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Sample records for subjected saos2 human

  1. Interaction of human osteoblast-like Saos-2 cells with stainless steel coated by silicalite-1 films

    Czech Academy of Sciences Publication Activity Database

    Jirka, Ivan; Vandrovcová, Marta; Plšek, Jan; Bouša, Milan; Brabec, Libor; Dragounová, Helena; Bačáková, Lucie

    2017-01-01

    Roč. 76, JUL 2017 (2017), s. 775-781 ISSN 0928-4931 R&D Projects: GA ČR(CZ) GA16-02681S Institutional support: RVO:61388955 ; RVO:67985823 Keywords : silicalite-1 film * biocompatibility * human osteoblast-like Saos-2 cells Subject RIV: CF - Physical ; Theoretical Chemistry; EI - Biotechnology ; Bionics (FGU-C) OBOR OECD: Physical chemistry; Biomaterials (as related to medical implants, devices, sensors) (FGU-C)

  2. Characteristics of minerals in vesicles produced by human osteoblasts hFOB 1.19 and osteosarcoma Saos-2 cells stimulated for mineralization.

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    Strzelecka-Kiliszek, Agnieszka; Bozycki, Lukasz; Mebarek, Saida; Buchet, Rene; Pikula, Slawomir

    2017-06-01

    Bone cells control initial steps of mineralization by producing extracellular matrix (ECM) proteins and releasing vesicles that trigger apatite nucleation. Using transmission electron microscopy with energy dispersive X-ray microanalysis (TEM-EDX) we compared the quality of minerals in vesicles produced by two distinct human cell lines: fetal osteoblastic hFOB 1.19 and osteosarcoma Saos-2. Both cell lines, subjected to osteogenic medium with ascorbic acid (AA) and β-glycerophosphate (β-GP), undergo the entire osteoblastic differentiation program from proliferation to mineralization, produce the ECM and spontaneously release vesicles. We observed that Saos-2 cells mineralized better than hFOB 1.19, as probed by Alizarin Red-S (AR-S) staining, tissue nonspecific alkaline phosphatase (TNAP) activity and by analyzing the composition of minerals in vesicles. Vesicles released from Saos-2 cells contained and were surrounded by more minerals than vesicles released from hFOB 1.19. In addition, there were more F and Cl substituted apatites in vesicles from hFOB 1.19 than in those from Saos-2 cells as determined by ion ratios. Saos-2 and h-FOB 1.19 cells revealed distinct mineralization profiles, indicating that the process of mineralization may proceed differently in various types of cells. Our findings suggest that TNAP activity is correlated with the relative proportions of mineral-filled vesicles and mineral-surrounded vesicles. The origin of vesicles and their properties predetermine the onset of mineralization at the cellular level. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Thin films of single-walled carbon nanotubes promote human osteoblastic cells (Saos-2) proliferation in low serum concentrations

    International Nuclear Information System (INIS)

    Akasaka, Tsukasa; Yokoyama, Atsuro; Matsuoka, Makoto; Hashimoto, Takeshi; Watari, Fumio

    2010-01-01

    One strategy used for the regeneration of bone is the development of cell culture substrates and scaffolds that can control osteoblast proliferation and differentiation. In recent investigations, carbon nanotubes (CNTs) have been utilized as scaffolds for osteoblastic cell cultures; however, there are only a few reports describing the proliferation of osteoblastic cells on thin CNT films; in particular, the effects of serum concentration on cell proliferation have not been studied. In the present study, we prepared culture dishes with homogeneous thin or thick films of non-modified CNTs and examined the effect of serum concentrations on human osteoblastic cells (Saos-2) proliferation in these culture dishes. We demonstrated that the ratio of cell proliferation was strongly affected by the concentration of serum. Interestingly, single-walled carbon nanotube (SWNT) thin films were found to be the most effective substrate for the proliferation of Saos-2 cells in low concentrations of serum. Thus, thin SWNT films may be used as an effective biomaterial for the culture of Saos-2 cells in low serum concentrations.

  4. Anti-citrullinated protein antibodies promote apoptosis of mature human Saos-2 osteoblasts via cell-surface binding to citrullinated heat shock protein 60.

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    Lu, Ming-Chi; Yu, Chia-Li; Yu, Hui-Chun; Huang, Hsien-Bin; Koo, Malcolm; Lai, Ning-Sheng

    2016-01-01

    We hypothesized that anti-citrullinated protein antibodies (ACPAs) react with osteoblast surface citrullinated proteins and affect cell function, leading to joint damage in patients with rheumatoid arthritis (RA). First, we purified ACPAs by cyclic citrullinated peptide (CCP)-conjugated affinity column chromatography. The cognate antigens of ACPAs on Saos-2 cells, a sarcoma osteogenic cell line generated from human osteoblasts, were probed by ACPAs, and the reactive bands were analyzed using proteomic analyses. We found that ACPAs bind to Saos-2 cell membrane, and several protein candidates, including HSP60, were identified. We then cloned and purified recombinant heat shock protein 60 (HSP60) and citrullinated HSP60 (citHSP60) and investigated the effect of ACPAs on Saos-2 cell. We confirmed that HSP60 obtained from Saos-2 cell membrane were citrullinated and reacted with ACPAs, which induces Saos-2 cells apoptosis via binding to surface-expressed citHSP60 through Toll-like receptor 4 signaling. ACPAs promoted interleukin (IL)-6 and IL-8 expression in Saos-2 cells. Finally, sera from patients with RA and healthy controls were examined for their titers of anti-HSP60 and anti-citHSP60 antibodies using an enzyme-linked immunosorbent assay. The radiographic change in patients with RA was evaluated using the Genant-modified Sharp scoring system. Patients with RA showed higher sera titers of anti-citHSP60, but not anti-HSP60, antibodies when compared with controls. In addition, the anti-citHSP60 level was positively associated with increased joint damage in patients with RA. In conclusion, Saos-2 cell apoptosis was mediated by ACPAs via binding to cell surface-expressed citHSP60 and the titer of anti-citHSP60 in patients with RA positively associated with joint damage. Copyright © 2015 Elsevier GmbH. All rights reserved.

  5. Effect of human granulocyte macrophage-colony stimulating factor on differentiation and apoptosis of the human osteosarcoma cell line SaOS-2

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    L Postiglione

    2009-06-01

    Full Text Available We investigated the effects of human granulocyte macrophage- colony stimulating factor (GM-CSF on the relation between differentiation and apoptosis in SaOS-2 cells, an osteoblast-like cell line. To determine the relationship between these cellular processes, SaOS-2 cells were treated in vitro for 1, 7 and 14 days with 200 ng/mL GM-CSF and compared with untreated cells. Five nM insulin-like growth factor (IGF-I and 30 nM okadaic acid were used as negative and positive controls of apoptosis, respectively. Effects on cell differentiation were determined by ECM (extracellular matrix mineralization, morphology of some typical mature osteoblast differentiation markers, such as osteopontin and sialoprotein II (BSP-II, and production of bone ECM components such as collagen I. The results showed that treatment with GM-CSF caused cell differentiation accompanied by increased production of osteopontin and BSP-II, together with increased ECM deposition and mineralization. Flow cytometric analysis of annexin V and propidium iodide incorporation showed that GM-CSF up-regulated apoptotic cell death of SaOS-2 cells after 14 days of culture in contrast to okadaic acid, which stimulated SaOS-2 apoptosis only during the early period of culture. Endonucleolytic cleavage of genomic DNA, detected by “laddering analysis”, confirmed these data. The results suggest that GM-CSF induces osteoblastic differentiation and long-term apoptotic cell death of the SaOS-2 human osteosarcoma cell line, which in turn suggests a possible in vivo physiological role for GM-CSF on human osteoblast cells.

  6. Sp1/Sp3 and DNA-methylation contribute to basal transcriptional activation of human podoplanin in MG63 versus Saos-2 osteoblastic cells

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    Puri Christina

    2007-03-01

    Full Text Available Abstract Background Podoplanin is a membrane mucin that, among a series of tissues, is expressed on late osteoblasts and osteocytes. Since recent findings have focussed on podoplanin's potential role as a tumour progression factor, we aimed at identifying regulatory elements conferring PDPN promoter activity. Here, we characterized the molecular mechanism controlling basal PDPN transcription in human osteoblast-like MG63 versus Saos-2 cells. Results We cloned and sequenced 2056 nucleotides from the 5'-flanking region of the PDPN gene and a computational search revealed that the TATA and CAAT box-lacking promoter possesses features of a growth-related gene, such as a GC-rich 5' region and the presence of multiple putative Sp1, AP-4 and NF-1 sites. Reporter gene assays demonstrated a functional promoter in MG63 cells exhibiting 30-fold more activity than in Saos-2 cells. In vitro DNase I footprinting revealed eight protected regions flanked by DNaseI hypersensitive sites within the region bp -728 to -39 present in MG63, but not in Saos-2 cells. Among these regions, mutation and supershift electrophoretic mobility shift assays (EMSA identified four Sp1/Sp3 binding sites and two binding sites for yet unknown transcription factors. Deletion studies demonstrated the functional importance of two Sp1/Sp3 sites for PDPN promoter activity. Overexpression of Sp1 and Sp3 independently increased the stimulatory effect of the promoter and podoplanin mRNA levels in MG63 and Saos-2 cells. In SL2 cells, Sp3 functioned as a repressor, while Sp1 and Sp3 acted positively synergistic. Weak PDPN promoter activity of Saos-2 cells correlated with low Sp1/Sp3 nuclear levels, which was confirmed by Sp1/Sp3 chromatin immunoprecipitations in vivo. Moreover, methylation-sensitive Southern blot analyses and bisulfite sequencing detected strong methylation of CpG sites upstream of bp -464 in MG63 cells, but hypomethylation of these sites in Saos-2 cells. Concomitantly

  7. Experimental study of inhibitory effects of diallyl trisulfide on the growth of human osteosarcoma Saos-2 cells by downregulating expression of glucose-regulated protein 78

    Directory of Open Access Journals (Sweden)

    Zhang Y

    2018-01-01

    Full Text Available Yue Zhang,1,* Wen-Peng Xie,1,* Yong-Kui Zhang,2 Yi-Qiang Chen,3 Dong-Li Wang,2 Gang Li,2 Dong-Hui Guan2 1First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 2Department of Orthopedics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 3Department of Orthopedics, The First People’s Hospital of Taian City, Taian, People’s Republic of China *These authors contributed equally to the paper Background: Diallyl trisulfide (DATS is a natural organic sulfur compound isolated from garlic that has good anticancer activity according to many previous reports. There are many studies pointing out that DATS can downregulate expression of the glucose-regulated protein 78 (GRP78, which is associated with poor prognosis and drug resistance in various types of human cancers. However, it remains unknown whether DATS has the same effect on human osteosarcoma cells. This study attempted to clarify the potential molecular mechanisms of the action of DATS in human osteosarcoma Saos-2 cells.Methods: We used an inverted phase microscope and immunofluorescent staining to observe the morphological changes of Saos-2 cells after being cultured in different concentrations of DATS (0, 25, 50, and 100 µM for 24 h, or for four time periods (24, 48, 72, and 96 h in the same DATS concentration (50 µM. Quantitative real-time polymerase chain reaction and Western blot were used to detect the expression level of GRP78 mRNA and proteins in Saos-2 cells. GRP78 expression was suppressed in Saos-2 cells by utilizing small-interfering RNA, and the cells were subsequently used to study the anti-proliferative effects of DATS treatment.Results: The expression level of GRP78 mRNA and proteins was significantly downregulated due to the increased concentration and effective times of DATS (P<0.05. In addition, there were significant associations between GRP78

  8. Comparison of the Influence of Phospholipid-Coated Porous Ti-6Al-4V Material on the Osteosarcoma Cell Line Saos-2 and Primary Human Bone Derived Cells

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    Axel Deing

    2016-03-01

    Full Text Available Biomaterial surface functionalization remains of great interest in the promotion of cell osteogenic induction. Previous studies highlighted the positive effects of porous Ti-6Al-4V and phospholipid coating on osteoblast differentiation and bone remodeling. Therefore, the first objective of this study was to evaluate the potential synergistic effects of material porosity and phospholipid coating. Primary human osteoblasts and Saos-2 cells were cultured on different Ti-6Al-4V specimens (mirror-like polished or porous specimens and were coated or not with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE for three weeks or five weeks. Selected gene expressions (e.g., classical bone markers: alkaline phosphatase, osteocalcin, osteoprotegerin (OPG, receptor activator of nuclear factor kappa-β ligand (RANKL and runt-related transcription factor 2 were estimated in vitro. Furthermore, the expressions of osteocalcin and osteopontin were examined via fluorescent microscopy at five weeks (immunocytochemistry. Consequently, it was observed that phospholipid coating potentiates preferences for low and high porosities in Saos-2 and primary cells, respectively, at the gene and protein levels. Additionally, RANKL and OPG exhibited different gene expression patterns; primary cells showed dramatically increased RANKL expression, whereas OPG expression was decreased in the presence of POPE. A synergistic effect of increased porosity and phospholipid coating was observed in primary osteoblasts in bone remodeling. This study showed the advantage of primary cells over the standard bone cell model.

  9. In vitro cytotoxicity of galvanically coupled magnesium-titanium particles on human osteosarcoma SAOS2 cells: A potential cancer therapy.

    Science.gov (United States)

    Kim, Jua; Gilbert, Jeremy L

    2018-04-10

    Osteosarcoma is a malignant bone cancer that occurs mostly in children and young adults. This study investigated the cytotoxicity of Mg and Mg-Ti microparticles to human osteosarcoma cells. Osteosarcoma cells were killed in a dosage-dependent manner when cells, with a cell seeding density of 30,000 cells/cm 2 , were cultured with 0 to 2500 µg/mL of Mg or Mg-Ti in cell culture media for 24-72 h. Mg-Ti killed cells more effectively, where 1250 µg/mL of Mg-Ti killed cells completely by 24 h, while 2500 µg/mL of Mg killed nearly all cells, but not all. Killing due to particle corrosion occurred mostly during the first 24 h, and so the percent cell viability between 24 and 72 h showed not much variability. However, the measurement of live and dead cell numbers, over the timeframe of 24-72 h, showed more insight, such as cell recovery. If particle concentrations were low, the number of live cells increased after 24 h, indicating cell proliferation. If particle concentrations were high, the number of live cells either remained steady or decreased, indicating cell quiescence or continued killing, respectively. Increase in the number of dead cells also indicated killing, while plateau meant discontinued killing. In addition, repeated killing of recovered cells exhibited the same dose-dependent killing profile as the initial experiment, implying little development of cell resistance to treatment. These results, together, show that osteosarcoma cells are susceptible to killing by way of exposure to corroding particles, showing highly effective killing using the galvanic couple of Mg-Ti. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018. © 2018 Wiley Periodicals, Inc.

  10. A Sclerostin super-producer cell line derived from the human cell line SaOS-2: a new tool for the study of the molecular mechanisms driving Sclerostin expression.

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    Pérez-Campo, Flor M; Sañudo, Carolina; Delgado-Calle, Jesús; Arozamena, Jana; Zarrabeitia, María T; Riancho, José A

    2014-08-01

    Sclerostin, the product of the SOST gene, is a key regulator of bone homeostasis. Sclerostin interferes with the Wnt signalling pathway and, therefore, has a negative effect on bone formation. Although the importance of sclerostin in bone homeostasis is well established, many aspects of its biology are still unknown. Due to its restricted pattern of expression, in vitro studies of SOST gene regulation are technically challenging. Furthermore, a more profound investigation of the molecular mechanism controlling sclerostin expression has been hampered by the lack of a good human in vitro model. Here, we describe two cell lines derived from the human osteosarcoma cell line SaOS-2 that produce elevated levels of sclerostin. Analysis of the super-producer cell lines showed that sclerostin levels were still reduced in response to parathyroid hormone treatment or in response to mechanical loading, indicating that these regulatory mechanisms were not affected in the presented cell lines. In addition, we did not find differences between the promoter or ECR5 sequences of our clones and the SaOS-2 parental line. However, the methylation of the proximal CpG island located at the SOST promoter was lower in the super-producer clones, in agreement with a higher level of SOST transcription. Although the underlying biological causes of the elevated levels of sclerostin production in this cell line are not yet clear, we believe that it could be an extremely useful tool to study the molecular mechanisms driving sclerostin expression in humans.

  11. Engineering a morphogenetically active hydrogel for bioprinting of bioartificial tissue derived from human osteoblast-like SaOS-2 cells.

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    Neufurth, Meik; Wang, Xiaohong; Schröder, Heinz C; Feng, Qingling; Diehl-Seifert, Bärbel; Ziebart, Thomas; Steffen, Renate; Wang, Shunfeng; Müller, Werner E G

    2014-10-01

    Sodium alginate hydrogel, stabilized with gelatin, is a suitable, biologically inert matrix that can be used for encapsulating and 3D bioprinting of bone-related SaOS-2 cells. However, the cells, embedded in this matrix, remain in a non-proliferating state. Here we show that addition of an overlay onto the bioprinted alginate/gelatine/SaOS-2 cell scaffold, consisting of agarose and the calcium salt of polyphosphate [polyP·Ca(2+)-complex], resulted in a marked increase in cell proliferation. In the presence of 100 μm polyP·Ca(2+)-complex, the cells proliferate with a generation time of approximately 47-55 h. In addition, the hardness of the alginate/gelatin hydrogel substantially increases in the presence of the polymer. The reduced Young's modulus for the alginate/gelatin hydrogel is approximately 13-14 kPa, and this value drops to approximately 0.5 kPa after incubation of the cell containing scaffolds for 5 d. In the presence of 100 μm polyP·Ca(2+)-complex, the reduced Young's modulus increases to about 22 kPa. The hardness of the polyP·Ca(2+)-complex containing hydrogel remains essentially constant if cells are absent in the matrix, but it drops to 3.2 kPa after a 5 d incubation period in the presence of SaOS-2 cells, indicating that polyP·Ca(2+)-complex becomes metabolized, degraded, by the cells. The alginate/gelatine-agarose system with polyP·Ca(2+)-complex cause a significant increase in the mineralization of the cells. SEM analyses revealed that the morphology of the mineral nodules formed on the surface of the cells embedded in the alginate/gelatin hydrogel do not significantly differ from the nodules on cells growing in monolayer cultures. The newly developed technique, using cells encapsulated into an alginate/gelatin hydrogel and a secondary layer containing the morphogenetically active, growth promoting polymer polyP·Ca(2+)-complex opens new possibilities for the application of 3D bioprinting in bone tissue engineering. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Interaction of Human Osteoblast-Like Saos-2 and MG-63 Cells with Thermally Oxidized Surfaces of a Titanium-Niobium Alloy

    Czech Academy of Sciences Publication Activity Database

    Vandrovcová, Marta; Jirka, Ivan; Novotná, Katarína; Lisá, Věra; Frank, Otakar; Kolská, Z.; Starý, V.; Bačáková, Lucie

    2014-01-01

    Roč. 9, č. 6 (2014), e100475 E-ISSN 1932-6203 R&D Projects: GA ČR(CZ) GAP108/10/1858; GA ČR(CZ) GAP107/12/1025; GA MPO FR-TI3/088 Institutional support: RVO:67985823 ; RVO:61388955 Keywords : thermally oxidized surface * titanium-niobium * TiO2 * osteoblast * macrophage Subject RIV: EI - Biotechnology ; Bionics Impact factor: 3.234, year: 2014

  13. Antisense targeting of TGF-β1 augments BMP-induced upregulation of osteopontin, type I collagen and Cbfa1 in human Saos-2 cells

    International Nuclear Information System (INIS)

    Shen, Zhong-Jian; Kook Kim, Sang; Youn Jun, Do; Park, Wan; Ho Kim, Young; Malter, James S.; Jo Moon, Byung

    2007-01-01

    Despite commonalities in signal transduction in osteoblasts from different species, the role of TGF-β1 on bone formation remains elusive. In particular, the role of autocrine TGF-β1 on human osteoblasts is largely unknown. Here we show the effect of TGF-β1 knock-down on the proliferation and differentiation of osteoblasts induced by BMP2. Treatment with antisense TGF-β1 moderately increased the rate of cell proliferation, which was completely reversed by the exogenous addition of TGF-β1. Notably, TGF-β1 blockade significantly enhanced BMP2-induced upregulation of mRNAs encoding osteopontin, type I collagen and Cbfa1, which was suppressed by exogenous TGF-β1. Moreover, TGF-β1 knock-down increased BMP2-induced phosphorylation of Smad1/5 as well as their nuclear import, which paralleled a reduction of inhibitory Smad6. These data suggest autocrine TGF-β1 antagonizes BMP signaling through modulation of inducible Smad6 and the activity of BMP specific Smad1/5

  14. SAOS-2 osteosarcoma cells bind fibroblasts via ICAM-1 and this is increased by tumour necrosis factor-α.

    Science.gov (United States)

    David, Manu S; Kelly, Elizabeth; Cheung, Ivan; Xaymardan, Munira; Moore, Malcolm A S; Zoellner, Hans

    2014-01-01

    We recently reported exchange of membrane and cytoplasmic markers between SAOS-2 osteosarcoma cells and human gingival fibroblasts (h-GF) without comparable exchange of nuclear markers, while similar h-GF exchange was seen for melanoma and ovarian carcinoma cells. This process of "cellular sipping" changes phenotype such that cells sharing markers of both SAOS-2 and h-GF have morphology intermediate to that of either cell population cultured alone, evidencing increased tumour cell diversity without genetic change. TNF-α increases cellular sipping between h-GF and SAOS-2, and we here study binding of SAOS-2 to TNF-α treated h-GF to determine if increased cellular sipping can be accounted for by cytokine stimulated SAOS-2 binding. More SAOS-2 bound h-GF pe-seeded wells than culture plastic alone (pcells migrating across different microenvironments can influence subsequent interactions with fibroblasts. Since cytokine stimulated binding was comparable in magnitude to earlier reported TNF-α stimulated cellular sipping, we conclude that TNF-α stimulated cellular sipping likely reflects increased SAOS-2 binding as opposed to enhanced exchange mechanisms.

  15. Strong adhesion of Saos-2 cells to multi-walled carbon nanotubes

    International Nuclear Information System (INIS)

    Matsuoka, Makoto; Akasaka, Tsukasa; Totsuka, Yasunori; Watari, Fumio

    2010-01-01

    In recent years, carbon nanotubes (CNTs) have been considered potential biomedical materials because of their unique character. The aim of this study was to investigate the response of a human osteoblast-like cell line - Saos-2 - on single-walled CNTs (SWCNTs) and multi-walled CNTs (MWCNTs). The surface of a culture dish was coated with CNTs, and Saos-2 cells were cultured for three days. Cell morphology, viability, alkaline phosphatase (ALP) activity, adhesion, and vinculin expression were evaluated. The result showed high cell viability and strong adhesion to MWCNTs. Saos-2 cultured on MWCNTs exhibited vinculin expression throughout the cell body, while the cells attached to SWCNTs and glass were mostly limited to their periphery. Our results suggest that CNT coatings promote cell activity and adhesiveness. These findings indicate that MWCNTs could be used as surface coating materials to promote cell adhesion.

  16. SAOS-2 osteosarcoma cells bind fibroblasts via ICAM-1 and this is increased by tumour necrosis factor-α.

    Directory of Open Access Journals (Sweden)

    Manu S David

    Full Text Available We recently reported exchange of membrane and cytoplasmic markers between SAOS-2 osteosarcoma cells and human gingival fibroblasts (h-GF without comparable exchange of nuclear markers, while similar h-GF exchange was seen for melanoma and ovarian carcinoma cells. This process of "cellular sipping" changes phenotype such that cells sharing markers of both SAOS-2 and h-GF have morphology intermediate to that of either cell population cultured alone, evidencing increased tumour cell diversity without genetic change. TNF-α increases cellular sipping between h-GF and SAOS-2, and we here study binding of SAOS-2 to TNF-α treated h-GF to determine if increased cellular sipping can be accounted for by cytokine stimulated SAOS-2 binding. More SAOS-2 bound h-GF pe-seeded wells than culture plastic alone (p<0.001, and this was increased by h-GF pre-treatment with TNF-α (p<0.001. TNF-α stimulated binding was dose dependent and maximal at 1.16 nM (p<0.05 with no activity below 0.006 nM. SAOS-2 binding to h-GF was independent of serum, while the lipopolysaccharide antagonist Polymyxin B did not affect results, and TNF-α activity was lost on boiling. h-GF binding of SAOS-2 started to increase after 30min TNF-α stimulation and was maximal by 1.5 hr pre-treatment (p<0.001. h-GF retained maximal binding up to 6 hrs after TNF-α stimulation, but this was lost by 18 hrs (p<0.001. FACS analysis demonstrated increased ICAM-1 consistent with the time course of SAOS-2 binding, while antibody against ICAM-1 inhibited SAOS-2 adhesion (p<0.04. Pre-treating SAOS-2 with TNF-α reduced h-GF binding to background levels (p<0.003, and this opposite effect to h-GF cytokine stimulation suggests that the history of cytokine exposure of malignant cells migrating across different microenvironments can influence subsequent interactions with fibroblasts. Since cytokine stimulated binding was comparable in magnitude to earlier reported TNF-α stimulated cellular sipping, we

  17. Tissue transglutaminase (TG2 activity regulates osteoblast differentiation and mineralization in the SAOS-2 cell line

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    Xiaoxue Yin

    2012-08-01

    Full Text Available Tissue transglutaminase (type II, TG2 has long been postulated to directly promote skeletal matrix calcification and play an important role in ossification. However, limited information is available on the expression, function and modulating mechanism of TG2 during osteoblast differentiation and mineralization. To address these issues, we cultured the well-established human osteosarcoma cell line SAOS-2 with osteo-inductive conditioned medium and set up three time points (culture days 4, 7, and 14 to represent different stages of SAOS-2 differentiation. Osteoblast markers, mineralization, as well as TG2 expression and activity, were then assayed in each stage. Furthermore, we inhibited TG activity with cystamine and then checked SAOS-2 differentiation and mineralization in each stage. The results showed that during the progression of osteoblast differentiation SAOS-2 cells presented significantly high levels of osteocalcin (OC mRNA, bone morphogenetic protein-2 (BMP-2 and collagen I, significantly high alkaline phosphatase (ALP activity, and the increased formation of calcified matrix. With the same tendency, TG2 expression and activity were up-regulated. Furthermore, inhibition of TG activity resulted in a significant decrease of OC, collagen I, and BMP-2 mRNA and of ALP activity and mineralization. This study demonstrated that TG2 is involved in osteoblast differentiation and may play a role in the initiation and regulation of the mineralization processes. Moreover, the modulating effects of TG2 on osteoblasts may be related to BMP-2.

  18. In vitro electromagnetically stimulated SAOS-2 osteoblasts inside porous hydroxyapatite

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    Fassina, Lorenzo; Saino, Enrica; Sbarra, Maria Sonia; Visai, Livia; De Angelis, Maria Gabriella Cusella; Magenes, Giovanni; Benazzo, Francesco

    2009-01-01

    One of the key challenges in reconstructive bone surgery is to provide living constructs that possess the ability to integrate in the surrounding tissue. Bone graft substitutes, such as autografts, allografts, xenografts, and biomaterials have been widely used to heal critical-size long bone defects due to trauma, tumor resection, congenital deformity, and tissue degeneration. In particular, porous hydroxyapatite is widely used in reconstructive bone surgery owing to its biocompatibility. In addition, the in vitro modification of hydroxyapatite with osteogenic signals enhances the tissue regeneration in vivo, suggesting that the biomaterial modification could play an important role in tissue engineering. In this study we have followed a biomimetic strategy where electromagnetically stimulated SAOS-2 human osteoblasts proliferated and built their extracellular matrix inside a porous hydroxyapatite scaffold. The electromagnetic stimulus had the following parameters: intensity of the magnetic field equal to 2 mT, amplitude of the induced electric tension equal to 5 mV, frequency of 75 Hz, and pulse duration of 1.3 ms. In comparison with control conditions, the electromagnetic stimulus increased the cell proliferation and the surface coating with bone proteins (decorin, osteocalcin, osteopontin, type-I collagen, and type-III collagen). The physical stimulus aimed at obtaining a better modification of the biomaterial internal surface in terms of cell colonization and coating with bone matrix. PMID:19827111

  19. Phenotypic instability of Saos-2 cells in long-term culture

    International Nuclear Information System (INIS)

    Hausser, Heinz-Juergen; Brenner, Rolf E.

    2005-01-01

    The human osteosarcoma cell line Saos-2 is widely used as a model system for human osteoblastic cells, though its phenotypic stability has not been ascertained. We therefore propagated these cells over 100 passages and compared relevant phenotypic properties. In general, higher passage cells exhibited higher proliferation rates and lower specific alkaline phosphatase activities, though mineralization was significantly more pronounced in cultures of late passage cells. Whereas expression of most genes investigated did not vary profoundly, some genes exhibited remarkable differences. Decorin, for instance, that has been discussed as a regulator of proliferation and mineralization, is strongly expressed only in early passage cells, and two receptors for pleiotrophin and midkine exhibited an almost mutually exclusive expression pattern in early and late passage cells, respectively. Our observations indicate that special care is required when results obtained with Saos-2 cells with different culture history are to be compared

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

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    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.

  1. A point mutation of human p53, which was not detected as a mutation by a yeast functional assay, led to apoptosis but not p21Waf1/Cip1/Sdi1 expression in response to ionizing radiation in a human osteosarcoma cell line, Saos-2

    International Nuclear Information System (INIS)

    Okaichi, Kumio; Wang Lihong; Sasaki, Ji-ichiro; Saya, Hideyuki; Tada, Mitsuhiro; Okumura, Yutaka

    1999-01-01

    Purpose: The 123A point mutation of p53 showed increased radiosensitivity, whereas other mutations (143A, 175H, and 273H) were not affected. To determine the reason for increased radiosensitivity of the 123A mutation, the response of the transformant of 123A mutation to ionizing radiation (IR) was examined and compared to those of transformants with the wild type p53 or other point mutations (143A, 175H, and 273H). Methods and Materials: Stable transformants with a mutant or wild type p53 made by introducing cDNA into the human osteosarcoma cell line, Saos-2, which lacks an endogenous p53 were used. The transcriptional activity of mutant p53 was examined using a yeast functional assay. The transformants were examined for the accumulation of p53, the induction of p21 Waf1/Cip1/Sdi1 (hereafter referred to as p21), and the other response of p53-responsive genes (MDM2, Bax, and Bcl-2) by Western blotting. Apoptosis was analyzed by detection of DNA fragmentation. Results: The 123A point mutation of p53 was detected as a wild type in the yeast functional assay. The 123A mutant accumulated p53 in response to IR. The 123A mutant did not induce p21, but normally responded to MDM2, Bax, and Bcl-2. The 123A mutant entered apoptosis earlier than the wild type p53 transformant, and induced Fas at earlier in response to IR. Conclusion: The 123A mutant led to apoptosis, but not p21 expression in response to IR. The occurrence of apoptosis, but not induction of p21, corresponded to the radiosensitivity in the transformant. The early occurrence of apoptosis in 123A transformants may depend on the early induction of Fas

  2. Human subjects and experimental irradiation

    International Nuclear Information System (INIS)

    Rosen, R.

    1985-01-01

    In recent years the public has expressed concern about the use of human subjects in scientific research. Some professional institutions have adopted codes of practice to guide them in this matter. At the University of New South Wales, where human subjects are used in teaching and research programmes, a committee ensures that high ethical standards are maintained. As the volunteer subjects do not gain any benefit themselves from the procedures, their level of risk is kept low. One type of procedure in which risk is becoming quantifiable, is the irradiation of human subjects. To assist peer review groups, the ICRP, WHO and the National Health and Medical Research Council have enunciated principles which should be followed in the irradiation of human volunteer subjects. In general the role of the Committee is advisory to protect the rights of the investigator, the subject, and the institution. Some of the inherent problems are discussed

  3. Maturation of osteoblast-like SaoS2 induced by carbon nanotubes

    International Nuclear Information System (INIS)

    Li Xiaoming; Uo, Motohiro; Akasaka, Tsukasa; Abe, Shigeaki; Watari, Fumio; Gao Hong; Sato, Yoshinori; Feng Qingling; Cui Fuzhai

    2009-01-01

    Osteogenic maturation of the osteoblast is crucial for bone formation. In this study, multi-walled carbon nanotubes (MWCNTs) and graphite (GP) were pressed as compacts. The greater ability of carbon nanotubes to adsorb proteins, compared with graphite, was shown. Human osteoblast-like SaoS2 cells were cultured and the cell response to the two kinds of compacts was compared in vitro. Meanwhile, we used cell culture on the culture plate as a control. Assays for osteonectin, osteopontin and osteocalcin gene expression, total protein (TP) amount, alkaline phosphatase activity (ALP) and DNA of cells cultured on the samples were done. During the conventional culture, significantly higher osteonectin, osteopontin and osteocalcin gene expression level, ALP/DNA and TP/DNA on carbon nanotubes were found. To confirm the hypothesis that the larger amount of specific proteins adsorbed on the carbon nanotubes was crucial for this, the compacts were pre-soaked in culture medium having additional recombinant human bone morphogenetic protein-2 (rhBMP-2) before cell culture. Compared with GP, osteonectin, osteopontin and osteocalcin gene expression level, ALP/DNA and TP/DNA of the cells tested increased more on the MWCNTs after the compacts were pre-soaked in the culture medium with rhBMP-2. The results indicated that the carbon nanotubes might induce osteogenic maturation of the osteoblast by adsorbing more specific proteins.

  4. The diameter of nanotubes formed on Ti-6Al-4V alloy controls the adhesion and differentiation of Saos-2 cells

    Czech Academy of Sciences Publication Activity Database

    Filová, Elena; Fojt, J.; Krýslová, Markéta; Moravec, H.; Joska, L.; Bačáková, Lucie

    2015-01-01

    Roč. 10, 20 Nov (2015), s. 7145-7163 E-ISSN 1178-2013 R&D Projects: GA MZd(CZ) NT13297; GA ČR(CZ) GA15-01558S; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:67985823 Keywords : nanostructure * titanium nanotubes * cell adhesion * Saos-2 cells * osteogenic differentiation Subject RIV: EI - Biotechnology ; Bionics Impact factor: 4.320, year: 2015

  5. subjective approach to subjective approach to human physiological

    African Journals Online (AJOL)

    eobe

    the only physiological variables that influence the heat balance [4]. Yao et al [2] .... between the human responses and outdoor climate. 4.1 Subjective Response ... months seem to be influenced by cloud cover rather than the altitude.

  6. Hyperthermia effects in the presence of gold nanoparticles together with chemotherapy on Saos-2 cell line

    International Nuclear Information System (INIS)

    Sazgarnia, A.; Bahreyni Toosi, M. H.; Haji Ghahremani, F.; Rajabi, O.; Aledavood, A.; Esmaily, H.

    2011-01-01

    Hyperthermia created by microwave, infrared, ultrasound and other methods, is often utilized as an adjuvant to sensitize cancer cells to the effects of chemotherapy and radiation therapy. We investigated the efficacy of hyperthermia using microwave in synergy with chemotherapy in the presence and absence and gold nanoparticles. Material and Methods: After culturing and proliferation of the Saos-2 cell line derived from human osteogenic sarcoma, the cells were incubated at two concentrations of gold nanoparticles in two diameters of 20 and 40 nm and in the absence and presence of doxorubicin in different groups. Forty eight hours after irradiating the cells with microwave up to a temperature of 42 d egree C , cell survival rate was determined using the MTT method, in order to study the effectiveness of the therapeutic parameters. Results: Cell survival in the presence of gold nanoparticles was greater than 95%. After chemotherapy by doxorubicin with and without 40 nm gold nanoparticles, cell survival rates were determined as 62.8% and 37.1 %, declining down to 17% and 4.1% respectively following the combined treatment with microwave and chemotherapy in the presence of 20 and 40 nm gold nanoparticles. Discussion and Conclusions: Gold nanoparticles did not induce any cytotoxicity by themselves; their presence along with microwave provided a reduction in survival rate that was comparable in severity with the lethal effects of doxorubicin. microwave hyperthermia with gold nanoparticles produced a higher treatment efficiency in comparison to similar groups in which gold nanoparticles were absent. The synergism observed between hyperthermia and chemotherapy was dependent in gold nanoparticles' size and concentration. This finding could be caused by increased uptake of doxorubicin by the cells in the presence of gold nanoparticles.

  7. 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 ...

  8. 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…

  9. Photodegradation of carotenoids in human subjects

    International Nuclear Information System (INIS)

    Roe, D.A.

    1987-01-01

    Photodegradation of vitamins in vitro is responsible for large losses of these nutrients in foods, beverages, and semisynthetic liquid formula diets. In vivo photodegradation of vitamins has been reported for riboflavin in jaundiced infants exposed to blue light and for folate in patients with chronic psoriasis given photochemotherapy. Two recent studies of normal subjects have also shown that photodegradation of carotenoids in plasma occurs with cumulative exposure of the skin to an artificial light source having maximal spectral emission in the UVA range. Females showed a larger effect of the UV light on their plasma carotenoid levels than males. These observations have identified a need for further investigation of the role of sunlight exposure as a determinant of plasma carotenoid levels and vitamin A status in human subjects

  10. Adhesion and differentiation of Saos-2 osteoblast-like cells on chromium-doped diamond-like carbon coatings.

    Science.gov (United States)

    Filova, Elena; Vandrovcova, Marta; Jelinek, Miroslav; Zemek, Josef; Houdkova, Jana; Jan Remsa; Kocourek, Tomas; Stankova, Lubica; Bacakova, Lucie

    2017-01-01

    Diamond-like carbon (DLC) thin films are promising for use in coating orthopaedic, dental and cardiovascular implants. The problem of DLC layers lies in their weak layer adhesion to metal implants. Chromium is used as a dopant for improving the adhesion of DLC films. Cr-DLC layers were prepared by a hybrid technology, using a combination of pulsed laser deposition (PLD) from a graphite target and magnetron sputtering. Depending on the deposition conditions, the concentration of Cr in the DLC layers moved from zero to 10.0 at.%. The effect of DLC layers with 0.0, 0.9, 1.8, 7.3, 7.7 and 10.0 at.% Cr content on the adhesion and osteogenic differentiation of human osteoblast-like Saos-2 cells was assessed in vitro. The DLC samples that contained 7.7 and 10.0 at.% of Cr supported cell spreading on day 1 after seeding. On day three after seeding, the most apparent vinculin-containing focal adhesion plaques were also found on samples with higher concentrations of chromium. On the other hand, the expression of type I collagen and alkaline phosphatase at the mRNA and protein level was the highest on Cr-DLC samples with a lower concentration of Cr (0-1.8 at.%). We can conclude that higher concentrations of chromium supported cell adhesion; however DLC and DLC doped with a lower concentration of chromium supported osteogenic cell differentiation.

  11. The human subject in the organization

    Directory of Open Access Journals (Sweden)

    Marcela Pérez Pazmiño

    2015-12-01

    Full Text Available This article puts the human subject into the center of the discussion, by finding common factors of representative authors in the field, revealing what was their predominant concern. From the Weberian bureaucratic tradition, organizational theory has witnessed that economic target was in the very center of organizations. For current assumptions, legitimate forms of domination would be substantiated by the inability to resolve most everyday affairs, those that handle to the rentability. It starts to show that organizations, far from being a rational set of actions, are places of unsound decisions, most often used for personal than community goals. The conclusion brings a new topic of discussion for organizational theory: the concept of a free agent within the organization.

  12. [Ethics and laws related to human subject research].

    Science.gov (United States)

    Chiu, Hui-Ju; Lee, Ya-Ling; Chang, Su-Fen

    2011-10-01

    Advances in medical technology rely on human subject research to test the effects on real patients of unproven new drugs, equipment and techniques. Illegal human subject research happens occasionally and has led to subject injury and medical disputes. Familiarity with the laws and established ethics related to human subject research can minimize both injury and disputes. History is a mirror that permits reflection today on past experience. Discussing the Nuremberg Code, the Declaration of Helsinki and Belmont Report, this article describes the laws, ethics, history and news related to human subject research as well as the current definition and characteristics of human subject research. Increasing numbers of nurses serve as research nurses and participate in human subject research. The authors hope this article can increase research nurse knowledge regarding laws and ethics in order to protect human research subjects adequately.

  13. Effect of bioglass on growth and biomineralization of SaOS-2 cells in hydrogel after 3D cell bioprinting.

    Directory of Open Access Journals (Sweden)

    Xiaohong Wang

    Full Text Available We investigated the effect of bioglass (bioactive glass on growth and mineralization of bone-related SaOS-2 cells, encapsulated into a printable and biodegradable alginate/gelatine hydrogel. The hydrogel was supplemented either with polyphosphate (polyP, administered as polyP • Ca2+-complex, or silica, or as biosilica that had been enzymatically prepared from ortho-silicate by silicatein. These hydrogels, together with SaOS-2 cells, were bioprinted to computer-designed scaffolds. The results revealed that bioglass (nanoparticles, with a size of 55 nm and a molar ratio of SiO2 : CaO : P2O5 of 55 : 40 : 5, did not affect the growth of the encapsulated cells. If silica, biosilica, or polyP • Ca2+-complex is co-added to the cell-containing alginate/gelatin hydrogel the growth behavior of the cells is not changed. Addition of 5 mg/ml of bioglass particles to this hydrogel significantly enhanced the potency of the entrapped SaOS-2 cells to mineralize. If compared with the extent of the cells to form mineral deposits in the absence of bioglass, the cells exposed to bioglass together with 100 µmoles/L polyP • Ca2+-complex increased their mineralization activity from 2.1- to 3.9-fold, or with 50 µmoles/L silica from 1.8- to 2.9-fold, or with 50 µmoles/L biosilica from 2.7- to 4.8-fold or with the two components together (100 µmoles/L polyP • Ca2+-complex and 50 µmoles/L biosilica from 4.1- to 6.8-fold. Element analysis by EDX spectrometry of the mineral nodules formed by SaOS-2 revealed an accumulation of O, P, Ca and C, indicating that the mineral deposits contain, besides Ca-phosphate also Ca-carbonate. The results show that bioglass added to alginate/gelatin hydrogel increases the proliferation and mineralization of bioprinted SaOS-2 cells. We conclude that the development of cell-containing scaffolds consisting of a bioprintable, solid and cell-compatible inner matrix surrounded by a printable hard and flexible outer matrix containing bioglass, provide a suitable strategy for the fabrication of morphogenetically active and biodegradable implants.

  14. Formation of Human Subjectivity in Psychological Interactions with Nature

    Directory of Open Access Journals (Sweden)

    S A Mudrak

    2014-12-01

    Full Text Available The article outlines the current trends in the environmental psychological research of the peculiarities of developing the subject-subjective human relationship with nature: considering human habitat environment as a set of natural objects; studying certain natural sites as psychologically attributive elements of the environment; determining the psychological meaning of the «Human Habitat Environment»; giving the analysis of the problem of the subjectivity development in human interaction with the natural objects.

  15. 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.

  16. Inhalation of road dust by human subjects.

    Science.gov (United States)

    Takishima, T; Nakamura, M; Sasaki, M; Miyano, M; Yamaya, M; Sasaki, H

    1987-11-01

    We measured pneumomagnetic field strength (PMFS) in 42 healthy control subjects living in districts of Northern Japan with low levels of road dust pollution and in 39 healthy subjects living in areas with high levels of road dust pollution. Suspended road dust produced by studded tires increases from 30 micrograms/m3 during the summer season to levels as high as 400 micrograms/m3 during the snow season in the downtown areas of Sendai, Japan. Road dust retained in the lungs, containing 3% iron, was magnetized from the surface of the chest wall, and PMFS was measured. Three to 5 sequential PMFS measurements were made in each subject in March and October of 1984 and 1985, and in March 1986. The PMFS in control subjects in March 1984 was 37 +/- 14 pico-Tesla (mean +/- SD) and did not significantly differ from the PMFS in October 1984 or that in March 1985. In March 1984, the PMFS of the subjects in highly polluted areas was 95 +/- 100 pico-Tesla (mean +/- SD) and was significantly higher than that of control subjects (p less than 0.01) and subsequently decreased in March 1985 and in March 1986, corresponding to a decrease in suspended road dust brought about by a campaign to eliminate the use of studded tires. Our findings suggest that some road dust caused by studded tires is retained in the lungs.

  17. 76 FR 54408 - Human Subjects Research Protections: Enhancing Protections for Research Subjects and Reducing...

    Science.gov (United States)

    2011-09-01

    ... and Drug Administration 21 CFR Parts 50 and 56 Human Subjects Research Protections: Enhancing Protections for Research Subjects and Reducing Burden, Delay, and Ambiguity for Investigators; Extension of... Secretary of the Department of Health and Human Services (HHS) in coordination with the Office of Science...

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

    African Journals Online (AJOL)

    Items 1 - 50 of 55 ... The Eastern Africa Social Science Research Review (EASSRR) is a ... as well as research from other disciplines working on ideas of relevance to the ..... It publishes New Research from every aspect of the Humanities and the ...

  19. 42 CFR 86.19 - Human subjects; animal welfare.

    Science.gov (United States)

    2010-10-01

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

  20. 42 CFR 86.33 - Human subjects; animal welfare.

    Science.gov (United States)

    2010-10-01

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

  1. 34 CFR 75.681 - Protection of human research subjects.

    Science.gov (United States)

    2010-07-01

    ... Conditions Must Be Met by a Grantee? Other Requirements for Certain Projects § 75.681 Protection of human research subjects. If a grantee uses a human subject in a research project, the grantee shall protect the person from physical, psychological, or social injury resulting from the project. (Authority: 20 U.S.C...

  2. 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...

  3. Differential Scavenging Among Pig, Rabbit, and Human Subjects.

    Science.gov (United States)

    Steadman, Dawnie Wolfe; Dautartas, Angela; Kenyhercz, Michael W; Jantz, Lee M; Mundorff, Amy; Vidoli, Giovanna M

    2018-04-12

    Different animal species have been used as proxies for human remains in decomposition studies for decades, although few studies have sought to validate their use in research aimed at estimating the postmortem interval. This study examines 45 pig, rabbit, and human subjects placed in three seasonal trials at the Anthropology Research Facility. In an earlier paper, we found that overall decomposition trends did vary between species that could be due to differential insect and scavenger behavior. This study specifically examines if scavenger behavior differs by carrion species. Daily photographs, game camera photographs, written observations, and Total Body Score (TBS) documented scavenging and decomposition changes. Results show that raccoons were the most commonly observed vertebrate scavenger, that scavenging was most extensive in winter, and that certain human subjects were preferred over other humans and all non-human subjects. Finally, scavenging activity greatly reduces the accuracy of postmortem interval estimates based on TBS. © 2018 American Academy of Forensic Sciences.

  4. Subject Retrieval from Full-Text Databases in the Humanities

    Science.gov (United States)

    East, John W.

    2007-01-01

    This paper examines the problems involved in subject retrieval from full-text databases of secondary materials in the humanities. Ten such databases were studied and their search functionality evaluated, focusing on factors such as Boolean operators, document surrogates, limiting by subject area, proximity operators, phrase searching, wildcards,…

  5. Committees for Ethics in Research involving human subjects.

    Science.gov (United States)

    Hossne, William Saad; Vieira, Sonia; De Freitas, Corina Bontempo Duca

    2008-01-01

    In Brazil since October 1996 there have been guidelines for research involving human subjects. Now human subjects know when their treatment is part of research. Deceit is no longer tolerated. But is not enough to say we offer an explanation to the potential subject and we offer a choice before he or she is confronted with an informed consent form. As in all professional activity, scientific investigation needs social controls. In Brazil, the ultimate responsibility of an investigation lies on the investigator, but in every institution where research is carried out there is a Committee for Ethics in Research. All Committees are subordinated to the National Commission of Ethics in Research, which is submitted to the Brazilian Institute of Health. During 2005 around 17,000 protocols involving 700,000 human subjects were revised by 475 Committees distributed all over the country. Approximately 7,000 people are now working in these Committees.

  6. Radar cross section of human cardiopulmonary activity for recumbent subject.

    Science.gov (United States)

    Kiriazi, John E; Boric-Lubecke, Olga; Lubecke, Victor M

    2009-01-01

    The radar cross section (RCS) corresponding to human cardio-respiratory motion is measured for a subject in two different recumbent positions. Lying face-up (supine), the subject showed an RCS of 0.326 m(2). But when lying face-down (prone), the RCS increased to 2.9 m(2). This is the first reported RCS measurement corresponding to human cardio-respiratory motion. The results obtained in this experiment suggest modeling the upper part of the human body as a half-cylinder where the front body corresponds to the cylindrical surface and the back corresponds to the rectangular one.

  7. Issues in protection of human subjects in internet research.

    Science.gov (United States)

    Im, Eun-Ok; Chee, Wonshik

    2002-01-01

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

  8. 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.

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

    Science.gov (United States)

    Napier, Stephen

    2013-02-01

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

  10. Assessment of emerging biomarkers of liver injury in human subjects.

    Science.gov (United States)

    Schomaker, Shelli; Warner, Roscoe; Bock, Jeff; Johnson, Kent; Potter, David; Van Winkle, Joyce; Aubrecht, Jiri

    2013-04-01

    Hepatotoxicity remains a major challenge in drug development. Although alanine aminotransferase (ALT) remains the gold standard biomarker of liver injury, alternative biomarker strategies to better predict the potential for severe drug-induced liver injury (DILI) are essential. In this study, we evaluated the utility of glutamate dehydrogenase (GLDH), purine nucleoside phosphorylase (PNP), malate dehydrogenase (MDH), and paraxonase 1 (PON1) as indicators of liver injury in cohorts of human subjects, including healthy subjects across age and gender, subjects with a variety of liver impairments, and several cases of acetaminophen poisoning. In the healthy subjects, levels of GLDH and MDH were not affected by age or gender. Reference ranges for GLDH and MDH in healthy subjects were 1-10 and 79-176U/L, respectively. In contrast, the levels of PON1 and PNP were not consistent across cohorts of healthy subjects. Furthermore, GLDH and MDH had a strong correlation with elevated ALT levels and possessed a high predictive power for liver injury, as determined by ROC analysis. In contrast, PON1 and PNP did not detect liver injury in our study. Finally, evaluation of patients with acetaminophen-induced liver injury provided evidence that both GLDH and MDH might have utility as biomarkers of DILI in humans. This study is the first to evaluate GLDH, MDH, PON1, and PNP in a large number of human subjects and, and it provides an impetus for prospective clinical studies to fully evaluate the diagnostic value of GLDH and MDH for detection of liver injury.

  11. Trust in health research relationships: accounts of human subjects.

    Science.gov (United States)

    McDonald, Michael; Townsend, Anne; Cox, Susan M; Paterson, Natasha Damiano; Lafrenière, Darquise

    2008-12-01

    TRUST IS FUNDAMENTAL in health research, yet there is little empirical evidence that explores the meaning of trust from the perspective of human subjects. The analysis presented here focuses on how human subjects talked about trust in the in-depth interviews. It emerged from the accounts that trust could not be assumed in the research setting, rather it was portrayed as a dynamic concept, built and easily broken, characterized by reciprocity and negotiation. Human subjects were ambivalent about who, when, what, and how much to trust in the research endeavor. This paper adds a fresh perspective to the literature on trust, and so offers a currently neglected, and little understood dimension to the discourse around health research ethics.

  12. Protecting human research subjects: the past defines the future.

    Science.gov (United States)

    Breault, Joseph L

    2006-01-01

    The creation of Institutional Review Boards to assure the protection of research subjects came out of terrible research abuses that resulted in the Belmont Report and federal regulations establishing rules for federally funded research and its independent review. The Common Rule became widely accepted as the way to oversee human research that is funded by federal agencies, or used in FDA submissions. The Office of Human Research Protections, now under the Secretary of DHHS, created Federalwide Assurances with groups that receive federal funding and others, the vast majority of which have agreed to apply the same ethical rules to all research regardless of funding source. There are controversies over the best methods to protect human research subjects, confusion about how to handle some of the gray areas, increased regulatory burdens, and debates about the adequacy of the IRB system. New exciting directions have evolved and overall, research subjects appear better protected than ever.

  13. 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…

  14. Biomineralisation with Saos-2 bone cells on TiSiN sputtered Ti alloys.

    Science.gov (United States)

    V V, Anusha Thampi; Bendavid, Avi; Martin, P J; Vaithilingam, Vijay; Bean, Penelope A; Evans, Margaret D M; Subramanian, B

    2017-07-01

    Surface modifications of metallic implants are important in order to protect the underlying metals from the harsh corrosive environment inside the human body and to minimize the losses caused by wear. Recently, researches are carried out in developing bioactive surfaces on metallic implants, which supports the growth and proliferation of cells on to these surfaces. Titanium silicon nitride (TiSiN) hard nanocomposites thin films were fabricated on Ti alloys (Ti-6Al-4V) by pulsed direct current (DC) reactive magnetron sputtering. The films were characterized for its microstructural and electrochemical behavior. The higher charge transfer resistance (Rct) and positive shift in Ecorr value of TiSiN/Ti alloys than the bare Ti-alloys indicates a better corrosion resistance offered by the TiSiN thin films to the underlying substrates. The biological response to TiSiN/Ti alloys and control bare Ti-alloys was measured in vitro using cell-based assays with two main outcomes. Firstly, neither the Ti alloy nor the TiSiN thin film was cytotoxic to cells. Secondly, the TiSiN thin film promoted differentiation of human bone cells above the bare control Ti alloy as measured by alkaline phosphatase and calcium production. TiSiN thin films provide better corrosion resistance and protect the underlying metal from the corrosive environment. The thin film surface is both biocompatible and bioactive as indicated from the cytotoxicity and biomineralization studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Absorption of orally administered 65Zn by normal human subjects

    International Nuclear Information System (INIS)

    Aamodt, R.L.; Rumble, W.F.; Johnston, G.S.; Markley, E.J.; Henkin, R.I.

    1981-01-01

    Despite studies by several investigators of human gastrointestinal 65Zn absorption, implications of these data for evaluation of functional zinc status are unclear because limited numbers of normal subjects have been studied. To evaluated zinc absorption in normal humans, 75 subjects (31 women, 44 men, ages 18 to 84 yr) were given 10 micro Ci carrier-free 65Zn orally after an overnight fast. Absorption calculated from total body retention measured 7, 14, and 21 days after administration of tracer was 65 +/- 11% (mean +/- 1 SD), range from 40 to 86%. Comparison of these results with those for patients with a variety of diseases indicate that patients exhibit a wider range of absorption and, in four of six studies patients exhibit decreased mean zinc absorption. These results of gastrointestinal zinc absorption in a large number of normal humans offer a basis for a clearer comparison with data from patients who exhibit abnormalities of zinc absorption

  16. Validating in vivo Raman spectroscopy of bone in human subjects

    Science.gov (United States)

    Esmonde-White, Francis W. L.; Morris, Michael D.

    2013-03-01

    Raman spectroscopy can non-destructively measure properties of bone related to mineral density, mineral composition, and collagen composition. Bone properties can be measured through the skin in animal and human subjects, but correlations between the transcutaneous and exposed bone measurements have only been reported for human cadavers. In this study, we examine human subjects to collect measurements transcutaneously, on surgically exposed bone, and on recovered bone fragments. This data will be used to demonstrate in vivo feasibility and to compare transcutaneous and exposed Raman spectroscopy of bone. A commercially available Raman spectrograph and optical probe operating at 785 nm excitation are used for the in vivo measurements. Requirements for applying Raman spectroscopy during a surgery are also discussed.

  17. Response of SAOS-2 cells to simulated microgravity and effect of biocompatible sol-gel hybrid coatings

    Science.gov (United States)

    Catauro, M.; Bollino, F.; Papale, F.

    2016-05-01

    The health of astronauts, during space flight, is threatened by bone loss induced by microgravity, mainly attributed to an imbalance in the bone remodeling process. In the present work, the response to the microgravity of bone cells has been studied using the SAOS-2 cell line grown under the condition of weightlessness, simulated by means of a Random Positioning Machine (RPM). Cell viability after 72 h of rotation has been evaluated by means of WST-8 assay and compared to that of control cells. Although no significant difference between the two cell groups has been observed in terms of viability, F-actin staining showed that microgravity environment induces cell apoptosis and altered F-actin organization. To investigate the possibility of hindering the trend of the cells towards the death, after 72 h of rotation the cells have been seeded onto biocompatible ZrO2/PCL hybrid coatings, previously obtained using a sol-gel dip coating procedure. WST-8 assay, carried out after 24 h, showed that the materials are able to inhibit the pro-apoptotic effect of microgravity on cells.

  18. Administration of ionizing radiation to human subjects in medical research

    International Nuclear Information System (INIS)

    1985-01-01

    Any administration of ionizing radiation to human subjects for the purposes of diagnostic or therapeutic research involving either irradiation or the administration of radionuclides, should be undertaken only after approval by an institutional ethics committee. The ethics committee should obtain advice from a person experienced in radiation protection before granting approval. The research proposal must conform to regulatory requirements relating to the use of ionizing radiation

  19. Wheat bran cereal, human gut bacteria and subjective wellbeing

    OpenAIRE

    Smith, Andrew; Deaville, Eddie; Gibson, Glenn

    2018-01-01

    Research has shown that consumption of high fiber breakfast cereal is associated with improved subjective well-being, especially increased energy. One possible explanation of these results is through metabolism by gut bacteria and concomitant production of metabolites that influence psychological and gastrointestinal (GI) welfare. This was examined in the present study to determine whether consumption of wheat bran could modulate the composition of the GI microbiota. This human volunteer stud...

  20. ETHICS IN HEALTH CARE: INDUCEMENT AND HUMAN SUBJECTS

    Directory of Open Access Journals (Sweden)

    MUNIR HOSSAIN TALUKDER

    2011-05-01

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

  1. Influence of SaOS-2 cells on corrosion behavior of cast Mg-2.0Zn0.98Mn magnesium alloy.

    Science.gov (United States)

    Witecka, Agnieszka; Yamamoto, Akiko; Święszkowski, Wojciech

    2017-02-01

    In this research, the effect of the presence of living cells (SaOS-2) on in vitro degradation of Mg-2.0Zn-0.98Mn (ZM21) magnesium alloy was examined by two methods simple immersion/cell culture tests and electrochemical measurements (electrochemical impedance spectroscopy and potentiodynamic polarization) under cell culture conditions. In immersion/cell culture tests, when SaOS-2 cells were cultured on ZM21 samples, pH of cell culture medium decreased, therefore weight loss and Mg 2+ ion release from the samples increased. Electrochemical measurements revealed the presence of living cells increased corrosion rate (I corr ) and decreased polarization resistance (R p ) after 48h of incubation. This acceleration of ZM21 corrosion can mainly be attributed to the decrease of medium pH due to cellular metabolic activities. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. The irradiation of human volunteer subjects in research

    International Nuclear Information System (INIS)

    Rosen, R.

    1980-01-01

    In medical research radiation is sometimes used to obtain data from healthy individuals. These subjects gain no specific benefit from the research. To safeguard their welfare, constraints are imposed on the dose to be received, on the selection of volunteer subjects, on ensuring their understanding of the procedures and risks, and on obtaining their free consent to participate. The research proposals are assessed by peer review prior to being approved by the host institution. The first example presented describes the use of diagnostic radiography to obtain in vivo data on the femur bone. Conservative dosimetry indicates an expected dose-equivalent per film of 0.5 mSv in bone and 0.18 mSv in bone marrow and gonad tissue. The critical organ total dose-equivalent is estimated to be 7% of the dose-equivalent limit for a volunteer. The second example involves the internal administration of radioactive tracers. Dosimetric calculations indicate an expected whole-body dose-equivalent of 0.5 mSv in the case of C-14 and 0.37 mSv in the case of H-3, these values bejng 10% and 7% of the relevant dose-equivalent limit. Both proposals were given conditional approval. In the generalized research use of volunteer human subjects the rights of the subject, the investigator and the institution need to be protected. At the University of New South Wales procedures have been introduced to govern all experjmental procedures involving human subjects. Some interesting problems which have arisen are discussed. (author)

  3. Microarray expression profiling of human dental pulp from single subject.

    Science.gov (United States)

    Tete, Stefano; Mastrangelo, Filiberto; Scioletti, Anna Paola; Tranasi, Michelangelo; Raicu, Florina; Paolantonio, Michele; Stuppia, Liborio; Vinci, Raffaele; Gherlone, Enrico; Ciampoli, Cristian; Sberna, Maria Teresa; Conti, Pio

    2008-01-01

    Microarray is a recently developed simultaneous analysis of expression patterns of thousand of genes. The aim of this research was to evaluate the expression profile of human healthy dental pulp in order to find the presence of genes activated and encoding for proteins involved in the physiological process of human dental pulp. We report data obtained by analyzing expression profiles of human tooth pulp from single subjects, using an approach based on the amplification of the total RNA. Experiments were performed on a high-density array able to analyse about 21,000 oligonucleotide sequences of about 70 bases in duplicate, using an approach based on the amplification of the total RNA from the pulp of a single tooth. Obtained data were analyzed using the S.A.M. system (Significance Analysis of Microarray) and genes were merged according to their molecular functions and biological process by the Onto-Express software. The microarray analysis revealed 362 genes with specific pulp expression. Genes showing significant high expression were classified in genes involved in tooth development, protoncogenes, genes of collagen, DNAse, Metallopeptidases and Growth factors. We report a microarray analysis, carried out by extraction of total RNA from specimens of healthy human dental pulp tissue. This approach represents a powerful tool in the study of human normal and pathological pulp, allowing minimization of the genetic variability due to the pooling of samples from different individuals.

  4. Insulin resistance in human subjects having impaired glucose regulation

    International Nuclear Information System (INIS)

    Khan, S.H.; Khan, F.A.; Ijaz, A.

    2007-01-01

    To determine insulin resistance in human subjects having impaired glucose regulation (IGR) by Homeostasis Model Assessment for Insulin Resistance (HOMA-IR). A total of 100 subjects with impaired glucose regulation were selected for evaluation of metabolic syndrome as per the criteria of National Cholesterol Education Program, Adult Treatment Panel III (NCEP, ATP III), along with 47 healthy age and gender-matched controls. Physical examination to determine blood pressure and waist circumference was carried out and so was sampling for plasma glucose, serum triglycerides, HDL-cholesterol and insulin. Insulin resistance was calculated by the HOMA-IR. Finally, subjects with and without metabolic syndrome were compared with controls (n=47), using one-way ANOVA for studying insulin resistance between groups, with Tukey's post-hoc comparison. The frequency of finding metabolic syndrome in cases of IGR remained 47%. The insulin resistance demonstrated stepwise worsening from control population (mean=1.54, 95 % CI: 1.77 - 2.37) to subjects suffering from only IGR (mean=2.07, 95 % CI: 1.77- 2.37) to metabolic syndrome (mean=2.67, 95 %, CI: 2.34 - 3.00) (p < 0.001). Patients with impaired glucose regulation may have significant insulin resistance. It is, thus, recommended that a vigorous search be made to measure insulin resistance in all cases diagnosed to have impaired glucose regulation. (author)

  5. Cranberry juice suppressed the diclofenac metabolism by human liver microsomes, but not in healthy human subjects

    Science.gov (United States)

    Ushijima, Kentarou; Tsuruoka, Shu-ichi; Tsuda, Hidetoshi; Hasegawa, Gohki; Obi, Yuri; Kaneda, Tae; Takahashi, Masaki; Maekawa, Tomohiro; Sasaki, Tomohiro; Koshimizu, Taka-aki; Fujimura, Akio

    2009-01-01

    AIM To investigate a potential interaction between cranberry juice and diclofenac, a substrate of CYP2C9. METHODS The inhibitory effect of cranberry juice on diclofenac metabolism was determined using human liver microsome assay. Subsequently, we performed a clinical trial in healthy human subjects to determine whether the repeated consumption of cranberry juice changed the diclofenac pharmacokinetics. RESULTS Cranberry juice significantly suppressed diclofenac metabolism by human liver microsomes. On the other hand, repeated consumption of cranberry juice did not influence the diclofenac pharmacokinetics in human subjects. CONCLUSIONS Cranberry juice inhibited diclofenac metabolism by human liver microsomes, but not in human subjects. Based on the present and previous findings, we think that although cranberry juice inhibits CYP2C9 activity in vitro, it does not change the pharmacokinetics of medications metabolized by CYP2C9 in clinical situations. PMID:19694738

  6. Ethical issues in neonatal research involving human subjects.

    Science.gov (United States)

    Fleischman, Alan R

    2016-06-01

    Research involving critically ill neonates creates many ethical challenges. Neonatal clinical research has always been hard to perform, is very expensive, and may generate some unique ethical concerns. This article describes some examples of historical and modern controversies in neonatal research, discusses the justification for research involving such vulnerable and fragile patients, clarifies current federal regulations that govern research involving neonates, and suggests ways that clinical investigators can develop and implement ethically grounded human subjects research. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. SaOS-2 cell response to macro-porous boron-incorporated TiO{sub 2} coating prepared by micro-arc oxidation on titanium

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Qianli [State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Elkhooly, Tarek A. [State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Department of Ceramics, Inorganic Chemical Industries Division, National Research Centre, Dokki, 12622 Cairo (Egypt); Liu, Xujie [State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055 (China); Zhang, Ranran; Yang, Xing; Shen, Zhijian [State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Feng, Qingling, E-mail: biomater@mail.tsinghua.edu.cn [State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Key Laboratory of Advanced Materials of Ministry of Education of China, School of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China)

    2016-10-01

    The aims of the present study were to develop boron-incorporated TiO{sub 2} coating (B-TiO{sub 2} coating) through micro-arc oxidation (MAO) and subsequently evaluate the effect of boron incorporation on the in vitro biological performance of the coatings. The physicochemical properties of B-TiO{sub 2} coating and its response to osteoblast like cells (SaOS-2) were investigated compared to the control group without boron (TiO{sub 2} coating). The morphological and X-ray diffraction results showed that both coatings exhibited similar surface topography and phase composition, respectively. However, the incorporation of B led to an enhancement in the surface hydrophilicity of B-TiO{sub 2} coating. The spreading of SaOS-2 cells on B-TiO{sub 2} coating was faster than that on TiO{sub 2} coating. The proliferation rate of SaOS-2 cells cultured on B-TiO{sub 2} decreased after 5 days of culture compared to that on TiO{sub 2} coating. SaOS-2 cells cultured on B-TiO{sub 2} coating exhibited an enhanced alkaline phosphatase (ALP) activity, Collagen I synthesis and in vitro mineralization compared to those on TiO{sub 2} coating. The present findings suggest that B-TiO{sub 2} coating is a promising candidate surface for orthopedic implants. - Highlights: • SaOS-2 cell response to pure TiO{sub 2} and B-TiO{sub 2} coatings was investigated. • Initial cell spreading on B-TiO{sub 2} coating was accelerated compared to that on TiO{sub 2} coating. • Cell proliferation on B-TiO{sub 2} coating was inhibited compared to that on TiO{sub 2} coating. • Cell differentiation on B-TiO{sub 2} coating was enhanced compared to that on TiO{sub 2} coating.

  8. Human autonomic rhythms: vagal cardiac mechanisms in tetraplegic subjects

    Science.gov (United States)

    Koh, J.; Brown, T. E.; Beightol, L. A.; Ha, C. Y.; Eckberg, D. L.

    1994-01-01

    1. We studied eight young men (age range: 20-37 years) with chronic, clinically complete high cervical spinal cord injuries and ten age-matched healthy men to determine how interruption of connections between the central nervous system and spinal sympathetic motoneurones affects autonomic cardiovascular control. 2. Baseline diastolic pressures and R-R intervals (heart periods) were similar in the two groups. Slopes of R-R interval responses to brief neck pressure changes were significantly lower in tetraplegic than in healthy subjects, but slopes of R-R interval responses to steady-state arterial pressure reductions and increases were comparable. Plasma noradrenaline levels did not change significantly during steady-state arterial pressure reductions in tetraplegic patients, but rose sharply in healthy subjects. The range of arterial pressure and R-R interval responses to vasoactive drugs (nitroprusside and phenylephrine) was significantly greater in tetraplegic than healthy subjects. 3. Resting R-R interval spectral power at respiratory and low frequencies was similar in the two groups. During infusions of vasoactive drugs, low-frequency R-R interval spectral power was directly proportional to arterial pressure in tetraplegic patients, but was unrelated to arterial pressure in healthy subjects. Vagolytic doses of atropine nearly abolished both low- and respiratory-frequency R-R interval spectral power in both groups. 4. Our conclusions are as follows. First, since tetraplegic patients have significant levels of low-frequency arterial pressure and R-R interval spectral power, human Mayer arterial pressure waves may result from mechanisms that do not involve stimulation of spinal sympathetic motoneurones by brainstem neurones. Second, since in tetraplegic patients, low-frequency R-R interval spectral power is proportional to arterial pressure, it is likely to be mediated by a baroreflex mechanism. Third, since low-frequency R-R interval rhythms were nearly abolished

  9. Bioavailability and Pharmacodynamics of Promethazine in Human Subjects

    Science.gov (United States)

    Boyd, J. L.; Boster, B.; Wang, Z.; Shah, V.; Berens, K. L.; Sipes, W. E.; Anderson, K. E.; Putcha, L.

    2004-01-01

    The acute effects of exposure to microgravity include the development of space motion sickness, which usually requires therapeutic intervention. The current drug of choice, promethazine (PMZ), is available to astronauts in three different dosage forms during space flight; its side effects include nausea, dizziness, sedation and impaired psychomotor performance. This ground-based study is designed to validate flight-suitable methods for pharmacodynamic evaluation of PMZ and to estimate bioavailability and pharmacodynamics of PMZ. Experimental design consists of intramuscular administration of three doses of PMZ (12.5,25 and 50 mg) and placebo in a randomized double blind fashion to human subjects and collecting blood, urine and saliva samples for 72 h. Subjects also complete cognitive performance test batteries, WinSCAT (Windows based Space Cognitive Assessment Test) and ARES (ANAM Readiness Evaluation System). Preliminary results indicate a significant relationship (p=9.88e-05) between circulating PMZ levels and cognitive performance parameters. Time to accurately complete memory tasks increases significantly with concentrations; higher concentrations also increase response time and decrease accuracy of substitution and matching tasks. AUC and half-life estimates for PMZ ranged between 0.12 and 1.7 mg.h/L and 15 and 50 h, respectively. These preliminary results indicate that PMZ may exhibit dose-dependent pharmacokinetics in humans; also, WinSCAT and ARES are sensitive for pharmacodynamic assessment of PMZ, and may be applicable for assessing the pharmacodynamics of other neurocognitive drugs.

  10. 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. 

  11. Medical students as human subjects in educational research

    Directory of Open Access Journals (Sweden)

    Adina L. Kalet

    2013-02-01

    Full Text Available Introduction: Special concerns often arise when medical students are themselves the subjects of education research. A recently completed large, multi-center randomized controlled trial of computer-assisted learning modules for surgical clerks provided the opportunity to explore the perceived level of risk of studies where medical students serve as human subjects by reporting on: 1 the response of Institutional Review Boards (IRBs at seven institutions to the same study protocol; and 2 the thoughts and feelings of students across study sites about being research subjects. Methods: From July 2009 to August 2010, all third-year medical students at seven collaborating institutions were eligible to participate. Patterns of IRB review of the same protocol were compared. Participation burden was calculated in terms of the time spent interacting with the modules. Focus groups were conducted with medical students at each site. Transcripts were coded by three independent reviewers and analyzed using Atlas.ti. Results: The IRBs at the seven participating institutions granted full (n=1, expedited (n=4, or exempt (n=2 review of the WISE Trial protocol. 995 (73% of those eligible consented to participate, and 207 (20% of these students completed all outcome measures. The average time to complete the computer modules and associated measures was 175 min. Common themes in focus groups with participant students included the desire to contribute to medical education research, the absence of coercion to consent, and the low-risk nature of the research. Discussion: Our findings demonstrate that risk assessment and the extent of review utilized for medical education research vary among IRBs. Despite variability in the perception of risk implied by differing IRB requirements, students themselves felt education research was low risk and did not consider themselves to be vulnerable. The vast majority of eligible medical students were willing to participate as research

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

    NARCIS (Netherlands)

    van der Graaf - Verhave, R.

    2010-01-01

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

  13. 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%.

  14. Managing incidental findings in human subjects research: analysis and recommendations.

    Science.gov (United States)

    Wolf, Susan M; Lawrenz, Frances P; Nelson, Charles A; Kahn, Jeffrey P; Cho, Mildred K; Clayton, Ellen Wright; Fletcher, Joel G; Georgieff, Michael K; Hammerschmidt, Dale; Hudson, Kathy; Illes, Judy; Kapur, Vivek; Keane, Moira A; Koenig, Barbara A; Leroy, Bonnie S; McFarland, Elizabeth G; Paradise, Jordan; Parker, Lisa S; Terry, Sharon F; Van Ness, Brian; Wilfond, Benjamin S

    2008-01-01

    No consensus yet exists on how to handle incidental findings (IFs) in human subjects research. Yet empirical studies document IFs in a wide range of research studies, where IFs are findings beyond the aims of the study that are of potential health or reproductive importance to the individual research participant. This paper reports recommendations of a two-year project group funded by NIH to study how to manage IFs in genetic and genomic research, as well as imaging research. We conclude that researchers have an obligation to address the possibility of discovering IFs in their protocol and communications with the IRB, and in their consent forms and communications with research participants. Researchers should establish a pathway for handling IFs and communicate that to the IRB and research participants. We recommend a pathway and categorize IFs into those that must be disclosed to research participants, those that may be disclosed, and those that should not be disclosed.

  15. 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.

  16. 34 CFR 97.118 - Applications and proposals lacking definite plans for involvement of human subjects.

    Science.gov (United States)

    2010-07-01

    ... Education PROTECTION OF HUMAN SUBJECTS Federal Policy for the Protection of Human Subjects (Basic ED Policy for Protection of Human Research Subjects) § 97.118 Applications and proposals lacking definite plans..., or contracts are submitted to departments or agencies with the knowledge that subjects may be...

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

    Science.gov (United States)

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

    2012-10-28

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

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

    Science.gov (United States)

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

    2013-01-01

    Drugs absorbed poorly through the skin are commonly delivered via injection with a hypodermic needle, which is painful and increases the risk of transmitting infectious diseases. Microneedles (MNs) selectively and painlessly permeabilize the outermost skin layer, allowing otherwise skin-impermeable drugs to cross the skin through micron-sized pores and reach therapeutic concentrations. However, rapid healing of the micropores prevents further drug delivery, blunting the clinical utility of this unique transdermal technique. We present the first human study demonstrating that micropore lifetime can be extended following MN treatment. Subjects received one-time MN treatment and daily topical application of diclofenac sodium. Micropore closure was measured with impedance spectroscopy, and area under the admittance–time curve (AUC) was calculated. AUC was significantly higher at MN + diclofenac sodium sites vs. placebo, suggesting slower rates of micropore healing. Colorimetry measurements confirmed the absence of local erythema and irritation. This mechanistic human proof-of-concept study demonstrates that micropore lifetime can be prolonged with simple topical administration of a non-specific cyclooxygenase inhibitor, suggesting the involvement of subclinical inflammation in micropore healing. These results will allow for longer patch wear time with MN-enhanced delivery, thus increasing patient compliance and expanding the transdermal field to a wider variety of clinical conditions. PMID:22929967

  19. Utilidad de la relación Sao2/Fio2 en la evaluación del grado de compromiso pulmonar en pacientes críticos

    Directory of Open Access Journals (Sweden)

    Alonso Gómez Duque

    2002-01-01

    Full Text Available Background: Arteriovenous admixture or intrapulmonary shunt and the relation between PaO2 and FI02 (PaO2/FiO2 have been advocated as the main indicators of pulmonary function. Because the Pa02 is a measure of the oxygen given to the tissues, as well as the Sa02, we could expect a close relationship between the Pa02IFI02 index and a new one, the SaO2/FiO2 index, Methods: We conducted a prospective study in a cohortofl07 patients with different pathologies in an Intensive Care Unit, collecting 507 samples of arterial and central venous gases and measuring the Sa02 by pulse oximeter at the same time. PaO2/FiO2 and Sa O2/FiO2, as well as intrapulmonary shunt using invasive and noninvasive methods, were caIculated. The Lung Injury Score (LIS and the Multiple Organ Dysfunction score were calculated too. Results: We found a good correlation between Sa O2/FiO2 and PaO2/FiO2. (R2=0,81,R=0.9, and between the intrapulmonary shuntfraction calculated with invasive and noninvasive methods.(R2=0.75, R=0.86. The data were correlationed with a simple linear regression analysis. Five groups of SaO2/FiO2 were found and a punctuation from Oto 4 was established for them, in a similar approach to the one used by Murray in the Lung Injury Score (LIS and Marshall in the Multiple Organ Dysfunction score. By using this punctuation, we replaced the PaO2/FiO2 by the SaO2/FiO2 in the scale and recalculated the LIS finding a good correlation between the score with PaO2/FiO2 and the one with SaO2/FiO2 (R2=0.94,R=0.96. The same was true for the correlation between the Marshall score with PaO2/FiO2 and the one with SaO2/FiO2. (R2=O.85, R=0.92. The correlation was mantained when a stratified analysis was made according to the degree of severity of the pulmonary injury. Conclusions: SaO2/FiO2 is an useful indicator of the oxygenation in a similar way as the PaO2/FiO2 índex, It could be incorporated into the LIS and Marshall score with similar results. The usefulness of the intrapulmonary shunt calculated by noninvasive methods is confirmed.

  20. 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

  1. 48 CFR 352.270-4 - Protection of human subjects.

    Science.gov (United States)

    2010-10-01

    ... subjects as well as to graphic, written, or recorded information derived from individually identifiable... relation to both the potential benefits, if any, to the subjects and the importance of the knowledge to be... contract until the Contractor corrects the noncompliance. The Contracting Officer may communicate the...

  2. 75 FR 62738 - Revisions to EPA's Rule on Protections for Subjects in Human Research Involving Pesticides...

    Science.gov (United States)

    2010-10-13

    ... addressed in EPA science and ethics reviews of proposed and completed human research for pesticides, based... Revisions to EPA's Rule on Protections for Subjects in Human Research Involving Pesticides; Notification to... protection of human subjects of research that apply to third parties who conduct or support research for...

  3. 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'…

  4. Ethical issues in Alzheimer's disease research involving human subjects.

    Science.gov (United States)

    Davis, Dena S

    2017-12-01

    As we aggressively pursue research to cure and prevent Alzheimer's disease, we encounter important ethical challenges. None of these challenges, if handled thoughtfully, would pose insurmountable barriers to research. But if they are ignored, they could slow the research process, alienate potential study subjects and do damage to research recruits and others. These challenges are (1) the necessity of very large cohorts of research subjects, recruited for lengthy studies, probably ending only in the subjects' death; (2) the creation of cohorts of 'study ready' volunteers, many of whom will be competent to consent at the beginning of the process, but move into cognitive impairment later; (3) reliance on adaptive trial design, creating challenges for informed consent, equipoise and justice; (4) the use of biomarkers and predictive tests that describe risk rather than certainty, and that can threaten participants' welfare if the information is obtained by insurance companies or long-term care providers; (5) the use of study partners that creates unique risks of harm to the relationship of subject and study partner. We need greater attention, at all levels, to these complex ethical issues. Work on these issues should be included in research plans, from the federal to the local, and should be supported through NIH in the same way that it supported work on the ethical, legal and social implications of genetic research. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  5. Instrumental analysis for mercury in thumbnails of human subjects

    Energy Technology Data Exchange (ETDEWEB)

    Kanabrocki, E L; Kanabrocki, J A; Greco, J [Veterans Administration Hospital, Hines, Ill. (USA)

    1977-07-01

    Mercury levels in thumbnails were determined by instrumental analysis using thermal neutron activation technique. Samples were obtained from 14 subjects employed in the hospital dental service (a), 19 in the clinical laboratories (b), and from 16 hospitalized patients who were not employed in laboratory occupations (c). The average mercury levels in ppM for the respective groups were: (a) dentists, 2.7; technicians, 3.9; assistants, 6.6; (b) male technicians, 0.4; female technicians, 1.9; (c) patients, 0.3.

  6. Robot Tracking of Human Subjects in Field Environments

    Science.gov (United States)

    Graham, Jeffrey; Shillcutt, Kimberly

    2003-01-01

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

  7. Adhesion and differentiation of Saos-2 osteoblast-like cells on chromium-doped diamond-like carbon coatings

    Czech Academy of Sciences Publication Activity Database

    Filová, Elena; Vandrovcová, Marta; Jelínek, Miroslav; Zemek, Josef; Houdková, Jana; Remsa, Jan; Kocourek, Tomáš; Staňková, Ľubica; Bačáková, Lucie

    2017-01-01

    Roč. 28, č. 1 (2017), č. článku 17. ISSN 0957-4530 R&D Projects: GA ČR(CZ) GA15-05864S; GA ČR(CZ) GA14-04790S; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:67985823 ; RVO:68378271 Keywords : osteocalcin * osteogenic differentiation * hexavalent chromium * focal adhesion contact * cell spreading area Subject RIV: EI - Biotechnology ; Bionics OBOR OECD: Biomaterials (as related to medical implants, devices, sensors) Impact factor: 2.325, year: 2016

  8. 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.

  9. 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.

  10. Ethical and social implications of microdosing clinical trial (3). Radiological protection of human subjects in research

    International Nuclear Information System (INIS)

    Kurihara, Chieko

    2008-01-01

    Internal irradiation of human subjects in research is discussed. Radiological protection of human subjects in medical research in a framework of radiation protection is surveyed from a viewpoint of general life-ethics and research-ethics. A workshop 'On the internal irradiation of human subjects' to summarize special and systematic knowledge was organized by Research Center for Radiation Protection, National Institute of Radiological Sciences in the beginning of 2008. Activities of this workshop are introduced. Discussion covers also (1) Research ethics and radiation protection, (2) Fundamentals and applications of risk-benefit assessment, (3) Human subjects risk assessment in ICRP recommendation, (4) Mechanism of human subjects internal irradiation assessment, and (5) Present status and future prospects in Japan. (K.Y.)

  11. Bioavailability and Pharmacodynamics of Promethazine in Human Subjects

    Science.gov (United States)

    Putcha, Lakshmi; Flynn, Chris; Paloski, W. H. (Technical Monitor)

    2000-01-01

    Space Motion Sickness (SMS) is often treated in space with promethazine (PMZ). Anecdotal reports indicate that the common side effects of drowsiness and decrements in cognitive performance that are associated with PMZ administration (50 mg IM on the ground, are absent or less pronounced in space suggesting I that-the bioavailability and/or pharmacodynamic behavior of PMZ may be altered during space flight. There are limited flight opportunities available for clinical research in space, the NRA-99, therefore, solicits research required to improve, or answer specific questions about in-flight diagnosis, therapy, and post-flight rehabilitation. We propose here, to establish a noninvasive method for pharmacodynamic and therapeutic assessment of PMZ. The specific objectives of the proposed research are to, 1. Establish a saliva to plasma ratio of PMZ after administration, 2. Estimate the relative bioavailability of the three flight-specific dosage forms of PMZ, and 3. Establish the dose-response relationship of PMZ. We will estimate the bioavailability of intramuscular injection (IM), oral tablets and rectal suppositories in normal subjects during ambulatory and antiorthostatic; bed rest (ABR) conditions using novel stable isotope techniques. Drowsiness, cognitive performance and salivary flow rate will be measured as a function of circulating drug concentrations after administration of three IM doses of PMZ. We will compare and contrast the bioavailability of PMZ during normal and ABR conditions to examine whether or not ABR can simulate changes in drug, absorption and availability similar to those anticipated in a microgravity environment. Results of this study will validate methods for an approved study with this medication awaiting a flight opportunity for manifestation. These data will also provide the much needed information on the dynamics and therapeutic index. of this medication and their implications on crew fatigue and performance in space. Key words

  12. Lipolytic response to glucose infusion in human subjects

    International Nuclear Information System (INIS)

    Wolfe, R.R.; Peters, E.J.

    1987-01-01

    The authors have determined the effect of various rates of glucose infusion on the rates of release of glycerol (R/sub a/ glycerol), free fatty acids (R/sub a/ FFA), and on energy metabolism in normal human volunteers. Plasma kinetics were determined with use of the stable isotopic tracers D-5-glycerol and [1- 13 C]palmitate, and energy metabolism was determined by indirect calorimetry. The effect of glucose infusion on R/sub a/ glycerol and R/sub a/ FFA was dose-dependent. At 4 mg x kg -1 x min -1 , both R/sub a/ glycerol and R/sub a/ FFA were suppressed; at 8 mg x kg -1 x min -1 , R/sub a/ FFA was even more depressed, but R/sub a/ glycerol was similar to the value during the 4 mg x kg -1 x min -1 infusion. At all infusion rates tested, the amount of potential energy available from the sum of the glucose infusion and endogenously mobilized fat was always greater than when no glucose was infused. Glucose decreased fat mobilization by both inhibiting lipolysis and stimulating reesterification, thus causing a significant increase in triglyceride-fatty acid substrate cycling within the adipose tissue. Plasma insulin was determined by radioimmunoassay

  13. 76 FR 5735 - Revisions to EPA's Rule on Protections for Subjects in Human Research Involving Pesticides

    Science.gov (United States)

    2011-02-02

    ... addressed in EPA science and ethics reviews of proposed and completed human research with pesticides, drawn..., which suggest ethical considerations relevant to evaluation of human studies. Third, Petitioners argued... Revisions to EPA's Rule on Protections for Subjects in Human Research Involving Pesticides AGENCY...

  14. Researcher liability for negligence in human subject research: informed consent and researcher malpractice actions.

    Science.gov (United States)

    Jansson, Roger L

    2003-02-01

    Two sets of federal regulations, the "Common Rule" and Food and Drug Administration (FDA) regulations, govern human subject research that is either federally-funded or involves FDA regulated products. These regulations require, inter alia, that: (1) researchers obtain informed consent from human subjects, and (2) that an Institutional Review Board (IRB) independently review and approve the research protocol. Although the federal regulations do not provide an express cause of action against researchers, research subjects should be able to bring informed consent and malpractice actions against researchers by establishing a duty of care and standard of care. Researchers owe human subjects a duty of care analogous to the special relationship between physicians and patients. The federal regulations should provide the minimum standard of care for informed consent in human subject research, and complying with them should be a partial defense. In contrast, expert testimony should establish the standard of care for researcher malpractice, and IRB approval should be a partial defense.

  15. Ethics is for human subjects too: participant perspectives on responsibility in health research.

    Science.gov (United States)

    Cox, Susan M; McDonald, Michael

    2013-12-01

    Despite the significant literature as well as energy devoted to ethical review of research involving human subjects, little attention has been given to understanding the experiences of those who volunteer as human subjects. Why and how do they decide to participate in research? Is research participation viewed as a form of social responsibility or as a way of obtaining individual benefits? What if anything do research subjects feel they are owed for participation? And what do they feel that they owe the researcher? Drawing on in-depth individual interviews conducted in 2006 and 2007 with 41 subjects who participated in a variety of types of health research in Canada, this paper focuses on subject perspectives on responsibility in research. Highlighting the range of ways that subjects describe their involvement in research and commitments to being a 'good' subject, we present a typology of narratives that sheds new light on the diverse meanings of research participation. These narratives are not mutually exclusive or prescriptive but are presented as ideal types typifying a set of circumstances and values. As such, they collectively illuminate a range of motivations expressed by human subjects as well as potential sources of vulnerability. The typology adds a new dimension to the literature in this area and has significant implications for researchers seeking more human-subject centred approaches to research recruitment and retention, as well as research ethics boards trying to better anticipate the perspectives of prospective participants. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

    African Journals Online (AJOL)

    Dr Olaleye

    use animals for research and experimentations to research on human subjects. Jonas upholds the ..... examples of ethical theory, the less said about it the better. But what is allowable .... Also, man seeks self-gratification and self- promotion.

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

    OpenAIRE

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

    2016-01-01

    Internet-connected devices are changing the way people live, work, and relate to one another. For prevention scientists, technological advances create opportunities to promote the welfare of human subjects and society. The challenge is to obtain the benefits while minimizing risks. In this article, we use the guiding principles for ethical human subjects research and proposed changes to the Common Rule regulations, as a basis for discussing selected opportunities and challenges that new techn...

  18. Metabolic mapping of functional activity in human subjects with the [18F]fluorodeoxyglucose technique

    International Nuclear Information System (INIS)

    Greenberg, J.H.; Reivich, M.; Alavi, A.

    1981-01-01

    The 2-[ 18 F]fluoro-2-deoxy-D-glucose technique was used to measure regional cerebral glucose utilization by human subjects during functional activation. Normal male volunteers subjected to one or more sensory stimuli exhibited focal increases in glucose metabolism in response to the stimulus. These results demonstrate that the technique is capable of providing functional maps in vivo related to both body region and submodality of sensory information in the human brain

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

    African Journals Online (AJOL)

    Hans Jonas' thought on the ethics of research on human subjects and its implications for contemporary medical research in Nigeria was examined. 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 ...

  20. The Impact of the Protection of Human Subjects on Research. Working Paper No. 70.

    Science.gov (United States)

    Halpern, Andrew S.

    The author discusses the experimenter's responsibility for the protection of human subjects (such as the handicapped) in research and the impact of this responsibility on methods of doing research. Considered are the types of human rights that are most frequently in need of protection within a research setting (such as the right to privacy); the…

  1. 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...

  2. [The physical therapy undergraduate students' responses to the gross human anatomy subjects].

    Science.gov (United States)

    Anahara, Reiko; Kawashiro, Yukiko; Matsuno, Yoshiharu; Mori, Chisato; Kohno, Toshihiko

    2008-09-01

    Instruction in gross human anatomy is one of the important items in the subject for co-medical students of the physical therapist course. The physical therapy undergraduate students are required to have a solid understanding of the structure and formation of the human body. Therefore, their good-understanding of the course on the gross human anatomy and their experience of the gross human anatomy laboratory (observation practice) are acquired to improve their knowledge of the human body. To clarify the student responses to the gross human anatomy course including the gross human anatomy laboratory, several questionnaires were administered to the freshman physical therapy undergraduate student for two years. We found that more than 80% of the students, who felt a negative attitude for gross human anatomy before the course started, had a positive attitude about the gross human anatomy after going through the course. The experience of the gross human anatomy laboratory increased the students' activity of learning and they thought more about the dignity of being human after the course than before viewing. In addition, the results suggested that the multiple experiences of the gross human anatomy course are useful for the physical therapy undergraduate students to improve the quality of their understanding of the human body.

  3. A Subject-Specific Kinematic Model to Predict Human Motion in Exoskeleton-Assisted Gait.

    Science.gov (United States)

    Torricelli, Diego; Cortés, Camilo; Lete, Nerea; Bertelsen, Álvaro; Gonzalez-Vargas, Jose E; Del-Ama, Antonio J; Dimbwadyo, Iris; Moreno, Juan C; Florez, Julian; Pons, Jose L

    2018-01-01

    The relative motion between human and exoskeleton is a crucial factor that has remarkable consequences on the efficiency, reliability and safety of human-robot interaction. Unfortunately, its quantitative assessment has been largely overlooked in the literature. Here, we present a methodology that allows predicting the motion of the human joints from the knowledge of the angular motion of the exoskeleton frame. Our method combines a subject-specific skeletal model with a kinematic model of a lower limb exoskeleton (H2, Technaid), imposing specific kinematic constraints between them. To calibrate the model and validate its ability to predict the relative motion in a subject-specific way, we performed experiments on seven healthy subjects during treadmill walking tasks. We demonstrate a prediction accuracy lower than 3.5° globally, and around 1.5° at the hip level, which represent an improvement up to 66% compared to the traditional approach assuming no relative motion between the user and the exoskeleton.

  4. How to do human-subjects research if you do not have an institutional review board.

    Science.gov (United States)

    Rice, Todd W

    2008-10-01

    Biomedical research with human subjects has expanded outside of traditional medical centers and hospitals into other health care entities, such as rehabilitation facilities, free-standing out-patient treatment centers, and even home-health agencies. Regardless of the location, federal regulations mandate that all human-subjects research must be overseen by an institutional review board (IRB) or ethics committee to ensure the research abide by the Code of Federal Regulations. Consequently, all human-subjects research must be reviewed and approved by an IRB prior to initiation of any research procedures. Unfortunately, many of these nontraditional research facilities do not have easy access to an IRB. This does not render such research exempt from federal oversight. Clinicians at these facilities have viable options for obtaining IRB approval and legally conducting such research. This paper outlines the available options and their pros and cons.

  5. [Autoshaping of a button-push response and eye movement in human subjects].

    Science.gov (United States)

    Kimura, H; Fukui, I; Inaki, K

    1990-12-01

    Two experiments were conducted with human subjects to investigate the similarities and differences between animal and human behaviors under autoshaping procedures. In these experiments, light served as CS, and display on TV served as US. Whether the pushing button response or gazing response to CS could be obtained in human subjects under Pavlovian conditioning procedure was examined. In Experiment 1, uninstructed naive subjects were placed in a room containing a push-button and a TV display. Within the experimental sessions, the push-button was lit for 8 s as CS, and then paired with the display of a soft pornographic program on TV for 10 s. The result indicated that the modeling of pushing button promoted the increase of response probability among the subjects. The trials conducted after the rest period indicated an increase of response probability. In Experiment 2, a 4 cm square translucent panel was lit for 20 s as CS, and then paired with the display of a computer graphic picture on TV for 8 s as US. Some subjects started gazing at the CS for several seconds. These results indicated that some subjects could acquire the gazing response under the autoshaping procedure.

  6. 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.

  7. The AIR's policy on research involving the irradiation of human subjects

    International Nuclear Information System (INIS)

    Smith, A.N.

    1995-01-01

    The policy of the Australian Institute of Radiography with regards to the human subject irradiation is outlined. It is stated that members will not irradiate another individual, nor themselves, solely for the purposes of experimentation or research without gaining the prior approval of an institutional ethics committee. Where possible, researchers should consider the use of patient equivalent or human tissue equivalent phantoms. A short list of references has been compiled to assist members in designing research protocols which comply with the stated policy

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

    International Nuclear Information System (INIS)

    Wolf, Susan M.; Jones, Cortney M.

    2011-01-01

    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 and 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.

  9. 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.

  10. Human subject research: reporting ethics approval and informed consent in 3 chiropractic journals.

    Science.gov (United States)

    Lawrence, Dana J

    2011-11-01

    To date, there have been no reports of ethics board approval or informed consent within the chiropractic literature or within chiropractic research. The purpose of this study was to assess the reporting of ethics approval and informed consent in articles published during the 2008 volume year of 3 chiropractic research journals included in PubMed. A quantitative assessment of the articles published in each journal for the 2008 volume year was performed. Information collected included if the article involved human subject research, if it reported ethics board approval, and if informed consent was given to subjects. Data were collected as descriptive statistics (frequency counts and percentages). In aggregate, 50 articles of a total of 143 published involved human subject research (35%). 44 reported ethics board approval (88%), and 28 reported that informed consent had been obtained (56%). Forty-five percent of articles published in the Journal of Manipulative and Physiological Therapeutics involved human subject research (39/87), of which 95% reported ethics board approval (37/39) and 64% reported informed consent (25/39); 12.5% of articles from the Journal of the Canadian Chiropractic Association involved human subject research (5/40), of which 80% reported ethics board approval (4/5) and 40% reported informed consent (2/5); and 37.5% of articles published in Chiropractic and Osteopathy involved human subject research (6/16), of which 50% reported ethics board approval (3/6) and 17% reported informed consent (1/6). Overall, most articles reported ethics approval, and more than half reported consent. This was harmonious with research on this topic from other disciplines. This situation indicates a need for continued quality improvement and for better instruction and dissemination of information on these issues to researchers, to manuscript reviewers, to journal editors, and to the readers. Copyright © 2011 National University of Health Sciences. Published by Mosby

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

    Science.gov (United States)

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

  12. Human Subjects Protection: A Source for Ethical Service-Learning Practice

    Science.gov (United States)

    Wendler, Rachael

    2012-01-01

    Human subjects research ethics were developed to ensure responsible conduct when university researchers learn by interacting with community members. As service-learning students also learn by interacting with community members, a similar set of principles may strengthen the ethical practice of service-learning. This article identifies ethical…

  13. 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...

  14. 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

    , 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...

  15. 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

  16. 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.

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

    DEFF Research Database (Denmark)

    Simone, Angela; Kolarik, Jakub; Iwamatsu, Toshiya

    2011-01-01

    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...

  18. Human subjects protection training for community workers: an example from "Faith Moves Mountains".

    Science.gov (United States)

    Hatcher, Jennifer; Schoenberg, Nancy E

    2007-01-01

    Despite widespread agreement on the necessity of protecting human subjects, questions regarding ethical treatment and protection of human subjects remain and are particularly vexing for community-based participatory research (CBPR). There has been a notable lack of attention paid to what type of training should be provided and how to balance "real-life" concerns with official requirements. The purpose of this article is to demonstrate how, in consultation with the Office of Research Integrity (ORI) at our institution and our community partners, we developed training that overcame concerns related to instruction of community workers on protection of human subjects. We developed a training module written in lay terms and containing only information pertinent to non-key personnel and their role in the CBPR project. We designed and piloted this material in collaboration with our community partners who work with us to recruit and train lay health advisors (LHAs) and oversee the day-to-day operations of the CBPR project. The educational module was presented to the community workers as a part of a day-long training session. The written materials were a part of a notebook of information accompanied by an oral Power Point presentation. Each of the workers was given a written test to evaluate knowledge of the content presented. The test was administered by the project director, a community member herself, and then sent to our institution for grading by personnel not involved in this project. To date, all community workers have passed the written test. The community members, research partners, and the ORI are satisfied with the scope and simplicity of the training program developed. Our team's collaborative approach to community-based human subjects training contributes to advancing a grounded, feasible, and rigorous process of protecting human subjects while implementing CBPR ideals.

  19. 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.

  20. Predictive modeling of human perception subjectivity: feasibility study of mammographic lesion similarity

    Science.gov (United States)

    Xu, Songhua; Hudson, Kathleen; Bradley, Yong; Daley, Brian J.; Frederick-Dyer, Katherine; Tourassi, Georgia

    2012-02-01

    The majority of clinical content-based image retrieval (CBIR) studies disregard human perception subjectivity, aiming to duplicate the consensus expert assessment of the visual similarity on example cases. The purpose of our study is twofold: i) discern better the extent of human perception subjectivity when assessing the visual similarity of two images with similar semantic content, and (ii) explore the feasibility of personalized predictive modeling of visual similarity. We conducted a human observer study in which five observers of various expertise were shown ninety-nine triplets of mammographic masses with similar BI-RADS descriptors and were asked to select the two masses with the highest visual relevance. Pairwise agreement ranged between poor and fair among the five observers, as assessed by the kappa statistic. The observers' self-consistency rate was remarkably low, based on repeated questions where either the orientation or the presentation order of a mass was changed. Various machine learning algorithms were explored to determine whether they can predict each observer's personalized selection using textural features. Many algorithms performed with accuracy that exceeded each observer's self-consistency rate, as determined using a cross-validation scheme. This accuracy was statistically significantly higher than would be expected by chance alone (two-tailed p-value ranged between 0.001 and 0.01 for all five personalized models). The study confirmed that human perception subjectivity should be taken into account when developing CBIR-based medical applications.

  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

    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...... 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...

  2. 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

    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......-term effects in healthy human subjects....

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    Indirect evidence that the motor cortex and the corticospinal tract contribute to the control of walking in human subjects has been provided in previous studies. In the present study we used coherence analysis of the coupling between EEG and EMG from active leg muscles during human walking...... area and EMG from the anterior tibial muscle was found in the frequency band 24–40 Hz prior to heel strike during the swing phase of walking. This signifies that rhythmic cortical activity in the 24–40 Hz frequency band is transmitted via the corticospinal tract to the active muscles during walking...

  4. Human subjects concerns in ground based ECLSS testing - Managing uncertainty in closely recycled systems

    Science.gov (United States)

    Crump, William J.; Janik, Daniel S.; Thomas, L. Dale

    1990-01-01

    U.S. space missions have to this point used water either made on board or carried from earth and discarded after use. For Space Station Freedom, long duration life support will include air and water recycling using a series of physical-chemical subsystems. The Environmental Control and Life Support System (ECLSS) designed for this application must be tested extensively at all stages of hardware maturity. Human test subjects are required to conduct some of these tests, and the risks associated with the use of development hardware must be addressed. Federal guidelines for protection of human subjects require careful consideration of risks and potential benefits by an Institutional Review Board (IRB) before and during testing. This paper reviews the ethical principles guiding this consideration, details the problems and uncertainties inherent in current hardware testing, and presents an incremental approach to risk assessment for ECLSS testing.

  5. Bench-to-bedside review: Human subjects research – are more standards needed?

    Science.gov (United States)

    Huang, David T; Hadian, Mehrnaz

    2006-01-01

    There are many controversial issues surrounding ethics in study design and conduct of human subjects research. In this review we briefly touch on the origin of ethics in clinical research and how the current regulations and standards came into practice. We then discuss current controversies regarding informed consent, conflicts of interest, institutional review boards, and other relevant issues such as innovative procedures and quality improvement projects. The question of whether we need more standards is a very important yet challenging one to which there is no simple answer. We address this question by reviewing and commenting on relevant literature. We conclude that what is needed are not more standards per se, but rather refinement and uniformity of current standards, and their interpretation and application both to protect human subjects and to advance medicine. PMID:17184560

  6. Bench-to-bedside review: human subjects research--are more standards needed?

    Science.gov (United States)

    Huang, David T; Hadian, Mehrnaz

    2006-01-01

    There are many controversial issues surrounding ethics in study design and conduct of human subjects research. In this review we briefly touch on the origin of ethics in clinical research and how the current regulations and standards came into practice. We then discuss current controversies regarding informed consent, conflicts of interest, institutional review boards, and other relevant issues such as innovative procedures and quality improvement projects. The question of whether we need more standards is a very important yet challenging one to which there is no simple answer. We address this question by reviewing and commenting on relevant literature. We conclude that what is needed are not more standards per se, but rather refinement and uniformity of current standards, and their interpretation and application both to protect human subjects and to advance medicine.

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

    Science.gov (United States)

    Sheehan, Mark; Marti, Vernon; Roberts, Tony

    2014-07-01

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

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

    OpenAIRE

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

    2007-01-01

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

  10. Canadian governance of health research involving human subjects: is anybody minding the store?

    Science.gov (United States)

    McDonald, M

    2001-01-01

    From an ethical perspective, good governance involves the translation of collective moral intentions into effective and accountable institutional actions. With respect to the use of human subjects in Canadian health research, I contend that there have been many good intentions but very little in the way of appropriate governance arrangements. Hence, the question, "who minds the store?" is especially acute with respect to the protection of vulnerable individuals and groups that are typically recruited as subjects for health research in Canada. Beyond diagnosing failures in governance and their causes, I offer suggestions for significant reforms, including evidence-based ethics assessment, independent oversight, and greater participation of research subjects in governance. I will close with some more general reflections on ethics, law, and governance.

  11. A Subject-Specific Kinematic Model to Predict Human Motion in Exoskeleton-Assisted Gait

    Science.gov (United States)

    Torricelli, Diego; Cortés, Camilo; Lete, Nerea; Bertelsen, Álvaro; Gonzalez-Vargas, Jose E.; del-Ama, Antonio J.; Dimbwadyo, Iris; Moreno, Juan C.; Florez, Julian; Pons, Jose L.

    2018-01-01

    The relative motion between human and exoskeleton is a crucial factor that has remarkable consequences on the efficiency, reliability and safety of human-robot interaction. Unfortunately, its quantitative assessment has been largely overlooked in the literature. Here, we present a methodology that allows predicting the motion of the human joints from the knowledge of the angular motion of the exoskeleton frame. Our method combines a subject-specific skeletal model with a kinematic model of a lower limb exoskeleton (H2, Technaid), imposing specific kinematic constraints between them. To calibrate the model and validate its ability to predict the relative motion in a subject-specific way, we performed experiments on seven healthy subjects during treadmill walking tasks. We demonstrate a prediction accuracy lower than 3.5° globally, and around 1.5° at the hip level, which represent an improvement up to 66% compared to the traditional approach assuming no relative motion between the user and the exoskeleton. PMID:29755336

  12. 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.

  13. Inter-subject variability in human atrial action potential in sinus rhythm versus chronic atrial fibrillation.

    Directory of Open Access Journals (Sweden)

    Carlos Sánchez

    Full Text Available Human atrial electrophysiology exhibits high inter-subject variability in both sinus rhythm (SR and chronic atrial fibrillation (cAF patients. Variability is however rarely investigated in experimental and theoretical electrophysiological studies, thus hampering the understanding of its underlying causes but also its implications in explaining differences in the response to disease and treatment. In our study, we aim at investigating the ability of populations of human atrial cell models to capture the inter-subject variability in action potential (AP recorded in 363 patients both under SR and cAF conditions.Human AP recordings in atrial trabeculae (n = 469 from SR and cAF patients were used to calibrate populations of computational SR and cAF atrial AP models. Three populations of over 2000 sampled models were generated, based on three different human atrial AP models. Experimental calibration selected populations of AP models yielding AP with morphology and duration in range with experimental recordings. Populations using the three original models can mimic variability in experimental AP in both SR and cAF, with median conductance values in SR for most ionic currents deviating less than 30% from their original peak values. All cAF populations show similar variations in G(K1, G(Kur and G(to, consistent with AF-related remodeling as reported in experiments. In all SR and cAF model populations, inter-subject variability in I(K1 and I(NaK underlies variability in APD90, variability in I(Kur, I(CaL and I(NaK modulates variability in APD50 and combined variability in Ito and I(Kur determines variability in APD20. The large variability in human atrial AP triangulation is mostly determined by I(K1 and either I(NaK or I(NaCa depending on the model.Experimentally-calibrated human atrial AP models populations mimic AP variability in SR and cAF patient recordings, and identify potential ionic determinants of inter-subject variability in human atrial AP

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

    Science.gov (United States)

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

    2011-11-01

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

  15. Analysis of angiotensin II binding to human platelets: Differences in young and old subjects

    International Nuclear Information System (INIS)

    Siebers, M.J.; Goodfriend, T.L.; Ball, D.; Elliott, M.E.

    1990-01-01

    We examined the binding of radiolabeled angiotensin II (AII) to human platelets to characterize the apparent increase in AII receptors observed in older subjects. At 22 degrees C, the amount of radioactivity associated with platelets from older subjects increased continuously for more than 2 hours. The same amount of radioactivity was displaced by addition of unlabeled AII at 30 min and 60 min. In the presence of phenylarsine oxide, in the cold, or when labeled antagonist was the ligand, binding came to equilibrium by 30 min. High pressure liquid chromatography demonstrated that 125 I-AII was the major radioactive compound in the supernatant and platelets after incubation, but the platelets also contained radiolabeled AII fragments. Thus, some degradation accompanied interaction of AII and platelets. Phenylarsine oxide did not prevent degradation of bound AII, suggesting that degradation precedes internalization. On average, maximum binding was greater in older subjects whether platelets were incubated with 125 I-AII alone, with 125 I-AII and phenylarsine oxide to prevent internalization, or when the competitive inhibitor 125 I-sar1,ile8-AII was the radioligand. Variability of binding among subjects also increased with age. Thus, platelets bind, degrade, and internalize AII, and the three processes occur to a greater extent in platelets from some, but not all older subjects

  16. Differential effects of airway anesthesia on ozone-induced pulmonary responses in human subjects.

    Science.gov (United States)

    Schelegle, E S; Eldridge, M W; Cross, C E; Walby, W F; Adams, W C

    2001-04-01

    We examined the effect of tetracaine aerosol inhalation, a local anesthetic, on lung volume decrements, rapid shallow breathing, and subjective symptoms of breathing discomfort induced by the acute inhalation of 0.30 ppm ozone for 65 min in 22 ozone-sensitive healthy human subjects. After 50 min of ozone inhalation FEV(1) was reduced 24%, breathing frequency was increased 40%, tidal volume was decreased 31%, and total subjective symptom score was increased (71.2, compared with 3.8 for filtered air exposure). Inhalation of tetracaine aerosol resulted in marked reductions in ozone-induced subjective symptoms of throat tickle and/or irritation (92.1%), cough (78.5%), shortness of breath (72.5%), and pain on deep inspiration (69.4%). In contrast, inhalation of tetracaine aerosol (mass median aerodynamic diameter of 3.52 microm with a geometric standard deviation of 1.92) resulted in only minor and inconsistent rectification of FEV(1) decrements (5.0%) and breathing frequency (-3.8%) that was not significantly different from that produced by saline aerosol alone (FEV(1), 5.1% and breathing frequency, -2.7%). Our data are consistent with afferent endings located within the large conducting airways of the tracheobronchial tree being primarily responsible for ozone-induced subjective symptoms and provides strong evidence that ozone-induced inhibition of maximal inspiratory effort is not dependent on conscious sensations of inspiratory discomfort.

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

    Directory of Open Access Journals (Sweden)

    Karl E Zelik

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

  18. 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

  19. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Simone, Angela; Kolarik, Jakub; Olesen, Bjarne W. [ICIEE/BYG, Technical University of Denmark (Denmark); Iwamatsu, Toshiya [Faculty of Urban Environmental Science, Tokyo Metropolitan University (Japan); Asada, Hideo [Architech Consulting Co., Tokyo (Japan); Dovjak, Mateja [Faculty of Civil and Geodetic Engineering, University of Ljubljana (Slovenia); Schellen, Lisje [Eindhoven University of Technology, Faculty of Architecture Building and Planning (Netherlands); Shukuya, Masanori [Laboratory of Building Environment, Tokyo City University, Yokohama (Japan)

    2011-01-15

    Application of the exergy concept to research on the built environment is a relatively new approach. It helps to optimize climate conditioning systems so that they meet the requirements of sustainable building design. As the building should provide a healthy and comfortable environment for its 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 consumption rates increase as the operative temperature increases above 24 C or decreases below 22 C. With the data available so far, a second-order polynomial relationship between thermal sensation and the exergy consumption rate was established. (author)

  1. 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

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

    DEFF Research Database (Denmark)

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

    2004-01-01

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

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

    Science.gov (United States)

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

    2008-05-01

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

  4. 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.

  5. Ultrasound evidence of altered lumbar connective tissue structure in human subjects with chronic low back pain

    Directory of Open Access Journals (Sweden)

    Bouffard Nicole A

    2009-12-01

    Full Text Available Abstract Background Although the connective tissues forming the fascial planes of the back have been hypothesized to play a role in the pathogenesis of chronic low back pain (LBP, there have been no previous studies quantitatively evaluating connective tissue structure in this condition. The goal of this study was to perform an ultrasound-based comparison of perimuscular connective tissue structure in the lumbar region in a group of human subjects with chronic or recurrent LBP for more than 12 months, compared with a group of subjects without LBP. Methods In each of 107 human subjects (60 with LBP and 47 without LBP, parasagittal ultrasound images were acquired bilaterally centered on a point 2 cm lateral to the midpoint of the L2-3 interspinous ligament. The outcome measures based on these images were subcutaneous and perimuscular connective tissue thickness and echogenicity measured by ultrasound. Results There were no significant differences in age, sex, body mass index (BMI or activity levels between LBP and No-LBP groups. Perimuscular thickness and echogenicity were not correlated with age but were positively correlated with BMI. The LBP group had ~25% greater perimuscular thickness and echogenicity compared with the No-LBP group (ANCOVA adjusted for BMI, p Conclusion This is the first report of abnormal connective tissue structure in the lumbar region in a group of subjects with chronic or recurrent LBP. This finding was not attributable to differences in age, sex, BMI or activity level between groups. Possible causes include genetic factors, abnormal movement patterns and chronic inflammation.

  6. Goodbye to all that. The end of moderate protectionism in human subjects research.

    Science.gov (United States)

    Moreno, J D

    2001-01-01

    Federal policies on human subjects research have undergone a progressive transformation. In the early decades of the twentieth century, federal policies largely relied on the discretion of investigators to decide when and how to conduct research. This approach gradually gave way to policies that augmented investigator discretion with externally imposed protections. We may now be entering an era of even more stringent external protections. Whether the new policies effectively absolve investigators of personal responsibility for conducting ethical research, and whether it is wise to do so, remains to be seen.

  7. 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...

  8. Impact Response Comparison Between Parametric Human Models and Postmortem Human Subjects with a Wide Range of Obesity Levels.

    Science.gov (United States)

    Zhang, Kai; Cao, Libo; Wang, Yulong; Hwang, Eunjoo; Reed, Matthew P; Forman, Jason; Hu, Jingwen

    2017-10-01

    Field data analyses have shown that obesity significantly increases the occupant injury risks in motor vehicle crashes, but the injury assessment tools for people with obesity are largely lacking. The objectives of this study were to use a mesh morphing method to rapidly generate parametric finite element models with a wide range of obesity levels and to evaluate their biofidelity against impact tests using postmortem human subjects (PMHS). Frontal crash tests using three PMHS seated in a vehicle rear seat compartment with body mass index (BMI) from 24 to 40 kg/m 2 were selected. To develop the human models matching the PMHS geometry, statistical models of external body shape, rib cage, pelvis, and femur were applied to predict the target geometry using age, sex, stature, and BMI. A mesh morphing method based on radial basis functions was used to rapidly morph a baseline human model into the target geometry. The model-predicted body excursions and injury measures were compared to the PMHS tests. Comparisons of occupant kinematics and injury measures between the tests and simulations showed reasonable correlations across the wide range of BMI levels. The parametric human models have the capability to account for the obesity effects on the occupant impact responses and injury risks. © 2017 The Obesity Society.

  9. 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.

  10. 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.

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

    Science.gov (United States)

    Resnik, David B

    2017-01-01

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

  12. 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.

  13. Tolerability, usability and acceptability of dissolving microneedle patch administration in human subjects.

    Science.gov (United States)

    Arya, Jaya; Henry, Sebastien; Kalluri, Haripriya; McAllister, Devin V; Pewin, Winston P; Prausnitz, Mark R

    2017-06-01

    To support translation of microneedle patches from pre-clinical development into clinical trials, this study examined the effect of microneedle patch application on local skin reactions, reliability of use and acceptability to patients. Placebo patches containing dissolving microneedles were administered to fifteen human participants. Microneedle patches were well tolerated in the skin with no pain or swelling and only mild erythema localized to the site of patch administration that resolved fully within seven days. Microneedle patches could be administered by hand without the need of an applicator and delivery efficiencies were similar for investigator-administration and self-administration. Microneedle patch administration was not considered painful and the large majority of subjects were somewhat or fully confident that they self-administered patches correctly. Microneedle patches were overwhelmingly preferred over conventional needle and syringe injection. Altogether, these results demonstrate that dissolving microneedle patches were well tolerated, easily usable and strongly accepted by human subjects, which will facilitate further clinical translation of this technology. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. 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

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    David W Evans

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

  17. Relationship between eye dominance and pattern electroretinograms in normal human subjects.

    Science.gov (United States)

    Kamis, Umit; Gunduz, Kemal; Okudan, Nilsel; Gokbel, Hakki; Bodur, Sait; Tan, Uner

    2005-02-01

    The authors conducted a study in 100 non-smoker healthy normal human subjects to find a relationship between eye dominance and macular function as tested by using transient stimulus and electroretinography. Eye preference procedure was carried out using two reference points and pattern electroretinograms (PERGs) were recorded using black and white checks, each check subtending 23'. Trace averager was retriggered every 300 milliseconds (ms) with data collection time of 150 ms. The difference in PERG P50 amplitudes between right and left eyes was analyzed using Student's t test. There was no significant difference in PERG P50 amplitudes between the right and left eye dominant subjects as well as no significant differences between the right and left eyes in right eye dominants and left eye dominants, but in the left-eye dominant group the left eye PERG P50 amplitudes were significantly higher in females than males. Although pattern-reversal visual evoked potentials of healthy subjects provide electrophysiological evidence of lateralization in the nervous system, sensory eye dominance seems to have no correlation with macular function.

  18. Hydrogen peroxide production is not primarily increased in human myotubes established from type 2 diabetic subjects.

    Science.gov (United States)

    Minet, A D; Gaster, M

    2011-09-01

    Increased oxidative stress and mitochondrial dysfunction have been implicated in the development of insulin resistance in type 2 diabetes. To date, it is unknown whether increased mitochondrial reactive oxygen species (ROS) production in skeletal muscle from patients with type 2 diabetes is primarily increased or a secondary adaptation to environmental, lifestyle, and hormonal factors. This study investigates whether ROS production is primarily increased in isolated diabetic myotubes. Mitochondrial membrane potential, hydrogen peroxide (H(2)O(2)), superoxide, and mitochondrial mass were determined in human myotubes precultured under normophysiological conditions. Furthermore, the corresponding ATP synthesis was measured in isolated mitochondria. Muscle biopsies were taken from 10 lean subjects, 10 obese subjects, and 10 subjects with type 2 diabetes; satellite cells were isolated, cultured, and differentiated to myotubes. Mitochondrial mass, membrane potential/mitochondrial mass, and superoxide-production/mitochondrial mass were not different between groups. In contrast, H(2)O(2) production/mitochondrial mass and ATP production were significantly reduced in diabetic myotubes compared to lean controls (P production is not primarily increased in diabetic myotubes but rather is reduced. Moreover, the comparable ATP/H(2)O(2) ratios indicate that the reduced ROS production in diabetic myotubes parallels the reduced ATP production because ROS production in diabetic myotubes must be considered to be in a proportion comparable to lean. Thus, the increased ROS production seen in skeletal muscle of type 2 diabetic patients is an adaptation to the in vivo conditions.

  19. Theoretical modeling of the subject: Western and Eastern types of human reflexion.

    Science.gov (United States)

    Lefebvre, Vladimir A

    2017-12-01

    The author puts forth the hypothesis that mental phenomena are connected with thermodynamic properties of large neural network. A model of the subject with reflexion and capable for meditation is constructed. The processes of reflexion and meditation are presented as the sequence of heat engines. Each subsequent engine compensates for the imperfectness of the preceding engine by performing work equal to the lost available work of the preceding one. The sequence of heat engines is regarded as a chain of the subject's mental images of the self. Each engine can be interpreted as an image of the self that the engine next to it has, and the work performed by engines as the emotions that the subject and his images are experiencing. Two types of meditation are analyzed: The dissolution in nothingness and union with the Absolute. In the first type, the initial engine is the one that yields heat to the coldest reservoir, and in the second type, the initial engine is the one that takes heat from the hottest reservoir. The main concepts of thermodynamics are reviewed in relation to the process of human reflexion. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Effects of corn silk aqueous extract on intraocular pressure of ocular hypertensive human subjects

    Directory of Open Access Journals (Sweden)

    G.O. George

    2013-01-01

    Full Text Available Stigma/style of Zea mays L (Corn silk has been documented to have hypotensive effect on blood pressure and to relieve oedema. However we are not aware of any literature on its hypotensive effect on intraocular pressure (IOP of humans or animals. We studied the effects of water only, masked doses of corn silk aqueous extract (60 mg/kg, 130 mg/kg, 192.5 mg/kg and 260 mg/kg body weight on the IOP and blood pressure (BP of twenty normotensives and twenty ocular hypertensive subjects. Also we compared the effects of the varied doses of corn silk aqueous extract (CSAE with masked doses (5 mg/kg and 10 mg/kg body weight of acetazolamide on IOP of ocular hypertensive subjects only. The results showed that the last three doses of CSAE lowered IOP and BP significantly (p<0.001 within eight hours of administration. The peak effect on IOP was observed after four hours while the peak effect on BP was observed after three hours of administration in the normotensives and ocular hypertensive subjects likewise the hypotensive effect was dose-dependent. The results also showed that 130 mg/kg body weight of CSAE produced the same hypotensive effect on IOP of ocular hypertensive subjects as 5 mg/kg body weight of acetazolamide. Therefore CSAE may have some IOP lowering effects that require further investigation in the management of ocular hypertension. (S Afr Optom 2013 72(3 133-143

  1. Microarray analysis of gene expression in peripheral blood mononuclear cells from dioxin-exposed human subjects

    International Nuclear Information System (INIS)

    McHale, Cliona M.; Zhang, Luoping; Hubbard, Alan E.; Zhao, Xin; Baccarelli, Andrea; Pesatori, Angela C.; Smith, Martyn T.; Landi, Maria Teresa

    2007-01-01

    Tetrachlorodibenzo-p-dioxin (TCDD) is classified as a human carcinogen and exerts toxic effects on the skin (chloracne). Effects on reproductive, immunological, and endocrine systems have also been observed in animal models. TCDD acts through the aryl hydrocarbon receptor (AhR) pathway influencing largely unknown gene networks. An industrial accident in Seveso, Italy in 1976 exposed thousands of people to substantial quantities of TCDD. Twenty years after the exposure, this study examines global gene expression in the mononuclear cells of 26 Seveso female never smokers, with similar age, alcohol consumption, use of medications, and background plasma levels of 22 dioxin congeners unrelated to the Seveso accident. Plasma dioxin levels were still elevated in the exposed subjects. We performed analyses in two different comparison groups. The first included high-exposed study subjects compared with individuals with background TCDD levels (average plasma levels 99.4 and 6.7 ppt, respectively); the second compared subjects who developed chloracne after the accident, and those who did not develop this disease. Overall, we observed a modest alteration of gene expression based on dioxin levels or on chloracne status. In the comparison between high levels and background levels of TCDD, four histone genes were up-regulated and modified expression of HIST1H3H was confirmed by real-time PCR. In the comparison between chloracne case-control subjects, five hemoglobin genes were up-regulated. Pathway analysis revealed two major networks for each comparison, involving cell proliferation, apoptosis, immunological and hematological disease, and other pathways. Further examination of the role of these genes in dioxin induced-toxicity is warranted

  2. 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.

  3. 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

  4. A radioimmunoassay for erythropoietin: serum levels in normal human subjects and patients with hemopoietic disorders

    International Nuclear Information System (INIS)

    Rege, A.B.; Brookins, J.; Fisher, J.W.

    1982-01-01

    An RIA for Ep has been developed that is highly sensitive and specific. A homogeneous Ep preparation was labeled with 125 I by the chloramine-T method to a specific activity of 90 to 136 micro Ci/microgram and immunoreactivity of 80%. Ep antiserum, which was produced to a human urinary Ep preparation (80 U/mg of protein), was adsorbed with normal human urinary and serum proteins without any loss in sensitivity of the RIA to increase the specificity of the assay. A good correlation was seen between the RIA and the exhypoxic polycythemic mouse assay (corr. coef. 0.967; slope 1.05 and y intercept 0.75). Ep titers in sera from 175 hematologically normal human subjects exhibited a normal frequency distribution and ranged between 5.8 and 36.6 mU/ml with a mean of 14.9 +/- 4.7 (S.D.) and median of 14.3 Serum Ep titers were markedly elevated in seven patients with aplastic anemia and one patient with pure red cell aplasia (1350 to 20,640 mU/ml) and were lower than normal in two patients with polycythemia vera (8.1 and 9.4 mU/ml). The serum Ep titers in a prenephrectomy patient with chronic glomerulonephritis (32.1 mU/ml) decreased to below normal levels (9.04 mU/ml) after nephrectomy. The cord serum erythropoietin titers in 10 IDM [90.82 +/- 134.1 (S.D.) mu/ml] returned to values within the normal range (13.86 +/- 5.55) on day 3 after birth, suggesting the utility of the RIA in elucidating the role of hypoxia and/or insulin in increased erythropoiesis in IDM. The serum Ep titers in patients with anemias and polycythemias were compared to those of normal human subjects and agreed well with pathophysiologic mechanisms of these hemopoietic disorders, confirming the validity of the RIA

  5. A radioimmunoassay for erythropoietin: serum levels in normal human subjects and patients with hemopoietic disorders

    International Nuclear Information System (INIS)

    Rege, A.B.; Brookins, J.; Fisher, J.W.

    1982-01-01

    An RIA for Ep has been developed that is highly sensitive and specific. A homogeneous Ep preparation was labeled with 125 I by the chloramine-T method to a specific activity of 90 to 136 μCi/μg and immunoreactivity of 80%. Ep antiserum, which was produced to a human urinary Ep preparation (80 U/mg of protein), was adsorbed with normal human urinary and serum proteins without any loss in sensitivity of the RIA to increase the specificity of the assay. A good correlation was seen between the RIA and the exhypoxic polycythemic mouse assay (corr. coef. 0.967; slope 1.05 and ''y'' intercept 0.75). Ep titers in sera from 175 hematologically normal human subjects exhibited a normal frequency distribution and ranged between 5.8 and 36.6 mU/ml with a mean of 14.9 +/- 4.7 (S.D.) and median of 14.3. Serum Ep titers were markedly elevated in seven patients with aplastic anemia and one patient with pure red cell aplasia (1350 to 20,640 mU/ml) and were lower than normal in two patients with polycythemia vera (8.1 and 9.4 mU/ml). The serum Ep titers in a prenephrectomy patient with chronic glomerulonephritis (31.1 mU/ml) decreased to below normal levels (9.04 mU/ml) after nephrectomy. The cord serum erythropoietin titers in 10 IDM [90.82 +/- 134.1 (S.D.) mu/ml] returned to values within the normal range (13.86 +/- 5.55) on day 3 after birth, suggesting the utility of the RIA in elucidating the role of hypoxia and/or insulin in increased erythropoiesis in IDM. The serum Ep titers in patients with anemias and polycythemias were compared to those of normal human subjects and agreed well with pathophysiologic mechanisms of these hemopoietic disorders, confirming the validity of the RIA

  6. Spectrum of lipid and lipoprotein indices in human subjects with insulin resistance syndrome

    International Nuclear Information System (INIS)

    Khan, S.H.; Khan, F.A.; Mohammad, A.S.

    2008-01-01

    Insulin resistance syndrome or metabolic syndrome is one of the major metabolic threats our recently urbanized society is going to face in near future. The management of this syndrome requires a very effective biochemical marker for screening. The objective of this cross sectional study were to compare various lipid and lipoprotein indices in human subjects with insulin resistance syndrome This study was carried out between April 2004 to January 2006 at the department of chemical pathology and endocrinology, Armed Forces Institute of Pathology, Rawalpindi. A total of forty-seven subjects with metabolic syndrome were selected as per the criteria of National Cholesterol Education Program, Adult Treatment Panel III (NCEP, ATP III) from a target population diagnosed to have impaired glucose regulation at AFIP. Forty-seven age and sex-matched healthy controls were also included in the study. Insulin resistance was calculated by the method of HOMA-IR, using the formula of Mathew's et al. The various lipid and lipoproteins, their ratios and log-transformed versions were evaluated for differences between subjects with metabolic syndrome and controls. Finally the diagnostic performances of these candidate lipid markers were evaluated. Results between subjects with metabolic syndrome and controls were found to be significant for serum triglyceride (p<0.05), HDL-C (p<0.05), triglyceride/HDLC (p<0.01), Log triglyceride/HDL-C (p<0.01), total cholesterol/HDL-C (p<0.01), LDL-C/HDL-C (p<0.01). However there was weak correlation between these lipid based markers and HOMA-IR ((serum triglyceride: r= 0.225), (HDL-C: r= -0.235), (triglyceride/HDL-C: r= 0.333), (total cholesterol/HDL-C: r= 0.239)). The AUCs for the diagnosis of metabolic syndrome remained highest for HOMA-IR (0.727 (95%CI: 0.642-0.812)), followed by triglyceride/HDL-C (0.669 (95%CI: 0.572-0.766)) and LDLC/ HDL-C (0.639 (95%CI: 0.537-0.742)). The differences for lipids and lipoproteins between subjects with metabolic

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

    DEFF Research Database (Denmark)

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

    2001-01-01

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

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    Key points  Several biochemical measures of mitochondrial components are used as biomarkers of mitochondrial content and muscle oxidative capacity. However, no studies have validated these surrogates against a morphological measure of mitochondrial content in human subjects.  The most commonly used...... markers (citrate synthase activity, cardiolipin content, mitochondrial DNA content (mtDNA), complex I-V protein, and complex I-IV activity) were correlated with a measure of mitochondrial content (transmission electron microscopy) and muscle oxidative capacity (respiration in permeabilized fibres......).  Cardiolipin content followed by citrate synthase activity and complex I activity were the biomarkers showing the strongest association with mitochondrial content.  mtDNA was found to be a poor biomarker of mitochondrial content.  Complex IV activity was closely associated with mitochondrial oxidative...

  9. Deuterium labelling of the antidepressant drug doxepin for disposition studies in human subjects

    International Nuclear Information System (INIS)

    Prakash, Chandra; Saleh, Samir; Wilkinson, G.R.; Blair, I.A.; Taber, D.F.

    1990-01-01

    Two methods have been developed for the introduction of deuterium into the doxepin molecule. The key intermediate (6,11-dihydro-1,2,3,4- 2 H 4 -dibenz[b,e]oxepin-11-one) was prepared by condensation of ethyl 2-bromomethylbenzoate with [ 2 H 6 ]-phenol, saponification of the resulting ester, and dehydration with trifluoroacetic anhydride. Using this key intermediate, E-(1,2,3,4)- 2 H 4 -doxepin was prepared for administration to human subjects. (1,2,3,4)- 2 H 4 -N-desmethyldoxepin, (1,2,3,4,1',2',2')- 2 H 7 -doxepin, (1,2,3,4)- 2 H 4 -(H 2 H 3 ) 2 -doxepin ( 2 H 10 -doxepin) and (1,2,3,4,1',2',2')- 2 H 7 -N-desmethyldoxepin were also prepared for use as internal standards in GC/MS assays. The deuterated compounds contained less than 0.5% protium impurity. (author)

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

    DEFF Research Database (Denmark)

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

    2002-01-01

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

  11. 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

    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......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...

  12. Aspirin effects on lymphocyte cyclic AMP levels in normal human subjects.

    Science.gov (United States)

    Snider, D E; Parker, C W

    1976-01-01

    In purified lymphocytes from the peripheral blood of healthy human subjects who had ingested therapeutic doses of aspirin, there was a significant decrease in resting cyclic AMP levels as well as a partial inhibition of the rise in cyclic AMP with isoproterenol or prostaglandin E1. These changes were seen as early as 30 min after aspirin ingestion and did not appear to result from aspirin effects on lymphocyte recovery, purity, viability, or relative number of thymus- or bone marrow-derived lymphocytes. In contrast, the direct addition of aspirin to suspensions of purified peripheral lymphocytes did not significantly alter their cyclic AMP levels. However, an effect of aspirin could be obtained in vitro if aspirin was added to unprocessed whole blood during the dextran sedimentation phase of the cell purification. Thus the effect of aspirin on lymphocyte cyclic AMP metabolism, may be indirect, through other cells present in the peripheral blood. PMID:182720

  13. Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies.

    Science.gov (United States)

    Braff, D L; Geyer, M A; Swerdlow, N R

    2001-07-01

    , blepharospasm, temporal lobe epilepsy with psychosis, enuresis, and perhaps posttraumatic stress disorder (PTSD). Several pharmacological manipulations have been examined for their effects on PPI in healthy human subjects. In some cases, the alterations in PPI produced by these drugs in animals correspond to similar effects in humans. Specifically, dopamine agonists disrupt and nicotine increases PPI in at least some human studies. With some other compounds, however, the effects seen in humans appear to differ from those reported in animals. For example, the PPI-increasing effects of the glutamate antagonist ketamine and the serotonin releaser MDMA in humans are opposite to the PPI-disruptive effects of these compounds in rodents. Considerable evidence supports a high degree of homology between measures of PPI in rodents and humans, consistent with the use of PPI as a cross-species measure of sensorimotor gating. Multiple investigations of PPI using a variety of methods and parameters confirm that deficits in PPI are evident in schizophrenia-spectrum patients and in certain other disorders in which gating mechanisms are disturbed. In contrast to the extensive literature on clinical populations, much more work is required to clarify the degree of correspondence between pharmacological effects on PPI in healthy humans and those reported in animals.

  14. Recommendations for Nanomedicine Human Subjects Research Oversight: An Evolutionary Approach for an Emerging Field

    Science.gov (United States)

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

    2015-01-01

    The nanomedicine field is fast evolving toward complex, “active,” and interactive formulations. Like many emerging technologies, nanomedicine raises questions of how human subjects research (HSR) should be conducted and the adequacy of current oversight, as well as how to integrate concerns over occupational, bystander, and environmental exposures. The history of oversight for HSR investigating emerging technologies is a patchwork quilt without systematic justification of when ordinary oversight for HSR is enough versus when added oversight is warranted. Nanomedicine HSR provides an occasion to think systematically about appropriate oversight, especially early in the evolution of a technology, when hazard and risk information may remain incomplete. This paper presents the consensus recommendations of a multidisciplinary, NIH-funded project group, to ensure a science-based and ethically informed approach to HSR issues in nanomedicine, and integrate HSR analysis with analysis of occupational, bystander, and environmental concerns. We recommend creating two bodies, an interagency Human Subjects Research in Nanomedicine (HSR/N) Working Group and a Secretary’s Advisory Committee on Nanomedicine (SAC/N). HSR/N and SAC/N should perform 3 primary functions: (1) analysis of the attributes and subsets of nanomedicine interventions that raise HSR challenges and current gaps in oversight; (2) providing advice to relevant agencies and institutional bodies on the HSR issues, as well as federal and federal-institutional coordination; and (3) gathering and analyzing information on HSR issues as they emerge in nanomedicine. HSR/N and SAC/N will create a home for HSR analysis and coordination in DHHS (the key agency for relevant HSR oversight), optimize federal and institutional approaches, and allow HSR review to evolve with greater knowledge about nanomedicine interventions and greater clarity about attributes of concern. PMID:23289677

  15. 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.

  16. Sensitivity analysis of a validated subject-specific finite element model of the human craniofacial skeleton.

    Science.gov (United States)

    Szwedowski, T D; Fialkov, J; Whyne, C M

    2011-01-01

    Developing a more complete understanding of the mechanical response of the craniofacial skeleton (CFS) to physiological loads is fundamental to improving treatment for traumatic injuries, reconstruction due to neoplasia, and deformities. Characterization of the biomechanics of the CFS is challenging due to its highly complex structure and heterogeneity, motivating the utilization of experimentally validated computational models. As such, the objective of this study was to develop, experimentally validate, and parametrically analyse a patient-specific finite element (FE) model of the CFS to elucidate a better understanding of the factors that are of intrinsic importance to the skeletal structural behaviour of the human CFS. An FE model of a cadaveric craniofacial skeleton was created from subject-specific computed tomography data. The model was validated based on bone strain measurements taken under simulated physiological-like loading through the masseter and temporalis muscles (which are responsible for the majority of craniofacial physiologic loading due to mastication). The baseline subject-specific model using locally defined cortical bone thicknesses produced the strongest correlation to the experimental data (r2 = 0.73). Large effects on strain patterns arising from small parametric changes in cortical thickness suggest that the very thin bony structures present in the CFS are crucial to characterizing the local load distribution in the CFS accurately.

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

    International Nuclear Information System (INIS)

    Bringel, Fabiana de A.; Isaac, Cesar; Herson, Marisa R.; Freitas, Anderson Z. de; Martinho Junior, Antonio C.; Mathor, Monica B.

    2011-01-01

    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 rd , 7 th , 21 st and 90 th days; optical coherence tomography on the 90 th day and histological assay on the 3 rd , 7 th , 21 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)

  18. 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)

  19. A compositional look at the human gastrointestinal microbiome and immune activation parameters in HIV infected subjects.

    Directory of Open Access Journals (Sweden)

    Ece A Mutlu

    2014-02-01

    Full Text Available HIV progression is characterized by immune activation and microbial translocation. One factor that may be contributing to HIV progression could be a dysbiotic microbiome. We therefore hypothesized that the GI mucosal microbiome is altered in HIV patients and this alteration correlates with immune activation in HIV. 121 specimens were collected from 21 HIV positive and 22 control human subjects during colonoscopy. The composition of the lower gastrointestinal tract mucosal and luminal bacterial microbiome was characterized using 16S rDNA pyrosequencing and was correlated to clinical parameters as well as immune activation and circulating bacterial products in HIV patients on ART. The composition of the HIV microbiome was significantly different than that of controls; it was less diverse in the right colon and terminal ileum, and was characterized by loss of bacterial taxa that are typically considered commensals. In HIV samples, there was a gain of some pathogenic bacterial taxa. This is the first report characterizing the terminal ileal and colonic mucosal microbiome in HIV patients with next generation sequencing. Limitations include use of HIV-infected subjects on HAART therapy.

  20. Morphology and Three-Dimensional Inhalation Flow in Human Airways in Healthy and Diseased Subjects

    Science.gov (United States)

    Van de Moortele, Tristan

    We investigate experimentally the relation between anatomical structure and respiratory function in healthy and diseased airways. Computed Tomography (CT) scans of human lungs are analyzed from the data base of a large multi-institution clinical study on Chronic Obstructive Pulmonary Disease (COPD). Through segmentation, the 3D volumes of the airways are determined at total lung capacity. A geometric analysis provides data on the morphometry of the airways, including the length and diameter of branches, the child-to-parent diameter ratio, and branching angles. While several geometric parameters are confirmed to match past studies for healthy subjects, previously unreported trends are reported on the length of branches. Specifically, in most dichotomous airway bifurcation, the branch of smaller diameter tends to be significantly longer than the one of larger diameter. Additionally, the branch diameter tends to be smaller in diseased airways than in healthy airways up to the 7th generation of bronchial branching. 3D fractal analysis is also performed on the airway volume. Fractal dimensions of 1.89 and 1.83 are found for healthy non-smokers and declining COPD subjects, respectively, furthering the belief that COPD (and lung disease in general) significantly affects the morphometry of the airways already in early stages of the disease. To investigate the inspiratory flow, 3D flow models of the airways are generated using Computer Aided Design (CAD) software and 3D printed. Using Magnetic Resonance Velocimetry (MRV), 3-component 3D flow fields are acquired for steady inhalation at Reynolds number Re 2000 defined at the trachea. Analysis of the flow data reveals that diseased subjects may experience greater secondary flow strength in their conducting airways, especially in deeper generations.

  1. 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.

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

    International Nuclear Information System (INIS)

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

    2000-01-01

    β-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 β-[ 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 β-carotene was lost slowly via urine in accord with the slow body turnover of β-carotene and vitamin A [4]. HPLC fractionation of plasma taken at early time points (0-24-h) showed the label was distributed between β-carotene and retinyl esters (vitamin A) derived from intestinal metabolism

  3. Report on {open_quotes}inspection of human subject research in intelligence and intelligence-related projects{close_quotes}

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-01-16

    Executive Order 12333, {open_quotes}United States Intelligence Activities,{close_quotes} (1) designates the Department`s intelligence element as a member of the Intelligence Community, and (2) states that no agency within the Intelligence community shall sponsor, contract for or conduct research on human subjects except in accordance with guidelines issued by the Department of Health and Human Services. The Federal policy for the Protection of Human Subjects, which was based on Department of Health and Human Services regulations, was promulgated in Title 10 Code of Federal Regulations Part 745 by the Department of Energy. The purpose of this inspection was to review the internal control procedures used by the Office of Nonproliferation and National Security to manage selected intelligence and intelligence-related projects that involve human subject research.

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

    Science.gov (United States)

    Jamison, David, IV

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

  5. Biomarkers of Dose and Effect of inhaled ozone in resting versus exercising human subjects: comparison with resting rats

    Science.gov (United States)

    Background: Human controlled exposure studies have generally focused on subjects exposed to ozone (O3) while exercising while exposures in rats have been done at rest. We exposed resting subjects to labeled O3 (18O3, 0.4 ppm, for 2 hr) and compared O3 dose and effects with our...

  6. Coming of Age of Human Biology: A Study of the Birth and Growth of a Subject in the School Curriculum.

    Science.gov (United States)

    Denny, M.

    1983-01-01

    Human biology is a school subject whose utilitarian/pedagogical traditions enjoy support at the School Certificate level but whose academic tradition is under threat at the General Certificate of Education level. An interpretation of the issues involved are discussed in terms of the subject's historical background. (JN)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-01-15

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

  8. 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

  9. "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…

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

    Science.gov (United States)

    Roof, David; Polush, Elena

    2016-01-01

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

  11. 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

    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.......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...

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

    International Nuclear Information System (INIS)

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

    2015-01-01

    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

  13. 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

  14. Engaging Institutional Review Boards in Developing a Brief, Community-Responsive Human Subjects Training for Community Partners

    Science.gov (United States)

    Calzo, Jerel P.; Bogart, Laura M.; Francis, Evelyn; Kornetsky, Susan Z.; Winkler, Sabune J.; Kaberry, Julie M.

    2017-01-01

    BACKGROUND Engaging community partners as co-investigators in community-based participatory research (CBPR) requires certification in the rules, ethics, and principles governing research. Despite developments in making human research protection trainings more convenient and standardized (e.g., self-paced Internet modules), time constraints and the structure of the content (which may favor academic audiences) may hinder the training of community partners. OBJECTIVES This paper is motivated by a case example in which academic and community partners, and stakeholders of a community-based organization actively engaged the leadership of a pediatric hospital-based Institutional Review Board (IRB) in implementing a brief, community-responsive human subjects training session. METHODS A two hour, discussion-based human subjects training was developed via collaborations between the IRB and the community and academic partners. Interviews with trainees and facilitators after the training were used to evaluate its acceptability and possible future applications. CONCLUSIONS Local Institutional Review Boards have the potential to assist community partners in building sufficient knowledge of human subjects research protections to engage in specific projects, thereby expediting the progress of vital research to address community needs. We propose the need for developing truncated human subjects education materials to train and certify community partners, and creating formally organized entities within academic and medical institutions that specialize in community-based research to guide the development and implementation of alternative human subjects training certification opportunities for community partners. PMID:28230554

  15. Engaging Institutional Review Boards in Developing a Brief, Community-Responsive Human Subjects Training for Community Partners.

    Science.gov (United States)

    Calzo, Jerel P; Bogart, Laura M; Francis, Evelyn; Kornetsky, Susan Z; Winkler, Sabune J; Kaberry, Julie

    2016-01-01

    Engaging community partners as co-investigators in community-based participatory research (CBPR) requires certification in the rules, ethics, and principles governing research. Despite developments in making human research protection trainings more convenient and standardized (eg, self-paced Internet modules), time constraints and the structure of the content (which may favor academic audiences) may hinder the training of community partners. This paper is motivated by a case example in which academic and community partners, and stakeholders of a community-based organization actively engaged the leadership of a pediatric hospital-based institutional review board (IRB) in implementing a brief, community-responsive human subjects training session. A 2-hour, discussion-based human subjects training was developed via collaborations between the IRB and the community and academic partners. Interviews with trainees and facilitators after the training were used to evaluate its acceptability and possible future applications. Local IRBs have the potential to assist community partners in building sufficient knowledge of human subjects research protections to engage in specific projects, thereby expediting the progress of vital research to address community needs. We propose the need for developing truncated human subjects education materials to train and certify community partners, and creating formally organized entities within academic and medical institutions that specialize in community-based research to guide the development and implementation of alternative human subjects training certification opportunities for community partners.

  16. Channel heads in mountain catchments subject to human impact - The Skrzyczne range in Southern Poland

    Science.gov (United States)

    Wrońska-Wałach, Dominika; Żelazny, Mirosław; Małek, Stanisław; Krakowian, Katarzyna; Dąbek, Natalia

    2018-05-01

    Channel heads in mountain catchments are increasingly influenced by human activity. The disturbance of mountain headwater areas in moderate latitudes by the clearing of trees and the associated logging, road building and hydrotechnical constructions contribute to changes in the water cycle and consequently may induce a change in channel head development. Here we examine channel heads in the Beskid Śląski Mts., one of the areas most affected by ecological disaster in the Polish Flysch Carpathians. An ecological disaster associated with the decline of spruce trees in the 1980s and 1990s caused a substantial decrease (of about 50%) in the land area occupied by spruce forest in the Beskid Śląski Mts. As a result, headwater areas were subject to multidirectional changes in the environment. The purpose of this paper is to determine the detailed characteristics of channel heads currently developing in the analyzed headwater areas, as well as to identify independent factors that affect the evolution of channel heads. Geomorphological mapping was conducted in 2012 in the vicinity of springs in the study area. One-way ANOVA was used to determine the significance of differences between mean values calculated for groups identified based on: i) geomorphologic processes (hollows with rock veneer - h, spring niches - sn, gullies - g), ii) location vs. transformation of channel heads (forested areas vs., deforested areas with road constructions). Principal component analysis (PCA) was used to determine the structure and general patterns associated with relationships between the parameters of a channel head and its contribution area, as well as to identify and interpret new (orthogonal) spaces defined using distinct factors. As far as we know, this kind of approach has been never applied before. A total of 80 channel heads surrounding 104 springs were surveyed close to the main ridge in the study area. A total of 14 morphometric parameters were taken into account in this study

  17. 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

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

    International Nuclear Information System (INIS)

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

    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 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 spatiotemporal

  19. When does quality improvement count as research? Human subject protection and theories of knowledge.

    Science.gov (United States)

    Lynn, J

    2004-02-01

    The publication of insights from a quality improvement project recently precipitated a ruling by the lead federal regulatory agency that regulations providing protection for human subjects of research should apply. The required research review process did not match the rapid changes, small samples, limited documentation, clinician management, and type of information commonly used in quality improvement. Yet quality improvement can risk harm to patients, so some review might be in order. The boundaries and processes are not clear. Efforts have been made to determine what constitutes "research", but this has proved difficult and often yields irrational guidance with regard to protection of patients. Society needs a workable way to separate activities that will improve care, on the one hand, and those that constitute research, on the other. Practitioners who lead both quality improvement and research projects claim that those which rapidly give feedback to the care system that generated the data, aiming to change practices within that system, are "quality improvement" no matter whether the findings are published, whether the project is grant funded, and whether contemporaneous controls do not have the intervention. This criterion has not previously been proposed as a possible demarcation. The quandaries of which projects to put through research review and how to ensure ethical implementation of quality improvement need to be resolved.

  20. Dermal absorption and disposition of musk ambrette, musk ketone and musk xylene in human subjects.

    Science.gov (United States)

    Hawkins, David R; Elsom, Lionel F; Kirkpatrick, David; Ford, Richard A; Api, Anne Marie

    2002-05-28

    Musk ambrette, musk ketone and musk xylene have a long history of use as fragrance ingredients, although musk ambrette is no longer used in fragrances. As part of the review of the safety of these uses, it is important to consider the systemic exposure that results from these uses. Since the primary route of exposure to fragrances is on the skin, dermal doses of carbon-14 labelled musk ambrette, musk ketone and musk xylene were applied to the backs (100 cm2) of healthy human volunteers (two to three subjects) at a nominal dose level of 10-20 microg/cm2 and excess material removed at 6 h. Means of 2.0% musk ambrette, 0.5% musk ketone and 0.3% musk xylene were absorbed based on the amounts excreted in urine and faeces during 5 days. Most of the material was excreted in the urine with less than 10% of the amount excreted being found in faeces. No radioactivity was detected in any plasma sample, consistent with low absorption, and no radioactivity was detected (<0.02% dose) in skin strips taken at 120 h. Analysis of urine samples indicated that all three compounds were excreted mainly as single glucuronide conjugates. The aglycones were chromatographically different, but of similar polarity, to the major rat metabolites excreted in bile also as glucuronides.

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

    Directory of Open Access Journals (Sweden)

    Aditya Mungee

    2016-11-01

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

  2. Radioactive mercury distribution in biological fluids and excretion in human subjects after inhalation of mercury vapor

    International Nuclear Information System (INIS)

    Cherian, M.G.; Hursh, J.B.; Clarkson, T.W.; Allen, J.

    1978-01-01

    The distribution of mercury in red blood cells (RBCs) and plasma, and its excretion in urine and feces are described in five human subjects during the first 7 days following inhalation of radioactive mercury vapor. A major portion (98%) of radioactive mercury in whole blood is initially accumulated in the RBCs and is transferred partly to the plasma compartment until the ratio of mercury in RBCs to plasma is about 2 within 20 h. The cumulative urinary and fecal excretion of mercury for 7 days is about 11.6% of the retained dose, and is closely related to the percent decline in body burden of mercury. There is little correlation between either the urinary excretion and plasma radioactivity of mercury, or the specific activities of urine and plasma mercury, suggesting a mechanism other than a direct glomerular filtration involved in the urinary excretion of recently exposed mercury. These studies suggest that blood mercury levels can be used as an index of recent exposure, while urinary levels may be an index of renal concentration of mercury. However, there is no reliable index for mercury concentration in the brain

  3. Infusion pressure and pain during microneedle injection into skin of human subjects

    Science.gov (United States)

    Gupta, Jyoti; Park, Sohyun; Bondy, Brian; Felner, Eric I.; Prausnitz, Mark R.

    2011-01-01

    Infusion into skin using hollow microneedles offers an attractive alternative to hypodermic needle injections. However, the fluid mechanics and pain associated with injection into skin using a microneedle have not been studied in detail before. Here, we report on the effect of microneedle insertion depth into skin, partial needle retraction, fluid infusion flow rate and the co-administration of hyaluronidase on infusion pressure during microneedle-based saline infusion, as well as on associated pain in human subjects. Infusion of up to a few hundred microliters of fluid required pressures of a few hundred mmHg, caused little to no pain, and showed weak dependence on infusion parameters. Infusion of larger volumes up to 1 mL required pressures up to a few thousand mmHg, but still usually caused little pain. In general, injection of larger volumes of fluid required larger pressures and application of larger pressures cause more pain, although other experimental parameters also played a significant role. Among the intradermal microneedle groups, microneedle length had little effect; microneedle retraction lowered infusion pressure but increased pain; lower flow rate reduced infusion pressure and kept pain low; and use of hyaluronidase also lowered infusion pressure and kept pain low. We conclude that microneedles offer a simple method to infuse fluid into the skin that can be carried out with little to no pain. PMID:21684001

  4. Culturally Relevant Human Subjects Protection Training: A Case Study in Community-Engaged Research in the United States.

    Science.gov (United States)

    Kue, Jennifer; Szalacha, Laura A; Happ, Mary Beth; Crisp, Abigail L; Menon, Usha

    2018-02-01

    Non-academic members of research teams, such as community members, can perceive traditional human subjects protection training as lacking in cultural relevance. We present a case exemplar of the development of a human subjects protection training for research staff with limited English proficiency and/or no or limited research experience. Seven modules were adapted for language, cultural examples, etc., from the standard Collaborative Institutional Training Initiative (CITI) human subjects protection training. Non-academic research staff completed a day-long training in human subjects protection (six modules) and our research protocol (one module). We assessed comprehension of content with PowerPoint slides and module quizzes. All participants successfully passed each module quiz with ≥ 80% correct. Questions answered incorrectly were discussed before proceeding to the next module. To meet the increasing demand for collaborative community-engaged research with underserved minority populations, human subjects protection training protocols can be adapted successfully to reflect real-world situations and provide culturally relevant materials to help non-academic research staff better understand the importance and necessity of research ethics.

  5. Do people with intellectual disability require special human subjects research protections? The interplay of history, ethics, and policy.

    Science.gov (United States)

    Feudtner, Chris; Brosco, Jeffrey P

    2011-01-01

    People with intellectual disability (ID) have a long history of discrimination and stigmatization, and a more recent history of pride and self-advocacy. The early history suggests that people with ID are a vulnerable population and deserve special research protections as do some other groups; the disability rights movement of the late 20th century aligns people with ID more closely with the principle of autonomy that has guided clinical and research ethics for the last 40 years. In examining the history of people with ID and the prevailing framework of human subjects research protections in the United States, we conclude that people with ID do not require special protection in human subjects research. The protections that have already been put in place for all individuals, if conscientiously and effectively implemented, achieve the right balance between safeguarding the interest of human research subjects and empowering individuals who choose to do so to participate in research. Copyright © 2012 Wiley Periodicals, Inc.

  6. Tangible and intangible costs of "protecting human subjects": The impact of the National Research Act of 1974 onuniversity research activities

    Directory of Open Access Journals (Sweden)

    Frederic Jacobs

    2004-11-01

    Full Text Available This article (1 examines the overall structure of regulatory research oversight in the United States; (2 details the origins and evolution of federal legislation pertaining to the protection of human subjects in biomedical and behavioral treatment and research; and (3 describes the expansion of oversight regulation from biomedical and behavioral treatment areas to the social sciences. In addition, the paper describes three areas identified by compliance administrators as susceptible to abuse: (1 informed consent, (2 assessment of risks and benefits, and (3 equitable selection of human subjects. There is a discussion of existing tensions in the implementation of oversight policies and procedures. Finally, the paper identifies four issues for future consideration: (1 scope of the mandate regarding protection of human subjects, (2 impact on the nature of research being undertaken, (3 financial burden of compliance and oversight activities, and (4 ethical standards, constraints, and potential.

  7. 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.

  8. 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.

  9. Truncation artifact suppression in cone-beam radionuclide transmission CT using maximum likelihood techniques: evaluation with human subjects

    International Nuclear Information System (INIS)

    Manglos, S.H.

    1992-01-01

    Transverse image truncation can be a serious problem for human imaging using cone-beam transmission CT (CB-CT) implemented on a conventional rotating gamma camera. This paper presents a reconstruction method to reduce or eliminate the artifacts resulting from the truncation. The method uses a previously published transmission maximum likelihood EM algorithm, adapted to the cone-beam geometry. The reconstruction method is evaluated qualitatively using three human subjects of various dimensions and various degrees of truncation. (author)

  10. Cerebrospinal fluid GABA concentration: relationship with impulsivity and history of suicidal behavior, but not aggression, in human subjects.

    Science.gov (United States)

    Lee, Royce; Petty, Frederick; Coccaro, Emil F

    2009-01-01

    The objective of this study was to assess the relationship between cerebrospinal fluid concentrations of the neurotransmitter gamma-aminobutyric acid (GABA) and measures of impulsivity and related behaviors (aggression and suicidality) in healthy volunteer and personality disordered subjects. CSF GABA levels, and measures of impulsivity, aggression, and history of suicidal behavior were obtained by morning lumbar puncture in 57 healthy volunteer subjects and in subjects with personality disorder. CSF GABA levels were not found to correlate with measures of aggression but were found to correlate directly with measures of impulsivity; e.g., a composite measure of impulsivity in all subjects (r=0.35, df=46, P=0.015) and in personality disordered subjects examined separately (r=0.39, df=30, P=0.029). In the personality disorder group, CSF GABA levels were higher among subjects with a history of suicidal behavior compared with those without this history. These data suggest that central GABAergic function correlates directly with impulsiveness and history of suicidal behavior, but not aggressiveness, in personality disordered subjects. This may be consistent with observations that high doses of benzodiazepines can lead to "behavioral disinhibition" in human subjects. Further work assessing this and other aspects of the central GABA system in personality disordered subjects are warranted.

  11. 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.

  12. 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

  13. Effects of inhibition of interleukin-6 signalling on insulin sensitivity and lipoprotein (a levels in human subjects with rheumatoid diseases.

    Directory of Open Access Journals (Sweden)

    Olaf Schultz

    2010-12-01

    Full Text Available Interleukin-6 (IL-6 is a pro-inflammatory cytokine that has been found to be increased in type 2 diabetic subjects. However, it still remains unclear if these elevated IL-6 levels are co-incidental or if this cytokine is causally related to the development of insulin resistance and type 2 diabetes in humans. Therefore, in the present study we examined insulin sensitivity, serum adipokine levels and lipid parameters in human subjects before and after treatment with the IL-6 receptor antibody Tocilizumab.11 non-diabetic patients with rheumatoid disease were included in the study. HOMA-IR was calculated and serum levels for leptin, adiponectin, triglycerides, LDL-cholesterol, HDL-cholesterol and lipoprotein (a (Lp (a were measured before as well as one and three months after Tocilizumab treatment. The HOMA index for insulin resistance decreased significantly. While leptin concentrations were not altered by inhibition of IL-6 signalling, adiponectin concentrations significantly increased. Thus the leptin to adiponectin ratio, a novel marker for insulin resistance, exhibited a significant decrease. Serum triglycerides, LDL-cholesterol and HDL-cholesterol tended to be increased whereas Lp (a levels significantly decreased.Inhibition of IL-6 signalling improves insulin sensitivity in humans with immunological disease suggesting that elevated IL-6 levels in type 2 diabetic subjects might be causally involved in the pathogenesis of insulin resistance. Furthermore, our data indicate that inhibition of IL-6 signalling decreases Lp (a serum levels, which might reduce the cardiovascular risk of human subjects.

  14. 40 CFR 26.1703 - Prohibition of reliance on research involving intentional exposure of human subjects who are...

    Science.gov (United States)

    2010-07-01

    ...), nursing women, or children. 26.1703 Section 26.1703 Protection of Environment ENVIRONMENTAL PROTECTION... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Prohibition of reliance on research... intentional exposure of human subjects who are pregnant women (and therefore their fetuses), nursing women, or...

  15. 40 CFR 26.1203 - Prohibition of research involving intentional exposure of any human subject who is a pregnant...

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Prohibition of research involving intentional exposure of any human subject who is a pregnant woman (and therefore her fetus), a nursing woman, or a child. 26.1203 Section 26.1203 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL...

  16. 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

  17. Sanguinarine induces apoptosis of human osteosarcoma cells through the extrinsic and intrinsic pathways

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hyunjin; Bergeron, Eric; Senta, Helena; Guillemette, Kim [Cell-Biomaterial Biohybrid Systems, Universite de Sherbrooke, Department of Chemical Engineering and Biotechnological Engineering, Canada J1K 2R1 (Canada); Beauvais, Sabrina [Cell-Biomaterial Biohybrid Systems, Universite de Sherbrooke, Department of Chemical Engineering and Biotechnological Engineering, Canada J1K 2R1 (Canada); Development of Bioprocess, Universite de Sherbrooke, Department of Chemical Engineering and Biotechnological Engineering, Canada J1K 2R1 (Canada); Blouin, Richard [Universite de Sherbrooke, Department of Biology, Canada J1K 2R1 (Canada); Sirois, Joel [Development of Bioprocess, Universite de Sherbrooke, Department of Chemical Engineering and Biotechnological Engineering, Canada J1K 2R1 (Canada); Faucheux, Nathalie, E-mail: Nathalie.Faucheux@Usherbrooke.ca [Cell-Biomaterial Biohybrid Systems, Universite de Sherbrooke, Department of Chemical Engineering and Biotechnological Engineering, Canada J1K 2R1 (Canada)

    2010-08-27

    Research highlights: {yields} We show for the first time the effect of sanguinarine (SA) on MG63 and SaOS-2 cells. {yields} SA altered osteosarcoma cell viability in a concentration and time dependent manner. {yields} SA induced osteosarcoma cell apoptosis and increased caspase-8 and -9 activities. {yields} SA decreased dose dependently the Bcl-2 protein level only in MG63 cells. {yields} SaOS-2 which are osteoblast-derived, seemed more resistant to SA than MG63. -- Abstract: The quaternary benzo[c]phenanthridine alkaloid sanguinarine inhibits the proliferation of cancerous cells from different origins, including lung, breast, pancreatic and colon, but nothing is known of its effects on osteosarcoma, a primary malignant bone tumour. We have found that sanguinarine alters the morphology and reduces the viability of MG-63 and SaOS-2 human osteosarcoma cell lines in concentration- and time-dependent manner. Incubation with 1 {mu}mol/L sanguinarine for 4 and 24 h killed more efficiently MG-63 cells than SaOS-2 cells, while incubation with 5 {mu}mol/L sanguinarine killed almost 100% of both cell populations within 24 h. This treatment also changed the mitochondrial membrane potential in both MG-63 and SaOS-2 cells within 1 h, caused chromatin condensation and the formation of apoptotic bodies. It activated multicaspases, and increased the activities of caspase-8 and caspase-9 in both MG-63 and SaOS-2 cells. These data highlight sanguinarine as a novel potential agent for bone cancer therapy.

  18. 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

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

    Science.gov (United States)

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

    1997-04-18

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

  20. 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

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. [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.

  7. The dynamic response of human subjects while seated in car seats.

    Science.gov (United States)

    Pope, M H; Magnusson, M; Broman, N H; Hasson, T

    1998-01-01

    A pendulum impact method was used to establish the dynamic response of the seated subject. Threaded K wires were placed in the L3 spinous process. The gain and phase angle between the platform and the vertebra were established. The response of the subject was observed while seated on a platform and a variety of other seats. The seats were found to be very important in the attenuation of the impulse, leading to a higher transmissibility. Clinical Relevance Skeletal impact through the lower extremity is quite common in many occupations. The importance of posture and seat design in attenuation of impulses has been established.

  8. The dynamic response of human subjects while seated in car seats.

    OpenAIRE

    Pope, M. H.; Magnusson, M.; Broman, N. H.; Hasson, T.

    1998-01-01

    A pendulum impact method was used to establish the dynamic response of the seated subject. Threaded K wires were placed in the L3 spinous process. The gain and phase angle between the platform and the vertebra were established. The response of the subject was observed while seated on a platform and a variety of other seats. The seats were found to be very important in the attenuation of the impulse, leading to a higher transmissibility. Clinical Relevance Skeletal impact through the lower ext...

  9. 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

    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...... drive responsible for the motor unit synchronization during gait may be similar to that responsible for short-term synchronization during tonic voluntary contraction....

  10. Characterization of human myotubes from type 2 diabetic and non-diabetic subjects using complementary quantitative mass spectrometric methods

    DEFF Research Database (Denmark)

    Thingholm, Tine E; Bak, Steffen; Beck-Nielsen, Henning

    2011-01-01

    2 diabetes. Several abnormalities have been identified in skeletal muscle from type 2 diabetic subjects, however, the exact molecular mechanisms leading to the diabetic phenotype has still not been found. Here we present a large-scale study in which we combine a quantitative proteomic discovery...... 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...

  11. 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

    in central and local postural sympathetic vasoconstrictor activity. During sleep, characteristic variations in subcutaneous blood flow were disclosed. The 133Xe washout curve could be divided into three segments with significantly different slopes. Approximately 90 min after the subject went to sleep...

  12. 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

    enriched diet and one non-enriched supplemented diet in a double-blinded crossover design with a 25 days wash-out period in between. Six of the subjects delivered fecal samples on the last two days before starting on the diet and on the two last days of the 14 day diet. Total DNA was isolated from...

  13. Deep pain thresholds in the distal limbs of healthy human subjects.

    Science.gov (United States)

    Rolke, R; Andrews Campbell, K; Magerl, W; Treede, R-D

    2005-02-01

    Pressure pain thresholds (PPTs) in distal limbs have been under-investigated despite their potential clinical importance. Therefore, we compared PPTs over nail bed, bony prominences, and muscle in distal parts of upper and lower limbs. We investigated 12 healthy subjects using three handheld devices: a spring-loaded, analogue pressure threshold meter (PTM) with two operating ranges, and an electronic Algometer. PPTs were determined with three series of ascending stimulus intensities with a ramp of about 50 kPa/s. PPTs were normally distributed in logarithmic space. PPTs over different tissues varied significantly (ANOVA, pAlgometer than with PTMs (ANOVA, ptesting over muscle. There was no significant right-left difference (ANOVA, p=0.33). In spite of considerable variability across subjects, reproducibility within subjects was high (correlation coefficients>0.90). For within-subject comparisons, threshold elevations beyond 33-43% would be abnormal (95% confidence intervals), whereas only deviations from the group mean by at least a factor of two would be abnormal with respect to absolute normative values. PPTs over distal muscles were comparable to published values on proximal limb and trunk muscles. These findings suggest that pressure pain testing over distal muscles may be a sensitive test for deep pain sensitivity and that the simple and less expensive devices are sufficient for testing this tissue type. Intra-individual site-to-site comparisons will be more sensitive than absolute normative values.

  14. 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.

  15. Bilateral responses of upper limb muscles to transcranial magnetic stimulation in human subjects.

    Science.gov (United States)

    Bawa, P; Hamm, J D; Dhillon, P; Gross, P A

    2004-10-01

    Anatomical and behavioural work on primates has shown bilateral innervation of axial and proximal limb muscles, and contralateral control of distal limb muscles. The following study examined if a clear boundary exists between the distal and proximal upper limb muscles that are controlled contralaterally or bilaterally. The right motor cortical area representing the upper limb was stimulated, while surface EMG was recorded bilaterally from various upper limb muscles during rest and phasic voluntary contractions. Peak-to-peak amplitude of motor evoked potential (MEP) was measured for each muscle on both sides. The ratio R = (ipsilateral MEP: contralateral MEP) was calculated for seven pairs of muscles. For each of the seven pairs, R was less than 1.0, implying that for each muscle and subject, the contralateral control is stronger. The boundary where R changed from almost zero to a clearly measurable magnitude depended on the subject. Ipsilateral MEPs from trapezius and pectoralis could be recorded with a small background contraction from almost all subjects; on the other hand, in deltoid and biceps brachii, ipsilateral MEPs were observed only with bimanual phasic contractions. The forearm and hand muscles, in general, did not show any ipsilateral MEPs. Major differences between subjects lay in the presence or the absence of ipsilateral MEPs in biceps brachii and deltoid, without defining a sharp boundary between proximal and distal muscles.

  16. 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.

  17. 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.

  18. Comparing the subjective task difficulty of human operators with task description levels

    International Nuclear Information System (INIS)

    Park, Jin Kyun; Jung, Won Dea; Yang, Joon Eon

    2011-01-01

    Without the loss of generality, it is reasonable to say that an operating procedure consists of many steps including detailed descriptions that provide necessary information in conducting the required tasks safely and effectively. In this regard, since it is widely perceived that procedures are effective for reducing the occurrence of human performance related problems, the use of procedures is very popular in large process control systems including nuclear power plants (NPPs), commercial airplanes and railway systems. However, the secure of an operational safety by using an operating procedure can be accomplished only if human operators are able to effectively obtain necessary information from it. In other words, it is hard to expect the reduction of human performance related problems, if task descriptions are so ambiguous or incomplete that human operators feel an undue difficulty in identifying 'what have to be done' and 'how to do it' from procedures. Unfortunately, it seems that a systematic method that can be used to distinguish the proper level of task descriptions is rare. For this reason, Park et al. developed a decision chart that could be helpful for characterizing the level of task descriptions. In this study, in order to ensure the appropriateness of the suggested decision chart, more detailed investigations were conducted with the support of human operators who are working as the operating personnel of NPPs

  19. 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; Spelman, Kevin

    2009-08-01

    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. 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. 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. For the entire population (n = 17) there was a significant (p officinale ethanolic extract shows promise as a diuretic in humans. Further studies are needed to establish the value of this herb for induction of diuresis in human subjects.

  20. The Public Health Service guidelines. Governing research involving human subjects: An analysis of the policy-making process

    Science.gov (United States)

    Frankel, M. S.

    1972-01-01

    The policy making process which led to development of the Public Health Service Guidelines governing research involving human subjects is outlined. Part 1 examines the evolution of PHS Guidelines, tracing (1) evolution of thought and legal interpretation regarding research using human subjects; (2) initial involvement of the Federal government; (3) development of the government's research program; (4) the social-political environment in which formal government policy was developed; and (5) various policy statements issued by the government. Part 2 analyzes the process by which PHS Guidelines were developed and examines the values and other underlying factors which contributed to their development. It was concluded that the evolution of the Guidelines is best understood within the context of a mixed-scanning strategy. In such a strategy, policy makers make fundamental decisions regarding the basic direction of policy and subsequent decisions are made incrementally and within the contexts set by the original fundamental decisions.

  1. Squeeze-Film Lubrication of the Human Ankle Joint Subjected to the Cyclic Loading Encountered in Walking

    Czech Academy of Sciences Publication Activity Database

    Hlaváček, Miroslav

    2005-01-01

    Roč. 127, č. 1 (2005), s. 141-147 ISSN 0742-4787 R&D Projects: GA ČR(CZ) GA103/04/0150 Institutional research plan: CEZ:AV0Z20710524 Keywords : cyclic loading * human ankle joint * squeeze-film lubrication * synovial fluid filtration * synovial gel formation Subject RIV: JJ - Other Materials Impact factor: 0.682, year: 2005

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    in women when compared with men (P=0.01). IGF1, SOCS1, SOCS2, SOCS3, and CISH mRNA expression increased significantly in muscle after 120 min in all subjects with no impact of age and gender. GH-induced pSTAT5b correlated inversely with lean body mass (LBM; r=-0.56, P=0.01) and positively with the CISH m...

  3. Association of DNA repair polymorphisms with DNA repair functional outcomes in healthy human subjects

    Czech Academy of Sciences Publication Activity Database

    Vodička, Pavel; Štětina, R.; Poláková, Veronika; Tulupová, Elena; Naccarati, Alessio; Vodičková, Ludmila; Kumar, R.; Hánová, Monika; Pardini, Barbara; Slyšková, Jana; Musak, L.; De Palma, G.; Souček, P.; Hemminki, K.

    2007-01-01

    Roč. 28, č. 3 (2007), s. 657-664 ISSN 0143-3334 R&D Projects: GA MZd NR8563; GA ČR GA310/05/2626 Institutional research plan: CEZ:AV0Z50390512 Keywords : Base excision DNA * Single-strand breaks * Peripheral blood lymphocytes Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.406, year: 2007

  4. 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. Copyright © 2017 by the Endocrine Society

  5. Effect of short-term fasting on lipolytic responsiveness in normal and obese human subjects

    International Nuclear Information System (INIS)

    Wolfe, R.R.; Peters, E.J.; Klein, S.; Holland, O.B.; Rosenblatt, J.; Gary, H. Jr.

    1987-01-01

    In this study the rate of lipolysis (fatty acid and glycerol release into blood) has been quantified in both normal weight and obese volunteers after both 15 and 87 h of fasting. In each study, the basal rate and subsequent response to epinephrine infusion were determined. The rate of appearance (R/sub a/) of free fatty acids (FFA) and glycerol were quantified by infusion of [1- 13 C]palmitate and D-5-glycerol, respectively. Substrate flux rates per unit of body fat mass and lean body mass were calculated from total body water measurements using H 2 18 O dilution. In normal volunteers, the basal R/sub a/ FFA and R/sub a/ glycerol rose markedly with 87 h of fasting, whereas the increases were more modest in the obese subjects. However, the rate of mobilization of fat, in relation to the lean body mass, was higher in the obese subjects than in the normal subjects after 15 h of fasting, and the values were similar in both groups after 87 h of fasting. There was an increased lipolytic response to epinephrine after fasting in both groups. This increased sensitivity may have resulted from the enhancement of fatty acid-triglyceride substrate cycling that occurred after fasting

  6. Post-approval monitoring and oversight of U.S.-initiated human subjects research in resource-constrained countries.

    Science.gov (United States)

    Brown, Brandon; Kinsler, Janni; Folayan, Morenike O; Allen, Karen; Cáceres, Carlos F

    2014-06-01

    The history of human subjects research and controversial procedures in relation to it has helped form the field of bioethics. Ethically questionable elements may be identified during research design, research implementation, management at the study site, or actions by a study's investigator or other staff. Post-approval monitoring (PAM) may prevent violations from occurring or enable their identification at an early stage. In U.S.-initiated human subjects research taking place in resource-constrained countries with limited development of research regulatory structures, arranging a site visit from a U.S. research ethics committee (REC) becomes difficult, thus creating a potential barrier to regulatory oversight by the parent REC. However, this barrier may be overcome through the use of digital technologies, since much of the world has at least remote access to the Internet. Empirical research is needed to pilot test the use of these technologies for research oversight to ensure the protection of human subjects taking part in research worldwide.

  7. 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

    AIMS/HYPOTHESIS: In the isolated perfused pancreas, gastric inhibitory polypeptide (GIP) has been shown to enhance glucagon secretion at basal glucose concentrations, but in healthy humans no glucagonotropic effect of GIP has yet been reported. Therefore, we studied the effect of GIP on glucagon ...

  8. 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.

  9. Frequent detection of human papillomavirus 16 E2-specific T-helper immunity in healthy subjects

    NARCIS (Netherlands)

    de Jong, Annemieke; van der Burg, Sjoerd H.; Kwappenberg, Kitty M. C.; van der Hulst, Jeanette M.; Franken, Kees L. M. C.; Geluk, Annemieke; van Meijgaarden, Krista E.; Drijfhout, Jan Wouter; Kenter, Gemma; Vermeij, Pieter; Melief, Cornelis J. M.; Offringa, Rienk

    2002-01-01

    The incidence of genital human papillomavirus (HPV) infections is high in young, sexually active individuals. Most infections are cleared within 1 year after infection. The targets for the cellular immune response in this process of viral clearance remain to be identified, but the expression pattern

  10. Characterization of Common Measures of Heart Period Variability in Healthy Human Subjects: Implications for Patient Monitoring

    Science.gov (United States)

    2010-01-01

    sports medicine and science. Sports Med 2000; 30: 1–15. 41. Eckberg DL. The human respiratory gate. J Physiol 2003; 548: 339–352. 42. Kamen PW, Krum H...in short-term HRV analysis. Biomed Tech 2006; 51: 190–193. 45. Hayano J, Taylor JA, Yamada A, et al. Continuous assessment of hemodynamic control by

  11. 78 FR 12664 - Human Subject Protection; Acceptance of Data From Clinical Studies for Medical Devices

    Science.gov (United States)

    2013-02-25

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 807, 812, and... this document) identifying ethical and other principles that provide assurance of the quality and... communities as ``a standard for the design, conduct, performance, monitoring, auditing, recording, analyses...

  12. 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; ...

  13. 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

    enzymes and genes previously not linked to myogenesis, including IL32, metallothioneins, and pregnancy-specific beta-1-glycoproteins. Functional studies demonstrated IL-32 as a novel target that regulates human myogenesis, insulin sensitivity and ATP levels in muscle cells. Furthermore, IL32 transgenic...

  14. 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.

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

    Science.gov (United States)

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

    2014-01-01

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

  16. Single-neuron correlates of subjective vision in the human medial temporal lobe

    OpenAIRE

    Kreiman, Gabriel; Fried, Itzhak; Koch, Christof

    2002-01-01

    Visual information from the environment is transformed into perceptual sensations through several stages of neuronal processing. Flash suppression constitutes a striking example in which the same retinal input can give rise to two different conscious visual percepts. We directly recorded the responses of individual neurons during flash suppression in the human amygdala, entorhinal cortex, hippocampus, and parahippocampal gyrus, allowing us to explore the neuronal responses in untrained subjec...

  17. Ingestible roasted barley for contrast-enhanced photoacoustic imaging in animal and human subjects.

    Science.gov (United States)

    Wang, Depeng; Lee, Dong Hyeun; Huang, Haoyuan; Vu, Tri; Lim, Rachel Su Ann; Nyayapathi, Nikhila; Chitgupi, Upendra; Liu, Maggie; Geng, Jumin; Xia, Jun; Lovell, Jonathan F

    2018-08-01

    Photoacoustic computed tomography (PACT) is an emerging imaging modality. While many contrast agents have been developed for PACT, these typically cannot immediately be used in humans due to the lengthy regulatory process. We screened two hundred types of ingestible foodstuff samples for photoacoustic contrast with 1064 nm pulse laser excitation, and identified roasted barley as a promising candidate. Twenty brands of roasted barley were further screened to identify the one with the strongest contrast, presumably based on complex chemical modifications incurred during the roasting process. Individual roasted barley particles could be detected through 3.5 cm of chicken-breast tissue and through the whole hand of healthy human volunteers. With PACT, but not ultrasound imaging, a single grain of roasted barley was detected in a field of hundreds of non-roasted particles. Upon oral administration, roasted barley enabled imaging of the gut and peristalsis in mice. Prepared roasted barley tea could be detected through 2.5 cm chicken breast tissue. When barley tea was administered to humans, photoacoustic imaging visualized swallowing dynamics in healthy volunteers. Thus, roasted barley represents an edible foodstuff that should be considered for photoacoustic contrast imaging of swallowing and gut processes, with immediate potential for clinical translation. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Nazila Alizadeh

    2016-07-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  20. 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.

  1. 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.

  2. 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 cortisol levels did not correlate with age or urinary cortisol. There was a negative correlation between hair testosterone and age (r = -0.47, p 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 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.

  3. Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects

    International Nuclear Information System (INIS)

    Fox, P.T.; Raichle, M.E.

    1986-01-01

    Coupling between cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO 2 ) was studied using multiple sequential administrations of 15 O-labeled radiotracers and positron emission tomography. In the resting state an excellent correlation between CBF and CMRO 2 was found when paired measurements of CBF and CMRO 2 from multiple (30-48) brain regions were tested in each of 33 normal subjects. Regional uncoupling of CBF and CMRO 2 was found, however, during neuronal activation induced by somatosensory stimulation. Stimulus-induced focal augmentation of cerebral blood flow (29% mean) far exceeded the concomitant local increase in tissue metabolic rate (mean, 5%), when resting-state and stimulated-state measurements were obtained in each of 9 subjects. Stimulus duration had no significant effect on response magnitude or on the degree of CBF-CMRO 2 uncoupling observed. Dynamic, physiological regulation of CBF by a mechanism (neuronal or biochemical) dependent on neuronal firing per se, but independent of the cerebral metabolic rate of oxygen, is hypothesized

  4. 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

  5. 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

    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 performed well

  6. Some aspects of choice of specimen for biomedical trace element research studies in human subjects

    International Nuclear Information System (INIS)

    Iyengar, G.V.; Kollmer, W.E.

    1984-01-01

    An attempt is made to extend the examination of the biological background of human specimens in order to identify their suitability to reflect the desired elemental composition status meaningfully, and to view the analytical aspects to ensure reliability. A few examples, which have shown consistent results of practical value are presented. They include: blood, hair, urine, feces, and milk. The most meaningful analysis can be done in the organs which are damaged if an essential element is not present in a sufficient amount or a harmful element is present at a toxic level. e.g., liver and kidney. 20 references, 2 tables

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Power of theta waves in the EEG of human subjects increases during recall of haptic information.

    Science.gov (United States)

    Grunwald, M; Weiss, T; Krause, W; Beyer, L; Rost, R; Gutberlet, I; Gertz, H J

    1999-02-05

    Several studies have reported a functional relationship between spectral power within the theta-band of the EEG (theta-power) and memory load while processing visual or semantic information. We investigated theta power during the processing of different complex haptic stimuli using a delayed recall design. The haptic explorations consisted of palpating the structure of twelve sunken reliefs with closed eyes. Subjects had to reproduce each relief by drawing it 10 s after the end of the exploration. The relationship between mean theta power and mean exploration time was analysed using a regression model. A linear relationship was found between the exploration time and theta power over fronto-central regions (Fp1, Fp2, F3, F7, F8, Fz, C3) directly before the recall of the relief. This result is interpreted in favour of the hypothesis that fronto-central theta power of the EEG correlates with the load of working memory independent of stimulus modality.

  9. Nonlinear dynamics analysis of the human balance control subjected to physical and sensory perturbations.

    Science.gov (United States)

    Ashtiani, Mohammed N; Mahmood-Reza, Azghani

    2017-01-01

    Postural control after applying perturbation involves neural and muscular efforts to limit the center of mass (CoM) motion. Linear dynamical approaches may not unveil all complexities of body efforts. This study was aimed at determining two nonlinear dynamics parameters (fractal dimension (FD) and largest Lyapunov exponent (LLE)) in addition to the linear standing metrics of balance in perturbed stance. Sixteen healthy young males were subjected to sudden rotations of the standing platform. The vision and cognition during the standing were also interfered. Motion capturing was used to measure the lower limb joints and the CoM displacements. The CoM path length as a linear parameter was increased by elimination of vision (pnonlinear metric FD was decreased due to the cognitive loads (pnonlinear metrics of the perturbed stance showed that a combination of them may properly represent the body behavior.

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    and the proportional hazard model for generating individual lifespan. Family genotype data is generated using a genetic linkage program for given SNP allele frequency. Power is estimated by setting the type I error rate at 0.05 and by calculating the Armitage's chi-squared test statistic for 200 replicate samples...... the direct approach. It also has low power in detecting non-additive effect genes. Indirect genetic association using offspring from families with both parents as nonagenarians is nearly as powerful as using offspring from families with one centenarian parent. In conclusion, the indirect design can be a good......Recently, an indirect genetic association approach that compares genotype frequencies in offspring of long-lived subjects and offspring from random families has been introduced to study gene-longevity associations. Although the indirect genetic association has certain advantages over the direct...

  11. 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...

  12. The effects of diet and physical activity on plasma homovanillic acid in normal human subjects.

    Science.gov (United States)

    Kendler, K S; Mohs, R C; Davis, K L

    1983-03-01

    This study examines the effect of diet and moderate physical activity on plasma levels of the dopamine metabolite homovanillic acid (HVA) in healthy young males. At weekly intervals, subjects were fed four isocaloric meals: polycose (pure carbohydrate), sustecal, low monoamine, and high monoamine. Moderate physical activity consisted of 30 minutes of exercise on a bicycle ergometer. The effect of diet on plasma HVA (pHVA) was highly significant. Compared to the polycose meal, the high monoamine meal significantly increased pHVA. Moderate physical activity also significantly increased pHVA. Future clinical studies using pHVA in man as an index of brain dopamine function should control for the effects of both diet and physical activity.

  13. Effect of mental stress on plasma homovanillic acid in healthy human subjects.

    Science.gov (United States)

    Sumiyoshi, T; Yotsutsuji, T; Kurachi, M; Itoh, H; Kurokawa, K; Saitoh, O

    1998-07-01

    Plasma levels of homovanillic acid (pHVA) have been suggested to provide a measure of dopaminergic activity in the central nervous system. The present study investigated the effect of mental stress by the Kraepelin test, a test of continuous arithmetic addition of single-digit figures for 30 min, on pHVA levels in 13 male psychiatrically normal healthy volunteers. Following an overnight fast and restricted physical activity, plasma samples were collected immediately before and after the administration of the Kraepelin test. Plasma HVA levels following the administration of the Kraepelin test were significantly lower than the pretest pHVA levels. The percent change in pHVA levels by the Kraepelin test positively correlated with pretest pHVA levels. The observed reduction in pHVA levels by mental stress in normal subjects may reflect some aspects of a dopamine-dependent restitutive system in the brain.

  14. Velocity storage contribution to vestibular self-motion perception in healthy human subjects.

    Science.gov (United States)

    Bertolini, G; Ramat, S; Laurens, J; Bockisch, C J; Marti, S; Straumann, D; Palla, A

    2011-01-01

    Self-motion perception after a sudden stop from a sustained rotation in darkness lasts approximately as long as reflexive eye movements. We hypothesized that, after an angular velocity step, self-motion perception and reflexive eye movements are driven by the same vestibular pathways. In 16 healthy subjects (25-71 years of age), perceived rotational velocity (PRV) and the vestibulo-ocular reflex (rVOR) after sudden decelerations (90°/s(2)) from constant-velocity (90°/s) earth-vertical axis rotations were simultaneously measured (PRV reported by hand-lever turning; rVOR recorded by search coils). Subjects were upright (yaw) or 90° left-ear-down (pitch). After both yaw and pitch decelerations, PRV rose rapidly and showed a plateau before decaying. In contrast, slow-phase eye velocity (SPV) decayed immediately after the initial increase. SPV and PRV were fitted with the sum of two exponentials: one time constant accounting for the semicircular canal (SCC) dynamics and one time constant accounting for a central process, known as velocity storage mechanism (VSM). Parameters were constrained by requiring equal SCC time constant and VSM time constant for SPV and PRV. The gains weighting the two exponential functions were free to change. SPV were accurately fitted (variance-accounted-for: 0.85 ± 0.10) and PRV (variance-accounted-for: 0.86 ± 0.07), showing that SPV and PRV curve differences can be explained by a greater relative weight of VSM in PRV compared with SPV (twofold for yaw, threefold for pitch). These results support our hypothesis that self-motion perception after angular velocity steps is be driven by the same central vestibular processes as reflexive eye movements and that no additional mechanisms are required to explain the perceptual dynamics.

  15. Recombinant DNA derived monomeric insulin analogue: comparison with soluble human insulin in normal subjects.

    Science.gov (United States)

    Vora, J P; Owens, D R; Dolben, J; Atiea, J A; Dean, J D; Kang, S; Burch, A; Brange, J

    1988-11-12

    To compare the rate of absorption from subcutaneous tissue and the resulting hypoglycaemic effect of iodine-125 labelled soluble human insulin and a monomeric insulin analogue derived by recombinant DNA technology. Single blind randomised comparison of equimolar doses of 125I labelled soluble human insulin and insulin analogue. Study in normal people at a diabetes research unit and a university department of medical physics. Seven healthy male volunteers aged 20-39 not receiving any other drugs. After an overnight fast and a basal period of one hour two doses (0.05 and 0.1 U/kg) of 125I labelled soluble human insulin and insulin analogue were injected subcutaneously into the anterior abdominal wall on four separate days. To find a fast acting insulin for meal related requirements in insulin dependent diabetics. MEASUREMENTS and main results--Residual radioactivity at the injection site was measured continuously for the first two hours after injection of the 125I labelled preparations and thereafter for five minutes simultaneously with blood sampling. Frequent venous blood samples were obtained over six hours for determination of plasma immunoreactive insulin, insulin analogue, glucose, and glucagon values. Time to 50% of initial radioactivity at the injection site for the insulin analogue compared with soluble insulin was 61 v 135 minutes (p less than 0.05) with 0.05 U/kg and 67 v 145 minutes (p less than 0.001) with 0.1 U/kg. Concentrations in plasma increased faster after the insulin analogue compared with soluble insulin, resulting in higher plasma concentrations between 10 and 150 minutes (0.001 less than p less than 0.05) after 0.05 U/kg and between 40 and 360 minutes (0.001 less than p less than 0.05) after 0.1 U/kg. The hypoglycaemic response to insulin analogue was a plasma glucose nadir at 60 minutes with both doses compared with 90 and 120 minutes with soluble insulin at 0.5 and 0.1 U/kg respectively. The response of glucagon substantiated the earlier and

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    Gilpin Heather

    2008-08-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Hays, M.T.

    1979-03-01

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

  19. Effect of gemfibrozil on the metabolism of brivaracetam in vitro and in human subjects.

    Science.gov (United States)

    Nicolas, J-M; Chanteux, H; Rosa, M; Watanabe, S; Stockis, A

    2012-08-01

    Brivaracetam (BRV) is a new high-affinity synaptic vesicle protein 2A ligand in phase III for epilepsy. Initial studies suggested that the hydroxylation of BRV into BRV-OH is supported by CYP2C8. Other metabolic routes include hydrolysis into a carboxylic acid derivative (BRV-AC), which could be further oxidized into a hydroxy acid derivative (BRV-OHAC). The aim of the present study was to investigate the effect of gemfibrozil (CYP2C9 inhibitor) and its 1-O-β-glucuronide (CYP2C8 inhibitor) on BRV disposition both in vivo (healthy participants) and in vitro (human liver microsomes and hepatocytes). In a two-period randomized crossover study, 26 healthy male participants received a single oral dose of 150 mg of BRV alone or at steady state of gemfibrozil (600 mg b.i.d). Gemfibrozil did not modify plasma and urinary excreted BRV, BRV-OH, or BRV-AC. The only observed change was a modest decrease (approximately -40%) in plasma and urinary BRV-OHAC. In human hepatocytes and/or liver microsomes, gemfibrozil potently inhibited the hydroxylation of BRV-AC into BRV-OHAC (K(I) 12 μM) while having a marginal effect on BRV-OH formation (K(I) ≥153 μM). Gemfibrozil-1-O-β-glucuronide had no relevant effect on either reaction (K(I) >200 μM). In conclusion, gemfibrozil did not influence the pharmacokinetics of BRV and its hydroxylation into BRV-OH. Overall, in vitro and in vivo data suggest that CYP2C8 and CYP2C9 are not involved in BRV hydroxylation, whereas hydroxylation of BRV-AC to BRV-OHAC is likely to be mediated by CYP2C9.

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

    International Nuclear Information System (INIS)

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

    1984-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Go-Eun Lee

    2017-01-01

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

  2. A mixed diet supplemented with l-arabinose does not alter glycaemic or insulinaemic responses in healthy human subjects

    DEFF Research Database (Denmark)

    Halschou-Jensen, Kia; Knudsen, Knud E Bach; Nielsen, Soren

    2015-01-01

    of the present study showed that the peak plasma concentration, time to reach peak plasma concentration or AUC values of glucose, insulin and C-peptide were not altered after consumption of the test meals. Overall, it was not possible to reproduce the beneficial effects of L-arabinose added to sucrose drinks...... effects on postprandial blood glucose, insulin and C-peptide responses in humans. However, the effects of adding L-arabinose to mixed meals on the indices of glucose control are unknown. The purpose of the present study was to investigate whether the positive effects of L-arabinose added to a sugar drink...... could be reproduced in subjects consuming a mixed meal containing sucrose and/or starch from wheat flour. A total of seventeen healthy men participated in study 1, a randomised, double-blind, cross-over trial. In this study, the subjects consumed two different breakfast meals containing sucrose...

  3. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  5. Radiation absorbed dose estimate for rubidium-82 determined from in vivo measurements in human subjects

    International Nuclear Information System (INIS)

    Ryan, J. W.; Harper, P.V.; Stark, V.S.; Peterson, E.L.; Lathrop, K.A.

    1986-01-01

    Radiation absorbed doses from rubidium-82 injected intravenously were determined in two young men, aged 23 and 27, using a dynamic conjugate counting technique to provide data for the net organ integrated time-activity curves in five organs: kidneys, lungs, liver, heart, and testes. This technique utilized a tungsten collimated Anger camera and the accuracy was validated in a prestwood phantom. The data for each organ were compared with conjugate count rates of a reference Ge-68/Ga-68 standard which had been calibrated against the Rb-82 injected. The effects of attenuation in the body were eliminated. The MIRD method was used to calculate the organ self absorbed doses and the total organ absorbed doses. The mean total absorbed doses were as follows (mrads/mCi injected): kidneys 30.9, heart walls 7.5, lungs 6.0, liver 3.0, testes 2.0 (one subject only), red marrow 1.3, remainder of body 1.3 and, extrapolating to women, ovaries 1.2. This absorbed dose to the kidney is significantly less than the pessimistic estimate of 59.4 mrads/mCi, made assuming instantaneous uptake and complete extraction of activity with no excretion by the kidneys, which receive 20% of the cardiac output. Further, in a 68 year old man the renal self absorbed dose was approximately 40% less than the mean renal self absorbed dose of the younger men. This decrease is probably related to the decline in renal blood flow which occurs with advancing age but other factors may also contribute to the observed difference. 14 references, 4 figures, 2 tables

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    Cai Weibo

    2007-01-01

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

  8. 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.

  9. CSF proteomics of secondary phase spinal cord injury in human subjects: perturbed molecular pathways post injury.

    Directory of Open Access Journals (Sweden)

    Mohor Biplab Sengupta

    Full Text Available Recovery of sensory and motor functions following traumatic spinal cord injury (SCI is dependent on injury severity. Here we identified 49 proteins from cerebrospinal fluid (CSF of SCI patients, eight of which were differentially abundant among two severity groups of SCI. It was observed that the abundance profiles of these proteins change over a time period of days to months post SCI. Statistical analysis revealed that these proteins take part in several molecular pathways including DNA repair, protein phosphorylation, tRNA transcription, iron transport, mRNA metabolism, immune response and lipid and ATP catabolism. These pathways reflect a set of mechanisms that the system may adopt to cope up with the assault depending on the injury severity, thus leading to observed physiological responses. Apart from putting forward a picture of the molecular scenario at the injury site in a human study, this finding further delineates consequent pathways and molecules that may be altered by external intervention to restrict neural degeneration.

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

    Science.gov (United States)

    Wu, Haoming; Padhi, Abinash; Xu, Junqiang; Gong, Xiaoyan; Tien, Po

    2016-01-01

    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.

  11. Presence of Human Herpesvirus 6B in the Pancreas of Subjects With and Without Type 1 Diabetes.

    Science.gov (United States)

    Ericsson, Maja; Skog, Oskar

    The aims of this study were to investigate the presence of human herpesvirus 6 (HHV6) A and B in human pancreata and to search for signs of active infection in this organ of subjects with and without type 1 diabetes (T1D). Pancreata from brain-dead organ donors with and without T1D were examined for the presence of HHV6 genomic sequences by polymerase chain reaction (PCR), transcripts by reverse transcriptase-PCR, and protein by immunohistochemistry. Quantitative PCR of isolated pancreatic islets and exocrine cell clusters was used to determine the intrapancreatic location of HHV6 DNA. Human herpesvirus 6B genomic sequences were present in 1 of 2 donors who died of acute-onset T1D, 4 of 6 donors with long-standing T1D, and 9 of 12 nondiabetic donors. Higher copy numbers of HHV6B DNA were present in isolated islets than in exocrine tissue from the same donors. No signs of active HHV6 transcription were found. Human herpesvirus 6A was not present in any tested pancreas. The herein presented data demonstrate, for the first time, the presence of a latent HHV6B infection in the pancreas and islets of Langerhans. Whether this virus can contribute to disease in the pancreas remains to be determined.

  12. In vivo EPR dosimetry of accidental exposures to radiation: experimental results indicating the feasibility of practical use in human subjects

    International Nuclear Information System (INIS)

    Miyake, Minoru; Liu, K.J.; Walczak, T.M.; Swartz, H.M.

    2000-01-01

    Low frequency electron paramagnetic resonance (EPR) provides the potential advantage of making accurate and sensitive measurements of absorbed radiation dose in teeth in situ, i.e. without removing the teeth from the potential victim. The potential limiting factors for making such measurements are: (1) whether low frequency EPR is sufficiently sensitive to detect radiation-induced signal in human teeth; (2) whether sufficient sensitivity can be maintained under in vivo conditions. In this manuscript, we summarize results indicating that this approach is feasible. Using 1.2 GHz EPR spectroscopy, we found that the lower limit for these measurements in isolated human teeth is 0.2 Gy or lower. Measurements of radiation-induced EPR signals in the teeth of living rats were achieved with sufficient sensitivity to indicate that, when taking into consideration the larger mass of human teeth, similar measurements in human teeth in situ would provide sensitivity in the dose range for potential accidental exposures. We estimate that the current lower limit for detecting radiation doses in human teeth in situ (in vivo) is 0.5-1.0 Gy; this would be sufficient for determining if a person has been exposed to potentially life threatening doses of ionizing radiation. The limiting factor for sensitivity appears to be background signals rather than signal/noise, and there are feasible means to overcome this problem and further increase sensitivity. The additional instrumental developments required to make an effective in vivo EPR dosimetric spectrometer for the measurements in teeth in human subjects in situ, seem quite achievable

  13. In vitro analysis of low-level laser irradiation on human osteoblast-like cells proliferation

    Science.gov (United States)

    Bloise, Nora; Saino, Enrica; Bragheri, Francesca; Minzioni, Paolo; Cristiani, Ilaria; Imbriani, Marcello; Visai, Livia

    2011-07-01

    The objective of this study was to examine the in vitro effect of a single or a multiple doses of low-level laser irradiation (LLLI) on proliferation of the human osteosarcoma cell line, SAOS-2. SAOS-2 cells were divided in five groups and exposed to LLLI (659 nm diode laser; 11 mW power output): group I as a control (dark), group II exposed to a single laser dose of 1 J/cm2, group III irradiated with a single dose of 3 J/cm2, and group IV and V exposed for three consecutive days to 1 or 3 J/cm², respectively. Cellular proliferation was assessed daily up to 7 days of culturing. The obtained results showed an increase in proliferative capacity of SAOS-2 cells during the first 96 h of culturing time in once-irradiated cells, as compared to control cells. Furthermore, a significantly higher proliferation in the group IV and V was detected if compared to a single dose or to control group after 96 h and 7 days. In conclusion, the effect of the single dose on cell proliferation was transitory and repeated irradiations were necessary to observe a strong enhancement of SAOS-2 growth. As a future perspective, we would like to determine the potential of LLLI as a new approach for promoting bone regeneration onto biomaterials.

  14. 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.

  15. Undergraduate research involving human subjects should not be granted ethical approval unless it is likely to be of publishable quality.

    Science.gov (United States)

    Gallagher, Cathal T; McDonald, Lisa J; McCormack, Niamh P

    2014-06-01

    Small-scale research projects involving human subjects have been identified as being effective in developing critical appraisal skills in undergraduate students. In deciding whether to grant ethical approval to such projects, university research ethics committees must weigh the benefits of the research against the risk of harm or discomfort to the participants. As the learning objectives associated with student research can be met without the need for human subjects, the benefit associated with training new healthcare professionals cannot, in itself, justify such risks. The outputs of research must be shared with the wider scientific community if it is to influence future practice. Our survey of 19 UK universities indicates that undergraduate dissertations associated with the disciplines of medicine, dentistry and pharmacy are not routinely retained in their library catalogues, thus closing a major avenue to the dissemination of their findings. If such research is unlikely to be published in a peer-reviewed journal, presented at a conference, or otherwise made available to other researchers, then the risks of harm, discomfort or inconvenience to participants are unlikely to be offset by societal benefits. Ethics committees should be satisfied that undergraduate research will be funnelled into further research that is likely to inform clinical practice before granting ethical approval.

  16. 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.

  17. 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.

  18. Molecular Monitoring of the Fecal Microbiota of Healthy Human Subjects during Administration of Lactulose and Saccharomyces boulardii

    Science.gov (United States)

    Vanhoutte, Tom; De Preter, Vicky; De Brandt, Evie; Verbeke, Kristin; Swings, Jean; Huys, Geert

    2006-01-01

    Diet is a major factor in maintaining a healthy human gastrointestinal tract, and this has triggered the development of functional foods containing a probiotic and/or prebiotic component intended to improve the host's health via modulation of the intestinal microbiota. In this study, a long-term placebo-controlled crossover feeding study in which each subject received several treatments was performed to monitor the effect of a prebiotic substrate (i.e., lactulose), a probiotic organism (i.e., Saccharomyces boulardii), and their synbiotic combination on the fecal microbiota of three groups of 10 healthy human subjects differing in prebiotic dose and/or intake of placebo versus synbiotic. For this purpose, denaturing gradient gel electrophoresis (DGGE) analysis of 16S rRNA gene amplicons was used to detect possible changes in the overall bacterial composition using the universal V3 primer and to detect possible changes at the subpopulation level using group-specific primers targeting the Bacteroides fragilis subgroup, the genus Bifidobacterium, the Clostridium lituseburense group (cluster XI), and the Clostridium coccoides-Eubacterium rectale group (cluster XIVa). Although these populations remained fairly stable based on DGGE profiling, one pronounced change was observed in the universal fingerprint profiles after lactulose ingestion. Band position analysis and band sequencing revealed that a band appearing or intensifying following lactulose administration could be assigned to the species Bifidobacterium adolescentis. Subsequent analysis with real-time PCR (RT-PCR) indicated a statistically significant increase (P < 0.05) in total bifidobacteria in one of the three subject groups after lactulose administration, whereas a similar but nonsignificant trend was observed in the other two groups. Combined RT-PCR results from two subject groups indicated a borderline significant increase (P = 0.074) of B. adolescentis following lactulose intake. The probiotic yeast S

  19. Effect of mental challenge induced by movie clips on action potential duration in normal human subjects independent of heart rate.

    Science.gov (United States)

    Child, Nicholas; Hanson, Ben; Bishop, Martin; Rinaldi, Christopher A; Bostock, Julian; Western, David; Cooklin, Michael; O'Neil, Mark; Wright, Matthew; Razavi, Reza; Gill, Jaswinder; Taggart, Peter

    2014-06-01

    Mental stress and emotion have long been associated with ventricular arrhythmias and sudden death in animal models and humans. The effect of mental challenge on ventricular action potential duration (APD) in conscious healthy humans has not been reported. Activation recovery intervals measured from unipolar electrograms as a surrogate for APD (n=19) were recorded from right and left ventricular endocardium during steady-state pacing, whilst subjects watched an emotionally charged film clip. To assess the possible modulating role of altered respiration on APD, the subjects then repeated the same breathing pattern they had during the stress, but without the movie clip. Hemodynamic parameters (mean, systolic, and diastolic blood pressure, and rate of pressure increase) and respiration rate increased during the stressful part of the film clip (P=0.001). APD decreased during the stressful parts of the film clip, for example, for global right ventricular activation recovery interval at end of film clip 193.8 ms (SD, 14) versus 198.0 ms (SD, 13) during the matched breathing control (end film left ventricle 199.8 ms [SD, 16] versus control 201.6 ms [SD, 15]; P=0.004). Respiration rate increased during the stressful part of the film clip (by 2 breaths per minute) and was well matched in the respective control period without any hemodynamic or activation recovery interval changes. Our results document for the first time direct recordings of the effect of a mental challenge protocol on ventricular APD in conscious humans. The effect of mental challenge on APD was not secondary to emotionally induced altered respiration or heart rate. © 2014 American Heart Association, Inc.

  20. 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.

  1. A low dose lipid infusion is sufficient to induce insulin resistance and a pro-inflammatory response in human subjects.

    Science.gov (United States)

    Liang, Hanyu; Lum, Helen; Alvarez, Andrea; Garduno-Garcia, Jose de Jesus; Daniel, Benjamin J; Musi, Nicolas

    2018-01-01

    The root cause behind the low-grade inflammatory state seen in insulin resistant (obesity and type 2 diabetes) states is unclear. Insulin resistant subjects have elevations in plasma free fatty acids (FFA), which are ligands for the pro-inflammatory toll-like receptor (TLR)4 pathway. We tested the hypothesis that an experimental elevation in plasma FFA (within physiological levels) in lean individuals would upregulate TLR4 and activate downstream pathways (e.g., MAPK) in circulating monocytes. Twelve lean, normal glucose-tolerant subjects received a low dose (30 ml/h) 48 h lipid or saline infusion on two different occasions. Monocyte TLR4 protein level, MAPK phosphorylation, and expression of genes in the TLR pathway were determined before and after each infusion. The lipid infusion significantly increased monocyte TLR4 protein and phosphorylation of JNK and p38 MAPK. Lipid-mediated increases in TLR4 and p38 phosphorylation directly correlated with reduced peripheral insulin sensitivity (M value). Lipid increased levels of multiple genes linked to inflammation, including several TLRs, CD180, MAP3K7, and CXCL10. Monocytes exposed in vivo to lipid infusion exhibited enhanced in vitro basal and LPS-stimulated IL-1β secretion. In lean subjects, a small increase in plasma FFA (as seen in insulin resistant subjects) is sufficient to upregulate TLR4 and stimulate inflammatory pathways (MAPK) in monocytes. Moreover, lipids prime monocytes to endotoxin. We provide proof-of-concept data in humans indicating that the low-grade inflammatory state characteristic of obesity and type 2 diabetes could be caused (at least partially) by pro-inflammatory monocytes activated by excess lipids present in these individuals.

  2. The RID2 biofidelic rear impact dummy: a pilot study using human subjects in low speed rear impact full scale crash tests.

    Science.gov (United States)

    Croft, Arthur C; Philippens, Mathieu M G M

    2007-03-01

    Human subjects and the recently developed RID2 rear impact crash test dummy were exposed to a series of full scale, vehicle-to-vehicle crash tests. To evaluate the biofidelity of the RID2 anthropometric test dummy on the basis of calculated neck injury criterion (NIC) values by comparing these values to those obtained from human subjects exposed in the very same crashes. The widely used and familiar hybrid III dummy has been said to lack biofidelity in the special application of low speed rear impact crashes. Several attempts have been made to modify this dummy with only marginal success. Two completely new dummies have been developed; the BioRID and the RID2. Neither have been tested under real world crash boundary conditions in side-by-side comparisons with live human subjects. Volunteer subjects, including a 50th percentile male, a 95th percentile male, and a 50th percentile female, were placed in the driver's seat of a vehicle and subjected to a series of three low speed rear impact crashes each. The RID2 dummy, which is modeled after a 50th percentile male, was placed in the passenger seat in each case. Both subjects and dummy were fully instrumented and acceleration-time histories were recorded. From this data, velocities of the heads and torsos were determined and both were used to calculate the NIC values for both crash test subjects and the RID2. The RID2 demonstrated generally higher head accelerations and NIC values than those of the human subjects. Most of the observed variations might be explained on the basis of differing head restraint geometry, posture, and body size. The RID2 NIC values compared most favorably with those of the 50th percentile male subject. For the whole group, the correlations between RID2 and human subjects did not reach statistical significance. The small number of test subjects and crash tests limited the statistical power of this pilot study, and the correlation between the RID2 and human subject NIC values were not

  3. 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.

  4. Olfactory sensitivity for sperm-attractant aromatic aldehydes: a comparative study in human subjects and spider monkeys.

    Science.gov (United States)

    Kjeldmand, Luna; Salazar, Laura Teresa Hernandez; Laska, Matthias

    2011-01-01

    Using a three-alternative forced-choice ascending staircase procedure, we determined olfactory detection thresholds in 20 human subjects for seven aromatic aldehydes and compared them to those of four spider monkeys tested in parallel using an operant conditioning paradigm. With all seven odorants, both species detected concentrations lyral, and 3-phenylpropanal. No significant correlation between presence/absence of an oxygen-containing moiety attached to the benzene ring or presence/absence of an additional alkyl group next to the functional aldehyde group, and olfactory sensitivity was found in any of the species. However, the presence of a tertiary butyl group in para position (relative to the functional aldehyde group) combined with a lack of an additional alkyl group next to the functional aldehyde group may be responsible for the finding that both species were most sensitive to bourgeonal.

  5. 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

    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.......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...

  6. 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.

  7. 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.

  8. In vivo emergence of vicriviroc resistance in a human immunodeficiency virus type 1 subtype C-infected subject.

    Science.gov (United States)

    Tsibris, Athe M N; Sagar, Manish; Gulick, Roy M; Su, Zhaohui; Hughes, Michael; Greaves, Wayne; Subramanian, Mani; Flexner, Charles; Giguel, Françoise; Leopold, Kay E; Coakley, Eoin; Kuritzkes, Daniel R

    2008-08-01

    Little is known about the in vivo development of resistance to human immunodeficiency virus type 1 (HIV-1) CCR5 antagonists. We studied 29 subjects with virologic failure from a phase IIb study of the CCR5 antagonist vicriviroc (VCV) and identified one individual with HIV-1 subtype C who developed VCV resistance. Studies with chimeric envelopes demonstrated that changes within the V3 loop were sufficient to confer VCV resistance. Resistant virus showed VCV-enhanced replication, cross-resistance to another CCR5 antagonist, TAK779, and increased sensitivity to aminooxypentane-RANTES and the CCR5 monoclonal antibody HGS004. Pretreatment V3 loop sequences reemerged following VCV discontinuation, implying that VCV resistance has associated fitness costs.

  9. 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.

  10. 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

  11. 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

  12. 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

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

  14. 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.

  15. An acetone breath analyzer using cavity ringdown spectroscopy: an initial test with human subjects under various situations

    International Nuclear Information System (INIS)

    Wang, Chuji; Surampudi, Anand B

    2008-01-01

    We have developed a portable breath acetone analyzer using cavity ringdown spectroscopy (CRDS). The instrument was initially tested by measuring the absorbance of breath gases at a single wavelength (266 nm) from 32 human subjects under various conditions. A background subtraction method, implemented to obtain absorbance differences, from which an upper limit of breath acetone concentration was obtained, is described. The upper limits of breath acetone concentration in the four Type 1 diabetes (T1D) subjects, tested after a 14 h overnight fast, range from 0.80 to 3.97 parts per million by volume (ppmv), higher than the mean acetone concentration (0.49 ppmv) in non-diabetic healthy breath reported in the literature. The preliminary results show that the instrument can tell distinctive differences between the breath from individuals who are healthy and those with T1D. On-line monitoring of breath gases in healthy people post-exercise, post-meals and post-alcohol-consumption was also conducted. This exploratory study demonstrates the first CRDS-based acetone breath analyzer and its potential application for point-of-care, non-invasive, diabetic monitoring

  16. The effect of trimethoprim on CYP2C8 mediated rosiglitazone metabolism in human liver microsomes and healthy subjects

    Science.gov (United States)

    Hruska, M W; Amico, J A; Langaee, T Y; Ferrell, R E; Fitzgerald, S M; Frye, R F

    2005-01-01

    Aims Rosiglitazone, a thiazolidinedione antidiabetic medication used in the treatment of Type 2 diabetes mellitus, is predominantly metabolized by the cytochrome P450 (CYP) enzyme CYP2C8. The anti-infective drug trimethoprim has been shown in vitro to be a selective inhibitor of CYP2C8. The purpose of this study was to evaluate the effect of trimethoprim on the CYP2C8 mediated metabolism of rosiglitazone in vivo and in vitro. Methods The effect of trimethoprim on the metabolism of rosiglitazone in vitro was assessed in pooled human liver microsomes. The effect in vivo was determined by evaluating rosiglitazone pharmacokinetics in the presence and absence of trimethoprim. Eight healthy subjects (four men and four women) completed a randomized, cross-over study. Subjects received single dose rosiglitazone (8 mg) in the presence and absence of trimethoprim 200 mg given twice daily for 5 days. Results Trimethoprim inhibited rosiglitazone metabolism both in vitro and in vivo. Inhibition of rosiglitazone para-hydroxylation by trimethoprim in vitro was found to be competitive with apparent Ki and IC50 values of 29 µm and 54.5 µm, respectively. In the presence of trimethoprim, rosiglitazone plasma AUC was increased by 31% (P = 0.01) from 2774 ± 645 µg l−1 h to 3643 ± 1051 µg l−1 h (95% confidence interval (Cl) for difference 189, 1549), and half-life was increased by 27% (P = 0.006) from 3.3 ± 0.5 to 4.2 ± 0.8 h (95% Cl for difference 0.36, 1.5). Trimethoprim reduced the para-O-sulphate rosiglitazone/rosiglitazone and the N-desmethylrosiglitazone/rosiglitazone AUC(0–24) ratios by 22% and 38%, respectively. Conclusions These results indicate that trimethoprim is a competitive inhibitor of CYP2C8-mediated rosiglitazone metabolism in vitro and that trimethoprim administration increases plasma rosiglitazone concentrations in healthy subjects. PMID:15606443

  17. Transcriptional Regulation of Frizzled-1 in Human Osteoblasts by Sp1.

    Directory of Open Access Journals (Sweden)

    Shibing Yu

    Full Text Available The wingless pathway has a powerful influence on bone metabolism and is a therapeutic target in skeletal disorders. Wingless signaling is mediated in part through the Frizzled (FZD receptor family. FZD transcriptional regulation is poorly understood. Herein we tested the hypothesis that Sp1 plays an important role in the transcriptional regulation of FZD1 expression in osteoblasts and osteoblast mineralization. To test this hypothesis, we conducted FZD1 promoter assays in Saos2 cells with and without Sp1 overexpression. We found that Sp1 significantly up-regulates FZD1 promoter activity in Saos2 cells. Chromatin immunoprecipitation (ChIP and electrophoretic mobility shift (EMSA assays identified a novel and functional Sp1 binding site at -44 to -40 from the translation start site in the FZD1 promoter. The Sp1-dependent activation of the FZD1 promoter was abolished by mithramycin A (MMA, an antibiotic affecting both Sp1 binding and Sp1 protein levels in Saos2 cells. Similarly, down-regulation of Sp1 in hFOB cells resulted in less FZD1 expression and lower alkaline phosphatase activity. Moreover, over-expression of Sp1 increased FZD1 expression and Saos2 cell mineralization while MMA decreased Sp1 and FZD1 expression and Saos2 cell mineralization. Knockdown of FZD1 prior to Sp1 overexpression partially abolished Sp1 stimulation of osteoblast differentiation markers. Taken together, our results suggest that Sp1 plays a role in human osteoblast differentiation and mineralization, which is at least partially mediated by Sp1-dependent transactivation of FZD1.

  18. Lansoprazole enhances the antidiabetic effect of sitagliptin in mice with diet-induced obesity and healthy human subjects.

    Science.gov (United States)

    Hao, ShaoJun; Sun, JianHua; Tian, XiKui; Sun, Xu; Zhang, ZhenXing; Gao, Yuan

    2014-08-01

    Proton pump inhibitors as adjunctive therapy would improve diabetes control and could enhance the hypoglycaemic activity of DPP-4 inhibitors. The aim of the study was to investigate the short-term effects of lansoprazole (LPZ), sitagliptin (SITA) and their combination therapy on glucose regulation and gut peptide secretion. Glucose and gut peptide were determined and compared after short-term administration of LPZ or SITA, or in combination to mice with diet-induced obesity (DIO) and to healthy human subjects (n = 16) in a 75 g oral glucose tolerance test (OGTT) by a crossover design. In DIO mice, LPZ significantly improve glucose metabolism, increase plasma C-peptide and insulin compared with vehicle treatment. Furthermore, the combination of LPZ and SITA improved glucose tolerance additively, with higher plasma insulin and C-peptide levels compared with SITA-treated mice. Similarly, in human in the OGTT, the combination showed significant improvement in glucose-lowering and insulin increase vs SITA-treated group. However, no significant differences in area under curve (AUC) of insulin, glucose and C-peptide between the LPZ-treated group and baseline, except that mean AUCgastrin was significantly increased by LPZ. LPZ and SITA combination therapy appears to have complementary mechanisms of action and additive antidiabetic effect. © 2014 Royal Pharmaceutical Society.

  19. Compliance with National Ethics Requirements for Human-Subject Research in Non-biomedical Sciences in Brazil: A Changing Culture?

    Science.gov (United States)

    de Albuquerque Rocha, Karina; Vasconcelos, Sonia M R

    2018-02-06

    Ethics regulation for human-subject research (HSR) has been established for about 20 years in Brazil. However, compliance with this regulation is controversial for non-biomedical sciences, particularly for human and social sciences (HSS), the source of a recent debate at the National Commission for Research Ethics. We hypothesized that for these fields, formal requirements for compliance with HSR regulation in graduate programs, responsible for the greatest share of Brazilian science, would be small in number. We analyzed institutional documents (collected from June 2014 to May 2015) from 171 graduate programs at six prestigious Brazilian universities in São Paulo and Rio de Janeiro, the states that fund most of the science conducted in Brazil. Among these programs, 149 were in HSS. The results suggest that non-compliance with standard regulation seems to be the rule in most of these programs. The data may reflect not only a resistance from scientists in these fields to comply with standard regulations for ethics in HSR but also a disciplinary tradition that seems prevalent when it comes to research ethics in HSR. However, recent encounters between Brazilian biomedical and non-biomedical scientists for debates over ethics in HSR point to a changing culture in the approach to research ethics in the country.

  20. Safety, pharmacokinetics, metabolism and radiation dosimetry of 18F-tetrafluoroborate (18F-TFB) in healthy human subjects.

    Science.gov (United States)

    Jiang, Huailei; Schmit, Nicholas R; Koenen, Alex R; Bansal, Aditya; Pandey, Mukesh K; Glynn, Robert B; Kemp, Bradley J; Delaney, Kera L; Dispenzieri, Angela; Bakkum-Gamez, Jamie N; Peng, Kah-Whye; Russell, Stephen J; Gunderson, Tina M; Lowe, Val J; DeGrado, Timothy R

    2017-10-27

    18 F-Tetrafluoroborate ( 18 F-TFB) is a promising iodide analog for PET imaging of thyroid cancer and sodium/iodide symporter (NIS) reporter activity in viral therapy applications. The aim of this study was to evaluate the safety, pharmacokinetics, biodistribution, and radiation dosimetry of high-specific activity 18 F-TFB in healthy human subjects. 18 F-TFB was synthesized with specific activity of 3.2 ± 1.3 GBq/μmol (at the end of synthesis). Dynamic and whole-body static PET/CT scans over 4 h were performed after intravenous administration of 18 F-TFB (333-407 MBq) in four female and four male healthy volunteers (35 ± 11 years old). Samples of venous blood and urine were collected over the imaging period and analyzed by ion-chromatography HPLC to determine tracer stability. Vital signs and clinical laboratory safety assays were measured to evaluate safety. 18 F-TFB administration was well tolerated with no significant findings on vital signs and no clinically meaningful changes in clinical laboratory assays. Left-ventricular blood pool time-activity curves showed a multi-phasic blood clearance of 18 F-radioactivity with the two rapid clearance phases over the first 20 min, followed by a slower clearance phase. HPLC analysis showed insignificant 18 F-labeled metabolites in the blood and urine over the length of the study (4 h). High uptakes were seen in the thyroid, stomach, salivary glands, and bladder. Urinary clearance of 18 F-TFB was prominent. Metabolic stability was evidenced by low accumulation of 18 F-radioactivity in the bone. Effective doses were 0.036 mSv/MBq in males and 0.064 mSv/MBq in females (p = 0.08, not significant). This initial study in healthy human subjects showed 18 F-TFB was safe and distributed in the human body similar to other iodide analogs. These data support further translational studies with 18 F-TFB as NIS gene reporter and imaging biomarker for thyroid cancer and other disease processes that import iodide.

  1. Striatal D1- and D2-type dopamine receptors are linked to motor response inhibition in human subjects.

    Science.gov (United States)

    Robertson, Chelsea L; Ishibashi, Kenji; Mandelkern, Mark A; Brown, Amira K; Ghahremani, Dara G; Sabb, Fred; Bilder, Robert; Cannon, Tyrone; Borg, Jacqueline; London, Edythe D

    2015-04-15

    Motor response inhibition is mediated by neural circuits involving dopaminergic transmission; however, the relative contributions of dopaminergic signaling via D1- and D2-type receptors are unclear. Although evidence supports dissociable contributions of D1- and D2-type receptors to response inhibition in rats and associations of D2-type receptors to response inhibition in humans, the relationship between D1-type receptors and response inhibition has not been evaluated in humans. Here, we tested whether individual differences in striatal D1- and D2-type receptors are related to response inhibition in human subjects, possibly in opposing ways. Thirty-one volunteers participated. Response inhibition was indexed by stop-signal reaction time on the stop-signal task and commission errors on the continuous performance task, and tested for association with striatal D1- and D2-type receptor availability [binding potential referred to nondisplaceable uptake (BPND)], measured using positron emission tomography with [(11)C]NNC-112 and [(18)F]fallypride, respectively. Stop-signal reaction time was negatively correlated with D1- and D2-type BPND in whole striatum, with significant relationships involving the dorsal striatum, but not the ventral striatum, and no significant correlations involving the continuous performance task. The results indicate that dopamine D1- and D2-type receptors are associated with response inhibition, and identify the dorsal striatum as an important locus of dopaminergic control in stopping. Moreover, the similar contribution of both receptor subtypes suggests the importance of a relative balance between phasic and tonic dopaminergic activity subserved by D1- and D2-type receptors, respectively, in support of response inhibition. The results also suggest that the stop-signal task and the continuous performance task use different neurochemical mechanisms subserving motor response inhibition. Copyright © 2015 the authors 0270-6474/15/355990-08$15.00/0.

  2. Effects of diazepam and levodopa single doses on motor cortex plasticity modulation in healthy human subjects: A TMS study

    Directory of Open Access Journals (Sweden)

    Ilić Nela V.

    2012-01-01

    Full Text Available Introduction. Administration of pharmacological agents with specific actions on neurotransmitter systems is a powerful driver of functional cortical reorganization. Plastic reorganization of the motor cortex in humans studies by the use of non-invasive stimulation protocols, which mimic the Hebbian model of associative plasticity. Objective. Aiming to explore pharmacological modulation on human motor cortex plasticity, we tested healthy subjects after each dosage of diazepam, levodopa i placebo administration, using paired associative stimulation protocol (PAS that induce fenomena similar to a long-term potentiation and depression, as defined on the synaptic level. Methods. We analyzed effects of benzodiazepines (10 mg, levodopa (200 mg and placebo on PAS protocol in 14 healthy volunteers, using a double-blind placebo-controlled study design. PAS consisted of electrical stimuli pairs at n.medianus and magnetic pulses over the scalp (transcranial magnetic stimulation in precisely defined intervals (ISI was 10 and 25 ms for a total of about 15 minutes (200 pairs. MEP amplitudes before and after (0, 10, 20 and 30 minutes later interventional protocols were compared. Results. When protocols were applied with placebo depending on ISI (10 ms - inhibitory, 25 ms - facilitatory effects, MEP amplitudes decreased or increased, while values in the postinterventional period (0, 10, 20 and 30 min were compared with initial values before the use of SAS. The use of benzodiazepines caused the occlusion of LTP-like effect, in contrast to amplification effects recorded after the administration of levodopa. With respect to the LTD-like protocol, the reverse was true (ANOVA for repeat measurements p<0.001. Conclusion. Administration of GABA-ergic agonist diazepam interferes with the induction of associative plasticity in the motor cortex of healthy individuals, as opposed to the use of levodopa, which stimulates these processes. The observed effects point at a

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

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    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.

  4. Different gene expression in human heart tissue and progenitor cells from control and diabetic subjects: relevance to the pathogenesis of human diabetic cardiomyopathy.

    Science.gov (United States)

    de Cillis, Emanuela; Leonardini, Anna; Laviola, Luigi; Giorgino, Francesco; Tupputi Schinosa, Luigi de Luca; Bortone, Alessandro Santo

    2010-04-01

    The The aim of our study is to investigate the molecular mechanisms of diabetic cardiomyopathy through the identification of remarkable genes for the myocardial function that are expressed differently between diabetic and normal subjects. Moreover, we intend to characterize both in human myocardial tissue and in the related cardiac progenitor cells the pattern of gene expression and the levels of expression and protein activation of molecular effectors involved in the regulation of the myocardial function and differentiation to clarify whether in specific human pathological conditions (type 2 diabetes mellitus, cardiac failure, coronary artery disease) specific alterations of the aforementioned factors could take place. Thirty-five patients scheduled for coronary artery bypass grafting (CABG) or for aortic or mitral valve replacement were recruited into the study. There were 13 men and 22 women with a mean age of 64.8 +/- 13.4 years. A list of anamnestic, anthropometric, clinical, and instrumental data required for an optimal phenotypical characterization of the patients is reported. The small cardiac biopsy specimens were placed in the nourishing buffer, in a sterile tube provided the day of the procedure, to maintain the stability of the sample for several hours at room temperature. The cells were isolated by a dedicated protocol and then cultured in vitro. The sample was processed for total RNA extraction and levels of gene expression and protein activation of molecular effectors involved in the regulation of function and differentiation of human myocardium was analyzed. In particular, cardiac genes that modulate the oxidative stress response or the stress induced by pro-inflammatory cytokines (p66Shc, SOCS-1, SOCS-3) were analyzed. From a small sample of myocardium cardiac stem cells and cardiomyoblasts were also isolated and characterized. These cells showed a considerable proliferative capacity due to the fact that they demonstrate stability up to the

  5. Knowledge on the subject of human physiology among Polish high school students--a cross-sectional study.

    Science.gov (United States)

    Zwinczewska, Helena; Rozwadowska, Joanna; Traczyk, Anna; Majda, Szymon; Wysocki, Michał; Grabowski, Kamil; Kopeć, Sylwia; Głowacki, Roman; Węgrzyn, Katarzyna; Tomaszewski, Krzysztof A; Walocha, Jerzy A

    2014-01-01

    responsible decisions regarding their health. Our results suggest that more emphasis should be put on properly teaching human physiology in high school, especially to those students who do not plan a career in medicine-related fields. This study brings to light the disturbing fact that about a year after a student finishes his basic physiology course his knowledge of the subject returns to a pre high school level.

  6. The biologic effects of grounding the human body during sleep as measured by cortisol levels and subjective reporting of sleep, pain, and stress.

    Science.gov (United States)

    Ghaly, Maurice; Teplitz, Dale

    2004-10-01

    Diurnal cortisol secretion levels were measured and circadian cortisol profiles were evaluated in a pilot study conducted to test the hypothesis that grounding the human body to earth during sleep will result in quantifiable changes in cortisol. It was also hypothesized that grounding the human body would result in changes in sleep, pain, and stress (anxiety, depression, irritability), as measured by subjective reporting. Twelve (12) subjects with complaints of sleep dysfunction, pain, and stress were grounded to earth during sleep for 8 weeks in their own beds using a conductive mattress pad. Saliva tests were administered to establish pregrounding baseline cortisol levels. Levels were obtained at 4-hour intervals for a 24-hour period to determine the circadian cortisol profile. Cortisol testing was repeated at week 6. Subjective symptoms of sleep dysfunction, pain, and stress were reported daily throughout the 8-week test period. Measurable improvements in diurnal cortisol profiles were observed, with cortisol levels significantly reduced during night-time sleep. Subjects' 24-hour circadian cortisol profiles showed a trend toward normalization. Subjectively reported symptoms, including sleep dysfunction, pain, and stress, were reduced or eliminated in nearly all subjects. Results indicate that grounding the human body to earth ("earthing") during sleep reduces night-time levels of cortisol and resynchronizes cortisol hormone secretion more in alignment with the natural 24-hour circadian rhythm profile. Changes were most apparent in females. Furthermore, subjective reporting indicates that grounding the human body to earth during sleep improves sleep and reduces pain and stress.

  7. 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

  8. 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.

  9. 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.

  10. "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.

  11. Mass balance, metabolic disposition, and pharmacokinetics of a single oral dose of regorafenib in healthy human subjects.

    Science.gov (United States)

    Gerisch, Michael; Hafner, Frank-Thorsten; Lang, Dieter; Radtke, Martin; Diefenbach, Konstanze; Cleton, Adriaan; Lettieri, John

    2018-01-01

    To evaluate the mass balance, metabolic disposition, and pharmacokinetics of a single dose of regorafenib in healthy volunteers. In addition, in vitro metabolism of regorafenib in human hepatocytes was investigated. Four healthy male subjects received one 120 mg oral dose of regorafenib containing approximately 100 µCi (3.7 MBq) [ 14 C]regorafenib. Plasma concentrations of parent drug were derived from HPLC-MS/MS analysis and total radioactivity from liquid scintillation counting (LSC). Radiocarbon analyses used HPLC with fraction collection followed by LSC for all urine samples, plasma, and fecal homogenate extracts. For the in vitro study, [ 14 C]regorafenib was incubated with human hepatocytes and analyzed using HPLC-LSC and HPLC-HRMS/MS. Regorafenib was the major component in plasma, while metabolite M-2 (pyridine N-oxide) was the most prominent metabolite. Metabolites M-5 (demethylated pyridine N-oxide) and M-7 (N-glucuronide) were identified as minor plasma components. The mean concentration of total radioactivity in plasma/whole blood appeared to plateau at 1-4 h and again at 6-24 h post-dose. In total, 90.5% of administered radioactivity was recovered in the excreta within a collection interval of 12 days, most of which (71.2%) was eliminated in feces, while excretion via urine accounted for 19.3%. Regorafenib (47.2%) was the most prominent component in feces and was not excreted into urine. Excreted metabolites resulted from oxidative metabolism and glucuronidation. Regorafenib was eliminated predominantly in feces as well as by hepatic biotransformation. The multiple biotransformation pathways of regorafenib decrease the risk of pharmacokinetic drug-drug interactions.

  12. Effect of Guava in Blood Glucose and Lipid Profile in Healthy Human Subjects: A Randomized Controlled Study

    Science.gov (United States)

    Rakavi, R; Mangaraj, Manaswini

    2016-01-01

    Introduction The fruit of Psidium guajava (P.guajava) is known to contain free sugars yet the fruit juice showed hypoglycaemic effect. Hypoglycaemic activity of guava leaves has been well documented but not for guava fruit. Aim So we aimed to evaluate the effect of ripe guava (with peel and without peel) fruit supplementation on blood glucose and lipid profile in healthy human subjects. Materials and Methods Randomized Controlled study undertaken in: 1) Baseline; 2) 6 weeks supplementation phase. Forty five healthy MBBS students were included and randomly enrolled into Group A, Group B and Group C. In Baseline phase: Fasting Plasma Glucose (FPG) and serum lipid profile was done in all 3 groups. Group A were supplemented with 400g of ripe guava with peel and group B without peel, for 6 weeks. Rest 15 treated as control i.e., Group C. Result Supplementation of ripe guava fruit with peel reduced BMI as well as blood pressure (pguava pulp supplementation was not significant. Serum Total cholesterol, Triglycerides and Low Density Lipoprotein Cholesterol (LDLc) levels decreased significantly (pguava pulp without peel may have a favourable effect on lipid levels and blood sugar as well. Conclusion Guava fruit without peel is more effective in lowering blood sugar as well as serum total cholesterol, triglycerides and LDLc. It increases HDLc levels also. PMID:27790420

  13. Dosimetry of intravenously administered oxygen-15 labelled water in man: a model based on experimental human data from 21 subjects

    International Nuclear Information System (INIS)

    Smith, T.; Tong, C.; Lammertsma, A.A.; Butler, K.R.; Schnorr, L.; Watson, J.D.G.; Ramsay, S.; Clark, J.C.; Jones, T.

    1994-01-01

    Models based on uniform distribution of tracer in total body water underestimate the absorbed dose from H 2 15 O because of the short half-life (2.04 min) of 15 O, which leads to non-uniform distribution of absorbed dose and also complicates the direct measurement of organ retention curves. However, organ absorbed doses can be predicted by the present kinetic model based on the convolution technique. The measured time course of arterial H 2 15 O concentration following intravenous administration represents the input function to organs. The impulse response of a given organ is its transit time function determined by blood flow and the partition of water between tissue and blood. Values of these two parameters were taken from the literature. Integrals of the arterial input function and organ transit time functions were used to derive integrals of organ retention functions (organ residence times). The latter were used with absorbed dose calculation software (MIRDOSE-2) to obtain estimates for 24 organs. From the mean values of organ absorbed doses, the effective dose equivalent (EDE) and effective dose (ED) were calculated. From measurements on 21 subjects, the average value for both EDE and ED was calculated to be 1.2 μSv.MBq -1 compared with a value of about 0.5 μSv.MBq -1 predicted by uniform water distribution models. Based on the human data, a method of approximating H 2 15 O absorbed dose values from body surface area is described. (orig.)

  14. The influence of race and ethnicity on becoming a human subject: Factors associated with participation in research

    Directory of Open Access Journals (Sweden)

    Mary A. Garza, PhD

    2017-09-01

    Full Text Available Inroduction: The purpose of this study was to explore factors associated with willingness of African Americans and Latinos to participate in biomedical and public health research and to delineate factors that influence the decision to become a human subject. Methods: We present results from a 2010 random digit-dial telephone survey of 2,455 African American (N = 1191 and Latino (N = 1264 adults. We used standard measures to assess knowledge of research, terminology, informed consent procedures, previous participation in research, health care experiences, social support, risk perception, religiousness, and trust. Results: Over 60% of both African Americans and Latinos reported they believed people in medical research are pressured into participating. Over 50% said that it was not at all important to have someone of the same race/ethnicity ask them to participate. In a sub-sample of 322 African Americans and 190 Latinos who had previously been asked to participate in a research study, 63% of African Americans and 65% of Latinos consented to participate in a study. Finally, both African Americans (57% and Latinos (68% reported willingness to participate in future research. Overall, the multivariate analysis explained 29% of the variability in willingness to participate in future research. Conclusions: Results suggest that African Americans and Latinos have no automatic predisposition to decline participation in research studies. These results can inform culturally tailored interventions for ethical recruitment of minorities into research and clinical trials.

  15. Disposable swim diaper retention of Cryptosporidium-sized particles on human subjects in a recreational water setting.

    Science.gov (United States)

    Amburgey, James E; Anderson, J Brian

    2011-12-01

    Cryptosporidium is a chlorine-resistant protozoan parasite responsible for the majority of waterborne disease outbreaks in recreational water venues in the USA. Swim diapers are commonly used by diaper-aged children participating in aquatic activities. This research was intended to evaluate disposable swim diapers for retaining 5-μm diameter polystyrene microspheres, which were used as non-infectious surrogates for Cryptosporidium oocysts. A hot tub recirculating water without a filter was used for this research. The microsphere concentration in the water was monitored at regular intervals following introduction of microspheres inside of a swim diaper while a human subject undertook normal swim/play activities. Microsphere concentrations in the bulk water showed that the majority (50-97%) of Cryptosporidium-sized particles were released from the swim diaper within 1 to 5 min regardless of the swim diaper type or configuration. After only 10 min of play, 77-100% of the microspheres had been released from all swim diapers tested. This research suggests that the swim diapers commonly used by diaper-aged children in swimming pools and other aquatic activities are of limited value in retaining Cryptosporidium-sized particles. Improved swim diaper solutions are necessary to efficiently retain pathogens and effectively safeguard public health in recreational water venues.

  16. Different Expression and Localization of Phosphoinositide Specific Phospholipases C in Human Osteoblasts, Osteosarcoma Cell Lines, Ewing Sarcoma and Synovial Sarcoma

    Directory of Open Access Journals (Sweden)

    V.Vasco

    2017-06-01

    Full Text Available Background: Bone hardness and strength depends on mineralization, which involves a complex process in which calcium phosphate, produced by bone-forming cells, was shed around the fibrous matrix. This process is strictly regulated, and a number of signal transduction systems were interested in calcium metabolism, such as the phosphoinositide (PI pathway and related phospholipase C (PLC enzymes. Objectives: Our aim was to search for common patterns of expression in osteoblasts, as well as in ES and SS. Methods: We analysed the PLC enzymes in human osteoblasts and osteosarcoma cell lines MG-63 and SaOS-2. We compared the obtained results to the expression of PLCs in samples of patients affected with Ewing sarcoma (ES and synovial sarcoma (SS. Results: In osteoblasts, MG-63 cells and SaOS-2 significant differences were identified in the expression of PLC δ4 and PLC η subfamily isoforms. Differences were also identified regarding the expression of PLCs in ES and SS. Most ES and SS did not express PLCB1, which was expressed in most osteoblasts, MG-63 and SaOS-2 cells. Conversely, PLCB2, unexpressed in the cell lines, was expressed in some ES and SS. However, PLCH1 was expressed in SaOS-2 and inconstantly expressed in osteoblasts, while it was expressed in ES and unexpressed in SS. The most relevant difference observed in ES compared to SS regarded PLC ε and PLC η isoforms. Conclusion: MG-63 and SaOS-2 osteosarcoma cell lines might represent an inappropriate experimental model for studies about the analysis of signal transduction in osteoblasts

  17. GLP-1 and Calcitonin Concentration in Humans: Lack of Evidence of Calcitonin Release from Sequential Screening in over 5000 Subjects with Type 2 Diabetes or Nondiabetic Obese Subjects Treated with the Human GLP-1 Analog, Liraglutide

    DEFF Research Database (Denmark)

    Hegedüs, Laszlo; Moses, Alan C; Zdravkovic, Milan

    2011-01-01

    to the GLP-1 receptor agonist liraglutide in subjects with type 2 diabetes mellitus or nondiabetic obese subjects. Methods: Unstimulated serum CT concentrations were measured at 3-month intervals for no more than 2 yr in a series of trials in over 5000 subjects receiving liraglutide or control therapy....... 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...

  18. 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.

  19. 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.

  20. Measurement of Cue-Induced Craving in Human Methamphetamine- Dependent Subjects New Methodological Hopes for Reliable Assessment of Treatment Efficacy

    Directory of Open Access Journals (Sweden)

    Zahra Alam Mehrjerdi

    2011-09-01

    Full Text Available Methamphetamine (MA is a highly addictive psychostimulant drug with crucial impacts on individuals on various levels. Exposure to methamphetamine-associated cues in laboratory can elicit measureable craving and autonomic reactivity in most individuals with methamphetamine dependence and the cue reactivity can model how craving would result in continued drug seeking behaviors and relapse in real environments but study on this notion is still limited. In this brief article, the authors review studies on cue-induced craving in human methamphetamine- dependent subjects in a laboratory-based approach. Craving for methamphetamine is elicited by a variety of methods in laboratory such as paraphernalia, verbal and visual cues and imaginary scripts. In this article, we review the studies applying different cues as main methods of craving incubation in laboratory settings. The brief reviewed literature provides strong evidence that craving for methamphetamine in laboratory conditions is significantly evoked by different cues. Cue-induced craving has important treatment and clinical implications for psychotherapists and clinicians when we consider the role of induced craving in evoking intense desire or urge to use methamphetamine after or during a period of successful craving prevention program. Elicited craving for methamphetamine in laboratory conditions is significantly influenced by methamphetamine-associated cues and results in rapid craving response toward methamphetamine use. This notion can be used as a main core for laboratory-based assessment of treatment efficacy for methamphetamine-dependent patients. In addition, the laboratory settings for studying craving can bridge the gap between somehow-non-reliable preclinical animal model studies and budget demanding randomized clinical trials.

  1. Cholesterol Metabolism and Weight Reduction in Subjects with Mild Obstructive Sleep Apnoea: A Randomised, Controlled Study

    Directory of Open Access Journals (Sweden)

    Maarit Hallikainen

    2013-01-01

    Full Text Available To evaluate whether parameters of obstructive sleep apnoea (OSA associate with cholesterol metabolism before and after weight reduction, 42 middle-aged overweight subjects with mild OSA were randomised to intensive lifestyle intervention (N=23 or to control group (N=18 with routine lifestyle counselling only. Cholesterol metabolism was evaluated with serum noncholesterol sterol ratios to cholesterol, surrogate markers of cholesterol absorption (cholestanol and plant sterols and synthesis (cholestenol, desmosterol, and lathosterol at baseline and after 1-year intervention. At baseline, arterial oxygen saturation (SaO2 was associated with serum campesterol (P<0.05 and inversely with desmosterol ratios (P<0.001 independently of gender, BMI, and homeostasis model assessment index of insulin resistance (HOMA-IR. Apnoea-hypopnoea index (AHI was not associated with cholesterol metabolism. Weight reduction significantly increased SaO2and serum cholestanol and decreased AHI and serum cholestenol ratios. In the groups combined, the changes in AHI were inversely associated with changes of cholestanol and positively with cholestenol ratios independent of gender and the changes of BMI and HOMA-IR (P<0.05. In conclusion, mild OSA seemed to be associated with cholesterol metabolism independent of BMI and HOMA-IR. Weight reduction increased the markers of cholesterol absorption and decreased those of cholesterol synthesis in the overweight subjects with mild OSA.

  2. Device orientation of a leadless pacemaker and subcutaneous implantable cardioverter-defibrillator in canine and human subjects and the effect on intrabody communication.

    Science.gov (United States)

    Quast, Anne-Floor B E; Tjong, Fleur V Y; Koop, Brendan E; Wilde, Arthur A M; Knops, Reinoud E; Burke, Martin C

    2018-02-14

    The development of communicating modular cardiac rhythm management systems relies on effective intrabody communication between a subcutaneous implantable cardioverter-defibrillator (S-ICD) and a leadless pacemaker (LP), using conducted communication. Communication success is affected by the LP and S-ICD orientation. This study is designed to evaluate the orientation of the LP and S-ICD in canine subjects and measure success and threshold of intrabody communication. To gain more human insights, we will explore device orientation in LP and S-ICD patients. Canine subjects implanted with a prototype S-ICD and LP (both Boston Scientific, MA, USA) with anterior-posterior fluoroscopy images were included in this analysis. For comparison, a retrospective analysis of human S-ICD and LP patients was performed. The angle of the long axis of the LP towards the vertical axis of 0°, and distance between the coil and LP were measured. Twenty-three canine subjects were analysed. Median angle of the LP was 29° and median distance of the S-ICD coil to LP was 0.8 cm. All canine subjects had successful communication. The median communicating threshold was 2.5 V. In the human retrospective analysis, 72 LP patients and 100 S-ICD patients were included. The mean angle of the LP was 56° and the median distance between the S-ICD coil and LP was 4.6 cm. Despite the less favourable LP orientation in canine subjects, all communication attempts were successful. In the human subjects, we observed a greater and in theory more favourable LP angle towards the communication vector. These data suggests suitability of human anatomy for conductive intrabody communication.

  3. A Comparison of Sacroiliac and Pubic Rami Fracture Occurrences in Oblique Side Impact Tests on Nine Post Mortem Human Subjects.

    Science.gov (United States)

    Petit, Philippe; Trosseille, Xavier; Lebarbé, Mathieu; Baudrit, Pascal; Potier, Pascal; Compigne, Sabine; Masuda, Mitsutoshi; Yamaoka, Akira; Yasuki, Tsuyoshi; Douard, Richard

    2015-11-01

    The WorldSID dummy can be equipped with both a pubic and a sacroiliac joint (S-I joint) loadcell. Although a pubic force criterion and the associated injury risk curve are currently available and used in regulation (ECE95, FMVSS214), as of today injury mechanisms, injury criteria, and injury assessment reference values are not available for the sacroiliac joint itself. The aim of this study was to investigate the sacroiliac joint injury mechanism. Three configurations were identified from full-scale car crashes conducted with the WorldSID 50th percentile male where the force passing through the pubis in all three tests was approximately 1500 N while the sacroiliac Fy/Mx peak values were 4500 N/50 Nm, 2400 N/130 Nm, and 5300 N/150 Nm, respectively. These tests were reproduced using a 150 kg guided probe impacting Post Mortem Human Subjects (PMHS) at 8 m/s, 5.4 m/s and 7.5 m/s. The shape and the orientation of the impacting face of the probe were selected to match the WorldSID pubic Fy and sacroiliac Fy/Mx loads of the three vehicle test configurations. Three PMHS were tested in each of the three configurations (nine PMHS in total). In the first PMHS configuration, one specimen sustained an AIS 3 injury and one sustained an AIS 4 injury (an unstable pelvis with complete disruption of the posterior arch, a sacroiliac joint disruption associated with an iliac fracture, and a pubic symphysis separation). In the second configuration, all specimens sustained a fracture of the superior lateral iliac wing (AIS 2). In the third configuration, one specimen sustained a partial disruption of the anterior arch (AIS 2). Based on the data from strain gauges located on the pubic rami and near the sacroiliac joint, the pubic rami fractures were identified as occurring prior to the sacroiliac fractures. Out of nine impactor tests performed, the PMHS S-I joint injuries were observed to consistently be associated with pelvic anterior arch fractures. In addition, from the injury

  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. High-dose interferon-alpha2a exerts potent activity against human immunodeficiency virus type 1 not associated with antitumor activity in subjects with Kaposi's sarcoma

    NARCIS (Netherlands)

    Frissen, P. H.; de Wolf, F.; Reiss, P.; Bakker, P. J.; Veenhof, C. H.; Danner, S. A.; Goudsmit, J.; Lange, J. M.

    1997-01-01

    Anti-human immunodeficiency virus type 1 (HIV-1) activity was assessed in HIV-1-infected homosexual and bisexual men receiving 18-36 MIU/day of recombinant interferon (IFN)-alpha2a for Kaposi's sarcoma (KS). The median baseline HIV-1 RNA level was 4.99 log10 copies/mL. Seventeen subjects (68%)

  6. 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.

  7. Talinum triangulare Whole wheat meal fortified with soy flour consumed with Talinum triangulare (gbure) soup glycemic index and the test human subjects' lipid profiles.

    Science.gov (United States)

    Emaleku, Sunday Adeola; Omueti, Olusola D; Emaleku, Godsent Oluwakemi

    2017-08-24

    Cardiovascular diseases (CVDs) and diabetes mellitus (DM) are some of the leading causes of death in the world, and diet has roles in their etiology. This research study therefore investigates the glycemic index (GI) of soy flour fortified whole wheat meal (SFFWWM) consumed with Talinum triangulare (gbure) soup and the effects of the meal on the lipid profiles of the test human subjects. The control human subjects and test human subjects were fed D-glucose (DG) and whole wheat meal (WWM) with Talinum triangulare soup respectively on the first day of the experiment, and SFFWWM with the same soup the next day (for test subjects only) after 10-12h overnight fasting. Blood glucose levels of the subjects were taken before and 2h after meals' consumption at 30min interval and blood samples collected for lipid profiles evaluations. The result of the study showed that; SFFWWM consumed with Talinum trianguilare soup has a non-significant lower GI than WWM consumed with the same soup, but a significant lower GI than DG at (P<0.05). Furthermore, there was no significant difference in lipid profiles of the test human subjects between when they consumed WWM and SFFWWM with the soup however, SFFWWM reduced TC, TG, LDL-C and VDL-C and increased HDL-C and TP than WMM at (P<0.05). In addition, GI is positively correlated with TC, TG, LDL-C and VLDL-C, but is negatively correlated with TP and HDL-C. It can therefore be concluded that; fortifying WWM with soy flour would reduce the risk factors of CVDs and DM, the diseases recently claiming thousands of today. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  8. 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

  9. Therapeutic touch affects DNA synthesis and mineralization of human osteoblasts in culture.

    Science.gov (United States)

    Jhaveri, Ankur; Walsh, Stephen J; Wang, Yatzen; McCarthy, MaryBeth; Gronowicz, Gloria

    2008-11-01

    Complementary and alternative medicine (CAM) techniques are commonly used in hospitals and private medical facilities; however, the effectiveness of many of these practices has not been thoroughly studied in a scientific manner. Developed by Dr. Dolores Krieger and Dora Kunz, Therapeutic Touch is one of these CAM practices and is a highly disciplined five-step process by which a practitioner can generate energy through their hands to promote healing. There are numerous clinical studies on the effects of TT but few in vitro studies. Our purpose was to determine if Therapeutic Touch had any effect on osteoblast proliferation, differentiation, and mineralization in vitro. TT was performed twice a week for 10 min each on human osteoblasts (HOBs) and on an osteosarcoma-derived cell line, SaOs-2. No significant differences were found in DNA synthesis, assayed by [(3)H]-thymidine incorporation at 1 or 2 weeks for SaOs-2 or 1 week for HOBs. However, after four TT treatments in 2 weeks, TT significantly (p = 0.03) increased HOB DNA synthesis compared to controls. Immunocytochemistry for Proliferating Cell Nuclear Antigen (PCNA) confirmed these data. At 2 weeks in differentiation medium, TT significantly increased mineralization in HOBs (p = 0.016) and decreased mineralization in SaOs-2 (p = 0.0007), compared to controls. Additionally, Northern blot analysis indicated a TT-induced increase in mRNA expression for Type I collagen, bone sialoprotein, and alkaline phosphatase in HOBs and a decrease of these bone markers in SaOs-2 cells. In conclusion, Therapeutic Touch appears to increase human osteoblast DNA synthesis, differentiation and mineralization, and decrease differentiation and mineralization in a human osteosarcoma-derived cell line. (c) 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  10. Male and female WorldSID and post mortem human subject responses in full-scale vehicle tests.

    Science.gov (United States)

    Yoganandan, Narayan; Humm, John; Pintar, Frank; Rhule, Heather; Moorhouse, Kevin; Suntay, Brian; Stricklin, Jim; Rudd, Rodney; Craig, Matthew

    2017-05-29

    This study compares the responses of male and female WorldSID dummies with post mortem human subject (PMHS) responses in full-scale vehicle tests. Tests were conducted according to the FMVSS-214 protocols and using the U.S. Side Impact New Car Assessment Program change in velocity to match PMHS experiments, published earlier. Moving deformable barrier (MDB) tests were conducted with the male and female surrogates in the left front and left rear seats. Pole tests were performed with the male surrogate in the left front seat. Three-point belt restraints were used. Sedan-type vehicles were used from the same manufacturer with side airbags. The PMHS head was instrumented with a pyramid-shaped nine-axis accelerometer package, with angular velocity transducers on the head. Accelerometers and angular velocity transducers were secured to T1, T6, and T12 spinous processes and sacrum. Three chest bands were secured around the upper, middle, and lower thoraces. Dummy instrumentation included five infrared telescoping rods for assessment of chest compression (IR-TRACC) and a chest band at the first abdomen rib, head angular velocity transducer, and head, T1, T4, T12, and pelvis accelerometers. Morphological responses of the kinematics of the head, thoracic spine, and pelvis matched in both surrogates for each pair. The peak magnitudes of the torso accelerations were lower for the dummy than for the biological surrogate. The brain rotational injury criterion (BrIC) response was the highest in the male dummy for the MDB test and PMHS. The probability of AIS3+ injuries, based on the head injury criterion, ranged from 3% to 13% for the PMHS and from 3% to 21% for the dummy from all tests. The BrIC-based metrics ranged from 0 to 21% for the biological and 0 to 48% for the dummy surrogates. The deflection profiles from the IR-TRACC sensors were unimodal. The maximum deflections from the chest band placed on the first abdominal rib were 31.7 mm and 25.4 mm for the male and female

  11. Relationship of tumor necrosis factor alpha genotypes with various biochemical parameters of normal, over weight and obese human subjects

    International Nuclear Information System (INIS)

    Raza, M.; Chaudhary, B.; Shakoori, A.R.

    2008-01-01

    Tumor Necrosis Factor (TNF-alpha) is expressed primarily in adipocytes and elevated levels of this cytokine have been associated with obesity. The purpose of this investigation was to test whether the TNF-alpha -308 polymorphism were associated with insulin resistance or obesity related traits in non-diabetic and diabetic patients visiting Sheikh Zayed Hospital, Lahore, Fatima Hospital and Irfan Clinic in Sargodha. In non diabetic subjects the AA allele carriers, compared with homozygous G allele carriers had significantly lower (28%) triglyceride values and 15% higher HDL yal ues, whereas other parameters tested 81id not show any significant variation. In diabetic patients the AA allele carriers, compared with GG allele carriers, besides having 31 % higher FBS and 26% higher creatinine, had 20% higher cholesterol and 34% higher triglycerides. The HDL values were 14% less, compared to GG allele carriers. In normal subjects (BMI 22.85:1:0.25 kgim2), the AA allele carriers showed 132%, 125%, 65% and 112% higher triglycerides, cholesterol and LDL values compared with GG allele carriers. The HDL and creatinine did not show any significant change. In the overweight subjects (BMI: 27.17+-0.17 kgim/sup 2/) all these values were lower than in AA allele carriers compared with GG allele carriers. The AA allele carries had FBS, triglycerides, cholesterol and LDL 28%, 48%, 14% and 14% lower than in the GG allele' carriers, respectively. In obese subjects, (BMI: 36.73+-0.78kgm/sup 2/), however, the FBS, triglycerides, cholesterol and creatinine values were 5%, 8%, 7% and 14% higher in AA allele carries compared to GG allele carriers, respectively. The LDL content was 8% lower in AA allele carrier as compared with the respective GG allele carriers, It is concluded that replacement of G at -308 with A leads to reduced risk for cardiovascular disease in non-diabetic subject, whereas in diabetic patients this mutation-increases the risk of CVD. Using BMI as index of obesity, it was

  12. Effect of a sustained reduction in plasma free fatty acid concentration on insulin signalling and inflammation in skeletal muscle from human subjects.

    Science.gov (United States)

    Liang, Hanyu; Tantiwong, Puntip; Sriwijitkamol, Apiradee; Shanmugasundaram, Karthigayan; Mohan, Sumathy; Espinoza, Sara; Defronzo, Ralph A; Dubé, John J; Musi, Nicolas

    2013-06-01

    Free fatty acids (FFAs) have been implicated in the pathogenesis of insulin resistance. Reducing plasma FFA concentration in obese and type 2 diabetic (T2DM) subjects improves insulin sensitivity. However, the molecular mechanism by which FFA reduction improves insulin sensitivity in human subjects is not fully understood. In the present study, we tested the hypothesis that pharmacological FFA reduction enhances insulin action by reducing local (muscle) inflammation, leading to improved insulin signalling. Insulin-stimulated total glucose disposal (TGD), plasma FFA species, muscle insulin signalling, IBα protein, c-Jun phosphorylation, inflammatory gene (toll-like receptor 4 and monocyte chemotactic protein 1) expression, and ceramide and diacylglycerol (DAG) content were measured in muscle from a group of obese and T2DM subjects before and after administration of the antilipolytic drug acipimox for 7 days, and the results were compared to lean individuals. We found that obese and T2DM subjects had elevated saturated and unsaturated FFAs in plasma, and acipimox reduced all FFA species. Acipimox-induced reductions in plasma FFAs improved TGD and insulin signalling in obese and T2DM subjects. Acipimox increased IBα protein (an indication of decreased IB kinase-nuclear factor B signalling) in both obese and T2DM subjects, but did not affect c-Jun phosphorylation in any group. Acipimox also decreased inflammatory gene expression, although this reduction only occurred in T2DM subjects. Ceramide and DAG content did not change. To summarize, pharmacological FFA reduction improves insulin signalling in muscle from insulin-resistant subjects. This beneficial effect on insulin action could be related to a decrease in local inflammation. Notably, the improvements in insulin action were more pronounced in T2DM, indicating that these subjects are more susceptible to the toxic effect of FFAs.

  13. 77 FR 25533 - Agency Requests for Approval of a New Information Collection(s): Human Subjects Experiments...

    Science.gov (United States)

    2012-04-30

    ... collection involves recruitment of participants, balancing the subject sample and debriefing questionnaires...Rulemaking Portal: http://www.regulations.gov . Follow the online instructions for submitting comments. Fax... information consists of: (1) Recruitment material and a brief eligibility questionnaire for applicants and (2...

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

    NARCIS (Netherlands)

    Jacobs, Bart A W; Deenen, Maarten J; Pluim, Dick; van Hasselt, J G Coen; Krähenbühl, Martin D; van Geel, Robin M J M; de Vries, Niels; Rosing, Hilde; Meulendijks, Didier; Burylo, Artur M; Cats, Annemieke; Beijnen, Jos H; Huitema, Alwin D R; Schellens, Jan H M

    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

  15. Guidelines for Biomedical and Pharmacological Research Procedures and the Protection of Human Subjects in Residential Facilities for Mentally Retarded Persons.

    Science.gov (United States)

    National Association for Retarded Citizens, Arlington, TX. Research and Demonstration Inst.

    Guidelines are presented which were developed to aid federal, state, and local agencies prepare regulations concerning the use of mentally retarded subjects in biomedical and pharmacological research projects. Guidelines are set forth for the following topic areas (sample subtopics in parentheses): the formation of a Professional Review Committee…

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

    NARCIS (Netherlands)

    R.N. Mekuria (Rufael); P.S. Cesar Garcia (Pablo Santiago); A. Frisiello (Antonella); I. Doumanis (Ioannis)

    2015-01-01

    htmlabstractCompression 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

  17. A Comparison of National Policies on Research Involving Human Subjects to Facilitate Review and Approval of Collaborative Research

    Science.gov (United States)

    2008-11-26

    torture Prohibition on slavery and forced labour Right to liberty and security Right to a fair trial No punishment without law Right to respect...NOT BE TOLERATED. IT IS BOTH A BREACH OF REGULATIONS AND UNETHICAL . UNAUTHORIZED RESEARCH MAY THEREFORE BE SUBJECT TO INVESTIGATION AND

  18. Homo sapiens-Specific Binding Site Variants within Brain Exclusive Enhancers Are Subject to Accelerated Divergence across Human Population.

    Science.gov (United States)

    Zehra, Rabail; Abbasi, Amir Ali

    2018-03-01

    Empirical assessments of human accelerated noncoding DNA frgaments have delineated presence of many cis-regulatory elements. Enhancers make up an important category of such accelerated cis-regulatory elements that efficiently control the spatiotemporal expression of many developmental genes. Establishing plausible reasons for accelerated enhancer sequence divergence in Homo sapiens has been termed significant in various previously published studies. This acceleration by including closely related primates and archaic human data has the potential to open up evolutionary avenues for deducing present-day brain structure. This study relied on empirically confirmed brain exclusive enhancers to avoid any misjudgments about their regulatory status and categorized among them a subset of enhancers with an exceptionally accelerated rate of lineage specific divergence in humans. In this assorted set, 13 distinct transcription factor binding sites were located that possessed unique existence in humans. Three of 13 such sites belonging to transcription factors SOX2, RUNX1/3, and FOS/JUND possessed single nucleotide variants that made them unique to H. sapiens upon comparisons with Neandertal and Denisovan orthologous sequences. These variants modifying the binding sites in modern human lineage were further substantiated as single nucleotide polymorphisms via exploiting 1000 Genomes Project Phase3 data. Long range haplotype based tests laid out evidence of positive selection to be governing in African population on two of the modern human motif modifying alleles with strongest results for SOX2 binding site. In sum, our study acknowledges acceleration in noncoding regulatory landscape of the genome and highlights functional parts within it to have undergone accelerated divergence in present-day human population.

  19. An ultrastructural study of the effect of neomycin on the colon in the human subject and in the conventional and the germ-free mouse.

    Science.gov (United States)

    Aluwihare, A P

    1971-05-01

    An electron microscopic study of the colon of normal mice and human subjects and those treated with neomycin is reported; there is a close resemblance between the mouse and human colons. After rapid disinfection of the colon, there is epithelial cell damage due to a toxic effect of the drug, a reduction in epithelial turnover accompanying the change in flora, and an important reduction in the cellularity of the lamina propria mainly due to a reduction in inflammatory cells. The changes in the lamina propria probably represent changes in the antipathogenetic defences of the host.

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

    Science.gov (United States)

    Kaeberlein, M

    2016-03-01

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

  1. GH receptor signaling in skeletal muscle and adipose tissue in human subjects following exposure to an intravenous GH bolus

    DEFF Research Database (Denmark)

    Jørgensen, Jens O L; Jessen, Niels; Pedersen, Steen Bønløkke

    2006-01-01

    Growth hormone (GH) regulates muscle and fat metabolism, which impacts on body composition and insulin sensitivity, but the underlying GH signaling pathways have not been studied in vivo in humans. We investigated GH signaling in biopsies from muscle and abdominal fat obtained 30 (n = 3) or 60 (n...... was measured by in vitro phosphorylation of PI. STAT5 DNA binding activity was assessed with EMSA, and the expression of IGF-I and SOCS mRNA was measured by real-time RT-PCR. GH induced a 52% increase in circulating FFA levels with peak values after 155 min (P = 0.03). Tyrosine-phosphorylated STAT5...... tended to increase after GH in muscle and fat, respectively. We conclude that 1) STAT5 is acutely activated in human muscle and fat after a GH bolus, but additional downstream GH signaling was significant only in fat; 2) the direct GH effects in muscle need further characterization; and 3) this human...

  2. 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.

  3. 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 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.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.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.Obesity is associated with elevated serum levels of pro-inflammatory wnt5a in humans. Furthermore, caloric restriction beneficially affects serum concentrations of anti-inflammatory sFRP5 in such subjects. These findings suggest a

  4. Objective confirmation of subjective measures of human well-being: evidence from the U.S.A.

    Science.gov (United States)

    Oswald, Andrew J; Wu, Stephen

    2010-01-29

    A huge research literature, across the behavioral and social sciences, uses information on individuals' subjective well-being. These are responses to questions--asked by survey interviewers or medical personnel--such as, "How happy do you feel on a scale from 1 to 4?" Yet there is little scientific evidence that such data are meaningful. This study examines a 2005-2008 Behavioral Risk Factor Surveillance System random sample of 1.3 million U.S. citizens. Life satisfaction in each U.S. state is measured. Across America, people's answers trace out the same pattern of quality of life as previously estimated, from solely nonsubjective data, in one branch of economics (so-called "compensating differentials" neoclassical theory, originally from Adam Smith). There is a state-by-state match (r = 0.6, P < 0.001) between subjective and objective well-being. This result has some potential to help to unify disciplines.

  5. Randomized comparison of reduced fat and reduced carbohydrate hypocaloric diets on intrahepatic fat in overweight and obese human subjects.

    Science.gov (United States)

    Haufe, Sven; Engeli, Stefan; Kast, Petra; Böhnke, Jana; Utz, Wolfgang; Haas, Verena; Hermsdorf, Mario; Mähler, Anja; Wiesner, Susanne; Birkenfeld, Andreas L; Sell, Henrike; Otto, Christoph; Mehling, Heidrun; Luft, Friedrich C; Eckel, Juergen; Schulz-Menger, Jeanette; Boschmann, Michael; Jordan, Jens

    2011-05-01

    Obesity-related hepatic steatosis is a major risk factor for metabolic and cardiovascular disease. Fat reduced hypocaloric diets are able to relieve the liver from ectopically stored lipids. We hypothesized that the widely used low carbohydrate hypocaloric diets are similarly effective in this regard. A total of 170 overweight and obese, otherwise healthy subjects were randomized to either reduced carbohydrate (n = 84) or reduced fat (n = 86), total energy restricted diet (-30% of energy intake before diet) for 6 months. Body composition was estimated by bioimpedance analyses and abdominal fat distribution by magnetic resonance tomography. Subjects were also submitted to fat spectroscopy of liver and oral glucose tolerance testing. In all, 102 subjects completed the diet intervention with measurements of intrahepatic lipid content. Both hypocaloric diets decreased body weight, total body fat, visceral fat, and intrahepatic lipid content. Subjects with high baseline intrahepatic lipids (>5.56%) lost ≈7-fold more intrahepatic lipids compared with those with low baseline values (diet composition. In contrast, changes in visceral fat mass and insulin sensitivity were similar between subgroups, with low and high baseline intrahepatic lipids. A prolonged hypocaloric diet low in carbohydrates and high in fat has the same beneficial effects on intrahepatic lipid accumulation as the traditional low-fat hypocaloric diet. The decrease in intrahepatic lipids appears to be independent of visceral fat loss and is not tightly coupled with changes in whole body insulin sensitivity during 6 months of an energy restricted diet. Copyright © 2011 American Association for the Study of Liver Diseases.

  6. Effects of rectilinear acceleration, caloric and optokinetic stimulation of human subjects in the Spacelab D-1 mission

    Science.gov (United States)

    Wetzig, J.; von Baumgarten, R.

    A set of vestibular experiments was performed during the course of the German Spacelab D-1 mission from 30 October to 6 November 1985 by a consortium of experimenters from various european countries. Similar to the Spacelab SL-1 mission all of the scientific crew members were theoretically and practically trained for the experiments. Baseline measurements for all tests were collected 113, 86, 44, 30 and 18 days prior to the mission and compared with data taken inflight, on the landing day and the consecutive 7 to 14 days. The hardware comprised mainly a motordriven accelerating platform, the SPACE SLED, and the vestibular helmet, a multi-purpose instrument in support of a variety of vestibular experiments including air-calorisation of the ears, optokinetic stimulation pattern presentation and optical and nystagmographic recording of eye movements. Measurements of the threshold for the perception of detection of whole body movement did not reveal any dramatic changes in the 2 measured axes inflight when compared to preflight values. Early postflight values show a significantly elevated threshold for all axes in 3 out of 4 subjects. The caloric nystagmus, already found during the SL-1 mission, was confirmed on all three tested subjects during the D-1 mission. It's amplitude and in some instances it's direction were influenced by horizontal acceleration on the SLED. The amplitude of optokinetic nystagmus increased when subjects were allowed to free-float over that seen when subjects were fixed. Stimulation of the neck receptors by roll movements of the body against the fixated head resulted in illusory object motion to the contralateral side. Torsional movements of the eyes during such neck receptor stimulation was present inflight and postflight, while it had not been observed preflight. Most results point to a reduction of otolithic effects in favour of visual and proprioceptive influences for spatial orientation.

  7. Human Analogue of the Morris Water Maze for Testing Subjects at Risk of Alzheimer’s Disease

    Czech Academy of Sciences Publication Activity Database

    Laczó, J.; Andel, R.; Vyhnálek, M.; Vlček, Kamil; Magerová, H.; Varjassyova, A.; Tolar, M.; Hort, J.

    2010-01-01

    Roč. 7, 1-3 (2010), s. 148-152 ISSN 1660-2854 R&D Projects: GA ČR(CZ) GA309/09/1053; GA ČR(CZ) GA309/09/0286 Institutional research plan: CEZ:AV0Z50110509 Keywords : mild cognitive impairment * spatial navigation * Alzheimer’s Disease Subject RIV: FH - Neurology Impact factor: 3.791, year: 2010

  8. 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.

  9. 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

  10. Visual Compensatory Tracking Performance after Exposure to Flashblinding Pulses. I. Comparison of Human and Rhesus Monkey Subjects

    Science.gov (United States)

    1981-04-01

    If different Irom Report) 18. SUPPLEMENTARY NOTES 19. KEY WOROS rContlnuo nrn rever.se ., vde it nee.ssary and rdenrlfy hv brock number) Flashbl...control strategy plays a minor or secondary role in predicting the effects of an insult to the system would be more acceptable. CONCLUSIONS Humans and

  11. 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

  12. Modeling personal particle-bound polycyclic aromatic hydrocarbon (pb-pah) exposure in human subjects in Southern California.

    Science.gov (United States)

    Wu, Jun; Tjoa, Thomas; Li, Lianfa; Jaimes, Guillermo; Delfino, Ralph J

    2012-07-11

    Exposure to polycyclic aromatic hydrocarbon (PAH) has been linked to various adverse health outcomes. Personal PAH exposures are usually measured by personal monitoring or biomarkers, which are costly and impractical for a large population. Modeling is a cost-effective alternative to characterize personal PAH exposure although challenges exist because the PAH exposure can be highly variable between locations and individuals in non-occupational settings. In this study we developed models to estimate personal inhalation exposures to particle-bound PAH (PB-PAH) using data from global positioning system (GPS) time-activity tracking data, traffic activity, and questionnaire information. We conducted real-time (1-min interval) personal PB-PAH exposure sampling coupled with GPS tracking in 28 non-smoking women for one to three sessions and one to nine days each session from August 2009 to November 2010 in Los Angeles and Orange Counties, California. Each subject filled out a baseline questionnaire and environmental and behavior questionnaires on their typical activities in the previous three months. A validated model was used to classify major time-activity patterns (indoor, in-vehicle, and other) based on the raw GPS data. Multiple-linear regression and mixed effect models were developed to estimate averaged daily and subject-level PB-PAH exposures. The covariates we examined included day of week and time of day, GPS-based time-activity and GPS speed, traffic- and roadway-related parameters, meteorological variables (i.e. temperature, wind speed, relative humidity), and socio-demographic variables and occupational exposures from the questionnaire. We measured personal PB-PAH exposures for 180 days with more than 6 h of valid data on each day. The adjusted R2 of the model was 0.58 for personal daily exposures, 0.61 for subject-level personal exposures, and 0.75 for subject-level micro-environmental exposures. The amount of time in vehicle (averaging 4.5% of total

  13. Finite element analysis of high modal dynamic responses of a composite floor subjected to human motion under passive live load

    Directory of Open Access Journals (Sweden)

    Arash Behnia

    Full Text Available Light weight and long span composite floors are common place in modern construction. A critical consequence of this application is undesired vibration which may cause excessive discomfort to occupants. This work investigates the composite floor vibration behavior of an existing building based on a comprehensive study of high modal dynamic responses, the range of which has been absent in previous studies and major analytical templates, of different panels under the influence of loads induced by human motion. The resulting fundamental natural frequency and vibration modes are first validated with respect to experimental and numerical evidences from literature. Departing from close correlation established in comparison, this study explores in detail the effects of intensity of passive live load as additional stationary mass due to crowd jumping as well as considering human structure interaction. From observation, a new approach in the simulation of passive live load through the consideration of human structure interaction and human body characteristics is proposed. It is concluded that higher vibration modes are essential to determine the minimum required modes and mass participation ratio in the case of vertical vibration. The results indicate the need to consider 30 modes of vibration to obtain all possible important excitations and thereby making third harmonic of load frequency available to excite the critical modes. In addition, presence of different intensities of passive live load on the composite floor showed completely different behavior in each particular panel associated with load location of panel and passive live load intensity. Furthermore, implementing human body characteristics in simulation causes an obvious increase in modal damping and hence better practicality and economical presentation can be achieved in structural dynamic behavior.

  14. Trend analysis of nuclear reactor automatic trip events subjected to operator's human error at United States nuclear power plants

    International Nuclear Information System (INIS)

    Takagawa, Kenichi

    2009-01-01

    Trends in nuclear reactor automatic trip events due to human errors during plant operating mode have been analyzed by extracting 20 events which took place in the United States during the period of seven years from 2002 to 2008, cited in the LERs (Licensee Event Reports) submitted to the US Nuclear Regulatory Commission (NRC). It was shown that the yearly number of events was relatively large before 2005, and thereafter the number decreased. A period of stable operation, in which the yearly number was kept very small, continued for about three years, and then the yearly number turned to increase again. Before 2005, automatic trip events occurred more frequently during periodic inspections or start-up/shut-down operations. The recent trends, however, indicate that trip events became more frequent due to human errors during daily operations. Human errors were mostly caused by the self-conceit and carelessness of operators through the whole period. The before mentioned trends in the yearly number of events might be explained as follows. The decrease in the automatic trip events is attributed to sharing trouble information, leading as a consequence to improvement of the manual and training for the operations which have a higher potential risk of automatic trip. Then, while the period of stable operation continued, some operators came to pay less attention to preventing human errors and not interest in the training, leading to automatic trip events in reality due to miss-operation. From these analyses on trouble experiences in the US, we learnt the followings to prevent the occurrence similar troubles in Japan: Operators should be thoroughly skilled in basic actions to prevent human errors as persons concerned. And it should be further emphasized that they should elaborate by imaging actual plant operations even though the simulator training gives them successful experiences. (author)

  15. 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.

  16. Noradrenergic α1 Receptor Antagonist Treatment Attenuates Positive Subjective Effects of Cocaine in Humans: A Randomized Trial

    Science.gov (United States)

    Newton, Thomas F.; De La Garza, Richard; Brown, Gregory; Kosten, Thomas R.; Mahoney, James J.; Haile, Colin N.

    2012-01-01

    Background 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 α1 receptor antagonist doxazosin on the positive subjective effects of cocaine. Methods 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. Results 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). Conclusions Medications that block noradrenergic α1 receptors, such as doxazosin, may be useful as treatments for cocaine dependence, and should be evaluated further. Trial

  17. FKBP5 methylation as a possible marker for cortisol state and transient cortisol exposure in healthy human subjects.

    Science.gov (United States)

    Winkler, Britta K; Lehnert, Hendrik; Oster, Henrik; Kirchner, Henriette; Harbeck, Birgit

    2017-10-01

    Current glucocorticoid replacement regimens, in adrenal insufficiency, fail to mimic the physiological cortisol secretion, thereby fostering serious side effects. To experimentally evaluate the impact of CpG methylation within the FKBP5 gene as a possible short- and long-term marker for cortisol exposure in humans. An ACTH-stimulation test was carried out and methylation status of the FKBP5 gene in leukocytes was determined. A negative correlation between basal levels of methylation and serum cortisol was observed. Individual changes in FKBP5 methylation after 24 h correlated with cortisol responses. Considering previous studies conducted with murine leucocytes, FKBP5 methylation may be suitable as a long-term biomarker, rather than acute glucocorticoid exposure, also in humans.

  18. Cosmology and Particle Physics/Human evolution and infectious disease/Cognitive evolution (1 page - 3 subjects)

    CERN Multimedia

    Carroll, Sean; Hauser, Marc D

    2007-01-01

    "On the theoretical side, particle phenomenologists will continue to develop physics beyond the Standard Model; string theorists are connecting ore strongly to cosmology and astrophysics/With the recent advent of whole-genome sequencing and increasingly complete surveys of genetic variation, we are now routinely studying 500 thousand variations at a time, enabling complete genome wide surveys in many human populations and in specific disease populations./The most exciting developments today sit at the intersection between science and philosophy.

  19. A study of the relationship between variables from the model of human occupation and subjective well-being among university students in jordan.

    Science.gov (United States)

    Yazdani, Farzaneh; Jibril, Musa; Kielhofner, Gary

    2008-01-01

    The occupational role of a university student can create challenges that negatively affect subjective well-being. Cultural factors can make these problems particularly acute for students from Arab backgrounds. This study examined the relationship between variables derived from the Model of Human Occupation (MOHO) and Jordanian university students' subjective well-being. Using cluster sampling, a total of 670 participants were recruited from the undergraduate student body at the University of Jordan. Data were collected from these students using the Role checklist, the Occupational Self-Assessment, the Affectometer 2, and the Satisfaction with Life Scale. As hypothesized, reported roles, valuation of roles, perceived competence in volition, habituation, performance capacity/skills, and the environment were significantly correlated with subjective well-being. A discriminant analysis using the most strongly correlated items significantly classified students into known groups of high and low subjective well-being. Overall, MOHO-based variables offered an effective explanation of factors that influence subjective well-being in Jordanian university students.

  20. A pharmacokinetic evaluation of five H(1) antagonists after an oral and intravenous microdose to human subjects.

    Science.gov (United States)

    Madan, Ajay; O'Brien, Zhihong; Wen, Jianyun; O'Brien, Chris; Farber, Robert H; Beaton, Graham; Crowe, Paul; Oosterhuis, Berend; Garner, R Colin; Lappin, Graham; Bozigian, Haig P

    2009-03-01

    To evaluate the pharmacokinetics (PK) of five H(1) receptor antagonists in human volunteers after a single oral and intravenous (i.v.) microdose (0.1 mg). Five H(1) receptor antagonists, namely NBI-1, NBI-2, NBI-3, NBI-4 and diphenhydramine, were administered to human volunteers as a single 0.1-mg oral and i.v. dose. Blood samples were collected up to 48 h, and the parent compound in the plasma extract was quantified by high-performance liquid chromatography and accelerator mass spectroscopy. The median clearance (CL), apparent volume of distribution (V(d)) and apparent terminal elimination half-life (t(1/2)) of diphenhydramine after an i.v. microdose were 24.7 l h(-1), 302 l and 9.3 h, and the oral C(max) and AUC(0-infinity) were 0.195 ng ml(-1) and 1.52 ng h ml(-1), respectively. These data were consistent with previously published diphenhydramine data at 500 times the microdose. The rank order of oral bioavailability of the five compounds was as follows: NBI-2 > NBI-1 > NBI-3 > diphenhydramine > NBI-4, whereas the rank order for CL was NBI-4 > diphenhydramine > NBI-1 > NBI-3 > NBI-2. Human microdosing provided estimates of clinical PK of four structurally related compounds, which were deemed useful for compound selection.

  1. A pharmacokinetic evaluation of five H1 antagonists after an oral and intravenous microdose to human subjects

    Science.gov (United States)

    Madan, Ajay; O'Brien, Zhihong; Wen, Jianyun; O'Brien, Chris; Farber, Robert H; Beaton, Graham; Crowe, Paul; Oosterhuis, Berend; Garner, R Colin; Lappin, Graham; Bozigian, Haig P

    2009-01-01

    AIMS To evaluate the pharmacokinetics (PK) of five H1 receptor antagonists in human volunteers after a single oral and intravenous (i.v.) microdose (0.1 mg). METHODS Five H1 receptor antagonists, namely NBI-1, NBI-2, NBI-3, NBI-4 and diphenhydramine, were administered to human volunteers as a single 0.1-mg oral and i.v. dose. Blood samples were collected up to 48 h, and the parent compound in the plasma extract was quantified by high-performance liquid chromatography and accelerator mass spectroscopy. RESULTS The median clearance (CL), apparent volume of distribution (Vd) and apparent terminal elimination half-life (t1/2) of diphenhydramine after an i.v. microdose were 24.7 l h−1, 302 l and 9.3 h, and the oral Cmax and AUC0–∞ were 0.195 ng ml−1 and 1.52 ng h ml−1, respectively. These data were consistent with previously published diphenhydramine data at 500 times the microdose. The rank order of oral bioavailability of the five compounds was as follows: NBI-2 > NBI-1 > NBI-3 > diphenhydramine > NBI-4, whereas the rank order for CL was NBI-4 > diphenhydramine > NBI-1 > NBI-3 > NBI-2. CONCLUSIONS Human microdosing provided estimates of clinical PK of four structurally related compounds, which were deemed useful for compound selection. PMID:19523012

  2. Toll-like receptor 7/8 agonists stimulate plasmacytoid dendritic cells to initiate TH17-deviated acute contact dermatitis in human subjects.

    Science.gov (United States)

    Garzorz-Stark, Natalie; Lauffer, Felix; Krause, Linda; Thomas, Jenny; Atenhan, Anne; Franz, Regina; Roenneberg, Sophie; Boehner, Alexander; Jargosch, Manja; Batra, Richa; Mueller, Nikola S; Haak, Stefan; Groß, Christina; Groß, Olaf; Traidl-Hoffmann, Claudia; Theis, Fabian J; Schmidt-Weber, Carsten B; Biedermann, Tilo; Eyerich, Stefanie; Eyerich, Kilian

    2018-04-01

    A standardized human model to study early pathogenic events in patients with psoriasis is missing. Activation of Toll-like receptor 7/8 by means of topical application of imiquimod is the most commonly used mouse model of psoriasis. We sought to investigate the potential of a human imiquimod patch test model to resemble human psoriasis. Imiquimod (Aldara 5% cream; 3M Pharmaceuticals, St Paul, Minn) was applied twice a week to the backs of volunteers (n = 18), and development of skin lesions was monitored over a period of 4 weeks. Consecutive biopsy specimens were taken for whole-genome expression analysis, histology, and T-cell isolation. Plasmacytoid dendritic cells (pDCs) were isolated from whole blood, stimulated with Toll-like receptor 7 agonist, and analyzed by means of extracellular flux analysis and real-time PCR. We demonstrate that imiquimod induces a monomorphic and self-limited inflammatory response in healthy subjects, as well as patients with psoriasis or eczema. The clinical and histologic phenotype, as well as the transcriptome, of imiquimod-induced inflammation in human skin resembles acute contact dermatitis rather than psoriasis. Nevertheless, the imiquimod model mimics the hallmarks of psoriasis. In contrast to classical contact dermatitis, in which myeloid dendritic cells sense haptens, pDCs are primary sensors of imiquimod. They respond with production of proinflammatory and T H 17-skewing cytokines, resulting in a T H 17 immune response with IL-23 as a key driver. In a proof-of-concept setting systemic treatment with ustekinumab diminished imiquimod-induced inflammation. In human subjects imiquimod induces contact dermatitis with the distinctive feature that pDCs are the primary sensors, leading to an IL-23/T H 17 deviation. Despite these shortcomings, the human imiquimod model might be useful to investigate early pathogenic events and prove molecular concepts in patients with psoriasis. Copyright © 2017 The Authors. Published by Elsevier

  3. 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

  4. Human papillomavirus genotypes and phylogenetic analysis of HPV-16 variants in HIV-1 infected subjects in Italy.

    Science.gov (United States)

    Tanzi, Elisabetta; Amendola, Antonella; Bianchi, Silvia; Fasolo, M Michela; Beretta, Rosangela; Pariani, Elena; Zappa, Alessandra; Frati, Elena; Orlando, Giovanna

    2009-05-29

    A cross-sectional study was carried out to improve the state of evidence regarding the spectrum of HPV types and HPV-16 LCR variants circulating among men and women infected with HIV-1 in Italy. This study, conducted in 518 HIV-positive subjects (346 males and 172 females), showed a high prevalence of HPV anal infections (88.7%) in men and of cervical infections (65.1%) in women. A wide spectrum of HPV genotypes has been observed, as both single and multiple infections. Low-risk HPV types 6, 11 and 61 were frequently detected. HPV-16 was the prevalent high-risk type. Fourteen different HPV-16 LCR variants were found. Ten belonged to the European lineage (78.7% were detected in Italian subjects and 21.3% in foreign-born, all homo/bisexual men), two to the Asiatic lineage and two to the African-2 lineage. This study underlines the great genotypic heterogeneity characterizing anal and cervical HPV infections and the marked polymorphism of the predominant HPV-16 in this high-risk population in Italy.

  5. Modeling personal particle-bound polycyclic aromatic hydrocarbon (pb-pah exposure in human subjects in Southern California

    Directory of Open Access Journals (Sweden)

    Wu Jun

    2012-07-01

    Full Text Available Abstract Background Exposure to polycyclic aromatic hydrocarbon (PAH has been linked to various adverse health outcomes. Personal PAH exposures are usually measured by personal monitoring or biomarkers, which are costly and impractical for a large population. Modeling is a cost-effective alternative to characterize personal PAH exposure although challenges exist because the PAH exposure can be highly variable between locations and individuals in non-occupational settings. In this study we developed models to estimate personal inhalation exposures to particle-bound PAH (PB-PAH using data from global positioning system (GPS time-activity tracking data, traffic activity, and questionnaire information. Methods We conducted real-time (1-min interval personal PB-PAH exposure sampling coupled with GPS tracking in 28 non-smoking women for one to three sessions and one to nine days each session from August 2009 to November 2010 in Los Angeles and Orange Counties, California. Each subject filled out a baseline questionnaire and environmental and behavior questionnaires on their typical activities in the previous three months. A validated model was used to classify major time-activity patterns (indoor, in-vehicle, and other based on the raw GPS data. Multiple-linear regression and mixed effect models were developed to estimate averaged daily and subject-level PB-PAH exposures. The covariates we examined included day of week and time of day, GPS-based time-activity and GPS speed, traffic- and roadway-related parameters, meteorological variables (i.e. temperature, wind speed, relative humidity, and socio-demographic variables and occupational exposures from the questionnaire. Results We measured personal PB-PAH exposures for 180 days with more than 6 h of valid data on each day. The adjusted R2 of the model was 0.58 for personal daily exposures, 0.61 for subject-level personal exposures, and 0.75 for subject-level micro-environmental exposures. The amount

  6. Interaction of Protein Phosphatase 1δ with Nucleophosmin in Human Osteoblastic Cells

    International Nuclear Information System (INIS)

    Haneji, Tatsuji; Teramachi, Jumpei; Hirashima, Kanji; Kimura, Koji; Morimoto, Hiroyuki

    2012-01-01

    Protein phosphorylation and dephosphorylation has been recognized as an essential mechanism in the regulation of cellular metabolism and function in various tissues. Serine and threonine protein phosphatases (PP) are divided into four categories: PP1, PP2A, PP2B, and PP2C. At least four isoforms of PP1 catalytic subunit in rat, PP1α, PP1γ1, PP1γ2, and PP1δ, were isolated. In the present study, we examined the localization and expression of PP1δ in human osteoblastic Saos-2 cells. Anti-PP1δ antibody recognized a protein present in the nucleolar regions in Saos-2 cells. Cellular fractionation revealed that PP1δ is a 37 kDa protein localized in the nucleolus. Nucleophosmin is a nucleolar phosphoprotein and located mainly in the nucleolus. Staining pattern of nucleophosmin in Saos-2 cells was similar to that of PP1δ. PP1δ and nucleophosmin were specifically stained as dots in the nucleus. Dual fluorescence images revealed that PP1δ and nucleophosmin were localized in the same regions in the nucleolus. Similar distribution patterns of PP1δ and nucleophosmin were observed in osteoblastic MG63 cells. The interaction of PP1δ and nucleophosmin was also shown by immunoprecipitation and Western analysis. These results indicated that PP1δ associate with nucleophosmin directly in the nucleolus and suggested that nucleophosmin is one of the candidate substrate for PP1δ

  7. Kinetic Modeling of the Tau PET Tracer 18F-AV-1451 in Human Healthy Volunteers and Alzheimer Disease Subjects.

    Science.gov (United States)

    Barret, Olivier; Alagille, David; Sanabria, Sandra; Comley, Robert A; Weimer, Robby M; Borroni, Edilio; Mintun, Mark; Seneca, Nicholas; Papin, Caroline; Morley, Thomas; Marek, Ken; Seibyl, John P; Tamagnan, Gilles D; Jennings, Danna

    2017-07-01

    18 F-AV-1451 is currently the most widely used of several experimental tau PET tracers. The objective of this study was to evaluate 18 F-AV-1451 binding with full kinetic analysis using a metabolite-corrected arterial input function and to compare parameters derived from kinetic analysis with SUV ratio (SUVR) calculated over different imaging time intervals. Methods: 18 F-AV-1451 PET brain imaging was completed in 16 subjects: 4 young healthy volunteers (YHV), 4 aged healthy volunteers (AHV), and 8 Alzheimer disease (AD) subjects. Subjects were imaged for 3.5 h, with arterial blood samples obtained throughout. PET data were analyzed using plasma and reference tissue-based methods to estimate the distribution volume, binding potential (BP ND ), and SUVR. BP ND and SUVR were calculated using the cerebellar cortex as a reference region and were compared across the different methods and across the 3 groups (YHV, AHV, and AD). Results: AD demonstrated increased 18 F-AV-1451 retention compared with YHV and AHV based on both invasive and noninvasive analyses in cortical regions in which paired helical filament tau accumulation is expected in AD. A correlation of R 2 > 0.93 was found between BP ND (130 min) and SUVR-1 at all time intervals. Cortical SUVR curves reached a relative plateau around 1.0-1.2 for YHV and AHV by approximately 50 min, but increased in AD by up to approximately 20% at 110-130 min and approximately 30% at 160-180 min relative to 80-100 min. Distribution volume (130 min) was lower by 30%-35% in the YHV than AHV. Conclusion: Our data suggest that although 18 F-AV-1451 SUVR curves do not reach a plateau and are still increasing in AD, an SUVR calculated over an imaging window of 80-100 min (as currently used in clinical studies) provides estimates of paired helical filament tau burden in good correlation with BP ND , whereas SUVR sensitivity to regional cerebral blood changes needs further investigation. © 2017 by the Society of Nuclear Medicine and

  8. Effects of synthetic TRH on plasma human prolactin levels in normal subjects and in patients with various endocrine disorders

    International Nuclear Information System (INIS)

    Ogawa, Norio; Miyoshi, Masanori; Suzuki, Shinya; Ofuji, Tadashi; Furuno, Katsushi

    1974-01-01

    HPRL was iodinated a modification of the enzymatic method using lactoperoxidase. By solid-phase RIA using antibody-coated disposable plastic microtiter trays, it was confirmed that the second peak consisted of the immunoreactive material that was used for RIA. For the measurement of plasma hPRL levels, the double antibody technique was used to separate bound from free labeled hormones. Basal plasma hPRL levels in normal subjects were less than 20 ng/ml. The mean basal hPRL levels were 10.2 +- 4.9 (Mean+-SD) ng/ml in 13 normal men and 9.6+-5.4 ng/ml in 8 normal women; no statistically significant sex difference was observed. When synthetic TRH was administered intravenously to a normal male subject, the maximum increase in plasma hPRL above the baseline level increased linearly as a function of the log of the TRH dose between 25 and 100 μg of TRH. Intravenous administration of 500 μg of TRH caused a significant increase in plasma hPRL in all of the 10 normal subjects tested. Plasma hPRL levels in 2 patients with Sheehan's syndrome and in a patient with operated-irradiated chromophobe adenoma tended to be low, and they showed no significant increase in plasma hPRL after TRH injection. Basal plasma hPRL levels in most of the patients with hypothalamopituitary tumor tended to be high. Plasma hPRL levels were normal in most patients with pituitary dwarfism. Plasma hPRL levels in 2 patients with hyperthyroidism tended to be low, and they showed no significant hPRL response to TRH, while patients with hypothyroidism showed normal or rather exaggerated hPRL response to TRH. Plasma hPRL levels were normal in most of the patients with Cushing's syndrome and plasma hPRL responses to TRH in these patients were normal. TRH-induced hPRL secretion tended to be impaired in patients receiving long-term and high doses of glucocorticoid. (auth.)

  9. Memory in humans is unaffected by central H1-antagonism, while objectively and subjectively measured sedation is increased.

    Science.gov (United States)

    Van Ruitenbeek, P; Vermeeren, A; Riedel, W J

    2010-04-01

    Animal literature suggests an important role for histamine in memory. In humans, this hypothesis has been scarcely tested and results from studies that have addressed this are conflicting. Second, impaired memory performance may be secondary to sedation. This study aimed to determine whether a centrally active antihistamine impairs memory performance and to dissociate such effects from sedation. Eighteen healthy volunteers received single oral doses of dexchlorpheniramine 4 mg, lorazepam 1mg and placebo in a 3-way, double blind, crossover designed study. The active control lorazepam impaired episodic- and working memory performance and increased sedation, while dexchlorpheniramine only increased sedation. 2009 Elsevier B.V. and ECNP. All rights reserved.

  10. Retrieval of long and short lists from long term memory: a functional magnetic resonance imaging study with human subjects.

    Science.gov (United States)

    Zysset, S; Müller, K; Lehmann, C; Thöne-Otto, A I; von Cramon, D Y

    2001-11-13

    Previous studies have shown that reaction time in an item-recognition task with both short and long lists is a quadratic function of list length. This suggests that either different memory retrieval processes are implied for short and long lists or an adaptive process is involved. An event-related functional magnetic resonance imaging study with nine subjects and list lengths varying between 3 and 18 words was conducted to identify the underlying neuronal structures of retrieval from long and short lists. For the retrieval and processing of word-lists a single fronto-parietal network, including premotor, left prefrontal, left precuneal and left parietal regions, was activated. With increasing list length, no additional regions became involved in retrieving information from long-term memory, suggesting that not necessarily different, but highly adaptive retrieval processes are involved.

  11. Influence of age, spatial memory, and ocular fixation on localization of auditory, visual, and bimodal targets by human subjects.

    Science.gov (United States)

    Dobreva, Marina S; O'Neill, William E; Paige, Gary D

    2012-12-01

    A common complaint of the elderly is difficulty identifying and localizing auditory and visual sources, particularly in competing background noise. Spatial errors in the elderly may pose challenges and even threats to self and others during everyday activities, such as localizing sounds in a crowded room or driving in traffic. In this study, we investigated the influence of aging, spatial memory, and ocular fixation on the localization of auditory, visual, and combined auditory-visual (bimodal) targets. Head-restrained young and elderly subjects localized targets in a dark, echo-attenuated room using a manual laser pointer. Localization accuracy and precision (repeatability) were quantified for both ongoing and transient (remembered) targets at response delays up to 10 s. Because eye movements bias auditory spatial perception, localization was assessed under target fixation (eyes free, pointer guided by foveal vision) and central fixation (eyes fixed straight ahead, pointer guided by peripheral vision) conditions. Spatial localization across the frontal field in young adults demonstrated (1) horizontal overshoot and vertical undershoot for ongoing auditory targets under target fixation conditions, but near-ideal horizontal localization with central fixation; (2) accurate and precise localization of ongoing visual targets guided by foveal vision under target fixation that degraded when guided by peripheral vision during central fixation; (3) overestimation in horizontal central space (±10°) of remembered auditory, visual, and bimodal targets with increasing response delay. In comparison with young adults, elderly subjects showed (1) worse precision in most paradigms, especially when localizing with peripheral vision under central fixation; (2) greatly impaired vertical localization of auditory and bimodal targets; (3) increased horizontal overshoot in the central field for remembered visual and bimodal targets across response delays; (4) greater vulnerability to

  12. Medical application of neutron capture γ-ray spectroscopy: measurement of cadmium and nitrogen in living human subjects

    International Nuclear Information System (INIS)

    Vartsky, D.; Ellis, K.J.; Cohn, S.H.

    1978-01-01

    In-vivo measurement of small quantities of Cd is possible due to the high radiative neutron-capture cross-section of 113 Cd (12.3%, 20000 b). Under slow neutron capture in 113 Cd, the excited 114 Cd decays by prompt emission of cascade of gamma-rays of which the most intense is the 559 keV transition from the first excited state to the ground state. For a total kidney or liver dose of 670 mrem, the detection limits are 2.5 mg or 1.5 μg/g respectively. A table shows the results of a study on normal subjects with smoking and non-smoking history. The study indicates higher cadmium levels in the group of smokers. The method of measuring body N utilizes the 14 N(n,γ) 15 N reaction. The total energy available on slow neutron capture is 10.83 MeV and approximately 15% of the de-excitations take place directly to the ground state of 15 N. The irradiation facility is basically the same as that described for measurement of Cd. The Cd collimator, however is replaced by a second collimator designed to provide a wide beam 13 x 60 cm at the level of the bed. During the irradiation the subject lies on a motorized bed which moves across the neutron beam. The precision or reproducibility of the measurements was performed using an Alderson phantom. For a standard 70 kg man having 2000 g of N, the accuracy of the measurement is +-2% with an error of 1.3% for reproducibility, based on several measurements over a 6-month period. The total radiation dose for a bilateral irradiation is 45 mrem. Initial clinical studies will concentrate on sequential measurements of body N

  13. Angiotensin IV and the human esophageal mucosa: An exploratory study in healthy subjects and gastroesophageal reflux disease patients.

    Science.gov (United States)

    Björkman, Eleonora; Edebo, Anders; Fändriks, Lars; Casselbrant, Anna

    2015-09-01

    The human esophageal mucosa expresses various components of the renin-angiotensin system (RAS), e.g. the main effector peptide angiotensin II (AngII). The aim of this study was to investigate the esophageal presence of angiotensin III (AngIII) and angiotensin IV (AngIV) forming enzymes and the AngIV receptor (AT4R). The aim was also to study the actions of AngIV and to look for aberrations in patients with gastroesophageal reflux disease (GERD). Esophageal biopsies were collected from healthy volunteers (n: 19) and individuals with erosive reflux disease (n: 14). Gene transcripts and protein expression of aminopeptidase A, -B and -M, and the AT4R were investigated by reverse transcriptase polymerase chain reaction (rt-PCR), western blot (WB) and immunohistochemistry (IHC). The functional impact of AngIV was examined in an Ussing chamber. Aminopeptidase A, -B and -M and the AT4R were expressed in the esophageal epithelium. The AT4R was less prominent in certain areas in the mucosa of reflux patients. AngIV influenced the esophageal epithelial ion transport. The impact was lower in patients with GERD. The AT4R and formation enzymes of AngIII and AngIV are present in the human esophageal epithelium. Moreover, the present results suggest that AngIV exert regulatory impact on the epithelium and that RAS is involved in mucosal aberrations associated with GERD. © The Author(s) 2014.

  14. Chemical variability of water and sediment over time and along a mountain river subjected to natural and human impact

    Directory of Open Access Journals (Sweden)

    Szarek-Gwiazda Ewa

    2018-01-01

    Full Text Available We studied the variability of physico-chemical parameters in water, and heavy metal contents in water and sediment over time and along the Carpathian Biała Tarnowska River (southern Poland and related them to catchment geology, human impact and the effect of barriers as a side aspect. The river water was well oxygenated, had pH 7.7–9.5 and was characterised by low and average flow. Temperature, pH and dissolved oxygen did not change significantly, while the contents of major ions, NO3−, NH4+, Mn and Fe increased gradually along the river. The major ion contents were negatively, and nitrate, Mn, and Fe positively, correlated with the flow. We recognise correlations between nitrate, Fe and Mn to be good indicators of soil erosion processes in the catchment. River sediment was unpolluted by most of the studied metals (slightly polluted by Ni and Cd. The differences in the values of some parameters (pH and NH4+, PO43−, HCO3−, Mn, Cd and Pb concentrations in the water, and heavy metals in the sediment upstream and downstream of some of the barriers were determined. Spatiotemporal changes in the values of studied parameters and the results of statistical calculation indicate the impact of human activity in the catchment basin (land use, wastewater on the water chemistry.

  15. Activated human neonatal CD8+ T cells are subject to immunomodulation by direct TLR2 or TLR5 stimulation.

    LENUS (Irish Health Repository)

    McCarron, Mark

    2012-02-01

    In conditions of optimal priming, the neonate possesses competency to mount quantitatively adult-like responses. Vaccine formulations containing sufficiently potent adjuvants may overcome the neonate\\'s natural tendency for immunosuppression and provoke a similarly robust immune response. TLR expression on T cells represents the possibility of directly enhancing T cell immunity. We examined the ex vivo responsiveness of highly purified human cord blood-derived CD8(+) T cells to direct TLR ligation by a repertoire of TLR agonists. In concert with TCR stimulation, only Pam(3)Cys (palmitoyl-3-Cys-Ser-(Lys)(4)) and flagellin monomers significantly enhanced proliferation, CD25(+) expression, IL-2, IFN-gamma, TNF-alpha, and intracellular granzyme B expression. TLR2 and TLR5 mRNA was detected in the CD8(+) T cells. Blocking studies confirmed that the increase in IFN-gamma production was by the direct triggering of surface TLR2 or TLR5. The simultaneous exposure of CD8(+) T cells to both TLR agonists had an additive effect on IFN-gamma production. These data suggest that a combination of the two TLR ligands would be a potent T cell adjuvant. This may represent a new approach to TLR agonist-based adjuvant design for future human neonatal vaccination strategies requiring a CD8(+) component.

  16. 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.

  17. Safety analysis of a Russian phage cocktail: From MetaGenomic analysis to oral application in healthy human subjects

    International Nuclear Information System (INIS)

    McCallin, Shawna; Alam Sarker, Shafiqul; Barretto, Caroline; Sultana, Shamima; Berger, Bernard; Huq, Sayeda; Krause, Lutz; Bibiloni, Rodrigo; Schmitt, Bertrand; Reuteler, Gloria; Brüssow, Harald

    2013-01-01

    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

  18. Acute topiramate differentially affects human aggressive responding at low vs. moderate doses in subjects with histories of substance abuse and antisocial behavior.

    Science.gov (United States)

    Lane, Scott D; Gowin, Joshua L; Green, Charles E; Steinberg, Joel L; Moeller, F Gerard; Cherek, Don R

    2009-04-01

    Anticonvulsant drugs have demonstrated efficacy in the management of irritability and aggression in a variety of psychiatric populations. We examined the acute effects of topiramate on aggression using a laboratory model of human aggression (PSAP) in individuals at high risk for aggressive and violent behavior.Twelve subjects, on parole/probation and with an Axis-II personality disorder and/or a substance use disorder, received 100, 200, 300, and 400 mg in an ascending sequence, with intervening placebo doses.Subjects participated 2-3 days per week over 4-6 weeks. Due to cognitive side effects at 300 mg, two subjects only completed through the 200 mg dose. Topiramate produced an inverted U-shaped dose response curve, with increases in aggression peaking at 200 mg and a modest decrease at 400 mg. Statistical analysis revealed a polynomial trend for dose (p=0.001). The observed inverted U-shaped function in aggressive responding is consistent with non-human aggression studies of GABA-A modulators. Acute topiramate doses >400 mg may have anti-aggressive effects, but dose levels in the 200-300 mg range may produce increases in aggression and side effects.

  19. Research on DNA methylation of human osteosarcoma cell MGMT and its relationship with cell resistance to alkylating agents.

    Science.gov (United States)

    Guo, Jun; Cui, Qiu; Jiang, WeiHao; Liu, Cheng; Li, DingFeng; Zeng, Yanjun

    2013-08-01

    The objective of this study was to explore the O(6)-methylguanine-DNA methyltransferase (MGMT) gene methylation status and its protein expression, as well as the effects of demethylating agent 5-Aza-2'-deoxycytidine (5-Aza-CdR) on MGMT gene expression and its resistance to alkylating agents, and to elucidate MGMT expression mechanism and significance in osteosarcoma. The human osteosarcoma cell lines Saos-2 and MG-63 were collected and treated with 5-Aza-CdR for 6 days. The cells not treated with 5-Aza-CdR were set as a negative control. The genomic DNA was extracted from the Saos-2 and MG-63 cells using methylation-specific PCR to detect the promoter CpG island methylation status of the MGMT gene. Cell sensitivity to alkylating agents before and after drug administration was detected by the MTT method. The variation in MGMT gene mRNA and protein was detected by reverse transcription PCR (RT-PCR) and Western blotting. The MGMT promoter gene of normal Saos-2 cells was methylated, with reduced MGMT mRNA and protein expression; the MGMT mRNA and protein expression of Saos-2 cells treated with 5-Aza-CdR was obviously enhanced, and its sensitivity to alkylating agents was reversed. Meanwhile, with promoter CpG island unmethylation of the MGMT gene, MGMT protein was expressed in the normal MG-63 cells and the MG-63 cells treated with 5-Aza-CdR, and both showed resistance to alkylating agents. The methylation status of the MGMT gene promoter in human osteosarcoma cells reflected the cells' ability to induce MGMT protein expression and can be used as a molecular marker to project the sensitivity of cancer tissues to alkylating agent drugs.

  20. S-acylation of SOD1, CCS, and a stable SOD1-CCS heterodimer in human spinal cords from ALS and non-ALS subjects.

    Science.gov (United States)

    Antinone, Sarah E; Ghadge, Ghanashyam D; Ostrow, Lyle W; Roos, Raymond P; Green, William N

    2017-01-25

    Previously, we found that human Cu, Zn-superoxide dismutase (SOD1) is S-acylated (palmitoylated) in vitro and in amyotrophic lateral sclerosis (ALS) mouse models, and that S-acylation increased for ALS-causing SOD1 mutants relative to wild type. Here, we use the acyl resin-assisted capture (acyl-RAC) assay to demonstrate S-acylation of SOD1 in human post-mortem spinal cord homogenates from ALS and non-ALS subjects. Acyl-RAC further revealed that endogenous copper chaperone for SOD1 (CCS) is S-acylated in both human and mouse spinal cords, and in vitro in HEK293 cells. SOD1 and CCS formed a highly stable heterodimer in human spinal cord homogenates that was resistant to dissociation by boiling, denaturants, or reducing agents and was not observed in vitro unless both SOD1 and CCS were overexpressed. Cysteine mutations that attenuate SOD1 maturation prevented the SOD1-CCS heterodimer formation. The degree of S-acylation was highest for SOD1-CCS heterodimers, intermediate for CCS monomers, and lowest for SOD1 monomers. Given that S-acylation facilitates anchoring of soluble proteins to cell membranes, our findings suggest that S-acylation and membrane localization may play an important role in CCS-mediated SOD1 maturation. Furthermore, the highly stable S-acylated SOD1-CCS heterodimer may serve as a long-lived maturation intermediate in human spinal cord.

  1. Neural networks engaged in short-term memory rehearsal are disrupted by irrelevant speech in human subjects.

    Science.gov (United States)

    Kopp, Franziska; Schröger, Erich; Lipka, Sigrid

    2004-01-02

    Rehearsal mechanisms in human short-term memory are increasingly understood in the light of both behavioural and neuroanatomical findings. However, little is known about the cooperation of participating brain structures and how such cooperations are affected when memory performance is disrupted. In this paper we use EEG coherence as a measure of synchronization to investigate rehearsal processes and their disruption by irrelevant speech in a delayed serial recall paradigm. Fronto-central and fronto-parietal theta (4-7.5 Hz), beta (13-20 Hz), and gamma (35-47 Hz) synchronizations are shown to be involved in our short-term memory task. Moreover, the impairment in serial recall due to irrelevant speech was preceded by a reduction of gamma band coherence. Results suggest that the irrelevant speech effect has its neural basis in the disruption of left-lateralized fronto-central networks. This stresses the importance of gamma band activity for short-term memory operations.

  2. Justice, fairness, and membership in a class: conceptual confusions and moral puzzles in the regulation of human subjects research.

    Science.gov (United States)

    Iltis, Ana S

    2011-01-01

    This essay examines conceptual difficulties with one of the ways in which justice has been understood and applied the ethical and regulatory review of human research. Justice requires the fair distribution of the benefits and burdens of research. Class membership is seen as justifying inclusion in higher hazard-no benefit research from which members of potentially vulnerable classes, such as children, typically would be excluded. I argue that class membership does not do the justificatory work it is thought to do and that the use of class membership to justify inclusion in higher hazard-no benefit research leads to unjustified discrimination of sick children and offers special protections to healthy children. © 2011 American Society of Law, Medicine & Ethics, Inc.

  3. Sequence typing of human adenoviruses isolated from Polish patients subjected to allogeneic hematopoietic stem cell transplantation - a single center experience.

    Science.gov (United States)

    Przybylski, Maciej; Rynans, Sylwia; Waszczuk-Gajda, Anna; Bilinski, Jarosław; Basak, Grzegorz W; Jędrzejczak, Wiesław W; Wróblewska, Marta; Młynarczyk, Grażyna; Dzieciątkowski, Tomasz

    2018-03-28

    Human adenoviruses (HAdV) from species A, B and C are commonly recognized as pathogens causing severe morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients. The purpose of the present study was to determine HAdV types responsible for viremia in HSCT recipients at a large tertiary hospital in Poland. Analysis of partial nucleotide sequences of HAdV hexon gene was used to type 40 clinical isolates of HAdV obtained from 40 HSCT recipients. We identified six different HAdV serotypes belonging to species B, C and E. We demonstrated high variability in sequences of detected HAdV types, and patients infected with the same HAdV types were not hospitalized at the same time, which suggests the low possibility of cross-infection. In almost all patients, anti-HAdV antibodies in IgG class were detected, which indicates a history of HAdV infection in the past. Clinical symptoms accompanying HAdV viremia were in 89%, and in 61.5% of individuals, HAdV was a sole pathogen detected. There were no cases with high-level HAdV viremia and severe systemic or organ infections. Graft-versus-host disease (GvHD) was present in patients infected with species B and C, but grade II of GvHD was observed only in patients infected with HAdV-B. The predominance of HAdV-C and common presence of anti-HAdV antibodies in IgG class may strongly suggest that most infections in the present study were reactivations of HAdV persisting into the patient's mucosa-associated lymphoid tissues. Variability of HAdV sequences suggests that cross-infections between patients were very rare. GvHD: graft-versus-host disease; HAdV: human adenoviruses; HSCT: hematopoietic stem cell transplantation.

  4. Quantitative determination of caffeine and alcohol in energy drinks and the potential to produce positive transdermal alcohol concentrations in human subjects.

    Science.gov (United States)

    Ayala, Jessica; Simons, Kelsie; Kerrigan, Sarah

    2009-01-01

    The purpose of this study was to determine whether non-alcoholic energy drinks could result in positive "alcohol alerts" based on transdermal alcohol concentration (TAC) using a commercially available electrochemical monitoring device. Eleven energy drinks were quantitatively assayed for both ethanol and caffeine. Ethanol concentrations for all of the non-alcoholic energy drinks ranged in concentration from 0.03 to 0.230% (w/v) and caffeine content per 8-oz serving ranged from 65 to 126 mg. A total of 15 human subjects participated in the study. Subjects consumed between 6 and 8 energy drinks over an 8-h period. The SCRAM II monitoring device was used to determine TACs every 30 min before, during, and after the study. None of the subjects produced TAC readings that resulted in positive "alcohol alerts". TAC measurements for all subjects before, during and after the energy drink study period (16 h total) were study consumed a quantity of non-alcoholic energy drink that greatly exceeds what would be considered typical. Based on these results, it appears that energy drink consumption is an unlikely explanation for elevated TACs that might be identified as potential drinking episodes or "alcohol alerts" using this device.

  5. Subcutaneously administered Menopur(R, a new highly purified human menopausal gonadotropin, causes significantly fewer injection site reactions than Repronex(R in subjects undergoing in vitro fertilization

    Directory of Open Access Journals (Sweden)

    Somkuti Stephen

    2005-11-01

    Full Text Available Abstract Background The safety and tolerability of a new highly purified, urine-derived human menopausal gonadotropin (hMG preparation [Menopur(R] was compared with a currently available hMG [Repronex (R] in women undergoing in vitro fertilization (IVF. Methods This was a randomized, open-label, parallel-group, multicenter study conducted in subjects undergoing IVF. Women (N = 125, 18–39 years of age, underwent pituitary down-regulation with leuprolide acetate beginning 7 days prior to onset of menses and continuing up to the day before hCG administration. Subjects were randomized to receive subcutaneous (SC Menopur (R (n = 61 or Repronex (R SC (n = 64 for a maximum of 12 days. All adverse events (AEs were recorded and subject self-assessments of injection site reactions were recorded in a daily diary. Results Significantly fewer subjects in the Menopur (R group reported injection site reactions (P Conclusion Menopur (R SC offers a greater safety and tolerability profile compared to Repronex (R SC.

  6. Expanding subjectivities

    DEFF Research Database (Denmark)

    Lundgaard Andersen, Linda; Soldz, Stephen

    2012-01-01

    A major theme in recent psychoanalytic thinking concerns the use of therapist subjectivity, especially “countertransference,” in understanding patients. This thinking converges with and expands developments in qualitative research regarding the use of researcher subjectivity as a tool......-Saxon and continental traditions, this special issue provides examples of the use of researcher subjectivity, informed by psychoanalytic thinking, in expanding research understanding....

  7. Absence of an increase in the duration of the circadian melatonin secretory episode in totally blind human subjects

    Science.gov (United States)

    Klerman, E. B.; Zeitzer, J. M.; Duffy, J. F.; Khalsa, S. B.; Czeisler, C. A.

    2001-01-01

    The daily rhythm of melatonin influences multiple physiological measures, including sleep tendency, circadian rhythms, and reproductive function in seasonally breeding mammals. The biological signal for photoperiodic changes in seasonally breeding mammals is a change in the duration of melatonin secretion, which in a natural environment reflects the different durations of daylight across the year, with longer nights leading to a longer duration of melatonin secretion. These seasonal changes in the duration of melatonin secretion do not simply reflect the known acute suppression of melatonin secretion by ocular light exposure, but also represent long-term changes in the endogenous nocturnal melatonin episode that persist in constant conditions. As the eyes of totally blind individuals do not transmit ocular light information, we hypothesized that the duration of the melatonin secretory episode in blind subjects would be longer than those in sighted individuals, who are exposed to light for all their waking hours in an urban environment. We assessed the melatonin secretory profile during constant posture, dim light conditions in 17 blind and 157 sighted adults, all of whom were healthy and using no prescription or nonprescription medications. The duration of melatonin secretion was not significantly different between blind and sighted individuals. Healthy blind individuals after years without ocular light exposure do not have a longer duration of melatonin secretion than healthy sighted individuals.

  8. Pre-attentive processing of spectrally complex sounds with asynchronous onsets: an event-related potential study with human subjects.

    Science.gov (United States)

    Tervaniemi, M; Schröger, E; Näätänen, R

    1997-05-23

    Neuronal mechanisms involved in the processing of complex sounds with asynchronous onsets were studied in reading subjects. The sound onset asynchrony (SOA) between the leading partial and the remaining complex tone was varied between 0 and 360 ms. Infrequently occurring deviant sounds (in which one out of 10 harmonics was different in pitch relative to the frequently occurring standard sound) elicited the mismatch negativity (MMN), a change-specific cortical event-related potential (ERP) component. This indicates that the pitch of standard stimuli had been pre-attentively coded by sensory-memory traces. Moreover, when the complex-tone onset fell within temporal integration window initiated by the leading-partial onset, the deviants elicited the N2b component. This indexes that involuntary attention switch towards the sound change occurred. In summary, the present results support the existence of pre-perceptual integration mechanism of 100-200 ms duration and emphasize its importance in switching attention towards the stimulus change.

  9. Human occupants in low-speed frontal sled tests: effects of pre-impact bracing on chest compression, reaction forces, and subject acceleration.

    Science.gov (United States)

    Kemper, Andrew R; Beeman, Stephanie M; Madigan, Michael L; Duma, Stefan M

    2014-01-01

    The purpose of this study was to investigate the effects of pre-impact bracing on the chest compression, reaction forces, and accelerations experienced by human occupants during low-speed frontal sled tests. A total of twenty low-speed frontal sled tests, ten low severity (∼2.5g, Δv=5 kph) and ten medium severity (∼5g, Δv=10 kph), were performed on five 50th-percentile male human volunteers. Each volunteer was exposed to two impulses at each severity, one relaxed and the other braced prior to the impulse. A 59-channel chestband, aligned at the nipple line, was used to quantify the chest contour and anterior-posterior sternum deflection. Three-axis accelerometer cubes were attached to the sternum, 7th cervical vertebra, and sacrum of each subject. In addition, three linear accelerometers and a three-axis angular rate sensor were mounted to a metal mouthpiece worn by each subject. Seatbelt tension load cells were attached to the retractor, shoulder, and lap portions of the standard three-point driver-side seatbelt. In addition, multi-axis load cells were mounted to each interface between the subject and the test buck to quantify reaction forces. For relaxed tests, the higher test severity resulted in significantly larger peak values for all resultant accelerations, all belt forces, and three resultant reaction forces (right foot, seatpan, and seatback). For braced tests, the higher test severity resulted in significantly larger peak values for all resultant accelerations, and two resultant reaction forces (right foot and seatpan). Bracing did not have a significant effect on the occupant accelerations during the low severity tests, but did result in a significant decrease in peak resultant sacrum linear acceleration during the medium severity tests. Bracing was also found to significantly reduce peak shoulder and retractor belt forces for both test severities, and peak lap belt force for the medium test severity. In contrast, bracing resulted in a significant

  10. Inactivation of the Haemophilus ducreyi luxS gene affects the virulence of this pathogen in human subjects.

    Science.gov (United States)

    Labandeira-Rey, Maria; Janowicz, Diane M; Blick, Robert J; Fortney, Kate R; Zwickl, Beth; Katz, Barry P; Spinola, Stanley M; Hansen, Eric J

    2009-08-01

    Haemophilus ducreyi 35000HP contains a homologue of the luxS gene, which encodes an enzyme that synthesizes autoinducer 2 (AI-2) in other gram-negative bacteria. H. ducreyi 35000HP produced AI-2 that functioned in a Vibrio harveyi-based reporter system. A H. ducreyi luxS mutant was constructed by insertional inactivation of the luxS gene and lost the ability to produce AI-2. Provision of the H. ducreyi luxS gene in trans partially restored AI-2 production by the mutant. The luxS mutant was compared with its parent for virulence in the human challenge model of experimental chancroid. The pustule-formation rate in 5 volunteers was 93.3% (95% confidence interval, 81.7%-99.9%) at 15 parent sites and 60.0% (95% confidence interval, 48.3%-71.7%) at 15 mutant sites (1-tailed P < .001). Thus, the luxS mutant was partially attenuated for virulence. This is the first report of AI-2 production contributing to the pathogenesis of a genital ulcer disease.

  11. [Disability, inability and vulnerability: on ableism or the pre-eminence of ableist and biomedical approaches of the Human Subjects Ethics Committee of UFSC].

    Science.gov (United States)

    Mello, Anahi Guedes de

    2016-10-01

    Anthropology has increasingly questioned the hegemony of biomedical knowledge in ethical review processes of social research projects prevailing in Brazil, which was governed until 2012 by the Human Research Ethics Committee of each institution under the auspices of the National Research Ethics Commission (CONEP). This was mandated through Resolution No. 196/1996 prevailing in 2012 when this field research was conducted. The scope of this study is to recount and reflect upon the barriers to obtaining approval in 2012 for my master's research project from the Human Research Ethics Committee of the Federal University of Santa Catarina (CEP/UFSC) in Florianopolis. In this ethnographic experience, in the light of Crip theory, I observed how the "disability," "vulnerability" and "inability" categories are articulated to reveal the ableism and the primacy of the biomedical model in the case of an ethics review at UFSC regarding the participation and legal capacity of persons with disabilities as subjects of research.

  12. 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

  13. Suppressive response of confections containing the extractive from leaves of Morus Alba on postprandial blood glucose and insulin in healthy human subjects

    Directory of Open Access Journals (Sweden)

    Oku Tsuneyuki

    2009-07-01

    Full Text Available Abstract Background The first aim of this study was to clarify the effective ratio of extractive from leaves of Morus Alba (ELM to sucrose so as to apply this knowledge to the preparation of confections that could effectively suppress the elevation of postprandial blood glucose and insulin. The second aim was to identify the efficacy of confections prepared with the optimally effective ratio determined from the first study, using healthy human subjects. Methods Ten healthy females (22.3 years, BMI 21.4 kg/m2 participated in this within-subject, repeated measures study. For the first aim of this study, the test solutions containing 30 g of sucrose and 1.2 or 3.0 g of ELM were repeatedly and randomly given to each subject. To identify the practically suppressive effects on postprandial blood glucose and insulin, some confections with added ELM were prepared as follows: Mizu-yokan, 30 g of sucrose with the addition of 1.5 or 3.0 g ELM; Daifuku-mochi, 9.0 g of starch in addition to 30 g of sucrose and 1.5 or 3.0 g ELM; Chiffon-cake, 24 g of sucrose, starch, and 3.0 or 6.0 g of ELM, and were ingested by each subject. Blood and end-expiration were collected at selected periods after test food ingestion. Results When 30 g of sucrose with 1.2 or 3.0 g of ELM were ingested by subjects, the elevations of postprandial blood glucose and insulin were effectively suppressed (p p Conclusion ELM-containing confections for which the ratio of ELM and sucrose is one-tenth effectively suppress the postprandial blood glucose and insulin by inhibiting the intestinal sucrase, thus creating a prebiotic effect. The development of confections with ELM can therefore contribute to the prevention and the quality of life for prediabetic and diabetic patients.

  14. Building research capacity with members of underserved American Indian/Alaskan Native communities: training in research ethics and the protection of human subjects.

    Science.gov (United States)

    Jetter, Karen M; Yarborough, Mark; Cassady, Diana L; Styne, Dennis M

    2015-05-01

    To develop a research ethics training course for American Indian/Alaskan Native health clinic staff and community researchers who would be conducting human subjects research. Community-based participatory research methods were used in facilitated discussions of research ethics centered around topics included in the Collaborative Institutional Training Initiative research ethics course. The community-based participatory research approach allowed all partners to jointly develop a research ethics training program that was relevant for American Indian/Alaskan Native communities. All community and clinic partners were able to pass the Collaborative Institutional Training Initiative course they were required to pass so that they could be certified to conduct research with human subjects on federally funded projects. In addition, the training sessions provided a foundation for increased community oversight of research. By using a collaborative process to engage community partners in research ethics discussions, rather than either an asynchronous online or a lecture/presentation format, resulted in significant mutual learning about research ethics and community concerns about research. This approach requires university researchers to invest time in learning about the communities in which they will be working prior to the training. © 2014 Society for Public Health Education.

  15. 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 (<6 month) studies amongst overweight or obese individuals indicate that 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.

  16. In-vivo tissue uptake and retention of Sn-117m(4+)DTPA in a human subject with metastatic bone pain and in normal mice

    International Nuclear Information System (INIS)

    Swailem, Fayez M.; Krishnamurthy, Gerbail T.; Srivastava, Suresh C.; Aguirre, Maria L.; Ellerson, Dawn L.; Walsh, T. Kent; Simpson, Laura

    1998-01-01

    Organ and tissue uptake and retention of Sn-117m(4+)DTPA were studied in a human subject treated for metastatic bone pain, and the results were compared with the biodistribution studies in five normal mice. The explanted organs from a patient who received a therapy dose of 18.6 mCi (688.2 MBq) Sn-117m(4+)DTPA and who died 47 days later were imaged with a γ-camera, and tissue samples were counted and also autoradiographed. Bone, muscle, liver, fat, lungs, kidneys, spleen, heart and pancreas tissue samples were assayed in a well counter for radioactivity. Regions of interest were drawn over bone and major organs to calculate and quantify clearance times using three in vivo Sn-117m(4+)DTPA whole-body scintigrams acquired at 1, 24 and 168 h after injection. Five normal mice injected with the same batch of Sn-117m(4+)DTPA as used for the human subject were sacrificed at 24 h, and tissue samples were collected and assayed for radioactivity for comparison with the human data. For the human subject, whole-body retention at 47 days postinjection was 81% of the injected dose, and the rest (19%) was excreted in urine. Of the whole-body retained activity at 47 days, 82.4% was in bone, 7.8% in the muscle and 1.5% in the liver, and the rest was distributed among other tissues. γ-Ray scintigrams and electron autoradiographs of coronal slices of the thoracolumbar vertebral body showed heterogenous metastatic involvement with normal bone between metastatic lesions. There was nonuniform distribution of radioactivity even within a single vertebral body, indicating normal bone between metastatic lesions. Lesion-to-nonlesion ratios ranged from 3 to 5. However, the osteoid-to-marrow cavity deposition ratio, from the microautoradiographs, was 11:1. The peak uptake in the human bone was seen at 137 h with no biological clearance. Soft tissues showed peak uptake at 1 h and exhibited three compartmental clearance components. Whole-body retention in normal mice was 38.7% of the injected

  17. Striking differences in glucose and lactate levels between brain extracellular fluid and plasma in conscious human subjects: effects of hyperglycemia and hypoglycemia.

    Science.gov (United States)

    Abi-Saab, Walid M; Maggs, David G; Jones, Tim; Jacob, Ralph; Srihari, Vinod; Thompson, James; Kerr, David; Leone, Paola; Krystal, John H; Spencer, Dennis D; During, Matthew J; Sherwin, Robert S

    2002-03-01

    Brain levels of glucose and lactate in the extracellular fluid (ECF), which reflects the environment to which neurons are exposed, have never been studied in humans under conditions of varying glycemia. The authors used intracerebral microdialysis in conscious human subjects undergoing electrophysiologic evaluation for medically intractable epilepsy and measured ECF levels of glucose and lactate under basal conditions and during a hyperglycemia-hypoglycemia clamp study. Only measurements from nonepileptogenic areas were included. Under basal conditions, the authors found the metabolic milieu in the brain to be strikingly different from that in the circulation. In contrast to plasma, lactate levels in brain ECF were threefold higher than glucose. Results from complementary studies in rats were consistent with the human data. During the hyperglycemia-hypoglycemia clamp study the relationship between plasma and brain ECF levels of glucose remained similar, but changes in brain ECF glucose lagged approximately 30 minutes behind changes in plasma. The data demonstrate that the brain is exposed to substantially lower levels of glucose and higher levels of lactate than those in plasma; moreover, the brain appears to be a site of significant anaerobic glycolysis, raising the possibility that glucose-derived lactate is an important fuel for the brain.

  18. Sandwich-type enzyme immunoassay for big endothelin-I in plasma: concentrations in healthy human subjects unaffected by sex or posture.

    Science.gov (United States)

    Aubin, P; Le Brun, G; Moldovan, F; Villette, J M; Créminon, C; Dumas, J; Homyrda, L; Soliman, H; Azizi, M; Fiet, J

    1997-01-01

    A sandwich-type enzyme immunoassay has been developed for measuring human big endothelin-1 (big ET-1) in human plasma and supernatant fluids from human cell cultures. Big ET-1 is the precursor of endothelin 1 (ET-1), the most potent vasoconstrictor known. A rabbit antibody raised against the big ET-1 COOH-terminus fragment was used as an immobilized antibody (anti-P16). The Fab' fragment of a monoclonal antibody (1B3) raised against the ET-1 loop fragment was used as the enzyme-labeled antibody, after being coupled to acetylcholinesterase. The lowest detectable value in the assay was 1.2 pg/mL (0.12 pg/well). The assay was highly specific for big ET-1, demonstrating no cross-reactivity with ET-1, big endothelin-2 (big ET-2), and big endothelin-3 (big ET-3). We used this assay to evaluate the effect of two different postural positions (supine and standing) on plasma big ET-1 concentrations in 11 male and 11 female healthy subjects. Data analysis revealed that neither sex nor body position influenced plasma big ET-1 concentrations. This assay should thus permit the detection of possible variations in plasma concentrations of big ET-1 in certain pathologies and, in association with ET-1 assay, make possible in vitro study of endothelin-converting enzyme activity in cell models. Such studies could clarify the physiological and clinical roles of this family of peptides.

  19. 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.

  20. Suppressive response of confections containing the extractive from leaves of Morus Alba on postprandial blood glucose and insulin in healthy human subjects

    Science.gov (United States)

    Nakamura, Mariko; Nakamura, Sadako; Oku, Tsuneyuki

    2009-01-01

    Background The first aim of this study was to clarify the effective ratio of extractive from leaves of Morus Alba (ELM) to sucrose so as to apply this knowledge to the preparation of confections that could effectively suppress the elevation of postprandial blood glucose and insulin. The second aim was to identify the efficacy of confections prepared with the optimally effective ratio determined from the first study, using healthy human subjects. Methods Ten healthy females (22.3 years, BMI 21.4 kg/m2) participated in this within-subject, repeated measures study. For the first aim of this study, the test solutions containing 30 g of sucrose and 1.2 or 3.0 g of ELM were repeatedly and randomly given to each subject. To identify the practically suppressive effects on postprandial blood glucose and insulin, some confections with added ELM were prepared as follows: Mizu-yokan, 30 g of sucrose with the addition of 1.5 or 3.0 g ELM; Daifuku-mochi, 9.0 g of starch in addition to 30 g of sucrose and 1.5 or 3.0 g ELM; Chiffon-cake, 24 g of sucrose, starch, and 3.0 or 6.0 g of ELM, and were ingested by each subject. Blood and end-expiration were collected at selected periods after test food ingestion. Results When 30 g of sucrose with 1.2 or 3.0 g of ELM were ingested by subjects, the elevations of postprandial blood glucose and insulin were effectively suppressed (p < 0.01), and the most effective ratio of ELM to sucrose was evaluated to be 1:10. AUC (area under the curve) of breath hydrogen excretion for 6 h after the ingestion of an added 3 g of ELM significantly increased (p < 0.01). When AUCs-3h of incremental blood glucose of confections without ELM was 100, that of Mizu-yokan and Daifuku-mochi with the ratio (1:10) of ELM to sucrose was decreased to 53.4 and 58.2, respectively. Chiffon-cake added one-fourth ELM was 29.0. Conclusion ELM-containing confections for which the ratio of ELM and sucrose is one-tenth effectively suppress the postprandial blood glucose and

  1. Validation of the 133Xe inhalation method for measuring brain stem and cerebellar blood flow in human subjects and the baboon

    International Nuclear Information System (INIS)

    Sakai, F.; Meyer, J. St.; Yamaguchi, F.; Yamamoto, M.; Shaw, T.; Juge, O.

    1979-01-01

    Regional cerebral blood flow (rCBF) measurements recorded by probes placed over the posterior fossa after 133 Xe inhalation have been validated here in. After inhalation, 133 Xe gas is distributed via arterial blood of both carotid an vertebrobasilar systems, so that it should be possible to measure rCBF of the brain stem and cerebellum if appropriate collimation, probe placement and selection of activity are employed. Detectors placed over the suboccipital regions may be subject to distortion by radioactivity derived from extracerebral sources so that the following questions were asked: 1) What is the counting geometry for each probe looking at this area 2) What is the extent of contamination from surrounding tissues 3) Are the flow values reproducible and in accordance with values obtained by other techniques 4) Are the flow values able to show predictable changes under physiological and pathological conditions Animal and human experiments designed to answer these questions are reported. (Auth.)

  2. A sensitive radioimmunoassay measuring endothelin-like immunoreactivity in human plasma: comparison of levels in patients with essential hypertension and normotensive control subjects

    International Nuclear Information System (INIS)

    Davenport, A.P.; Ashby, M.J.; Easton, Patricia

    1990-01-01

    A radioimmunoassay was developed to measure endothelin-like immunoreactivity in human plasma using antibody raised against endothelin-1 which also cross-reacts with big endothelin-1 and endothelin-2 but not endothelin-3. The sensitivity was 1 fmol/tube with inter- and intra-assay coefficients of variation of 13% and 9%, respectively. Cross-reactivity with endothelin-3 and non-endothelin peptides was less than 1%. Endothelin-like immunoreactivity was present in plasma of hypertensive patients (n = 25) at 5.7±0.5 pmol/1 (mean±SEM), not significantly different from that of age-matched control subjects (5.1±0.5 pmol/1). At these levels, endothelin-1 is unlikely to function as a circulating hormone. In the normotensive group, the concentration of endothelin-like immunoreactivity in plasma was positively correlated with mean arterial blood pressure, but in hypertensive patients it showed significant negative correlation. (author)

  3. Potentiation by caffeine of x-ray damage to cultured human skin fibroblasts from normal subjects and ataxia-telangiectasia patients

    International Nuclear Information System (INIS)

    Furcinitti, P.S.

    1983-01-01

    Caffeine was found to potentiate x-ray-induced killing of human diploid fibroblasts from a normal subject and an ataxia-telangiectasia (AT) patient when it was present at 2 mM concentration for 30 to 66 h postirradiation. The dose-modifying factor for caffeine-treated normal cells had an average value of 1.26 +- 0.13 which did not vary significantly with treatment time or x-ray dose. The dose-modifying factor for caffeine-treated AT cells was 1.12 +- 0.12 at 30 h, rose to 1.66 +- 0.17 at 41 h, and decreased to 1.31 +- 0.13 at 66 h. Thus no clear difference was observed between these two cell strains' susceptibility to postirradiation caffeine treatment

  4. Studies on immunoproteasome in human liver. Part I: Absence in fetuses, presence in normal subjects, and increased levels in chronic active hepatitis and cirrhosis

    International Nuclear Information System (INIS)

    Vasuri, Francesco; Capizzi, Elisa; Bellavista, Elena; Mishto, Michele; Santoro, Aurelia; Fiorentino, Michelangelo; Capri, Miriam; Cescon, Matteo; Grazi, Gian Luca; Grigioni, Walter Franco; D'Errico-Grigioni, Antonia; Franceschi, Claudio

    2010-01-01

    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 (α4 and β1) and inducible (LMP2 and LMP7) proteasome subunits, and for the PA28αβ 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 PA28αβ. 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.

  5. 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.

  6. 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.

  7. Association of HLA-DR3 with human immune response to Lol p I and Lol p II allergens in allergic subjects.

    Science.gov (United States)

    Freidhoff, L R; Ehrlich-Kautzky, E; Meyers, D A; Ansari, A A; Bias, W B; Marsh, D G

    1988-04-01

    Associations between HLA type and IgE or IgG antibody (Ab) responses to two well-characterized, antigenetically non-crossreactive components of Lolium perenne (rye grass) pollen extract, Lol p I (Rye I) and Lol p II (Rye II) were studied in two groups of skin-test positive (ST+) Caucasoid adults. By both nonparametric and parametric statistical methods, significant associations were found between Ab responses to both Lol I and Lol II and the possession of HLA-DR3. In view of the well-known associations of both DR3 and B8 (which are in linkage disequilibrium) with many autoimmune diseases, differences in anti-Lol I and anti-Lol II mean log[Ab] levels between B8+, DR3- vs B8-, DR3- subjects and B8+, DR3+ vs B8-, DR3+ subjects were investigated. No differences were found. Our data, along with recent RFLP and DNA sequence studies, suggest that an Ia molecule involved in immune recognition of a similar major Ia recognition site of both the Lol molecules may consist of a DR3 alpha-beta I pair. Abbreviations used: Ab: Antibody. HLA: Human leukocyte antigen. Lol p I, Lol I: Group I allergen from Lolium perenne pollen (Rye I). Lol p II, Lol II: Group II allergen from Lolium perenne pollen (Rye II). Mr: Relative molecular mass. Rx: Immunotherapy with grass pollen extracts. ST: Skin test.

  8. Changes in markers of oxidative stress and DNA damage in human visceral adipose tissue from subjects with obesity and type 2 diabetes.

    Science.gov (United States)

    Jones, D A; Prior, S L; Barry, J D; Caplin, S; Baxter, J N; Stephens, J W

    2014-12-01

    In the past 30 years, prevalence of obesity has almost trebled resulting in an increased incidence of type 2 diabetes mellitus and other co-morbidities. Visceral adipose tissue is believed to play a vital role, but underlying mechanisms remain unclear. Our aim was to investigate changes in markers of oxidative damage in human visceral adipose tissue to determine levels of oxidative burden that may be attributed to obesity and/or diabetes. Visceral adipose tissue samples from 61 subjects undergoing abdominal surgery grouped as lean, obese and obese with type 2 diabetes mellitus, were examined using 3 different markers of oxidative stress. Malondialdehyde (MDA) concentration was measured as a marker of lipid peroxidation, telomere length and Comet assay as markers of oxidative DNA damage. No significant difference in MDA concentration, telomere length and DNA damage was observed between groups, although longer telomere lengths were seen in the obese with diabetes group compared to the obese group (Pstress and DNA damage was observed in samples from subjects with type 2 diabetes mellitus. Further work is required to investigate this further, however this phenomenon may be due to an up regulation of antioxidant defences in adipose tissue. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. Military chemical warfare agent human subjects testing: part 1--history of six-decades of military experiments with chemical warfare agents.

    Science.gov (United States)

    Brown, Mark

    2009-10-01

    Military chemical warfare agent testing from World War I to 1975 produced thousands of veterans with concerns of possible long-term health consequences. Clinical and research evaluation of potential long-term health effects has been difficult because the exposures occurred decades ago, the identity of troops exposed and exposure magnitudes are uncertain, and acute effects during experiments poorly documented. In contrast, a companion article describes the large amount of information available about the specific agents tested and their long-term health effects. This short history describes U.S. military chemical-agent experiments with human subjects and identifies tested agents. Finally, the demonstrated need to anticipate future health concerns from military personnel involved in such military testing suggests current and future military researchers should be required, by law and regulation, to fully record the identity of those exposed, relevant exposure magnitude, and complete medical information for all subjects. New study protocols and institutional review board approvals for research involving military personnel should reflect this need.

  10. Evidence for Non-Opponent Coding of Colour Information in Human Visual Cortex: Selective Loss of "Green" Sensitivity in a Subject with Damaged Ventral Occipito-Temporal Cortex.

    Science.gov (United States)

    Rauscher, Franziska G; Plant, Gordon T; James-Galton, Merle; Barbur, John L

    2011-01-01

    Damage to ventral occipito-temporal extrastriate visual cortex leads to the syndrome of prosopagnosia often with coexisting cerebral achromatopsia. A patient with this syndrome resulting in a left upper homonymous quadrantanopia, prosopagnosia, and incomplete achromatopsia is described. Chromatic sensitivity was assessed at a number of locations in the intact visual field using a dynamic luminance contrast masking technique that isolates the use of colour signals. In normal subjects chromatic detection thresholds form an elliptical contour when plotted in the Commission Internationale d'Eclairage, (x-y), chromaticity diagram. Because the extraction of colour signals in early visual processing involves opponent mechanisms, subjects with Daltonism (congenital red/green loss of sensitivity) show symmetric increase in thresholds towards the long wavelength ("red") and middle wavelength ("green") regions of the spectrum locus. This is also the case with acquired loss of chromatic sensitivity as a result of retinal or optic nerve disease. Our patient's results were an exception to this rule. Whilst his chromatic sensitivity in the central region of the visual field was reduced symmetrically for both "red/green" and "yellow/blue" directions in colour space, the subject's lower left quadrant showed a marked asymmetry in "red/green" thresholds with the greatest loss of sensitivity towards the "green" region of the spectrum locus. This spatially localized asymmetric loss of "green" but not "red" sensitivity has not been reported previously in human vision. Such loss is consistent with selective damage of neural substrates in the visual cortex that process colour information, but are spectrally non-opponent.

  11. Divergence of canonical danger signals: The genome-level expression patterns of human mononuclear cells subjected to heat shock or lipopolysaccharide

    Directory of Open Access Journals (Sweden)

    Sakthivel Bhuvaneswari

    2008-05-01

    Full Text Available Abstract Background Peripheral blood mononuclear cells (PBMC serve a sentinel role allowing the host to efficiently sense and adapt to the presence of danger signals. Herein we have directly compared the genome-level expression patterns (microarray of a human PBMC model (THP-1 cells subjected to one of two canonical danger signals, heat shock or lipopolysaccharide (LPS. Results and Discussion Based on sequential expression and statistical filters, and in comparison to control cells, we found that 3,988 genes were differentially regulated in THP-1 cells subjected to LPS stress, and 2,921 genes were differentially regulated in THP-1 cells subjected to heat shock stress. Venn analyses demonstrated that the majority of differentially regulated genes (≥ 70% were uniquely expressed in response to one of the two danger signals. Functional analyses demonstrated that the two danger signals induced expression or repression of genes corresponding to unique pathways, molecular functions, biological processes, and gene networks. In contrast, there were 184 genes that were commonly upregulated by both stress signals, and 430 genes that were commonly downregulated by both stress signals. Interestingly, the 184 commonly upregulated genes corresponded to a gene network broadly related to inflammation, and more specifically to chemokine signaling. Conclusion These data demonstrate that the mononuclear cell responses to the canonical stress signals, heat shock and LPS, are highly divergent. However, there is a heretofore unrecognized common pattern of gene network expression corresponding to chemokine-related biology. The data also serve as a reference database for investigators in the field of stress signaling.

  12. Impact of Gluten-Friendly Bread on the Metabolism and Function of In Vitro Gut Microbiota in Healthy Human and Coeliac Subjects

    Science.gov (United States)

    Bevilacqua, Antonio; Costabile, Adele; Bergillos-Meca, Triana; Gonzalez, Isidro; Landriscina, Loretta; Ciuffreda, Emanuela; D’Agnello, Paola; Corbo, Maria Rosaria; Sinigaglia, Milena; Lamacchia, Carmela

    2016-01-01

    The main aim of this paper was to assess the in vitro response of healthy and coeliac human faecal microbiota to gluten-friendly bread (GFB). Thus, GFB and control bread (CB) were fermented with faecal microbiota in pH-controlled batch cultures. The effects on the major groups of microbiota were monitored over 48 h incubations by fluorescence in situ hybridisation. Short-chain fatty acids (SCFAs) were measured by high-performance liquid chromatography (HPLC). Furthermore, the death kinetics of Lactobacillus acidophilus, Bifidobacterium animalis subsp. lactis, Staphylococcus aureus, and Salmonella Typhimurium in a saline solution supplemented with GFB or CB were also assessed. The experiments in saline solution pinpointed that GFB prolonged the survival of L. acidophilus and exerted an antibacterial effect towards S. aureus and S. Typhimurium. Moreover, GFB modulated the intestinal microbiota in vitro, promoting changes in lactobacilli and bifidobacteria members in coeliac subjects. A final multivariate approach combining both viable counts and metabolites suggested that GFB could beneficially modulate the coeliac gut microbiome; however, human studies are needed to prove its efficacy. PMID:27632361

  13. Whole-body biodistribution, radiation absorbed dose, and brain SPET imaging with [{sup 123}I]5-I-A-85380 in healthy human subjects

    Energy Technology Data Exchange (ETDEWEB)

    Fujita, Masahiro; Tamagnan, G.; Baldwin, R.M.; Khan, S.; Bozkurt, A. [Yale Univ., New Haven, CT (United States). School of Medicine; Seibyl, J.P.; Early, M. [Institute for Neurodegenerative Disorders, New Haven, CT (United States); Vaupel, B.D.; Horti, A.G.; Mukhin, A.G.; Kimes, A.S. [Brain Imaging Center, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD (United States); Zoghbi, S.S. [Yale Univ., New Haven, CT (United States). Dept. of Radiology; Koren, A.O.; London, E.D. [Brain Imaging Center, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD (United States); Departments of Psychiatry and Biobehavioral Sciences, UCLA, Los Angeles, CA (United States); Innis, R.B. [Molecular Imaging Branch, National Institutes of Mental Health (United States)

    2002-02-01

    The biodistribution of radioactivity after the administration of a new tracer for {alpha}4{beta}2 nicotinic acetylcholine receptors (nAChRs), [{sup 123}I]5-iodo-3-[2(S)-2-azetidinylmethoxy]pyridine (5-I-A-85380), was studied in ten healthy human subjects. Following administration of 98{+-}6 MBq [{sup 123}I]5-I-A-85380, serial whole-body images were acquired over 24 h and corrected for attenuation. One to four brain single-photon emission tomography (SPET) images were also acquired between 2.5 and 24 h. Estimates of radiation absorbed dose were calculated using MIRDOSE 3.1 with a dynamic bladder model and a dynamic gastrointestinal tract model. The estimates of the highest absorbed dose ({mu}Gy/MBq) were for the urinary bladder wall (71 and 140), lower large intestine wall (70 and 72), and upper large intestine wall (63 and 64), with 2.4-h and 4.8-h urine voiding intervals, respectively. The whole brain activity at the time of the initial whole-body imaging at 14 min was 5.0% of the injected dose. Consistent with the known distribution of {alpha}4{beta}2 nAChRs, SPET images showed the highest activity in the thalamus. These results suggest that [{sup 123}I]5-I-A-85380 is a promising SPET agent to image {alpha}4{beta}2 nAChRs in humans, with acceptable dosimetry and high brain uptake. (orig.)

  14. A comparative analysis of biomedical research ethics regulation systems in Europe and Latin America with regard to the protection of human subjects.

    Science.gov (United States)

    Lamas, Eugenia; Ferrer, Marcela; Molina, Alberto; Salinas, Rodrigo; Hevia, Adriana; Bota, Alexandre; Feinholz, Dafna; Fuchs, Michael; Schramm, Roland; Tealdi, Juan-Carlos; Zorrilla, Sergio

    2010-12-01

    The European project European and Latin American Systems of Ethics Regulation of Biomedical Research Project (EULABOR) has carried out the first comparative analysis of ethics regulation systems for biomedical research in seven countries in Europe and Latin America, evaluating their roles in the protection of human subjects. We developed a conceptual and methodological framework defining 'ethics regulation system for biomedical research' as a set of actors, institutions, codes and laws involved in overseeing the ethics of biomedical research on humans. This framework allowed us to develop comprehensive national reports by conducting semi-structured interviews to key informants. These reports were summarised and analysed in a comparative analysis. The study showed that the regulatory framework for clinical research in these countries differ in scope. It showed that despite the different political contexts, actors involved and motivations for creating the regulation, in most of the studied countries it was the government who took the lead in setting up the system. The study also showed that Europe and Latin America are similar regarding national bodies and research ethics committees, but the Brazilian system has strong and noteworthy specificities.

  15. Beneficial effects of metformin on energy metabolism and visceral fat volume through a possible mechanism of fatty acid oxidation in human subjects and rats.

    Directory of Open Access Journals (Sweden)

    Ichiro Tokubuchi

    Full Text Available Metformin is known to have a beneficial effect on body weight and body composition, although the precise mechanism has not been elucidated yet. The aim of this study is to investigate the effects of metformin on energy metabolism and anthropometric factors in both human subjects and rats.In human studies, metformin (1500mg/day was administered to 23 healthy subjects and 18 patients with type 2 diabetes for 2 weeks. Metabolic parameters and energy metabolism were measured during a meal tolerance test in the morning before and after the treatment of metformin. In animal studies, 13 weeks old SD rats were fed 25-26 g of standard chow only during 12-hours dark phase with either treated by metformin (2.5mg/ml in drinking water or not for 2 weeks, and metabolic parameters, anthropometric factors and energy metabolism together with expressions related to fat oxidation and adaptive thermogenesis were measured either in fasting or post-prandial state at 15 weeks old.Post-prandial plasma lactate concentration was significantly increased after the metformin treatment in both healthy subjects and diabetic patients. Although energy expenditure (EE did not change, baseline respiratory quotient (RQ was significantly decreased and post-prandial RQ was significantly increased vice versa following the metformin treatment in both groups. By the administration of metformin to SD rats for 2 weeks, plasma levels of lactate and pyruvate were significantly increased in both fasting and post-prandial states. RQ during a fasting state was significantly decreased in metformin-treated rats compared to controls with no effect on EE. Metformin treatment brought about a significant reduction of visceral fat mass compared to controls accompanied by an up-regulation of fat oxidation-related enzyme in the liver, UCP-1 in the brown adipose tissue and UCP-3 in the skeletal muscle.From the results obtained, beneficial effects of metformin on visceral fat reduction has been

  16. Genomic research with human samples. Points of view from scientists and research subjects about disclosure of results and risks of genomic research. Ethical and empirical approach.

    Science.gov (United States)

    Valle Mansilla, José Ignacio

    2011-01-01

    Biomedical researchers often now ask subjects to donate samples to be deposited in biobanks. This is not only of interest to researchers, patients and society as a whole can benefit from the improvements in diagnosis, treatment, and prevention that the advent of genomic medicine portends. However, there is a growing debate regarding the social and ethical implications of creating biobanks and using stored human tissue samples for genomic research. Our aim was to identify factors related to both scientists and patients' preferences regarding the sort of information to convey to subjects about the results of the study and the risks related to genomic research. The method used was a survey addressed to 204 scientists and 279 donors from the U.S. and Spain. In this sample, researchers had already published genomic epidemiology studies; and research subjects had actually volunteered to donate a human sample for genomic research. Concerning the results, patients supported more frequently than scientists their right to know individual results from future genomic research. These differences were statistically significant after adjusting by the opportunity to receive genetic research results from the research they had previously participated and their perception of risks regarding genetic information compared to other clinical data. A slight majority of researchers supported informing participants about individual genomic results only if the reliability and clinical validity of the information had been established. Men were more likely than women to believe that patients should be informed of research results even if these conditions were not met. Also among patients, almost half of them would always prefer to be informed about individual results from future genomic research. The three main factors associated to a higher support of a non-limited access to individual results were: being from the US, having previously been offered individual information and considering

  17. Apoptosis may determine the release of skeletal alkaline phosphatase activity from human osteoblast-line cells.

    Science.gov (United States)

    Farley, J R; Stilt-Coffing, B

    2001-01-01

    Although quantitative measurement of skeletal alkaline phosphatase (sALP) activity in serum can provide an index of the rate of bone formation, the metabolic process that determines the release of sALP - from the surface of osteoblasts, into circulation-is unknown. The current studies were intended to examine the hypothesis that the release of sALP from human osteoblasts is a consequence of apoptotic cell death. We measured the release of sALP activity from human osteosarcoma (SaOS-2) cells and normal human bone cells, under basal conditions and in response to agents that increased apoptosis (TNF-a, okadiac acid) and agents that inhibit apoptosis (IGF-I, calpain, and caspase inhibitors). Apoptosis was determined by the presence of nucleosomes (histone-associated DNA) in the cytoplasm of the cells by using a commercial kit. The results of these studies showed that TNF-a and okadiac acid caused dose- and time-dependent increases in apoptosis in the SaOS-2 cells (r = 0.78 for doses of TNF-a and r = 0.93 for doses of okadiac acid, P sALP activity (e.g., r = 0.89 for TNF-a and r = 0.75 for okadiac acid, P sALP activity (P sALP activity (P sALP release. The associations between apoptosis and sALP release were not unique to osteosarcoma (i.e., SaOS-2) cells, but also seen with osteoblast-line cells derived from normal human bone. Together, these data demonstrate that the release of sALP activity from human osteoblast-line cells in vitro is associated with, and may be a consequence of, apoptotic cell death. These findings are consistent with the general hypothesis that the appearance of sALP activity in serum may reflect the turnover of osteoblast-line cells.

  18. Differences in the subjective and motivational properties of alcohol across alcohol use severity: application of a novel translational human laboratory paradigm.

    Science.gov (United States)

    Bujarski, Spencer; Jentsch, J David; Roche, Daniel J O; Ramchandani, Vijay A; Miotto, Karen; Ray, Lara A

    2018-05-08

    The Allostatic Model proposes that Alcohol Use Disorder (AUD) is associated with a transition in the motivational structure of alcohol drinking: from positive reinforcement in early-stage drinking to negative reinforcement in late-stage dependence. However, direct empirical support for this preclinical model from human experiments is limited. This study tests predictions derived from the Allostatic Model in humans. Specifically, this study tested whether alcohol use severity (1) independently predicts subjective responses to alcohol (SR; comprised of stimulation/hedonia, negative affect, sedation and craving domains), and alcohol self-administration and 2) moderates associations between domains of SR and alcohol self-administration. Heavy drinking participants ranging in severity of alcohol use and problems (N = 67) completed an intravenous alcohol administration paradigm combining an alcohol challenge (target BrAC = 60 mg%), with progressive ratio self-administration. Alcohol use severity was associated with greater baseline negative affect, sedation, and craving but did not predict changes in any SR domain during the alcohol challenge. Alcohol use severity also predicted greater self-administration. Craving during the alcohol challenge strongly predicted self-administration and sedation predicted lower self-administration. Neither stimulation, nor negative affect predicted self-administration. This study represents a novel approach to translating preclinical neuroscientific theories to the human laboratory. As expected, craving predicted self-administration and sedation was protective. Contrary to the predictions of the Allostatic Model, however, these results were inconsistent with a transition from positively to negatively reinforced alcohol consumption in severe AUD. Future studies that assess negative reinforcement in the context of an acute stressor are warranted.

  19. White Grape Juice Elicits a Lower Breath Hydrogen Response Compared with Apple Juice in Healthy Human Subjects: A Randomized Controlled Trial.

    Science.gov (United States)

    Erickson, Jennifer; Wang, Qi; Slavin, Joanne

    2017-06-01

    Diets low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPS) are used to manage symptoms in individuals with irritable bowel syndrome. Although effective at reducing symptoms, the diet can be complex and restrictive. In addition, there are still large gaps in the literature and many foods with unclear effects in the gastrointestinal (GI) tract, like fruit juice. Although many fruits are allowable on a low-FODMAP diet, consumption of all fruit juice is generally cautioned due to the large fructose load contained in juice, regardless of the glucose concentration. Very little research exists regarding the importance of limiting fructose load during a low-FODMAP diet; therefore, individuals following a low-FODMAP diet may be unnecessarily restricting their diets. To determine whether there is a difference in GI tolerance between juice from a high-FODMAP fruit (apple juice) and juice from a low-FODMAP fruit (white grape juice) in healthy human subjects. The goal is to provide insight into the role of juice in a low-FODMAP diet. A double-blind, randomized, controlled crossover study was conducted with 40 healthy adults. Fasted subjects consumed 12 oz of either apple juice or white grape juice. Breath hydrogen measures were taken at baseline, 1, 2, and 3 hours. Subjective GI tolerance surveys were completed at the same time intervals and at 12 and 24 hours. Breath hydrogen and GI symptoms were assessed with area under the curve analysis. Significance was determined with a two-sided t test with a P value juice resulted in a greater mean breath hydrogen area under the curve at 23.3 ppm/hour (95% CI 13.0 to 33.6) compared with white grape juice at 5.8 ppm/hour (95% CI -4.6 to 16.1) (Pjuices were well tolerated and neither produced any severe symptoms in healthy adults. White grape juice consumption resulted in only a small rise in breath hydrogen, which may suggest excluding foods only because of the high fructose load could be

  20. IMAGE-BASED IN VIVO QUANTITATIVE ASSESSMENT OF HUMAN AIRWAY OPENING AND CONTRACTILITY BY FIBER OPTICAL NASOPHARYNGOSCOPY IN HEALTHY AND ASTHMATIC SUBJECTS

    Directory of Open Access Journals (Sweden)

    LINHONG DENG

    2013-04-01

    Full Text Available Assessment of human airway lumen opening is important in diagnosing and understanding the mechanisms of airway dysfunctions such as the excessive airway narrowing in asthma and chronic obstructive pulmonary disease (COPD. Although there are indirect methods to evaluate the airway calibre, direct in vivo measurement of the airway calibre has not been commonly available. With recent advent of the flexible fiber optical nasopharyngoscope with video recording it has become possible to directly visualize the passages of upper and lower airways. However, quantitative analysis of the recorded video images has been technically challenging. Here, we describe an automatic image processing and analysis method that allows for batch analysis of the images recorded during the endoscopic procedure, thus facilitates image-based quantification of the airway opening. Video images of the airway lumen of volunteer subject were acquired using a fiber optical nasopharyngoscope, and subsequently processed using Gaussian smoothing filter, threshold segmentation, differentiation, and Canny image edge detection, respectively. Thus the area of the open airway lumen was identified and computed using a predetermined converter of the image scale to true dimension of the imaged object. With this method we measured the opening/narrowing of the glottis during tidal breathing with or without making "Hee" sound or cough. We also used this method to measure the opening/narrowing of the primary bronchus of either healthy or asthmatic subjects in response to histamine and/or albuterol treatment, which also provided an indicator of the airway contractility. Our results demonstrate that the image-based method accurately quantified the area change waveform of either the glottis or the bronchus as observed by using the optical nasopharygoscope. Importantly, the opening/narrowing of the airway lumen generally correlated with the airflow and resistance of the airways, and could

  1. Investigation of pH and Temperature Profiles in the GI Tract of Fasted Human Subjects Using the Intellicap(®) System.

    Science.gov (United States)

    Koziolek, Mirko; Grimm, Michael; Becker, Dieter; Iordanov, Ventzeslav; Zou, Hans; Shimizu, Jeff; Wanke, Christoph; Garbacz, Grzegorz; Weitschies, Werner

    2015-09-01

    Gastrointestinal (GI) pH and temperature profiles under fasted-state conditions were investigated in two studies with each 10 healthy human subjects using the IntelliCap(®) system. This telemetric drug delivery device enabled the determination of gastric emptying time, small bowel transit time, and colon arrival time by significant pH and temperature changes. The study results revealed high variability of GI pH and transit times. The gastric transit of IntelliCap(®) was characterized by high fluctuations of the pH with mean values ranging from pH 1.7 to pH 4.7. Gastric emptying was observed after 7-202 min (median: 30 min). During small bowel transit, which had a duration of 67-532 min (median: 247 min), pH values increased slightly from pH 5.9-6.3 in proximal parts to pH 7.4-7.8 in distal parts. Colonic pH conditions were characterized by values fluctuating mainly between pH 5 and pH 8. The pH profiles and transit times described in this work are highly relevant for the comprehension of drug delivery of solid oral dosage forms comprising ionizable drugs and excipients with pH-dependent solubility. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  2. Disturbances in the cerebral perfusion of human immune deficiency virus-1 seropositive asymptomatic subjects: A quantitative tomography study of 18 cases

    International Nuclear Information System (INIS)

    Tran Dinh, Y.R.; Mamo, H.; Cervoni, J.; Caulin, C.; Saimot, A.C.

    1990-01-01

    Quantitative measurements of cerebral blood flow (CBF) by xenon-133 ( 133 Xe) tomography, together with magnetic resonance imaging (MRI), electroencephalography (EEG), psychometric tests, and laboratory analyses were performed on 18 human immunodeficiency virus 1 (HIV-1) seropositive asymptomatic subjects. Abnormalities of cerebral perfusion were observed in 16 cases (88%). These abnormalities were particularly frequent in the frontal regions (77% of cases). MRI demonstrated leucoencephalopathy in only two cases. EEG showed only induced diffuse abnormalities in two cases. Psychometric tests showed restricted moderate disturbances in 55% of patients. These disturbances mostly concerned those sectors involved in cognitive functions and memorization. These results indicate that quantitative measurements of CBF by 133 Xe-SPECT is capable of detecting abnormalities of cerebral perfusion at a very early stage (Phase II) of HIV-1 infection. These abnormalities are indications of disturbances resulting from unidentified metabolic or vascular lesions. This technique appears to be superior to MRI at this stage of the disease's development. It could provide objective information leading to earlier treatment, and prove useful in evaluating potential antiviral chemotherapy

  3. L’Homme, un itinéraire vietnamien. Humanisme et sujet humain au xxe siècle Man, a Vietnamese Itinerary. Humanism and the Human Subject in the 20th Century

    Directory of Open Access Journals (Sweden)

    Daniel Hémery

    2009-10-01

    Full Text Available Cette étude interroge la confrontation qui s’est instaurée au Vietnam depuis le milieu du xixe siècle – et sans doute bien avant – entre la conception de l’homme-individu importée par les Occidentaux en Asie orientale et les philosophies du sujet qui s’y étaient développées depuis l’antiquité chinoise. Cette confrontation a-t-elle abouti dans la culture vietnamienne à une réévaluation socialement acceptée du statut du sujet et sur une nouvelle figure de l’humanisme ? Quel bilan provisoire dresser ?This paper examines the mid 19th century encounter in Vietnamese culture of the concept of the individual imported by Westerners to Far East Asia with the philosophical tradition of the human subject that has developed in China since the classic period. Did this conflictual encounter result in a new, socially acceptable evaluation of the human statute and in a renewed Vietnamese humanism? This article concludes with a provisional assessment of a cultural confrontation.

  4. The Impact of Energy Substrates, Hormone Level and Subject-Related Factors on Physiologic Myocardial {sup 18}F-FDG Uptake in Normal Humans

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Juhye; Kong, Eunjung; Chun, Kyungah; Cho, Ihnho [Yeung-Nam Univ. Hoepital, Daegu (Korea, Republic of)

    2013-12-15

    In a whole-body {sup 18}F-FDG PET/CT, non-specific {sup 18}F-FDG uptake of the myocardium is a common finding and can be very variable, ranging from background activity to intense accumulation and inhomogeneity. We investigated the effect of energy substrates and plasma/serum hormones that may have an influence on myocardial {sup 18}F-FDG uptake. F-FDG PET/CT was performed on 100 normal volunteers from November 2007 to August 2008. Blood samples were taken just before {sup 18}F-FDG injection from all subjects. Myocardial {sup 18}F-FDG uptake was measured as the mean (SUVmean) and maximal (SUV{sub max}) standardized uptake value. The myocardium was delineated on the PET/CT image by a manual volume of interest (VOI).We analyzed the influence of age, sex, presence of diabetes, fasting duration, insulin, glucagon, fasting glucose, lactate, free fatty acid (FFA), epinephrine (EPi), norepinephrine (NEp), free triiodothyronine (T3), free thyroxine (T4), thyroid-stimulating hormone (TSH) and body mass index (BMI). Overall, 92 subjects (mean age 50.28±8.30, male 57) were enrolled. The average of myocardial SUVmean was 2.08 and of myocardial SUV{sub max} was 4.57, respectively and there was a strong linear correlation between SUVmean and SUV{sub max} (r =0.98). FFA and fasting duration showed significant negative correlation with myocardial {sup 18}F-FDG uptake, respectively (r =-0.40 in FFA; r =-0.41 in fasting duration). No significant relationships were observed between myocardial uptake and age, sex, presence of diabetics, insulin, glucagon, fasting glucose, lactate, EPi, NEp, free T3, free T4, TSH and BMI. Myocardial {sup 18}F-FDG uptake decreases with longer fasting duration and higher FFA level in normal humans. Modulating myocardial uptake could improve {sup 18}F-FDG PET/CT imaging for specific oncologic and cardiovascular indications.

  5. FA1 Induces Pro-Inflammatory and Anti-Adipogenic Pathways/Markers in Human Myotubes Established from Lean, Obese, and Type 2 Diabetic Subjects but Not Insulin Resistance

    DEFF Research Database (Denmark)

    Abdallah, Basem M; Beck-Nielsen, Henning; Gaster, Michael

    2013-01-01

    Aims: Delta like 1/fetal antigen 1 (Dlk1/FA1) is a protein secreted by hormone producing cells in adult human and mice that is known to inhibit adipogenesis. Recent studies demonstrated the role of Dlk1/FA1 in inducing insulin resistance in mice. To investigate the involvement of circulating Dlk1....../FA1 in insulin resistance and type 2 diabetes in human subjects, we studied the effects of chronic FA1 on the intermediary metabolism in myotubes established from lean, obese, and type 2 diabetic (T2D) subjects. Methods: Myotube cultures were established from lean and obese control subjects......, and obese T2D subjects and treated with soluble FA1 for 4 days supplemented with/without palmitate (PA). Lipid- and glucose metabolism were studied with labeled precursors while quantitative expression of genes was analyzed using real-time PCR. Results: Diabetic myotubes express significantly reduced...

  6. The Effect of Upper Body Mass and Initial Knee Flexion on the Injury Outcome of Post Mortem Human Subject Pedestrian Isolated Legs.

    Science.gov (United States)

    Petit, Philippe; Trosseille, Xavier; Dufaure, Nicolas; Dubois, Denis; Potier, Pascal; Vallancien, Guy

    2014-11-01

    In the ECE 127 Regulation on pedestrian leg protection, as well as in the Euro NCAP test protocol, a legform impactor hits the vehicle at the speed of 40 kph. In these tests, the knee is fully extended and the leg is not coupled to the upper body. However, the typical configuration of a pedestrian impact differs since the knee is flexed during most of the gait cycle and the hip joint applies an unknown force to the femur. This study aimed at investigating the influence of the inertia of the upper body (modelled using an upper body mass fixed at the proximal end of the femur) and the initial knee flexion angle on the lower limb injury outcome. In total, 18 tests were conducted on 18 legs from 9 Post Mortem Human Subjects (PMHS). The principle of these tests was to impact the leg at 40 kph using a sled equipped with 3 crushing steel tubes, the stiffness of which were representative of the front face of a European sedan (bonnet leading edge, bumper and spoiler). The mass of the equipped sled was 74.5 kg. The test matrix was designed to perform 4 tests in 4 configurations combining two upper body masses (either 0 or 3 kg) and two knee angles (0 or 20 degrees) at 40 kph (11 m/s) plus 2 tests at 9 m/s. Autopsies were performed on the lower limbs and an injury assessment was established. The findings of this study were first that the increase of the upper body mass resulted in more severe injuries, second that an initial flexion of the knee, corresponding to its natural position during the gait cycle, decreased the severity of the injuries, and third that based on the injury outcome, a test conducted with no upper body mass and the knee fully extended was as severe as a test conducted with a 3 kg upper body mass and an initial knee flexion of 20°.

  7. Clinical progress of human papillomavirus genotypes and their persistent infection in subjects with atypical squamous cells of undetermined significance cytology: Statistical and latent Dirichlet allocation analysis

    Science.gov (United States)

    Kim, Yee Suk; Lee, Sungin; Zong, Nansu; Kahng, Jimin

    2017-01-01

    The present study aimed to investigate differences in prognosis based on human papillomavirus (HPV) infection, persistent infection and genotype variations for patients exhibiting atypical squamous cells of undetermined significance (ASCUS) in their initial Papanicolaou (PAP) test results. A latent Dirichlet allocation (LDA)-based tool was developed that may offer a facilitated means of communication to be employed during patient-doctor consultations. The present study assessed 491 patients (139 HPV-positive and 352 HPV-negative cases) with a PAP test result of ASCUS with a follow-up period ≥2 years. Patients underwent PAP and HPV DNA chip tests between January 2006 and January 2009. The HPV-positive subjects were followed up with at least 2 instances of PAP and HPV DNA chip tests. The most common genotypes observed were HPV-16 (25.9%, 36/139), HPV-52 (14.4%, 20/139), HPV-58 (13.7%, 19/139), HPV-56 (11.5%, 16/139), HPV-51 (9.4%, 13/139) and HPV-18 (8.6%, 12/139). A total of 33.3% (12/36) patients positive for HPV-16 had cervical intraepithelial neoplasia (CIN)2 or a worse result, which was significantly higher than the prevalence of CIN2 of 1.8% (8/455) in patients negative for HPV-16 (Paged ≥51 years (38.7%) than in those aged ≤50 years (20.4%; P=0.036). Progression from persistent infection to CIN2 or worse (19/34, 55.9%) was higher than clearance (0/105, 0.0%; Page and long infection period with a clinical progression of CIN2 or worse. Therefore, LDA results may be presented as explanatory evidence during time-constrained patient-doctor consultations in order to deliver information regarding the patient's status. PMID:28587376

  8. Impact of Periodontal Therapy on the Subgingival Microbiota of Severe Periodontitis: Comparison between Good Responders and “Refractory” Subjects by the Human Oral Microbe Identification Microarray (HOMIM)

    Science.gov (United States)

    Colombo, Ana Paula V.; Bennet, Susan; Cotton, Sean L.; Goodson, J. Max; Kent, Ralph; Haffajee, Anne D.; Socransky, Sigmund S.; Hasturk, Hatice; Van Dyke, Thomas E.; Dewhirst, Floyd E.; Paster, Bruce J.

    2014-01-01

    Aim This study compared the changes on the subgingival microbiota of subjects with “refractory” periodontitis (RP) or treatable periodontitis (GR) before and after periodontal therapy by using the Human Oral Microbe Identification Microarray (HOMIM). Methods Individuals with chronic periodontitis were classified as RP (n=17) based on mean attachment loss (AL) and/or >3 sites with AL ≥2.5 mm after scaling and root planing, surgery and systemically administered amoxicillin and metronidazole or as GR (n=30) based on mean attachment gain and no sites with AL ≥2.5 mm after treatment. Subgingival plaque samples were taken at baseline and 15 months after treatment and analyzed for the presence of 300 species by HOMIM analysis. Significant differences in taxa before and after therapy were sought using the Wilcoxon test. Results The majority of species evaluated decreased in prevalence in both groups after treatment; however, only a small subset of organisms was significantly affected. Species that increased or persisted in high frequency in RP but were significantly reduced in GR included Bacteroidetes sp., Porphyromonas endodontalis, Porphyromonas gingivalis, Prevotella spp., Tannerella forsythia, Dialister spp., Selenomonas spp., Catonella morbi, Eubacterium spp., Filifactor alocis, Parvimonas micra, Peptostreptococcus sp. OT113, Fusobacterium sp. OT203, Pseudoramibacter alactolyticus, Streptococcus intermedius or Streptococcus constellatus and Shuttlesworthia satelles. In contrast, Capnocytophaga sputigena, Cardiobacterium hominis, Gemella haemolysans, Haemophilus parainfluenzae, Kingella oralis, Lautropia mirabilis, Neisseria elongata, Rothia dentocariosa, Streptococcus australis and Veillonella spp. were more associated with therapeutic success. Conclusion Persistence of putative and novel periodontal pathogens, as well as low prevalence of beneficial species was associated with chronic “refractory” periodontitis. PMID:22324467

  9. The relation between maximal voluntary force in m. palmaris longus and the temporal and spatial summation of muscle fiber recruitment in human subjects

    DEFF Research Database (Denmark)

    Claudel, Cécyl G.; Ahmed, Waqas; Elbrønd, Vibeke S.

    2018-01-01

    that AMG is a noninvasive method which can be readily applied to accurately describe how a subject uses a given muscle during any given movement. These findings have relevance when considering training strategies in subjects with muscle trauma or disease, in the elderly, or for both amateur and top...

  10. The effect of covert changes in energy density of preloads on subsequent ad libitum energy intake in lean and obese human subjects.

    Science.gov (United States)

    Durrant, M L; Royston, J P; Wloch, R T; Garrow, J S

    1982-01-01

    1. Covert changes in energy intake were made by giving preloads of disguised energy density three times daily to 14 obese and 6 lean subjects. 2. The preloads contained 2.51 MJ (600 kcal)/d on days 2 and 3 and either 3.77 MJ (900 kcal)/d or 1.26 MJ (300 kcal/d) on days 4 and 5 and 1.26 MJ (300 kcal)/d or 3.77 MJ (900 kcal)/d on days 6 and 7. The order of testing was alternated for each subject. 3. Subsequent energy intake at each meal (lunch, dinner and breakfast) was measured with an automated food-dispensing machine. 4. Overall the obese subjects ate significantly less from the machine, 3.28 +/- 1.89 MJ (785 +/- 452 kcal)/d, than the lean subjects, 6.03 +/- 1.26 MJ (1442 +/- 300 kcal)/d. 5. Both groups of subjects adjusted their energy intake in the right direction to counterbalance the effect of the preloads but the lean subjects changed their intake by an average of 0.74 MJ (176 kcal)/d compared with the obese subjects who changed their intake by an average of 0.29 MJ (70 kcal)/d. 6. Although the lean subjects were better at adjusting their energy intake than the obese subjects, regulation was still imprecise relative to the 2.51 MJ (600 kcal)/d difference in energy intake that was imposed. 7. There were no significant differences in hunger or appetite between subjects or test situations.

  11. Acquisition of anoikis resistance in human osteosarcoma cells does not alter sensitivity to chemotherapeutic agents

    International Nuclear Information System (INIS)

    Díaz-Montero, C Marcela; McIntyre, Bradley W

    2005-01-01

    Chemotherapy-induced cell death can involve the induction of apoptosis. Thus, aberrant function of the pathways involved might result in chemoresistance. Since cell adhesion to the extracellular matrix acts as a survival factor that homeostatically maintains normal tissue architecture, it was tested whether acquisition of resistance to deadhesion-induced apoptosis (anoikis) in human osteosarcoma would result in resistance to chemotherapy. Osteosarcoma cell lines (SAOS-2 and TE-85) obtained from ATCC and were maintained in complete Eagle's MEM medium. Suspension culture was established by placing cells in tissue culture wells coated with poly-HEMA. Cell cytotoxicity was determined using a live/dead cytotoxicity assay. Cell cycle/apoptosis analyses were performed using propidium iodide (PI) staining with subsequent FACS analysis. Apoptosis was also assayed by Annexin-FITC/PI staining. Etoposide, adriamycin, vinblastine, cisplatin and paclitaxel were able to induce apoptosis in human osteosarcoma cells SAOS-2 regardless of their anoikis resistance phenotype or the culture conditions (adhered vs. suspended). Moreover, suspended anoikis resistant TE-85 cells (TE-85ar) retained their sensitivity to chemotherapy as well. Acquisition of anoikis resistance in human osteosarcoma cells does not result in a generalized resistance to all apoptotic stimuli, including chemotherapy. Moreover, our results suggest that the pathways regulating anoikis resistance and chemotherapy resistance might involve the action of different mediators

  12. Acquisition of anoikis resistance in human osteosarcoma cells does not alter sensitivity to chemotherapeutic agents

    Directory of Open Access Journals (Sweden)

    McIntyre Bradley W

    2005-04-01

    Full Text Available Abstract Background Chemotherapy-induced cell death can involve the induction of apoptosis. Thus, aberrant function of the pathways involved might result in chemoresistance. Since cell adhesion to the extracellular matrix acts as a survival factor that homeostatically maintains normal tissue architecture, it was tested whether acquisition of resistance to deadhesion-induced apoptosis (anoikis in human osteosarcoma would result in resistance to chemotherapy. Methods Osteosarcoma cell lines (SAOS-2 and TE-85 obtained from ATCC and were maintained in complete Eagle's MEM medium. Suspension culture was established by placing cells in tissue culture wells coated with poly-HEMA. Cell cytotoxicity was determined using a live/dead cytotoxicity assay. Cell cycle/apoptosis analyses were performed using propidium iodide (PI staining with subsequent FACS analysis. Apoptosis was also assayed by Annexin-FITC/PI staining. Results Etoposide, adriamycin, vinblastine, cisplatin and paclitaxel were able to induce apoptosis in human osteosarcoma cells SAOS-2 regardless of their anoikis resistance phenotype or the culture conditions (adhered vs. suspended. Moreover, suspended anoikis resistant TE-85 cells (TE-85ar retained their sensitivity to chemotherapy as well. Conclusion Acquisition of anoikis resistance in human osteosarcoma cells does not result in a generalized resistance to all apoptotic stimuli, including chemotherapy. Moreover, our results suggest that the pathways regulating anoikis resistance and chemotherapy resistance might involve the action of different mediators.

  13. Human Papillomavirus neutralizing and cross-reactive antibodies induced in HIV-positive subjects after vaccination with quadrivalent and bivalent HPV vaccines

    DEFF Research Database (Denmark)

    Faust, Helena; Nielsen, Lars Toft; Sehr, Peter

    2016-01-01

    Ninety-one HIV-infected individuals (61 men and 30 women) were randomized to vaccination either with quadrivalent (Gardasil™) or bivalent (Cervarix™) HPV vaccine. Neutralizing and specific HPV-binding serum antibodies were measured at baseline and 12 months after the first vaccine dose. Presence...... of neutralizing and binding antibodies had good agreement (average Kappa for HPV types 6, 11, 16, 18, 31, 33 and 45 was 0.65). At baseline, 88% of subjects had antibodies against at least one genital HPV. Following vaccination with Cervarix™, all subjects became seropositive for HPV16 and 18. After Gardasil......™ vaccination, 96% of subjects seroconverted for HPV16 and 73% for HPV18. Levels of HPV16-specific antibodies were 10IU in 85% of study subjects after vaccination. Antibodies against non-vaccine HPV types appeared after Gardasil...

  14. An investigation of human body model morphing for the assessment of abdomen responses to impact against a population of test subjects.

    Science.gov (United States)

    Beillas, Philippe; Berthet, Fabien

    2017-05-29

    Human body models have the potential to better describe the human anatomy and variability than dummies. However, data sets available to verify the human response to impact are typically limited in numbers, and they are not size or gender specific. The objective of this study was to investigate the use of model morphing methodologies within that context. In this study, a simple human model scaling methodology was developed to morph two detailed human models (Global Human Body Model Consortium models 50th male, M50, and 5th female, F05) to the dimensions of post mortem human surrogates (PMHS) used in published literature. The methodology was then successfully applied to 52 PMHS tested in 14 impact conditions loading the abdomen. The corresponding 104 simulations were compared to the responses of the PMHS and to the responses of the baseline models without scaling (28 simulations). The responses were analysed using the CORA method and peak values. The results suggest that model scaling leads to an improvement of the predicted force and deflection but has more marginal effects on the predicted abdominal compressions. M50 and F05 models scaled to the same PMHS were also found to have similar external responses, but large differences were found between the two sets of models for the strain energy densities in the liver and the spleen for mid-abdomen impact simulations. These differences, which were attributed to the anatomical differences in the abdomen of the baseline models, highlight the importance of the selection of the impact condition for simulation studies, especially if the organ location is not known in the test. While the methodology could be further improved, it shows the feasibility of using model scaling methodologies to compare human models of different sizes and to evaluate scaling approaches within the context of human model validation.

  15. FORMATION OF THE SUBJECTIVE (VIRTUAL) MODELS OF PHYSICAL AND SOCIAL REALITY BY HUMAN CONSCIOUSNESS AND GIVING THEM UNDUE ONTOLOGICAL STATUS (HYPOSTATIZATIONS)

    OpenAIRE

    Lutsenko Y. V.

    2015-01-01

    On the one hand, man is a physical object and a person. Therefore, we interact with the reality, on one hand, directly as a physical object, but on the other hand as a person, i.e. indirectly through our psyche. On the basis of information from the senses, the consciousness of a person creates a subjective model of reality. A man mistakes his subjective model of reality for reality itself, i.e. unnecessarily assigns an ontological status, by the hypostatizations. In fact, as the reality a man...

  16. Fetal and perinatal outcomes in type 1 diabetes pregnancy: a randomized study comparing insulin aspart with human insulin in 322 subjects

    DEFF Research Database (Denmark)

    Hod, Moshe; Damm, Peter; Kaaja, Risto

    2008-01-01

    The objective of the study was a comparison of insulin aspart (IAsp) with human insulin (HI) in basal-bolus therapy with neutral protamine Hagedorn for fetal and perinatal outcomes of type 1 diabetes in pregnancy.......The objective of the study was a comparison of insulin aspart (IAsp) with human insulin (HI) in basal-bolus therapy with neutral protamine Hagedorn for fetal and perinatal outcomes of type 1 diabetes in pregnancy....

  17. Using Academic Journals to Help Students Learn Subject Matter Content, Develop and Practice Critical Reasoning Skills, and Reflect on Personal Values in Food Science and Human Nutrition Classes

    Science.gov (United States)

    Iwaoka, Wayne T.; Crosetti, Lea M.

    2008-01-01

    It has been reported that students learn best when they use a wide variety of techniques to understand the information of the discipline, be it visual, auditory, discussion with others, metacognition, hands-on activities, or writing about the subject. We report in this article the use of academic journals not only as an aid for students to learn…

  18. Safety and Efficacy of NEXT-II®, a Novel Water-Soluble, Undenatured Type II Collagen inHealthy Human SubjectsSuffering from Occasional Knee Joint Pain

    Directory of Open Access Journals (Sweden)

    Orie Yoshinari

    2015-07-01

    Full Text Available Background: Oral administration of a novel water-soluble undenatured type II collagen (NEXT-II® has been demonstrated to ameliorate the signs and symptoms of rheumatoid arthritis (RA in animal models. In the present investigation, we conducted a pilot study to examine the efficacy and safety of NEXT-II® in borderline subjects defined as healthy and non-diseased state, but with potential risks in knee joint health. Method: We employed Western Ontario McMaster Index (WOMAC score and Visual Analog Scale (VAS scores to assess the extent of improvement in the knee joints in these volunteers following supplementation of 40 mg NEXT-II® (10 mg as undenatured type II collagen over a period of 12 weeks. Result: The results demonstrated that NEXT-II® treatment significantly reduced WOMAC and VAS scores compared to subjects at baseline. Specifically, in the evaluation using VAS, the borderline subjects at resting, walking, and going up and down the stairs revealed significant improvement when compared to the baseline. Conclusion: The results of the studies demonstrated that NEXT-II® might be an ingredient which is safe and effective in the application of dietary supplement in ameliorating joint pain and symptoms of the borderline subjects without any adverse events.

  19. Steady-State pharmacokinetics and tolerability of trans-resveratrol 2000 mg twice daily with food, quercetin and alcohol (ethanol) in healthy human subjects.

    Science.gov (United States)

    la Porte, Charles; Voduc, Nha; Zhang, Guijun; Seguin, Isabelle; Tardiff, Danielle; Singhal, Neera; Cameron, D William

    2010-07-01

    Trans-resveratrol is a polyphenol, which is found in red wine and has cancer chemo-preventive properties and disease-preventive properties. The pharmacokinetics of trans-resveratrol have been investigated in single-dose studies and in studies with relatively low dosages. The present study aimed to investigate the steady-state pharmacokinetics and tolerability of trans-resveratrol 2000 mg twice daily with food, quercetin and alcohol (ethanol). This was a two-period, open-label, single-arm, within-subject control study in eight healthy subjects. The steady-state 12-hour pharmacokinetics of trans-resveratrol 2000 mg twice daily were studied with a standard breakfast, a high-fat breakfast, quercetin 500 mg twice daily and 5% alcohol 100 mL. Trans-resveratrol plasma concentrations were determined using liquid chromatography with tandem mass spectrometry. The mean (SD) area under the plasma concentration-time curve from 0 to 12 hours (AUC(12)) and maximum plasma concentration (C(max)) of trans-resveratrol were 3558 (2195) ng * h/mL and 1274 (790) ng/mL, respectively, after the standard breakfast. The high-fat breakfast significantly decreased the AUC(12) and C(max) by 45% and 46%, respectively, when compared with the standard breakfast. Quercetin 500 mg twice daily or 5% alcohol 100 mL did not influence trans-resveratrol pharmacokinetics. Diarrhoea was reported in six of the eight subjects. Significant but not clinically relevant changes from baseline were observed in serum potassium and total bilirubin levels. Trans-resveratrol 2000 mg twice daily resulted in adequate exposure and was well tolerated by healthy subjects, although diarrhoea was frequently observed. In order to maximize trans-resveratrol exposure, it should be taken with a standard breakfast and not with a high-fat meal. Furthermore, combined intake with quercetin or alcohol did not influence trans-resveratrol exposure.

  20. The relationship of normal body temperature, end-expired breath temperature, and BAC/BrAC ratio in 98 physically fit human test subjects.

    Science.gov (United States)

    Cowan, J Mack; Burris, James M; Hughes, James R; Cunningham, Margaret P

    2010-06-01

    The relationship between normal body temperature, end-expired breath temperature, and blood alcohol concentration (BAC)/breath alcohol concentration (BrAC) ratio was studied in 98 subjects (84 men, 14 women). Subjects consumed alcohol sufficient to produce a BrAC of at least 0.06 g/210 L 45-75 min after drinking. Breath samples were analyzed using an Intoxilyzer 8000 specially equipped to measure breath temperature. Venous blood samples and body temperatures were then taken. The mean body temperature of the men (36.6 degrees C) was lower than the women (37.0 degrees C); however, their mean breath temperatures were virtually identical (men: 34.5 degrees C; women: 34.6 degrees C). The BAC exceeded the BrAC for every subject. BAC/BrAC ratios were calculated from the BAC and BrAC analytical results. There was no difference in the BAC/BrAC ratios for men (1:2379) and women (1:2385). The correlation between BAC and BrAC was high (r = 0.938, p body temperature and end-expired breath temperature, body temperature and BAC/BrAC ratio, and breath temperature and BAC/BrAC ratio were much lower. Neither normal body temperature nor end-expired breath temperature was strongly associated with BAC/BrAC ratio.

  1. p53-dependent and p53-independent anticancer activity of a new indole derivative in human osteosarcoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Cappadone, C., E-mail: concettina.cappadone@unibo.it [Department of Pharmacy and Biotechnology, University of Bologna, Bologna (Italy); Stefanelli, C. [Department for Life Quality Studies, University of Bologna, Rimini Campus, Rimini (Italy); Malucelli, E. [Department of Pharmacy and Biotechnology, University of Bologna, Bologna (Italy); Zini, M. [Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna (Italy); Onofrillo, C. [Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna (Italy); Locatelli, A.; Rambaldi, M.; Sargenti, A. [Department of Pharmacy and Biotechnology, University of Bologna, Bologna (Italy); Merolle, L. [ELETTRA–Sincrotrone Trieste S.C.p.A., Trieste (Italy); Farruggia, G. [Department of Pharmacy and Biotechnology, University of Bologna, Bologna (Italy); National Institute of Biostructures and Biosystems, Roma (Italy); Graziadio, A. [Department of Pharmacy and Biotechnology, University of Bologna, Bologna (Italy); Montanaro, L. [Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna (Italy); Iotti, S. [Department of Pharmacy and Biotechnology, University of Bologna, Bologna (Italy); National Institute of Biostructures and Biosystems, Roma (Italy)

    2015-11-13

    Osteosarcoma (OS) is the most common primary malignant tumor of bone, occurring most frequently in children and adolescents. The mechanism of formation and development of OS have been studied for a long time. Tumor suppressor pathway governed by p53 gene are known to be involved in the pathogenesis of osteosarcoma. Moreover, loss of wild-type p53 activity is thought to be a major predictor of failure to respond to chemotherapy in various human cancers. In previous studies, we described the activity of a new indole derivative, NSC743420, belonging to the tubulin inhibitors family, capable to induce apoptosis and arrest of the cell cycle in the G2/M phase of various cancer cell lines. However, this molecule has never been tested on OS cell line. Here we address the activity of NSC743420 by examine whether differences in the p53 status could influence its effects on cell proliferation and death of OS cells. In particular, we compared the effect of the tested molecule on p53-wild type and p53-silenced U2OS cells, and on SaOS2 cell line, which is null for p53. Our results demonstrated that NSC743420 reduces OS cell proliferation by p53-dependent and p53-independent mechanisms. In particular, the molecule induces proliferative arrest that culminate to apoptosis in SaOS2 p53-null cells, while it brings a cytostatic and differentiating effect in U2OS cells, characterized by the cell cycle arrest in G0/G1 phase and increased alkaline phosphatase activity. - Highlights: • The indole derivative NSC743420 induces antitumor effects on osteosarcoma cells. • p53 status could drive the activity of antitumor agents on osteosarcoma cells. • NSC743420 induces cytostatic and differentiating effects on U2OS cells. • NSC743420 causes apoptosis on p53-null SaOS2 cells.

  2. p53-dependent and p53-independent anticancer activity of a new indole derivative in human osteosarcoma cells

    International Nuclear Information System (INIS)

    Cappadone, C.; Stefanelli, C.; Malucelli, E.; Zini, M.; Onofrillo, C.; Locatelli, A.; Rambaldi, M.; Sargenti, A.; Merolle, L.; Farruggia, G.; Graziadio, A.; Montanaro, L.; Iotti, S.

    2015-01-01

    Osteosarcoma (OS) is the most common primary malignant tumor of bone, occurring most frequently in children and adolescents. The mechanism of formation and development of OS have been studied for a long time. Tumor suppressor pathway governed by p53 gene are known to be involved in the pathogenesis of osteosarcoma. Moreover, loss of wild-type p53 activity is thought to be a major predictor of failure to respond to chemotherapy in various human cancers. In previous studies, we described the activity of a new indole derivative, NSC743420, belonging to the tubulin inhibitors family, capable to induce apoptosis and arrest of the cell cycle in the G2/M phase of various cancer cell lines. However, this molecule has never been tested on OS cell line. Here we address the activity of NSC743420 by examine whether differences in the p53 status could influence its effects on cell proliferation and death of OS cells. In particular, we compared the effect of the tested molecule on p53-wild type and p53-silenced U2OS cells, and on SaOS2 cell line, which is null for p53. Our results demonstrated that NSC743420 reduces OS cell proliferation by p53-dependent and p53-independent mechanisms. In particular, the molecule induces proliferative arrest that culminate to apoptosis in SaOS2 p53-null cells, while it brings a cytostatic and differentiating effect in U2OS cells, characterized by the cell cycle arrest in G0/G1 phase and increased alkaline phosphatase activity. - Highlights: • The indole derivative NSC743420 induces antitumor effects on osteosarcoma cells. • p53 status could drive the activity of antitumor agents on osteosarcoma cells. • NSC743420 induces cytostatic and differentiating effects on U2OS cells. • NSC743420 causes apoptosis on p53-null SaOS2 cells.

  3. Vision as subjective perception

    International Nuclear Information System (INIS)

    Reppas, J.B.; Dale, A.; Sereno, M.; Tootell, R.

    1996-01-01

    The human brain is not very different of the monkey's one: at least, its visual cortex is organized as a similar scheme. Specialized areas in the movement analysis are found and others in the forms perception. In this work, the author tries to answer to the following questions: 1)why so many visual areas? What are exactly their role in vision? Thirteen years of experimentation have not allowed to answer to these questions. The cerebral NMR imaging gives the opportunity of understanding the subjective perception of the visual world. One step which is particularly described in this work is to know how the visual cortex reacts to the optical illusions. (O.M.)

  4. Experimental characterization of post rigor mortis human muscle subjected to small tensile strains and application of a simple hyper-viscoelastic model.

    Science.gov (United States)

    Gras, Laure-Lise; Laporte, Sébastien; Viot, Philippe; Mitton, David

    2014-10-01

    In models developed for impact biomechanics, muscles are usually represented with one-dimensional elements having active and passive properties. The passive properties of muscles are most often obtained from experiments performed on animal muscles, because limited data on human muscle are available. The aim of this study is thus to characterize the passive response of a human muscle in tension. Tensile tests at different strain rates (0.0045, 0.045, and 0.45 s⁻¹) were performed on 10 extensor carpi ulnaris muscles. A model composed of a nonlinear element defined with an exponential law in parallel with one or two Maxwell elements and considering basic geometrical features was proposed. The experimental results were used to identify the parameters of the model. The results for the first- and second-order model were similar. For the first-order model, the mean parameters of the exponential law are as follows: Young's modulus E (6.8 MPa) and curvature parameter α (31.6). The Maxwell element mean values are as follows: viscosity parameter η (1.2 MPa s) and relaxation time τ (0.25 s). Our results provide new data on a human muscle tested in vitro and a simple model with basic geometrical features that represent its behavior in tension under three different strain rates. This approach could be used to assess the behavior of other human muscles. © IMechE 2014.

  5. A comparison of human jaw muscle cross-sectional area and volume in long- and short-face subjects, using MRI

    NARCIS (Netherlands)

    van Spronsena, P. H.; van Ginkel, F. C.; van Schijndel, R. A.; Castelijns, J. A.; Tuinzing, D. B.

    Objective: In humans, the vertical craniofacial dimensions vary significantly with the size of the jaw muscles, which are regarded as important controlling factors of craniofacial growth. The functional relevance of the maximum cross-sectional area (CSA), indicating maximum muscle strength, is

  6. A comparison of human jaw muscle cross-sectional area and volume in long- and short-face subjects, using MRI

    NARCIS (Netherlands)

    Boom, H.P.W.; van Spronsen, P.H.; van Ginkel, F.C.; van Schijndel, R.A.; Castelijns, J.A.; Tuinzing, D.B.

    2008-01-01

    Objective In humans, the vertical craniofacial dimensions vary significantly with the size of the jaw muscles, which are regarded as important controlling factors of craniofacial growth. The functional relevance of the maximum cross-sectional area (CSA), indicating maximum muscle strength, is

  7. A comparison of human jaw muscle cross-sectional area and volume in long- and short-face subjects, using MRI

    NARCIS (Netherlands)

    Boom, H.P.; van Spronsen, P.H.; van Ginkel, F.C.; van Schijndel, R.A.; Castelijns, J.A.; Tuinzing, D.B.

    2008-01-01

    Objective: In humans, the vertical craniofacial dimensions vary significantly with the size of the jaw muscles, which are regarded as important controlling factors of craniofacial growth. The functional relevance of the maximum cross-sectional area (CSA), indicating maximum muscle strength, is

  8. TiO2 nanoparticles disrupt cell adhesion and the architecture of cytoskeletal networks of human osteoblast-like cells in a size dependent manner.

    Science.gov (United States)

    Ibrahim, Mohamed; Schoelermann, Julia; Mustafa, Kamal; Cimpan, Mihaela R

    2018-04-30

    Human exposure to titanium dioxide nanoparticles (nano-TiO 2 ) is increasing. An internal source of nano-TiO 2 is represented by titanium-based orthopedic and dental implants can release nanoparticles (NPs) upon abrasion. Little is known about how the size of NPs influences their interaction with cytoskeletal protein networks and the functional/homeostatic consequences that might follow at the implant-bone interface with regard to osteoblasts. We investigated the effects of size of anatase nano-TiO 2 on SaOS-2 human osteoblast-like cells exposed to clinically relevant concentrations (0.05, 0.5, 5 mg/L) of 5 and 40 nm spherical nano-TiO 2 . Cell viability and proliferation, adhesion, spread and migration were assessed, as well as the orientation of actin and microtubule cytoskeletal networks. The phosphorylation of focal adhesion kinase (p-FAK Y397 ) and the expression of vinculin in response to nano-TiO 2 were also assessed. Treatment with nano-TiO 2 disrupted the actin and microtubule cytoskeletal networks leading to morphological modifications of SaOS-2 cells. The phosphorylation of p-FAK Y397 and the expression of vinculin were also modified depending on the particle size, which affected cell adhesion. Consequently, the cell migration was significantly impaired in the 5 nm-exposed cells compared to unexposed cells. The present work shows that the orientation of cytoskeletal networks and the focal adhesion proteins and subsequently the adhesion, spread and migration of SaOS-2 cells were affected by the selected nano-TiO 2 in a size dependent manner. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

  9. Quantification of nimesulide in human plasma by high-performance liquid chromatography with ultraviolet detector (HPLC-UV): application to pharmacokinetic studies in 28 healthy Korean subjects.

    Science.gov (United States)

    Kim, Mi-Sun; Park, Yoo-Sin; Kim, Shin-Hee; Kim, Sang-Yeon; Lee, Min-Ho; Kim, Youn-Hee; Kim, Do-Wan; Yang, Seok-Chul; Kang, Ju-Seop

    2012-05-01

    Nimesulide is a selective COX-2 inhibitor that is as effective as the classical non-acidic nonsteroidal anti-inflammatory drugs in the relief of various pain and inflammatory conditions, but is better tolerated with lower incidences of adverse effects than other drugs. After oral dose of 100 mg nimesulide to western subjects, a mean maximal concentration (C(max)) of 2.86 ∼ 6.5 µg/mL was reached at 1.22 ∼ 2.75 h and mean t(1/2β) of 1.8 ∼ 4.74 h. This study developed a robust method for quantification of nimesulide for the pharmacokinetics and suitability of its dosage in Korea and compared its suitability with other racial populations. Nimesulide and internal standard were extracted from acidified samples with methyl tert-butyl ether and analyzed by high-performance liquid chromatography with ultraviolet detection (HPLC-UV). The 28 healthy volunteers took 2 tablets of 100 mg nimesulide and blood concentrations were analyzed during the 24 h post dose. Several pharmacokinetic parameters were represented: AUC(0-infinity) = 113.0 mg-h/mL, C(max) = 12.06 mg/mL, time for maximal concentrations (T(max)) = 3.19 h and t(1/2β) = 4.51 h. These were different from those of western populations as follows: AUC was 14.5% and C(max) was 28% that of of Korean subjects and T(max) and t(1/2β) were also different. The validated HPLC-UV method was successfully applied for the pharmacokinetic studies of nimesulide in Korean subjects. Because the pharmacokinetics of nimesulide were different from western populations, its dosage regimen needs to be adjusted for Koreans. © The Author [2012]. Published by Oxford University Press. All rights reserved.

  10. Acute oral intake of a higenamine-based dietary supplement increases circulating free fatty acids and energy expenditure in human subjects

    OpenAIRE

    Lee, Sang-Rok; Schriefer, JohnHenry M; Gunnels, Trint A; Harvey, Innocence C; Bloomer, Richard J

    2013-01-01

    Background Higenamine, also known as norcoclaurine, is an herbal constituent thought to act as a beta-2 adrenergic receptor agonist—possibly stimulating lipolysis. It was the purpose of this study to determine the impact of a higenamine-based dietary supplement on plasma free fatty acids and energy expenditure following acute oral ingestion. Methods Sixteen healthy subjects (8 men; 26.1 ± 2.5 yrs; 8 women 22.4 ± 3.1 yrs) ingested a dietary supplement containing a combination of higenamine, ca...

  11. Effect of subcutaneous injection of a long-acting analogue of somatostatin (SMS 201-995) on plasma thyroid-stimulating hormone in normal human subjects

    Energy Technology Data Exchange (ETDEWEB)

    Itoh, S.; Tanaka, K.; Kumagae, M.; Takeda, F.; Morio, K.; Kogure, M.; Hasegawa, M.; Horiuchi, T.; Watabe, T.; Miyabe, S.

    1988-01-01

    SMS 201-995 (SMS), a synthetic analogue of somatostatin (SRIF) has been shown to be effective in the treatment of the hypersecretion of hormones such as in acromegaly. However, little is known about the effects of SMS on the secretion of thyroid-stimulating hormone (TSH) in normal subjects. In this study, plasma TSH was determined with a highly sensitive immunoradiometric assay, in addition to the concentration of SMS in plasma and urine with a radioimmunoassay, following subcutaneous injection of 25, 50, 100 ..mu..g of SMS or a placebo to normal male subjects, at 0900 h after an overnight fast. The plasma concentrations of SMS were dose-responsive and the peak levels were 1.61 +/- 0.09, 4.91 +/- 0.30 and 8.52 +/- 1.18 ng/ml, which were observed at 30, 15 and 45 min after the injection of 25, 50, and 100 ..mu..g of SMS, respectively. Mean plasma disappearance half-time of SMS was estimated to be 110 +/- 3 min. Plasma TSH was suppressed in a dose dependent manner and the suppression lasted for at least 8 hours. At 8 hours after the injection of 25, 50, and 100 ..mu..g of SMS, the plasma TSH levels were 43.8 +/- 19.4, 33.9 +/- 9.4 and 24.9 +/- 3.2%, respectively, of the basal values.

  12. Amyloid precursor protein expression is enhanced in human platelets from subjects with Alzheimer's disease and frontotemporal lobar degeneration: a real-time PCR study.

    Science.gov (United States)

    Vignini, Arianna; Morganti, Stefano; Salvolini, Eleonora; Sartini, Davide; Luzzi, Simona; Fiorini, Rosamaria; Provinciali, Leandro; Di Primio, Roberto; Mazzanti, Laura; Emanuelli, Monica

    2013-12-01

    Frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD) represent the most frequent causes of early-onset and late-onset degenerative dementia, respectively. A correct diagnosis entails the choice of appropriate therapies. In this view the present study aimed to identify biomarkers that could improve the differential diagnosis. We recently found an overexpression of platelet amyloid precursor protein (APP) in AD; furthermore, recent studies have suggested the presence of changes in APP processing in FTLD. In this context, we analyzed the mRNA expression level of Total APP (TOT) and APP containing a Kunitz-type serine protease inhibitor domain (KPI) in platelets obtained from AD patients, subjects with FTLD, and healthy subjects. In addition, we evaluated the correlation between platelet APP mRNA expression levels and cognitive impairment.Differential gene expression measurements revealed a significant up-regulation of APP TOT and APP KPI in both AD and FTLD patients compared to the controls (being AD/Controls: 1.67 for APP TOT and 1.47 for APP KPI; FTLD/Controls: 1.62 for APP TOT and 1.51 for APP KPI; p < 0.05), although it is interesting to note that in FTLD patients this expression did not correlate with the severity of cognitive impairment.This could be related to a reduced beta-amyloid (Aβ) formation, caused by an alteration of secretase enzymatic activity, even though a post-transcriptional regulation of APP mRNAs in FTLD cannot be excluded.

  13. Initial evaluation of 123I-5-I-R91150, a selective 5-HT2Aligand for single-photon emission tomography, in healthy human subjects

    International Nuclear Information System (INIS)

    Busatto, G.F.; Pilowsky, L.S.; Costa, D.C.; Mertens, J.; Terriere, D.; Ell, P.J.; Mulligan, R.; Travis, M.J.; Leysen, J.E.; Lui, D.; Gacinovic, S.; Waddington, W.; Lingford-Hughes, A.; Kerwin, R.W.

    1997-01-01

    The mapping of 5-HT 2 receptors in the brain using functional imaging techniques has been limited by a relative lack of selective radioligands. Iodine-123 labelled 4-amino-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]-5-iodo-2-methox ybenzamide ( 123 I-5-I-R91150 or 123 I-R93274) is a new ligand for single-photon emission tomography (SPET), with high affinity and selectivity for 5-HT 2A receptors. This study reports on preliminary 123 I-5-I-R91150 SPET, whole-body and blood distribution findings in five healthy human volunteers. Maximal brain uptake was approximately 2% of total body counts at 180 min post injection (p.i.). Dynamic SPET sequences were acquired with the brain-dedicated, single-slice multi-detector system SME-810 over 200 min p.i. Early peak uptake (at 5 min p.i.) was seen in the cerebellum, a region free from 5HT 2A receptors. In contrast, radioligand binding in the frontal cortex increased steadily over time, up to a peak at approximately 100-120 min p.i. Frontal cortex-cerebellum activity ratios reached values of 1.4, and remained stable from approximately 100 min p.i. onwards. Multi-slice SPET sequences showed a pattern of regional variation of binding compatible with the autoradiographic data on the distribution of 5-HT 2A receptors in humans (cerebral cortex >striatum >cerebellum). These findings suggest that 123 I-5-I-R91150 may be used for the imaging of 5-HT 2A receptors in the living human brain with SPET. (orig.). With 4 figs., 2 tabs

  14. The issue of constitutional law legitimacy on "human assisted reproduction" between reasonableness of the choices and effectiveness of the protection of all involved subjects.

    Science.gov (United States)

    Penasa, Simone

    2006-01-01

    This artiche analyzes the constitutionality petition to the constitutional Court against Law 40 of 2004 on "human assisted reproduction", where it prohibits the "preimplantatory genetical diagnosis", because it could be against the mother's right to health (art. 32 Italian Constitution) and the egalitarian protection clause (art. 3 Italian Constitution). In the constitutionally petition the ordinary judge proposes an interpretation in accordance with Constitution of the contested disposition (art. 13 of Law 40 of 2004) and this could be the possibility to teste the "living law" theory and its relation with the "adequate interpretation" of the law and the Constitution.

  15. Assessment of muscle function using hybrid PET/MRI: comparison of 18F-FDG PET and T2-weighted MRI for quantifying muscle activation in human subjects

    International Nuclear Information System (INIS)

    Haddock, Bryan; Holm, Soeren; Poulsen, Jakup M.; Enevoldsen, Lotte H.; Larsson, Henrik B.W.; Kjaer, Andreas; Suetta, Charlotte

    2017-01-01

    The aim of this study was to determine the relationship between relative glucose uptake and MRI T 2 changes in skeletal muscles following resistance exercise using simultaneous PET/MRI scans. Ten young healthy recreationally active men (age 21 - 28 years) were injected with 18 F-FDG while activating the quadriceps of one leg with repeated knee extension exercises followed by hand-grip exercises for one arm. Immediately following the exercises, the subjects were scanned simultaneously with 18 F-FDG PET/MRI and muscle groups were evaluated for increases in 18 F-FDG uptake and MRI T 2 values. A significant linear correlation between 18 F-FDG uptake and changes in muscle T 2 (R 2 = 0.71) was found. for both small and large muscles and in voxel to voxel comparisons. Despite large intersubject differences in muscle recruitment, the linear correlation between 18 F-FDG uptake and changes in muscle T 2 did not vary among subjects. This is the first assessment of skeletal muscle activation using hybrid PET/MRI and the first study to demonstrate a high correlation between 18 F-FDG uptake and changes in muscle T 2 with physical exercise. Accordingly, it seems that changes in muscle T 2 may be used as a surrogate marker for glucose uptake and lead to an improved insight into the metabolic changes that occur with muscle activation. Such knowledge may lead to improved treatment strategies in patients with neuromuscular pathologies such as stroke, spinal cord injuries and muscular dystrophies. (orig.)

  16. Weight and Glucose Reduction Observed with a Combination of Nutritional Agents in Rodent Models Does Not Translate to Humans in a Randomized Clinical Trial with Healthy Volunteers and Subjects with Type 2 Diabetes.

    Directory of Open Access Journals (Sweden)

    Rebecca J Hodge

    Full Text Available Nutritional agents have modest efficacy in reducing weight and blood glucose in animal models and humans, but combinations are less well characterized. GSK2890457 (GSK457 is a combination of 4 nutritional agents, discovered by the systematic assessment of 16 potential components using the diet-induced obese mouse model, which was subsequently evaluated in a human study.In the diet-induced obese mouse model, GSK457 (15% w/w in chow given with a long-acting glucagon-like peptide -1 receptor agonist, exendin-4 AlbudAb, produced weight loss of 30.8% after 28 days of treatment. In db/db mice, a model of diabetes, GSK457 (10% w/w combined with the exendin-4 AlbudAb reduced glucose by 217 mg/dL and HbA1c by 1.2% after 14 days.GSK457 was evaluated in a 6 week randomized, placebo-controlled study that enrolled healthy subjects and subjects with type 2 diabetes to investigate changes in weight and glucose. In healthy subjects, GSK457 well tolerated when titrated up to 40 g/day, and it reduced systemic exposure of metformin by ~ 30%. In subjects with diabetes taking liraglutide 1.8 mg/day, GSK457 did not reduce weight, but it slightly decreased mean glucose by 0.356 mmol/L (95% CI: -1.409, 0.698 and HbAlc by 0.065% (95% CI: -0.495, 0.365, compared to placebo. In subjects with diabetes taking metformin, weight increased in the GSK457-treated group [adjusted mean % increase from baseline: 1.26% (95% CI: -0.24, 2.75], and mean glucose and HbA1c were decreased slightly compared to placebo [adjusted mean glucose change from baseline: -1.22 mmol/L (95% CI: -2.45, 0.01; adjusted mean HbA1c change from baseline: -0.219% (95% CI: -0.910, 0.472].Our data demonstrate remarkable effects of GSK457 in rodent models of obesity and diabetes, but a marked lack of translation to humans. Caution should be exercised with nutritional agents when predicting human efficacy from rodent models of obesity and diabetes.ClinicalTrials.gov NCT01725126.

  17. What is rational about killing a patient with an overdose?: enlightenment, continental philosophy and the role of the human subject in system failure.

    Science.gov (United States)

    Dekker, Sidney W A

    2011-08-01

    This paper raises the issue of ergonomics' role in giving primacy to fully rational individual human actors in the creation of system failure, despite its commitment to see action as constrained by design and operational features of work. Reflecting on recent contributions to the journal, ergonomics' dilemma is considered against Enlightenment assumptions about individual human reason as the route to truth and goodness and its critics in continental philosophy. There is a pervasive, unstated pact here. What ergonomics chooses to call certain things (violations, errors, non-compliance, situation awareness) not only simultaneously affirms and denies full rationality on part of the people it studies, it also coincides with what the West sees as scientific, true and instrumental. Thus, ergonomics research legitimates its findings in terms it is expected to explain itself in. But by doing so, it reprod