 vs. 74% (P = 0.012); positive likelihood ratio 4.39 vs. 1.64 (P = 0.0001); and negative likelihood ratio 0.14 vs. 0.35 (P = 0.0001). Adding NAFLD to ATP III criteria significantly improved their diagnostic accuracy for insulin resistance. Furthermore, NAFLD independently predicted HOMA-IR, nitrotyrosine, and soluble adhesion molecules on logistic regression analysis; the presence of NAFLD entailed more severe oxidative stress and endothelial dysfunction, independent of adiposity or any feature of the metabolic syndrome in insulin-resistant subjects. NAFLD is more tightly associated with insulin resistance and with markers of oxidative stress and endothelial dysfunction than with ATP III criteria in nonobese nondiabetic subjects and may help identify individuals with increased cardiometabolic risk in this population.

  12. Absorption of anthocyanins from blueberries and serum antioxidant status in human subjects.

    Science.gov (United States)

    Mazza, G; Kay, Colin D; Cottrell, Tony; Holub, Bruce J

    2002-12-18

    In recent years, numerous studies have shown that the polyphenolics present in fruit and vegetable products exhibit a wide range of biological effects. However, there is little reliable information on the absorption of glycosylated and acylated anthocyanins in humans. In the present study, the absorption of anthocyanins in humans was investigated after the consumption of a high-fat meal with a freeze-dried blueberry powder containing 25 individual anthocyanins including 6 acylated structures. Nineteen of the 25 anthocyanins present in the blueberries were detected in human blood serum. Furthermore, the appearance of total anthocyanins in the serum was directly correlated with an increase in serum antioxidant capacity (ORAC(acetone), P blueberries, a food source with high in vitro antioxidant properties, is associated with a diet-induced increase in ex vivo serum antioxidant status.

  13. 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.

  14. 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.

  15. The pharmaceutical industry's responsibility for protecting human subjects of clinical trials in developing nations.

    Science.gov (United States)

    Kelleher, Finnuala

    2004-01-01

    Pharmaceutical companies increasingly perform clinical trials in developing nations. Governments of host nations see the trials as a way to provide otherwise unaffordable medical care, while trial sponsors are drawn to those countries by lower costs, the prevalence of diseases rare in developed nations, and large numbers of impoverished patients. Local governments, however, fail to police trials, and the FDA does not monitor trials in foreign countries, resulting in the routine violation of international standards for the protection of human subjects. This Note proposes independent accreditation of those institutions involved in clinical trials--the institutional review boards which oversee trial protocol; the organizations, such as pharmaceutical companies, which sponsor the trials; and the research organizations that conduct the trials. Accreditation, similar to that used in the footwear and apparel industries, would increase the transparency of pharmaceutical trials and would enable the United States government and consumers to hold trial sponsors accountable for their actions.

  16. 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...

  17. 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.

  18. Including indigestible carbohydrates in the evening meal of healthy subjects improves glucose tolerance, lowers inflammatory markers, and increases satiety after a subsequent standardized breakfast

    DEFF Research Database (Denmark)

    Nilsson, Anne C; Ostman, Elin M; Holst, Jens Juul

    2008-01-01

    tolerance and related variables after a subsequent standardized breakfast in healthy subjects (n = 15). At breakfast, blood was sampled for 3 h for analysis of blood glucose, serum insulin, serum FFA, serum triacylglycerides, plasma glucagon, plasma gastric-inhibitory peptide, plasma glucagon-like peptide-1...... (GLP-1), serum interleukin (IL)-6, serum IL-8, and plasma adiponectin. Satiety was subjectively rated after breakfast and the gastric emptying rate (GER) was determined using paracetamol as a marker. Breath hydrogen was measured as an indicator of colonic fermentation. Evening meals with barley kernel......-kernel bread compared with WWB. Breath hydrogen correlated positively with satiety (r = 0.27; P metabolic risk variables at breakfast...

  19. 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

    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...

  20. 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

    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...

  1. The effect of ozone exposure on the dispersion of inhaled aerosol boluses in healthy human subjects

    Energy Technology Data Exchange (ETDEWEB)

    Keefe, M.J.; Bennett, W.D.; DeWitt, P.; Seal, E.; Strong, A.A.; Gerrity, T.R. (Clinical Research Branch, U.S. Environmental Protection Agency, Research Triangle Park, NC (USA))

    1991-07-01

    Acute exposure of humans to low levels of ozone are known to cause decreases in FVC and increases in SRaw. These alterations in lung function do not, however, elucidate the potential for acute small airway responses. In this study we employed a test of aerosol dispersion to examine the potential effects of ozone on small airways in humans. Twenty-two healthy nonsmoking male volunteers were exposed to 0.4 ppm ozone for 1 h while exercising at 20 L/min/m2 body surface area. Before and immediately after exposure, tests of spirometry (FVC, FEV1, and FEF25-75) and plethysmography (Raw and SRaw) were performed. Subjects also performed an aerosol dispersion test before and after exposure. Each test involved a subject inhaling five to seven breaths of a 300-ml bolus of a 0.5 micron triphenyl phosphate aerosol injected into a 2-L tidal volume. The bolus was injected into the tidal breath at three different depths: at Depth A the bolus was injected after 1.6 L of clean air were inhaled from FRC, at Depth B after 1.2 L, and at Depth C after 1.2 L but with inhalation beginning from RV. The primary measure of bolus dispersion was the expired half-width (HW). Secondary measures were the ratio (expressed as percent) of peak exhaled aerosol concentration to peak inhaled concentration (PR), shift in the median bolus volume between inspiration and expiration (VS), and percent of total aerosol recovered (RC). Changes in pulmonary function after ozone exposure were consistent with previous findings.

  2. Intracardiac electrocardiographic assessment of precordial TASER shocks in human subjects: A pilot study.

    Science.gov (United States)

    Stopyra, Jason P; Winslow, James E; Fitzgerald, David M; Bozeman, William P

    2017-11-01

    Case reports of cardiac arrest in temporal proximity to Conducted Electrical Weapon(CEW) exposure raise legitimate concerns about this as a rare possibility. In this pilot study, we respectfully navigate the oversight and regulatory hurdles and demonstrate the intra-shock electrocardiographic effects of an intentional transcardiac CEW discharge using subcutaneous probes placed directly across the precordium of patients with a previously implanted intracardiac EKG sensing lead. Adults scheduled to undergo diagnostic EP studies or replacement of an implanted cardiac device were enrolled. Sterile subcutaneous electrodes were placed at the right sternoclavicular junction and the left lower costal margin at the midclavicular line. A standard police issue TASER Model X26 CEW was attached to the subcutaneous electrodes and a 5 s discharge was delivered. Continuous surface and intracardiac EKG monitoring was performed. A total of 157 subjects were reviewed for possible inclusion and 21 were interviewed. Among these, 4 subjects agreed and completed the study protocol. All subjects tolerated the 5 s CEW discharge without clinical complications. There were no significant changes in mean heart rate or blood pressure. Interrogation of the devices after CEW discharge revealed no ventricular pacing, dysrhythmias, damage or interference with the implanted devices. In this pilot study, we have successfully navigated the regulatory hurdles and demonstrated the feasibility of performing intracardiac EKG recording during intentional precordial CEW discharges in humans. While no CEW-associated dysrhythmias were noted, the size of this preliminary dataset precludes making conclusions about the risk of such events. Larger studies are warranted and should consider exploring variations of the CEW electrode position in relation to the cardiac silhouette. Copyright © 2017. Published by Elsevier Ltd.

  3. The effect of wild blueberry (Vaccinium angustifolium) consumption on postprandial serum antioxidant status in human subjects.

    Science.gov (United States)

    Kay, Colin D; Holub, Bruce J

    2002-10-01

    The aim of the present study was to determine whether the consumption of wild blueberries (Vaccinium angustifolium), a concentrated source of non-nutritive antioxidant phytochemicals, would enhance postprandial serum antioxidant status in healthy human subjects. A single-blinded crossover study was performed in a group of eight middle-aged male subjects (38-54 years). Subjects consumed a high-fat meal and a control supplement followed 1 week later by the same high-fat meal supplemented with 100.0 g freeze-dried wild blueberry powder. Upon brachial vein catheterization, fasting and postprandial serum samples were taken sequentially and analysed for lipids and glucose and for serum antioxidant status. Serum antioxidant status was determined using the oxygen radical absorbance capacity (ORAC) assay and the total antioxidant status (TAS) assay. The wild-blueberry treatment was associated with a significant treatment effect as determined by the ORAC assay (water-soluble fraction ORAC(perchloric acid (PCA)), P=0.04). Significant increases in serum antioxidant status above the controls were observed at 1 h (ORAC(PCA) (8.5 % greater), P=0.02; TAS (4.5 % greater), P=0.05), and 4 h (ORAC(total) (15.0 % greater), P=0.009; ORAC(acetone) (16.0 % greater), P=0.007) post-consumption of the high-fat meal. In conclusion, the consumption of wild blueberries, a food source with high in vitro antioxidant properties, is associated with a diet-induced increase in ex vivo serum antioxidant status. It has been suggested that increasing the antioxidant status of serum may result in the reduced risk of many chronic degenerative diseases.

  4. 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)

  5. 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...

  6. Human circadian pacemaker is sensitive to light throughout subjective day without evidence of transients

    Science.gov (United States)

    Jewett, M. E.; Rimmer, D. W.; Duffy, J. F.; Klerman, E. B.; Kronauer, R. E.; Czeisler, C. A.

    1997-01-01

    Fifty-six resetting trials were conducted across the subjective day in 43 young men using a three-cycle bright-light (approximately 10,000 lx). The phase-response curve (PRC) to these trials was assessed for the presence of a "dead zone" of photic insensitivity and was compared with another three-cycle PRC that had used a background of approximately 150 lx. To assess possible transients after the light stimulus, the trials were divided into 43 steady-state trials, which occurred after several baseline days, and 13 consecutive trials, which occurred immediately after a previous resetting trial. We found that 1) bright light induces phase shifts throughout subjective day with no apparent dead zone; 2) there is no evidence of transients in constant routine assessments of the fitted temperature minimum 1-2 days after completion of the resetting stimulus; and 3) the timing of background room light modulates the resetting response to bright light. These data indicate that the human circadian pacemaker is sensitive to light at virtually all circadian phases, implying that the entire 24-h pattern of light exposure contributes to entrainment.

  7. The effects of auditory perception and musical preference on anxiety in naive human subjects.

    Science.gov (United States)

    Salamon, Elliott; Bernstein, Steven R; Kim, Seung-A; Kim, Minsun; Stefano, George B

    2003-09-01

    The use of music as a method of relieving anxiety has been studied extensively by researchers from varying disciplines. The abundance of these reports focused on which genre of music best aided in the relief of stress. Little work has been performed in the area of auditory preference in an attempt to ascertain whether an individual's preferred music type aids in their anxiety reduction at levels greater than music that they have little or no propensity for. In the present report we seek to determine whether naive human subjects exposed to music of their preference show a decrease in anxiety, as measured by systolic and diastolic blood pressure values. We furthermore contrast these values to those obtained during non-preferred music listening. We found statistically significant reduction of anxiety levels only when subjects were exposed to their preferred musical selections. Students participating in the study already had knowledge of what genre of music would best relax them. It is our belief, that within the general population, many people do not have this self understanding. We conclude that music therapy may provide a mechanism for this self-understanding and subsequently help alleviate anxiety and stress.

  8. An approach to including protein quality when assessing the net contribution of livestock to human food supply.

    Science.gov (United States)

    Ertl, P; Knaus, W; Zollitsch, W

    2016-11-01

    The production of protein from animal sources is often criticized because of the low efficiency of converting plant protein from feeds into protein in the animal products. However, this critique does not consider the fact that large portions of the plant-based proteins fed to animals may be human-inedible and that the quality of animal proteins is usually superior as compared with plant proteins. The aim of the present study was therefore to assess changes in protein quality in the course of the transformation of potentially human-edible plant proteins into animal products via livestock production; data from 30 Austrian dairy farms were used as a case study. A second aim was to develop an approach for combining these changes with quantitative aspects (e.g. with the human-edible feed conversion efficiency (heFCE), defined as kilogram protein in the animal product divided by kilogram potentially human-edible protein in the feeds). Protein quality of potentially human-edible inputs and outputs was assessed using the protein digestibility-corrected amino acid score and the digestible indispensable amino acid score, two methods proposed by the Food and Agriculture Organization of the United Nations to describe the nutritional value of proteins for humans. Depending on the method used, protein scores were between 1.40 and 1.87 times higher for the animal products than for the potentially human-edible plant protein input on a barn-gate level (=protein quality ratio (PQR)). Combining the PQR of 1.87 with the heFCE for the same farms resulted in heFCE×PQR of 2.15. Thus, considering both quantity and quality, the value of the proteins in the animal products for human consumption (in this case in milk and beef) is 2.15 times higher than that of proteins in the potentially human-edible plant protein inputs. The results of this study emphasize the necessity of including protein quality changes resulting from the transformation of plant proteins to animal proteins when

  9. 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.

  10. Long-term wheat germ intake beneficially affects plasma lipids and lipoproteins in hypercholesterolemic human subjects.

    Science.gov (United States)

    Cara, L; Armand, M; Borel, P; Senft, M; Portugal, H; Pauli, A M; Lafont, H; Lairon, D

    1992-02-01

    In previous short-term studies in rats and humans, the ingestion of raw wheat germ lowered plasma triglycerides and cholesterol. Thus, the present study was designed to investigate the possible long-term effects of wheat germ intake. Diet supplementation with raw wheat germ or partially defatted wheat germ was tested in two separate groups of 10 and 9 free-living human subjects, respectively. They all exhibited hypercholesterolemia (6.14-9.67 mmol/L cholesterol) and 11 had hypertriglyceridemia. None was diabetic. Fasting blood samples were taken at the beginning of the study, after 4 wk of 20 g/d wheat germ intake, after 14 additional weeks of 30 g/d wheat germ intake and after 12 wk without any supplementation. Dietary records were kept for seven and three consecutive days, before and during the wheat germ intake periods, respectively. Raw wheat germ intake significantly decreased plasma cholesterol (-8.7%) and tended to reduce VLDL cholesterol (-19.6%) after 4 wk. After 14 additional weeks, plasma cholesterol (-7.2%) and LDL cholesterol (-15.4%) remained lower and plasma triglycerides (-11.3%) tended to be lower. The apo B:apo A1 ratio significantly decreased after both periods. Partially defatted wheat germ transiently decreased plasma triglycerides and cholesterol after a 4-wk intake. The present data indicate that wheat germ reduces cholesterolemia in the long term and could play a beneficial role in the dietary management of type IIa and IIb hyperlipidemia.

  11. 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.

  12. Effect of flavonoids on human health: old subjects but new challenges.

    Science.gov (United States)

    Lee, Eung-Ryoung; Kang, Geun-Ho; Cho, Ssang-Goo

    2007-01-01

    Flavonoids are highly diversified plant pigments that are present in a wide range of fruits, vegetables, nuts, and beverages. They are regularly consumed in the human diet and have various biological activities including anti-inflammatory, anti-cancer, and anti-viral properties. The flavonoids maybe one of the safest non-immunogenic drugs because they are small organic compounds which have been normally absorbed by the human body for long time. During the past decades, the patents on their health effects have inflated very much and the yearly number of the patents is on an increasing trend. This review summarizes the current patents on the health effects of various flavonoids, and suggests the possible expectation that a wide variety of diseases are successful treated with newly-developed specific flavonoids or their derivatives in the near future. In recent patents, specific flavonoids were described to function as anti-oxidants, enzyme inhibitors, hormones, or immune modulators. Moreover, the recent patents also tried to provide the molecular mechanism of the flavonoid compounds on treating or preventing various human diseases. Recent mechanistic studies in molecular level make it possible that specific flavonoids are identified to have a wide range of biological properties that can contribute to the beneficial effects on human health.

  13. Including indigestible carbohydrates in the evening meal of healthy subjects improves glucose tolerance, lowers inflammatory markers, and increases satiety after a subsequent standardized breakfast.

    Science.gov (United States)

    Nilsson, Anne C; Ostman, Elin M; Holst, Jens J; Björck, Inger M E

    2008-04-01

    Low-glycemic index (GI) foods and foods rich in whole grain are associated with reduced risk of type 2 diabetes and cardiovascular disease. We studied the effect of cereal-based bread evening meals (50 g available starch), varying in GI and content of indigestible carbohydrates, on glucose tolerance and related variables after a subsequent standardized breakfast in healthy subjects (n = 15). At breakfast, blood was sampled for 3 h for analysis of blood glucose, serum insulin, serum FFA, serum triacylglycerides, plasma glucagon, plasma gastric-inhibitory peptide, plasma glucagon-like peptide-1 (GLP-1), serum interleukin (IL)-6, serum IL-8, and plasma adiponectin. Satiety was subjectively rated after breakfast and the gastric emptying rate (GER) was determined using paracetamol as a marker. Breath hydrogen was measured as an indicator of colonic fermentation. Evening meals with barley kernel based bread (ordinary, high-amylose- or beta-glucan-rich genotypes) or an evening meal with white wheat flour bread (WWB) enriched with a mixture of barley fiber and resistant starch improved glucose tolerance at the subsequent breakfast compared with unsupplemented WWB (P carbohydrates of the evening meal may affect glycemic excursions and related metabolic risk variables at breakfast through a mechanism involving colonic fermentation. The results provide evidence for a link between gut microbial metabolism and key factors associated with insulin resistance.

  14. "Being an English Major, Being a Humanities Student": Connecting Academic Subject Identity in Literary Studies to Other Social Domains

    Science.gov (United States)

    Chan, Evelyn T. Y.

    2016-01-01

    This study examined students' construction of academic subject identity in a university humanities discipline, English literary studies. In so doing, the study aimed to provide an empirically grounded intervention in current debates on the value of the humanities in higher education. Eight students participated in interviews lasting 15-20 minutes…

  15. Prevalence of Arcobacter spp. in humans, animals and foods of animal origin including sea food from India.

    Science.gov (United States)

    Patyal, A; Rathore, R S; Mohan, H V; Dhama, K; Kumar, A

    2011-10-01

    The present study reports the prevalence of Arcobacter, an emerging pathogen in human, animals and foods of animal origin in India. A total of 600 samples from various sources, viz. diarrhoeal stools of humans and dogs, faecal swabs of animals (pig, poultry), preputial washings of breeding bulls and food samples (chicken, pork, fish) were examined for presence of Arcobacter spp. Using cultural methods, a total of 63 Arcobacter spp. were isolated of 600 (10.50%) samples with highest isolation rate were from pig faeces (21.33%) followed by sea foods (17.33%), poultry faeces (14.67%), pork (16.00%), chicken meat (12.00%) and human stools (2.67%). The isolates were confirmed as arcobacters by genus-based PCR. PCR screening of all the enriched samples revealed the overall prevalence of Arcobacter spp. to be 12.00% with highest in pig (25.33%), followed by sea food (21.33%), poultry (17.33%), pork (16%), chicken meat (12%) and human stools (4.00%). No Arcobacter spp. was isolated or detected from diarrhoeal faecal samples of dogs and preputial washings. With multiplex PCR, three different species were detected (A. butzleri, A. cryaerophilus and A. skirrowii) with most of the samples showing mixed infections. There are only two recent reports from India; one with cultural isolation and another with PCR detection of Arcobacter spp. in stool samples of humans with clinical diarrhoea. In this context, our present report is the first report of isolation and detection of Arcobacter spp. from various sources of animals and foods including diarrhoeic human stool samples, utilizing both cultural and molecular tools identifying arcobacters at genus and species level. These results support the importance of arcobacters as an emerging food-borne pathogen, possessing zoonotic potential. © 2011 Blackwell Verlag GmbH.

  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. 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

  18. 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...... 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...... of the present study confirmed previously indicated trends that lowest human body exergy consumption rate is associated with thermal sensation close to neutrality. Moreover, higher acceptability was in general associated with lower human body exergy consumption rate. (C) 2016 Elsevier B.V. All rights reserved....

  19. Postprandial effects of test meals including concentrated arabinoxylan and whole grain rye in subjects with the metabolic syndrome: a randomised study.

    Science.gov (United States)

    Hartvigsen, M L; Lærke, H N; Overgaard, A; Holst, J J; Bach Knudsen, K E; Hermansen, K

    2014-05-01

    Prospective studies have shown an inverse relationship between whole grain consumption and the risk of type 2 diabetes, where short chain fatty acids (SCFA) may be involved. Our objective was to determine the effect of isolated arabinoxylan alone or in combination with whole grain rye kernels on postprandial glucose, insulin, free fatty acids (FFA), gut hormones, SCFA and appetite in subjects with the metabolic syndrome (MetS). Fifteen subjects with MetS participated in this acute, randomised, cross-over study. The test meals each providing 50 g of digestible carbohydrate were as follows: semolina porridge added concentrated arabinoxylan (AX), rye kernels (RK) or concentrated arabinoxylan combined with rye kernels (AXRK) and semolina porridge as control (SE). A standard lunch was served 4 h after the test meals. Blood samples were drawn during a 6-h period, and appetite scores and breath hydrogen were assessed every 30 min. The AXRK meal reduced the acute glucose (P=0.005) and insulin responses (P<0.001) and the feeling of hunger (P=0.005; 0-360 min) compared with the control meal. The AX and AXRK meals increased butyrate and acetate concentrations after 6 h. No significant differences were found for the second meal responses of glucose, insulin, FFA, glucagon-like peptide-1 or ghrelin. Our results indicate a stimulatory effect of arabinoxylan on butyrate and acetate production, however, with no detectable effect on the second meal glucose response. It remains to be tested in a long-term study if a beneficial effect on the glucose response of the isolated arabinoxylan will be related to the SCFA production.

  20. 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.

  1. The Saccharomyces cerevisiae poly(A)-binding protein is subject to multiple post-translational modifications, including the methylation of glutamic acid.

    Science.gov (United States)

    Low, Jason K K; Hart-Smith, Gene; Erce, Melissa A; Wilkins, Marc R

    2014-01-10

    Poly(A)-binding protein in mouse and man was recently found to be highly post-translationally modified. Here we analysed an ortholog of this protein, Pab1 from Saccharomyces cerevisiae, to assess the conservation and thus likely importance of these modifications. Pab1 showed the presence of six sites of methylated glutamate, five sites of lysine acetylation, and one phosphorylation of serine. Many modifications on Pab1 showed either complete conservation with those on human or mouse PABPC1, were present on nearby residues and/or were present in the same domain(s). The conservation of methylated glutamate, an unusual modification, was of particular note and suggests a conserved function. Comparison of methylated glutamate sites in human, mouse and yeast poly(A)-binding protein, along with methylation sites catalysed by CheR L-glutamyl protein methyltransferase from Salmonella typhimurium, revealed that the methylation of glutamate preferentially occurs in EE and DE motifs or other small regions of acidic amino acids. The conservation of methylated glutamate in the same protein between mouse, man and yeast suggests the presence of a eukaryotic l-glutamyl protein methyltransferase and that the modification is of functional significance. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Competitive debate classroom as a cooperative learning technique for the human resources subject

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    Guillermo A. SANCHEZ PRIETO

    2018-01-01

    Full Text Available The paper shows an academic debate model as a cooperative learning technique for teaching human resources at University. The general objective of this paper is to conclude if academic debate can be included in the category of cooperative learning. The Specific objective it is presenting a model to implement this technique. Thus the first part of the paper shows the concept of cooperative learning and its main characteristics. The second part presents the debate model believed to be labelled as cooperative learning. Last part concludes with the characteristics of the model that match different aspects or not of the cooperative learning.

  3. Fasting and refeeding differentially regulate NLRP3 inflammasome activation in human subjects.

    Science.gov (United States)

    Traba, Javier; Kwarteng-Siaw, Miriam; Okoli, Tracy C; Li, Jessica; Huffstutler, Rebecca D; Bray, Amanda; Waclawiw, Myron A; Han, Kim; Pelletier, Martin; Sauve, Anthony A; Siegel, Richard M; Sack, Michael N

    2015-11-03

    Activation of the NLRP3 inflammasome is associated with metabolic dysfunction, and intermittent fasting has been shown to improve clinical presentation of NLRP3 inflammasome-linked diseases. As mitochondrial perturbations, which function as a damage-associated molecular pattern, exacerbate NLRP3 inflammasome activation, we investigated whether fasting blunts inflammasome activation via sirtuin-mediated augmentation of mitochondrial integrity. We performed a clinical study of 19 healthy volunteers. Each subject underwent a 24-hour fast and then was fed a fixed-calorie meal. Blood was drawn during the fasted and fed states and analyzed for NRLP3 inflammasome activation. We enrolled an additional group of 8 healthy volunteers to assess the effects of the sirtuin activator, nicotinamide riboside, on NLRP3 inflammasome activation. In the fasting/refeeding study, individuals showed less NLRP3 inflammasome activation in the fasted state compared with that in refed conditions. In a human macrophage line, depletion of the mitochondrial-enriched sirtuin deacetylase SIRT3 increased NLRP3 inflammasome activation in association with excessive mitochondrial ROS production. Furthermore, genetic and pharmacologic SIRT3 activation blunted NLRP3 activity in parallel with enhanced mitochondrial function in cultured cells and in leukocytes extracted from healthy volunteers and from refed individuals but not in those collected during fasting. Together, our data indicate that nutrient levels regulate the NLRP3 inflammasome, in part through SIRT3-mediated mitochondrial homeostatic control. Moreover, these results suggest that deacetylase-dependent inflammasome attenuation may be amenable to targeting in human disease. ClinicalTrials.gov NCT02122575 and NCT00442195. Division of Intramural Research, NHLBI of the NIH.

  4. Broad-spectrum antiviral activity including human immunodeficiency and hepatitis C viruses mediated by a novel retinoid thiosemicarbazone derivative.

    Science.gov (United States)

    Kesel, Andreas J

    2011-05-01

    Aromatic aldehyde-derived thiosemicarbazones 4-6, the S-substituted modified thiosemicarbazones 7/8, and a vitamin A-derived (retinoid) thiosemicarbazone derivative 12 were investigated as inhibitors of human hepatitis C virus (HCV) subgenomic RNA replicon Huh7 ET (luc-ubi-neo/ET) replication. Compounds 4-6 and 12 were found to be potent suppressors of HCV RNA replicon replication. The trifluoromethoxy-substituted thiosemicarbazone 6 and the retinoid thiosemicarbazone derivative 12 were even superior in selectivity to the included reference agent recombinant human alpha-interferon-2b, showing potencies in the nanomolar range of concentration. In addition, compounds 5, 6, 8 and 12 were tested as inhibitors of cytopathic effect (CPE) induced by human varicella-zoster virus (VZV) and/or human cytomegalovirus (HCMV). Compounds 4-6, 8 and 12 were additionally examined as inhibitors of CPE induced by cowpox virus and vaccinia virus. Thiosemicarbazone 4 was inhibitory on cowpox and vaccinia virus replication comparable in potency and selectivity to the reference agent cidofovir. Retinoid thiosemicarbazone derivative 12 was active as micromolar inhibitor of VZV, HCMV, and, in addition, human immunodeficiency virus type 1 (HIV-1) replication. These results indicate that thiosemicarbazone derivatives are appropriate lead structures to be evaluated in targeted antiviral therapies for hepatitis C (STAT-C), and that the vitamin A-related thiosemicarbazone derivative 12 emerges as a broad-spectrum antiviral agent, co-suppressing the multiplication of important RNA and DNA viruses. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

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

    Science.gov (United States)

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

    2017-01-01

    18F-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 18F-T807 pharmacokinetics in human subjects using dynamic PET imaging and metabolite-corrected arterial input functions. Methods Nine subjects (4 control, 3 with history of TBI, 2 mild cognitive impairment (MCI) due to suspected AD) underwent dynamic PET imaging for up to 120 minutes after bolus injection of 18F-T807 with arterial blood sampling. Total volume of distribution (VT) was estimated using compartmental modeling (one- and two-tissue configurations) and graphical analysis techniques (Logan and MA1 regression methods). Reference region-based methods of quantification were explored including Logan distribution volume ratio (DVR) and static standardized uptake value ratio (SUVR) utilizing the cerebellum as a reference tissue. Results Percent unmetabolized 18F-T807 in plasma followed a single exponential with T1/2 of 17.0±4.2 minutes. Metabolite corrected plasma radioactivity concentration fit a bi-exponential (T1/2: 18.1±5.8; 2.4±0.5 minutes). 18F-T807 in gray matter peaked quickly (SUV >2 at ∼5 minutes). Compartmental modeling resulted in good fits and the two-tissue model with estimated blood volume correction (2Tv) performed best, particularly in regions with elevated binding. VT was greater in MCI subjects than controls in the occipital, parietal, and temporal cortices as well as the posterior cingulate gyrus, precuneus, and mesial temporal cortex. High focal uptake was found in the posterior corpus callosum of a TBI subject. Plots from Logan and MA1 graphical methods became linear by 30 minutes, yielding regional estimates of VT in excellent agreement with compartmental analysis and providing high quality parametric maps when applied in voxelwise fashion. Reference region based approaches including Logan DVR (t*=55 min) and SUVR

  6. 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.

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

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    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.

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

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    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.

  9. Steady Flow in Subject-Specific Human Airways from Mouth to Sixth Bronchial Generation

    Science.gov (United States)

    Banko, Andrew; Coletti, Filippo; Schiavazzi, Daniele; Elkins, Christopher; Eaton, John

    2013-11-01

    Understanding the complex flow topology within the human lung is critical to assess gas exchange and particle transport as they relate to the development and treatment of respiratory diseases. While idealized airway models have been investigated extensively, only limited information is available for anatomically accurate geometries. We have measured the full three-dimensional, mean velocity field from the mouth to the sixth bronchial generation in a patient-specific geometry at steady inspiration. Magnetic resonance velocimetry is used to measure the flow of water at realistic Reynolds number in a 3D-printed model derived from the CT scan of a healthy subject. The canonical laryngeal jet is observed; however, its structure is altered by an upstream jet behind the tongue, which is not discussed in the literature. Regions of separation in the supraglottic space are found to generate streamwise vortices. The resulting swirl persists to the first bifurcation and modifies the vorticity distribution in the main bronchi relative to that of a symmetric bifurcation with uniform inlet conditions. An integral momentum distortion parameter is calculated along several complete bronchial paths to assess the impact of branching angle and generation length on the flow field.

  10. Vibration Analysis and Design of a Structure Subjected to Human Walking Excitations

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    M. Setareh

    2010-01-01

    Full Text Available Annoying building floor vibrations have become a serious serviceability issue. This is mainly due to decrease in the system mass resulting from the use of higher strength materials; use of computer-assisted design and the Load and Resistance Factor Design Method to optimize the structure based on the strength requirements; fewer partitions and more innovative designs by architects achieving long, column free spans resulting in a reduction in the natural frequency and damping. This paper provides details of the vibration analysis and design of a novel office building. Three-dimensional computer models of the structure were created and various modifications were made to the original structure, designed based on static loads, to reduce the possible excessive floor vibrations when subjected to walking excitations. Tuned mass dampers were also designed as a back-up vibration control system. A series of dynamic tests were conducted on the building floor to identify the dynamic properties of the structure and these were then used to update the original computer model. Finally, various forcing functions representing human walks and the updated computer model of the structure were used to evaluate the accuracy of the walking excitation force models to predict the structural response. Conclusions are made on the validity of each forcing function studied here.

  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

    2012-01-21

    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

  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.

    2012-01-01

    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

  13. Small Ubiquitin-Like Modifier 4 (SUMO4 Gene M55V Polymorphism and Type 2 Diabetes Mellitus: A Meta-analysis Including 6,823 Subjects

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    Yan-yan Li

    2017-11-01

    Full Text Available BackgroundMany studies suggest that the small ubiquitin-like modifier 4 (SUMO4 M55V gene polymorphism (rs237025 may be associated with an increased risk of type 2 diabetes mellitus (T2DM. However, due to other conflicting results, a clear consensus is lacking in the matter.Objective and methodsA meta-analysis consisting of 6,823 subjects from 10 studies was conducted to elucidate relationship between the SUMO4 M55V gene polymorphism and T2DM. Depending on the heterogeneity of the data, either a fixed or random-effects model would be used to assess the combined odds ratio (ORs and their corresponding 95% confidence interval (CI.ResultsSUMO4 gene M55V polymorphism was significantly associated with T2DM in the whole population under allelic (OR: 1.18, 95% CI: 1.10–1.28, P = 1.63 × 10−5, recessive (OR: 1.59, 95% CI: 1.14–2.23, P = 0.006, dominant (OR: 0.815, 95% CI: 0.737–0.901, P = 6.89 × 10−5, homozygous (OR: 1.415, 95% CI: 1.170–1.710, P = 0.0003, heterozygous (OR: 1.191, 95% CI: 1.072–1.323, P = 0.001, and additive genetic models (OR: 1.184, 95% CI: 1.097–1.279, P = 1.63 × 10−5. In our subgroup analysis, a significant association was found again in the Chinese population, but not in Japanese or Iranian population.ConclusionSUMO4 gene M55V polymorphism may correlate with increased T2DM risk. Chinese carriers of the V allele of the SUMO4 gene M55V polymorphism may be predisposed to developing T2DM.

  14. Genetic variants in human CLOCK associate with total energy intake and cytokine sleep factors in overweight subjects (GOLDN population).

    Science.gov (United States)

    Garaulet, Marta; Lee, Yu-Chi; Shen, Jian; Parnell, Laurence D; Arnett, Donna K; Tsai, Michael Y; Lai, Chao-Qiang; Ordovas, Jose M

    2010-03-01

    Despite the importance of total energy intake in circadian system regulation, no study has related human CLOCK gene polymorphisms and food-intake measures. The aim of this study was to analyze the associations of CLOCK single-nucleotide polymorphisms (SNPs) with food intake and to explore the specific role of the cytokine system. A total of 1100 individual participants in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study were included. Dietary intake was estimated with a validated questionnaire. Interleukin-6 (IL-6), monocyte chemotactic protein 1 (MCP1), tumor necrosis factor-alpha (TNF-alpha), IL-2 soluble receptor-alpha (IL-2sR-alpha) and adiponectin plasma concentrations were measured. Our results showed that four of five CLOCK SNPs selected were significantly associated with total energy intake (PSNP rs3749474, the energy intake and total fat, protein and carbohydrate intakes were significantly higher in minor allele carriers than in non-carriers. Frequency of the minor allele was greater in subjects with high energy intake than in those with low intake. Subjects with the minor allele were 1.33 times more likely to have high energy intake than non-carriers (95% CI 1.09-1.72, P=0.0350). All CLOCK SNPs were associated with plasma cytokine values, in particular with those that were highly correlated with energy intake: MCP1, IL-6 and adiponectin. Interestingly, minor allele carriers with high energy intake showed decreased cytokine values, which could be related with a lower anorectic effect and decreased sleep in these subjects. In conclusion, we show a novel association of genetic variation at CLOCK with total energy intake, which was particularly relevant for SNP rs3749474. Associations could be mediated through the alteration of cytokine levels that may influence energy intake and sleep pattern.

  15. NINE KEY FUNCTIONS FOR A HUMAN SUBJECTS PROTECTION PROGRAM FOR COMMUNITY-ENGAGED RESEARCH: POINTS TO CONSIDER1

    Science.gov (United States)

    Ross, Lainie Friedman; Loup, Allan; Nelson, Robert M.; Botkin, Jeffrey R.; Kost, Rhonda; Smith, George R.; Gehlert, Sarah

    2010-01-01

    The Ethical Conduct of Community-engaged research (CEnR), of which the Community-Based Participatory Research (CBPR) model is the partnership model most widely discussed in the CEnR literature and is the primary model we draw upon in this discussion, requires an integrated and comprehensive human subjects protection (HSP) program that addresses the additional concerns salient to CEnR where members of a community are both research partners and participants. As delineated in the federal regulations, the backbone of a HSP program is the fulfillment of nine functions: (1) minimize risks; (2) reasonable benefit-risk ratio; (3) fair subject selection; (4) adequate monitoring; (5) informed consent; (6) privacy and confidentiality; (7) conflicts of interest; (8) address vulnerabilities; and (9) HSP training. The federal regulations, however, do not consider the risks and harms that may occur to groups, and these risks have not traditionally been included in the benefit: risk analysis nor have they been incorporated into an HSP framework. We explore additional HSP issues raised by CEnR within these nine ethical functions. Various entities exist that can provide HSP—the investigator, the Institutional Review Board, the Conflict of Interest Committee, the Research Ethics Consultation program, the Research Subject Advocacy program, the Data and Safety Monitoring Plan, and the Community Advisory Board. Protection is best achieved if these entities are coordinated to ensure that no gaps exist, to minimize unnecessary redundancy, and to provide checks and balances between the different entities of HSP and the nine functions that they must realize. The document is structured to provide a “points-to-consider” roadmap for HSP entities to help them adequately address the nine key functions necessary to provide adequate protection of individuals and communities in CEnR. PMID:20235862

  16. A human in vitro whole blood assay to predict the systemic cytokine response to therapeutic oligonucleotides including siRNA.

    Directory of Open Access Journals (Sweden)

    Christoph Coch

    Full Text Available Therapeutic oligonucleotides including siRNA and immunostimulatory ligands of Toll-like receptors (TLR or RIG-I like helicases (RLH are a promising novel class of drugs. They are in clinical development for a broad spectrum of applications, e.g. as adjuvants in vaccines and for the immunotherapy of cancer. Species-specific immune activation leading to cytokine release is characteristic for therapeutic oligonucleotides either as an unwanted side effect or intended pharmacology. Reliable in vitro tests designed for therapeutic oligonucleotides are therefore urgently needed in order to predict clinical efficacy and to prevent unexpected harmful effects in clinical development. To serve this purpose, we here established a human whole blood assay (WBA that is fast and easy to perform. Its response to synthetic TLR ligands (R848: TLR7/8, LPS: TLR4 was on a comparable threshold to the more time consuming peripheral blood mononuclear cell (PBMC based assay. By contrast, the type I IFN profile provoked by intravenous CpG-DNA (TLR9 ligand in humans in vivo was more precisely replicated in the WBA than in stimulated PBMC. Since Heparin and EDTA, but not Hirudin, displaced oligonucleotides from their delivery agent, only Hirudin qualified as the anticoagulant to be used in the WBA. The Hirudin WBA exhibited a similar capacity as the PBMC assay to distinguish between TLR7-activating and modified non-stimulatory siRNA sequences. RNA-based immunoactivating TLR7/8- and RIG-I-ligands induced substantial amounts of IFN-α in the Hirudin-WBA dependent on delivery agent used. In conclusion, we present a human Hirudin WBA to determine therapeutic oligonucleotide-induced cytokine release during preclinical development that can readily be performed and offers a close reflection of human cytokine response in vivo.

  17. A human in vitro whole blood assay to predict the systemic cytokine response to therapeutic oligonucleotides including siRNA.

    Science.gov (United States)

    Coch, Christoph; Lück, Christian; Schwickart, Anna; Putschli, Bastian; Renn, Marcel; Höller, Tobias; Barchet, Winfried; Hartmann, Gunther; Schlee, Martin

    2013-01-01

    Therapeutic oligonucleotides including siRNA and immunostimulatory ligands of Toll-like receptors (TLR) or RIG-I like helicases (RLH) are a promising novel class of drugs. They are in clinical development for a broad spectrum of applications, e.g. as adjuvants in vaccines and for the immunotherapy of cancer. Species-specific immune activation leading to cytokine release is characteristic for therapeutic oligonucleotides either as an unwanted side effect or intended pharmacology. Reliable in vitro tests designed for therapeutic oligonucleotides are therefore urgently needed in order to predict clinical efficacy and to prevent unexpected harmful effects in clinical development. To serve this purpose, we here established a human whole blood assay (WBA) that is fast and easy to perform. Its response to synthetic TLR ligands (R848: TLR7/8, LPS: TLR4) was on a comparable threshold to the more time consuming peripheral blood mononuclear cell (PBMC) based assay. By contrast, the type I IFN profile provoked by intravenous CpG-DNA (TLR9 ligand) in humans in vivo was more precisely replicated in the WBA than in stimulated PBMC. Since Heparin and EDTA, but not Hirudin, displaced oligonucleotides from their delivery agent, only Hirudin qualified as the anticoagulant to be used in the WBA. The Hirudin WBA exhibited a similar capacity as the PBMC assay to distinguish between TLR7-activating and modified non-stimulatory siRNA sequences. RNA-based immunoactivating TLR7/8- and RIG-I-ligands induced substantial amounts of IFN-α in the Hirudin-WBA dependent on delivery agent used. In conclusion, we present a human Hirudin WBA to determine therapeutic oligonucleotide-induced cytokine release during preclinical development that can readily be performed and offers a close reflection of human cytokine response in vivo.

  18. 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.

  19. Evolutionary diversity of bile salts in reptiles and mammals, including analysis of ancient human and extinct giant ground sloth coprolites

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    Hofmann Alan F

    2010-05-01

    Full Text Available Abstract Background Bile salts are the major end-metabolites of cholesterol and are also important in lipid and protein digestion and in influencing the intestinal microflora. We greatly extend prior surveys of bile salt diversity in both reptiles and mammals, including analysis of 8,000 year old human coprolites and coprolites from the extinct Shasta ground sloth (Nothrotherium shastense. Results While there is significant variation of bile salts across species, bile salt profiles are generally stable within families and often within orders of reptiles and mammals, and do not directly correlate with differences in diet. The variation of bile salts generally accords with current molecular phylogenies of reptiles and mammals, including more recent groupings of squamate reptiles. For mammals, the most unusual finding was that the Paenungulates (elephants, manatees, and the rock hyrax have a very different bile salt profile from the Rufous sengi and South American aardvark, two other mammals classified with Paenungulates in the cohort Afrotheria in molecular phylogenies. Analyses of the approximately 8,000 year old human coprolites yielded a bile salt profile very similar to that found in modern human feces. Analysis of the Shasta ground sloth coprolites (approximately 12,000 years old showed the predominant presence of glycine-conjugated bile acids, similar to analyses of bile and feces of living sloths, in addition to a complex mixture of plant sterols and stanols expected from an herbivorous diet. Conclusions The bile salt synthetic pathway has become longer and more complex throughout vertebrate evolution, with some bile salt modifications only found within single groups such as marsupials. Analysis of the evolution of bile salt structures in different species provides a potentially rich model system for the evolution of a complex biochemical pathway in vertebrates. Our results also demonstrate the stability of bile salts in coprolites

  20. Evolutionary diversity of bile salts in reptiles and mammals, including analysis of ancient human and extinct giant ground sloth coprolites

    Science.gov (United States)

    2010-01-01

    Background Bile salts are the major end-metabolites of cholesterol and are also important in lipid and protein digestion and in influencing the intestinal microflora. We greatly extend prior surveys of bile salt diversity in both reptiles and mammals, including analysis of 8,000 year old human coprolites and coprolites from the extinct Shasta ground sloth (Nothrotherium shastense). Results While there is significant variation of bile salts across species, bile salt profiles are generally stable within families and often within orders of reptiles and mammals, and do not directly correlate with differences in diet. The variation of bile salts generally accords with current molecular phylogenies of reptiles and mammals, including more recent groupings of squamate reptiles. For mammals, the most unusual finding was that the Paenungulates (elephants, manatees, and the rock hyrax) have a very different bile salt profile from the Rufous sengi and South American aardvark, two other mammals classified with Paenungulates in the cohort Afrotheria in molecular phylogenies. Analyses of the approximately 8,000 year old human coprolites yielded a bile salt profile very similar to that found in modern human feces. Analysis of the Shasta ground sloth coprolites (approximately 12,000 years old) showed the predominant presence of glycine-conjugated bile acids, similar to analyses of bile and feces of living sloths, in addition to a complex mixture of plant sterols and stanols expected from an herbivorous diet. Conclusions The bile salt synthetic pathway has become longer and more complex throughout vertebrate evolution, with some bile salt modifications only found within single groups such as marsupials. Analysis of the evolution of bile salt structures in different species provides a potentially rich model system for the evolution of a complex biochemical pathway in vertebrates. Our results also demonstrate the stability of bile salts in coprolites preserved in arid climates

  1. Minocycline ameliorates LPS-induced inflammation in human monocytes by novel mechanisms including LOX-1, Nur77 and LITAF inhibition

    Science.gov (United States)

    Pang, Tao; Wang, Juan; Benicky, Julius; Saavedra, Juan M.

    2012-01-01

    Background Minocycline exhibits anti-inflammatory properties independent of its antibiotic activity, ameliorating inflammatory responses in monocytes and macrophages. However, the mechanisms of minocycline anti-inflammatory effects are only partially understood. Methods Human circulating monocytes were cultured in the presence of lipopolysaccharide (LPS), 50 ng/ml, and minocycline (10–40 µM). Gene expression was determined by RT-PCR, cytokine and prostaglandin E2 (PGE2) release by ELISA, protein expression, phosphorylation and nuclear translocation by Western blotting. Results Minocycline significantly reduced the inflammatory response in LPS-challenged monocytes, decreasing LPS-induced transcription of pro-inflammatory tumor-necrosis factor alpha (TNF-α), interleukin-1 beta, interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2), and the LPS-stimulated TNF-α, IL-6 and PGE2 release. Minocycline inhibited LPS-induced activation of the lectin-like oxidized low density lipoprotein receptor-1 (LOX-1), NF-κB, LPS-induced TNF-α factor (LITAF) and the Nur77 nuclear receptor. Mechanisms involved in the anti-inflammatory effects of minocycline include a reduction of LPS-stimulated p38 mitogen-activated protein kinase (p38 MAPK) activation and stimulation of the phosphoinositide 3-kinase (PI3K)/Akt pathway. Conclusions We provide novel evidence demonstrating that the anti-inflammatory effects of minocycline in human monocytes include, in addition to decreased NF-κB activation, abrogation of the LPS-stimulated LOX-1, LITAF, Nur77 pathways, p38 MAPK inhibition and PI3K/Akt activation. Our results reveal that minocycline inhibits points of convergence of distinct and interacting signaling pathways mediating multiple inflammatory signals which may influence monocyte activation, traffic and recruitment into the brain. General significance Our results in primary human monocytes contribute to explain the profound anti-inflammatory and protective effects of minocycline in

  2. Radioreceptor assay to study the affinity of benzodiazepines and their receptor binding activity in human plasma including their active metabolites

    Energy Technology Data Exchange (ETDEWEB)

    Dorow, R.G.; Seidler, J.; Schneider, H.H. (Schering A.G., Berlin (Germany, F.R.))

    1982-04-01

    A radioreceptor assay has been established to measure the receptor affinities of numerous benzodiazepines in clinical use. The time course of receptor binding activity was studied by this method in the plasma of eight healthy subjects randomly treated with 1mg lormetazepam (Noctamid(R)), 2mg flunitrazepam (Rohypnol(R)), and 10mg diazepam (Valium(R)), and placebo on a cross-over basis. Blood samples were collected up to 154h after treatment. Receptor affinities of numerous benzodiazepines in vitro show good correlation with therapeutic human doses (r=0.96) and may be predictive of drug potency in man. Mean peak plasma levels of lormetazepam binding equivalents were 4.8+-1 ng/ml at 2h after lormetazepam, 7.2+-1.8 ng/ml at 8h after flunitrazepam, and 17.9+-2.7 ng/ml at 15h after diazepam. Plasma elimination halflives of benzodiazepine binding equivalents were 9.3, 23 and 63h, respectively. Slow elimination of benzodiazepine binding equivalents following flunitrazepam and diazepam may be due to persistent active metabolites.

  3. 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.

  4. The relationship between porosity and specific surface in human cortical bone is subject specific.

    Science.gov (United States)

    Lerebours, C; Thomas, C D L; Clement, J G; Buenzli, P R; Pivonka, P

    2015-03-01

    A characteristic relationship for bone between bone volume fraction (BV/TV) and specific surface (BS/TV) has previously been proposed based on 2D histological measurements. This relationship has been suggested to be bone intrinsic, i.e., to not depend on bone type, bone site and health state. In these studies, only limited data comes from cortical bone. The aim of this paper was to investigate the relationship between BV/TV and BS/TV in human cortical bone using high-resolution micro-CT imaging and the correlations with subject-specific biometric data such as height, weight, age and sex. Images from femoral cortical bone samples of the Melbourne Femur Collection were obtained using synchrotron radiation micro-CT (SPring8, Japan). Sixteen bone samples from thirteen individuals were analysed in order to find bone volume fraction values ranging from 0.20 to 1. Finally, morphological models of the tissue microstructure were developed to help explain the relationship between BV/TV and BS/TV. Our experimental findings indicate that the BV/TV vs BS/TV relationship is subject specific rather than intrinsic. Sex and pore density were statistically correlated with the individual curves. However no correlation was found with body height, weight or age. Experimental cortical data points deviate from interpolating curves previously proposed in the literature. However, these curves are largely based on data points from trabecular bone samples. This finding challenges the universality of the curve: highly porous cortical bone is significantly different to trabecular bone of the same porosity. Finally, our morphological models suggest that changes in BV/TV within the same sample can be explained by an increase in pore area rather than in pore density. This is consistent with the proposed mechanisms of age-related endocortical bone loss. In addition, these morphological models highlight that the relationship between BV/TV and BS/TV is not linear at high BV/TV as suggested in the

  5. Gastrointestinal tolerance of low FODMAP oral nutrition supplements in healthy human subjects: a randomized controlled trial.

    Science.gov (United States)

    Erickson, Jennifer; Korczak, Renee; Wang, Qi; Slavin, Joanne

    2017-05-25

    There has been increasing interest in utilizing a diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) for the treatment of irritable bowel syndrome (IBS), a functional gastrointestinal disease. While studies have indicated that this diet can be effective at symptom reduction, it is a restrictive diet and patients may find it challenging to find low FODMAP products to meet their nutrient needs. The primary objective of this study was to assess the gastrointestinal (GI) tolerance of three low FODMAP oral nutrition supplements (ONS) in healthy adults. A double-blind randomized controlled crossover study was conducted in 21 healthy adults (19-32 years). Fasted subjects consumed one of four treatments at each visit, with a one week wash out period between visits. Each participant received all treatments. Treatments included three low FODMAP ONS formulas (A, B, and C) as well as a positive control consisting of 5 g fructooligosaccharides (FOS) mixed in lactose-free milk. Breath hydrogen was measured at baseline, 1, 2, 3, and 4 h post treatment consumption. Subjective GI symptom questionnaires were completed at baseline, 0.5, 1, 1.5, 2, 3, 4, 12, 24 and 48 h following treatment consumption. Mean breath hydrogen concentrations and baseline corrected area under the curve for both breath hydrogen and GI symptoms were analyzed and compared between treatments. Significance was determined at P FODMAP ONS beverages at 3 and 4 h after consumption. There were no differences in GI symptom response between treatments. All treatments were well tolerated in healthy participants. The low FODMAP formulas resulted in a lower breath hydrogen response compared to the positive control, and may be better tolerated in individuals with IBS. More research should be conducted to better understand the GI tolerance of low FODMAP ONS in individuals with IBS. The protocol for this study was registered on ClinicalTrials.gov in January 2016 (Clinical

  6. Inactivation of single-chain urokinase-type plasminogen activator by thrombin in human subjects.

    Science.gov (United States)

    Braat, E A; Levi, M; Bos, R; Haverkate, F; Lassen, M R; de Maat, M P; Rijken, D C

    1999-08-01

    Thrombin cleaves single-chain urokinase-type plasminogen activator (scu-PA) into a virtually inactive two-chain form (tcu-PA/T), a process that may protect a blood clot from early fibrinolysis. It is not known under what circumstances tcu-PA/T can be generated in vivo. We have studied the occurrence of tcu-PA/T in human subjects with a varying degree of hypercoagulability. tcu-PA/T was assessed in the plasma of patients with disseminated intravascular coagulation (DIC), endotoxin-treated volunteers, patients with unstable angina pectoris, and patients selected for hip replacement. Relationships between tcu-PA/T and several markers reflecting thrombin generation were examined. tcu-PA/T was observed only in the plasma of patients with DIC and was associated with all thrombin markers and with scu-PA and urokinase antigen. Prothrombin fragment 1 + 2 and urokinase antigen were independent predictors of tcu-PA/T. The fact that tcu-PA/T could not be detected in the other three groups was explained by a lower extent of thrombin generation, a greater inhibition of thrombin by antithrombin, or less available urokinase antigen in these groups. The contribution of scu-PA to total urokinase antigen was decreased in the patients with DIC because of inactivation by thrombin, which may be an additional explanation for the inadequate fibrinolysis observed in these patients. These findings show that scu-PA can be inactivated in the circulation under severe pathophysiologic circumstances and that the process of inactivation depends not only on the generation of thrombin but also on the control of thrombin activity by its inhibitor antithrombin.

  7. 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.

  8. Assessment of net postprandial protein utilization of 15N-labelled milk nitrogen in human subjects.

    Science.gov (United States)

    Bos, C; Mahé, S; Gaudichon, C; Benamouzig, R; Gausserès, N; Luengo, C; Ferrière, F; Rautureau, J; Tomé, D

    1999-03-01

    The nutritional quality of milk proteins, evaluated both in terms of digestibility and postprandial oxidation and retention in human subjects, was investigated in this study. Five healthy adult volunteers were given 480 ml 15N-labelled milk (i.e. 190 mmol N). 15N was subsequently determined at the ileal level, using a naso-intestinal intubation technique, as well as at the faecal level. Plasma and urine were sampled for 8 h after meal ingestion. Dietary exogenous N recovered at the terminal ileum after 8 h reached 8.6 (SE 0.8) mmol while the amount collected in the faeces was 6.5 (SE 0.7) mmol after 5 d. The true ileal and faecal digestibilities were 95.5 (SE 0.4)% and 96.6 (SE 0.4)% respectively. The appearance of [15N]amino acids in the plasma was rapid and prolonged. The measurement of 15N in the body urea pool and in the N excreted in the urine allowed us to calculate the deamination occurring after [15N]milk protein absorption. The net postprandial protein utilization (i.e. NPPU = (Nabsorbed-Ndeaminated)/Ningested), calculated as an index of protein quality 8 h after milk ingestion, was 81.0 (SE 1.9)%. Our data confirm that milk protein has a high oro-ileal digestibility in man and demonstrate that milk protein has a high NPPU, an index corresponding to a period in which the dietary protein retention is maximal.

  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 vol...... 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....

  10. Morphometric analysis of osteonal architecture in bones from healthy young human male subjects using scanning electron microscopy.

    Science.gov (United States)

    Pazzaglia, Ugo E; Congiu, Terenzio; Pienazza, Alberto; Zakaria, Mohammed; Gnecchi, Michele; Dell'orbo, Carlo

    2013-09-01

    The shape and structure of bones is a topic that has been studied for a long time by morphologists and biologists with the goal of explaining the laws governing their development, aging and pathology. The osteonal architecture of tibial and femoral mid-diaphyses was examined morphometrically with scanning electron microscopy in four healthy young male subjects. In transverse sections of the mid-diaphysis, the total area of the anterior, posterior, lateral and medial cortex sectors was measured and analysed for osteonal parameters including osteon number and density, osteon total and bone area and vascular space area. Osteons were grouped into four classes including cutting heads (A), transversely cut osteons (B), longitudinally cut osteons (C) and sealed osteons (D). The morphometric parameters were compared between the inner (endosteal) and outer (periosteal) half of the cortex. Of 5927 examined osteons, 24.4% cutting heads, 71.1% transversely cut osteons, 2.3% longitudinally cut osteons and 2.2% sealed osteons were found. The interosteonic bone (measured as the area in a lamellar system that has lost contact with its own central canal) corresponded to 51.2% of the endosteal and 52.4% of the periosteal half-cortex. The mean number of class A cutting heads and class B osteons was significantly higher in the periosteal than in the endosteal half-cortex (P healthy human bone for studies on bone aging and metabolic bone diseases. © 2013 Anatomical Society.

  11. 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.

  12. 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 physiology, obtained better results than those in their third year who had already finished the biology course (10.70 ± 3.27 vs. 9.81 ± 3.74 respectively; p human physiology (10.70 ± 3.27 vs. 9.63 ± 2.74 respectively; p = 0.003). Over 23% of 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

  13. Integron, Plasmid and Host Strain Characteristics of Escherichia coli from Humans and Food Included in the Norwegian Antimicrobial Resistance Monitoring Programs.

    Directory of Open Access Journals (Sweden)

    Marianne Sunde

    Full Text Available Antimicrobial resistant Escherichia coli (n=331 isolates from humans with bloodstream infections were investigated for the presence of class 1 and class 2 integrons. The integron cassettes arrays were characterized and the findings were compared with data from similar investigations on resistant E. coli from meat and meat products (n=241 produced during the same time period. All isolates were obtained from the Norwegian monitoring programs for antimicrobial resistance in human pathogens and in the veterinary sector. Methods used included PCR, sequencing, conjugation experiments, plasmid replicon typing and subtyping, pulsed-field-gel-electrophoresis and serotyping. Integrons of class 1 and 2 occurred significantly more frequently among human isolates; 45.4% (95% CI: 39.9-50.9 than among isolates from meat; 18% (95% CI: 13.2 -23.3, (p<0.01, Chi-square test. Identical cassette arrays including dfrA1-aadA1, aadA1, dfrA12-orfF-aadA2, oxa-30-aadA1 (class 1 integrons and dfrA1-sat1-aadA1 (class 2 integrons were detected from both humans and meat. However, the most prevalent cassette array in human isolates, dfrA17-aadA5, did not occur in isolates from meat, suggesting a possible linkage between this class 1 integron and a subpopulation of E. coli adapted to a human host. The drfA1-aadA1 and aadA1 class 1 integrons were found frequently in both human and meat isolates. These isolates were subjected to further studies to investigate similarities with regard to transferability, plasmid and host strain characteristics. We detected incF plasmids with pMLST profile F24:A-:B1 carrying drfA1-aadA1 integrons in isolates from pork and in a more distantly related E. coli strain from a human with septicaemia. Furthermore, we showed that most of the class 1 integrons with aadA1 were located on incF plasmids with pMLST profile F51:A-:B10 in human isolates. The plasmid was present in unrelated as well as closely related host strains, demonstrating that dissemination

  14. Density profile and cholesterol concentration of serum lipoproteins in experimental animals and human subjects on hypercholesterolaemic diets

    NARCIS (Netherlands)

    Beynen, A.C.; Terpstra, A.H.M.

    1984-01-01

    1. 1. The density profile of Sudan black stained serum lipoproteins was studied in human subjects and various animal species on diets supplemented with cholesterol. 2. 2. In the animals studied (rabbits, calves, mice, chickens, rats and guinea-pigs), the feeding of cholesterol resulted in an

  15. Statistical analysis of the spontaneously emitted photon signals from palm and dorsal sides of both hands in human subjects

    NARCIS (Netherlands)

    Wijk, E.P.A. van; Wijk, R.V.; Bajpai, R.P.; Greef, J. van der

    2010-01-01

    Photon signals emitted spontaneously from dorsal and palm sides of both hands were recorded using 6000 time windows of size T=50. ms in 50 healthy human subjects. These photon signals demonstrated universal behaviour by variance and mean. The data sets for larger time windows up to T=50. s were

  16. 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 oran...

  17. 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

  18. Accurate identification of the six human Plasmodium spp. causing imported malaria, including Plasmodium ovale wallikeri and Plasmodium knowlesi.

    Science.gov (United States)

    Calderaro, Adriana; Piccolo, Giovanna; Gorrini, Chiara; Rossi, Sabina; Montecchini, Sara; Dell'Anna, Maria Loretana; De Conto, Flora; Medici, Maria Cristina; Chezzi, Carlo; Arcangeletti, Maria Cristina

    2013-09-13

    Accurate identification of Plasmodium infections in non-endemic countries is of critical importance with regard to the administration of a targeted therapy having a positive impact on patient health and management and allowing the prevention of the risk of re-introduction of endemic malaria in such countries. Malaria is no longer endemic in Italy where it is the most commonly imported disease, with one of the highest rates of imported malaria among European non-endemic countries including France, the UK and Germany, and with a prevalence of 24.3% at the University Hospital of Parma. Molecular methods showed high sensitivity and specificity and changed the epidemiology of imported malaria in several non-endemic countries, highlighted a higher prevalence of Plasmodium ovale, Plasmodium vivax and Plasmodium malariae underestimated by microscopy and, not least, brought to light both the existence of two species of P. ovale (Plasmodium ovale curtisi and Plasmodium ovale wallikeri) and the infection in humans by Plasmodium knowlesi, otherwise not detectable by microscopy. In this retrospective study an evaluation of two real-time PCR assays able to identify P. ovale wallikeri, distinguishing it from P. ovale curtisi, and to detect P. knowlesi, respectively, was performed applying them on a subset of 398 blood samples belonging to patients with the clinical suspicion of malaria. These assays revealed an excellent analytical sensitivity and no cross-reactivity versus other Plasmodium spp. infecting humans, suggesting their usefulness for an accurate and complete diagnosis of imported malaria. Among the 128 patients with malaria, eight P. ovale curtisi and four P. ovale wallikeri infections were detected, while no cases of P. knowlesi infection were observed. Real-time PCR assays specific for P. ovale wallikeri and P. knowlesi were included in the panel currently used in the University Hospital of Parma for the diagnosis of imported malaria, accomplishing the goal of

  19. Sample preparation and orthogonal chromatography for broad polarity range plasma metabolomics: application to human subjects with neurodegenerative dementia.

    Science.gov (United States)

    Armirotti, Andrea; Basit, Abdul; Realini, Natalia; Caltagirone, Carlo; Bossù, Paola; Spalletta, Gianfranco; Piomelli, Daniele

    2014-06-15

    We describe a simple protocol for the preparation and orthogonal hydrophobic/hydrophilic LC-MS/MS analysis of mouse and human plasma samples, which enables the untargeted ("shotgun") or targeted profiling of hydrophilic, amphipathic, and hydrophobic constituents of plasma metabolome. The protocol is rapid, efficient, and reliable, and offers several advantages compared to current procedures. When applied to a training set of human plasma samples, the protocol allowed for the rapid acquisition of full LogP metabolic profiles in plasma samples obtained from cognitively healthy human subjects and age-matched subjects with mild cognitive impairment or Alzheimer's disease (n=15 each). Targeted analyses confirmed these findings, which are consistent with data previously published by other groups. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Influence of isotretinoin on hippocampal-based learning in human subjects.

    Science.gov (United States)

    Ormerod, Anthony D; Thind, Chamandeep K; Rice, Shantini A; Reid, Ian C; Williams, Justin H G; McCaffery, Peter J A

    2012-06-01

    The acne drug isotretinoin has 13-cis retinoic acid as its active agent. Adverse effects that have been described include severe depression. Animal studies indicate that the hippocampus is particularly sensitive to retinoic acid. Changes induced by isotretinoin to hippocampal function could contribute to depression but may be more evident in altered visuospatial learning and memory, the primary function of the hippocampus. We aimed to test the hypothesis that a course of oral isotretinoin therapy would result in declining visuospatial learning and memory. CANTAB tasks designed to assess visuospatial memory were performed repeatedly on 14 males and 3 females in an open prospective observational study of patients with severe acne undergoing isotretinoin therapy. Beck's Depression Inventory and Global Acne Grade were also administered. Performance stayed unchanged for DMS, SRM and PRM tasks, while surprisingly participants improved their speed on the PRM task. Performance improved across sessions on the PAL task, and moreover the dose of isotretinoin correlated with improvement in the total trial score, reduction in total error rate and stage completed at the first trial. Isotretinoin does not reduce learning and memory and our study suggests that it may instead lead to a dose-related improvement in specific aspects of hippocampal learning and memory. Retinoic acid functions in the hippocampus as the active metabolite of vitamin A, suggesting that this may be a limiting factor in the human hippocampus and addition of exogenous retinoic acid brings levels closer to an optimal state.

  1. 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.

  2. 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...... of the present study confirmed previously indicated trends that lowest human body exergy consumption rate is associated with thermal sensation close to neutrality. Moreover, higher acceptability was in general associated with lower human body exergy consumption rate. (C) 2016 Elsevier B.V. All rights reserved.......-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...

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

    National Research Council Canada - National Science Library

    Kumar, Haribalan; Jain, Ravi; Douglas, Richard G; Tawhai, Merryn H

    2016-01-01

    .... 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...

  4. 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

  5. Personality and the acute subjective effects of d-amphetamine in humans

    OpenAIRE

    Kirkpatrick, Matthew G; Johanson, Chris-Ellyn; de Wit, Harriet

    2013-01-01

    There is evidence that subjective responses to psychoactive drugs are related to personality traits. Here, we extend previous findings by examining personality measures in relation to acute responses to d-amphetamine (AMPH) in a large sample of healthy volunteers. Healthy adults (n=286) completed the Multidimensional Personality Questionnaire Brief Form (MPQ-BF) and participated in four sessions during which they received oral AMPH (0, 5,10, 20 mg), under double-blind conditions. Subjective r...

  6. Absence of diurnal variation of C-reactive protein concentrations in healthy human subjects

    Science.gov (United States)

    Meier-Ewert, H. K.; Ridker, P. M.; Rifai, N.; Price, N.; Dinges, D. F.; Mullington, J. M.

    2001-01-01

    BACKGROUND: The concentration of C-reactive protein (CRP) in otherwise healthy subjects has been shown to predict future risk of myocardial infarction and stroke. CRP is synthesized by the liver in response to interleukin-6, the serum concentration of which is subject to diurnal variation. METHODS: To examine the existence of a time-of-day effect for baseline CRP values, we determined CRP concentrations in hourly blood samples drawn from healthy subjects (10 males, 3 females; age range, 21-35 years) during a baseline day in a controlled environment (8 h of nighttime sleep). RESULTS: Overall CRP concentrations were low, with only three subjects having CRP concentrations >2 mg/L. Comparison of raw data showed stability of CRP concentrations throughout the 24 h studied. When compared with cutoff values of CRP quintile derived from population-based studies, misclassification of greater than one quintile did not occur as a result of diurnal variation in any of the subjects studied. Nonparametric ANOVA comparing different time points showed no significant differences for both raw and z-transformed data. Analysis for rhythmic diurnal variation using a method fitting a cosine curve to the group data was negative. CONCLUSIONS: Our data show that baseline CRP concentrations are not subject to time-of-day variation and thus help to explain why CRP concentrations are a better predictor of vascular risk than interleukin-6. Determination of CRP for cardiovascular risk prediction may be performed without concern for diurnal variation.

  7. Serum and macular response to carotenoid-enriched egg supplementation in human subjects: the Egg Xanthophyll Intervention clinical Trial (EXIT).

    Science.gov (United States)

    Kelly, David; Nolan, John M; Howard, Alan N; Stack, Jim; Akuffo, Kwadwo O; Moran, Rachel; Thurnham, David I; Dennison, Jessica; Meagher, Katherine A; Beatty, Stephen

    2017-01-01

    The macular carotenoids lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ) accumulate at the macula, where they are collectively referred to as macular pigment (MP). Augmentation of this pigment, typically achieved through diet and supplementation, enhances visual function and protects against progression of age-related macular degeneration. However, it is known that eggs are a rich dietary source of L and Z, in a highly bioavailable matrix. In this single-blind placebo-controlled study, L- and MZ-enriched eggs and control non-enriched eggs were fed to human subjects (mean age 41 and 35 years, respectively) over an 8-week period, and outcome measures included MP, visual function and serum concentrations of carotenoids and cholesterol. Serum carotenoid concentrations increased significantly in control and enriched egg groups, but to a significantly greater extent in the enriched egg group (Peggs may represent an effective dietary source of L, Z and MZ, reflected in significantly raised serum concentrations of these carotenoids, and consequentially improved bioavailability for capture by target tissues. However, benefits in terms of MP augmentation and /or improved visual performance were not realised over the 8-week study period, and a study of greater duration will be required to address these questions.

  8. 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

  9. Molecular systematics of five Onchocerca species (Nematoda: Filarioidea) including the human parasite, O. volvulus, suggest sympatric speciation.

    Science.gov (United States)

    Morales-Hojas, R; Cheke, R A; Post, R J

    2006-09-01

    The genus Onchocerca (Nematoda: Filarioidea) consists of parasites of ungulate mammals with the exception of O. volvulus, which is a human parasite. The relationship between O. volvulus, O. ochengi and O. gibsoni remains unresolved. Based on morphology of the microfilariae and infective larvae, vector transmission and geographical distribution, O. ochengi and O. volvulus have been placed as sister species. Nevertheless, the cuticle morphology and chromosomal data (O. volvulus and O. gibsoni have n=4 while O. ochengi is n=5) suggest that O. gibsoni could be more closely related to O. volvulus than O. ochengi. Sequences from the 12S rRNA, 16S rRNA and ND5 mitochondrial genes have been used to reconstruct the phylogeny of five Onchocerca species including O. volvulus. Analyses with maximum likelihood and maximum parsimony showed that O. ochengi is the sister species of O. volvulus, in accordance with the classification based on morphology and geographical location. The separate specific status of the species O. gutturosa and O. lienalis was supported, although their phylogenetic relationship was not well resolved. The analyses indicated that the basal species was O. gibsoni, a South-East Asian and Australasian species, but this result was not statistically significant. The possible involvement of sympatric speciation in the evolution of this group of parasites is discussed.

  10. Diallylthiosulfinate (Allicin, a Volatile Antimicrobial from Garlic (Allium sativum, Kills Human Lung Pathogenic Bacteria, Including MDR Strains, as a Vapor

    Directory of Open Access Journals (Sweden)

    Jana Reiter

    2017-10-01

    Full Text Available Garlic (Allium sativum has potent antimicrobial activity due to allicin (diallylthiosulfinate synthesized by enzyme catalysis in damaged garlic tissues. Allicin gives crushed garlic its characteristic odor and its volatility makes it potentially useful for combating lung infections. Allicin was synthesized (>98% pure by oxidation of diallyl disulfide by H2O2 using formic acid as a catalyst and the growth inhibitory effect of allicin vapor and allicin in solution to clinical isolates of lung pathogenic bacteria from the genera Pseudomonas, Streptococcus, and Staphylococcus, including multi-drug resistant (MDR strains, was demonstrated. Minimal inhibitory (MIC and minimal bactericidal concentrations (MBC were determined and compared to clinical antibiotics using standard European Committee on Antimicrobial Susceptibility Testing (EUCAST procedures. The cytotoxicity of allicin to human lung and colon epithelial and murine fibroblast cells was tested in vitro and shown to be ameliorated by glutathione (GSH. Similarly, the sensitivity of rat precision-cut lung slices (PCLS to allicin was decreased by raising the [GSH] to the approximate blood plasma level of 1 mM. Because allicin inhibited bacterial growth as a vapor, it could be used to combat bacterial lung infections via direct inhalation. Since there are no volatile antibiotics available to treat pulmonary infections, allicin, particularly at sublethal doses in combination with oral antibiotics, could make a valuable addition to currently available treatments.

  11. Diallylthiosulfinate (Allicin), a Volatile Antimicrobial from Garlic (Allium sativum), Kills Human Lung Pathogenic Bacteria, Including MDR Strains, as a Vapor.

    Science.gov (United States)

    Reiter, Jana; Levina, Natalja; van der Linden, Mark; Gruhlke, Martin; Martin, Christian; Slusarenko, Alan J

    2017-10-12

    Garlic ( Allium sativum ) has potent antimicrobial activity due to allicin (diallylthiosulfinate) synthesized by enzyme catalysis in damaged garlic tissues. Allicin gives crushed garlic its characteristic odor and its volatility makes it potentially useful for combating lung infections. Allicin was synthesized (>98% pure) by oxidation of diallyl disulfide by H₂O₂ using formic acid as a catalyst and the growth inhibitory effect of allicin vapor and allicin in solution to clinical isolates of lung pathogenic bacteria from the genera Pseudomonas , Streptococcus , and Staphylococcus , including multi-drug resistant (MDR) strains, was demonstrated. Minimal inhibitory (MIC) and minimal bactericidal concentrations (MBC) were determined and compared to clinical antibiotics using standard European Committee on Antimicrobial Susceptibility Testing (EUCAST) procedures. The cytotoxicity of allicin to human lung and colon epithelial and murine fibroblast cells was tested in vitro and shown to be ameliorated by glutathione (GSH). Similarly, the sensitivity of rat precision-cut lung slices (PCLS) to allicin was decreased by raising the [GSH] to the approximate blood plasma level of 1 mM. Because allicin inhibited bacterial growth as a vapor, it could be used to combat bacterial lung infections via direct inhalation. Since there are no volatile antibiotics available to treat pulmonary infections, allicin, particularly at sublethal doses in combination with oral antibiotics, could make a valuable addition to currently available treatments.

  12. The human capacity to reflect and decide: bioethics and the reconfiguration of the research subject in the British biomedical sciences.

    Science.gov (United States)

    Reubi, David

    2012-06-01

    This article examines how a fundamental element of the British bioethical assemblage - the literature on informed consent published between 1980 and 2000, a period when bioethics became a powerful force in the UK--has influenced contemporary understandings of the research subject. Drawing on Foucault, the article argues that this corpus of texts has created a sphere of possibilities in which research subjects can imagine themselves as human beings who reflect and decide whether they want to participate in medical experimentation. In particular, it shows how the narratives found in these texts portray relationships between researchers and their human subjects as 'paternalistic', and calls for their replacement by new, more ethical relationships characterized by both 'dialogue' and 'respect' and articulated around subjects who can 'think and take decisions'. It also discusses the different strategies- using patient information sheets, a list of possible questions and invitations to take time to reflect--which the bioethical literature has developed in order to realise these new, ethical relationships. As the article suggests, these narratives and strategies provide researchers and research subjects with models and examples of how to interact with each other that are very different from the ones that prevailed before the emergence of bioethics.

  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. Citrus limonin glucoside supplementation decreased biomarkers of liver disease in overweight human subjects

    Science.gov (United States)

    Orange juice and mixtures of citrus limonoid glucosides isolated from orange juice or its byproducts demonstrated health benefits in human and animal studies. However, the risks and benefits of purified limonin glucoside (LG) in humans are unknown. Aim of this study was to determine the safety and m...

  15. Light-scattering properties of undiluted human blood subjected to simple shear

    NARCIS (Netherlands)

    Steenbergen, Wiendelt; Kolkman, R.G.M.; de Mul, F.F.M.

    1999-01-01

    An experimental investigation was performed into the effect of simple shear on the light-scattering properties of undiluted human blood. Undiluted human blood was enclosed between two glass plates with an adjustable separation between 30 and 120 mm and with one plate moving parallel to the other.

  16. 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.

  17. 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...... strategy using iTRAQ and a label-free study with a targeted quantitative proteomic approach using selected reaction monitoring (SRM) to identify, quantify and validate changes in protein abundance between human myotubes obtained from non-diabetic lean, non-diabetic obese and type 2 diabetic subjects...

  18. 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.

  19. 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.

  20. [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.

  1. 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...

  2. Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects.

    Science.gov (United States)

    Hsia, Chien-Hsun; Shen, Ming-Ching; Lin, Jen-Shiou; Wen, Yao-Ke; Hwang, Kai-Lin; Cham, Thau-Ming; Yang, Nae-Cherng

    2009-03-01

    Nattokinase, a serine proteinase from Bacillus subtilis, is considered to be one of the most active functional ingredients found in natto. In this study, we hypothesized that nattokinase could reduce certain factors of blood clotting and lipids that are associated with an increase risk for cardiovascular disease (CVD). Thus, an open-label, self-controlled clinical trial was conducted on subjects of the following groups: healthy volunteers (Healthy Group), patients with cardiovascular risk factors (Cardiovascular Group), and patients undergoing dialysis (Dialysis Group). All subjects ingested 2 capsules of nattokinase (2000 fibrinolysis units per capsule) daily orally for 2 months. The laboratory measurements were performed on the screening visit and, subsequently, regularly after the initiation of the study. The intent-to-treat analysis was performed on all 45 enrolled subjects. By use of mixed model analysis, a significant time effect, but not group effect, was observed in the change from baseline of fibrinogen (P = .003), factor VII (P nattokinase. No significant changes of uric acid or notable adverse events were observed in any of the subjects. In summary, this study showed that oral administration of nattokinase could be considered as a CVD nutraceutical by decreasing plasma levels of fibrinogen, factor VII, and factor VIII.

  3. 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...

  4. 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.

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

    Science.gov (United States)

    Wagner Mackenzie, Brett; Waite, David W; Taylor, Michael W

    2015-01-01

    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.

  6. Influence of dietary fat ingestion on asymmetrical dimethylarginine in lean and obese human subjects.

    Science.gov (United States)

    Engeli, S; Tsikas, D; Lehmann, A C; Böhnke, J; Haas, V; Strauß, A; Janke, J; Gorzelniak, K; Luft, F C; Jordan, J

    2012-09-01

    Asymmetrical dimethylarginine (ADMA) may contribute to hypertension and cardiovascular disease by decreasing NO formation. In diabetic patients, a high fat meal acutely increased plasma ADMA while impairing endothelial function. We hypothesized that chronic and acute increases in dietary fat intake augment ADMA also in lean and in obese subjects without diabetes. Seventeen lean and twelve obese volunteers were randomized to two weeks of isocaloric diets with approximately 20% or >40% calories from fat in a cross-over fashion. At the end of the high and low fat periods, volunteers received corresponding test meals. ADMA was measured by GC-MS/MS using a deuterated standard. Mean fasting plasma ADMA concentration was 0.52 (0.49-0.54; 95% CI) μmol/l in lean and 0.53 (0.50-0.55) μmol/l in obese subjects (p = 0.55). The two week high fat diet did not influence ADMA. Both test meals elicited a 6%increase in circulating ADMA in lean subjects. In obese subjects, plasma ADMA concentration did not change with the low fat meal, and decreased by approximately 4% with the high fat meal. Our findings challenge the idea that obesity and dietary fat intake have a major effect on plasma ADMA, at least in subjects without overt cardiovascular and metabolic disease. This finding is important with regard to dietary recommendations for weight loss. Overestimation of the influence of dietary fat intake and obesity on circulating ADMA in previous reports was most likely due to methodological issues concerning ADMA measurements. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. An Independent Assessment of the Physiological and Cognitive Effects from the X-26 TASER Device in Volunteer Human Subjects

    Science.gov (United States)

    2009-06-05

    Final Report For Contract/PR No. W911QY-08-C-0023 An Independent Assessment of the Physiological and Cognitive Effects from the X-26 TASER ® Device...Cognitive Effects from the X-26 TASER Device in Volunteer Human Subjects 5a. CONTRACT NUMBER W911QY-08-C-0023 5b. GRANT NUMBER 5c. PROGRAM...STATEMENT Approved for public release; distribution unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Exposure to the X-26 TASER ? was studied in 32

  8. 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.

  9. [Sexuality and the human body: the subject's view through video images].

    Science.gov (United States)

    Vargas, E; Siqueira, V H

    1999-11-01

    This study analyzes images of the body linked to sexual and reproductive behavior found in the communication processes mediated by so-called educational videos. In the relationship between subject and technology, the paper is intended to characterize the discourses and the view or perspective currently shaping health education practices. Focusing on the potential in the relationship between the enunciator and subjects represented in the text and the interaction between health professionals and messages, the study attempts to characterize the discourses and questions providing the basis for a given view of the body and sexuality. The study was conducted in the years 1996-1997 and focused on health professionals from the public health system. The results show a concept of sexuality that tends to generalize the meaning ascribed to sexual experience, ignoring the various ways by which different culturally defined groups attribute meaning to the body.

  10. 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

  11. 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

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

    Science.gov (United States)

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

    2014-10-01

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

  13. 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.

  14. 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.

  15. Personality and the acute subjective effects of d-amphetamine in humans.

    Science.gov (United States)

    Kirkpatrick, Matthew G; Johanson, Chris-Ellyn; de Wit, Harriet

    2013-03-01

    There is evidence that subjective responses to psychoactive drugs are related to personality traits. Here, we extend previous findings by examining personality measures in relation to acute responses to d-amphetamine (AMPH) in a large sample of healthy volunteers. Healthy adults (n=286) completed the Multidimensional Personality Questionnaire Brief Form (MPQ-BF) and participated in four sessions during which they received oral AMPH (0, 5, 10, 20 mg), under double-blind conditions. Subjective responses to the drug were measured using the Profile of Mood States, Addiction Research Center Inventory, and Drug Effects Questionnaire. Drug responses were reduced via principal components analysis to three higher-order factors ('Euphoria', 'Arousal', 'Dysphoria'). Participants were rank ordered on selected MPQ-BF scales; the top and bottom third on each trait were compared on the drug response factors. High trait physical fearlessness was significantly associated with greater amphetamine-related Arousal, and high trait reward sensitivity was significantly associated with greater Euphoria. In addition, high trait impulsivity was significantly associated with greater Arousal and Euphoria. These results provide further evidence that individual differences in the subjective effects of AMPH are partially explained by differences in personality, and are consistent with the idea that both personality and responses to stimulants depend upon shared neurochemical systems.

  16. 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.

  17. Parietal electroencephalogram beta asymmetry and selective attention to angry facial expressions in healthy human subjects

    NARCIS (Netherlands)

    Schutter, D.J.L.G.; Putman, P.L.J.; Hermans, E.J.; Honk, E.J. van

    2001-01-01

    Research on cerebral affective processing in humans has concentrated on the lateralization of the prefrontal cortex. However, the parietal cortex also seems to play a role in motivation and emotion. In the present study the lateralized role of the parietal cortex in motivated attention was

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

    NARCIS (Netherlands)

    Davegardh, C.; Broholm, C.; Perfilyev, A.; Henriksen, T.; Garcia-Calzon, S.; Peijs, L.; Hansen, N.S.; Volkov, P.; Kjobsted, R.; Wojtaszewski, J.F.; Pedersen, M.; Pedersen, B.K.; Ballak, D.B.; Dinarello, C.A.; Heinhuis, B.; Joosten, L.A.B.; Nilsson, E.; Vaag, A.; Scheele, C.; Ling, C.

    2017-01-01

    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 is

  19. 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.

  20. 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, ...

  1. 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 lo...

  2. 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; ...

  3. 76 FR 5735 - Revisions to EPA's Rule on Protections for Subjects in Human Research Involving Pesticides

    Science.gov (United States)

    2011-02-02

    ... in its 2004 Report to EPA, and from the Nuremberg Code. The amendments proposed here would make no... the principles of the Nuremberg Code with respect to human experimentation; and shall establish an..., as suggested by Recommendation 5-5 from the 2004 NAS Report. 3. Inconsistency with the Nuremberg Code...

  4. 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.

  5. Modal Damping Ratio and Optimal Elastic Moduli of Human Body Segments for Anthropometric Vibratory Model of Standing Subjects.

    Science.gov (United States)

    Gupta, Manoj; Gupta, T C

    2017-10-01

    The present study aims to accurately estimate inertial, physical, and dynamic parameters of human body vibratory model consistent with physical structure of the human body that also replicates its dynamic response. A 13 degree-of-freedom (DOF) lumped parameter model for standing person subjected to support excitation is established. Model parameters are determined from anthropometric measurements, uniform mass density, elastic modulus of individual body segments, and modal damping ratios. Elastic moduli of ellipsoidal body segments are initially estimated by comparing stiffness of spring elements, calculated from a detailed scheme, and values available in literature for same. These values are further optimized by minimizing difference between theoretically calculated platform-to-head transmissibility ratio (TR) and experimental measurements. Modal damping ratios are estimated from experimental transmissibility response using two dominant peaks in the frequency range of 0-25 Hz. From comparison between dynamic response determined form modal analysis and experimental results, a set of elastic moduli for different segments of human body and a novel scheme to determine modal damping ratios from TR plots, are established. Acceptable match between transmissibility values calculated from the vibratory model and experimental measurements for 50th percentile U.S. male, except at very low frequencies, establishes the human body model developed. Also, reasonable agreement obtained between theoretical response curve and experimental response envelop for average Indian male, affirms the technique used for constructing vibratory model of a standing person. Present work attempts to develop effective technique for constructing subject specific damped vibratory model based on its physical measurements.

  6. Compartmentalized human immunodeficiency virus type 1 originates from long-lived cells in some subjects with HIV-1-associated dementia.

    Science.gov (United States)

    Schnell, Gretja; Spudich, Serena; Harrington, Patrick; Price, Richard W; Swanstrom, Ronald

    2009-04-01

    Human immunodeficiency virus type 1 (HIV-1) invades the central nervous system (CNS) shortly after systemic infection and can result in the subsequent development of HIV-1-associated dementia (HAD) in a subset of infected individuals. Genetically compartmentalized virus in the CNS is associated with HAD, suggesting autonomous viral replication as a factor in the disease process. We examined the source of compartmentalized HIV-1 in the CNS of subjects with HIV-1-associated neurological disease and in asymptomatic subjects who were initiating antiretroviral therapy. The heteroduplex tracking assay (HTA), targeting the variable regions of env, was used to determine which HIV-1 genetic variants in the cerebrospinal fluid (CSF) were compartmentalized and which variants were shared with the blood plasma. We then measured the viral decay kinetics of individual variants after the initiation of antiretroviral therapy. Compartmentalized HIV-1 variants in the CSF of asymptomatic subjects decayed rapidly after the initiation of antiretroviral therapy, with a mean half-life of 1.57 days. Rapid viral decay was also measured for CSF-compartmentalized variants in four HAD subjects (t(1/2) mean = 2.27 days). However, slow viral decay was measured for CSF-compartmentalized variants from an additional four subjects with neurological disease (t(1/2) range = 9.85 days to no initial decay). The slow decay detected for CSF-compartmentalized variants was not associated with poor CNS drug penetration, drug resistant virus in the CSF, or the presence of X4 virus genotypes. We found that the slow decay measured for CSF-compartmentalized variants in subjects with neurological disease was correlated with low peripheral CD4 cell count and reduced CSF pleocytosis. We propose a model in which infiltrating macrophages replace CD4(+) T cells as the primary source of productive viral replication in the CNS to maintain high viral loads in the CSF in a substantial subset of subjects with HAD.

  7. Compartmentalized human immunodeficiency virus type 1 originates from long-lived cells in some subjects with HIV-1-associated dementia.

    Directory of Open Access Journals (Sweden)

    Gretja Schnell

    2009-04-01

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 invades the central nervous system (CNS shortly after systemic infection and can result in the subsequent development of HIV-1-associated dementia (HAD in a subset of infected individuals. Genetically compartmentalized virus in the CNS is associated with HAD, suggesting autonomous viral replication as a factor in the disease process. We examined the source of compartmentalized HIV-1 in the CNS of subjects with HIV-1-associated neurological disease and in asymptomatic subjects who were initiating antiretroviral therapy. The heteroduplex tracking assay (HTA, targeting the variable regions of env, was used to determine which HIV-1 genetic variants in the cerebrospinal fluid (CSF were compartmentalized and which variants were shared with the blood plasma. We then measured the viral decay kinetics of individual variants after the initiation of antiretroviral therapy. Compartmentalized HIV-1 variants in the CSF of asymptomatic subjects decayed rapidly after the initiation of antiretroviral therapy, with a mean half-life of 1.57 days. Rapid viral decay was also measured for CSF-compartmentalized variants in four HAD subjects (t(1/2 mean = 2.27 days. However, slow viral decay was measured for CSF-compartmentalized variants from an additional four subjects with neurological disease (t(1/2 range = 9.85 days to no initial decay. The slow decay detected for CSF-compartmentalized variants was not associated with poor CNS drug penetration, drug resistant virus in the CSF, or the presence of X4 virus genotypes. We found that the slow decay measured for CSF-compartmentalized variants in subjects with neurological disease was correlated with low peripheral CD4 cell count and reduced CSF pleocytosis. We propose a model in which infiltrating macrophages replace CD4(+ T cells as the primary source of productive viral replication in the CNS to maintain high viral loads in the CSF in a substantial subset of subjects with HAD.

  8. 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.

  9. Human vestibular memory studied via measurement of the subjective horizontal during gondola centrifugation.

    Science.gov (United States)

    Tribukait, Arne

    2003-07-01

    Measurements of the subjective visual horizontal (SVH) were made in a large swing-out gondola centrifuge. Rotation of the centrifuge was anti-clockwise, as seen from above. Test subjects were seated upright in the gondola, facing forwards. In front of the subject, at a straight-ahead eye-level position, there was a narrow luminous line, which could be rotated, by remote control, about the visual axis. At gravitoinertial force levels of 1.1-1.3G the subjects were asked to indicate, by repeatedly setting the line in darkness, what they perceived as horizontal (the SVH). During gondola centrifugation, the head and body length axis is always parallel with the resultant gravitoinertial force vector (vectorial sum of earth gravity force and the centrifugal force) i.e., the horizontal plane of the head or body does not change with respect to the gravitoinertial horizontal. Hence, the otolith organs, as well as the somatosensory system, continually signal upright position. However, the swing-out of the gondola during acceleration of the centrifuge (25 degrees at 1.1G) is a roll (frontal plane) change-in-position stimulus to the vertical semicircular canals, thus creating an otolith-semicircular canal conflict. After acceleration of the centrifuge, the SVH was initially tilted up to 20 degrees to the right relative to the gravitoinertial horizontal. Since there was no roll-tilt stimulus to gravity receptors, this SVH tilt must be related to stimulation of the semicircular canals. However, it decayed much more slowly than any known effects of angular-velocity stimulation of the semicircular canals. The decay was bi-phasic with two time constants, the smaller in the region of 1-2 min, the other being too large to be reliably estimated on the basis of data collected during only 10 min. This persistence of the SVH tilt suggests a memory for angular changes in roll head position detected by the semicircular canals-a position-storage mechanism. Further, the SVH seems to be

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

    OpenAIRE

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

    2011-01-01

    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 tomograp...

  11. α-Synuclein Aggregated with Tau and β-Amyloid in Human Platelets from Healthy Subjects: Correlation with Physical Exercise

    Directory of Open Access Journals (Sweden)

    Simona Daniele

    2018-01-01

    Full Text Available The loss of protein homeostasis that has been associated with aging leads to altered levels and conformational instability of proteins, which tend to form toxic aggregates. In particular, brain aging presents characteristic patterns of misfolded oligomers, primarily constituted of β-amyloid (Aβ, tau, and α-synuclein (α-syn, which can accumulate in neuronal membranes or extracellular compartments. Such aging-related proteins can also reach peripheral compartments, thus suggesting the possibility to monitor their accumulation in more accessible fluids. In this respect, we have demonstrated that α-syn forms detectable hetero-aggregates with Aβ or tau in red blood cells (RBCs of healthy subjects. In particular, α-syn levels and its heteromeric interactions are modulated by plasma antioxidant capability (AOC, which increases in turn with physical activity. In order to understand if a specific distribution of misfolded proteins can occur in other blood cells, a cohort of human subjects was enrolled to establish a correlation among AOC, the level of physical exercise and the concentrations of aging-related proteins in platelets. The healthy subjects were divided depending on their level of physical exercise (i.e., athletes and sedentary subjects and their age (young and older subjects. Herein, aging-related proteins (i.e., α-syn, tau and Aβ were confirmed to be present in human platelets. Among such proteins, platelet tau concentration was demonstrated to decrease in athletes, while α-syn and Aβ did not correlate with physical exercise. For the first time, α-syn was shown to directly interact with Aβ and tau in platelets, forming detectable hetero-complexes. Interestingly, α-syn interaction with tau was inversely related to plasma AOC and to the level of physical activity. These results suggested that α-syn heterocomplexes, particularly with tau, could represent novel indicators to monitor aging-related proteins in platelets.

  12. Measurement of cortisol and testosterone in hair of obese and non-obese human subjects.

    Science.gov (United States)

    Chan, J; Sauvé, B; Tokmakejian, S; Koren, G; Van Uum, S

    2014-06-01

    Hair analysis has been demonstrated to accurately reflect exposure to drug abuse, environmental toxins and exogenous hormones. We tested the feasibility of measuring cortisol and testosterone in hair of healthy and obese subjects. A modified immunoassay (ELISA) originally developed for saliva was used. Hair, urine and blood samples were collected from young non-obese and obese patients. Perceived stress (PSS) was measured using a validated questionnaire. There was no difference in PSS between non-obese and obese subjects. Hair cortisol levels were significantly correlated with weight (r = 0.27, p significance (p = 0.063). Hair cortisol levels did not correlate with age or urinary cortisol. There was a negative correlation between hair testosterone and age (r = -0.47, p significance (p = 0.098). The ratio of hair cortisol over hair testosterone (C/T) was higher in the obese group than in the young non-obese group. The C/T ratio correlated positively with age (r = 0.56, p significance. Hair cortisol levels increase, while hair testosterone levels decrease with obesity. The hair C/T ratio was significantly correlated with age, BMI and waist circumference better than hair cortisol or testosterone alone. As hair collection is non-invasive and is not influenced by moment-to-moment variations, the measurement of hormones in hair is a useful tool in research and possibly clinical practice. © Georg Thieme Verlag KG Stuttgart · New York.

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

    Science.gov (United States)

    2016-04-19

    an elastomeric half- mask respirator fitted with an N95-rated filter cartridge and incorporates a pressure sensor to digitally log changes of in...particulate respirator and a surgical mask during human breathing: Two pathways for particle penetration. J Occup Environ Hyg. 2009; 6(10):593–603. [PubMed...Food, Drug and Cosmetic Act. J Occup Environ Hyg. Author manuscript; available in PMC 2015 June 17. A uthor M anuscript A uthor M anuscript A uthor M

  14. Modeling thermal responses in human subjects following extended exposure to radiofrequency energy

    Directory of Open Access Journals (Sweden)

    Foster Kenneth R

    2004-02-01

    Full Text Available Abstract Background This study examines the use of a simple thermoregulatory model for the human body exposed to extended (45 minute exposures to radiofrequency/microwave (RF/MW energy at different frequencies (100, 450, 2450 MHz and under different environmental conditions. The exposure levels were comparable to or above present limits for human exposure to RF energy. Methods We adapted a compartmental model for the human thermoregulatory system developed by Hardy and Stolwijk, adding power to the torso skin, fat, and muscle compartments to simulate exposure to RF energy. The model uses values for parameters for "standard man" that were originally determined by Hardy and Stolwijk, with no additional adjustment. The model predicts changes in core and skin temperatures, sweat rate, and changes in skin blood flow as a result of RF energy exposure. Results The model yielded remarkably good quantitative agreement between predicted and measured changes in skin and core temperatures, and qualitative agreement between predicted and measured changes in skin blood flow. The model considerably underpredicted the measured sweat rates. Conclusions The model, with previously determined parameter values, was successful in predicting major aspects of human thermoregulatory response to RF energy exposure over a wide frequency range, and at different environmental temperatures. The model was most successful in predicting changes in skin temperature, and it provides insights into the mechanisms by which the heat added to body by RF energy is dissipated to the environment. Several factors are discussed that may have contributed to the failure to account properly for sweat rate. Some features of the data, in particular heating of the legs and ankles during exposure at 100 MHz, would require a more complex model than that considered here.

  15. Pharmacokinetic Evaluation of Oral Levofloxacin in Human Immunodeficiency Virus-Infected Subjects Receiving Concomitant Antiretroviral Therapy

    OpenAIRE

    Villani, P.; Viale, P.; Signorini, L.; Cadeo, B.; Marchetti, F.; Villani, A.; Fiocchi, C; Regazzi, M B; Carosi, G

    2001-01-01

    The purpose of this study was to evaluate the pharmacokinetics (PK) profile of oral levofloxacin in human immunodeficiency virus-positive patients in steady-state treatment with nelfinavir (NFV) or with efavirenz (EFV) and to determine the effects of levofloxacin on the PK parameters of these two antiretroviral agents. For levofloxacin, plasma samples were obtained at steady state during a 24-h dosing interval. Plasma NFV and EFV concentrations were evaluated before and after 4 days of levofl...

  16. Designing a Curriculum Model to Include Sexuality and a Procedure for its Administration. Human Sexuality-Nursing 50383.

    Science.gov (United States)

    Hoffman, Elise; And Others

    In order to design and implement a plan to integrate human sexuality into the curriculum for associate degree nursing students at Alvin Community College (Texas), levels of knowledge, attitudes and skills necessary in promoting sexual health were defined. Of the four levels in the Mims and Swenson Sexual Health Model (life experiences, basic,…

  17. Including the Other: Regulation of the Human Rights of Mobile Students in a Nation-Bound World

    Science.gov (United States)

    Marginson, Simon

    2012-01-01

    The world's three million cross-border international students are located in a "gray zone" of regulation with incomplete human rights, security and capabilities. Like other mobile persons such as short-term business and labour entrants, and refugees, students located on foreign soil do not enjoy the same protections and entitlements as…

  18. Mechanism of Human Tooth Eruption: Review Article Including a New Theory for Future Studies on the Eruption Process

    Directory of Open Access Journals (Sweden)

    Inger Kjær

    2014-01-01

    Full Text Available Human eruption is a unique developmental process in the organism. The aetiology or the mechanism behind eruption has never been fully understood and the scientific literature in the field is extremely sparse. Human and animal tissues provide different possibilities for eruption analyses, briefly discussed in the introduction. Human studies, mainly clinical and radiological, have focused on normal eruption and gender differences. Why a tooth begins eruption and what enables it to move eruptively and later to end these eruptive movements is not known. Pathological eruption courses contribute to insight into the aetiology behind eruption. A new theory on the eruption mechanism is presented. Accordingly, the mechanism of eruption depends on the correlation between space in the eruption course, created by the crown follicle, eruption pressure triggered by innervation in the apical root membrane, and the ability of the periodontal ligament to adapt to eruptive movements. Animal studies and studies on normal and pathological eruption in humans can support and explain different aspects in the new theory. The eruption mechanism still needs elucidation and the paper recommends that future research on eruption keeps this new theory in mind. Understanding the aetiology of the eruption process is necessary for treating deviant eruption courses.

  19. Slit-scanning technique using standard cell sorter instruments for analyzing and sorting nonacrocentric human chromosomes, including small ones

    NARCIS (Netherlands)

    Rens, W.; van Oven, C. H.; Stap, J.; Jakobs, M. E.; Aten, J. A.

    1994-01-01

    We have investigated the performance of two types of standard flow cell sorter instruments, a System 50 Cytofluorograph and a FACSTar PLUS cell sorter, for the on-line centromeric index (CI) analysis of human chromosomes. To optimize the results, we improved the detection efficiency for centromeres

  20. Refining Time-Activity Classification of Human Subjects Using the Global Positioning System.

    Directory of Open Access Journals (Sweden)

    Maogui Hu

    Full Text Available Detailed spatial location information is important in accurately estimating personal exposure to air pollution. Global Position System (GPS has been widely used in tracking personal paths and activities. Previous researchers have developed time-activity classification models based on GPS data, most of them were developed for specific regions. An adaptive model for time-location classification can be widely applied to air pollution studies that use GPS to track individual level time-activity patterns.Time-activity data were collected for seven days using GPS loggers and accelerometers from thirteen adult participants from Southern California under free living conditions. We developed an automated model based on random forests to classify major time-activity patterns (i.e. indoor, outdoor-static, outdoor-walking, and in-vehicle travel. Sensitivity analysis was conducted to examine the contribution of the accelerometer data and the supplemental spatial data (i.e. roadway and tax parcel data to the accuracy of time-activity classification. Our model was evaluated using both leave-one-fold-out and leave-one-subject-out methods.Maximum speeds in averaging time intervals of 7 and 5 minutes, and distance to primary highways with limited access were found to be the three most important variables in the classification model. Leave-one-fold-out cross-validation showed an overall accuracy of 99.71%. Sensitivities varied from 84.62% (outdoor walking to 99.90% (indoor. Specificities varied from 96.33% (indoor to 99.98% (outdoor static. The exclusion of accelerometer and ambient light sensor variables caused a slight loss in sensitivity for outdoor walking, but little loss in overall accuracy. However, leave-one-subject-out cross-validation showed considerable loss in sensitivity for outdoor static and outdoor walking conditions.The random forests classification model can achieve high accuracy for the four major time-activity categories. The model also

  1. 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

  2. Refining Time-Activity Classification of Human Subjects Using the Global Positioning System

    Science.gov (United States)

    Hu, Maogui; Li, Wei; Li, Lianfa; Houston, Douglas; Wu, Jun

    2016-01-01

    Background Detailed spatial location information is important in accurately estimating personal exposure to air pollution. Global Position System (GPS) has been widely used in tracking personal paths and activities. Previous researchers have developed time-activity classification models based on GPS data, most of them were developed for specific regions. An adaptive model for time-location classification can be widely applied to air pollution studies that use GPS to track individual level time-activity patterns. Methods Time-activity data were collected for seven days using GPS loggers and accelerometers from thirteen adult participants from Southern California under free living conditions. We developed an automated model based on random forests to classify major time-activity patterns (i.e. indoor, outdoor-static, outdoor-walking, and in-vehicle travel). Sensitivity analysis was conducted to examine the contribution of the accelerometer data and the supplemental spatial data (i.e. roadway and tax parcel data) to the accuracy of time-activity classification. Our model was evaluated using both leave-one-fold-out and leave-one-subject-out methods. Results Maximum speeds in averaging time intervals of 7 and 5 minutes, and distance to primary highways with limited access were found to be the three most important variables in the classification model. Leave-one-fold-out cross-validation showed an overall accuracy of 99.71%. Sensitivities varied from 84.62% (outdoor walking) to 99.90% (indoor). Specificities varied from 96.33% (indoor) to 99.98% (outdoor static). The exclusion of accelerometer and ambient light sensor variables caused a slight loss in sensitivity for outdoor walking, but little loss in overall accuracy. However, leave-one-subject-out cross-validation showed considerable loss in sensitivity for outdoor static and outdoor walking conditions. Conclusions The random forests classification model can achieve high accuracy for the four major time

  3. 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

    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......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...... 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...

  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. Voclosporin food effect and single oral ascending dose pharmacokinetic and pharmacodynamic studies in healthy human subjects.

    Science.gov (United States)

    Mayo, Patrick R; Huizinga, Robert B; Ling, Spencer Y; Freitag, Derrick G; Aspeslet, Launa J; Foster, Robert T

    2013-08-01

    Voclosporin (VCS) is a novel calcineurin (CN) inhibitor intended for prevention of organ graft rejection and treatment of lupus nephritis. These studies evaluated the single ascending dose pharmacokinetics (PK) and pharmacodynamics (PD, CN activity) of VCS and the effect of food. VCS was administered orally in single doses of 0.25 through 4.5 mg/kg in 62 subjects in the single ascending dose study and as a single oral 1.5 mg/kg dose to 18 subjects after fasting, consumption of a low-fat and high-fat meal. Non-compartmental PK, PD, and PKPD correlation were evaluated. Following single oral doses, systemic exposure increased in a linear manner and demonstrated 1:1 dose-proportional, first-order linear PK above 1.5 mg/kg. VCS inhibited CN activity in a dose-related fashion with maximal inhibition peaking at 3.0 mg/kg. PKPD correlation indicated an EC50 of 78.3 ± 6.8 ng/mL. Administration of VCS with a low-fat and high-fat meal decreased C(max) by 29% and 53%, respectively, and AUC(inf) by 15% and 25%, respectively. Following ascending single doses of VCS, exposure increased in a linear fashion. A food effect on exposure was demonstrated, with a more pronounced effect following a high-fat meal. VCS concentrations were also found to correlate with CN activity. © The Author(s) 2013.

  6. 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.

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

    Science.gov (United States)

    Katsuura, Tetsuo; Ochiai, Yukifumi; Senoo, Toshihiro; Lee, Soomin; Takahashi, Yoshika; Shimomura, Yoshihiro

    2012-09-03

    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. 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. 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. 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

    . There are no longitudinal studies measuring CT in humans without medullary thyroid carcinoma or a family history of medullary thyroid carcinoma and no published studies on the effect of GLP-1 receptor agonists on human serum CT concentrations. Aim: The aim of the study was to determine serum CT response over time....... Results: Basal mean CT concentrations were at the low end of normal range in all treatment groups and remained low throughout the trials. At 2 yr, estimated geometric mean values were no greater than 1.0 ng/liter, well below upper normal ranges for males and females. Proportions of subjects whose CT...... levels increased above a clinically relevant cutoff of 20 ng/liter were very low in all groups. There was no consistent dose or time-dependent relationship and no consistent difference between treatment groups. Conclusions: These data do not support an effect of GLP-1 receptor activation on serum CT...

  9. Shilajit: evalution of its effects on blood chemistry of normal human subjects.

    Science.gov (United States)

    Sharma, Praveen; Jha, Jagrati; Shrinivas, V; Dwivedi, L K; Suresh, P; Sinha, M

    2003-10-01

    The effect of Shilajit on blood chemistry was studied in normal human volunteers. Administration of two gms of Shilajit for 45 days did not produced any significant change in physical parameters i.e. blood pressure, pulse rate and body weight and similarly no charge was observed in hematological parameters. A signification reduction in Serum Triglycerides, Serum cholesterol with simultaneous improvement in HDL Cholesterol was seen, besides Shilajit also improved antioxidant status of volunteers. Results of study suggest hypolipidemic and strong antioxidant activity of Shilajit.

  10. 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.

  11. Air toxics and epigenetic effects: ozone altered microRNAs in the sputum of human subjects

    Science.gov (United States)

    Ozone (03) is a criteria air pollutant that is associated with numerous adverse health effects, including altered respiratory immune responses. Despite its deleterious health effects, possible epigenetic mechanisms underlying 03-induced health effects remain understudied. MicroRN...

  12. Protection of human subjects of biomedical research in the United States. A contrast with recent experience in the United Kingdom.

    Science.gov (United States)

    Levine, R J

    1988-01-01

    In the U.S., the development of extensive regulations for the protection of human subjects of research began in the 1960s and continued through the 1970s. The substance of these regulations reflects the American social and political climate of the time. There is a focus on rights--e.g., to be left alone, to be self-determining--reflected in elaborate requirements to assure the validity and documentation of informed consent. There is also a focus on systems of disinterested review and monitoring procedures to assure uniform adherence to the requirements of the regulations. To the extent that the U.S. has developed extensive regulations in this field, it may be viewed as more advanced than the U.K. And yet, it is apparent that there remain on both sides of the Atlantic very difficult and similar problems regarding the definition of responsible research. Such problems are illustrated by consideration of current controversies about the ethical justification of RCTs. There are some features of the U.S. regulatory system that I can commend to the attention of other nations as they develop policies for the protection of human research subjects. For example, a uniform requirement for informed consent and committee review appears to be responsive to some problems currently encountered in the conduct of RCTs in the U.K. A note of caution is in order, however. Some features of our regulatory policy and practices are excessively inflexible, wasteful of human resources, and occasionally counterproductive.

  13. The effect of exposure to carcinogenic metals on histone tail modifications and gene expression in human subjects.

    Science.gov (United States)

    Arita, Adriana; Shamy, Magdy Y; Chervona, Yana; Clancy, Harriet A; Sun, Hong; Hall, Megan N; Qu, Qingshan; Gamble, Mary V; Costa, Max

    2012-06-01

    The precise mechanisms by which nickel and arsenic compounds exert their carcinogenic properties are not completely understood. In recent years, alterations of epigenetic mechanisms have been implicated in the carcinogenesis of compounds of these two metals. In vitro exposure to certain nickel or arsenic compounds induces changes in both DNA methylation patterns, as well as, in the levels of posttranslational modifications of histone tails. Changes in DNA methylation patterns have been reported in human subjects exposed to arsenic. Here we review our recent reports on the alterations in global levels of posttranslational histone modifications in peripheral blood mononuclear cells (PBMCs) of subjects with occupational exposure to nickel and subjects exposed to arsenic in their drinking water. Occupational exposure to nickel was associated with an increase in H3K4me3 and decrease in H3K9me2. A global increase in H3K9me2 and decrease in H3K9ac was found in subjects exposed to arsenic. Additionally, exposure to arsenic resulted in opposite changes in a number of histone modifications in males when compared with females in the arsenic population. The results of these two studies suggest that exposure to nickel or arsenic compounds, and possibly other carcinogenic metal compounds, can induce changes in global levels of posttranslational histone modifications in peripheral blood mononuclear cells. Copyright © 2012 Elsevier GmbH. All rights reserved.

  14. THE EFFECT OF EXPOSURE TO CARCINOGENIC METALS ON HISTONE TAIL MODIFICATIONS AND GENE EXPRESSION IN HUMAN SUBJECTS

    Science.gov (United States)

    Arita, Adriana; Shamy, Magdy Y.; Chervona, Yana; Clancy, Harriet A.; Sun, Hong; Hall, Megan N.; Qu, Qingshan; Gamble, Mary V.; Costa, Max

    2013-01-01

    The precise mechanisms for the carcinogenesis of nickel and arsenic compounds are not completely understood. In recent years, alterations of epigenetic mechanisms have been implicated in the carcinogenesis of these two metal compounds. In vitro exposure to nickel or arsenic induces changes in both DNA methylation patterns, as well as, in the levels of posttranslational modifications of histone tails. Changes in DNA methylation patterns have been reported in human subjects exposed to arsenic. Here we review our recent reports on the alterations in global levels of posttranslational histone modifications in peripheral blood mononuclear cells (PBMCs) of subjects with occupational exposure to nickel and subjects exposed to arsenic in their drinking water. Occupational exposure to nickel was associated with an increase in H3K4me3 and decrease in H3K9me2. A global increase in H3K9me2 and decrease in H3K9ac was found in subjects exposed to arsenic. Additionally, exposure to arsenic resulted in opposite changes in a number of histone modifications in males compared to females. The results of these two studies suggest that exposure to nickel or arsenic compounds, and possibly other carcinogenic metal compounds, can induce changes in global levels of posttranslational histone modifications in peripheral blood mononuclear cells. PMID:22633395

  15. Homelessness, unemployment, and divorce among human immunodeficiency virus infected subjects in Tabriz, North West of Iran, 2012

    Directory of Open Access Journals (Sweden)

    Ahmad Kousha

    2014-08-01

    Full Text Available Introduction: Human immunodeficiency virus (HIV attains high importance, because of its high fatality, disability, political, and socio-economic impacts. Individuals living with HIV infection are poorly affected in terms of their psychological and socioeconomic aspect of quality-of-life. The aim of this study was to identify residence, marital, and employment characteristics of HIV infected subjects and to compare these characteristics prior of getting infection. Methods: This study was cross-sectional, conducted on 64 HIV infected subjects referring the Counseling Center of Behavioral Disease in Tabriz, Iran, 2012. Required data were collected using self-administered questionnaire, which was validated by experts and reliability was ensured through respondent validity method. Finally, data were analyzed with the help of SPSS for Windows. Results: The result showed that 89.0% of patients were male. Mean age of participants was 37.00 ± 8.84 years. Homelessness rate was 0.0% before acquiring infection when compared to 7.8% afterwards. The rate of unemployed was 3.8% that raised up to 62.5% after infection. Finally, it could be said that, after infection, divorced subjects increased from 0 to 27.6%, respectively. Conclusion: The findings showed that, homelessness, unemployment, and divorce have increased dramatically among HIV infected subjects.

  16. Campylobacter jejuni strain CG8421: a refined model for the study of Campylobacteriosis and evaluation of Campylobacter vaccines in human subjects.

    Science.gov (United States)

    Tribble, David R; Baqar, Shahida; Carmolli, Marya P; Porter, Chad; Pierce, Kristen K; Sadigh, Katrin; Guerry, Patricia; Larsson, Catherine J; Rockabrand, David; Ventone, Cassandra H; Poly, Frederic; Lyon, Caroline E; Dakdouk, Sandra; Fingar, Ann; Gilliland, Theron; Daunais, Patrick; Jones, Erika; Rymarchyk, Stacia; Huston, Christopher; Darsley, Michael; Kirkpatrick, Beth D

    2009-11-15

    A robust human challenge model for Campylobacter jejuni is an important tool for the evaluation of candidate vaccines. The previously established model conveys a potential risk of Guillain-Barré syndrome attributable to lipooligosaccharide ganglioside mimicry. This work establishes a new C. jejuni human challenge model that uses a strain (CG8421) without ganglioside mimicry and that applies Campylobacter-specific cellular immunity screening to achieve high attack rates at lower inoculum doses. Healthy Campylobacter-naive adults participated in an open-label challenge trial. Participants were dosed with C. jejuni CG8421 and followed as inpatients. Pattern of illness, bacterial shedding, and immunologic responses were determined. Following screening, 23 subjects received 1 X 10(6) or 1 X 10(5) colony-forming units of C. jejuni, with attack rates (percentage of patients who became ill) of 100% (1 X 10(6) colony-forming units) or 93% (1 X 10(5) colony-forming units). Every subject shed CG8421; the median time to diarrhea onset was 72.3 h (interquartile range, 53.9-99.9 h). Symptoms included abdominal cramps (74%), nausea (65%), and fever (39%). No major safety concerns occurred, including bacteremia, hypotension, or postinfectious sequelae. Unexpectedly, recrudescent infection occurred in 2 subjects (1 subject without Campylobacter-specific adaptive immune responses and 1 with azithromycin resistance acquired in vivo); both infections cleared after receipt of additional antibiotics. Cumulative Campylobacter-specific immune responses were as follows: serologic response occurred in 87% (immunoglobulin [Ig] A) and 48% (IgG) of subjects, in vitro interferon-gamma production occurred in 91% of subjects, and 96% of subjects had IgA antibody-secreting cells and fecal IgA detected. The C. jejuni CG8421 challenge model provides a safe and effective tool, without the risk of Guillain-Barré syndrome. The model demonstrates high attack rates after lower doses of challenge

  17. Effects of alprazolam and clonidine on carbon dioxide-induced increases in anxiety rating in healthy human subjects

    Energy Technology Data Exchange (ETDEWEB)

    Woods, S.W.; Krystal, J.H.; Heninger, G.R.; Charney, D.S.

    1989-01-01

    In order to investigate possible neurobiologic mechanisms underlying carbon dioxide-induced anxiety, the effects of oral alprazolam 0.75 mg and intravenous clonidine 2 mcg/kg on CO/sub 2/-induced increases in ratings of subjective anxiety, pulse rate, and ventilation were measured in healthy human subjects. Pretreatment with alprazolam but not with clonidine significantly reduced the CO/sub 2/-induced increases in ratings of anxiety. Neither drug altered CO/sub 2/-induced increases in pulse rate or ventilatory responses. Clonidine did produce potent sedative and hypotensive effects. The behavioral data suggest that the mechanisms through which CO/sub 2/ induces anxiety-like effects involve neural systems regulated by benzodiazepine receptors and, secondly, that they appear not to require normal functioning of noradrenergic systems. Carbon dioxide may provide a useful model system for identification of new drugs with anxiolytic properties.

  18. The Diuretic Effect in Human Subjects of an Extract of Taraxacum officinale Folium over a Single Day

    Science.gov (United States)

    Clare, Bevin A.; Conroy, Richard S.

    2009-01-01

    Abstract Background Taraxacum officinale (L.) Weber (Asteraceae) has been extensively employed as a diuretic in traditional folk medicine and in modern phytotherapy in Europe, Asia, and the Americas without prior clinical trial substantiation. Objectives In this pilot study, a high-quality fresh leaf hydroethanolic extract of the medicinal plant T. officinale (dandelion) was ingested by volunteers to investigate whether an increased urinary frequency and volume would result. Design Volume of urinary output and fluid intake were recorded by subjects. Baseline values for urinary frequency and excretion ratio (urination volume:fluid intake) were established 2 days prior to dandelion dosing (8 mL TID) and monitored throughout a 1-day dosing period and 24 hours postdosing. Results For the entire population (n = 17) there was a significant (p diuresis in human subjects. PMID:19678785

  19. 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.

  20. 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.

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

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    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.

  2. Stochastic Resonance Activity Influences Serum Tryptophan Metabolism in Healthy Human Subjects

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    Berthold Kepplinger

    2011-01-01

    Full Text Available Background Stochastic resonance therapy (SRT is used for rehabilitation of patients with various neuropsychiatric diseases. An alteration in tryptophan metabolism along the kynurenine pathway has been identified in the central and peripheral nervous systems in patients with neuroinflammatory and neurodegenerative diseases and during the aging process. This study investigated the effect of SRT as an exercise activity on serum tryptophan metabolites in healthy subjects. Methods Serum L-tryptophan, L-kynurenine, kynurenic acid, and anthranilic acid levels were measured one minute before SRT and at one, 5, 15, 30, and 60 minutes after SRT. We found that SRT affected tryptophan metabolism. Serum levels of L-tryptophan, L-kynurenine, and kynurenic acid were significantly reduced for up to 60 minutes after SRT. Anthranilic acid levels were characterized by a moderate, non significant transient decrease for up to 15 minutes, followed by normalization at 60 minutes. Tryptophan metabolite ratios were moderately altered, suggesting activation of metabolism after SRT. Lowering of tryptophan would generally involve activation of tryptophan catabolism and neurotransmitter, protein, and bone biosynthesis. Lowering of kynurenic acid by SRT might be relevant for improving symptoms in patients with neuropsychiatric disorders, such as Parkinson's disease, Alzheimer's disease, schizophrenia, and depression, as well as certain pain conditions.

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

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    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.

  4. Human muscle fiber types in power lifters, distance runners and untrained subjects.

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    Prince, F P; Hikida, R S; Hagerman, F C

    1976-05-06

    Muscle biopsies were taken from the vastus lateralis of 12 males: 5 control subjects, 4 power lifters and 3 distance runners. Three fiber "types" were distinguished by comparing serial sections for alkaline myofibrillar adenosine triphosphatase (ATPase) and succinic dehydrogenase (SDH) activities: 1. high ATPase and low SDH; fast-twitch-glycolytic (FG). 2. High ATPase and high SDH; fast-twitch-oxidative-glycolytic (FOG). 3. Low ATPase and high SDH; slow-twitch-oxidative (SO). In some cases the distinction between the FOG and FG classess was not clear and a group termed "transitional" was employed. A variation in percentage of fiber types and fiber area was found among individuals. The percentage of SO fibers varied from 19.6-60.1% within all 3 groups, with a mean of 40.5%. In the control group approximately 75% of the fibers were oxidative (FOG + SO). The major characteristics of the lifters were a decrease in the percentage of FOG fibers and a hypertrophy of FOG and FG fibers. The distance runners had a high percentage of oxidative fibers with few FG fibers. It is suggested that the fast-twitch fibers are mainly involved in the adaptation of muscle to exercise since the percentage of SO fibers varies greatly among individuals within and between the 3 groups studied.

  5. Regional variations in certain cellular characteristics in human lumbar intervertebral discs, including the presence of alpha-smooth muscle actin.

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    Hastreiter, D; Ozuna, R M; Spector, M

    2001-07-01

    An evaluation of the regional variation of certain cellular features in the human intervertebral disc (IVD) could lead to a better understanding of site-specific properties relative to degradation, response to injury, and healing processes. The objective of this study was to determine how cell density, cell morphology, cell grouping, and expression of a specific actin isoform varied with location and degeneration in the human disc. A total of 41 human L4-L5 and L5-S1 discs removed postmortem from 21 individuals were analyzed. The discs were graded for degeneration based on the Thompson scale and processed for evaluation. Microtomed sections from paraffin-embedded specimens were stained with hematoxylin and eosin or a monoclonal antibody to alpha-smooth muscle actin (alpha-SMA), an actin isoform often associated with contraction. A significant regional dependence was found for most of the measured parameters. A fourfold increase in cell density was found in proceeding from the nucleus pulposus (NP) to the outer annulus (OA) of the IVD. Approximately 30% of the cells in the NP were present in groups. Virtually all of the cells in the NP and 40% of those in the OA were round. Moreover, notable percentages (12-15%) of the cells in the NP and inner annulus (IA) contained alpha-SMA. Only pair density was found to be correlated with Thompson grade, with more degenerated specimens having higher values. A greater effect was also observed on the percentage of cells in groups. These findings provide the basis for future work to investigate the importance of cells in groups, the role of alpha-SMA in the disc, and the changes in these cellular characteristics in pathological disc conditions.

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

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    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

  7. The human genome and sport, including epigenetics and athleticogenomics: a brief look at a rapidly changing field.

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    Sharp, N C Craig

    2008-09-01

    Since Hugh Montgomery discovered the first of what are now nearly 200 "fitness genes", together with rapid advances in human gene therapy, there is now a real prospect of the use of genes, genetic elements, and/or cells that have the capacity to enhance athletic performance (to paraphrase the World Anti-Doping Agency's definition of gene doping). This overview covers the main areas of interface between genetics and sport, attempts to provide a context against which gene doping may be viewed, and suggests a futuristic legitimate use of genomic (and possibly epigenetic) information in sport.

  8. [Sulfonamide-research on human subjects in Nazi concentration camps: a critical re-evaluation of the epistemological and ethical dimension].

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    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.

  9. DNA Damage Response and Radiosensitivity of Immune Cells from Subjects Undergoing Confinement in the NASA Human Exploration Research Analog

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    Moreno-Villanueva, Maria

    2017-01-01

    The Human Exploration Research Analog (HERA) represents an analog for simulation of isolation, confinement and remote conditions of mission exploration scenarios. HERA aims at investigating team performance and cooperation, reaction to stress, signs of early depression, anxiety and anger and their impact on human health. HERA is a collaborative project involving experts in different fields. Not only psychological but also clinical biomarkers of stress, e.g. adrenaline has been measured. It is known that stress hormones induce DNA strand breaks thus, within this project, my tasks was to determine the level of DNA strand breaks as well as expression of genes involved in DNA damage response in immune cells obtained from HERA subjects. Furthermore, the sensitivity of the cells to ex vivo radiation was also assessed.

  10. A comparison of Coomassie blue dye with radioiodinated albumin as an indicator for plasma volume estimation in human subjects

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    Menzies, Ian S.

    1966-01-01

    Plasma volume has been estimated in 10 human subjects using Coomassie blue and 131I radioiodinated human serum albumin dilution methods simultaneously. Three different methods of correction used by previous workers to overcome the error due to early dye loss were applied. Satisfactory agreement with the established radioiodinated albumin method was only obtained by extrapolation of the semilogarithmic plot of Coomassie blue plasma dye concentration between five and 10 minutes to the time of injection. The significance of the controversial Evans blue `mixing curve' is discussed. An analogous phase in the Coomassie blue disappearance slope is considered to be due to initial rapid loss of dye from the circulation rather than to the process of mixing. It is shown that Coomassie blue fulfils the criteria listed in the discussion for plasma volume estimation. PMID:4160095

  11. PREVALENCE OF SOME HELMINTHS IN RODENTS CAPTURED FROM DIFFERENT CITY STRUCTURES INCLUDING POULTRY FARMS AND HUMAN POPULATION OF FAISALABAD, PAKISTAN

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    A. RAFIQUE, S. A. RANA, H. A. KHAN AND A. SOHAIL1

    2009-07-01

    Full Text Available The aim of the present study was to investigate prevalence of zoonotic helminths from human, Rattus rattus (R. rattus, Rattus norvegicus (R. norvegicus and Mus musculus of eight different structures, namely grain shops in grain market, departmental stores, railway godowns, food processing plants (bakeries, poultry farms, houses in kachi-abadies, houses in departmental colonies and posh residences and banglows in Faisalabad city. All the structures were sampled for 2 months each and completed in 16 months. Highest prevalence (70% of Vsmpirolepis spp. was observed in R. rattus sampled from poultry farms, which was significantly higher (P<0.05 than the prevalence of all the helminths recovered from other structures. Hymenolepis nana (H. nana was observed in 60% of the sampled Mus musculus collected from kachi-abadies, which was significantly higher (P<0.05 than all other structures studies for H. nana, except R. rattus from kachi-abadies (55% and R. norvegicus from grain shops in grain market (55%. The rodent’s endo-parasites viz., Hymenolepis nana, Teania taenaeformis, Entrobius spps and Trichuiris spps observed in R. rattus, R. norvegicus and M. musculus at different percentages were also recorded in human stool samples with an incidence of 48, 21, 76 and 10%, respectively.

  12. Triple Staining Including FOXA2 Identifies Stem Cell Lineages Undergoing Hepatic and Biliary Differentiation in Cirrhotic Human Liver.

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    Rogler, Charles E; Bebawee, Remon; Matarlo, Joe; Locker, Joseph; Pattamanuch, Nicole; Gupta, Sanjeev; Rogler, Leslie E

    2017-01-01

    Recent investigations have reported many markers associated with human liver stem/progenitor cells, "oval cells," and identified "niches" in diseased livers where stem cells occur. However, there has remained a need to identify entire lineages of stem cells as they differentiate into bile ducts or hepatocytes. We have used combined immunohistochemical staining for a marker of hepatic commitment and specification (FOXA2 [Forkhead box A2]), hepatocyte maturation (Albumin and HepPar1), and features of bile ducts (CK19 [cytokeratin 19]) to identify lineages of stem cells differentiating toward the hepatocytic or bile ductular compartments of end-stage cirrhotic human liver. We identified large clusters of disorganized, FOXA2 expressing, oval cells in localized liver regions surrounded by fibrotic matrix, designated as "micro-niches." Specific FOXA2-positive cells within the micro-niches organize into primitive duct structures that support both hepatocytic and bile ductular differentiation enabling identification of entire lineages of cells forming the two types of structures. We also detected expression of hsa-miR-122 in primitive ductular reactions expected for hepatocytic differentiation and hsa-miR-23b cluster expression that drives liver cell fate decisions in cells undergoing lineage commitment. Our data establish the foundation for a mechanistic hypothesis on how stem cell lineages progress in specialized micro-niches in cirrhotic end-stage liver disease.

  13. Is the bronchus-associated lymphoid tissue (BALT) an integral structure of the lung in normal mammals, including humans?

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    Pabst, R; Gehrke, I

    1990-08-01

    In the respiratory tract, lymphoid aggregates with a specialized epithelium have been called bronchus-associated lymphoid tissue (BALT) and compared to the organized lymphoid tissue of the gut (GALT), e.g., Peyer's patches. BALT might play a central role in antigen uptake, initiating immune responses and disseminating primed lymphoid cells in the respiratory tract. In the present study, lungs of mice, rats, guinea pigs, rabbits, pigs, cats, and humans have been studied with respect to the presence and number of BALT and the dependence of BALT on age and microbial stimulation. BALT is not a constitutive structure in all these species. Its frequency varies widely, from 100% in rabbits and rats, 50% in guinea pigs, 33% in pigs, to its absence in cats and all normal human lungs. BALT seems to be a lymphoid structure which is not present in all the species studied but can develop in the lung after stimulation. This is in contrast to lymphoid organs, such as lymph nodes or Peyer's patches, which can always be found. These species differences are of major importance in interpreting the clinical relevance of experiments in animal models on the lung immune system, e.g., antigen uptake, immunostimulation, or lung transplantation.

  14. Habitual sleep durations and subjective sleep quality predict white matter differences in the human brain

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    Sakh Khalsa

    2017-06-01

    Full Text Available Self-imposed short sleep durations are increasingly commonplace in society, and have considerable health and performance implications for individuals. Reduced sleep duration over multiple nights has similar behavioural effects to those observed following acute total sleep deprivation, suggesting that lack of sleep affects brain function cumulatively. A link between habitual sleep patterns and functional connectivity has previously been observed, and the effect of sleep duration on the brain's intrinsic functional architecture may provide a link between sleep status and cognition. However, it is currently not known whether differences in habitual sleep patterns across individuals are related to changes in the brain's white matter, which underlies structural connectivity. In the present study we use diffusion–weighted imaging and a group comparison application of tract based spatial statistics (TBSS to investigate changes to fractional anisotropy (FA and mean diffusivity (MD in relation to sleep duration and quality, hypothesising that white matter metrics would be positively associated with sleep duration and quality. Diffusion weighted imaging data was acquired from a final cohort of 33 (23–29 years, 10 female, mean 25.4 years participants. Sleep patterns were assessed for a 14 day period using wrist actigraphs and sleep diaries, and subjective sleep quality with the Pittsburgh Sleep Quality Index (PSQI. Median splits based on total sleep time and PSQI were used to create groups of shorter/longer and poorer/better sleepers, whose imaging data was compared using TBSS followed by post-hoc correlation analysis in regions identified as significantly different between the groups. There were significant positive correlations between sleep duration and FA in the left orbito-frontal region and the right superior corona radiata, and significant negative correlations between sleep duration and MD in right orbito-frontal white matter and the right

  15. Pharmacokinetics of the citrus flavanone aglycones hesperetin and naringenin after single oral administration in human subjects.

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    Kanaze, F I; Bounartzi, M I; Georgarakis, M; Niopas, I

    2007-04-01

    Hesperetin and naringenin, the aglycones of the flavanone glycosides hesperidin and naringin, occur naturally in citrus fruits. They exert interesting pharmacological properties such as antioxidant, anti-inflammatory, blood lipid and cholesterol lowering and are considered to contribute to health benefits in humans. However, no information is available on the pharmacokinetics of the citrus flavanones hesperetin and naringenin after their oral administration to humans as pure aglycones. Therefore, the objective of the present investigation was the evaluation of the pharmacokinetic parameters of hesperetin and naringenin in plasma and urine, after their single oral administration in humans in the form of solid dispersion capsules, and also to improve the absorption rate of flavanones by using aglycones rather than the naturally occurring glycosides. Six healthy volunteers received orally 135 mg of each compound, hesperetin and naringenin, under fasting conditions. Blood samples were collected at 14 different time points over a 12 h period. Urine was collected over 24 h, in five sequential timed intervals. Plasma and urine hesperetin and naringenin concentrations, after enzymatic hydrolysis of their conjugated forms, were measured using validated high-pressure liquid chromatography methods. Pharmacokinetic parameters for hesperetin and naringenin, such as C(max), T(max), AUC(0-t), AUC(0-infinity), CL/F, V/F, t(1/2), MRT, A(e), A(e)((0-24)), and R(max) were calculated from their plasma or urine concentrations. Pharmacokinetic analysis showed that both hesperetin and naringenin were rapidly absorbed and their concentrations in plasma observed 20 min after dosing and reached a peak in 4.0 and 3.5 h, respectively. The mean peak plasma concentration (C(max)) for hesperetin and naringenin were 825.78+/-410.63 ng/ml (2731.8+/-1358.4 nmol/l) and 2009.51+/-770.82 ng/ml (7386.6+/-2833.4 nmol/l), respectively and the mean AUC(0-infinity) values were 4846.20+/-1675.99 ng h/ml and

  16. Pharmacokinetics of 6-, 8-, 10-Gingerols and 6-Shogaol and Conjugate Metabolites in Healthy Human Subjects

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    Zick, Suzanna M.; Djuric, Zora; Ruffin, Mack T.; Litzinger, Amie J.; Normolle, Daniel P.; Feng, Meihua Rose; Brenner, Dean E.

    2009-01-01

    Background Ginger demonstrates promising anticancer properties. No research has examined the pharmacokinetics of the ginger constituents 6-, 8-, 10-gingerol and 6-shogaol in humans. We conducted a clinical trial with 6-, 8-, 10-gingerol and 6-shogaol examining the pharmacokinetics and tolerability of these analytes and their conjugate metabolites Methods Human volunteers were given ginger at doses from 100 mg, to 2.0 g (N=27), and blood samples were obtained at 15 minutes to 72 hours after a single oral dose. Participants were allocated in a dose-escalation manner starting with 100 mg. There was a total of three participants at each dose except for 1.0 g (N=6) and 2.0 g (N=9). Results No participant had detectable free 6-, 8-, 10-gingerol or 6-shogaol, but 6-, 8-, 10-gingerol and 6-shogaol glucuronides were detected. The 6-gingerol sulfate conjugate was detected above the 1.0 g dose but there were no detectable 10-gingerol or 6-shogaol sulfates except for one participant with detectable 8-gingerol sulfate. The Cmax and AUC values (Mean±SE) estimated for the 2.0 g dose are 0.85±0.43, 0.23±0.16, 0.53±0.40, and 0.15±0.12 μg/mL ; and 65.6.33±44.4, 18.1±20.3, 50.1±49.3, and 10.9±13.0 μg·hr/mL for 6-, 8-, 10-gingerol, and 6-shogaol. The corresponding tmax values are 65.6±44.4, 73.1±29.4, 75.0±27.8, and 65.6±22.6 minutes and the analytes had elimination half-lives gingerol and 6-shogaol conjugates were present as either glucuronide or sulfate conjugates, not as mixed conjugates, although 6-, 10-gingerol were an exception. Conclusion Six-, 8-, 10-gingerol and 6-shogaol is absorbed after oral dosing and can be detected as glucuronide and sulfate conjugates. PMID:18708382

  17. Comparative Proteomic Profile of the Human Placenta in Normal and Fetal Growth Restriction Subjects

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    Zhijing Miao

    2014-11-01

    Full Text Available Background: Fetal growth restriction (FGR is the main cause of intrauterine fetal death and the second leading cause of death in the neonatal period. A large body of evidence suggests that FGR may be associated with the placenta, although its etiology and pathogenesis remain to be fully elucidated. Methods and Results: To better understand the molecular mechanisms underlying the pathological development of the placenta in FGR, we used tandem mass tags (TMTs to construct a large-scale comparative proteomic profile of human placentas from normal and FGR pregnancies. A total of 1,198 kinds of proteins were identified in the control and FGR placentas, of which 95 were differentially expressed between two groups. Ingenuity Pathway Analysis (IPA was used to organize these differentially expressed proteins into networks of interacting proteins and to identify the modules of functionally related proteins. Western blotting was used to verify the expression patterns of several randomly selected proteins. Conclusion: The placentas of women with FGR displayed significant proteome differences compared with normal pregnancy. The results indicate that a variety of mechanisms and proteins may contribute to the development of FGR. Further studies and validations are required to elucidate the exact roles of these proteins in FGR pathogenesis.

  18. Neuroprotective Effects of Castanea sativa Mill. Bark Extract in Human Neuroblastoma Cells Subjected to Oxidative Stress.

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    Brizi, Claudia; Santulli, Chiara; Micucci, Matteo; Budriesi, Roberta; Chiarini, Alberto; Aldinucci, Carlo; Frosini, Maria

    2016-02-01

    One of the major features of neurodegenerative disease is the selective vulnerability of different neuronal populations that are affected in a progressive and often stereotyped manner. Despite the susceptible neuronal population varies between diseases, oxidative stress is implicated as the major pathogenic process in all of them. Natural Extract of Castanea sativa Mill. bark (ENC), recently characterized in its phenolic composition, acts as antioxidant and cardioprotective agent. Its neuroprotettive properties, however, have never been investigated. The aim of this study was to assess neuroprotection of ENC in in vitro models of oxidative-stress-mediate injury. Human neuroblastoma SH-SY5Y cells treated with glutamate (50 mM for 24 h) or hydrogen peroxide (25 μM for 1 h followed by 24 with medium) were used. The results showed that the addition of ENC (1-50 μg/ml) to cell medium before the neuronal damage provided neuroprotection in both experimental models used, while its addition after the injury was ineffective. In conclusion, the present results suggest that ENC could be a valuable support as dietary supplement, combining beneficial preventive neuroprotettive effects with a high antioxidant activity. © 2015 Wiley Periodicals, Inc.

  19. Human spermatogenic failure purges deleterious mutation load from the autosomes and both sex chromosomes, including the gene DMRT1.

    Science.gov (United States)

    Lopes, Alexandra M; Aston, Kenneth I; Thompson, Emma; Carvalho, Filipa; Gonçalves, João; Huang, Ni; Matthiesen, Rune; Noordam, Michiel J; Quintela, Inés; Ramu, Avinash; Seabra, Catarina; Wilfert, Amy B; Dai, Juncheng; Downie, Jonathan M; Fernandes, Susana; Guo, Xuejiang; Sha, Jiahao; Amorim, António; Barros, Alberto; Carracedo, Angel; Hu, Zhibin; Hurles, Matthew E; Moskovtsev, Sergey; Ober, Carole; Paduch, Darius A; Schiffman, Joshua D; Schlegel, Peter N; Sousa, Mário; Carrell, Douglas T; Conrad, Donald F

    2013-03-01

    Gonadal failure, along with early pregnancy loss and perinatal death, may be an important filter that limits the propagation of harmful mutations in the human population. We hypothesized that men with spermatogenic impairment, a disease with unknown genetic architecture and a common cause of male infertility, are enriched for rare deleterious mutations compared to men with normal spermatogenesis. After assaying genomewide SNPs and CNVs in 323 Caucasian men with idiopathic spermatogenic impairment and more than 1,100 controls, we estimate that each rare autosomal deletion detected in our study multiplicatively changes a man's risk of disease by 10% (OR 1.10 [1.04-1.16], pautism, schizophrenia, bipolar disorder, and intellectual disability, we propose that the CNV burden in spermatogenic impairment is distinct from the burden of large, dominant mutations described for neurodevelopmental disorders. We identified two patients with deletions of DMRT1, a gene on chromosome 9p24.3 orthologous to the putative sex determination locus of the avian ZW chromosome system. In an independent sample of Han Chinese men, we identified 3 more DMRT1 deletions in 979 cases of idiopathic azoospermia and none in 1,734 controls, and found none in an additional 4,519 controls from public databases. The combined results indicate that DMRT1 loss-of-function mutations are a risk factor and potential genetic cause of human spermatogenic failure (frequency of 0.38% in 1306 cases and 0% in 7,754 controls, p = 6.2 × 10(-5)). Our study identifies other recurrent CNVs as potential causes of idiopathic azoospermia and generates hypotheses for directing future studies on the genetic basis of male infertility and IVF outcomes.

  20. Lactate: Brain Fuel in Human Traumatic Brain Injury: A Comparison with Normal Healthy Control Subjects

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    Martin, Neil A.; Horning, Michael A.; McArthur, David L.; Hovda, David A.; Vespa, Paul; Brooks, George A.

    2015-01-01

    Abstract We evaluated the hypothesis that lactate shuttling helps support the nutritive needs of injured brains. To that end, we utilized dual isotope tracer [6,6-2H2]glucose, that is, D2-glucose, and [3-13C]lactate techniques involving arm vein tracer infusion along with simultaneous cerebral (arterial [art] and jugular bulb [JB]) blood sampling. Traumatic brain injury (TBI) patients with nonpenetrating brain injuries (n=12) were entered into the study following consent of patients' legal representatives. Written and informed consent was obtained from control volunteers (n=6). Patients were studied 5.7±2.2 (mean±SD) days post-injury; during periods when arterial glucose concentration tended to be higher in TBI patients. As in previous investigations, the cerebral metabolic rate for glucose (CMRgluc, i.e., net glucose uptake) was significantly suppressed following TBI (pcerebral lactate uptake related to systemic lactate supply, approximated 11% in both healthy control subjects and TBI patients. Further, neither the CMR for lactate (CMRlac, i.e., net lactate release), nor the tracer-measured cerebral lactate uptake differed between healthy controls and TBI patients. The percentages of lactate tracer taken up and released as 13CO2 into the JB accounted for 92% and 91% for control and TBI conditions, respectively, suggesting that most cerebral lactate uptake was oxidized following TBI. Comparisons of isotopic enrichments of lactate oxidation from infused [3-13C]lactate tracer and 13C-glucose produced during hepatic and renal gluconeogenesis (GNG) showed that 75–80% of 13CO2 released into the JB was from lactate and that the remainder was from the oxidation of glucose secondarily labeled from lactate. Hence, either directly as lactate uptake, or indirectly via GNG, peripheral lactate production accounted for ∼70% of carbohydrate (direct lactate uptake+uptake of glucose from lactate) consumed by the injured brain. Undiminished cerebral lactate fractional

  1. Evidence for Within-Host Genetic Recombination among the Human Pegiviral Strains in HIV Infected Subjects.

    Directory of Open Access Journals (Sweden)

    Haoming Wu

    Full Text Available The non-pathogenic Human Pegivirus (HPgV, formerly GBV-C/HGV, the most prevalent RNA virus worldwide, is known to be associated with reduced morbidity and mortality in HIV-infected individuals. Although previous studies documented its ubiquity and important role in HIV-infected individuals, little is known about the underlying genetic mechanisms that maintain high genetic diversity of HPgV within the HIV-infected individuals. To assess the within-host genetic diversity of HPgV and forces that maintain such diversity within the co-infected hosts, we performed phylogenetic analyses taking into account 229 HPgV partial E1-E2 clonal sequences representing 15 male and 8 female co-infected HIV patients from Hubei province of central China. Our results revealed the presence of eleven strongly supported clades. While nine clades belonged to genotype 3, two clades belonged to genotype 2. Additionally, four clades that belonged to genotype 3 exhibited inter-clade recombination events. The presence of clonal sequences representing multiple clades within the HIV-infected individual provided the evidence of co-circulation of HPgV strains across the region. Of the 23 patients, six patients (i.e., five males and one female were detected to have HPgV recombinant sequences. Our results also revealed that while male patients shared the viral strains with other patients, viral strains from the female patients had restricted dispersal. Taken together, the present study revealed that multiple infections with divergent HPgV viral strains may have caused within-host genetic recombination, predominantly in male patients, and therefore, could be the major driver in shaping genetic diversity of HPgV.

  2. 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.

  3. 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.

  4. 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.

    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. PMID:28575032

  5. Effects of visual demonstration, verbal instructions, and prompted verbal descriptions on the performance of human subjects in conditional discriminations

    Science.gov (United States)

    Ribes-Iñesta, Emilio; Cepeda, Ma. Luisa; Hickman, Hortencia; Moreno, Diana; Peñalosa, Eduardo

    1992-01-01

    A study was conducted to confirm prior results concerning the role of prompted verbal descriptions of visually demonstrated stimulus relations in the acquisition and transfer of identity, difference, and similarity-matching relations (Ribes et al., 1988). Four groups of human adults were trained with these three matching relations under four different procedures: (1) visual demonstration without response requirement, (2) verbal instructions, (3) visual demonstration plus prompted verbal description, and (4) visual demonstration plus verbal instructions. These procedures were presented at the beginning of the training period before subjects could respond to the experimental task. Although most subjects in the four groups acquired the conditional discrimination under the three matching relations, only those in the two instruction-related groups showed some intramodal and extramodal transfer in tests with stimuli that had not been used in training. These results suggest the importance of measuring extra-situational and trans-situational generalization, and raise the need to distinguish between formal and functional verbal factors in the regulation of human behavior. ImagesFig. 3Fig. 4 PMID:22477044

  6. Distribution of glycosphingolipids in the serum lipoproteins of normal human subjects and patients with hypo- and hyperlipidemias

    Energy Technology Data Exchange (ETDEWEB)

    Dawson, G.; Kruski, A.W.; Scanu, A.M.

    1976-01-01

    Five glycosphingolipids (GSL), glucosylceramide, lactosylceramide, trihexosylceramide, globoside, and hematoside (G/sub m//sub 3/) were studied in serum from normal human subjects and patients with dyslipoproteinemia and found to be exclusively associated with the various classes of serum lipoproteins. Based on a unit weight of lipoprotein protein, the total amount of GSL in serum from normal subjects was twice as high in very low density lipoprotein (VLDL) (d < 1.006 g/ml) and low density lipoprotein (LDL) (d 1.019-1.063 g/ml) as in high density lipoproteins HDL/sub 2/ (d 1.063-1.125 g/ml) or HDL/sub 3/ (d 1.125-1.21 g/ml). In abetalipoproteinemia the levels of serum GSL were slightly reduced when compared to normal serum and were all found in the only existing lipoprotein, HDL; this contained 2-3 moles of GSL/mole of lipoprotein as compared to 0.5 GSL/mole in normal HDL. In hypobetalipoproteinemia and Tangier disease, the serum glycosphingolipids were 10 to 30% reduced in concentration compared to the 75% reduction in other lipids, and were again found to be associated only with the serum lipoproteins. The relative proportions of GSL did not vary substantially in the normo- and hypolipidemic subjects studied. Although results establish that glycosphingolipids are intimately associated with serum lipoproteins, the mode of association or the structural and functional significance of such an association remains undetermined.

  7. The Fiction of Respect Individual Autonomy as a Kind Of Clínical Research Human Subject Explotation

    Directory of Open Access Journals (Sweden)

    Natalia Petersen Nascimento Santos

    2015-12-01

    Full Text Available This article promotes a discussion of western legal concept which sees individuals as subjects of rights, discussing the advisability of such a formulation in the context of clinical trials in humans, since the commonly borderline situation of vulnerability in which they are volunteers who submit to such procedures. For this purpose, it was used as a theoretical framework to work "Critical Introduction to Law" Michel Mialle, in which the author states in a forceful way that the construction of the legal institute of the "subject of law" and the imposition of unrestricted recognition of individual autonomy constitute a construction of the bourgeois state to facilitate the domination of vulnerable, so that this, although not legally obliged to practice certain behaviors, see forced by circumstances to act in line with the interests of that institution. It is argued, therefore, that autonomy to consent to participation in scientific trials must be assessed in each case, with special attention to circumstances which might vulnerabilizar voluntary research and mitigate their individual autonomy in the face of the experiments, under penalty to be subjecting the individual to harmful procedures to their lives and health for the benefit of capital society's interests.

  8. Human histologic evaluation of a six-year-old threaded implant retrieved from a subject with osteoporosis.

    Science.gov (United States)

    de Melo, Leandro; Piattelli, Adriano; Lezzi, Giovanna; d'Avila, Susana; Zenóbio, Elton Golçalves; Shibli, Jamil Awad

    2008-03-01

    The aim of this case report was to present the evaluation of the bone-to-implant contact in an implant retrieved from a subject with osteoporosis after six years of load. Systemic conditions associated with osteoporosis have been postulated to contribute to the severity of alveolar bone loss. The increase in human life expectancy, the increased number of elderly subjects who are partially or totally edentulous, and the use of dental implants for oral habilitation in subjects with osteoporosis has raised several questions. A 68-year-old woman with postmenopausal osteoporosis received a prosthetic evaluation of an implant-supported restoration. Histologically, the peri-implant bone appeared healthy. The peri-implant bone appeared in close contact with the implant surface, whereas marrow spaces could be detected in other areas along with prominently stained cement lines. The mean of bone-to-implant contact was 62.51+1.96. The results of the evaluation of the dental implant reported here suggest the presence of osteoporosis may not be a contra-indication for implant placement at least after osseointegration has already been established.

  9. Evaluation of a Self-Administered Intravaginal Swab for PCR Detection of Genitourinary Tract Infections Including Chlamydia, Gonorrhea, Trichomonas and Human Papillomavirus in Active Duty Military Women

    Science.gov (United States)

    1998-10-01

    Trichomonas bmcei subsp. rhodesiense, K02836; Trypanosoma cmzi, M97956; Toxop/asma gon- gallinae ATCC 30002, Giardia lamblia ATCC SF-741 30888, Chilomastix...Administered Intravaginal Swab for PCR Detection of Genitourinary Tract Infections Including Chlamydia, Gonorrhea, Trichomonas and Human...FUNDING NUMBERS Intravaginal Swab for PCR Detection of Genitourinary DAMD17-96-1-6309 Tract Infections Including Chlamydia, Gonorrhea, Trichomonas

  10. Human spermatogenic failure purges deleterious mutation load from the autosomes and both sex chromosomes, including the gene DMRT1.

    Directory of Open Access Journals (Sweden)

    Alexandra M Lopes

    2013-03-01

    Full Text Available Gonadal failure, along with early pregnancy loss and perinatal death, may be an important filter that limits the propagation of harmful mutations in the human population. We hypothesized that men with spermatogenic impairment, a disease with unknown genetic architecture and a common cause of male infertility, are enriched for rare deleterious mutations compared to men with normal spermatogenesis. After assaying genomewide SNPs and CNVs in 323 Caucasian men with idiopathic spermatogenic impairment and more than 1,100 controls, we estimate that each rare autosomal deletion detected in our study multiplicatively changes a man's risk of disease by 10% (OR 1.10 [1.04-1.16], p<2 × 10(-3, rare X-linked CNVs by 29%, (OR 1.29 [1.11-1.50], p<1 × 10(-3, and rare Y-linked duplications by 88% (OR 1.88 [1.13-3.13], p<0.03. By contrasting the properties of our case-specific CNVs with those of CNV callsets from cases of autism, schizophrenia, bipolar disorder, and intellectual disability, we propose that the CNV burden in spermatogenic impairment is distinct from the burden of large, dominant mutations described for neurodevelopmental disorders. We identified two patients with deletions of DMRT1, a gene on chromosome 9p24.3 orthologous to the putative sex determination locus of the avian ZW chromosome system. In an independent sample of Han Chinese men, we identified 3 more DMRT1 deletions in 979 cases of idiopathic azoospermia and none in 1,734 controls, and found none in an additional 4,519 controls from public databases. The combined results indicate that DMRT1 loss-of-function mutations are a risk factor and potential genetic cause of human spermatogenic failure (frequency of 0.38% in 1306 cases and 0% in 7,754 controls, p = 6.2 × 10(-5. Our study identifies other recurrent CNVs as potential causes of idiopathic azoospermia and generates hypotheses for directing future studies on the genetic basis of male infertility and IVF outcomes.

  11. Certificates of Confidentiality: Protecting Human Subject Research Data in Law and Practice.

    Science.gov (United States)

    Wolf, Leslie E; Patel, Mayank J; Williams Tarver, Brett A; Austin, Jeffrey L; Dame, Lauren A; Beskow, Laura M

    2015-01-01

    The federal Certificate of Confidentiality plays an important role in research on sensitive topics by authorizing researchers to refuse to disclose identifiable research data in response to subpoenas in any legal setting. However, there is little known about how effective Certificates are in practice. This article draws on our legal and empirical research on this topic to fill this information gap. It includes a description of the purpose of Certificates, their legislative and regulatory history, and a summary of the few reported and unreported cases that have dealt with Certificates. In addition, we outline other statutory confidentiality protections, compare them to the Certificate's protections, and analyze some of the vulnerabilities of a Certificate's protections. This analysis allows us to make specific recommendations for strengthening the protections afforded to research data. © 2015 American Society of Law, Medicine & Ethics, Inc.

  12. 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.

  13. Central projection of pain arising from delayed onset muscle soreness (DOMS in human subjects.

    Directory of Open Access Journals (Sweden)

    Katharina Zimmermann

    Full Text Available Delayed onset muscle soreness (DOMS is a subacute pain state arising 24-48 hours after a bout of unaccustomed eccentric muscle contractions. Functional magnetic resonance imaging (fMRI was used to examine the patterns of cortical activation arising during DOMS-related pain in the quadriceps muscle of healthy volunteers evoked by either voluntary contraction or physical stimulation. The painful movement or physical stimulation of the DOMS-affected thigh disclosed widespread activation in the primary somatosensory and motor (S1, M1 cortices, stretching far beyond the corresponding areas somatotopically related to contraction or physical stimulation of the thigh; activation also included a large area within the cingulate cortex encompassing posteroanterior regions and the cingulate motor area. Pain-related activations were also found in premotor (M2 areas, bilateral in the insular cortex and the thalamic nuclei. In contrast, movement of a DOMS-affected limb led also to activation in the ipsilateral anterior cerebellum, while DOMS-related pain evoked by physical stimulation devoid of limb movement did not.

  14. 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; Riba, Jordi

    2016-07-01

    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. 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. 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. 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. © The Author 2016. Published by Oxford University Press on behalf of CINP.

  15. 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

  16. Mineralogical and Geochemical Studies of Bone Detritus of Pleistocene Mammals, Including the Earliest in Northern Eurasia Humans

    Directory of Open Access Journals (Sweden)

    V. I. Silaev

    2015-12-01

    Full Text Available Article presents the preliminary results of mineralogical and geochemical studies of the primary and epigenetic properties of the bio-mineral and protein components in the fossil bone detritus as an example of first step of continued interdisciplinary research program. During the further implementation of this program, it is expected not only to solve a set of interrelated mineralogical, paleontological, paleoecological, paleoclimatic, and archaeological problems, but also to obtain new knowledge about the coevolution of organic, organo-mineral and inorganic substances in the geological history. The main objects of study are the fossil remains of the large Pleistocene mammals (mammoths, woolly rhinoceroses, deer, elk, horses, bison, cave and brown bear found on the territory of the Pechora Urals (62-67 ° N , South Pri-Irtyshie in Western Siberia (57-58 ° N, and Northern Taymyr (75-77 ° N. The oldest bone of Homo sapiens (Ust-Ishim human found in Northern Eurasia and remains of medieval Tobol and Irtysh Turk will be investigated as well. The results of previous studies of skin and hair of biological material from today's wild fisheries (analogues Pleistocene mammals, wild and domestic animals are considered as the reliable prerequisites for planned isotopic and geochemical studies. Use of cutting-edge research techniques will allow determining the chemical composition of bones; the elemental composition of bone collagen and bone proteins; the degree of crystallinity of bone bioapatite, and phase composition of xenomineral impurities; the isotopic composition of carbon, oxygen, and nitrogen in bioapatite and collagen; the actual molecular and crystal structure of the protein biomineral, and bone substance; the concentration of trace elements; the conditions and duration of burial and reburial of bone detritus; bone collagen bacterial degradation at an early stage of fossilization. It is expected that the implementation of the proposed project

  17. Successful isolation of infectious and high titer human monocyte-derived HIV-1 from two subjects with discontinued therapy.

    Science.gov (United States)

    Wang, Tong; Xu, Younong; Zhu, Haiying; Andrus, Thomas; Ivanov, Sergei B; Pan, Charlotte; Dolores, Jazel; Dann, Gregory C; Zhou, Michael; Forte, Dominic; Yang, Zihuan; Holte, Sarah; Corey, Lawrence; Zhu, Tuofu

    2013-01-01

    HIV-1 DNA in blood monocytes is considered a viral source of various HIV-1 infected tissue macrophages, which is also known as "Trojan horse" hypothesis. However, whether these DNA can produce virions has been an open question for years, due to the inability of isolating high titer and infectious HIV-1 directly from monocytes. In this study, we demonstrated successful isolation of two strains of M-HIV-1 (1690 M and 1175 M) from two out of four study subjects, together with their in vivo controls, HIV-1 isolated from CD4+ T-cells (T-HIV-1), 1690 T and 1175 T. All M- and T- HIV-1 isolates were detected CCR5-tropic. Both M- HIV-1 exhibited higher levels of replication in monocyte-derived macrophages (MDM) than the two T- HIV-1. Consistent with our previous reports on the subject 1175 with late infection, compartmentalized env C2-V3-C3 sequences were identified between 1175 M and 1175 T. In contrast, 1690 M and 1690 T, which were isolated from subject 1690 with relatively earlier infection, showed homogenous env C2-V3-C3 sequences. However, multiple reverse transcriptase (RT) inhibitor resistance-associated variations were detected in the Gag-Pol region of 1690 M, but not of 1690 T. By further measuring HIV DNA intracellular copy numbers post-MDM infection, 1690 M was found to have significantly higher DNA synthesis efficiency than 1690 T in macrophages, indicating a higher RT activity, which was confirmed by AZT inhibitory assays. These results suggested that the M- and T- HIV-1 are compartmentalized in the two study subjects, respectively. Therefore, we demonstrated that under in vitro conditions, HIV-1 infected human monocytes can productively release live viruses while differentiating into macrophages.

  18. Comparison of caffeine disposition following administration by oral solution (energy drink) and inspired powder (AeroShot) in human subjects.

    Science.gov (United States)

    Laizure, S Casey; Meibohm, Bernd; Nelson, Kembral; Chen, Feng; Hu, Zhe-Yi; Parker, Robert B

    2017-12-01

    To determine the disposition and effects of caffeine after administration using a new dosage form (AeroShot) that delivers caffeine by inspiration of a fine powder into the oral cavity and compare it to an equivalent dose of an oral solution (energy drink) as the reference standard. Healthy human subjects (n = 17) inspired a 100 mg caffeine dose using the AeroShot device or consumed an energy drink on separate study days. Heart rate, blood pressure and subject assessments of effects were measured over an 8-h period. Plasma concentrations of caffeine and its major metabolites were determined by liquid chromatography-mass spectrometry. Pharmacokinetic, cardiovascular and perceived stimulant effects were compared between AeroShot and energy drink phases using a paired t test and standard bioequivalency analysis. Caffeine disposition was similar after caffeine administration by the AeroShot device and energy drink: peak plasma concentration 1790 and 1939 ng ml -1 , and area under the concentration-time curve (AUC) 15 579 and 17 569 ng ml -1 × h, respectively, but they were not bioequivalent: AeroShot AUC of 80.3% (confidence interval 71.2-104.7%) and peak plasma concentration of 86.3% (confidence interval 62.8-102.8%) compared to the energy drink. Female subjects did have a significantly larger AUC compared to males after consumption of the energy drink. The heart rate and blood pressure were not significantly affected by the 100 mg caffeine dose, and there were no consistently perceived stimulant effects by the subjects using visual analogue scales. Inspiration of caffeine as a fine powder using the AeroShot device produces a similar caffeine profile and effects compared to administration of an oral solution (energy drink). © 2017 The British Pharmacological Society.

  19. Human Subjects Protections in Community-Engaged Research: A Research Ethics Framework1

    Science.gov (United States)

    Ross, Lainie Friedman; Loup, Allan; Nelson, Robert M.; Botkin, Jeffrey R.; Kost, Rhonda; Smith, George R.; Gehlert, Sarah

    2010-01-01

    in the 30 years since the belmont Report, the role of the community in research has evolved and has taken on greater moral significance. Today, more and more translational research is being performed with the active engagement of individuals and communities rather than merely upon them. This engagement requires a critical examination of the range of risks that may arise when communities become partners in research. In attempting to provide such an examination, one must distinguish between established communities (groups that have their own organizational structure and leadership and exist regardless of the research) and unstructured groups (groups that may exist because of a shared trait but do not have defined leadership or internal cohesiveness). In order to participate in research as a community, unstructured groups must develop structure either by external means (by partnering with a Community-Based Organization) or by internal means (by empowering the group to organize and establish structure and leadership). When groups participate in research, one must consider risks to well-being due to process and outcomes. These risks may occur to the individual qua individual, but there are also risks that occur to the individual qua member of a group and also risks that occur to the group qua group. There are also risks to agency, both to the individual and the group. A 3-by-3 grid including 3 categories of risks (risks to well-being secondary to process, risks to well-being secondary to outcome and risks to agency) must be evaluated against the 3 distinct agents: individuals as individual participants, individuals as members of a group (both as participants and as non-participants) and to communities as a whole. This new framework for exploring the risks in community-engaged research can help academic researchers and community partners ensure the mutual respect that community-engaged research requires. PMID:20235860

  20. Zinc-α2-glycoprotein is associated with insulin resistance in humans and is regulated by hyperglycemia, hyperinsulinemia, or liraglutide administration: cross-sectional and interventional studies in normal subjects, insulin-resistant subjects, and subjects with newly diagnosed diabetes.

    Science.gov (United States)

    Yang, Mengliu; Liu, Rui; Li, Shu; Luo, Yu; Zhang, Yali; Zhang, Lili; Liu, Dongfang; Wang, Yaxu; Xiong, Zhengai; Boden, Guenther; Chen, Shirong; Li, Ling; Yang, Gangyi

    2013-05-01

    Zinc-α2-glycoprotein (ZAG) has been proposed to play a role in the pathogenesis of insulin resistance. Previous studies in humans and in rodents have produced conflicting results regarding the link between ZAG and insulin resistance. The objective of this study was to examine the relationships between ZAG and insulin resistance in cross-sectional and interventional studies. Serum ZAG (determined with ELISA) was compared with various parameters related to insulin resistance in subjects with normal glucose tolerance, impaired glucose tolerance (IGT), and newly diagnosed type 2 diabetes mellitus (T2DM), and in women with or without polycystic ovary syndrome (PCOS). Euglycemic-hyperinsulinemic clamps were performed in healthy and PCOS women. Real-time RT-PCR and Western blotting were used to assess mRNA and protein expression of ZAG. The effect of a glucagon-like peptide-1 agonist on ZAG was studied in a 12-week liraglutide treatment trial. Circulating ZAG was lower in patients with IGT and newly diagnosed T2DM than in controls. Circulating ZAG correlated positively with HDL cholesterol and adiponectin, and correlated inversely with BMI, waist-to-hip ratio, body fat percentage, triglycerides, fasting blood glucose, fasting insulin, HbA1c, and homeostasis model assessment of insulin resistance (HOMA-IR). On multivariate analysis, ZAG was independently associated with BMI, HOMA-IR, and adiponectin. ZAG mRNA and protein were decreased in adipose tissue of T2DM patients. Moreover, circulating ZAG levels were lower in women with PCOS than in women with high insulin sensitivity. Liraglutide treatment for 12 weeks significantly increased circulating ZAG levels. We conclude that ZAG may be an adipokine associated with insulin resistance.

  1. Pilot Subjective Assessments During an Investigation of Separation Function Allocation Using a Human-In-The-Loop Simulation

    Science.gov (United States)

    Burke, Kelly A.; Wing, David J.; Lewis, Timothy

    2013-01-01

    Two human-in-the-loop simulation experiments were conducted to investigate allocation of separation assurance functions between ground and air and between humans and automation. The experiments modeled a mixed-operations concept in which aircraft receiving ground-based separation services shared the airspace with aircraft providing their own separation service (i.e., self-separation). The two experiments, one pilot-focused and the other controller-focused, addressed selected key issues of mixed operations and modeling an emergence of NextGen technologies and procedures. This paper focuses on the results of the subjective assessments of pilots collected during the pilot-focused human-in-the-loop simulation, specifically workload and situation awareness. Generally the results revealed that across all conditions, pilots' perceived workload was low to medium, with the highest reported levels of workload occurring when the pilots experienced a loss of separation during the scenario. Furthermore, the results from the workload data and situation awareness data were complimentary such that when pilots reported lower levels of workload they also experienced higher levels of situation awareness.

  2. The Affective Core of the Self: A Neuro-Archetypical Perspective on the Foundations of Human (and Animal) Subjectivity.

    Science.gov (United States)

    Alcaro, Antonio; Carta, Stefano; Panksepp, Jaak

    2017-01-01

    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. 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.

  4. 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.

  5. Differential profiles of salivary proteins with affinity to Streptococcus mutans lipoteichoic acid in caries-free and caries-positive human subjects.

    Science.gov (United States)

    Hong, S W; Seo, D-G; Baik, J E; Cho, K; Yun, C-H; Han, S H

    2014-10-01

    Streptococcus mutans is a representative oral pathogen that causes dental caries and pulpal inflammation. Its lipoteichoic acid (Sm.LTA) is known to be an important cell-wall virulence factor involved in bacterial adhesion and induction of inflammation. Since Sm.LTA-binding proteins (Sm.LTA-BPs) might play an important role in pathogenesis and host immunity, we identified the Sm.LTA-BPs in the saliva of caries-free and caries-positive human subjects using Sm.LTA-conjugated beads and LTQ-Orbitrap hybrid Fourier transform mass spectrometry. Sm.LTA was conjugated to N-hydroxysuccinimidyl-Sepharose(®) 4 Fast Flow beads (Sm.LTA-beads). Sm.LTA retained its biological properties during conjugation, as determined by the expression of nitric oxide and interferon-γ-inducible protein 10 in a murine macrophage cell line and activation of Toll-like receptor 2 (TLR2) in CHO/CD14/TLR2 cells. Sm.LTA-BPs were isolated from pooled saliva prepared from 10 caries-free or caries-positive human subjects each, electrophoresed to see their differential expression in each group, and further identified by high-resolution mass spectrometry. A total of 8 and 12 Sm.LTA-BPs were identified with statistical significance in the pooled saliva from the caries-free and caries-positive human subjects, respectively. Unique Sm.LTA-BPs found in caries-free saliva included histone H4, profilin-1 and neutrophil defensin-1, and those in caries-positive saliva included cystatin-C, cystatin-SN, cystatin-S, cystatin-D, lysozyme C, calmodulin-like protein 3 and β-actin. The Sm.LTA-BPs found in both groups were hemoglobin subunits α and β, prolactin-inducible protein, protein S100-A9, and SPLUNC2. Collectively, we identified Sm.LTA-BPs in the saliva of caries-free and caries-positive subjects, which exhibit differential protein profiles. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Watson’s theory of human caring and subjective living experiences: carative factors/caritas processes as a disciplinary guide to the professional nursing practice

    OpenAIRE

    Jean Watson

    2007-01-01

    This article provides an overview of Watson’s theory of Human Caring, the notion of Caritas and human phenomena. Special emphasis is placed upon the theoretical structure of human caring theory referred to as 10 Carative Factors/Caritas Processes and subjective living processes and experiences. These core conceptual aspects of the theory and human living processes are grounded within the philosophical and ethical foundation of the body of my caring theory work. Together they serve as a guide ...

  7. Potential Benefits and Harms of Intermittent Energy Restriction and Intermittent Fasting Amongst Obese, Overweight and Normal Weight Subjects-A Narrative Review of Human and Animal Evidence.

    Science.gov (United States)

    Harvie, Michelle; Howell, Anthony

    2017-01-19

    Intermittent energy restriction (IER) has become popular as a means of weight control amongst people who are overweight and obese, and is also undertaken by normal weight people hoping spells of marked energy restriction will optimise their health. This review summarises randomised comparisons of intermittent and isoenergetic continuous energy restriction for weight loss to manage overweight and obesity. It also summarises the potential beneficial or adverse effects of IER on body composition, adipose stores and metabolic effects from human studies, including studies amongst normal weight subjects and relevant animal experimentation. Six small short term (intermittent energy restriction is equal to continuous restriction for weight loss, with one study reporting greater reductions in body fat, and two studies reporting greater reductions in HOMA insulin resistance in response to IER, with no obvious evidence of harm. Studies amongst normal weight subjects and different animal models highlight the potential beneficial and adverse effects of intermittent compared to continuous energy restriction on ectopic and visceral fat stores, adipocyte size, insulin resistance, and metabolic flexibility. The longer term benefits or harms of IER amongst people who are overweight or obese, and particularly amongst normal weight subjects, is not known and is a priority for further investigation.

  8. Supraclavicular skin temperature as a measure of 18F-FDG uptake by BAT in human subjects.

    Directory of Open Access Journals (Sweden)

    Mariëtte R Boon

    Full Text Available Brown adipose tissue (BAT has emerged as a novel player in energy homeostasis in humans and is considered a potential new target for combating obesity and related diseases. The current 'gold standard' for quantification of BAT volume and activity is cold-induced 18F-FDG uptake in BAT. However, use of this technique is limited by cost and radiation exposure. Given the fact that BAT is a thermogenic tissue, mainly located in the supraclavicular region, the aim of the current study was to investigate whether cold-induced supraclavicular skin temperature and core body temperature may be alternative markers of BAT activation in humans.BAT volume and activity were measured in 24 healthy lean adolescent males (mean age 24.1±0.8 years, using cold-induced 18F-FDG uptake with PET-CT. Core body temperature was measured continuously in the small intestine with use of an ingestible telemetric capsule and skin temperature was measured by eighteen wireless iButtons attached to the skin following ISO-defined locations.Proximal and distal (hand/feet skin temperatures markedly decreased upon cold exposure, while supraclavicular skin temperature significantly increased (35.2±0.1 vs. 35.5±0.1°C, p = 0.001. Furthermore, cold-induced supraclavicular skin temperature positively correlated with both total (R2 = 0.28, P = 0.010 and clavicular BAT volume (R2 = 0.20, P = 0.030 and clavicular SUVmax (R2 = 0.27, P = 0.010, while core body temperature did not.Supraclavicular skin temperature as measured by iButtons may have predictive value for BAT detection in adult humans. This is highly desirable considering the increasing interest in pharmacological interventions to stimulate BAT in human subjects.NTR 2473.

  9. 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.

  10. Supraclavicular skin temperature as a measure of 18F-FDG uptake by BAT in human subjects.

    Science.gov (United States)

    Boon, Mariëtte R; Bakker, Leontine E H; van der Linden, Rianne A D; Pereira Arias-Bouda, Lenka; Smit, Frits; Verberne, Hein J; van Marken Lichtenbelt, Wouter D; Jazet, Ingrid M; Rensen, Patrick C N

    2014-01-01

    Brown adipose tissue (BAT) has emerged as a novel player in energy homeostasis in humans and is considered a potential new target for combating obesity and related diseases. The current 'gold standard' for quantification of BAT volume and activity is cold-induced 18F-FDG uptake in BAT. However, use of this technique is limited by cost and radiation exposure. Given the fact that BAT is a thermogenic tissue, mainly located in the supraclavicular region, the aim of the current study was to investigate whether cold-induced supraclavicular skin temperature and core body temperature may be alternative markers of BAT activation in humans. BAT volume and activity were measured in 24 healthy lean adolescent males (mean age 24.1±0.8 years), using cold-induced 18F-FDG uptake with PET-CT. Core body temperature was measured continuously in the small intestine with use of an ingestible telemetric capsule and skin temperature was measured by eighteen wireless iButtons attached to the skin following ISO-defined locations. Proximal and distal (hand/feet) skin temperatures markedly decreased upon cold exposure, while supraclavicular skin temperature significantly increased (35.2±0.1 vs. 35.5±0.1°C, p = 0.001). Furthermore, cold-induced supraclavicular skin temperature positively correlated with both total (R2 = 0.28, P = 0.010) and clavicular BAT volume (R2 = 0.20, P = 0.030) and clavicular SUVmax (R2 = 0.27, P = 0.010), while core body temperature did not. Supraclavicular skin temperature as measured by iButtons may have predictive value for BAT detection in adult humans. This is highly desirable considering the increasing interest in pharmacological interventions to stimulate BAT in human subjects. NTR 2473.

  11. 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.

  12. 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

    The objectives of this study were to determine volatile organic compound (VOC) emission signatures of nine typical building materials by using proton transfer reaction-mass spectrometry (PTR-MS) and to explore the correlation between the PTR-MS measurements and the measurements of acceptability...... by human subjects. VOC emissions from each material were measured in a 50-l small-scale chamber. Chamber air was sampled by PTR-MS to determine emission signatures. Sorbent tube sampling and TD-GC/MS analysis were also performed to identify the major VOCs emitted and to compare the resulting data...... VOC odor indices was used to represent the emission level measured by PTR-MS....

  13. Frequency-domain photon migration measurements of normal and malignant tissue optical properties in a human subject

    Energy Technology Data Exchange (ETDEWEB)

    Fishkin, J.B.; Coquoz, O.; Anderson, E.R.; Brenner, M.; Tromberg, B.J. [Beckman Laser Institute and Medical Clinic, University of California at Irvine, 1002 Health Sciences Road East, Irvine, California 92612 (United States)]|[EA Photonics, 2515 Fisk Lane, Redondo Beach, California 90278 (United States)

    1997-01-01

    A 1-GHz multifrequency, multiwavelength frequency-domain photon migration instrument is used to measure quantitatively the optical absorption ({mu}{sub a}) and effective optical scattering ({mu}{sub s}{sup {prime}}) of normal and malignant tissues in a human subject. Large ellipsoidal ({approximately}10-cm major axis, {approximately}6-cm minor axes) subcutaneous malignant lesions were compared with adjacent normal sites in the abdomen and back. Absorption coefficients recorded at 674, 811, 849, and 956 nm were used to calculate tissue hemoglobin concentration (oxyhemoglobin, deoxyhemoglobin, and total), water concentration, hemoglobin oxygen saturation, and blood volume fraction {ital in vivo}. Our results show that the normal and the malignant tissues measured in the patient have clearly resolvable optical and physiological property differences that may be broadly useful in identifying and characterizing tumors.{copyright} 1997 Optical Society of America

  14. Effects of itopride hydrochloride on plasma gut-regulatory peptide and stress-related hormone levels in healthy human subjects.

    Science.gov (United States)

    Katagiri, Fumihiko; Shiga, Toru; Inoue, Shin; Sato, Yuhki; Itoh, Hiroki; Takeyama, Masaharu

    2006-01-01

    Itopride hydrochloride (itopride), a gastrokinetic drug, has recently been evaluated for its clinical usefulness in functional dyspepsia. We investigated effects of itopride on human plasma gastrin-, somatostatin-, motilin-, and cholecystokinin (CCK)-like immunoreactive substances (IS); adrenocorticotropic hormone (ACTH)-immunoreactive substances (IS), and cortisol under stress conditions in healthy subjects. A single administration of itopride caused significant increases in plasma somatostatin- and motilin-IS levels compared to placebo. Itopride significantly decreased plasma CCK-IS, and suppressed the ACTH-IS level compared to placebo. We hypothesize that itopride may have an accelerating gastric emptying effect, and a modulatory effect on the hypothalamo-pituitary-adrenal axis and autonomic nervous functions. These effects might be beneficial in stress-related diseases, suggesting that itopride has clinicopharmacological activities.

  15. Plasma hormone levels in human subject during stress loads in microgravity and at readaptation to Earth's gravity.

    Science.gov (United States)

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

    2001-07-01

    In great part of the investigations of endocrine system functions in astronauts during space flights the plasma levels of hormones and metabolites were determined only in resting conditions, usually from one blood sample collection. Such levels reflected the psychical and physical state and new hormonal homeostasis of organism at the time of blood collection, however, the functional capacity of neuroendocrine system to respond to various stress stimuli during space flight remained unknown. The aim of present investigations was to study dynamic changes of hormone levels during the stress and metabolic loads (insulin induced hypoglycemia, physical exercise and oral glucose tolerance test) at the exposure of human subject to microgravity on the space station MIR. The responses of sympatico-adrenomedullary system to these stress and workloads were presented by Kvetnansky et al.

  16. Slowing the rate of loss of mineral wetlands on human dominated landscapes - Diversification of farmers markets to include carbon (Invited)

    Science.gov (United States)

    Creed, I. F.; Badiou, P.; Lobb, D.

    2013-12-01

    Canada is the fourth-largest exporter of agriculture and agri-food products in the world (exports valued at 28B), but instability of agriculture markets can make it difficult for farmers to cope with variability, and new mechanisms are needed for farmers to achieve economic stability. Capitalizing on carbon markets will help farmers achieve environmentally sustainable economic performance. In order to have a viable carbon market, governments and industries need to know what the carbon capital is and what potential there is for growth, and farmers need financial incentives that will not only allow them to conserve existing wetlands but that will also enable them to restore wetlands while making a living. In southern Ontario, farmers' needs to maximize the return on investment on marginal lands have resulted in loss of 70-90% of wetlands, making this region one of the most threatened region in terms of wetland degradation and loss in Canada. Our project establishes the role that mineral wetlands have in the net carbon balance by contributing insight into the potential benefits to carbon management provided by wetland restoration efforts in these highly degraded landscapes. The goal was to establish the magnitude of carbon offsets that could be achieved through wetland conservation (securing existing carbon stocks) and restoration (creating new carbon stocks). The experimental design was to focus on (1) small (0.2-2.0 ha) and (2) isolated (no inflow or outflow) mineral wetlands with the greatest restoration potential that included (3) a range of restoration ages (drained (0 yr), 3 yr, 6 yr, 12 yr, 20 yr, 35 yr, intact marshes) to capture potential changes in rates of carbon sequestration with restoration age of wetland. From each wetland, wetland soil carbon pools samples were collected at four positions: centre of wetland (open-water); emergent vegetation zone; wet meadow zone where flooding often occurs (i.e., high water mark); and upland where flooding rarely

  17. Geospatial cryptography: enabling researchers to access private, spatially referenced, human subjects data for cancer control and prevention.

    Science.gov (United States)

    Jacquez, Geoffrey M; Essex, Aleksander; Curtis, Andrew; Kohler, Betsy; Sherman, Recinda; Emam, Khaled El; Shi, Chen; Kaufmann, Andy; Beale, Linda; Cusick, Thomas; Goldberg, Daniel; Goovaerts, Pierre

    2017-07-01

    As the volume, accuracy and precision of digital geographic information have increased, concerns regarding individual privacy and confidentiality have come to the forefront. Not only do these challenge a basic tenet underlying the advancement of science by posing substantial obstacles to the sharing of data to validate research results, but they are obstacles to conducting certain research projects in the first place. Geospatial cryptography involves the specification, design, implementation and application of cryptographic techniques to address privacy, confidentiality and security concerns for geographically referenced data. This article defines geospatial cryptography and demonstrates its application in cancer control and surveillance. Four use cases are considered: (1) national-level de-duplication among state or province-based cancer registries; (2) sharing of confidential data across cancer registries to support case aggregation across administrative geographies; (3) secure data linkage; and (4) cancer cluster investigation and surveillance. A secure multi-party system for geospatial cryptography is developed. Solutions under geospatial cryptography are presented and computation time is calculated. As services provided by cancer registries to the research community, de-duplication, case aggregation across administrative geographies and secure data linkage are often time-consuming and in some instances precluded by confidentiality and security concerns. Geospatial cryptography provides secure solutions that hold significant promise for addressing these concerns and for accelerating the pace of research with human subjects data residing in our nation's cancer registries. Pursuit of the research directions posed herein conceivably would lead to a geospatially encrypted geographic information system (GEGIS) designed specifically to promote the sharing and spatial analysis of confidential data. Geospatial cryptography holds substantial promise for accelerating the

  18. Peripheral erythrocytes decrease upon specific respiratory challenge with grass pollen allergen in sensitized mice and in human subjects.

    Science.gov (United States)

    Jordakieva, Galateja; Wallmann, Julia; Schmutz, René; Lemell, Patrick; Wegmann, Michael; Nittke, Thomas; Mittlböck, Martina; Fehrenbach, Heinz; Godnic-Cvar, Jasminka; Zieglmayer, René; Jensen-Jarolim, Erika

    2014-01-01

    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). 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. Our data revealed that, besides significant leukocyte dynamics, particularly erythrocytes are involved in acute hypersensitivity reactions to respiratory allergens. A rapid recruitment of erythrocytes to the lungs to compensate

  19. 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

  20. The Frequency of Reporting Ethical Issues in Human Subject Articles Published in Iranian Medical Journals: 2009-2013.

    Science.gov (United States)

    Astaneh, Behrooz; Khani, Parisa

    2017-11-10

    Researchers should strictly consider the participants' rights. They are required to document such protections as an ethical approval of the study proposal, the obtaining "informed consent", the authors' "conflict of interests", and the source of "financial support" in the published articles. The purpose of this study was to assess the frequency of reporting ethical issues in human subject articles published in Iranian medical journals during 2009-2013. In this cross-sectional study, we randomly reviewed 1460 human subject articles published in Iranian medical journals during 2009-2013 in two Persian and English language groups. Data collection was carried out by assessing articles, focusing on the documentation "ethics committee approval", patients' "informed consent", "financial support", "confidentiality", and "conflict of interest". Of 1460 evaluated articles, 443 (30.3%) reported "ethics committee approval", 686 (47.0%) reported "informed consent", 594 (40.7%) reported "financial support", and 341 (23.4%) reported "conflict of interest". 13% of the articles referred to patients' confidentiality in their text. There was a significant association between these ethical documentations and the year of publication. Articles published in English language journals reported "ethics committee approval", "financial support", and "conflict of interest" significantly more than Persian language journals, but the frequency of "informed consent" was similar. Ethical documentation rate in Iranian medical journals is not up to the expected standards of reputable journals which might be related to a lack of awareness and the education of the authors and the journal's editors. Precise reporting of ethical considerations in medical articles by authors are recommended. It is suggested journals and policymakers pay more attention to reporting this issue while providing standard guidelines in this regard.

  1. High water-stressed population estimated by world water resources assessment including human activities under SRES scenarios

    Science.gov (United States)

    Kiguchi, M.; Shen, Y.; Kanae, S.; Oki, T.

    2009-04-01

    In an argument of the reduction and the adaptation for the climate change, the evaluation of the influence by the climate change is important. When we argue in adaptation plan from a damage scale and balance with the cost, it is particularly important. Parry et al (2001) evaluated the risks in shortage of water, malaria, food, the risk of the coast flood by temperature function and clarified the level of critical climate change. According to their evaluation, the population to be affected by the shortage of water suddenly increases in the range where temperature increases from 1.5 to 2.0 degree in 2080s. They showed how much we need to reduce emissions in order to draw-down significantly the number at risk. This evaluation of critical climate change threats and targets of water shortage did not include the water withdrawal divided by water availability. Shen et al (2008a) estimated the water withdrawal of projection of future world water resources according to socio-economic driving factors predicted for scenarios A1b, A2, B1, and B2 of the Special Report on Emission Scenarios (SRES). However, these results were in function of not temperature but time. The assessment of the highly water-stressed population considered the socioeconomic development is necessary for a function of the temperature. Because of it is easy to understand to need to reduce emission. We present a multi-GCM analysis of the global and regional populations lived in highly water-stressed basin for a function of the temperature using the socioeconomic data and the outputs of GCMs. In scenario A2, the population increases gradually with warming. On the other hand, the future projection population in scenario A1b and B1 increase gradually until the temperature anomaly exceeds around from +1 to +1.5 degree. After that the population is almost constant. From Shen et al (2008b), we evaluated the HWSP and its ratio in the world with temperature function for scenarios A1B, A2, and B1 by the index of W

  2. Elevation of Fasting Ghrelin in Healthy Human Subjects Consuming a High-Salt Diet: A Novel Mechanism of Obesity?

    Science.gov (United States)

    Zhang, Yong; Li, Fenxia; Liu, Fu-Qiang; Chu, Chao; Wang, Yang; Wang, Dan; Guo, Tong-Shuai; Wang, Jun-Kui; Guan, Gong-Chang; Ren, Ke-Yu; Mu, Jian-Jun

    2016-05-26

    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 salt diet elevates fasting ghrelin in healthy human subjects, which may be a novel underlying mechanism of obesity.

  3. Objective and subjective quality assessment of geometry compression of reconstructed 3D humans in a 3D virtual room

    Science.gov (United States)

    Mekuria, Rufael; Cesar, Pablo; Doumanis, Ioannis; Frisiello, Antonella

    2015-09-01

    Compression of 3D object based video is relevant for 3D Immersive applications. Nevertheless, the perceptual aspects of the degradation introduced by codecs for meshes and point clouds are not well understood. In this paper we evaluate the subjective and objective degradations introduced by such codecs in a state of art 3D immersive virtual room. In the 3D immersive virtual room, users are captured with multiple cameras, and their surfaces are reconstructed as photorealistic colored/textured 3D meshes or point clouds. To test the perceptual effect of compression and transmission, we render degraded versions with different frame rates in different contexts (near/far) in the scene. A quantitative subjective study with 16 users shows that negligible distortion of decoded surfaces compared to the original reconstructions can be achieved in the 3D virtual room. In addition, a qualitative task based analysis in a full prototype field trial shows increased presence, emotion, user and state recognition of the reconstructed 3D Human representation compared to animated computer avatars.

  4. Search for the presence of six Mycoplasma species in peripheral blood mononuclear cells of subjects seropositive and seronegative for human immunodeficiency virus.

    OpenAIRE

    Kovacic, R; Launay, V; Tuppin, P; Lafeuillade, A; Feuillie, V; Montagnier, L; Grau, O

    1996-01-01

    The prevalence of Mycoplasma fermentans, Mycoplasma pirum, Mycoplasma genitalium, Mycoplasma pneumoniae, Mycoplasma hominis, and Mycoplasma penetrans was investigated by using specific PCR assays with peripheral blood mononuclear cells from subjects infected or not infected with the human immunodeficiency virus (HIV). Only M. fermentans was detected in 5.8% of 154 HIV-seropositive and 11.1% of 90 HIV-seronegative subjects.

  5. The effects of human CYP2C8 genotype and fluvoxamine on the pharmacokinetics of rosiglitazone in healthy subjects

    DEFF Research Database (Denmark)

    Pedersen, Rasmus S; Damkier, Per; Brosen, Kim

    2006-01-01

    AIMS: To determine the effect of CYP2C8 genotype and of fluvoxamine on the pharmacokinetics of rosiglitazone. METHODS: Twenty-three healthy subjects with the following genotypes were included in a two-phase, open-label, cross-over trial: CYP2C8*3/ *3 (n = 3), CYP2C8*1/ *3 (n = 10) and CYP2C8*1/ *1...... (n = 10). In Phase A, the subjects were given 4 mg rosiglitazone as a single oral dose. In Phase B, the subjects were treated with multiple oral doses of 50 mg fluvoxamine maleate for 3 days prior to the single oral administration of 4 mg rosiglitazone. Plasma concentrations of rosiglitazone...... and relative amounts of N-desmethylrosiglitazone were measured in both phases for 24 h after drug administration. RESULTS: The pharmacokinetics of rosiglitazone and N-desmethylrosiglitazone were not significantly different between the CYP2C8 genotypic groups. Fluvoxamine caused a statistically significant (P...

  6. 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

    : seven in two sessions, eight in three sessions, 14 in four sessions, and one in five sessions. Each treatment session was separated by approximately 20 days as per the manufacturer's instructions. The follow-up phase consisted of four observation periods over two years from the last injection. The primary efficacy endpoint was measurement of correction of human immunodeficiency virus highly active antiretroviral therapy induced facial lipoatrophy. Using a multipoint scale of facial divergence, correction was measured as a percentage of correction (diversion correction percentage) from baseline. A secondary endpoint was safety based upon the incidence and type of adverse events experienced. All 30 patients completed the active treatment phase with 100 percent (N=30) undergoing at least two treatments at Days 1 and 20 after entry into study. Seventy-four percent (n=23) underwent a third treatment at Day 60, and 50 percent (n=15) received a fourth treatment at Day 80. A single subject received a fifth treatment at Day 100. There were no serious adverse events and no adverse events noted during the study period. Histology through skin biopsy (2mm punch) was performed on 10 subjects, and all subjects had dermal skin thickness measured with ultrasound. Histology demonstrated a foreign body reaction with multinucleated giant cells with phagocytized lactate crystals. New collagen formation was demonstrated. United States measurements of dermal skin thickness increase ranged from 0.22cm to 0.37cm. All subjects were rated for expected injection events to include erythema, edema, ecchymosis, and hematoma. This dermal collagen stimulator containing glycolic acid and polylactic acid represents a tangible alternative in therapeutic and aesthetic medicine. More than four years of clinical trials have demonstrated that this dermal collagen stimulator helps to improve the exterior quality of the skin while restoring lost facial volumes. Patient satisfaction was high due to its

  7. Oxytocin can impair memory for social and non-social visual objects: a within-subject investigation of oxytocin's effects on human memory.

    Science.gov (United States)

    Herzmann, Grit; Young, Brent; Bird, Christopher W; Curran, Tim

    2012-04-27

    Oxytocin is important to social behavior and emotion regulation in humans. Oxytocin's role derives in part from its effect on memory performance. More specifically, previous research suggests that oxytocin facilitates recognition of social (e.g., faces), but not of non-social stimuli (e.g., words, visual objects). We conducted the first within-subject study to this hypothesis in a double-blind, placebo-controlled design. We administered oxytocin (24IU) and placebo (saline) in two separate sessions and in randomized order to healthy men. To obtain a baseline measure for session-dependent memory effects, which are caused by proactive interference, an additional group of male subjects in each session received placebo unbeknownst to them and the experimenter. After administration, participants studied faces and houses. Exactly one day after each study session, participants were asked to make memory judgments of new and old items. In the first study-test session, participants administered with oxytocin showed reduced recollection of previously studied faces and houses. Oxytocin also interacted with proactive-interference effects. By impeding memory in the first session, it reduced proactive interference in the second. But oxytocin contributed additionally to the memory-reducing effect of proactive interference when administered in the second session. These results demonstrate that oxytocin can have a memory-impairing effect on both social and non-social visual objects. The present study also emphasizes the necessity of including a non-treated, baseline group in within-subject designs when investigating oxytocin's effects on human memory. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. High-antioxidant potatoes: acute in vivo antioxidant source and hypotensive agent in humans after supplementation to hypertensive subjects.

    Science.gov (United States)

    Vinson, Joe A; Demkosky, Cheryil A; Navarre, Duroy A; Smyda, Melissa A

    2012-07-11

    Potatoes have the highest daily per capita consumption of all vegetables in the U.S. diet. Pigmented potatoes contain high concentrations of antioxidants, including phenolic acids, anthocyanins, and carotenoids. In a single-dose study six to eight microwaved potatoes with skins or a comparable amount of refined starch as cooked biscuits was given to eight normal fasting subjects; repeated samples of blood were taken over an 8 h period. Plasma antioxidant capacity was measured by ferric reducing antioxidant power (FRAP). A 24 h urine was taken before and after each regimen. Urine antioxidant capacity due to polyphenol was measured by Folin reagent after correction for nonphenolic interferences with a solid phase (Polyclar) procedure. Potato caused an increase in plasma and urine antioxidant capacity, whereas refined potato starch caused a decrease in both; that is, it acted as a pro-oxidant. In a crossover study 18 hypertensive subjects with an average BMI of 29 were given either six to eight small microwaved purple potatoes twice daily or no potatoes for 4 weeks and then given the other regimen for another 4 weeks. There was no significant effect of potato on fasting plasma glucose, lipids, or HbA1c. There was no significant body weight increase. Diastolic blood pressure significantly decreased 4.3%, a 4 mm reduction. Systolic blood pressure decreased 3.5%, a 5 mm reduction. This blood pressure drop occurred despite the fact that 14 of 18 subjects were taking antihypertensive drugs. This is the first study to investigate the effect of potatoes on blood pressure. Thus, purple potatoes are an effective hypotensive agent and lower the risk of heart disease and stroke in hypertensive subjects without weight gain.

  9. Demonstrating an approach for including pesticide use in life-cycle assessment: Estimating human and ecosystem toxicity of pesticide use in Midwest corn farming

    Science.gov (United States)

    PurposeThis study demonstrates an approach to assess human health and ecotoxicity impacts of pesticide use by including multiple environmental pathways and various exposure routes using the case of corn grown for bio-based fuel or chemical production in US Midwestern states.Metho...

  10. Demonstrating an Approach for Including Pesticide Use in Life Cycle Assessment: Estimating Human and Ecosystem Toxicity of Pesticide Use in Midwest Corn Farming

    Science.gov (United States)

    Purpose This study demonstrates an approach to assess human health and ecotoxicity impacts of pesticide use by including multiple environmental pathways and various exposure routes using the case of corn grown for bio-based fuel or chemical production in US Midwestern states.Meth...

  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

    Science.gov (United States)

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

    2013-01-01

    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: In 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. PMID:24255554

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

    Science.gov (United States)

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

    2013-07-01

    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. In 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. 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. 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.

  13. 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.

  14. The Affective Core of the Self: A Neuro-Archetypical Perspective on the Foundations of Human (and Animal) Subjectivity

    Science.gov (United States)

    Alcaro, Antonio; Carta, Stefano; Panksepp, Jaak

    2017-01-01

    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. PMID:28919868

  15. 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.

  16. Interaction of linear and angular vestibulo-ocular reflexes of human subjects in response to transient motion.

    Science.gov (United States)

    Anastasopoulos, D; Gianna, C C; Bronstein, A M; Gresty, M A

    1996-08-01

    The possibility of synergistic interaction between the canal and otolith components of the horizontal vestibulo-ocular reflex (VOR) was evaluated in human subjects by subtracting the response to pure angular rotation (AVOR) from the response to combined angular and translational motion (ALVOR) and comparing this difference with the VOR to isolated linear motion (LVOR). Assessments were made with target fixation at 60 cm and in darkness. Linear stimuli were acceleration steps attaining 0.25 g in less than 80 ms. To elicit responses to combined translational and angular head movements, the subjects were seated on a Barany chair with the head displaced forwards 40 cm from the axis of rotation. The chair was accelerated at approximately 300 deg/s2 to 127 deg/s peak angular velocity, the tangential acceleration of the head being comparable with that of isolated translation. Estimates of the contribution of smooth pursuit to responses in the light were made from comparisons of isolated pursuit of similar target trajectories. In the dark the slow phase eye movements evoked by combined canal-otolith stimuli were higher in magnitude by approximately a third than the sum of those produced by translation and rotation alone. In the light, the relative target displacement during isolated linear motion was similar to the difference in relative target displacements during eccentric and centred rotation. However, the gain of the translational component of compensatory eye movement during combined translational and angular motion was approximately unity, in contrast to the gain of the response to isolated linear motion, which was approximately a half. Pursuit performance was always poorer than target following during self-motion. The LVOR responses in the light were greater than the sum of the LVOR responses in the dark with pursuit eye movements. We conclude that, in response to transient motion, there is a synergistic enhancement of the translational VOR with concurrent canal

  17. 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

    2015-07-01

    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. 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. 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. 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. NCT00504894. © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions

  18. 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.

  19. B-cell depletion is protective against anti-AAV capsid immune response: a human subject case study

    Directory of Open Access Journals (Sweden)

    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.

  20. Noradrenergic α₁ receptor antagonist treatment attenuates positive subjective effects of cocaine in humans: a randomized trial.

    Directory of Open Access Journals (Sweden)

    Thomas F Newton

    Full Text Available Preclinical research implicates dopaminergic and noradrenergic mechanisms in mediating the reinforcing effects of drugs of abuse, including cocaine. The objective of this study was to evaluate the impact of treatment with the noradrenergic α(1 receptor antagonist doxazosin on the positive subjective effects of cocaine.Thirteen non-treatment seeking, cocaine-dependent volunteers completed this single-site, randomized, placebo-controlled, within-subjects study. In one study phase volunteers received placebo and in the other they received doxazosin, with the order counterbalanced across participants. Study medication was masked by over-encapsulating doxazosin tablets and matched placebo lactose served as the control. Study medication treatment was initiated at 1 mg doxazosin or equivalent number of placebo capsules PO/day and increased every three days by 1 mg. After receiving 4 mg doxazosin or equivalent number of placebo capsules participants received masked doses of 20 and 40 mg cocaine IV in that order with placebo saline randomly interspersed to maintain the blind.Doxazosin treatment was well tolerated and doxazosin alone produced minimal changes in heart rate and blood pressure. During treatment with placebo, cocaine produced dose-dependent increases in subjective effect ratings of "high", "stimulated", "like cocaine", "desire cocaine", "any drug effect", and "likely to use cocaine if had access" (p<.001. Doxazosin treatment significantly attenuated the effects of 20 mg cocaine on ratings of "stimulated", "like cocaine", and "likely to use cocaine if had access" (p<.05. There were trends for doxazosin to reduce ratings of "stimulated", "desire cocaine", and "likely to use cocaine if had access" (p<.10.Medications that block noradrenergic α₁ receptors, such as doxazosin, may be useful as treatments for cocaine dependence, and should be evaluated further.Clinicaltrials.gov NCT01062945.

  1. Effects of lipid-lowering drugs on irisin in human subjects in vivo and in human skeletal muscle cells ex vivo.

    Directory of Open Access Journals (Sweden)

    Ioanna Gouni-Berthold

    Full Text Available The myokine irisin has been proposed to regulate energy homeostasis. Little is known about its association with metabolic parameters and especially with parameters influencing pathways of lipid metabolism. In the context of a clinical trial, an exploratory post hoc analysis has been performed in healthy subjects to determine whether simvastatin and/or ezetimibe influence serum irisin levels. The direct effects of simvastatin on irisin were also examined in primary human skeletal muscle cells (HSKMCs.A randomized, parallel 3-group study was performed in 72 men with mild hypercholesterolemia and without apparent cardiovascular disease. Each group of 24 subjects received a 14-day treatment with either simvastatin 40 mg, ezetimibe 10 mg, or their combination.Baseline irisin concentrations were not significantly correlated with age, BMI, estimated GFR, thyroid parameters, glucose, insulin, lipoproteins, non-cholesterol sterols, adipokines, inflammation markers and various molecular markers of cholesterol metabolism. Circulating irisin increased significantly in simvastatin-treated but not in ezetimibe-treated subjects. The changes were independent of changes in LDL-cholesterol and were not correlated with changes in creatine kinase levels. In HSKMCs, simvastatin significantly increased irisin secretion as well as mRNA expression of its parent peptide hormone FNDC5. Simvastatin significantly induced cellular reactive oxygen species levels along with expression of pro- and anti-oxidative genes such as Nox2, and MnSOD and catalase, respectively. Markers of cellular stress such as atrogin-1 mRNA and Bax protein expression were also induced by simvastatin. Decreased cell viability and increased irisin secretion by simvastatin was reversed by antioxidant mito-TEMPO, implying in part that irisin is secreted as a result of increased mitochondrial oxidative stress and subsequent myocyte damage.Simvastatin increases irisin concentrations in vivo and in vitro

  2. Skin-derived precursors from human subjects with Type 2 diabetes yield dysfunctional vascular smooth muscle cells.

    Science.gov (United States)

    Steinbach, Sarah K; Yau, Terrence M; Ouzounian, Maral; Abdel-Qadir, Husam; Chandy, Mark; Waddell, Thomas K; Husain, Mansoor

    2017-08-01

    Objective : Few methods enable molecular and cellular studies of vascular aging or Type 2 diabetes (T2D). Here, we report a new approach to studying human vascular smooth muscle cell (VSMC) pathophysiology by examining VSMCs differentiated from progenitors found in skin. Approach and results : Skin-derived precursors (SKPs) were cultured from biopsies ( N =164, ∼1 cm 2 ) taken from the edges of surgical incisions of older adults ( N =158; males 72%; mean age 62.7 ± 13 years) undergoing cardiothoracic surgery, and differentiated into VSMCs at high efficiency (>80% yield). The number of SKPs isolated from subjects with T2D was ∼50% lower than those without T2D (cells/g: 0.18 ± 0.03, N =58 versus 0.40 ± 0.05, N =100, P <0.05). Importantly, SKP-derived VSMCs from subjects with T2D had higher Fluo-5F-determined baseline cytosolic Ca 2+ concentrations (AU: 1,968 ± 160, N =7 versus 1,386 ± 170, N =13, P <0.05), and a trend toward greater Ca 2+ cycling responses to norepinephrine (NE) (AUC: 177,207 ± 24,669, N =7 versus 101,537 ± 15,881, N =20, P <0.08) despite a reduced frequency of Ca 2+ cycling (events s -1 cell -1 : 0.011 ± 0.004, N =8 versus 0.021 ± 0.003, N =19, P <0.05) than those without T2D. SKP-derived VSMCs from subjects with T2D also manifest enhanced sensitivity to phenylephrine (PE) in an impedance-based assay (EC 50 nM: 72.3 ± 63.6, N =5 versus 3,684 ± 3,122, N =9, P <0.05), and impaired wound closure in vitro (% closure: 21.9 ± 3.6, N =4 versus 67.0 ± 10.3, N =4, P <0.05). Compared with aortic- and saphenous vein-derived primary VSMCs, SKP-derived VSMCs are functionally distinct, but mirror defects of T2D also exhibited by primary VSMCs. Skin biopsies from older adults yield sufficient SKPs to differentiate VSMCs, which reveal abnormal phenotypes of T2D that survive differentiation and persist even after long-term normoglycemic culture. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  3. "More human than human": instrumentalización y sublevación de los sujetos artificiales / «More Human than Human»: Instrumentalization and Uprising of Artificial Subjects

    Directory of Open Access Journals (Sweden)

    Jimena Escudero Pérez

    2016-08-01

    Full Text Available La vida sintética, orgánica y mixta creada artificialmente tiene siempre como fin satisfacer algún tipo de necesidad de su creador, el ser humano. La inteligencia de estos engendros, así como su interacción con el medio, puede ser muy variable proporcionándoles distintos grados de conciencia. Desde los robots de limpieza hasta los clones, pasando por cíborgs y replicantes o por superordenadores que toman el mando, el inventario de sujetos artificiales autoconscientes en el cine de ciencia ficción es prácticamente inagotable. En el presente artículo abordaremos algunas de sus representaciones más icónicas e influyentes para el género, así como el impacto que estas han tenido sobre nuestra concepción de la propia naturaleza humana.Palabras clave: artificial, sujeto, identidad, instrumentalización, robot, clon, cíborg, consciencia, humanidad, creación.AbstractArtificially created life, whether it is synthetic, organic or mixed, always has the purpose of fulfilling some need of its creator, human kind. The intelligence of these beings as well as their interaction with the environment can vary widely, providing them with different degrees of consciousness. From maintenance robots to clones, through cyborgs and replicants or supercomputers that take control, the inventory of self-conscious artificial subjects in science fiction is almost endless. In this article we will take a look at some of the most iconic and influential manifestations of artificial identities in Sci Fi and see how they have moulded our perception of human nature itself.Keywords: artificial, subject, identity, instrumentalization, robot, clone, cyborg, consciousness, humanity, creation.

  4. Sensitivity of [(11)C]ORM-13070 to increased extracellular noradrenaline in the CNS - a PET study in human subjects.

    Science.gov (United States)

    Lehto, Jussi; Johansson, Jarkko; Vuorilehto, Lauri; Luoto, Pauliina; Arponen, Eveliina; Scheinin, Harry; Rouru, Juha; Scheinin, Mika

    2015-11-01

    No validated methods have been available for studying brain noradrenergic neurotransmission in vivo in humans. Positron emission tomography (PET) radiotracers are widely used in clinical drug development targeted to brain receptors and can also in some cases be employed to monitor extracellular (synaptic) neurotransmitter concentrations. The objective of this study is to test the sensitivity of [(11)C]ORM-13070 uptake to increased concentrations of extracellular (synaptic) noradrenaline in the human brain. Eight subjects underwent a control PET scan with [(11)C]ORM-13070, a subtype-selective α2C-adrenoceptor antagonist radioligand, and two PET scans after two different noradrenaline challenges, i.e. during ketamine infusion and after a dose of atomoxetine combined with cold stimulation. Tracer uptake in the caudate nucleus and putamen was described with AUC values in scan time windows of 10-20 and 5-30 min post injection and quantified with the ratio method. Voxel-based analysis was performed with average bound per free (B/F) ratio images. Both noradrenaline challenges were consistently associated with 10-20 % (p < 0.05) reductions in tracer uptake in the dorsal striatum, as determined with region-of-interest-based analysis. Voxel-based analysis revealed significant reductions in B/F ratios in the dorsal striatum, in the brain stem and in several cortical areas. Reductions of 24 and 23 % were detected in the peak putamen clusters with ketamine and atomoxetine + cold, respectively. Direct experimental support was gained for the suitability of [(11)C]ORM-13070 for imaging of brain noradrenergic neurotransmission.

  5. 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.

  6. Sweet potato (Ipomoea batatas L.) leaves suppressed oxidation of low density lipoprotein (LDL) in vitro and in human subjects.

    Science.gov (United States)

    Nagai, Miu; Tani, Mariko; Kishimoto, Yoshimi; Iizuka, Maki; Saita, Emi; Toyozaki, Miku; Kamiya, Tomoyasu; Ikeguchi, Motoya; Kondo, Kazuo

    2011-05-01

    Sweet potato (Ipomoea batatas L.) leaves are consumed as vegetables around the world, especially in Southeast Asia. The aim of this study was to investigate the inhibitory effect of sweet potato leaves on low-density lipoprotein oxidation in vitro and in human subjects. We compared the antioxidant activity of 8 kinds of sweet potato leaves. Every sweet potato leaf had high radical scavenging activity and prolonged a lag time for starting low-density lipoprotein oxidation in vitro. We found that sweet potato leaves contained abundant polyphenol compounds and the radical scavenging activity and prolongation rate of lag time were highly correlated with total polyphenol content. We also confirmed that thiobarbituric acid reactive substances production was increased in endothelial cell-mediated low-density lipoprotein oxidation, which was decreased by treatment with sweet potato leaves. We further measured the low-density lipoprotein oxidizability in 13 healthy volunteers after their intake of 18 g of "Suioh", raw sweet potato leaves. "Suioh" prolonged a lag time for starting low-density lipoprotein oxidation and decreased low-density lipoprotein mobility. These results suggest that sweet potato leaves have antioxidant activity leading to the suppression of low-density lipoprotein oxidation.

  7. 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.

  8. 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.

  9. Cue-dependent memory-based smooth-pursuit in normal human subjects: importance of extra-retinal mechanisms for initial pursuit.

    Science.gov (United States)

    Ito, Norie; Barnes, Graham R; Fukushima, Junko; Fukushima, Kikuro; Warabi, Tateo

    2013-08-01

    Using a cue-dependent memory-based smooth-pursuit task previously applied to monkeys, we examined the effects of visual motion-memory on smooth-pursuit eye movements in normal human subjects and compared the results with those of the trained monkeys. These results were also compared with those during simple ramp-pursuit that did not require visual motion-memory. During memory-based pursuit, all subjects exhibited virtually no errors in either pursuit-direction or go/no-go selection. Tracking eye movements of humans and monkeys were similar in the two tasks, but tracking eye movements were different between the two tasks; latencies of the pursuit and corrective saccades were prolonged, initial pursuit eye velocity and acceleration were lower, peak velocities were lower, and time to reach peak velocities lengthened during memory-based pursuit. These characteristics were similar to anticipatory pursuit initiated by extra-retinal components during the initial extinction task of Barnes and Collins (J Neurophysiol 100:1135-1146, 2008b). We suggest that the differences between the two tasks reflect differences between the contribution of extra-retinal and retinal components. This interpretation is supported by two further studies: (1) during popping out of the correct spot to enhance retinal image-motion inputs during memory-based pursuit, pursuit eye velocities approached those during simple ramp-pursuit, and (2) during initial blanking of spot motion during memory-based pursuit, pursuit components appeared in the correct direction. Our results showed the importance of extra-retinal mechanisms for initial pursuit during memory-based pursuit, which include priming effects and extra-retinal drive components. Comparison with monkey studies on neuronal responses and model analysis suggested possible pathways for the extra-retinal mechanisms.

  10. How Are Gender Equality and Human Rights Interventions Included in Sexual and Reproductive Health Programmes and Policies: A Systematic Review of Existing Research Foci and Gaps

    Science.gov (United States)

    Khosla, Rajat; Krishnan, Suneeta; George, Asha; Gruskin, Sofia; Amin, Avni

    2016-01-01

    The importance of promoting gender equality and human rights in sexual and reproductive health (SRH) programmes and policies has been affirmed in numerous international and regional agreements, most recently the 2030 Agenda for Sustainable Development. Given the critical role of research to determine what works, we aimed to identify research gaps as part of a broader priority setting exercise on integrating gender equality and human rights approaches in SRH programmes and policies. A systematic literature review of reviews was conducted to examine the question: what do we know about how research in the context of SRH programmes and policies has addressed gender equality and human rights and what are the current gaps in research. We searched three databases for reviews that addressed the research question, were published between 1994–2014, and met methodological standards for systematic reviews, qualitative meta-syntheses and other reviews of relevance to the research question. Additional grey literature was identified based on expert input. Articles were appraised by the primary author and examined by an expert panel. An abstraction and thematic analysis process was used to synthesize findings. Of the 3,073 abstracts identified, 56 articles were reviewed in full and 23 were included along with 10 from the grey literature. The majority focused on interventions addressing gender inequalities; very few reviews explicitly included human rights based interventions. Across both topics, weak study designs and use of intermediate outcome measures limited evidence quality. Further, there was limited evidence on interventions that addressed marginalized groups. Better quality studies, longer-term indicators, and measurement of unintended consequences are needed to better understand the impact of these types of interventions on SRH outcomes. Further efforts are needed to cover research on gender equality and human rights issues as they pertain to a broader set of SRH topics

  11. How Are Gender Equality and Human Rights Interventions Included in Sexual and Reproductive Health Programmes and Policies: A Systematic Review of Existing Research Foci and Gaps.

    Science.gov (United States)

    Hartmann, Miriam; Khosla, Rajat; Krishnan, Suneeta; George, Asha; Gruskin, Sofia; Amin, Avni

    2016-01-01

    The importance of promoting gender equality and human rights in sexual and reproductive health (SRH) programmes and policies has been affirmed in numerous international and regional agreements, most recently the 2030 Agenda for Sustainable Development. Given the critical role of research to determine what works, we aimed to identify research gaps as part of a broader priority setting exercise on integrating gender equality and human rights approaches in SRH programmes and policies. A systematic literature review of reviews was conducted to examine the question: what do we know about how research in the context of SRH programmes and policies has addressed gender equality and human rights and what are the current gaps in research. We searched three databases for reviews that addressed the research question, were published between 1994-2014, and met methodological standards for systematic reviews, qualitative meta-syntheses and other reviews of relevance to the research question. Additional grey literature was identified based on expert input. Articles were appraised by the primary author and examined by an expert panel. An abstraction and thematic analysis process was used to synthesize findings. Of the 3,073 abstracts identified, 56 articles were reviewed in full and 23 were included along with 10 from the grey literature. The majority focused on interventions addressing gender inequalities; very few reviews explicitly included human rights based interventions. Across both topics, weak study designs and use of intermediate outcome measures limited evidence quality. Further, there was limited evidence on interventions that addressed marginalized groups. Better quality studies, longer-term indicators, and measurement of unintended consequences are needed to better understand the impact of these types of interventions on SRH outcomes. Further efforts are needed to cover research on gender equality and human rights issues as they pertain to a broader set of SRH topics

  12. Immune control of Chlamydial growth in the human epithelial cell line RT4 involves multiple mechanisms that include nitric oxide induction, tryptophan catabolism and iron deprivation.

    Science.gov (United States)

    Igietseme, J U; Ananaba, G A; Candal, D H; Lyn, D; Black, C M

    1998-01-01

    The antimicrobial activity of T cell-derived cytokines, especially interferon (IFN)-gamma, against intracellular pathogens, such as Chlamydia trachomatis, involves the induction of 3 major biochemical processes: tryptophan catabolism, nitric oxide (NO) induction and intracellular iron (Fe) deprivation. Since the epithelial cell is the natural target of chlamydial infection, the presence of these antimicrobial systems in the cell would suggest that they may be involved in T cell control of intracellular multiplication of Chlamydia. However, the controversy over whether these 3 antimicrobial processes are present in both mice and humans has precluded the assessment of the relative contribution of each of the 3 mechanisms to chlamydial inhibition in the same epithelial cell from either mice or humans. In the present study, we identified a Chlamydia-susceptible human epithelial cell line, RT4, that possesses the 3 antimicrobial systems, and we examined the role of nitric oxide (NO) induction, and deprivation of tryptophan or Fe in cytokine-induced inhibition of chlamydiae. It was found that the 3 antimicrobial systems contributed to cytokine-mediated inhibition of the intracellular growth of Chlamydia. NO induction accounted for approximately 20% of the growth inhibition; tryptophan catabolism contributed approximately 30%; iron deprivation was least effective; but the combination of the 3 systems accounted for greater than 60% of the inhibition observed. These results indicate that immune control of chlamydial growth in human epithelial cells may involve multiple mechanisms that include NO induction, tryptophan catabolism and Fe deprivation.

  13. Effect of Artocarpus heterophyllus and Asteracanthus longifolia on glucose tolerance in normal human subjects and in maturity-onset diabetic patients.

    Science.gov (United States)

    Fernando, M R; Wickramasinghe, N; Thabrew, M I; Ariyananda, P L; Karunanayake, E H

    1991-03-01

    Investigations were carried out to evaluate the effects of hot-water extracts of Artocarpus heterophyllus leaves and Asteracanthus longifolia whole plant material on the glucose tolerance of normal human subjects and maturity-onset diabetic patients. The extracts of both Artocarpus heterophyllus and Asteracanthus longifolia significantly improved glucose tolerance in the normal subjects and the diabetic patients when investigated at oral doses equivalent to 20 g/kg of starting material.

  14. Pronounced between‐subject and circadian variability in thymidylate synthase and dihydropyrimidine dehydrogenase enzyme activity in human volunteers

    Science.gov (United States)

    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.

    2016-01-01

    Abstract 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 human volunteers. Methods The BSVs in DPD activity (n = 20) in peripheral blood mononuclear cells (PBMCs) and in plasma, measured by means of the dihydrouracil (DHU) and uracil (U) plasma levels and DHU : U ratio (n = 40), and TS activity in PBMCs (n = 19), were examined. Samples were collected every 4 h throughout 1 day for assessment of circadian rhythmicity in DPD and TS activity in PBMCs (n = 12) and DHU : U plasma ratios (n = 23). In addition, the effects of genetic polymorphisms and gene expression on DPD and TS activity were explored. Results Population mean (± standard deviation) DPD activity in PBMCs and DHU : U plasma ratio were 9.2 (±2.1) nmol mg−1 h−1 and 10.6 (±2.4), respectively. Individual TS activity in PBMCs ranged from 0.024 nmol mg−1 h−1 to 0.596 nmol mg−1 h−1. Circadian rhythmicity was demonstrated for all phenotype markers. Between 00:30 h and 02:00 h, DPD activity in PBMCs peaked, while the DHU : U plasma ratio and TS activity in PBMCs showed trough activity. Peak‐to‐trough ratios for DPD and TS activity in PBMCs were 1.69 and 1.62, respectively. For the DHU : U plasma ratio, the peak‐to‐trough ratio was 1.43. Conclusions BSV and circadian variability in DPD and TS activity were demonstrated. Circadian rhythmicity in DPD might be tissue dependent. The results suggested an influence of circadian rhythms on phenotype‐guided fluoropyrimidine dosing and supported implications for chronotherapy with high‐dose fluoropyrimidine administration during the night. PMID:27161955

  15. Pronounced between-subject and circadian variability in thymidylate synthase and dihydropyrimidine dehydrogenase enzyme activity in human volunteers.

    Science.gov (United States)

    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

    2016-09-01

    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 human volunteers. The BSVs in DPD activity (n = 20) in peripheral blood mononuclear cells (PBMCs) and in plasma, measured by means of the dihydrouracil (DHU) and uracil (U) plasma levels and DHU : U ratio (n = 40), and TS activity in PBMCs (n = 19), were examined. Samples were collected every 4 h throughout 1 day for assessment of circadian rhythmicity in DPD and TS activity in PBMCs (n = 12) and DHU : U plasma ratios (n = 23). In addition, the effects of genetic polymorphisms and gene expression on DPD and TS activity were explored. Population mean (± standard deviation) DPD activity in PBMCs and DHU : U plasma ratio were 9.2 (±2.1) nmol mg(-1) h(-1) and 10.6 (±2.4), respectively. Individual TS activity in PBMCs ranged from 0.024 nmol mg(-1) h(-1) to 0.596 nmol mg(-1) h(-1) . Circadian rhythmicity was demonstrated for all phenotype markers. Between 00:30 h and 02:00 h, DPD activity in PBMCs peaked, while the DHU : U plasma ratio and TS activity in PBMCs showed trough activity. Peak-to-trough ratios for DPD and TS activity in PBMCs were 1.69 and 1.62, respectively. For the DHU : U plasma ratio, the peak-to-trough ratio was 1.43. BSV and circadian variability in DPD and TS activity were demonstrated. Circadian rhythmicity in DPD might be tissue dependent. The results suggested an influence of circadian rhythms on phenotype-guided fluoropyrimidine dosing and supported implications for chronotherapy with high-dose fluoropyrimidine administration during the night. © 2016 The British Pharmacological Society.

  16. 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.

  17. Emended description of Campylobacter sputorum and revision of its infrasubspecific (biovar) divisions, including C-sputorum biovar paraureolyticus, a urease-producing variant from cattle and humans

    DEFF Research Database (Denmark)

    On, S.L.W.; Atabay, H.I.; Corry, J.E.L.

    1998-01-01

    A polyphasic taxonomic study of 15 bovine and human strains assigned to the catalase-negative, urease-positive campylobacter (CNUPC) group identified these bacteria as a novel, ureolytic biovar of Campylobacter sputorum for which we propose the name C. sputorum bv. paraureolyticus: suitable...... should be revised to include by. sputorum for catalase-negative strains; by. fecalis for catalase-positive strains; and by. paraureolyticus for urease-positive strains. Strains classified previously as by. bubulus should be reclassified as by. sputorum. The species description of C. sputorum is revised...

  18. Using subject-specific three-dimensional (3D) anthropometry data in digital human modelling: case study in hand motion simulation.

    Science.gov (United States)

    Tsao, Liuxing; Ma, Liang

    2016-11-01

    Digital human modelling enables ergonomists and designers to consider ergonomic concerns and design alternatives in a timely and cost-efficient manner in the early stages of design. However, the reliability of the simulation could be limited due to the percentile-based approach used in constructing the digital human model. To enhance the accuracy of the size and shape of the models, we proposed a framework to generate digital human models using three-dimensional (3D) anthropometric data. The 3D scan data from specific subjects' hands were segmented based on the estimated centres of rotation. The segments were then driven in forward kinematics to perform several functional postures. The constructed hand models were then verified, thereby validating the feasibility of the framework. The proposed framework helps generate accurate subject-specific digital human models, which can be utilised to guide product design and workspace arrangement. Practitioner Summary: Subject-specific digital human models can be constructed under the proposed framework based on three-dimensional (3D) anthropometry. This approach enables more reliable digital human simulation to guide product design and workspace arrangement.

  19. Identification of direct and indirect social network effects in the pathophysiology of insulin resistance in obese human subjects.

    Science.gov (United States)

    Henning, Christian H C A; Zarnekow, Nana; Hedtrich, Johannes; Stark, Sascha; Türk, Kathrin; Laudes, Matthias

    2014-01-01

    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. We used nonparametric and parametric regression models to analyse whether individual BMI and HOMA-IR are determined by social network characteristics. 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. We found significant treatment effects for ALTERs frequent dieting (pnetwork 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. 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.

  20. Influence of cognitive strategies on the pattern of cortical activation during mental subtraction. A functional imaging study in human subjects.

    Science.gov (United States)

    Burbaud, P; Camus, O; Guehl, D; Bioulac, B; Caillé, J; Allard, M

    2000-06-16

    Functional magnetic resonance imaging (fMRI) at 1.5 T was used to investigate the influence of cognitive strategies on cortical activation during mental calculation. Twenty-nine right-handed subjects performed a serial subtraction of prime numbers. Even though a common corpus of brain areas was activated during this mental calculation, differences appeared between subjects in function of their spontaneous cognitive strategy. In subjects using a so called verbal strategy (n=15), the main activation was located in the whole left dorsolateral frontal cortex with a little activation of the inferior parietal cortex. In subjects using a so called visual strategy (n=14), a bilateral activation in the prefrontal cortex and a high activation in the left inferior parietal cortex were observed. These results demonstrate that numbers are processed through a distributed network of cortical areas, the lateralization of which is clearly influenced by subject strategy.

  1. Multiple-Dose Pharmacokinetic Behavior of Elvucitabine, a Nucleoside Reverse Transcriptase Inhibitor, Administered over 21 Days with Lopinavir-Ritonavir in Human Immunodeficiency Virus Type 1-Infected Subjects

    NARCIS (Netherlands)

    Colucci, Philippe; Pottage, John C.; Robison, Heather; Turgeon, Jacques; Schuermann, Dirk; Hoepelman, I. M.; Ducharme, Murray P.

    The purpose of this study was to describe the plasma pharmacokinetics (PK) of elvucitabine at different doses when administered daily or every other day for 21 days with lopinavir-ritonavir ( Kaletra) in human immunodeficiency virus (HIV)-infected subjects. Three different dosing regimens of

  2. Subjective sleepiness correlates negatively with global alpha (8–12 Hz) and positively with central frontal theta (4–8 Hz) frequencies in the human resting awake electroencephalogram

    NARCIS (Netherlands)

    Strijkstra, Arjen M.; Beersma, Domien G.M.; Drayer, Berdine; Halbesma, Nynke; Daan, Serge

    2003-01-01

    Subjective sleepiness is part of the system controlling the decision to go to sleep in humans. Extended periods of waking lead to increased sleepiness, as well as to changes in cortical electroencephalogram (EEG) during waking. We investigated the association of sleepiness and awake EEG spectra

  3. Subjective sleepiness correlates negatively with global alpha (8-12 Hz) and positively with central frontal theta (4-8 Hz) frequencies in the human resting awake electroencephalogram

    NARCIS (Netherlands)

    Strijkstra, AM; Beersma, DGM; Drayer, B; Halbesma, N; Daan, S

    2003-01-01

    Subjective sleepiness is part of the system controlling the decision to go to sleep in humans. Extended periods of waking lead to increased sleepiness, as well as to changes in cortical electroencephalogram (EEG) during waking. We investigated the association of sleepiness and awake EEG spectra

  4. 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

  5. Chronic inhibition of the respiratory chain in human fibroblast cultures: differential responses related to subject chronological and biological age.

    Science.gov (United States)

    Dekker, Pim; van Baalen, Laurens M; Dirks, Roeland W; Slagboom, P Eline; van Heemst, Diana; Tanke, Hans J; Westendorp, Rudi G J; Maier, Andrea B

    2012-05-01

    Respiratory chain function becomes less efficient with age resulting in increased levels of damaging reactive oxygen species. We compared rotenone-exposed fibroblast strains from young and old subjects and from offspring of nonagenarian siblings and the partners of the offspring. Rotenone increased reactive oxygen species levels, inhibited growth rate, and increased telomere shortening (all p < .05). Non-stressed strains from young subjects showed lower reactive oxygen species levels (p = .031) and higher growth rates (p = .002) than strains from old subjects. Stressed strains from young subjects showed smaller increases in reactive oxygen species levels (p = .014) and larger decreases in growth rate (p < .001) than strains from old subjects. Telomere-shortening rates were not different between groups. Stress-induced decreases in growth rate were larger in strains from offspring than from partners (p = .05). Strains from young and old subjects are differentially affected by chronic inhibition of the respiratory chain. Changed growth rates in strains from offspring resemble those from strains from young subjects.

  6. Exploration of Human Salivary Microbiomes--Insights into the Novel Characteristics of Microbial Community Structure in Caries and Caries-Free Subjects.

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    Jianye Zhou

    Full Text Available Recently, high-throughput sequencing has improved the understanding of the microbiological etiology of caries, but the characteristics of the microbial community structure in the human oral cavity with and without caries are not completely clear. To better understand these characteristics, Illumina MiSeq high-throughput sequencing was utilized to analyze 20 salivary samples (10 caries-free and 10 caries from subjects from the same town in Dongxiang, Gansu, China. A total of 5,113 OTUs (Operational Taxonomic Units, 97% cutoff were characterized in all of the salivary samples obtained from the 20 subjects. A comparison of the two groups revealed that (i the predominant phyla were constant between the two groups; (ii the relative abundance of the genera Veillonella, Bifidobacterium, Selenomonas, Olsenella, Parascardovia, Scardovia, Chryseobacterium, Terrimonas, Burkholderia and Sporobacter was significantly higher in the group with caries (P < 0.05; and (iii four genera with low relative abundance (< 0.01% on average, including two characteristic genera in caries (Chryseobacterium and Scardovia, significantly influenced the microbial community structure at the genus and OTU levels. Moreover, via co-occurrence and principal component analyses, the co-prevalence of the pathogenic genera was detected in the caries samples, but in the caries-free samples, the function of clustered genera was more random. This result suggests that a synergistic effect may be influencing the assembly of the caries microbial community, whereas competition may play a more dominant role in governing the microbial community in the caries-free group. Our findings regarding the characteristics of the microbial communities of the groups with and without caries might improve the understanding of the microbiological etiology of caries and might improve the prevention and cure of caries in the future.

  7. HIV-1 envelope glycoprotein resistance to monoclonal antibody 2G12 is subject-specific and context-dependent in macaques and humans.

    Science.gov (United States)

    Malherbe, Delphine C; Sanders, Rogier W; van Gils, Marit J; Park, Byung; Gomes, Michelle M; Schuitemaker, Hanneke; Barnett, Susan; Haigwood, Nancy L

    2013-01-01

    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.

  8. 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.

  9. 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.

  10. Impact of bariatric surgery on apolipoprotein C-III levels and lipoprotein distribution in obese human subjects.

    Science.gov (United States)

    Maraninchi, Marie; Padilla, Nadège; Béliard, Sophie; Berthet, Bruno; Nogueira, Juan-Patricio; Dupont-Roussel, Jeanine; Mancini, Julien; Bégu-Le Corroller, Audrey; Dubois, Noémie; Grangeot, Rachel; Mattei, Catherine; Monclar, Marion; Calabrese, Anastasia; Guérin, Carole; Desmarchelier, Charles; Nicolay, Alain; Xiao, Changting; Borel, Patrick; Lewis, Gary F; Valéro, René

    Elevated apolipoprotein C-III (apoC-III) has been postulated to contribute to the atherogenic dyslipidemia seen in obesity and insulin-resistant states, mainly by impairing plasma triglyceride-rich lipoprotein (TRL) metabolism. Bariatric surgery is associated with improvements of several obesity-associated metabolic abnormalities, including a reduction in plasma triglycerides (TGs) and an increase in plasma high-density lipoprotein cholesterol (HDL-C). We investigated the specific effect of bariatric surgery on apoC-III concentrations in plasma, non-HDL, and HDL fractions in relation to lipid profile parameters evolution. A total of 132 obese subjects undergoing bariatric surgery, gastric bypass (n = 61) or sleeve gastrectomy (n = 71), were studied 1 month before surgery and 6 and 12 months after surgery. Plasma apoC-III, non-HDL-apoC-III, and HDL-apoC-III concentrations were markedly reduced after surgery and strongly associated with reduction in plasma TG. This decrease was accompanied by a redistribution of apoC-III from TRL to HDL fractions. In multivariate analysis, plasma apoC-III was the strongest predictor of TG reduction after surgery, and the increase of HDL-C was positively associated with plasma adiponectin and negatively with body mass index. Marked reduction of apoC-III and changes in its distribution between TRL and HDL consistent with a better lipid profile are achieved in obese patients after bariatric surgery. These apoC-III beneficial modifications may have implications in dyslipidemia improvement and contribute to cardiovascular risk reduction after surgery. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  11. 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

  12. 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

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

    OpenAIRE

    Brett eWagner Mackenzie; David William Waite; Michael W Taylor

    2015-01-01

    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 extracti...

  14. 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...

  15. MAGI-1 expression is decreased in several types of human T-cell leukemia cell lines, including adult T-cell leukemia.

    Science.gov (United States)

    Kozakai, Takashi; Takahashi, Masahiko; Higuchi, Masaya; Hara, Toshifumi; Saito, Kousuke; Tanaka, Yuetsu; Masuko, Masayoshi; Takizawa, Jun; Sone, Hirohito; Fujii, Masahiro

    2018-03-01

    Membrane-associated guanylate kinase with inverted orientation protein 1 (MAGI-1) is a cytoplasmic scaffold protein that interacts with various signaling molecules; it negatively controls the cell growth of various types of cells and positively controls cell-cell interaction. In T cells, MAGI-1 has been shown to inhibit Akt activity through its interaction with PTEN and MEK1. In this study we found that MAGI-1 expression is decreased in multiple (9 out of 15) human T-cell leukemia cell lines, including adult T-cell leukemia (ATL), T-cell acute lymphoblastic leukemia and chronic T-cell lymphocytic leukemia. The overexpression of MAGI-1 protein in a MAGI-1-low ATL cell line reduced cellular growth. While the overexpression of MAGI-1 protein in a MAGI-1-low ATL cell line reduced the Akt and MEK activities, the knockdown of MAGI-1 in a MAGI-1-high ATL cell line augmented the Akt and MEK activities. Collectively, the findings of the present study suggest that the decreased expression of MAGI-1 in human T cells contributes to the development of several types of T-cell leukemia, partly through the stimulation of the Akt and MEK pathways.

  16. Lower Leg Injury Reference Values and Risk Curves from Survival Analysis for Male and Female Dummies: Meta-analysis of Postmortem Human Subject Tests.

    Science.gov (United States)

    Yoganandan, Narayan; Arun, Mike W J; Pintar, Frank A; Banerjee, Anjishnu

    2015-01-01

    Derive lower leg injury risk functions using survival analysis and determine injury reference values (IRV) applicable to human mid-size male and small-size female anthropometries by conducting a meta-analysis of experimental data from different studies under axial impact loading to the foot-ankle-leg complex. Specimen-specific dynamic peak force, age, total body mass, and injury data were obtained from tests conducted by applying the external load to the dorsal surface of the foot of postmortem human subject (PMHS) foot-ankle-leg preparations. Calcaneus and/or tibia injuries, alone or in combination and with/without involvement of adjacent articular complexes, were included in the injury group. Injury and noninjury tests were included. Maximum axial loads recorded by a load cell attached to the proximal end of the preparation were used. Data were analyzed by treating force as the primary variable. Age was considered as the covariate. Data were censored based on the number of tests conducted on each specimen and whether it remained intact or sustained injury; that is, right, left, and interval censoring. The best fits from different distributions were based on the Akaike information criterion; mean and plus and minus 95% confidence intervals were obtained; and normalized confidence interval sizes (quality indices) were determined at 5, 10, 25, and 50% risk levels. The normalization was based on the mean curve. Using human-equivalent age as 45 years, data were normalized and risk curves were developed for the 50th and 5th percentile human size of the dummies. Out of the available 114 tests (76 fracture and 38 no injury) from 5 groups of experiments, survival analysis was carried out using 3 groups consisting of 62 tests (35 fracture and 27 no injury). Peak forces associated with 4 specific risk levels at 25, 45, and 65 years of age are given along with probability curves (mean and plus and minus 95% confidence intervals) for PMHS and normalized data applicable to

  17. An investigation to determine if a single validated density-elasticity relationship can be used for subject specific finite element analyses of human long bones.

    Science.gov (United States)

    Eberle, Sebastian; Göttlinger, Michael; Augat, Peter

    2013-07-01

    Subject-specific FE-models of human long bones have to predict mechanical parameters with sufficient accuracy to be applicable in a clinical setting. One of the main aspects in subject-specific FE-models of bones regarding accuracy is the modeling of the material inhomogeneity. The goal of this study was therefore to develop FE-models of human femurs and investigate if a single validated density-elasticity relationship can be used for subject specific finite element analyses of human long bones, when the task is to predict the bone's mechanical response to load. To this aim, 23 human cadaver femurs were tested in axial compression with a load of 1000 N. Strains, local displacements, and axial bone stiffness were determined. Subject-specific FE-models were developed for each bone based on quantitative CT-scans. Three different density-elasticity relationships were retrieved from the literature, and were implemented in the FE-models. The predicted mechanical values depended largely on the used equation. The most reasonable equation showed a mean error of -11% in strain prediction, a mean error of -23% in local displacement prediction, and a mean error of +23% in axial stiffness prediction. The scatter of the predictions was very low in all three categories of measurements with a 1.96 standard deviation of about 30% to the mean errors. In conclusion, a framework for subject-specific FE-models was developed that was able to predict surface strains and bone deformation with good accuracy by using a single density-elasticity relationship. However, it was also found that the most appropriate density-elasticity relationship was specimen-specific. Copyright © 2012 IPEM. Published by Elsevier Ltd. All rights reserved.

  18. Variation of Mycobacterium tuberculosis antigen-specific IFN-γ and IL-17 responses in healthy tuberculin skin test (TST-positive human subjects.

    Directory of Open Access Journals (Sweden)

    Lin Fan

    Full Text Available OBJECTIVE: To determine the variation of IFN-γ and IL-17 responses to M. tuberculosis antigens in healthy TST+ humans. METHODS: We isolated peripheral blood mononuclear cells from 21 TST+ healthy adults, stimulated them with phytohemagglutinin (PHA, PPD, Ag85B, ESAT-6, and live M. bovis BCG, and assayed IFN-γ and IL-17 secretion by ELISA in supernatants after 24 or 72 hours of incubation respectively. RESULTS: As in other studies, we found a wide range of IFN-γ responses to M. tuberculosis antigens; the variation significantly exceeded that observed in the same donors to the polyclonal T cell stimulus, phytohemagglutinin (PHA. In addition, we assayed IL-17 secretion in response to the same stimuli, and found less subject-to-subject variation. Analysis of the ratio of IFN-γ to IL-17 secretion on a subject-to-subject basis also revealed a wide range, with the majority of results distributed in a narrow range, and a minority with extreme results all of which were greater than that in the majority of subjects. The data suggest that study of exceptional responses to M. tuberculosis antigens may reveal immunologic correlates with specific outcomes of M. tuberculosis infection. CONCLUSION: Variation of IFNγ and IFN-γ/IL-17 responses to mycobacterial antigens exceeds that of responses to the polyclonal stimulus, PHA, in TST positive healthy humans. This indicates a quantitative spectrum of human immune responses to infection with M. tuberculosis. Since the outcome of human infection with M. tuberculosis varies greatly, systematic study of multiple immune responses to multiple antigens is likely to reveal correlations between selected immune responses and the outcomes of infection.

  19. Optic nerve demyelination induced by human serum: patients with multiple sclerosis or optic neuritis and normal subjects.

    Science.gov (United States)

    Sergott, R C; Brown, M J; Polenta, R M; Lisak, R P; Silberberg, D H

    1985-10-01

    We injected guinea pig optic nerves with serum from patients with MS or acute optic neuritis (ON), or normal subjects. Serum from 12 of 17 MS patients, 3 of 3 patients with ON, and 5 of 11 normal age- and sex-matched controls produced myelin vesiculation and demyelination 24 hours after injection. Nerves injected with demyelinating serum contained oligodendrocytes with pyknotic nuclei and edematous, rarefied cytoplasm. Nerves injected with serum that did not cause demyelination did not have these oligodendrocyte changes. Serum from normal subjects or patients with MS may induce in vivo demyelination in mammalian CNS.

  20. A finite element model of the L4-L5-S1 human spine segment including the heterogeneity and anisotropy of the discs.

    Science.gov (United States)

    Jaramillo, Hector E; Gómez, Lessby; García, Jose J

    2015-01-01

    With the aim to study disc degeneration and the risk of injury during occupational activities, a new finite element (FE) model of the L4-L5-S1 segment of the human spine was developed based on the anthropometry of a typical Colombian worker. Beginning with medical images, the programs CATIA and SOLIDWORKS were used to generate and assemble the vertebrae and create the soft structures of the segment. The software ABAQUS was used to run the analyses, which included a detailed model calibration using the experimental step-wise reduction data for the L4-L5 component, while the L5-S1 segment was calibrated in the intact condition. The range of motion curves, the intradiscal pressure and the lateral bulging under pure moments were considered for the calibration. As opposed to other FE models that include the L5-S1 disc, the model developed in this study considered the regional variations and anisotropy of the annulus as well as a realistic description of the nucleus geometry, which allowed an improved representation of experimental data during the validation process. Hence, the model can be used to analyze the stress and strain distributions in the L4-L5 and L5-S1 discs of workers performing activities such as lifting and carrying tasks.

  1. Subjectivity and severe psychiatric disorders.

    Science.gov (United States)

    Strauss, John

    2011-01-01

    To have a complete human science in the mental health field it is essential to give adequate attention to both the objective and the subjective data related to people with psychiatric disorders. The tendency in the past has been to ignore or discount one or the other of these data sources. Subjective data are particularly neglected, sometimes considered (only) part of the "art" of medicine since the usual methodologies of the physical sciences in themselves are not adequate to reflect the nature, elusiveness, and complexity of human subjective experience. The complete experience of hallucinated voices, for instance, often includes not only the voices themselves but also terrible anguish and terrifying inability to concentrate. But even such descriptors fall unnecessarily short of reflecting the data of the experience, thus leaving research, theory, and treatment with incomplete information. To represent adequately the subjective data it is essential to recognize that besides the usual discursive knowledge and methods of traditional physical science, a second kind of knowledge and method is required to reflect the depth of human experience. To accomplish this, we must employ approaches to narrative and the arts that are uniquely capable of capturing the nature of these experiences. Only by attending seriously in our research, training, theory, and practice to the unique nature of subjective data is it possible to have a true human science for our field.

  2. 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…

  3. Sample preparation and orthogonal chromatography for broad polarity range plasma metabolomics: Application to human subjects with neurodegenerative dementia

    OpenAIRE

    Armirotti, Andrea; Basit, Abdul; Realini, Natalia; Caltagirone, Carlo; Bossù, Paola; Spalletta, Gianfranco; Piomelli, Daniele

    2014-01-01

    We describe a simple protocol for the preparation and orthogonal hydrophobic/hydrophilic LC-MS/MS analysis of mouse and human plasma samples, which enables the untargeted ("shotgun") or targeted profiling of hydrophilic, amphipathic, and hydrophobic constituents of plasma metabolome. The protocol is rapid, efficient, and reliable, and offers several advantages compared to current procedures. When applied to a training set of human plasma samples, the protocol allowed for the rapid acquisition...

  4. Synthesis and evaluation of the potential deleterious effects of ZnO nanomaterials (nanoneedles and nanoflowers) on blood components, including albumin, erythrocytes and human isolated primary neutrophils

    Energy Technology Data Exchange (ETDEWEB)

    Pastrello, Bruna [São Paulo State University (UNESP), Department of Chemistry, Faculty of Sciences (Brazil); Paracatu, Luana Chiquetto [São Paulo State University (UNESP), Department of Clinical Analysis, School of Pharmaceutical Sciences (Brazil); Carvalho Bertozo, Luiza de [São Paulo State University (UNESP), Department of Chemistry, Faculty of Sciences (Brazil); Paino, Iêda Maria Martinez [University of São Paulo (USP), Nanomedicine and Nanotoxicology Group, Physics Institute of São Carlos (IFSC) (Brazil); Lisboa-Filho, Paulo Noronha [São Paulo State University (UNESP), Department of Physics, Faculty of Sciences (Brazil); Ximenes, Valdecir Farias, E-mail: vfximenes@fc.unesp.br [São Paulo State University (UNESP), Department of Chemistry, Faculty of Sciences (Brazil)

    2016-07-15

    The application of zinc oxide (ZnO) nanoparticles in biomaterials has increased significantly in the recent years. Here, we aimed to study the potential deleterious effects of ZnO on blood components, including human serum albumin (HSA), erythrocytes and human isolated primary neutrophils. To test the influence of the morphology of the nanomaterials, ZnO nanoneedles (ZnO-nn) and nanoflowers (ZnO-nf) were synthesized. The zeta potential and mean size of ZnO-nf and ZnO-nn suspensions in phosphate-buffered saline were −10.73 mV and 3.81 nm and −5.27 mV and 18.26 nm, respectively. The incubation of ZnO with HSA did not cause its denaturation as verified by the absence of significant alterations in the intrinsic and extrinsic fluorescence and in the circular dichroism spectrum of the protein. The capacity of HSA as a drug carrier was not affected as verified by employing site I and II fluorescent markers. Neither type of ZnO was able to provoke the activation of neutrophils, as verified by lucigenin- and luminol-dependent chemiluminescence and by the extracellular release of hydrogen peroxide. ZnO-nf, but not ZnO-nn, induced the haemolysis of erythrocytes. In conclusion, our results reinforce the concept that ZnO nanomaterials are relatively safe for usage in biomaterials. A potential exception is the capacity of ZnO-nf to promote the lysis of erythrocytes, a discovery that shows the importance of the morphology in the toxicity of nanoparticles.

  5. Synthesis and evaluation of the potential deleterious effects of ZnO nanomaterials (nanoneedles and nanoflowers) on blood components, including albumin, erythrocytes and human isolated primary neutrophils

    Science.gov (United States)

    Pastrello, Bruna; Paracatu, Luana Chiquetto; de Carvalho Bertozo, Luiza; Paino, Iêda Maria Martinez; Lisboa-Filho, Paulo Noronha; Ximenes, Valdecir Farias

    2016-07-01

    The application of zinc oxide (ZnO) nanoparticles in biomaterials has increased significantly in the recent years. Here, we aimed to study the potential deleterious effects of ZnO on blood components, including human serum albumin (HSA), erythrocytes and human isolated primary neutrophils. To test the influence of the morphology of the nanomaterials, ZnO nanoneedles (ZnO-nn) and nanoflowers (ZnO-nf) were synthesized. The zeta potential and mean size of ZnO-nf and ZnO-nn suspensions in phosphate-buffered saline were -10.73 mV and 3.81 nm and -5.27 mV and 18.26 nm, respectively. The incubation of ZnO with HSA did not cause its denaturation as verified by the absence of significant alterations in the intrinsic and extrinsic fluorescence and in the circular dichroism spectrum of the protein. The capacity of HSA as a drug carrier was not affected as verified by employing site I and II fluorescent markers. Neither type of ZnO was able to provoke the activation of neutrophils, as verified by lucigenin- and luminol-dependent chemiluminescence and by the extracellular release of hydrogen peroxide. ZnO-nf, but not ZnO-nn, induced the haemolysis of erythrocytes. In conclusion, our results reinforce the concept that ZnO nanomaterials are relatively safe for usage in biomaterials. A potential exception is the capacity of ZnO-nf to promote the lysis of erythrocytes, a discovery that shows the importance of the morphology in the toxicity of nanoparticles.

  6. 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-...

  7. 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.

  8. Experimental investigation of biodynamic human body models subjected to whole-body vibration during a vehicle ride.

    Science.gov (United States)

    Taskin, Yener; Hacioglu, Yuksel; Ortes, Faruk; Karabulut, Derya; Arslan, Yunus Ziya

    2018-02-06

    In this study, responses of biodynamic human body models to whole-body vibration during a vehicle ride were investigated. Accelerations were acquired from three different body parts, such as the head, upper torso and lower torso, of 10 seated passengers during a car ride while two different road conditions were considered. The same multipurpose vehicle was used during all experiments. Additionally, by two widely used biodynamic models in the literature, a set of simulations were run to obtain theoretical accelerations of the models and were compared with those obtained experimentally. To sustain a quantified comparison between experimental and theoretical approaches, the root mean square acceleration and acceleration spectral density were calculated. Time and frequency responses of the models demonstrated that neither of the models showed the best prediction performance of the human body behaviour in all cases, indicating that further models are required for better prediction of the human body responses.

  9. Evaluation of the cardiovascular and subjective effects of rivastigmine in combination with methamphetamine in methamphetamine-dependent human volunteers.

    Science.gov (United States)

    De La Garza, Richard; Shoptaw, Steve; Newton, Thomas F

    2008-09-01

    Acetylcholine (ACh) has been implicated in the reinforcing and locomotor-activating effects produced by methamphetamine (Meth). Of interest, recent data suggest that acetylcholinesterase (AChE) inhibitors attenuate Meth-seeking behaviour in rats. We conducted this study in order to determine the safety (adverse events, mood changes, cardiovascular effects) and preliminary efficacy (subjective effects) of the AChE inhibitor rivastigmine (Riv) when tested in combination with Meth. Twenty-three non-treatment-seeking Meth-dependent participants resided in an in-patient unit at UCLA for 2mg i.v.) and Meth (day 5, 30mg, n=7) or Riv (1.5mg, n=9). On day 11, the subjects received saline and Meth infusions again (randomized to either 11:30 or 14:30 hours), under double-blind conditions. The data analyses compared across-study measures of adverse events and mood, and a post-randomization analysis of cardiovascular and subjective effects (on day 11). The data reveal that rivastigmine was not associated with increased adverse events or alterations in mood. As expected, acute Meth exposure (30mg, significantly attenuated Meth-induced increases in diastolic blood pressure, and self-reports of and (p<0.05). Taken together, the findings in the current report suggest that pharmacological manipulations that enhance brain ACh warrant continued investigation as potential treatments for Meth addiction.

  10. Clinical trials and E-health: impact of new information technology applied to clinical trials (including source data-medical records) and to human and drug research.

    Science.gov (United States)

    Béhier, Jehan-Michel; Reynier, Jean-Charles; Bertoye, Pierre-Henri; Vray, Muriel

    2010-01-01

    Within the last few years, new technology has come to play an important part in our professional and private daily environment. Healthcare has not escaped this progressive mutation with computers reaching the bedside. Clinical research has also shown growing interest in these new tools available to the clinical investigator, the patient, as well as to specialist departments for diagnosis and follow-up of patients, and to the different professions in clinical research. If the use of new technology seems to make life easier, by centralizing data or by simplifying data-sharing between different teams, it is still a matter of private data which must remain reliable, confidential and secure, whether it is being used in ordinary healthcare or in academic or industrial research. The aim of the round table was to estimate the impact of new information technology applied to clinical trials (including source data-medical records) and to human and drug research. First, an inventory was made of the development of these new technologies in the healthcare system. The second point developed was identification of expected benefits in order to issue guidelines for their good use and hazard warnings in clinical trials. Finally, the impact of these new technologies on the investigator as well as the project manager was analysed. © 2010 Société Française de Pharmacologie et de Thérapeutique.

  11. A novel two-component Tobacco mosaic virus-based vector system for high-level expression of multiple therapeutic proteins including a human monoclonal antibody in plants.

    Science.gov (United States)

    Roy, Gourgopal; Weisburg, Sangeetha; Rabindran, Shailaja; Yusibov, Vidadi

    2010-09-15

    Expression of multiple therapeutic proteins from Tobacco mosaic virus (TMV)-based vectors was not successful when plants were coinoculated with a mixture of two TMV vectors engineered to express two foreign genes individually. Here, we have engineered and developed a defective RNA (dRNA)-based TMV vector (dRT-V) that utilizes two components of the same virus, with the dRNA component depending on the helper virus for replication. Agrobacterium-mediated coinoculation of Nicotiana benthamiana plants with both components of the dRT-V resulted in high-level expression of a human growth hormone and a lichenase-fused lethal factor protein of Bacillus anthracis. Furthermore, both heavy and light chains were expressed and assembled into a monoclonal antibody (mAb) specific to the protective antigen of B. anthracis, and the average yield of the purified antibody obtained was 120 mg/kg of fresh tissue. Our data suggest that dRT-V has a potential for rapid, cost-effective, large-scale manufacturing of multiple therapeutic proteins including mAbs in response to any biological emergencies. Copyright 2010 Elsevier Inc. All rights reserved.

  12. "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.

  13. Supraclavicular skin temperature as a measure of 18F-FDG uptake by BAT in human subjects

    NARCIS (Netherlands)

    Boon, Mariëtte R.; Bakker, Leontine E. H.; van der Linden, Rianne A. D.; Pereira Arias-Bouda, Lenka; Smit, Frits; Verberne, Hein J.; van Marken Lichtenbelt, Wouter D.; Jazet, Ingrid M.; Rensen, Patrick C. N.

    2014-01-01

    Brown adipose tissue (BAT) has emerged as a novel player in energy homeostasis in humans and is considered a potential new target for combating obesity and related diseases. The current 'gold standard' for quantification of BAT volume and activity is cold-induced 18F-FDG uptake in BAT. However, use

  14. Initial and delayed circulatory responses to orthostatic stress in normal humans and in subjects with orthostatic intolerance

    NARCIS (Netherlands)

    Wieling, W.; Shepherd, J. T.

    1992-01-01

    Gravitational stresses, which are common daily event for humans, result in a diminution in central blood volume, due to displacement of blood to the lower parts of the body. They demand complex adjustments in the cardiovascular system to offset the decrease in cardiac filling pressure. Such changes

  15. Compartmentalized Human Immunodeficiency Virus Type 1 Originates from Long-Lived Cells in Some Subjects with HIV-1–Associated Dementia

    Science.gov (United States)

    Schnell, Gretja; Spudich, Serena; Harrington, Patrick; Price, Richard W.; Swanstrom, Ronald

    2009-01-01

    Human immunodeficiency virus type 1 (HIV-1) invades the central nervous system (CNS) shortly after systemic infection and can result in the subsequent development of HIV-1–associated dementia (HAD) in a subset of infected individuals. Genetically compartmentalized virus in the CNS is associated with HAD, suggesting autonomous viral replication as a factor in the disease process. We examined the source of compartmentalized HIV-1 in the CNS of subjects with HIV-1–associated neurological disease and in asymptomatic subjects who were initiating antiretroviral therapy. The heteroduplex tracking assay (HTA), targeting the variable regions of env, was used to determine which HIV-1 genetic variants in the cerebrospinal fluid (CSF) were compartmentalized and which variants were shared with the blood plasma. We then measured the viral decay kinetics of individual variants after the initiation of antiretroviral therapy. Compartmentalized HIV-1 variants in the CSF of asymptomatic subjects decayed rapidly after the initiation of antiretroviral therapy, with a mean half-life of 1.57 days. Rapid viral decay was also measured for CSF-compartmentalized variants in four HAD subjects (t1/2 mean = 2.27 days). However, slow viral decay was measured for CSF-compartmentalized variants from an additional four subjects with neurological disease (t1/2 range = 9.85 days to no initial decay). The slow decay detected for CSF-compartmentalized variants was not associated with poor CNS drug penetration, drug resistant virus in the CSF, or the presence of X4 virus genotypes. We found that the slow decay measured for CSF-compartmentalized variants in subjects with neurological disease was correlated with low peripheral CD4 cell count and reduced CSF pleocytosis. We propose a model in which infiltrating macrophages replace CD4+ T cells as the primary source of productive viral replication in the CNS to maintain high viral loads in the CSF in a substantial subset of subjects with HAD

  16. Distinction between hand dominance and hand preference in primates: a behavioral investigation of manual dexterity in nonhuman primates (macaques) and human subjects.

    Science.gov (United States)

    Chatagny, Pauline; Badoud, Simon; Kaeser, Mélanie; Gindrat, Anne-Dominique; Savidan, Julie; Fregosi, Michela; Moret, Véronique; Roulin, Christine; Schmidlin, Eric; Rouiller, Eric M

    2013-09-01

    Background The present study aimed to determine and confront hand preference (hand chosen in priority to perform a manual dexterity task) and hand dominance (hand with best motor performance) in eight macaques (Macaca fascicularis) and in 20 human subjects (10 left-handers and 10 right-handers). Methods Four manual dexterity tests have been executed by the monkeys, over several weeks during learning and stable performance phases (in controlled body position): the modified Brinkman board, the reach and grasp drawer, the tube and the bimanual board tasks. Three behavioral tests, adapted versions from the monkeys tasks (modified Brinkman board, tube and bimanual board tasks), as well as a handedness questionnaire, have been conducted in human subjects. Results In monkeys, there was a large disparity across individuals and motor tasks. For hand dominance, two monkeys were rather right lateralized, three monkeys rather left lateralized, whereas in three monkeys, the different parameters measured were not consistent. For hand preference, none of the eight monkeys exhibited a homogeneous lateralization across the four motor tasks. Macaca fascicularis do not exhibit a clear hand preference. Furthermore, hand preference often changed with task repetition, both during training and plateau phases. For human subjects, the hand preference mostly followed the self-assessment of lateralization by the subjects and the questionnaire (in the latter, right-handers were more lateralized than left-handers), except a few discrepancies based on the tube task. There was no hand dominance in seven right-handers (the other three performed better with the right hand) and in four left-handers. Five left-handers showed left-hand dominance, whereas surprisingly, one left-hander performed better with the right hand. In the modified Brinkman board task, females performed better than males, right-handers better than left-handers. Conclusions The present study argues for a distinction between hand

  17. Regulating stem-cell research and human cloning in an Australian context: an exercise in protecting the status of the human subject.

    Science.gov (United States)

    Harvey, Olivia

    2005-01-01

    Over 12 months prior to the recent United Nations decision to defer a decision about what type of international treaty should be developed in the global stem-cell research and human cloning debate, the Federal Parliament of Australia passed two separate pieces of legislation relating to both these concerns. After a five-year long process of community consultation, media spectacle and parliamentary debate, reproductive cloning has been banned in Australia and only embryos considered to be excess to assisted reproductive technologies in existence on the 5th of April 2002 are currently valid research material. This paper argues that underpinning both pieces of legislation is a profound belief in the disruptive potential of all types of human cloning for the very nature and integrity of human species being. A belief, moreover, that is based on a presumption that it is apparently possible to conceptualise what being human even means for all Australians.

  18. FKBP5 methylation as a possible marker for cortisol state and transient cortisol exposure in healthy human subjects.

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