Inflammatory Response of Human Gestational Membranes to Ureaplasma parvum Using a Novel Dual-Chamber Tissue Explant System.

PubMed

Potts, Lauren C; Feng, Liping; Seed, Patrick C; Jayes, Friederike L; Kuchibhatla, Maragatha; Antczak, Brian; Nazzal, Matthew K; Murtha, Amy P

2016-05-01

Preterm premature rupture of membranes (PPROM) is often associated with intra-amniotic inflammation and infection. Current understanding of the pathogenesis of PPROM includes activation of pro-inflammatory cytokines and proteolytic enzymes leading to compromise of membrane integrity. The impact of exposure to bacterial pathogens, including Ureaplasma parvum, on gestational membranes is poorly understood. Our objective was to develop a dual-chamber system to characterize the inflammatory response of gestational membranes to U. parvum in a directional nature. Full-thickness human gestational membrane explants, with either choriodecidua or amnion oriented superiorly, were suspended between two washers in a cylindrical device, creating two distinct compartments. Brilliant green dye was introduced into the top chamber to assess the integrity of the system. Tissue viability was evaluated after 72 h using a colorimetric cell proliferation assay. Choriodecidua or amnion was exposed to three doses of U. parvum and incubated for 24 h. Following treatment, media from each compartment were used for quantification of U. parvum (quantitative PCR), interleukin (IL)-8 (enzyme-linked immunosorbent assay), and matrix metalloproteinase (MMP)-2 and MMP-9 activity (zymography). We observed that system integrity and explant viability were maintained over 72 h. Dose-dependent increases in recovered U. parvum, IL-8 concentration, and MMP-2 activity were detected in both compartments. Significant differences in IL-8 concentration and MMP-9 activity were found between the choriodecidua and amnion. This tissue explant system can be used to investigate the inflammatory consequences of directional bacterial exposure for gestational membranes and provides insight into the pathogenesis of PPROM and infectious complications of pregnancy. © 2016 by the Society for the Study of Reproduction, Inc.

Decellularized amnion scaffold with activated PRP: a new paradigm dressing material for burn wound healing.

PubMed

Kshersagar, Jeevitaa; Kshirsagar, Ravi; Desai, Shashikant; Bohara, Raghvendra; Joshi, Meghnad

2018-03-05

Direct application of amnion has greater risk of immunological rejection and infection. Decellularization is an effective method to lower the risk of immune complications and infections. The bioreactor assembly with multiple cassettes was designed for decellurization of multiple amnions with different cell types simultaneously in single run. A detergent-based protocol was modified to remove all cellular components from amnion and diminish the DNA content to render it non-immunogenic. Amnion (n = 10) were treated with 2% sodium dodecyl sulphate (SDS), 5% dimethyl sulfoxide (DMSO) and 2% sodium deoxycholeate (SD). Decellularized amnion samples were analyzed by haematoxylin-eosin staining (HE), Alcian blue pH 1 (AB-pH-1), 4,6-diamnionidino-2-phenylindol (DAPI), Massion's trichrome stain, DNA quantification, mechanical testing and scanning electron microscopy (SEM). Histological analysis showed complete removal of cellular components and the histoarchitecture of scaffold remained intact. Amnion scaffold activated with platelet rich plasma (PRP) and calcium chloride composition supported better adherence to the wound than amnion alone. Only single application showed good healing. In vivo assessment of activated amnion revealed stable dressing. It has good promising outcome. At day 7, histologically the wounds treated with activated amnion were almost closed without scarring and showed well differentiated epidermis, proliferation of keratinocytes, hair follicles and basement membrane as compared to controls and silver nitrate gel dressings in a mouse (Mus musculus). Cryopreservation had no adverse effect on the mechanical properties of the amnion scaffold. Cryopreservation of decellularized amnion by Dulbecco's modified eagle medium (DMEM) was expected to prepare off-the-shelf skin substitutes and preserve them to be immediately available upon request of patients' needs.

Telomere Fragment Induced Amnion Cell Senescence: A Contributor to Parturition?

PubMed Central

Polettini, Jossimara; Behnia, Faranak; Taylor, Brandie D.; Saade, George R.; Taylor, Robert N.; Menon, Ramkumar

2015-01-01

Oxidative stress (OS)-induced senescence of the amniochorion has been associated with parturition at term. We investigated whether telomere fragments shed into the amniotic fluid (AF) correlated with labor status and tested if exogenous telomere fragments (T-oligos) could induce human and murine amnion cell senescence. In a cross-sectional clinical study, AF telomere fragment concentrations quantitated by a validated real-time PCR assay were higher in women in labor at term compared to those not in labor. In vitro treatment of primary human amnion epithelial cells with 40 μM T-oligos ([TTAGGG]2) that mimic telomere fragments, activated p38MAPK, produced senescence-associated (SA) β-gal staining and increased interleukin (IL)-6 and IL-8 production compared to cells treated with complementary DNA sequences (Cont-oligos, [AATCCC]2). T-oligos injected into the uteri of pregnant CD1 mice on day 14 of gestation, led to increased p38MAPK, SA-β-gal (SA β-gal) staining in murine amniotic sacs and higher AF IL-8 levels on day 18, compared to saline treated controls. In summary, term labor AF samples had higher telomere fragments than term not in labor AF. In vitro and in situ telomere fragments increased human and murine amnion p38MAPK, senescence and inflammatory cytokines. We propose that telomere fragments released from senescent fetal cells are indicative of fetal cell aging. Based on our data, these telomere fragments cause oxidative stress associated damages to the term amniotic sac and force them to release other DAMPS, which, in turn, provide a sterile immune response that may be one of the many inflammatory signals required to initiate parturition at term. PMID:26397719

Clinical application of decellularized and lyophilized human amnion/chorion membrane grafts for closing post‐laryngectomy pharyngocutaneous fistulas

PubMed Central

Mardaleishvili, Konstantine; Loladze, George; Javakhishvili, Ivane; Chakhunasvili, Konstantine; Karalashvili, Lika; Sukhitashvili, Natia; Chutkerashvili, Gocha; Kakabadze, Ann; Chakhunasvili, David

2016-01-01

Background and Objectives Squamous cell carcinoma is the most common pathological type among the cancers of the larynx. Standard treatment for squamous cell carcinoma of the larynx is the combination of chemotherapy, radiotherapy, and laryngectomy. Pharyngocutaneous fistula is a common complication of laryngectomy. We hypothesized that decellularized and lyophilized human amnion/chorion membrane can be an effective, non‐invasive method of treating pharyngocutaneous fistula. Methods A total of 67 patients with laryngeal squamous cell carcinoma were retrospectively analyzed after treatment in a prospective trial. After preoperative chemotherapy, radiotherapy, and total or extended laryngectomy, primary wound healing occurred in 42 (62.7%) patients. Pharyngocutaneous fistula developed in 8 (11.9%) patients. Decellularized and lyophilized human amnion/chorion membrane grafts were used to reconstruct the fistulas. Results The average time for the full healing of the wound in all patients after transplantation of these grafts was 18 days. Conclusion The advantages of using these grafts over other existing methods of pharyngocutaneous fistula treatment are that they are non‐invasive, prevent donor morbidity, and enable management of the wound without using classical wound gauze. J. Surg. Oncol. 2016;113:538–543. © 2016 The Authors. Journal of Surgical Oncology Published by Wiley Periodicals, Inc. PMID:26791912

Human amnion mesenchymal stem cells promote proliferation and osteogenic differentiation in human bone marrow mesenchymal stem cells.

PubMed

Wang, Yuli; Yin, Ying; Jiang, Fei; Chen, Ning

2015-02-01

Human amnion mesenchymal stem cells (HAMSCs) can be obtained from human amniotic membrane, a highly abundant and readily available tissue. HAMSC sources present fewer ethical issues, have low immunogenicity, anti-inflammatory properties, considerable advantageous characteristics, and are considered an attractive potential treatment material in the field of regenerative medicine. We used a co-culture system to determine whether HAMSCs could promote osteogenesis in human bone marrow mesenchymal stem cells (HBMSCs). We isolated HAMSCs from discarded amnion samples and collected them using pancreatin/collagenase digestion. We cultured HAMSCs and HBMSCSs in basal medium. Activity of alkaline phosphatase (ALP), an early osteogenesis marker, was increased in the co-culture system compared to the control single cultures, which we also confirmed by ALP staining. We used immunofluorescence testing to investigate the effects of co-culturing with HAMSCs on HBMSC proliferation, which revealed that the co-culturing enhanced EdU expression in HBMSCs. Western blotting and quantitative real-time PCR indicated that co-culturing promoted osteogenesis in HBMSCs. Furthermore, Alizarin red S staining revealed that extracellular matrix calcium levels in mineralized nodule formation produced by the co-cultures were higher than that in the controls. Using the same co-culture system, we further observed the effects of HAMSCs on osteogenic differentiation in primary osteoblasts by Western blotting, which better addressed the mechanism for HAMSCs in bone regeneration. The results showed HAMSCs are osteogenic and not only play a role in promoting HBMSC proliferation and osteogenic differentiation but also in osteoblasts, laying the foundation for new regenerative medicine methods.

Amnion-derived stem cells: in quest of clinical applications

PubMed Central

2011-01-01

In the promising field of regenerative medicine, human perinatal stem cells are of great interest as potential stem cells with clinical applications. Perinatal stem cells could be isolated from normally discarded human placentae, which are an ideal cell source in terms of availability, the fewer number of ethical concerns, less DNA damage, and so on. Numerous studies have demonstrated that some of the placenta-derived cells possess stem cell characteristics like pluripotent differentiation ability, particularly in amniotic epithelial (AE) cells. Term human amniotic epithelium contains a relatively large number of stem cell marker-positive cells as an adult stem cell source. In this review, we introduce a model theory of why so many AE cells possess stem cell characteristics. We also describe previous work concerning the therapeutic applications and discuss the pluripotency of the AE cells and potential pitfalls for amnion-derived stem cell research. PMID:21596003

Characterization of Amniotic Stem Cells

PubMed Central

Koike, Chika; Zhou, Kaixuan; Takeda, Yuji; Fathy, Moustafa; Okabe, Motonori; Yoshida, Toshiko; Nakamura, Yukio; Kato, Yukio

2014-01-01

Abstract The amnion membrane is developed from embryo-derived cells, and amniotic cells have been shown to exhibit multidifferentiation potential. These cells represent a desirable source for stem cells for a variety of reasons. However, to date very few molecular analyses of amnion-derived cells have been reported, and efficient markers for isolating the stem cells remain unclear. This paper assesses the characterization of amnion-derived cells as stem cells by examining stemness marker expressions for amnion-derived epithelial cells and mesenchymal cells by flow cytometry, immunocytochemistry, and quantitative PCR. Flow cytometry revealed that amnion epithelial cells expressed CD133, CD 271, and TRA-1-60, whereas mecenchymal cells expressed CD44, CD73, CD90, and CD105. Immunohistochemistry showed that both cells expressed the stemness markers Oct3/4, Sox2, Klf4, and SSEA4. Stemness genes' expression in amnion epithelial cells, mesenchymal cells, fibroblast, bone marrow–derived mesenchymal stem cells (MSCs), and induced pluripotent stem cells (iPSCs) was compared by quantitative reverse-transcription polymerase chain reaction (RT-PCR). Amnion-derived epithelial cells and mesenchymal cells expressed Oct3/4, Nanog, and Klf4 more than bone marrow–derived MSCs. The sorted TRA1-60–positive cells expressed Oct3/4, Nanog, and Klf4 more than unsorted cells or TRA1-60–negative cells. TRA1-60 can be a marker for isolating amnion epithelial stem cells. PMID:25068631

Amniotic therapeutic biomaterials in urology: current and future applications.

PubMed

Oottamasathien, Siam; Hotaling, James M; Craig, James R; Myers, Jeremy B; Brant, William O

2017-10-01

To examine the rationale and applications of amniotic tissue augmentation in urological surgery. Published literature in English-language was reviewed for basic science and clinical use of amniotic or amnion-chorionic tissue in genitourinary tissues. Basic science and animal studies support the likely benefit of clinical applications of amnion-derived tissues in a variety of urologic interventions. The broad number of properties found in amniotic membrane, coupled with its immunologically privileged status presents a number of future applications in the urological surgical realm. These applications are in their clinical infancy and suggest that further studies are warranted to investigate the use of these products in a systematic fashion.

Standardized limbal epithelial stem cell graft generation and transplantation.

PubMed

Zakaria, Nadia; Koppen, Carina; Van Tendeloo, Viggo; Berneman, Zwi; Hopkinson, Andrew; Tassignon, Marie-José

2010-10-01

To describe a standardized, xenogenic-free protocol for the manufacture of limbal epithelial stem cell grafts and a "no touch" surgical technique for its standardized transplantation. Antwerp University Hospital, Antwerp, Belgium. The limbo-amnion composite graft is generated by cultivating limbal epithelial stem cells on a standardized (thermolysin treated and spongy layer removed) amniotic membrane, stretched within an interlockable amnion ring. The cells are cultured in CnT-20 medium with the addition of 1% human AB serum for a period of 2 weeks. Fibrin glue is applied to the surgically prepared recipient's cornea and in one fluid motion, the composite graft within the amnion ring construct is transferred from culture and positioned onto the graft bed. The required size is cut out at the level of the limbus by means of a trephine and/or microsurgical scissors. The lightweight, plastic interlockable ring offered stability to the graft during culture, transport, and transplantation. The use of the standardized amniotic membrane, within the amnion ring construct, improves reproducibility of the results and therefore heralds elective surgery. Rapid transplantation of a wrinkle-free graft, using a sutureless, “no touch" technique was achieved and this allowed precise tailoring of the graft to the recipient bed. This is the first time a standardized, clinical grade protocol has been described for manufacturing limbal epithelial grafts with an efficient surgical technique that prevents postsurgical graft shrinkage and improves corneal integration. The quick, sutureless, and manipulation-free technique ensured transplantation of viable, proliferating limbal epithelial stem cells.

Mesenchymal Stem or Stromal Cells from Amnion and Umbilical Cord Tissue and Their Potential for Clinical Applications

PubMed Central

Lindenmair, Andrea; Hatlapatka, Tim; Kollwig, Gregor; Hennerbichler, Simone; Gabriel, Christian; Wolbank, Susanne; Redl, Heinz; Kasper, Cornelia

2012-01-01

Mesenchymal stem or stromal cells (MSC) have proven to offer great promise for cell-based therapies and tissue engineering applications, as these cells are capable of extensive self-renewal and display a multilineage differentiation potential. Furthermore, MSC were shown to exhibit immunomodulatory properties and display supportive functions through parakrine effects. Besides bone marrow (BM), still today the most common source of MSC, these cells were found to be present in a variety of postnatal and extraembryonic tissues and organs as well as in a large variety of fetal tissues. Over the last decade, the human umbilical cord and human amnion have been found to be a rich and valuable source of MSC that is bio-equivalent to BM-MSC. Since these tissues are discarded after birth, the cells are easily accessible without ethical concerns. PMID:24710543

Periodontal Regeneration Using Periodontal Ligament Stem Cell-Transferred Amnion

PubMed Central

Iwasaki, Kengo; Yokoyama, Naoki; Tanaka, Yuichi; Taki, Atsuko; Honda, Izumi; Kimura, Yasuyuki; Takeda, Masaki; Akazawa, Keiko; Oda, Shigeru; Izumi, Yuichi; Morita, Ikuo

2014-01-01

Periodontal disease is characterized by the destruction of tooth supporting tissues. Regeneration of periodontal tissues using ex vivo expanded cells has been introduced and studied, although appropriate methodology has not yet been established. We developed a novel cell transplant method for periodontal regeneration using periodontal ligament stem cell (PDLSC)-transferred amniotic membrane (PDLSC-amnion). The aim of this study was to investigate the regenerative potential of PDLSC-amnion in a rat periodontal defect model. Cultured PDLSCs were transferred onto amniotic membranes using a glass substrate treated with polyethylene glycol and photolithography. The properties of PDLSCs were investigated by flow cytometry and in vitro differentiation. PDLSC-amnion was transplanted into surgically created periodontal defects in rat maxillary molars. Periodontal regeneration was evaluated by microcomputed tomography (micro-CT) and histological analysis. PDLSCs showed mesenchymal stem cell-like characteristics such as cell surface marker expression (CD90, CD44, CD73, CD105, CD146, and STRO-1) and trilineage differentiation ability (i.e., into osteoblasts, adipocytes, and chondrocytes). PDLSC-amnion exhibited a single layer of PDLSCs on the amniotic membrane and stability of the sheet even with movement and deformation caused by surgical instruments. We observed that the PDLSC-amnion enhanced periodontal tissue regeneration as determined by micro-CT and histology by 4 weeks after transplantation. These data suggest that PDLSC-amnion has therapeutic potential as a novel cell-based regenerative periodontal therapy. PMID:24032400

Periodontal regeneration using periodontal ligament stem cell-transferred amnion.

PubMed

Iwasaki, Kengo; Komaki, Motohiro; Yokoyama, Naoki; Tanaka, Yuichi; Taki, Atsuko; Honda, Izumi; Kimura, Yasuyuki; Takeda, Masaki; Akazawa, Keiko; Oda, Shigeru; Izumi, Yuichi; Morita, Ikuo

2014-02-01

Periodontal disease is characterized by the destruction of tooth supporting tissues. Regeneration of periodontal tissues using ex vivo expanded cells has been introduced and studied, although appropriate methodology has not yet been established. We developed a novel cell transplant method for periodontal regeneration using periodontal ligament stem cell (PDLSC)-transferred amniotic membrane (PDLSC-amnion). The aim of this study was to investigate the regenerative potential of PDLSC-amnion in a rat periodontal defect model. Cultured PDLSCs were transferred onto amniotic membranes using a glass substrate treated with polyethylene glycol and photolithography. The properties of PDLSCs were investigated by flow cytometry and in vitro differentiation. PDLSC-amnion was transplanted into surgically created periodontal defects in rat maxillary molars. Periodontal regeneration was evaluated by microcomputed tomography (micro-CT) and histological analysis. PDLSCs showed mesenchymal stem cell-like characteristics such as cell surface marker expression (CD90, CD44, CD73, CD105, CD146, and STRO-1) and trilineage differentiation ability (i.e., into osteoblasts, adipocytes, and chondrocytes). PDLSC-amnion exhibited a single layer of PDLSCs on the amniotic membrane and stability of the sheet even with movement and deformation caused by surgical instruments. We observed that the PDLSC-amnion enhanced periodontal tissue regeneration as determined by micro-CT and histology by 4 weeks after transplantation. These data suggest that PDLSC-amnion has therapeutic potential as a novel cell-based regenerative periodontal therapy.

Grafting with Cryopreserved Amniotic Membrane versus Conservative Wound Care in Treatment of Pressure Ulcers: A Randomized Clinical Trial

PubMed Central

Dehghani, Mehdi; Azarpira, Negar; Mohammad Karimi, Vahid; Mossayebi, Hamid; Esfandiari, Elaheh

2017-01-01

Objective: To compare the healing process of pressure ulcers treated with cryopreserved human amniotic membrane allograft and routine pressure ulcer care in our hospital. Methods: From January 2012 to December 2013, in a prospective randomized clinical trial (IRCT201612041335N2), 24 patients with second and third stage of pressure ulcers were enrolled in this study. All patients needed split-thickness skin grafts for pressure ulcer-wound coverage. Selected patients had symmetric ulcers on both upper and lower extremities. The patients were randomly divided into two groups: amnion and control. In the amnion group, the ulcer was covered with cryopreserved amniotic membrane and in the control group it was treated with local Dilantin powder application. The duration and success rate of complete healing was compared between the two groups. Results: The study group was composed of 24 pressure ulcers in 24 patients (19 males and 5 females) with a mean age of 44±12.70 years. The demographic characteristics, ulcer area, and underlying diseases were similar in both groups. The early sign of response, such as decrease in wound discharge, was detected 12-14 days after biological dressing. Complete pressure ulcer healing occurred only in the amnion group (p< 0.001). Partial healing was significantly higher in the amnion group (p< 0.03). Healing time in this group was faster than that the control group (20 days versus 54 days). No major complication was recorded with amniotic membrane dressing Conclusion: Cryopreserved amniotic membrane is an effective biologic dressing that promotes re-epithelialization in pressure ulcers PMID:29177171

Biological properties of dehydrated human amnion/chorion composite graft: implications for chronic wound healing

PubMed Central

Koob, Thomas J; Rennert, Robert; Zabek, Nicole; Massee, Michelle; Lim, Jeremy J; Temenoff, Johnna S; Li, William W; Gurtner, Geoffrey

2013-01-01

Human amnion/chorion tissue derived from the placenta is rich in cytokines and growth factors known to promote wound healing; however, preservation of the biological activities of therapeutic allografts during processing remains a challenge. In this study, PURION® (MiMedx, Marietta, GA) processed dehydrated human amnion/chorion tissue allografts (dHACM, EpiFix®, MiMedx) were evaluated for the presence of growth factors, interleukins (ILs) and tissue inhibitors of metalloproteinases (TIMPs). Enzyme-linked immunosorbent assays (ELISA) were performed on samples of dHACM and showed quantifiable levels of the following growth factors: platelet-derived growth factor-AA (PDGF-AA), PDGF-BB, transforming growth factor α (TGFα), TGFβ1, basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), placental growth factor (PLGF) and granulocyte colony-stimulating factor (GCSF). The ELISA assays also confirmed the presence of IL-4, 6, 8 and 10, and TIMP 1, 2 and 4. Moreover, the relative elution of growth factors into saline from the allograft ranged from 4% to 62%, indicating that there are bound and unbound fractions of these compounds within the allograft. dHACM retained biological activities that cause human dermal fibroblast proliferation and migration of human mesenchymal stem cells (MSCs) in vitro. An in vivo mouse model showed that dHACM when tested in a skin flap model caused mesenchymal progenitor cell recruitment to the site of implantation. The results from both the in vitro and in vivo experiments clearly established that dHACM contains one or more soluble factors capable of stimulating MSC migration and recruitment. In summary, PURION® processed dHACM retains its biological activities related to wound healing, including the potential to positively affect four distinct and pivotal physiological processes intimately involved in wound healing: cell proliferation, inflammation, metalloproteinase activity and recruitment of progenitor cells. This suggests a paracrine mechanism of action for dHACM when used for wound healing applications. PMID:23902526

Properties of dehydrated human amnion/chorion composite grafts: Implications for wound repair and soft tissue regeneration.

PubMed

Koob, Thomas J; Lim, Jeremy J; Massee, Michelle; Zabek, Nicole; Denozière, Guilhem

2014-08-01

PURION(®) processed dehydrated human amnion/chorion membrane (dHACM; MiMedx Group, Marietta, GA) tissue products were analyzed for the effectiveness of the PURION(®) process in retaining the native composition of the amniotic membrane and preserving bioactivity in the resulting products. dHACM was analyzed for extracellular matrix (ECM) composition through histological staining and for growth factor content via multiplex ELISA arrays. Bioactivity was assessed by evaluating endogenous growth factor production by human dermal fibroblasts in response to dHACM and for thermal stability by mechanical tests and in vitro cell proliferation assays. Histology of dHACM demonstrated preservation of the native amnion and chorion layers with intact, nonviable cells, collagen, proteoglycan, and elastic fibers distributed in the individual layers. An array of 36 cytokines known to regulate processes involved in inflammation and wound healing were identified in dHACM. When treated with dHACM extracts, bioactivity was demonstrated through an upregulation of basic fibroblast growth factor, granulocyte colony-stimulating factor, and placental growth factor biosynthesis, three growth factors involved in wound healing, by dermal fibroblasts in vitro. After conditioning at temperatures ranging from -78.7 to +73.5°C, dHACM retained its tensile strength and ability to promote proliferation of dermal fibroblasts in vitro. Elution experiments demonstrated a soluble fraction of growth factors that eluted from the tissue and another fraction sequestered within the matrix. The PURION(®) process retains the native composition of ECM and signaling molecules and preserves bioactivity. The array of cytokines preserved in dHACM are in part responsible for its therapeutic efficacy in treating chronic wounds by orchestrating a "symphony of signals" to promote healing. © 2014 Wiley Periodicals, Inc.

Organotypic culture of human amnion cells in air-liquid interface as a potential substitute for skin regeneration.

PubMed

Fatimah, Simat Siti; Chua, Kienhui; Tan, Geok Chin; Azmi, Tengku Ibrahim; Tan, Ay Eeng; Abdul Rahman, Hayati

2013-08-01

The aim of the present study was to evaluate the effects of air-liquid interface on the differentiation potential of human amnion epithelial cells (HAECs) to skin-like substitute in organotypic culture. HAECs at passage 1-2 were seeded onto a fibrin layer populated with human amnion mesenchymal cells to form the organotypic cultures. The organotypic HAECs were then cultured for 7, 14 and 21 d in two types of culture system: the submerged culture and the air-liquid interface culture. Cell morphogenesis was examined under the light and electron microscopes (transmission and scanning) and analyzed by immunohistochemistry. Organotypic HAECs formed a single layer epithelium after 3 wk in submerged as well as air-liquid interface cultures. Ultrastructurally, desmosomes were observed in organotypic HAECs cultured in the air-liquid interface but not in the submerged culture. The presence of desmosomes marked the onset of early epidermal differentiation. Organotypic HAECs were positive against anti-CK18 and anti-CK14 in both the submerged and the air-liquid interface cultures. The co-expression of CK14 and CK18 suggested that differentiation of HAECs into skin may follow the process of embryonic skin development. However, weak expression of CK14 was observed after 2 and 3 wk of culture in air-liquid interface. CK10, involucrin, type IV collagen and laminin-5 expression was absent in organotypic HAECs. This observation reflects the initial process of embryonic epidermal differentiation and stratification. Results from the present study suggest that the air-liquid interface could stimulate early differentiation of organotypic HAECs to epidermal cells, with a potential use for skin regeneration. Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Inhibition of PIM1 kinase attenuates inflammation-induced pro-labour mediators in human foetal membranes in vitro.

PubMed

Lim, Ratana; Barker, Gillian; Lappas, Martha

2017-06-01

Does proviral integration site for Moloney murine leukaemic virus (PIM)1 kinase play a role in regulating the inflammatory processes of human labour and delivery? PIM1 kinase plays a critical role in foetal membranes in regulating pro-inflammatory and pro-labour mediators. Infection and inflammation have strong causal links to preterm delivery by stimulating pro-inflammatory cytokines and collagen degrading enzymes, which can lead to rupture of membranes. PIM1 has been shown to have a role in immune regulation and inflammation in non-gestational tissues; however, its role has not been explored in the field of human labour. PIM1 expression was analysed in myometrium and/or foetal membranes obtained at term and preterm (n = 8-9 patients per group). Foetal membranes, freshly isolated amnion cells and primary myometrial cells were used to investigate the effect of PIM1 inhibition on pro-labour mediators (n = 5 patients per treatment group). Foetal membranes, from term and preterm, were obtained from non-labouring and labouring women, and from preterm pre-labour rupture of membranes (PPROM) (n = 9 per group). Amnion was collected from women with and without preterm chorioamnionitis (n = 8 per group). Expression of PIM1 kinase was determined by qRT-PCR and western blotting. To determine the effect of PIM1 kinase inhibition on the expression of pro-inflammatory and pro-labour mediators induced by bacterial products lipopolysaccharide (LPS) (10 μg/ml) and flagellin (1 μg/ml) and pro-inflammatory cytokine tumour necrosis factor (TNF) (10 ng/ml), chemical inhibitors SMI-4a (20 μM) and AZD1208 (50 μM) were used in foetal membrane explants and siRNA against PIM1 was used in primary amnion cells. Statistical significance was set at P < 0.05. PIM1 expression was significantly increased in foetal membranes after spontaneous term labour compared to no labour at term and in amnion with preterm chorioamnionitis compared to preterm with no chorioamnionitis. There was no change in PIM1 expression with preterm labour or PPROM compared to preterm with no labour or PPROM. In human foetal membranes, PIM1 inhibitors SMI-4a and AZD1208 significantly decreased the expression of pro-inflammatory cytokine interleukin-6 (IL6) and chemokines CXCL8 and CCL2 mRNA and release, prostaglandin prostaglandin F2α (PGF2α) release, adhesion molecule intercellular adhesion molecule 1 mRNA expression and release, and oxidative stress marker 8-isoprostane release after stimulation with either LPS or flagellin. Primary amnion cells transfected with PIM1 siRNA also showed decreased expression of IL6, CXCL8 and CCL2, PTGS2 mRNA and PGF2α release, and matrix metalloproteinase-9 (MMP9) expression, when stimulated with TNF. None. The conclusions were drawn from in vitro experiments using foetal membrane explants and primary cells isolated from amnion. Animal models are necessary to determine whether PIM1 kinase inhibitors can prevent spontaneous preterm birth in vivo. PIM1 kinase inhibitors may provide a novel therapeutic approach for preventing spontaneous preterm birth. Associate Professor Martha Lappas is supported by a Career Development Fellowship from the National Health and Medical Research Council (NHMRC; grant no. 1047025). Funding for this study was provided by the NHMRC (grant no. 1058786), Norman Beischer Medical Research Foundation and the Mercy Research Foundation. The authors have no conflict of interest. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Establishment of donor Chimerism Using Allogeneic Bone Marrow with AMP Cell Co-infusion

DTIC Science & Technology

2017-09-01

the ideal solution. Combined mixed allogeneic chimerism induction and kidney transplantation has been shown to induce robust tolerance to the kidney ...induction to kidney allografts in non-human primates and humans despite the transience of donor chimerism. However, evidence indicates that durable mixed...chimerism may be required for tolerance induction to tissues or organs other than kidney . Amnion-derived multipotent progenitor (AMP) cells possess

Biological properties of dehydrated human amnion/chorion composite graft: implications for chronic wound healing.

PubMed

Koob, Thomas J; Rennert, Robert; Zabek, Nicole; Massee, Michelle; Lim, Jeremy J; Temenoff, Johnna S; Li, William W; Gurtner, Geoffrey

2013-10-01

Human amnion/chorion tissue derived from the placenta is rich in cytokines and growth factors known to promote wound healing; however, preservation of the biological activities of therapeutic allografts during processing remains a challenge. In this study, PURION® (MiMedx, Marietta, GA) processed dehydrated human amnion/chorion tissue allografts (dHACM, EpiFix®, MiMedx) were evaluated for the presence of growth factors, interleukins (ILs) and tissue inhibitors of metalloproteinases (TIMPs). Enzyme-linked immunosorbent assays (ELISA) were performed on samples of dHACM and showed quantifiable levels of the following growth factors: platelet-derived growth factor-AA (PDGF-AA), PDGF-BB, transforming growth factor α (TGFα), TGFβ1, basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), placental growth factor (PLGF) and granulocyte colony-stimulating factor (GCSF). The ELISA assays also confirmed the presence of IL-4, 6, 8 and 10, and TIMP 1, 2 and 4. Moreover, the relative elution of growth factors into saline from the allograft ranged from 4% to 62%, indicating that there are bound and unbound fractions of these compounds within the allograft. dHACM retained biological activities that cause human dermal fibroblast proliferation and migration of human mesenchymal stem cells (MSCs) in vitro. An in vivo mouse model showed that dHACM when tested in a skin flap model caused mesenchymal progenitor cell recruitment to the site of implantation. The results from both the in vitro and in vivo experiments clearly established that dHACM contains one or more soluble factors capable of stimulating MSC migration and recruitment. In summary, PURION® processed dHACM retains its biological activities related to wound healing, including the potential to positively affect four distinct and pivotal physiological processes intimately involved in wound healing: cell proliferation, inflammation, metalloproteinase activity and recruitment of progenitor cells. This suggests a paracrine mechanism of action for dHACM when used for wound healing applications. ©2013 The Authors. International Wound Journal published by John Wiley & Sons Ltd and Medicalhelplines.com Inc.

Regional expression of prostaglandin E2 and F2alpha receptors in human myometrium, amnion, and choriodecidua with advancing gestation and labor.

PubMed

Grigsby, Peta L; Sooranna, Suren R; Adu-Amankwa, Bernice; Pitzer, Brad; Brockman, Diane E; Johnson, Mark R; Myatt, Leslie

2006-08-01

The change from uterine quiescence to enhanced contractile activity may be due to the differential expression of prostaglandin receptors within the myometrium and fetal membranes, in a temporal and topographically distinct manner. To address this question, we determined the localization and expression of the PGE2 receptor subtypes (PTGER1-4) and the PGF2alpha receptor (PTGFR) in paired upper and lower segment myometrium, amnion, and choriodecidual samples throughout human pregnancy, with and without labor. All receptor subtypes were found throughout the muscle layers in both the upper and lower uterine segments, colocalizing with alpha smooth muscle actin. A change in intracellular localization was observed at term labor, where PTGER1 and PTGER4 were predominately associated with the nucleus. Minimal changes in the expression of the PGE2 and PGF2alpha receptor subtypes were observed with gestational age, labor, or between the upper and lower myometrial segments. Receptor expression in maternal and fetal tissues differed between the receptor subtypes; PTGER1 and PTGER4 were predominately expressed in the fetal membranes, PTGER2 was greatest in the myometrium, whereas PTGER3 and PTGFR were similarly expressed in the myometrium and fetal membranes. Myometrial activation through the prostaglandin receptors is perhaps more subtle and may be mediated by a balance between one or several of the prostaglandin receptor subtypes together with other known contraction associated proteins. Lack of coordination in receptor expression between the myometrium and fetal membranes may indicate different regulatory mechanisms between these tissues, or it may suggest a function for these receptors in the amnion and choriodecidua that is independent of that seen in the myometrium.

Modulation of Cytokine-Induced Cyclooxygenase 2 Expression by PPARG Ligands Through NFκB Signal Disruption in Human WISH and Amnion Cells1

PubMed Central

Ackerman, William E.; Zhang, Xiaolan L.; Rovin, Brad H.; Kniss, Douglas A.

2006-01-01

Cyclooxygenase (COX) activity increases in the human amnion in the settings of term and idiopathic preterm labor, contributing to the generation of uterotonic prostaglandins (PGs) known to participate in mammalian parturition. Augmented COX activity is highly correlated with increased COX2 (also known as prostaglandin-endoperoxide synthase 2, PTGS2) gene expression. We and others have demonstrated an essential role for nuclear factor κB (NFκB) in cytokine-driven COX2 expression. Peroxisome proliferator-activated receptor gamma (PPARG), a member of the nuclear hormone receptor superfamily, has been shown to antagonize NFκB activation and inflammatory gene expression, including COX2. We hypothesized that PPARG activation might suppress COX2 expression during pregnancy. Using primary amnion and WISH cells, we evaluated the effects of pharmacological (thiazolidinediones) and putative endogenous (15-deoxy-Δ12,14-prostaglandin J2, 15d-PGJ2) PPARG ligands on cytokine-induced NFκB activation, COX2 expression, and PGE2 production. We observed that COX2 expression and PGE2 production induced by tumor necrosis factor alpha (TNF) were significantly abrogated by 15d-PGJ2. The thiazolidinediones rosiglitazone (ROSI) and troglitazone (TRO) had relatively little effect on cytokine-induced COX2 expression except at high concentrations, at which these agents tended to increase COX2 abundance relative to cells treated with TNF alone. Interestingly, treatment with ROSI, but not TRO, led to augmentation of TNF-stimulated PGE2 production. Mechanistically, we observed that 15d-PGJ2 markedly diminished cytokine-induced activity of the NFκB transcription factor, whereas thiazolidinediones had no discernable effect on this system. Our data suggest that pharmacological and endogenous PPARG ligands use both receptor-dependent and -independent mechanisms to influence COX2 expression. PMID:15843495

Comparison of structural changes in skin and amnion tissue grafts for transplantation induced by gamma and electron beam irradiation for sterilization.

PubMed

Mrázová, H; Koller, J; Kubišová, K; Fujeríková, G; Klincová, E; Babál, P

2016-06-01

Sterilization is an important step in the preparation of biological material for transplantation. The aim of the study is to compare morphological changes in three types of biological tissues induced by different doses of gamma and electron beam radiation. Frozen biological tissues (porcine skin xenografts, human skin allografts and human amnion) were irradiated with different doses of gamma rays (12.5, 25, 35, 50 kGy) and electron beam (15, 25, 50 kGy). Not irradiated specimens served as controls. The tissue samples were then thawn and fixed in 10 % formalin, processed by routine paraffin technique and stained with hematoxylin and eosin, alcian blue at pH 2.5, orcein, periodic acid Schiff reaction, phosphotungstic acid hematoxylin, Sirius red and silver impregnation. The staining with hematoxylin and eosin showed vacuolar cytoplasmic changes of epidermal cells mainly in the samples of xenografts irradiated by the lowest doses of gamma and electron beam radiation. The staining with orcein revealed damage of fine elastic fibers in the xenograft dermis at the dose of 25 kGy of both radiation types. Disintegration of epithelial basement membrane, especially in the xenografts, was induced by the dose of 15 kGy of electron beam radiation. The silver impregnation disclosed nuclear chromatin condensation mainly in human amnion at the lowest doses of both radiation types and disintegration of the fine collagen fibers in the papillary dermis induced by the lowest dose of electron beam and by the higher doses of gamma radiation. Irradiation by both, gamma rays and the electron beam, causes similar changes on cells and extracellular matrix, with significant damage of the basement membrane and of the fine and elastic and collagen fibers in the papillary dermis, the last caused already by low dose electron beam radiation.

Enhanced differentiation potential of human amniotic mesenchymal stromal cells by using three-dimensional culturing.

PubMed

Lin, Xue; Li, Hao Yu; Chen, Lian Feng; Liu, Bo Jiang; Yao, Yian; Zhu, Wen Ling

2013-06-01

The therapeutic potential of human amniotic mesenchymal stromal cells (hAMSCs) remains limited because of their differentiation towards mesenchymal stem cells (MSCs) following adherence. The aim of this study was to develop a three-dimensional (3-D) culture system that would permit hAMSCs to differentiate into cardiomyocyte-like cells. hAMSCs were isolated from human amnions of full-term births collected after Cesarean section. Immunocytochemistry, immunofluorescence and flow cytometry analyses were undertaken to examine hAMSC marker expression for differentiation status after adherence. Membrane currents were determined by patch clamp analysis of hAMSCs grown with or without cardiac lysates. Freshly isolated hAMSCs were positive for human embryonic stem-cell-related markers but their marker profile significantly shifted towards that of MSCs following adherence. hAMSCs cultured in the 3-D culture system in the presence of cardiac lysate expressed cardiomyocyte-specific markers, in contrast to those maintained in standard adherent cultures or those in 3-D cultures without cardiac lysate. hAMSCs cultured in 3-D with cardiac lysate displayed a cardiomyocyte-like phenotype as observed by membrane currents, including a calcium-activated potassium current, a delayed rectifier potassium current and a Ca(2+)-resistant transient outward K(+) current. Thus, although adherence limits the potential of hAMSCs to differentiate into cardiomyocyte-like cells, the 3-D culture of hAMSCs represents a more effective method of their culture for use in regenerative medicine.

Role of human amnion-derived mesenchymal stem cells in promoting osteogenic differentiation by influencing p38 MAPK signaling in lipopolysaccharide -induced human bone marrow mesenchymal stem cells.

PubMed

Wang, Yuli; Wu, Hongxia; Shen, Ming; Ding, Siyang; Miao, Jing; Chen, Ning

2017-01-01

Periodontitis is a chronic inflammatory disease induced by bacterial pathogens, which not only affect connective tissue attachments but also cause alveolar bone loss. In this study, we investigated the anti-inflammatory effects of Human amnion-derived mesenchymal stem cells (HAMSCs) on human bone marrow mesenchymal stem cells (HBMSCs) under lipopolysaccharide (LPS)-induced inflammatory conditions. Proliferation levels were measured by flow cytometry and immunofluorescence staining of 5-ethynyl-2'-deoxyuridine (EdU). Osteoblastic differentiation and mineralization were investigated using chromogenic alkaline phosphatase activity (ALP) activity substrate assays, Alizarin red S staining, and RT-PCR analysis of HBMSCs osteogenic marker expression. Oxidative stress induced by LPS was investigated by assaying reactive oxygen species (ROS) level and superoxide dismutase (SOD) activity. Here, we demonstrated that HAMSCs increased the proliferation, osteoblastic differentiation, and SOD activity of LPS-induced HBMSCs, and down-regulated the ROS level. Moreover, our results suggested that the activation of p38 MAPK signal transduction pathway is essential for reversing the LPS-induced bone-destructive processes. SB203580, a selective inhibitor of p38 MAPK signaling, significantly suppressed the anti-inflammatory effects in HAMSCs. In conclusion, HAMSCs show a strong potential in treating inflammation-induced bone loss by influencing p38 MAPK signaling. Copyright © 2016 Elsevier Inc. All rights reserved.

The Role of Progesterone and a Novel Progesterone Receptor, Progesterone Receptor Membrane Component 1, in the Inflammatory Response of Fetal Membranes to Ureaplasma parvum Infection.

PubMed

Feng, Liping; Ransom, Carla E; Nazzal, Matthew K; Allen, Terrence K; Li, Yi-Ju; Truong, Tracy; Potts, Lauren C; Seed, Patrick C; Murtha, Amy P

2016-01-01

Ureaplasma parvum (U. parvum) is gaining recognition as an important pathogen for chorioamnionitis and preterm premature rupture of membranes. We aimed to investigate the roles of progesterone (P4) and a novel progesterone receptor, progesterone receptor membrane component 1 (PGRMC1), in the response of fetal membranes to U. parvum. Fetal membrane cells (amnion, chorion and decidua) were isolated and confirmed to be free of Mycoplasmataceae. Cells were treated with U. parvum (5x106 CFU), and adherence was quantified by qPCR. Amnion and chorion cells were transfected with scrambled siRNA or validated PGRMC1 siRNA for 72h. Cells were then treated with U. parvum for 4h with or without pretreatment with P4 (10-7 M) or ethanol for 1h. Interleukin-8 (IL-8), matrix metalloproteinase 9 (MMP9) and cyclooxygenase (COX-2) mRNA expression were quantified by qRT-PCR. Culture medium was harvested and analyzed for IL-8 and prostaglandin (PGE2) secretion by ELISA and MMP9 activity by zymography. U. parvum had a mean adherence of 15.0±0.6%, 16.9± 3.7% and 4.7±0.3% in cultured amnion, chorion and decidua cells, respectively. Exposure to U. parvum elicited significant inflammatory responses including induction of IL-8, COX-2, PGE2 and MMP9. A possible role of PGRMC1 was identified in the inhibition of U. parvum-stimulated COX-2 and MMP9 mRNA expression in chorion cells and MMP9 activity in amnion cells. On the other hand, it might enhance the U. parvum-stimulated IL-8 protein secretion in amnion cells. P4, mediated through PGRMC1, significantly inhibited U. Parvum-induced MMP9 mRNA and COX-2 mRNA expression in chorion cells. P4 appeared to attenuate U. parvum induced IL-8 mRNA expression in chorion cells, but this P4 effect might not mediated through PGRMC1. In summary, U. parvum preferentially adheres to and induces inflammatory responses in chorion and amnion cells. P4 and PGRMC1 appear to differentially modulate the inflammatory responses induced by U. parvum among amnion and chorion cells.

Large Extremity Peripheral Nerve Repair

DTIC Science & Technology

2013-10-01

approaching that of conventional microsurgery and that the PTB repair is unlikely to be disturbed in vivo. The results in Figure 5 were obtained with...with large nerve deficit reconstruction and long nerve grafts. As with the human amnion nerve wraps, it was important for us to confirm that, in...xHAM wrap compared to standard (suture) of care microsurgery . Demonstrated improved nerve regeneration in a muscle mass retention model

Large Extremity Peripheral Nerve Repair

DTIC Science & Technology

2013-10-01

show that the PTB method can provide fixation strengths approaching that of conventional microsurgery and that the PTB repair is unlikely to be...biomaterial during long periods of recovery associated with large nerve deficit reconstruction and long nerve grafts. As with the human amnion nerve...functional recovery model (SFI, sciatic function index) using PTB/xHAM wrap compared to standard (suture) of care microsurgery . Demonstrated improved nerve

Epidermal Growth Factor and Interleukin-1β Utilize Divergent Signaling Pathways to Synergistically Upregulate Cyclooxygenase-2 Gene Expression in Human Amnion-Derived WISH Cells1

PubMed Central

Ackerman, William E.; Rovin, Brad H.; Kniss, Douglas A.

2006-01-01

In human parturition, uterotonic prostaglandins (PGs) arise predominantly via increased expression of cyclooxygenase-2 (COX-2 [also known as prostaglandin synthase 2]) within intra-uterine tissues. Interleukin-1 (IL-1) and epidermal growth factor (EGF), both inducers of COX-2 transcription, are among numerous factors that accumulate within amniotic fluid with advancing gestation. It was previously demonstrated that EGF could potentiate IL-1β-driven PGE2 production in amnion and amnion-derived (WISH) cells. To define the mechanism for this observation, we hypothesized that EGF and IL-1β might exhibit synergism in regulating COX-2 gene expression. In WISH cells, combined treatment with EGF and IL-1β resulted in a greater-than-additive increase in COX-2 mRNA relative to challenge with either agent independently. Augmentation of IL-1β-induced transactivation by EGF was not observed in cells harboring reporter plasmids bearing nuclear factor-kappa B (NFκB) regulatory elements alone, but was evident when a fragment (−891/+9) of the COX-2 gene 5′-promoter was present. Both agents transiently activated intermediates of multiple signaling pathways potentially involved in the regulation of COX-2 gene expression. The 26 S proteasome inhibitor, MG-132, selectively abrogated IL-1β-driven NFκB activation and COX-2 mRNA expression. Only pharmacologic blockade of the p38 mitogen-activated protein kinase eliminated COX-2 expression following EGF stimulation. We conclude that EGF and IL-1β appear to signal through different signaling cascades leading to COX-2 gene expression. IL-1β employs the NFκB pathway predominantly, while the spectrum of EGF signaling is broader and includes p38 kinase. The synergism observed between IL-1β and EGF does not rely on augmented NFκB function, but rather, occurs through differential use of independent response elements within the COX-2 promoter. PMID:15329330

Cell recruitment by amnion chorion grafts promotes neovascularization.

PubMed

Maan, Zeshaan N; Rennert, Robert C; Koob, Thomas J; Januszyk, Michael; Li, William W; Gurtner, Geoffrey C

2015-02-01

Nonhealing wounds are a significant health burden. Stem and progenitor cells can accelerate wound repair and regeneration. Human amniotic membrane has demonstrated efficacy in promoting wound healing, though the underlying mechanisms remain unknown. A dehydrated human amnion chorion membrane (dHACM) was tested for its ability to recruit hematopoietic progenitor cells to a surgically implanted graft in a murine model of cutaneous ischemia. dHACM was subcutaneously implanted under elevated skin (ischemic stimulus) in either wild-type mice or mice surgically parabiosed to green fluorescent protein (GFP) + reporter mice. A control acellular dermal matrix, elevated skin without an implant, and normal unwounded skin were used as controls. Wound tissue was harvested and processed for histology and flow cytometric analysis. Implanted dHACMs recruited significantly more progenitor cells compared with controls (*P < 0.05) and displayed in vivo SDF-1 expression with incorporation of CD34 + progenitor cells within the matrix. Parabiosis modeling confirmed the circulatory origin of recruited cells, which coexpressed progenitor cell markers and were localized to foci of neovascularization within implanted matrices. In summary, dHACM effectively recruits circulating progenitor cells, likely because of stromal derived factor 1 (SDF-1) expression. The recruited cells express markers of "stemness" and localize to sites of neovascularization, providing a partial mechanism for the clinical efficacy of human amniotic membrane in the treatment of chronic wounds. Copyright © 2015 Elsevier Inc. All rights reserved.

Cell recruitment by amnion chorion grafts promotes neovascularization

PubMed Central

Koob, Thomas J.; Januszyk, Michael; Li, William W.; Gurtner, Geoffrey C.

2015-01-01

Background Nonhealing wounds are a significant health burden. Stem and progenitor cells can accelerate wound repair and regeneration. Human amniotic membrane has demonstrated efficacy in promoting wound healing, though the underlying mechanisms remain unknown. A dehydrated human amnion chorion membrane (dHACM) was tested for its ability to recruit hematopoietic progenitor cells to a surgically implanted graft in a murine model of cutaneous ischemia. Methods dHACM was subcutaneously implanted under elevated skin (ischemic stimulus) in either wild-type mice or mice surgically parabiosed to green fluorescent protein (GFP) + reporter mice. A control acellular dermal matrix, elevated skin without an implant, and normal unwounded skin were used as controls. Wound tissue was harvested and processed for histology and flow cytometric analysis. Results Implanted dHACMs recruited significantly more progenitor cells compared with controls (*P < 0.05) and displayed in vivo SDF-1 expression with incorporation of CD34 + progenitor cells within the matrix. Parabiosis modeling confirmed the circulatory origin of recruited cells, which coexpressed progenitor cell markers and were localized to foci of neovascularization within implanted matrices. Conclusions In summary, dHACM effectively recruits circulating progenitor cells, likely because of stromal derived factor 1 (SDF-1) expression. The recruited cells express markers of “stemness” and localize to sites of neovascularization, providing a partial mechanism for the clinical efficacy of human amniotic membrane in the treatment of chronic wounds. PMID:25266600

Evaluation of the cranial base in amnion rupture sequence involving the anterior neural tube: implications regarding recurrence risk.

PubMed

Jones, Kenneth Lyons; Robinson, Luther K; Benirschke, Kurt

2006-09-01

Amniotic bands can cause disruption of the cranial end of the developing fetus, leading in some cases to a neural tube closure defect. Although recurrence for unaffected parents of an affected child with a defect in which the neural tube closed normally but was subsequently disrupted by amniotic bands is negligible; for a primary defect in closure of the neural tube to which amnion has subsequently adhered, recurrence risk is 1.7%. In that primary defects of neural tube closure are characterized by typical abnormalities of the base of the skull, evaluation of the cranial base in such fetuses provides an approach for making a distinction between these 2 mechanisms. This distinction has implications regarding recurrence risk. The skull base of 2 fetuses with amnion rupture sequence involving the cranial end of the neural tube were compared to that of 1 fetus with anencephaly as well as that of a structurally normal fetus. The skulls were cleaned, fixed in 10% formalin, recleaned, and then exposed to 10% KOH solution. After washing and recleaning, the skulls were exposed to hydrogen peroxide for bleaching and photography. Despite involvement of the anterior neural tube in both fetuses with amnion rupture sequence, in Case 3 the cranial base was normal while in Case 4 the cranial base was similar to that seen in anencephaly. This technique provides a method for determining the developmental pathogenesis of anterior neural tube defects in cases of amnion rupture sequence. As such, it provides information that can be used to counsel parents of affected children with respect to recurrence risk.

A multicenter, randomized, controlled clinical trial evaluating the use of dehydrated human amnion/chorion membrane allografts and multilayer compression therapy vs. multilayer compression therapy alone in the treatment of venous leg ulcers.

PubMed

Serena, Thomas E; Carter, Marissa J; Le, Lam T; Sabo, Matthew J; DiMarco, Daniel T

2014-01-01

Venous leg ulcers produce significant clinical and economic burdens on society and often require advanced wound therapy. The purpose of this multicenter, randomized, controlled study is to evaluate the safety and efficacy of one or two applications of dehydrated human amnion/chorion membrane allograft and multilayer compression therapy vs. multilayer compression therapy alone in the treatment of venous leg ulcers. The primary study outcome was the proportion of patients achieving 40% wound closure at 4 weeks. Of the 84 participants enrolled, 53 were randomized to receive allograft and 31 were randomized to the control group of multilayer compression therapy alone. At 4 weeks, 62% in the allograft group and 32% in the control group showed a greater than 40% wound closure (p = 0.005), thus showing a significant difference between the allograft-treated groups and the multilayer compression therapy alone group at the 4-week surrogate endpoint. After 4 weeks, wounds treated with allograft had reduced in size a mean of 48.1% compared with 19.0% for controls. Venous leg ulcers treated with allograft had a significant improvement in healing at 4 weeks compared with multilayer compression therapy alone. © 2014 by the Wound Healing Society.

Placenta-an alternative source of stem cells

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

Matikainen, Tiina; Laine, Jarmo

2005-09-01

The two most promising practical applications of human stem cells are cellular replacement therapies in human disease and toxicological screening of candidate drug molecules. Both require a source of human stem cells that can be isolated, purified, expanded in number and differentiated into the cell type of choice in a controlled manner. Currently, uses of both embryonic and adult stem cells are investigated. While embryonic stem cells are pluripotent and can differentiate into any specialised cell type, their use requires establishment of embryonic stem cell lines using the inner cell mass of an early pre-implantation embryo. As the blastocyst ismore » destroyed during the process, ethical issues need to be carefully considered. The use of embryonic stem cells is also limited by the difficulties in growing large numbers of the cells without inducing spontaneous differentiation, and the problems in controlling directed differentiation of the cells. The use of adult stem cells, typically derived from bone marrow, but also from other tissues, is ethically non-controversial but their differentiation potential is more limited than that of the embryonic stem cells. Since human cord blood, umbilical cord, placenta and amnion are normally discarded at birth, they provide an easily accessible alternative source of stem cells. We review the potential and current status of the use of adult stem cells derived from the placenta or umbilical cord in therapeutic and toxicological applications.« less

Rolling the Human Amnion to Engineer Laminated Vascular Tissues

PubMed Central

Amensag, Salma

2012-01-01

The prevalence of cardiovascular disease and the limited availability of suitable autologous transplant vessels for coronary and peripheral bypass surgeries is a significant clinical problem. A great deal of progress has been made over recent years to develop biodegradable materials with the potential to remodel and regenerate vascular tissues. However, the creation of functional biological scaffolds capable of withstanding vascular stress within a clinically relevant time frame has proved to be a challenging proposition. As an alternative approach, we report the use of a multilaminate rolling approach using the human amnion to generate a tubular construct for blood vessel regeneration. The human amniotic membrane was decellularized by agitation in 0.03% (w/v) sodium dodecyl sulfate to generate an immune compliant material. The adhesion of human umbilical vein endothelial cells (EC) and human vascular smooth muscle cells (SMC) was assessed to determine initial binding and biocompatibility (monocultures). Extended cultures were either assessed as flat membranes, or rolled to form concentric multilayered conduits. Results showed positive EC adhesion and a progressive repopulation by SMC. Functional changes in SMC gene expression and the constructs' bulk mechanical properties were concomitant with vessel remodeling as assessed over a 40-day culture period. A significant advantage with this approach is the ability to rapidly produce a cell-dense construct with an extracellular matrix similar in architecture and composition to natural vessels. The capacity to control physical parameters such as vessel diameter, wall thickness, shape, and length are critical to match vessel compliance and tailor vessel specifications to distinct anatomical locations. As such, this approach opens new avenues in a range of tissue regenerative applications that may have a much wider clinical impact. PMID:22616610

Human amnion-derived mesenchymal stem cells protect against UVA irradiation-induced human dermal fibroblast senescence, in vitro

PubMed Central

Zhang, Chunli; Yuchi, Haishen; Sun, Lu; Zhou, Xiaoli; Lin, Jinde

2017-01-01

The aim of the present study was to determine if human amnion-derived mesenchymal stem cells (HAMSCs) exert a protective effect on ultraviolet A (UVA) irradiation-induced human dermal fibroblast (HDF) senescence. A senescence model was constructed as follows: HDFs (104–106 cells/well) were cultured in a six-well plate in vitro and then exposed to UVA irradiation at 9 J/cm2 for 30 min. Following the irradiation period, HDFs were co-cultured with HAMSCs, which were seeded on transwells. A total of 72 h following the co-culturing, senescence-associated β-galactosidase staining was performed and reactive oxygen species (ROS) content and mitochondrial membrane potential (Δψm) were detected in the HDFs via flow cytometric analysis. The results demonstrated that the percentage of HDFs, detected via staining with X-gal, were markedly decreased when co-cultured with human HAMSCs, compared with the group that were not co-cultured. The ROS content was decreased and the mitochondrial membrane potential (Δψm) recovered in cells treated with UVA and HAMSCs, compared with that of cells treated with UVA alone. Reverse transcription-quantitative polymerase chain reaction revealed the significant effects of HAMSCs on the HDF senescence marker genes p53 and matrix metalloproteinase-1 mRNA expression. In addition to this, western blot analysis verified the effects of HAMSCs on UVA induced senescence, providing a foundation for novel regenerative therapeutic methods. Furthermore, the results suggested that activation of the extracellular-signal regulated kinase 1/2 mitogen activated protein kinase signal transduction pathway, is essential for the HAMSC-mediated UVA protective effects. The decrease in ROS content additionally indicated that HAMSCs may exhibit the potential to treat oxidative stress-mediated UVA skin senescence in the future. PMID:28627622

Biological wound dressings sterilized with gamma radiation: Mexican clinical experience

NASA Astrophysics Data System (ADS)

Martínez-Pardo, M. E.; Ley-Chávez, E.; Reyes-Frías, M. L.; Rodríguez-Ferreyra, P.; Vázquez-Maya, L.; Salazar, M. A.

2007-11-01

Biological wound dressings sterilized with gamma radiation, such as amnion and pig skin, are a reality in Mexico. These tissues are currently processed in the tissue bank and sterilized in the Gamma Industrial Irradiation Plant; both facilities belong to the Instituto Nacional de Investigaciones Nucleares (ININ) (National Institute of Nuclear Research). With the strong support of the International Atomic Energy Agency, the bank was established at the ININ and the Mexican Ministry of Health issued its sanitary license on July 7, 1999. The Quality Management System of the bank was certified by ISO 9001:2000 on August 1, 2003; the scope of the system is "Research, Development and Processing of Biological Tissues Sterilized with Gamma Radiation". At present, more than 150 patients from 16 hospitals have been successfully treated with these tissues. This paper presents a brief description of the tissue processing, as well as the present Mexican clinical experience with children and adult patients who underwent medical treatment with radiosterilized amnion and pig skin, used as biological wound dressings on burns and ocular surface disorders.

Brief communication: sliding displacement of amnion and chorion following controlled laser wounding suggests a mechanism for short-term sealing of ruptured membranes.

PubMed

Behzad, F; Dickinson, M R; Charlton, A; Aplin, J D

1994-10-01

The Erbium-YAG laser was used to produce narrow wounds of defined depth in term amniochorion. The charring effect of the laser meant that sites could be readily localized in histological sections. During brief post-wounding incubations, sliding displacement of the amnion relative to the chorion occurred through the plane of the spongy layer. This suggests a possible short-term mechanism whereby a spontaneous rupture could be sealed in vivo.

Type I and II Diabetic Adipose-Derived Stem Cells Respond In Vitro to Dehydrated Human Amnion/Chorion Membrane Allograft Treatment by Increasing Proliferation, Migration, and Altering Cytokine Secretion

PubMed Central

Massee, Michelle; Chinn, Kathryn; Lim, Jeremy J.; Godwin, Lisa; Young, Conan S.; Koob, Thomas J.

2016-01-01

Objective: Human amniotic membranes have been shown to be effective for healing diabetic foot ulcers clinically and to regulate stem cell activity in vitro and in vivo; however, diabetic stem cells may be impaired as a sequela of the disease. In this study, dehydrated human amnion/chorion membrane (dHACM) allografts (EpiFix®; MiMedx Group) were evaluated for their ability to regulate diabetic stem cells in vitro. Approach: Human adipose-derived stem cells (ADSCs) from normal, type I diabetic, and type II diabetic donors were treated with soluble extracts of dHACM and evaluated for proliferation after 3 days by DNA assay, chemotactic migration after 1 day by transwell assay, cytokine secretion after 3 days by multiplex ELISA, and gene expression after 5 days by reverse transcription–polymerase chain reaction. Results: Although diabetic ADSCs demonstrated decreased responses compared to normal ADSCs, dHACM treatment stimulated diabetic ADSCs to proliferate after 3 days and enhanced migration over 24 h, similar to normal ADSCs. dHACM-treated diabetic ADSCs modulated secretion of soluble signals, including regulators of inflammation, angiogenesis, and healing. All ADSCs evaluated also responded to dHACM treatment with altered expression of immunomodulatory genes, including interleukins (IL)-1α, IL-1β, and IL-1RA. Innovation: This is the first reported case demonstrating that diabetic ADSCs respond to novel amniotic membrane therapies, specifically treatment with dHACM. Conclusion: dHACM stimulated diabetic ADSCs to migrate, proliferate, and alter cytokine expression suggesting that, despite their diabetic origin, ADSCs may respond to dHACM to accelerate diabetic wound healing. PMID:26862462

Type I and II Diabetic Adipose-Derived Stem Cells Respond In Vitro to Dehydrated Human Amnion/Chorion Membrane Allograft Treatment by Increasing Proliferation, Migration, and Altering Cytokine Secretion.

PubMed

Massee, Michelle; Chinn, Kathryn; Lim, Jeremy J; Godwin, Lisa; Young, Conan S; Koob, Thomas J

2016-02-01

Objective: Human amniotic membranes have been shown to be effective for healing diabetic foot ulcers clinically and to regulate stem cell activity in vitro and in vivo ; however, diabetic stem cells may be impaired as a sequela of the disease. In this study, dehydrated human amnion/chorion membrane (dHACM) allografts (EpiFix ® ; MiMedx Group) were evaluated for their ability to regulate diabetic stem cells in vitro . Approach: Human adipose-derived stem cells (ADSCs) from normal, type I diabetic, and type II diabetic donors were treated with soluble extracts of dHACM and evaluated for proliferation after 3 days by DNA assay, chemotactic migration after 1 day by transwell assay, cytokine secretion after 3 days by multiplex ELISA, and gene expression after 5 days by reverse transcription-polymerase chain reaction. Results: Although diabetic ADSCs demonstrated decreased responses compared to normal ADSCs, dHACM treatment stimulated diabetic ADSCs to proliferate after 3 days and enhanced migration over 24 h, similar to normal ADSCs. dHACM-treated diabetic ADSCs modulated secretion of soluble signals, including regulators of inflammation, angiogenesis, and healing. All ADSCs evaluated also responded to dHACM treatment with altered expression of immunomodulatory genes, including interleukins (IL)-1α, IL-1β, and IL-1RA. Innovation: This is the first reported case demonstrating that diabetic ADSCs respond to novel amniotic membrane therapies, specifically treatment with dHACM. Conclusion: dHACM stimulated diabetic ADSCs to migrate, proliferate, and alter cytokine expression suggesting that, despite their diabetic origin, ADSCs may respond to dHACM to accelerate diabetic wound healing.

Role of human amnion-derived mesenchymal stem cells in promoting osteogenic differentiation by influencing p38 MAPK signaling in lipopolysaccharide -induced human bone marrow mesenchymal stem cells

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

Wang, Yuli; Wu, Hongxia; Shen, Ming

Periodontitis is a chronic inflammatory disease induced by bacterial pathogens, which not only affect connective tissue attachments but also cause alveolar bone loss. In this study, we investigated the anti-inflammatory effects of Human amnion-derived mesenchymal stem cells (HAMSCs) on human bone marrow mesenchymal stem cells (HBMSCs) under lipopolysaccharide (LPS)-induced inflammatory conditions. Proliferation levels were measured by flow cytometry and immunofluorescence staining of 5-ethynyl-2′-deoxyuridine (EdU). Osteoblastic differentiation and mineralization were investigated using chromogenic alkaline phosphatase activity (ALP) activity substrate assays, Alizarin red S staining, and RT-PCR analysis of HBMSCs osteogenic marker expression. Oxidative stress induced by LPS was investigated by assayingmore » reactive oxygen species (ROS) level and superoxide dismutase (SOD) activity. Here, we demonstrated that HAMSCs increased the proliferation, osteoblastic differentiation, and SOD activity of LPS-induced HBMSCs, and down-regulated the ROS level. Moreover, our results suggested that the activation of p38 MAPK signal transduction pathway is essential for reversing the LPS-induced bone-destructive processes. SB203580, a selective inhibitor of p38 MAPK signaling, significantly suppressed the anti-inflammatory effects in HAMSCs. In conclusion, HAMSCs show a strong potential in treating inflammation-induced bone loss by influencing p38 MAPK signaling. - Highlights: • LPS inhibites osteogenic differentiation in HBMSCs via suppression of p38 MAPK signaling pathway. • HAMSCs promote LPS-induced HBMSCs osteogenic differentiation through p38 MAPK signaling pathway. • HAMSCs reverse LPS-induced oxidative stress in LPS-induced HBMSCs through p38 MAPK signaling pathway.« less

First steps to define murine amniotic fluid stem cell microenvironment.

PubMed

Bertin, E; Piccoli, M; Franzin, C; Spiro, G; Donà, S; Dedja, A; Schiavi, F; Taschin, E; Bonaldo, P; Braghetta, P; De Coppi, P; Pozzobon, M

2016-11-15

Stem cell niche refers to the microenvironment where stem cells reside in living organisms. Several elements define the niche and regulate stem cell characteristics, such as stromal support cells, gap junctions, soluble factors, extracellular matrix proteins, blood vessels and neural inputs. In the last years, different studies demonstrated the presence of cKit + cells in human and murine amniotic fluid, which have been defined as amniotic fluid stem (AFS) cells. Firstly, we characterized the murine cKit + cells present both in the amniotic fluid and in the amnion. Secondly, to analyze the AFS cell microenvironment, we injected murine YFP + embryonic stem cells (ESC) into the amniotic fluid of E13.5 wild type embryos. Four days after transplantation we found that YFP + sorted cells maintained the expression of pluripotency markers and that ESC adherent to the amnion were more similar to original ESC in respect to those isolated from the amniotic fluid. Moreover, cytokines evaluation and oxygen concentration analysis revealed in this microenvironment the presence of factors that are considered key regulators in stem cell niches. This is the first indication that AFS cells reside in a microenvironment that possess specific characteristics able to maintain stemness of resident and exogenous stem cells.

Evaluation of Amnion-derived Multipotent Progenitor (AMP) Cells and Amnion-derived Cellular Cytokine Solution (ST266) in Promoting Craniomaxillofacial Regenerative Bone Healing in Critical Size Calvarial Defects

DTIC Science & Technology

2017-10-10

action. MATERIALS AND METHODS Subjects Subjects used in the study include male Fischer 344 (CDF®) rats weighing 280-300 grams obtained from...PBS before being transferred to a flat bottom 96-well plate. Absorbance was then read at 450nm on a Biotek microplate reader. Live/Dead Staining of...incubation, live/dead staining of the scaffolds was imaged on a confocal microscope (Nikon). AMP Cell Differentiation To determine whether AMP

Effects of keratinocyte growth factor on skin epithelial differentiation of human amnion epithelial cells.

PubMed

Fatimah, Simat Siti; Tan, Geok Chin; Chua, Kienhui; Tan, Ay Eeng; Nur Azurah, Abdul Ghani; Hayati, Abdul Rahman

2013-08-01

The aim of the present study was to determine the effects of KGF on the differentiation of cultured human amnion epithelial cells (HAECs) towards skin keratinocyte. HAECs at passage 1 were cultured in medium HAM's F12: Dulbecco's Modified Eagles Medium (1:1) supplemented with different concentrations of KGF (0, 5, 10, 20, 30 and 50 ng/ml KGF). Dose-response of KGF on HAECs was determined by morphological assessment; growth kinetic evaluation; immunocytochemical analysis; stemness and epithelial gene expression quantification with two step real time RT-PCR. KGF promotes the proliferation of HAECs with maximal effect observed at 10 ng/ml KGF. However, KGF decreased the stemness genes expression: Oct-3/4, Sox-2, Nanog3, Rex-1, FGF-4, FZD-9 and BST-1. KGF also down-regulates epithelial genes expression: CK3, CK18, CK19, Integrin-β1, p63 and involucrin in cultured HAECs. No significant difference on the gene expression was detected for each Nestin, ABCG-2, CK1 and CK14 in KGF-treated HAECs. Immunocytochemical analysis for both control and KGF-treated HAECs demonstrated positive staining against CK14 and CK18 but negative staining against involucrin. The results suggested that KGF stimulates an early differentiation of HAECs towards epidermal cells. Differentiation of KGF-treated HAECs to corneal lineage is unfavourable. Therefore, further studies are needed to elucidate the roles of KGF in the differentiation of HAECs towards skin keratinocytes. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.

The fine structure of human germ layers in vivo: clues to the early differentiation of embryonic stem cells in vitro.

PubMed

Sathananthan, Henry; Selvaraj, Kamala; Clark, Joan

2011-08-01

The fine structure of the three germ layers in human ectopic embryos (stage 7) have been documented by digital light and electron microscopy. The formation of ectoderm, endoderm and mesoderm and notochordal cells, and also the extraembryonic membranes, amnion and yolk sac, are imaged. The germ layers give rise to all the cells and tissues of the human body. Possible clues to the early differentiation of embryonic stem cells (ESC) in vitro were obtained, since these events are more or less mimicked in cultures of ESC derived from the inner cell mass of human blastocysts. The findings are discussed with reference to previous studies on the fine structure of ESC using the same technique. Copyright © 2011. Published by Elsevier Ltd.

Intra-articular injection of micronized dehydrated human amnion/chorion membrane attenuates osteoarthritis development

PubMed Central

2014-01-01

Introduction Micronized dehydrated human amnion/chorion membrane (μ-dHACM) is derived from donated human placentae and has anti-inflammatory, low immunogenic and anti-fibrotic properties. The objective of this study was to quantitatively assess the efficacy of μ-dHACM as a disease modifying intervention in a rat model of osteoarthritis (OA). It was hypothesized that intra-articular injection of μ-dHACM would attenuate OA progression. Methods Lewis rats underwent medial meniscal transection (MMT) surgery to induce OA. Twenty four hours post-surgery, μ-dHACM or saline was injected intra-articularly into the rat joint. Naïve rats also received μ-dHACM injections. Microstructural changes in the tibial articular cartilage were assessed using equilibrium partitioning of an ionic contrast agent (EPIC-μCT) at 21 days post-surgery. The joint was also evaluated histologically and synovial fluid was analyzed for inflammatory markers at 3 and 21 days post-surgery. Results There was no measured baseline effect of μ-dHACM on cartilage in naïve animals. Histological staining of treated joints showed presence of μ-dHACM in the synovium along with local hypercellularity at 3 and 21 days post-surgery. In MMT animals, development of cartilage lesions at 21 days was prevented and number of partial erosions was significantly reduced by treatment with μ-dHACM. EPIC-μCT analysis quantitatively showed that μ-dHACM reduced proteoglycan loss in MMT animals. Conclusions μ-dHACM is rapidly sequestered in the synovial membrane following intra-articular injection and attenuates cartilage degradation in a rat OA model. These data suggest that intra-articular delivery of μ-dHACM may have a therapeutic effect on OA development. PMID:24499554

Dehydrated human amnion/chorion membrane regulates stem cell activity in vitro

PubMed Central

Massee, Michelle; Chinn, Kathryn; Lei, Jennifer; Lim, Jeremy J.; Young, Conan S.

2015-01-01

Abstract Human‐derived placental tissues have been shown in randomized clinical trials to be effective for healing chronic wounds, and have also demonstrated the ability to recruit stem cells to the wound site in vitro and in vivo. In this study, PURION® Processed dehydrated human amnion/chorion membrane allografts (dHACM, EpiFix®, MiMedx Group, Marietta, GA) were evaluated for their ability to alter stem cell activity in vitro. Human bone marrow mesenchymal stem cells (BM‐MSCs), adipose derived stem cells (ADSCs), and hematopoietic stem cells (HSCs) were treated with soluble extracts of dHACM tissue, and were evaluated for cellular proliferation, migration, and cytokine secretion. Stem cells were analyzed for cell number by DNA assay after 24 h, closure of an acellular zone using microscopy over 3 days, and soluble cytokine production in the medium of treated stem cells was analyzed after 3 days using a multiplex ELISA array. Treatment with soluble extracts of dHACM tissue stimulated BM‐MSCs, ADSCs, and HSCs to proliferate with a significant increase in cell number after 24 h. dHACM treatment accelerated closure of an acellular zone by ADSCs and BM‐MSCs after 3 days, compared to basal medium. BM‐MSCs, ADSCs, and HSCs also modulated endogenous production of a number of various soluble signals, including regulators of inflammation, mitogenesis, and wound healing. dHACM treatment promoted increased proliferation and migration of ADSCs, BM‐MSCs, and HSCs, along with modulation of secreted proteins from those cells. Therefore, dHACM may impact wound healing by amplifying host stem cell populations and modulating their responses in treated wound tissues. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1495–1503, 2016. PMID:26175122

Stemness and angiogenic gene expression changes of serial-passage human amnion mesenchymal cells.

PubMed

Fatimah, Simat Siti; Tan, Geok Chin; Chua, Kienhui; Fariha, Mohd Manzor Nur; Tan, Ay Eeng; Hayati, Abdul Rahman

2013-03-01

Particular attention has been directed towards human amnion mesenchymal stem cells (HAMCs) due to their accessibility, availability and immunomodulatory properties. Therefore, the aim of the present study was to determine the temporal changes of stemness and angiogenic gene expressions of serial-passage HAMCs. HAMCs were isolated from human term placenta and cultured in serial passages in culture medium supplemented with 10% fetal bovine serum. Morphological analysis, growth kinetic and CFU-F assay of HAMCs were assessed. In vitro differentiation and the immunophenotype of HAMCs at P5 were also analyzed. Quantitative PCR was used to determine the stemness, angiogenic and endothelial gene expression of cultured HAMCs after serial passage. Cultured HAMCs displayed intermediate epitheloid-fibroblastoid morphology at an initial culture and the fibroblastoid features became more pronounced in later passages. They showed high clonogenic activity and faster proliferation at later passages with colony forming efficiency of 0.88%. HAMCs were successfully differentiated into adipocytes, osteocytes and neuron-like cells. Most HAMCs expressed CD9, CD44, CD73, CD90 and HLA-A,B,C but negligibly expressed CD31, CD34, CD45, CD117 and HLA-DR,DP,DQ. After serial passage, stemness genes Oct-3/4, Sox-2, Nanog3, Rex-1, FGF-4 and FZD-9 expressions significantly decreased. Of the angiogenic genes PECAM-1, bFGF, eNOS, VEGFR-2, VEGF, and vWF expressions also decreased significantly except angiopoietin-1 which significantly increased. No significant differences were observed in ABCG-2, BST-1, nestin, PGF and HGF expressions after serial passage. These results suggested that cultured HAMCs could be an alternative source of stem cells and may have the potential for angiogenesis and hence its use in stem-cell based therapy. Copyright © 2012 Elsevier Inc. All rights reserved.

Inflammatory Gene Regulatory Networks in Amnion Cells Following Cytokine Stimulation: Translational Systems Approach to Modeling Human Parturition

PubMed Central

Summerfield, Taryn L.; Yu, Lianbo; Gulati, Parul; Zhang, Jie; Huang, Kun; Romero, Roberto; Kniss, Douglas A.

2011-01-01

A majority of the studies examining the molecular regulation of human labor have been conducted using single gene approaches. While the technology to produce multi-dimensional datasets is readily available, the means for facile analysis of such data are limited. The objective of this study was to develop a systems approach to infer regulatory mechanisms governing global gene expression in cytokine-challenged cells in vitro, and to apply these methods to predict gene regulatory networks (GRNs) in intrauterine tissues during term parturition. To this end, microarray analysis was applied to human amnion mesenchymal cells (AMCs) stimulated with interleukin-1β, and differentially expressed transcripts were subjected to hierarchical clustering, temporal expression profiling, and motif enrichment analysis, from which a GRN was constructed. These methods were then applied to fetal membrane specimens collected in the absence or presence of spontaneous term labor. Analysis of cytokine-responsive genes in AMCs revealed a sterile immune response signature, with promoters enriched in response elements for several inflammation-associated transcription factors. In comparison to the fetal membrane dataset, there were 34 genes commonly upregulated, many of which were part of an acute inflammation gene expression signature. Binding motifs for nuclear factor-κB were prominent in the gene interaction and regulatory networks for both datasets; however, we found little evidence to support the utilization of pathogen-associated molecular pattern (PAMP) signaling. The tissue specimens were also enriched for transcripts governed by hypoxia-inducible factor. The approach presented here provides an uncomplicated means to infer global relationships among gene clusters involved in cellular responses to labor-associated signals. PMID:21655103

Activation of AMPK in human fetal membranes alleviates infection-induced expression of pro-inflammatory and pro-labour mediators.

PubMed

Lim, R; Barker, G; Lappas, M

2015-04-01

In non-gestational tissues, the activation of adenosine monophosphate (AMP)-activated kinase (AMPK) is associated with potent anti-inflammatory actions. Infection and/or inflammation, by stimulating pro-inflammatory cytokines and matrix metalloproteinase (MMP)-9, play a central role in the rupture of fetal membranes. However, no studies have examined the role of AMPK in human labour. Fetal membranes, from term and preterm, were obtained from non-labouring and labouring women, and after preterm pre-labour rupture of membranes (PPROM). AMPK activity was assessed by Western blotting of phosphorylated AMPK expression. To determine the effect of AMPK activators on pro-inflammatory cytokines, fetal membranes were pre-treated with AMPK activators then stimulated with bacterial products LPS and flagellin or viral dsDNA analogue poly(I:C). Primary amnion cells were used to determine the effect of AMPK activators on IL-1β-stimulated MMP-9 expression. AMPK activity was decreased with term labour. There was no effect of preterm labour. AMPK activity was also decreased in preterm fetal membranes, in the absence of labour, with PROM compared to intact membranes. AMPK activators AICAR, phenformin and A769662 significantly decreased IL-6 and IL-8 stimulated by LPS, flagellin and poly(I:C). Primary amnion cells treated with AMPK activators significantly decreased IL-1β-induced MMP-9 expression. The decrease in AMPK activity in fetal membranes after spontaneous term labour and PPROM indicates an anti-inflammatory role for AMPK in human labour and delivery. The use of AMPK activators as possible therapeutics for threatened preterm labour would be an exciting future avenue of research. Copyright © 2015 Elsevier Ltd. All rights reserved.

Fetal Fibronectin Signaling Induces Matrix Metalloproteases and Cyclooxygenase-2 (COX-2) in Amnion Cells and Preterm Birth in Mice*

PubMed Central

Mogami, Haruta; Kishore, Annavarapu Hari; Shi, Haolin; Keller, Patrick W.; Akgul, Yucel; Word, R. Ann

2013-01-01

Fetal fibronectin (fFN) in cervical and vaginal secretions has been used as a predictor of preterm delivery. Here, we clarified the pathological function of fFN on cell type-specific matrix metalloproteinases (MMPs) and prostaglandin synthesis in fetal membranes. Treatment of amnion mesenchymal cells with fFN resulted in dramatic increases in MMP-1 and MMP-9 mRNA and enzymatic activity as well as COX-2 mRNA and prostaglandin E2 synthesis, activating both NFκB and ERK1/2 signaling. Fetal FN-induced increases in MMPs and COX-2 were mediated through its extra domain A and Toll-like receptor 4 expressed in mesenchymal cells. Lipopolysaccharide and TNF-α increased the release of free FN in medium of amnion epithelial cells in culture. Finally, injection of fFN in pregnant mice resulted in preterm birth. Collectively, these results indicate that fFN is not only a marker of preterm delivery but also plays a significant role in the pathogenesis of preterm labor and premature rupture of fetal membranes. PMID:23184961

Progesterone, Inflammatory Cytokine (TNF-α), and Oxidative Stress (H2O2) Regulate Progesterone Receptor Membrane Component 1 Expression in Fetal Membrane Cells.

PubMed

Meng, Yan; Murtha, Amy P; Feng, Liping

2016-09-01

Progesterone receptor membrane component 1 (PGRMC1) is an important novel mediator of progesterone (P4) function in fetal membrane cells. We demonstrated previously that PGRMC1 is differentially expressed in fetal membranes among pregnancy subjects and diminished in preterm premature rupture of membrane subjects. In the current study, we aim to elucidate whether PGRMC1 expression is regulated by P4, tumor necrosis factor α (TNF-α), and H2O2 in fetal membrane cells. Primary cultured membrane cells were serum starved for 24 hours followed by treatments of P4, 17 hydroxyprogesterone caproate, and medroxyprogesterone 17 acetate (MPA) at 10(-7) mol/L with ethanol as vehicle control; TNF-α at 10, 20, and 50 ng/mL with phosphate-buffered saline (PBS) as control; and H2O2 at 10 and 100 μmol/L with culture media as control for 24, 48, and 72 hours. The messenger RNA (mRNA) and protein expression of PGRMC1 was quantified using polymerase chain reaction and Western blotting, respectively. We found that PGRMC1 protein expression was regulated by MPA, TNF-α, and H2O2 in a dose-dependent manner. This regulation is also specific to the type of cell (amnion, chorion, or decidua). The upregulation of PGRMC1 by MPA might be mediated through glucocorticoid receptor (GR) demonstrated using amnion and chorion cells model with GR knockdown by specific small interfering RNA transfection. The mRNA expression of PGRMC1 was decreased by H2O2 (100 μmol/L) treatment in amnion cells, which might ultimately result in downregulation of PGRMC1 protein as our data demonstrated. None of other treatments changed PGRMC1 mRNA level in these cells. We conclude that these stimuli act as regulatory factors of PGRMC1 in a cell-specific manner. © The Author(s) 2016.

Production of Reference Enteroviruses

PubMed Central

Kalter, S. S.; Rodriguez, A. R.; Armour, V.

1968-01-01

Forty-five human enterovirus reagents of certified purity and quality were prepared for use as seed viruses and as immunizing antigens. One of the reagents was ampouled as “untreated” seed virus, whereas 14 were ampouled as “MgCl2-stabilized” reagents. The remaining 30 reagents were ampouled as “untreated” seed viruses and as “MgCl2-stabilized” reagents. Thirty of the reagents were propagated on primary African green monkey kidney cells, 3 on primary baboon kidney cells, 3 on primary rhesus monkey kidney cells, and the remaining 9 on human amnion cells. Forty-two of the viral antigens were concentrated for use in the production of high-titered specific antisera in large animals. PMID:4300898

The Use of a Dehydrated Amnion/Chorion Membrane Allograft in Patients Who Subsequently Undergo Reexploration after Posterior Lumbar Instrumentation

PubMed Central

Subach, Brian R.; Copay, Anne G.

2015-01-01

Background Context. Products that can reduce development of epidural fibrosis may reduce risk for ongoing pain associated with development of scar tissue and make subsequent epidural reexploration easier. Purpose. To evaluate the use of dehydrated human amnion/chorion membrane (dHACM) on the formation of soft tissue scarring in the epidural space. Study Design. Case series. Patient Sample. Five patients having transforaminal lumbar interbody lumbar fusion (TLIF) with posterior instrumentation and implantation of dHACM in the epidural space and subsequent epidural reexploration. Outcome Measures. Degree of scar tissue adjacent to the epidural space at reexploration. Intraoperative and postoperative complications related to dHACM and patient reported outcomes. Methods. The degree of scar tissue adjacent to the epidural space was assessed during the reexploration surgery. Patients' outcomes were collected using standard validated questionnaires. Results. Four of 5 cases had easily detachable tissue during epidural reexploration. Angiolipoma of 10% was noted in 1 case and 5% in 2 cases. Significant improvements in patient reported outcomes were observed. No intraoperative or postoperative complications occurred. Conclusions. Our findings suggest that dHACM implant during TLIF may have favorable effects on epidural fibrosis and is well tolerated. Further studies with larger cohorts are required to prove our results. PMID:25653880

Successful vitrification of human amnion-derived mesenchymal stem cells.

PubMed

Moon, Jeong Hee; Lee, Jung Ryeol; Jee, Byung Chul; Suh, Chang Suk; Kim, Seok Hyun; Lim, Hyun Jung; Kim, Hae Kwon

2008-08-01

A cryopreservation protocol for human amnion-derived mesenchymal stem cells (HAMs) is required because these cells cannot survive for long periods in culture. The aim of this study was to determine whether vitrification is a useful freezing method for storage of HAMs. HAMs were cryopreserved using vitrification method. The morphology and viability of thawed HAMs was evaluated by Trypan Blue staining. The expression of several embryonic stem cell (ESC) markers was evaluated using flow cytometry, RT-PCR and immunocytochemistry. Von Kossa, Oil Red O and Alcian Blue staining were used to asses the differentiation potential of thawed HAMs. The post-thawing viability of HAMs was 84.3 +/- 3.2% (Mean +/- SD, n = 10). The thawed HAMs showed morphological characteristics indistinguishable from the non-vitrified fresh HAMs. The expression of surface antigens (strong positive for CD44, CD49d, CD59, CD90, CD105 and HLA-ABC; weak positive for HLA-G; negative for CD31, CD34, CD45, CD106, CD117 and HLA-DR) and the expression of ESC markers [CK18, fibroblast growth factor-5, GATA-4, neural cell adhesion molecule, Nestin, Oct-4, stem cell factor, HLA-ABC, Vimentin, bone morphogenetic protein (BMP) 4, hepatocyte nuclear factor 4 alpha (HNF-4 alpha), Pax-6, alpha-fetoprotein, Brachyury, BMP-2, TRA-1-60, stage-specific embryonic antigen (SSEA-3, SSEA-4)] were maintained in the vitrified-thawed HAMs. The thawed HAMs retained ability to differentiate into osteoblasts, adipocytes and chondrocytes under appropriate culture conditions. Our results suggest that vitrification is a reliable and effective method for cryopreservation of HAMs.

Cinematographic observations of growth cycles of Chlamydia trachomatis in primary cultures of human amniotic cells.

PubMed Central

Neeper, I D; Patton, D L; Kuo, C C

1990-01-01

Time-lapse cinematography was used to study the growth cycle of Chlamydia trachomatis in primary cell cultures of human amnion. Twelve preterm and twelve term placentas were obtained within 8 h of delivery, and epithelial cells were dissociated from the amniotic membranes by trypsinization and grown in Rose chambers. The epithelial nature of the cultured cells was documented by morphology and by immunofluorescence staining for cytoskeletal proteins, which matched the staining of intact amnion. With regular feedings, uninfected cultures remained healthy for up to 30 days. Confluent cultures (7 to 10 days) were infected with a genital strain (E/UW-5/CX) of C. trachomatis at 10(5) infectious units per chamber. Infections were done in culture medium without cycloheximide, which is often used to induce susceptibility of the cells. Between 66 and 90% of the cells were infected. Intracytoplasmic inclusions were visible by 18 h post infection (p.i.) and grew larger as the organisms inside multiplied. By 72 h p.i., the inclusions occupied the entire cytoplasm of the host cells. Further growth of the inclusions overdistended and ruptured the host cells on days 3 to 7. Cells not infected by the original inoculum became infected on day 5 or 6 p.i. by the chlamydial particles released from the ruptured cells. No amniotic cell was ever observed to survive the infection. The data presented support the hypothesis that amniotic epithelium is susceptible to infection and damage by C. trachomatis. This culture system provided detailed and dynamic observations of chlamydial infection under conditions more nearly physiologic than previously reported. Images PMID:2365450

Dehydrated human amnion/chorion membrane regulates stem cell activity in vitro.

PubMed

Massee, Michelle; Chinn, Kathryn; Lei, Jennifer; Lim, Jeremy J; Young, Conan S; Koob, Thomas J

2016-10-01

Human-derived placental tissues have been shown in randomized clinical trials to be effective for healing chronic wounds, and have also demonstrated the ability to recruit stem cells to the wound site in vitro and in vivo. In this study, PURION(®) Processed dehydrated human amnion/chorion membrane allografts (dHACM, EpiFix(®) , MiMedx Group, Marietta, GA) were evaluated for their ability to alter stem cell activity in vitro. Human bone marrow mesenchymal stem cells (BM-MSCs), adipose derived stem cells (ADSCs), and hematopoietic stem cells (HSCs) were treated with soluble extracts of dHACM tissue, and were evaluated for cellular proliferation, migration, and cytokine secretion. Stem cells were analyzed for cell number by DNA assay after 24 h, closure of an acellular zone using microscopy over 3 days, and soluble cytokine production in the medium of treated stem cells was analyzed after 3 days using a multiplex ELISA array. Treatment with soluble extracts of dHACM tissue stimulated BM-MSCs, ADSCs, and HSCs to proliferate with a significant increase in cell number after 24 h. dHACM treatment accelerated closure of an acellular zone by ADSCs and BM-MSCs after 3 days, compared to basal medium. BM-MSCs, ADSCs, and HSCs also modulated endogenous production of a number of various soluble signals, including regulators of inflammation, mitogenesis, and wound healing. dHACM treatment promoted increased proliferation and migration of ADSCs, BM-MSCs, and HSCs, along with modulation of secreted proteins from those cells. Therefore, dHACM may impact wound healing by amplifying host stem cell populations and modulating their responses in treated wound tissues. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1495-1503, 2016. © 2015 The Authors. Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc.

Amnion and Chorion Membranes: Potential Stem Cell Reservoir with Wide Applications in Periodontics

PubMed Central

2015-01-01

The periodontal therapy usually aims at elimination of disease causing bacteria and resolution of inflammation. It involves either resective or regenerative surgery to resolve the inflammation associated defects. Over the years, several methods have been used for achievement of periodontal regeneration. One of the oldest biomaterials used for scaffolds is the fetal membrane. The amniotic membranes of developing embryo, that is, amnion (innermost lining) and chorion (a layer next to it), have the properties with significant potential uses in dentistry. This paper reviews the properties, mechanism of action, and various applications of these placental membranes in general and specifically in Periodontics. PMID:26770199

Amnion and Chorion Membranes: Potential Stem Cell Reservoir with Wide Applications in Periodontics.

PubMed

Gupta, Akanksha; Kedige, Suresh D; Jain, Kanu

2015-01-01

The periodontal therapy usually aims at elimination of disease causing bacteria and resolution of inflammation. It involves either resective or regenerative surgery to resolve the inflammation associated defects. Over the years, several methods have been used for achievement of periodontal regeneration. One of the oldest biomaterials used for scaffolds is the fetal membrane. The amniotic membranes of developing embryo, that is, amnion (innermost lining) and chorion (a layer next to it), have the properties with significant potential uses in dentistry. This paper reviews the properties, mechanism of action, and various applications of these placental membranes in general and specifically in Periodontics.

Minimally Invasive Surgical Device for Precise Application of Bioadhesives to Prevent iPPROM.

PubMed

Devaud, Yannick Robert; Züger, Silvia; Zimmermann, Roland; Ehrbar, Martin; Ochsenbein-Kölble, Nicole

2018-06-19

The benefits of endoscopic fetal surgery are deteriorated by the high risk of iatrogenic preterm prelabor rupture of fetal membranes (iPPROM). While previous studies have reported good sealing candidates to prevent membrane rupture, the delivery of these materials to the location of membrane puncture remains unsolved. We describe an approach to apply sealing materials onto the amnion through the fetoscopy port. We developed a device composed of an umbrella-shaped polyester coated nitinol mesh and an applicator. The spontaneously unfolding umbrella is pushed through the port, pulled against the amnion, and glued onto the amnion defect site. We tested the adhesion strength of multiple glues and tested the feasibility and reproducibility of this fetal membrane sealing approach in an ex vivo model. The umbrella unfolded and was well positioned in all tests (n = 18). When applied via the fetoscopy port, umbrellas were successfully glued onto the fetal membrane, and all of them completely covered the defect (n = 5). The mean time needed for the whole procedure was 3 min. This study is a proof of concept presenting a potential future solution for the precise local application of bioadhesives for the prevention of iPPROM. © 2018 S. Karger AG, Basel.

Myocytes of chorionic vessels from placentas with meconium-associated vascular necrosis exhibit apoptotic markers.

PubMed

King, Erin L; Redline, Raymond W; Smith, Steven D; Kraus, Frederick T; Sadovsky, Yoel; Nelson, D Michael

2004-04-01

Meconium-associated vascular necrosis (MAVN) is a histological abnormality of human placental chorionic vessels that is associated with poor neonatal outcome. We tested the hypothesis that MAVN shows apoptosis in the walls of chorionic vessels. Archival placental specimens with MAVN (n = 5) were compared with specimens from uncomplicated pregnancies at term (n = 5) and from placentas with intense chorionic vasculitis associated with acute chorioamnionitis with (n = 5) or without (n = 5) a clinical history of meconium in the amniotic fluid. Sections from all placentas were processed by the TUNEL method, and 2 observers who were blinded to specimen diagnosis quantified the immunofluorescent TUNEL staining in both the amnion-facing and villous-facing walls of the larger chorionic vessels in each specimen. Compared with the other 3 groups, only the amnion-facing wall of chorionic vessels in MAVN showed a significantly greater number of apoptotic cells. This was verified by morphological criteria and caspase 3 staining. There were limited or no detectable TUNEL-stained cells in either the villous-facing walls of vessels in the MAVN specimens or in any of the vessels of the placentas from uncomplicated pregnancies. There was a negligible level of apoptosis in chorionic vessels of placentas with intense chorionic vasculitis, with or without meconium, despite the inflammatory response or presence of meconium. We conclude that apoptosis contributes to the pathophysiology of MAVN.

Identification of Extracellular Matrix Components and Biological Factors in Micronized Dehydrated Human Amnion/Chorion Membrane

PubMed Central

Lei, Jennifer; Priddy, Lauren B.; Lim, Jeremy J.; Massee, Michelle; Koob, Thomas J.

2017-01-01

Objective: The use of bioactive extracellular matrix (ECM) grafts such as amniotic membranes is an attractive treatment option for enhancing wound repair. In this study, the concentrations, activity, and distribution of matrix components, growth factors, proteases, and inhibitors were evaluated in PURION® Processed, micronized, dehydrated human amnion/chorion membrane (dHACM; MiMedx Group, Inc.). Approach: ECM components in dHACM tissue were assessed by using immunohistochemical staining, and growth factors, cytokines, proteases, and inhibitors were quantified by using single and multiplex ELISAs. The activities of proteases that were native to the tissue were determined via gelatin zymography and EnzChek® activity assay. Results: dHACM tissue contained the ECM components collagens I and IV, hyaluronic acid, heparin sulfate proteoglycans, fibronectin, and laminin. In addition, numerous growth factors, cytokines, chemokines, proteases, and protease inhibitors that are known to play a role in the wound-healing process were quantified in dHACM. Though matrix metalloproteinases (MMPs) were present in dHACM tissues, inhibitors of MMPs overwhelmingly outnumbered the MMP enzymes by an overall molar ratio of 28:1. Protease activity assays revealed that the MMPs in the tissue existed primarily either in their latent form or complexed with inhibitors. Innovation: This is the first study to characterize components that function in wound healing, including inhibitor and protease content and activity, in micronized dHACM. Conclusion: A variety of matrix components and growth factors, as well as proteases and their inhibitors, were identified in micronized dHACM, providing a better understanding of how micronized dHACM tissue can be used to effectively promote wound repair. PMID:28224047

A prospective, randomised comparative study of weekly versus biweekly application of dehydrated human amnion/chorion membrane allograft in the management of diabetic foot ulcers

PubMed Central

Zelen, Charles M; Serena, Thomas E; Snyder, Robert J

2014-01-01

The aim of this study is to determine if weekly application of dehydrated human amnion/chorion membrane allograft reduce time to heal more effectively than biweekly application for treatment of diabetic foot ulcers. This was an institutional review board-approved, registered, prospective, randomised, comparative, non-blinded, single-centre clinical trial. Patients with non-infected ulcers of ≥ 4 weeks duration were included for the study. They were randomised to receive weekly or biweekly application of allograft in addition to a non-adherent, moist dressing with compressive wrapping. All wounds were offloaded. The primary study outcome was mean time to healing. Overall, during the 12-week study period, 92·5% (37/40) ulcers completely healed. Mean time to complete healing was 4·1 ± 2·9 versus 2·4 ± 1·8 weeks (P = 0·039) in the biweekly versus weekly groups, respectively. Complete healing occurred in 50% versus 90% by 4 weeks in the biweekly and weekly groups, respectively (P = 0·014). Number of grafts applied to healed wounds was similar at 2·4 ± 1·5 and 2·3 ± 1·8 for biweekly versus weekly groups, respectively (P = 0·841). These results validate previous studies showing that the allograft is an effective treatment for diabetic ulcers and show that wounds treated with weekly application heal more rapidly than with biweekly application. More rapid healing may decrease clinical operational costs and prevent long-term medical complications. PMID:24618401

Identification of Extracellular Matrix Components and Biological Factors in Micronized Dehydrated Human Amnion/Chorion Membrane.

PubMed

Lei, Jennifer; Priddy, Lauren B; Lim, Jeremy J; Massee, Michelle; Koob, Thomas J

2017-02-01

Objective: The use of bioactive extracellular matrix (ECM) grafts such as amniotic membranes is an attractive treatment option for enhancing wound repair. In this study, the concentrations, activity, and distribution of matrix components, growth factors, proteases, and inhibitors were evaluated in PURION ® Processed, micronized, dehydrated human amnion/chorion membrane (dHACM; MiMedx Group, Inc.). Approach: ECM components in dHACM tissue were assessed by using immunohistochemical staining, and growth factors, cytokines, proteases, and inhibitors were quantified by using single and multiplex ELISAs. The activities of proteases that were native to the tissue were determined via gelatin zymography and EnzChek ® activity assay. Results: dHACM tissue contained the ECM components collagens I and IV, hyaluronic acid, heparin sulfate proteoglycans, fibronectin, and laminin. In addition, numerous growth factors, cytokines, chemokines, proteases, and protease inhibitors that are known to play a role in the wound-healing process were quantified in dHACM. Though matrix metalloproteinases (MMPs) were present in dHACM tissues, inhibitors of MMPs overwhelmingly outnumbered the MMP enzymes by an overall molar ratio of 28:1. Protease activity assays revealed that the MMPs in the tissue existed primarily either in their latent form or complexed with inhibitors. Innovation: This is the first study to characterize components that function in wound healing, including inhibitor and protease content and activity, in micronized dHACM. Conclusion: A variety of matrix components and growth factors, as well as proteases and their inhibitors, were identified in micronized dHACM, providing a better understanding of how micronized dHACM tissue can be used to effectively promote wound repair.

Studies of hemidesmosomes in human amnion: the use of a detergent extraction protocol for compositional and ultrastructural analysis and preparation of a hemidesmosome-enriched fraction from tissue.

PubMed

Behzad, F; Jones, C J; Ball, S; Alvares, T; Aplin, J D

1995-01-01

A method is described for the sequential detergent and high ionic strength extraction of human amnion with the progressive enrichment of the intermediate filament (IF) cytoskeleton and its associated structures including hemidesmosomes (HD). TEM of the extracted epithelium in situ reveals IF bundles beneath the apical cell surface, around the nucleus and at the lateral edges of the cells where association with desmosomes occurs. IF bundles are also very prominent within basal cell processes where they loop through the cytoplasm adjacent to the HDs. A novel connecting filament network is observed running between the IFs and the hemidesmosomal dense plaque. The adjacent IF network contains both cytokeratin and vimentin, the latter revealed much more fully as a result of the extraction protocol. The hemidesmosomal plasma membrane contains integrin subunits alpha 6 and beta 4 and these are quantitatively retained as the basal cell surface during extraction, while nonjunctional plasma membrane is solubilised. Integrin beta 1 is found at the basolateral cell surface but, like actin, is extracted quantitatively and is not present in HDs. The extracted epithelial cells may be recovered by scraping and the IF network depolymerised to produce a particulate fraction containing short residual IFs, associated thin filaments and plaque material. This fraction contains immunoreactive cytokeratin and vimentin. Integrin alpha 6 beta 4 has been used as a biochemical criterion of the presence of HD material in the fraction. Both subunits are highly enriched. The fraction also contains the hemidesmosomal components HD1, BP230 and BP180. This method is likely to be useful in further characterisation of the HD.

Amniotic mesenchymal tissue cells inhibit dendritic cell differentiation of peripheral blood and amnion resident monocytes.

PubMed

Magatti, Marta; De Munari, Silvia; Vertua, Elsa; Nassauto, Claudia; Albertini, Alberto; Wengler, Georg S; Parolini, Ornella

2009-01-01

Cells derived from the amniotic membranes of human term placenta have drawn much interest for their characteristics of multipotency and low immunogenicity, supporting a variety of possible clinical applications in the field of cell transplantation and regenerative medicine. We have previously shown that cells derived from the mesenchymal region of human amnion (AMTC) can strongly inhibit T-lymphocyte proliferation. In this study, we demonstrate that AMTC can block differentiation and maturation of monocytes into dendritic cells (DC), preventing the expression of the DC marker CD1a and reducing the expression of HLA-DR, CD80, and CD83. The monocyte maturation block resulted in impaired allostimulatory ability of these cells on allogeneic T cells. In attempting to define the mechanisms responsible for these findings, we have observed that the presence of AMTC in differentiating DC cultures results in the arrest of the cells to the G(0) phase and abolishes the production of inflammatory cytokines such as TNF-alpha, CXCL10, CXCL9, and CCL5. Finally, we also demonstrate that the monocytic cells present in the amniotic mesenchymal region fail to differentiate toward the DC lineage. Taken together, our data suggest that the mechanisms by which AMTC exert immumodulatory effects do not only relate directly to T cells, but also include inhibition of the generation and maturation of antigen-presenting cells. In this context, AMTC represent a very attractive source of multipotent allogeneic cells that promise to be remarkably valuable for cell transplantation approaches, not only due to their low immunogenicity, but also because of the added potential of modulating immune responses, which could be fundamental both for controlling graft rejection after transplantation and also for controlling diseases characterized by inflammatory processes.

The advantages of the application of amnion membrane in the treatment of burns.

PubMed

Andonovska, D; Dzokic, Gj; Spasevska, L; Trajkovska, T; Popovska, K; Todorov, I; Petrovski, P; Kondov, G; Sapova, B; Marcikic, G; Atanasova, E; Obocki, E; Ugrinovska, J; Andonovski, D; Andonovski, D; Vasilevska, V; Mircevska-Zogovska, E

2008-07-01

A crucial and important factor for successful treatment of burns is the early covering of the burned area with skin substitutes. The covering of the burn requires material that restores the epidermal function and integrates itself into the process of healing. Biological dressings are the golden standard for the temporary covering of burns. All biological skin substitutes are susceptible to early graft reaction and the only exception is the amnion membrane. The importance of the amnion membrane as a biological dressing for burns amounts to: a barrier to bacterial colonization, hastens the epithelisation, and control of water loss. Amnioplasty is a method of application of amnion membrane on the recipient site. In this comparative study, 60 patients with dermal and sub-dermal burns were included. Research was made on an examination group of 30 patients with burns where the method of amnioplasty was applied, and for this amnion membrane conserved in 76% alcohol was used. The control group was made up of 30 patients with burns treated conventionally, and standard methods for the local treatment of burns were applied: exposition, occlusive dressing and initial excision with skin grafting. Pathohistological and microbiological analyses of the bioptical material were made. The degree of the burns was determined through a pathohistological analysis of the bioptical material taken the third day, and in some of the subjects where re-epithelialization was determined on the seventh day, the further re-epithelialization was observed clinically. Pathohistological examination enabled discrimination between bacterial colonization and the invasive bacterial infection. Furthermore, the type of bacterial colonization and infection was determined, which was confirmed with microbiological analysis. The analysis of the results from the microbiological and pathohistological researches of the bioptical material according to the bacterial colonization and infection showed that, although between the examined and the control group there was no statistically important difference, the value of p = 0.067 is close to the statistically important value of p < 0.05. The results of the pathohistological examination of the bioptical material taken the seventh day and analysed according to the re-epithelialization showed that there was a significant difference between the two groups of p < 0.035. It should be mentioned that, although according to the microbiological examinations of the bioptical material a statistically significant difference was not achieved, clinical significance was achieved. The obtained significance of p < 0.035 compared to the re-epithelialization in both groups approved the application of the method of amnioplasty. The histological analysis of the bioptical material not only determines the degree of the burns specifically, but facilitates the choice of method for further treatment, observes the speed of the re-epithelialization and plays an important part in the correct diagnosis and the early start of the specific therapy, important in preventing sepsis. The application of amnion membrane as a biological dressing speeds the re-epithelialization and prevents invasive bacterial infection. Pathohistological examination of the burns is recommended to be established as a standard method in clinical practice.

Transport and biodistribution of dendrimers across human fetal membranes: implications for intravaginal administration of dendrimer-drug conjugates.

PubMed

Menjoge, Anupa R; Navath, Raghavendra S; Asad, Abbas; Kannan, Sujatha; Kim, Chong J; Romero, Roberto; Kannan, Rangaramanujam M

2010-06-01

Dendrimers are emerging as promising topical antimicrobial agents, and as targeted nanoscale drug delivery vehicles. Topical intravaginal antimicrobial agents are prescribed to treat the ascending genital infections in pregnant women. The fetal membranes separate the extra-amniotic space and fetus. The purpose of the study is to determine if the dendrimers can be selectively used for local intravaginal application to pregnant women without crossing the membranes into the fetus. In the present study, the transport and permeability of PAMAM (poly (amidoamine)) dendrimers, across human fetal membrane (using a side by side diffusion chamber), and its biodistribution (using immunofluorescence) are evaluated ex-vivo. Transport across human fetal membranes (from the maternal side) was evaluated using Fluorescein (FITC), an established transplacental marker (positive control, size approximately 400 Da) and fluorophore-tagged G(4)-PAMAM dendrimers (approximately 16 kDa). The fluorophore-tagged G(4)-PAMAM dendrimers were synthesized and characterized using (1)H NMR, MALDI TOF MS and HPLC analysis. Transfer was measured across the intact fetal membrane (chorioamnion), and the separated chorion and amnion layers. Over a 5 h period, the dendrimer transport across all the three membranes was less than <3%, whereas the transport of FITC was relatively fast with as much as 49% transport across the amnion. The permeability of FITC (7.9 x 10(-7) cm(2)/s) through the chorioamnion was 7-fold higher than that of the dendrimer (5.8 x 10(-8) cm(2)/s). The biodistribution showed that the dendrimers were largely present in interstitial spaces in the decidual stromal cells and the chorionic trophoblast cells (in 2.5-4 h) and surprisingly, to a smaller extent internalized in nuclei of trophoblast cells and nuclei and cytoplasm of stromal cells. Passive diffusion and paracellular transport appear to be the major route for dendrimer transport. The overall findings further suggest that entry of drugs conjugated to dendrimers would be restricted across the human fetal membranes when administered topically by intravaginal route, suggesting new ways of selectively delivering therapeutics to the mother without affecting the fetus. (c) 2010 Elsevier Ltd. All rights reserved.

Transport and Biodistribution of Dendrimers Across Human Fetal Membranes: Implications for Intravaginal Administration of Dendrimers

PubMed Central

Menjoge, Anupa R.; Navath, Raghavendra S.; Asad, Abbas; Kannan, Sujatha; Kim, Chong Jai; Romero, Roberto; Kannan, Rangaramanujam M.

2010-01-01

Dendrimers are emerging as promising topical antimicrobial agents, and as targeted nanoscale drug delivery vehicles. Topical intravaginal antimicrobial agents are prescribed to treat the ascending genital infections in pregnant women. The fetal membranes separate the extra-amniotic space and fetus. The purpose of the study is to determine if the dendrimers can be selectively used for local intravaginal application to pregnant women without crossing the membranes into the fetus. In the present study, the transport and permeability of PAMAM (poly(amidoamine)) dendrimers, across human fetal membrane (using a side-by-side diffusion chamber), and its biodistribution (using immunofluorescence) are evaluated ex-vivo. Transport across human fetal membranes (from the maternal side) was evaluated using Fluorescein (FITC), an established transplacental marker (positive control, size~ 400 Da) and fluorophore-tagged G4-PAMAM dendrimers (~ 16 kDa). The fluorophore-tagged G4-PAMAM dendrimers were synthesized and characterized using 1H NMR, MALDI TOF-MS and HPLC analysis. Transfer was measured across the intact fetal membrane (chorioamnion), and the separated chorion and amnion layers. Over a five hour period, the dendrimer transport across all the three membranes was less than < 3 %, whereas the transport of FITC was relatively fast with as much as 49% transport across the amnion. The permeability of FITC (7.9 × 10-7 cm2/s) through the chorioamnion was 7-fold higher than that of the dendrimer (5.8 × 10-8 cm2/s). The biodistribution showed that the dendrimers were largely present in interstitial spaces in the decidual stromal cells and the chorionic trophoblast cells (in 2.5 to 4 h) and surprisingly, to a smaller extent internalized in nuclei of trophoblast cells and nuclei and cytoplasm of stromal cells. Passive diffusion and paracellular transport appear to be the major route for dendrimer transport. The overall findings further suggest that entry of drugs conjugated to dendrimers would be restricted across the human fetal membranes when administered topically by intravaginal route, suggesting new ways of selectively delivering therapeutics to the mother without affecting the fetus. PMID:20346497

CYTOPATHIC EFFECT OF THE ATYPICAL PNEUMONIA ORGANISM IN CULTURES OF HUMAN TISSUE

PubMed Central

Eaton, Monroe D.; Farnham, Ann E.; Levinthal, Jeana D.; Scala, Anthony R.

1962-01-01

Eaton, Monroe D. (Harvard Medical School, Boston, Mass.), Ann E. Farnham, Jeana D. Levinthal, and Anthony R. Scala. Cytopathic effect of the atypical pneumonia organism in cultures of human tissue. J. Bacteriol. 84:1330–1337. 1962.—Three strains of the atypical pneumonia agent were adapted to grow in continuous cell cultures of human amnion or human embryonic lung, with production of initial increased acidity followed by destruction of the cells. Evidence is presented that cytopathic effects of the organism were associated with intracellular growth and formation of microcolonies. Clumps of organisms stained specifically with fluorescein-labeled antibody, and showed distinctive tinctorial reactions with the May Grünwald-Giemsa stain. The cytopathic effect was prevented by fresh serum from a rabbit immunized with an egg-passage strain of the atypical pneumonia agent. Heating the immune serum to 56 C for 30 min abolished the neutralizing effect. The significance of heat-labile serum constituents in killing or inhibition of mycoplasma is discussed. Images PMID:16561984

Comparative Sensitivity of Tissue Cultures to Rubella Virus: Use of Guinea Pig Cells for Virus Titration

PubMed Central

Horta-Barbosa, L.; Warren, Joel

1969-01-01

A series of 19 different primary and serial tissue cultures were investigated for their sensitivity to virulent or attenuated rubella virus (RV). Primary guinea pig tissues, a serial passage of baby hamster kidney, and primary human amnion were comparable to African green monkey kidney tissue cultures in their sensitivity. In general, primary human tissues were relatively insusceptible to the Gilchrist strain of RV. RV interfered with the growth of vesicular stomatitis virus. Based on this finding, it was possible to develop an assay method in guinea pig tissue cultures by using VSV as the challenge virus. This system appeared to be comparable in sensitivity to the use of primary monkey kidney tissue cultures for the detection of small amounts of RV and offers the advantages of economy, rapidity, and safety. PMID:4979943

The impact of the International Atomic Energy Agency (IAEA) program on radiation and tissue banking in Mexico.

PubMed

Martínez-Pardo, María Esther; Morales Pedraza, Jorge; Sánchez Ramírez, Omar

2009-05-01

Tissue banking started in Mexico in 1948-1949, when two bone banks were established, one at the Infantile Hospital of Mexico and other at the Central Military Hospital. Mexico has benefited for the implementation of the IAEA program since through it has been able to settle down and to consolidate the Tissue Bank at the Instituto Nacional de Investigaciones Nucleares ININ (National Institute for Nuclear Research). This is the only bank in Latin America that has a Quality Management System in force, certified under ISO 9001:2000 since August 1, 2003. The first tissue processed was amnion. The main products of the BTR are amnion and pig skin. Both are biological tissues which their main use is as a wound dressing in patients with burns, scars, diabetic ulcers, epidermolysis bullosa, damaged ocular surface, etc. The General Health Law, published in 1984 and reformed in June 19, 2007, describes the procedure for the disposal of organs, tissues and human cadavers in its fourteenth title and in the Regulation for Sanitary Control. During the period 2001-2005, the ININ Tissue Bank produced 292 sterilised tissues (amnion, 86,668 cm(2), and frozen pig skin, 164,220 cm(2), at an estimated cost of 1,012,668 Mexican pesos. Until 2006, one hundred eighty five (185) patients have been treated with the use of sterilised tissues produced by the ININ Tissue Bank. The radiation source used for sterilisation of tissues is an industrial Cobalt-60 irradiator model JS-6500 AECL, which belongs to ININ. This equipment is located in other building, close to the BTR, in the Centro Nuclear de México "Dr. Nabor Carrillo Flores" (Nuclear Center of Mexico). Until 2006, six hospitals use in a routine way the sterilised tissues produced by the ININ Tissue Bank, for the treatment of burns originated by diverse agents like flame, electricity, liquids in boil, chemical reagents, as well as for the reconstruction of the ocular surface. Two of these hospitals treat patients of very low economic incomes, mainly needy individuals, who cannot afford to pay this type of treatments in other hospitals due to their high cost. The results obtained up to now are highly promising.

Uterine overdistention induces preterm labor mediated by inflammation: observations in pregnant women and nonhuman primates

PubMed Central

Waldorf, Kristina M. Adams; Singh, Natasha; Mohan, Aarthi R.; Young, Roger C.; Ngo, Lisa; Das, Ananya; Tsai, Jesse; Bansal, Aasthaa; Paolella, Louis; Herbert, Bronwen R.; Sooranna, Suren R.; Gough, G. Michael; Astley, Cliff; Vogel, Keith; Baldessari, Audrey E.; Bammler, Theodor K.; MacDonald, James; Gravett, Michael G.; Rajagopal, Lakshmi; Johnson, Mark R.

2015-01-01

OBJECTIVE Uterine overdistention is thought to induce preterm labor in women with twin and multiple pregnancies, but the pathophysiology remains unclear. We investigated for the first time the pathogenesis of preterm birth associated with rapid uterine distention in a pregnant nonhuman primate model. STUDY DESIGN A nonhuman primate model of uterine overdistention was created using preterm chronically catheterized pregnant pigtail macaques (Macaca nemestrina) by inflation of intraamniotic balloons (N = 6), which were compared to saline controls (N = 5). Cesarean delivery was performed due to preterm labor or at experimental end. Microarray, quantitative reverse transcriptase polymerase chain reaction, Luminex (Austin, TX), and enzyme-linked immunosorbent assay were used to measure messenger RNA (mRNA) and/or protein levels from monkey (amniotic fluid, myometrium, maternal plasma) and human (amniocytes, amnion, myometrium) tissues. Statistical analysis employed analysis of covariance and Wilcoxon rank sum. Biomechanical forces were calculated using the law of Laplace. RESULTS Preterm labor occurred in 3 of 6 animals after balloon inflation and correlated with greater balloon volume and uterine wall stress. Significant elevations of inflammatory cytokines and prostaglandins occurred following uterine overdistention in an “inflammatory pulse” that correlated with preterm labor (interleukin [IL]-1β, tumor necrosis factor [TNF]-α, IL-6, IL-8, CCL2, prostaglandin E2, prostaglandin F2α, all P < .05). A similar inflammatory response was observed in amniocytes in vitro following mechanical stretch (IL1β, IL6, and IL8 mRNA multiple time points, P < .05), in amnion of women with polyhydramnios (IL6 and TNF mRNA, P < .05) and in amnion (TNF-α) and myometrium of women with twins in early labor (IL6, IL8, CCL2, all P < .05). Genes differentially expressed in the nonhuman primate after balloon inflation and in women with polyhydramnios and twins are involved in tissue remodeling and muscle growth. CONCLUSION Uterine overdistention by inflation of an intraamniotic balloon is associated with an inflammatory pulse that precedes and correlates with preterm labor. Our results indicate that inflammation is an early event after a mechanical stress on the uterus and leads to preterm labor when the stress is sufficiently great. Further, we find evidence of uterine tissue remodeling and muscle growth as a common, perhaps compensatory, response to uterine distension. PMID:26284599

Amnion as a surrogate tissue reporter of the effects of maternal preeclampsia on the fetus.

PubMed

Suzuki, Masako; Maekawa, Ryo; Patterson, Nicole E; Reynolds, David M; Calder, Brent R; Reznik, Sandra E; Heo, Hye J; Einstein, Francine Hughes; Greally, John M

2016-01-01

Preeclampsia, traditionally characterized by high blood pressure and proteinuria, is a common pregnancy complication, which affects 2-8 % of all pregnancies. Although children born to women with preeclampsia have a higher risk of hypertension in later life, the mechanism of this increased risk is unknown. DNA methylation is an epigenetic modification that has been studied as a mediator of cellular memory of adverse exposures in utero. Since each cell type in the body has a unique DNA profile, cell subtype composition is a major confounding factor in studies of tissues with heterogeneous cell types. The best way to avoid this confounding effect is by using purified cell types. However, using purified cell types in large cohort translational studies is difficult. The amnion, the inner layer of the fetal membranes of the placenta, is derived from the epiblast and consists of two cell types, which are easy to isolate from the delivered placenta. In this study, we demonstrate the value of using amnion samples for DNA methylation studies, revealing distinctive patterns between fetuses exposed to proteinuria or hypertension and fetuses from normal pregnancies. We performed a genome-wide DNA methylation analysis, HpaII tiny fragment Enrichment by Ligation-mediated PCR (HELP)-tagging, on 62 amnion samples from the placentas of uncomplicated, normal pregnancies and from those with complications of preeclampsia or hypertension. Using a regression model approach, we found 123, 85, and 99 loci with high-confidence hypertension-associated, proteinuria-associated, and hypertension- and proteinuria-associated DNA methylation changes, respectively. A gene ontology analysis showed DNA methylation changes to be selecting genes with different biological processes in exposure status. We also found that these differentially methylated regions overlap loci previously reported as differentially methylated regions in preeclampsia. Our findings support prior observations that preeclampsia is associated with changes of DNA methylation near genes that have previously been found to be dysregulated in preeclampsia. We propose that amniotic membranes represent a valuable surrogate fetal tissue on which to perform epigenome-wide association studies of adverse intrauterine conditions.

Angiogenic properties of dehydrated human amnion/chorion allografts: therapeutic potential for soft tissue repair and regeneration

PubMed Central

2014-01-01

Background Chronic wounds are associated with a number of deficiencies in critical wound healing processes, including growth factor signaling and neovascularization. Human-derived placental tissues are rich in regenerative cytokines and have been shown in randomized clinical trials to be effective for healing chronic wounds. In this study, PURION® Processed (MiMedx Group, Marietta, GA) dehydrated human amnion/chorion membrane tissue allografts (dHACM, EpiFix®, MiMedx) were evaluated for properties to support wound angiogenesis. Methods Angiogenic growth factors were identified in dHACM tissues using enzyme-linked immunosorbent assays (ELISAs), and the effects of dHACM extract on human microvascular endothelial cell (HMVEC) proliferation and production of angiogenic growth factors was determined in vitro. Chemotactic migration of human umbilical vein endothelial cells (HUVECs) toward pieces of dHACM tissue was determined using a standard in vitro transwell assay. Neovascularization of dHACM in vivo was determined utilizing a murine subcutaneous implant model. Results Quantifiable levels of the angiogenic cytokines angiogenin, angiopoietin-2 (ANG-2), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), heparin binding epidermal growth factor (HB-EGF), hepatocyte growth factor (HGF), platelet derived growth factor BB (PDGF-BB), placental growth factor (PlGF), and vascular endothelial growth factor (VEGF) were measured in dHACM. Soluble cues promoted HMVEC proliferation in vitro and increased endogenous production of over 30 angiogenic factors by HMVECs, including granulocyte macrophage colony-stimulating factor (GM-CSF), angiogenin, transforming growth factor β3 (TGF-β3), and HB-EGF. 6.0 mm disks of dHACM tissue were also found to recruit migration of HUVECs in vitro. Moreover, subcutaneous dHACM implants displayed a steady increase in microvessels over a period of 4 weeks, indicative of a dynamic intra-implant neovascular process. Conclusions Taken together, these results demonstrate that dHACM grafts: 1) contain angiogenic growth factors retaining biological activity; 2) promote amplification of angiogenic cues by inducing endothelial cell proliferation and migration and by upregulating production of endogenous angiogenic growth factors by endothelial cells; and 3) support the formation of blood vessels in vivo. dHACM grafts are a promising wound care therapy with the potential to promote revascularization and tissue healing within poorly vascularized, non-healing wounds. PMID:24817999

Angiogenic properties of dehydrated human amnion/chorion allografts: therapeutic potential for soft tissue repair and regeneration.

PubMed

Koob, Thomas J; Lim, Jeremy J; Massee, Michelle; Zabek, Nicole; Rennert, Robert; Gurtner, Geoffrey; Li, William W

2014-01-01

Chronic wounds are associated with a number of deficiencies in critical wound healing processes, including growth factor signaling and neovascularization. Human-derived placental tissues are rich in regenerative cytokines and have been shown in randomized clinical trials to be effective for healing chronic wounds. In this study, PURION® Processed (MiMedx Group, Marietta, GA) dehydrated human amnion/chorion membrane tissue allografts (dHACM, EpiFix®, MiMedx) were evaluated for properties to support wound angiogenesis. Angiogenic growth factors were identified in dHACM tissues using enzyme-linked immunosorbent assays (ELISAs), and the effects of dHACM extract on human microvascular endothelial cell (HMVEC) proliferation and production of angiogenic growth factors was determined in vitro. Chemotactic migration of human umbilical vein endothelial cells (HUVECs) toward pieces of dHACM tissue was determined using a standard in vitro transwell assay. Neovascularization of dHACM in vivo was determined utilizing a murine subcutaneous implant model. Quantifiable levels of the angiogenic cytokines angiogenin, angiopoietin-2 (ANG-2), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), heparin binding epidermal growth factor (HB-EGF), hepatocyte growth factor (HGF), platelet derived growth factor BB (PDGF-BB), placental growth factor (PlGF), and vascular endothelial growth factor (VEGF) were measured in dHACM. Soluble cues promoted HMVEC proliferation in vitro and increased endogenous production of over 30 angiogenic factors by HMVECs, including granulocyte macrophage colony-stimulating factor (GM-CSF), angiogenin, transforming growth factor β3 (TGF-β3), and HB-EGF. 6.0 mm disks of dHACM tissue were also found to recruit migration of HUVECs in vitro. Moreover, subcutaneous dHACM implants displayed a steady increase in microvessels over a period of 4 weeks, indicative of a dynamic intra-implant neovascular process. TAKEN TOGETHER, THESE RESULTS DEMONSTRATE THAT DHACM GRAFTS: 1) contain angiogenic growth factors retaining biological activity; 2) promote amplification of angiogenic cues by inducing endothelial cell proliferation and migration and by upregulating production of endogenous angiogenic growth factors by endothelial cells; and 3) support the formation of blood vessels in vivo. dHACM grafts are a promising wound care therapy with the potential to promote revascularization and tissue healing within poorly vascularized, non-healing wounds.

Clinical application of amniotic membranes on a patient with epidermolysis bullosa.

PubMed

Martínez Pardo, M E; Reyes Frías, M L; Ramos Durón, L E; Gutiérrez Salgado, E; Gómez, J C; Marín, M A; Luna Zaragoza, D

1999-01-01

The case of a patient with dystrophic epidermolysis bullosa treated with radiosterilised amniotic membranes is presented. The disorder is a congenital disease characterised by a poor desmosomal junction in the keratinocyte membrane. After proper donor screening, amnios were collected at Hospital Central Sur de Alta Especialidad (HCSAE), PEMEX and microbiological analysis was performed at Universidad Nacional Autónoma de México, FQUNAM, (Biology Dept. of the Chemistry Faculty, National Autonomous University of Mexico), before and after radiation sterilisation. Processing, packaging and sterilisation were performed at Instituto Nacional de Investigaciones Nucleares, ININ, (National Nuclear Research Institute). The patient, a ten-year-old boy with severe malnutrition, extensive loss of skin and pseudomonad infection in the whole body, was treated with gentle debridement in a Hubbard bath. Later amnion application was performed with sterilised amnios by using two different processes, in one of which the amnion was sterilised with paracetic acid, preserved in glycerol, kindly donated by the German Institute for Tissue and Cell Replacement and applied by Dr. Johannes C. Bruck, IAEA visiting expert, and the other amnion was processed at ININ: air dried and sterilised by gamma radiation at dose of 30 kGy. After spontaneous epithelisation was successfully promoted for seven days, the pain was alleviated and mobility was improved in a few hours and the patient's general condition was so improved that in a month he was discharged. Unfortunately, because this disease is revertive and has malignant degeneration, the prognosis is not good.

Comparative study of regenerative effects of mesenchymal stem cells derived from placental amnion, chorion and umbilical cord on dermal wounds.

PubMed

Ertl, Juliane; Pichlsberger, Melanie; Tuca, Alexandru-Cristian; Wurzer, Paul; Fuchs, Jakob; Geyer, Stefan H; Maurer-Gesek, Barbara; Weninger, Wolfgang J; Pfeiffer, Dagmar; Bubalo, Vladimir; Parvizi, Daryousch; Kamolz, Lars-Peter; Lang, Ingrid

2018-05-01

Mesenchymal stem/stromal cells derived from human term placentas (PMSCs) are novel therapeutic agents and more topical than ever. Here we evaluated the effects of three types of PMSCs on wound healing in an in vivo mouse model: Amnion-derived MSCs (AMSCs), blood vessel-derived MSCs (BV-MSCs) from the chorionic plate and Wharton's jelly-derived MSCs (WJ-MSCs) from the umbilical cord. We topically applied PMSCs onto skin wounds in mice using the dermal substitute Matriderm ® as carrier and evaluated wound healing parameters. In addition, we investigated the effects of all PMSC types under co-application with placental endothelial cells (PLECs). After 8 days, we compared the percent of wound closure and the angiogenic potential between all groups. AMSCs, BV-MSCs and WJ-MSCs significantly induced a faster healing and a higher number of blood vessels in the wound when compared to controls (Matriderm ® -alone). PLECs did not further improve the advantageous effects of PMSC-treatment. Quantitative data and 3D analysis by high resolution episcopic microscopy confirmed a lower density of vessels in Matriderm ® /PMSCs/PLECs co-application compared to Matriderm ® /PMSCs treatment. Results indicate that all three PMSC types exert similar beneficial effects on wound closure and neovascularization in our mouse model. Using Matriderm ® as carrier for PMSCs propagates rapid cell migration towards the wound area that allows a fast and clinically practicable method for stem cell application. These promising effects warrant further investigation in clinical trials. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Hepatitis A virus cellular receptor 2 (HAVCR2) is decreased with viral infection and regulates pro-labour mediators OA.

PubMed

Liong, Stella; Lim, Ratana; Barker, Gillian; Lappas, Martha

2017-07-01

Intrauterine infection caused by viral infection has been implicated to contribute to preterm birth. Hepatitis A virus cellular receptor 2 (HAVCR2) regulates inflammation in non-gestational tissues in response to viral infection. The aims of this study were to determine the effect of: (i) viral dsRNA analogue polyinosinic:polycytidylic acid (poly(I:C)) on HAVCR2 expression; and (ii) HAVCR2 silencing by siRNA (siHAVCR2) in primary amnion and myometrial cells on poly(I:C)-induced inflammation. In human foetal membranes and myometrium, HAVCR2 mRNA and protein expression was decreased when exposed to poly(I:C). Treatment of primary amnion and myometrial cells with poly(I:C) significantly increased the expression and release of pro-inflammatory cytokines TNF, IL1A, IL1B and IL6; the expression of chemokines CXCL8 and CCL2; the expression and secretion of adhesion molecules ICAM1 and VCAM1; and PTGS2 and PTGFR mRNA expression and the release of prostaglandin PGF 2α . This increase was significantly augmented in cells transfected with siHAVCR2. Furthermore, mRNA expression of anti-inflammatory cytokines IL4 and IL10 was significantly decreased. Collectively, our data suggest that HAVCR2 regulates cytokines, chemokines, prostaglandins and cell adhesion molecules in the presence of viral infection. This suggests a potential for HAVCR2 activators as therapeutics for the management of preterm birth associated with viral infections. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Eosinophilic/T-cell Chorionic Vasculitis: Histological and Clinical Correlations.

PubMed

Cheek, Bradley; Heinrich, Stephen; Ward, Kenneth; Craver, Randall

2015-04-01

Eosinophilic T-cell chorionic vasculitis (E/TCV) is composed of eosinophils and T-lymphocytes originating within chorionic vessels, radiating toward the intervillous space and away from the amnion in a fashion different from the fetal vascular response seen in amnionitis. Clinical significance and risk factors are not well established. We report four pregnancies (five infants, one triplet was spared) with E/TCV, gestational ranging from 23 weeks to term. All had concurrent acute chorioamnionitis, three had the typical acute fetal inflammatory response. One had placental fetal obstructive vasculopathy and an upper extremity reduction defect (radio-ulnar synostosis), the mother had pre-eclampsia. A second case involved 2 of 3 23 week previable triplets. Our third case had a metatarsus varus resistant to casting, the mother had gestational diabetes. The last case was a normal infant. We review the literature, discuss the clinical findings and present the histologic characteristics of this infrequently recognized lesion.

Amnioinfusion in preterm PROM: effects on amnion and cord histology.

PubMed

Locatelli, A; Andreani, M; Ghidini, A; Verderio, M; Pizzardi, A; Vergani, P; Salafia, C M

2008-02-01

To investigate the effects of transabdominal amnioinfusion (TA) on the histology of amnion (A) and umbilical cord (UC). From a cohort of 56 singleton pregnancies with premature rupture of membranes (PROM) at

The forkhead transcription factor Foxf1 is required for differentiation of extra-embryonic and lateral plate mesoderm.

PubMed

Mahlapuu, M; Ormestad, M; Enerbäck, S; Carlsson, P

2001-01-01

The murine Foxf1 gene encodes a forkhead transcription factor expressed in extra-embryonic and lateral plate mesoderm and later in splanchnic mesenchyme surrounding the gut and its derivatives. We have disrupted Foxf1 and show that mutant embryos die at midgestation due to defects in mesodermal differentiation and cell adhesion. The embryos do not turn and become deformed by the constraints of a small, inflexible amnion. Extra-embryonic structures exhibit a number of differentiation defects: no vasculogenesis occurs in yolk sac or allantois; chorioallantoic fusion fails; the amnion does not expand with the growth of the embryo, but misexpresses vascular and hematopoietic markers. Separation of the bulk of yolk sac mesoderm from the endodermal layer and adherence between mesoderm of yolk sac and amnion, indicate altered cell adhesion properties and enhanced intramesodermal cohesion. A possible cause of this is misexpression of the cell-adhesion protein VCAM1 in Foxf1-deficient extra-embryonic mesoderm, which leads to co-expression of VCAM with its receptor, alpha(4)-integrin. The expression level of Bmp4 is decreased in the posterior part of the embryo proper. Consistent with this, mesodermal proliferation in the primitive streak is reduced and somite formation is retarded. Expression of Foxf1 and the homeobox gene Irx3 defines the splanchnic and somatic mesodermal layers, respectively. In Foxf1-deficient embryos incomplete separation of splanchnic and somatic mesoderm is accompanied by misexpression of Irx3 in the splanchnopleure, which implicates Foxf1 as a repressor of Irx3 and as a factor involved in coelom formation.

Phenotypic Screening Identifies Synergistically Acting Natural Product Enhancing the Performance of Biomaterial Based Wound Healing.

PubMed

Sivasubramanian, Srinivasan; Chandrasekar, Gayathri; Svensson Akusjärvi, Sara; Thangam, Ramar; Sathuvan, Malairaj; Kumar, R B S; Hussein, Hawraa; Vincent, Savariar; Madhan, Balaraman; Gunasekaran, Palani; Kitambi, Satish S

2017-01-01

The potential of multifunctional wound heal biomaterial relies on the optimal content of therapeutic constituents as well as the desirable physical, chemical, and biological properties to accelerate the healing process. Formulating biomaterials such as amnion or collagen based scaffolds with natural products offer an affordable strategy to develop dressing material with high efficiency in healing wounds. Using image based phenotyping and quantification, we screened natural product derived bioactive compounds for modulators of types I and III collagen production from human foreskin derived fibroblast cells. The identified hit was then formulated with amnion to develop a biomaterial, and its biophysical properties, in vitro and in vivo effects were characterized. In addition, we performed functional profiling analyses by PCR array to understand the effect of individual components of these materials on various genes such as inflammatory mediators including chemokines and cytokines, growth factors, fibroblast stimulating markers for collagen secretion, matrix metalloproteinases, etc., associated with wound healing. FACS based cell cycle analyses were carried out to evaluate the potential of biomaterials for induction of proliferation of fibroblasts. Western blot analyses was done to examine the effect of biomaterial on collagen synthesis by cells and compared to cells grown in the presence of growth factors. This work demonstrated an uncomplicated way of identifying components that synergistically promote healing. Besides, we demonstrated that modulating local wound environment using biomaterials with bioactive compounds could enhance healing. This study finds that the developed biomaterials offer immense scope for healing wounds by means of their skin regenerative features such as anti-inflammatory, fibroblast stimulation for collagen secretion as well as inhibition of enzymes and markers impeding the healing, hydrodynamic properties complemented with other features including non-toxicity, biocompatibility, and safety.

Phenotypic Screening Identifies Synergistically Acting Natural Product Enhancing the Performance of Biomaterial Based Wound Healing

PubMed Central

Sivasubramanian, Srinivasan; Chandrasekar, Gayathri; Svensson Akusjärvi, Sara; Thangam, Ramar; Sathuvan, Malairaj; Kumar, R. B. S.; Hussein, Hawraa; Vincent, Savariar; Madhan, Balaraman; Gunasekaran, Palani; Kitambi, Satish S.

2017-01-01

The potential of multifunctional wound heal biomaterial relies on the optimal content of therapeutic constituents as well as the desirable physical, chemical, and biological properties to accelerate the healing process. Formulating biomaterials such as amnion or collagen based scaffolds with natural products offer an affordable strategy to develop dressing material with high efficiency in healing wounds. Using image based phenotyping and quantification, we screened natural product derived bioactive compounds for modulators of types I and III collagen production from human foreskin derived fibroblast cells. The identified hit was then formulated with amnion to develop a biomaterial, and its biophysical properties, in vitro and in vivo effects were characterized. In addition, we performed functional profiling analyses by PCR array to understand the effect of individual components of these materials on various genes such as inflammatory mediators including chemokines and cytokines, growth factors, fibroblast stimulating markers for collagen secretion, matrix metalloproteinases, etc., associated with wound healing. FACS based cell cycle analyses were carried out to evaluate the potential of biomaterials for induction of proliferation of fibroblasts. Western blot analyses was done to examine the effect of biomaterial on collagen synthesis by cells and compared to cells grown in the presence of growth factors. This work demonstrated an uncomplicated way of identifying components that synergistically promote healing. Besides, we demonstrated that modulating local wound environment using biomaterials with bioactive compounds could enhance healing. This study finds that the developed biomaterials offer immense scope for healing wounds by means of their skin regenerative features such as anti-inflammatory, fibroblast stimulation for collagen secretion as well as inhibition of enzymes and markers impeding the healing, hydrodynamic properties complemented with other features including non-toxicity, biocompatibility, and safety. PMID:28769790

The impact of the International Atomic Energy Agency (IAEA) program on radiation and tissue banking in Indonesia.

PubMed

Hilmy, Nazly; Manjas, Menkher; Ferdiansyah; Abbas, Basril; Morales Pedraza, Jorge

2009-05-01

In 1986, the National Nuclear Energy Agency (Batan) in Jakarta started the research and development for the setting up of a tissue bank (Batan Research Tissue Bank/BRTB) by preserving fresh amnion or fetal membranes by lyophilisation and then sterilising by gamma irradiation. During the period of 1990 and 2000, three more tissue banks were set up, i.e., Biomaterial Centre in Surabaya, Jamil Tissue Bank in Padang, and Sitanala Tissue Bank in Tangerang. In 1994, BRTB produced bone allografts. The banks established under the IAEA program concentrated its work on the production of amnion, bone and soft tissues allografts, as well as bone xenografts. These tissues (allografts and xenografts) were sterilised using gamma irradiation (about 90%) and the rest were sterilized by ETO and those products have been used in the treatment of patients at more than 50 hospitals in Indonesia. In 2004, those tissue banks produced 8,500 grafts and 5,000 of them were amnion grafts for eye treatment and wound dressing. All of those grafts were used for patients as well as for research. In 2006, the production increased to 9,000 grafts. Although the capacity of those banks can produce more grafts, we are facing problems on getting raw materials from suitable donors. To fulfill the demand of bone grafts we also produced bone xenografts. The impact of the IAEA program in tissue banking activities in Indonesia can be summarised as follows: to support the national program on importing substitutes for medical devices. The price of imported tissues are between US$ 50 and US$ 6,000 per graft. Local tissue bank can produce tissues with the same quality with the price for about 10-30% of the imported tissues.

Dehydrated human amnion/chorion tissue in difficult-to-heal DFUs: a case series.

PubMed

Penny, H; Rifkah, M; Weaver, A; Zaki, P; Young, A; Meloy, G; Flores, R

2015-03-01

Diabetic foot ulcers (DFUs) occur as a result of multifactorial complications and are commonly found in the diabetic community. Underlying disease states such as neuropathy and peripheral vascular disease can slow healing rates, potentially leading to recurrence, amputation, and increased mortality. As with many other disease processes, DFUs have several treatment options, such as debriding agents, alginate seaweed extract, hydrocolloid gels, and amniotic membrane allografts. The presented cases all used a dehydrated human amniotic/chorionic membrane allograft (dHACM; EpiFix) to aid the healing process. Human amniotic epithelial membranes have seen increased usage due to their ability to enhance the healing process and accelerate cellular regeneration. The DFUs healed in all of the five patients treated, and patients saw a full recovery in 2.5-11 weeks. In addition, the healing time decreased in spite of the non-adherence seen in three of the patients. These results suggest another possible use for dHACM; however, further studies are required to confirm these data. This project was self-funded and had no influences outside the fact that Dr Penny is a speaker for MiMedx.

Two consecutive microtubule-based epithelial seaming events mediate dorsal closure in the scuttle fly Megaselia abdita.

PubMed

Fraire-Zamora, Juan Jose; Jaeger, Johannes; Solon, Jérôme

2018-03-14

Evolution of morphogenesis is generally associated with changes in genetic regulation. Here, we report evidence indicating that dorsal closure, a conserved morphogenetic process in dipterans, evolved as the consequence of rearrangements in epithelial organization rather than signaling regulation. In Drosophila melanogaster , dorsal closure consists of a two-tissue system where the contraction of extraembryonic amnioserosa and a JNK/Dpp-dependent epidermal actomyosin cable result in microtubule-dependent seaming of the epidermis. We find that dorsal closure in Megaselia abdita, a three-tissue system comprising serosa, amnion and epidermis, differs in morphogenetic rearrangements despite conservation of JNK/Dpp signaling. In addition to an actomyosin cable, M. abdita dorsal closure is driven by the rupture and contraction of the serosa and the consecutive microtubule-dependent seaming of amnion and epidermis. Our study indicates that the evolutionary transition to a reduced system of dorsal closure involves simplification of the seaming process without changing the signaling pathways of closure progression. © 2018, Fraire-Zamora et al.

Two consecutive microtubule-based epithelial seaming events mediate dorsal closure in the scuttle fly Megaselia abdita

PubMed Central

Jaeger, Johannes

2018-01-01

Evolution of morphogenesis is generally associated with changes in genetic regulation. Here, we report evidence indicating that dorsal closure, a conserved morphogenetic process in dipterans, evolved as the consequence of rearrangements in epithelial organization rather than signaling regulation. In Drosophila melanogaster, dorsal closure consists of a two-tissue system where the contraction of extraembryonic amnioserosa and a JNK/Dpp-dependent epidermal actomyosin cable result in microtubule-dependent seaming of the epidermis. We find that dorsal closure in Megaselia abdita, a three-tissue system comprising serosa, amnion and epidermis, differs in morphogenetic rearrangements despite conservation of JNK/Dpp signaling. In addition to an actomyosin cable, M. abdita dorsal closure is driven by the rupture and contraction of the serosa and the consecutive microtubule-dependent seaming of amnion and epidermis. Our study indicates that the evolutionary transition to a reduced system of dorsal closure involves simplification of the seaming process without changing the signaling pathways of closure progression. PMID:29537962

Encapsulating Non-Human Primate Multipotent Stromal Cells in Alginate via High Voltage for Cell-Based Therapies and Cryopreservation

PubMed Central

Gryshkov, Oleksandr; Pogozhykh, Denys; Hofmann, Nicola; Pogozhykh, Olena; Mueller, Thomas; Glasmacher, Birgit

2014-01-01

Alginate cell-based therapy requires further development focused on clinical application. To assess engraftment, risk of mutations and therapeutic benefit studies should be performed in an appropriate non-human primate model, such as the common marmoset (Callithrix jacchus). In this work we encapsulated amnion derived multipotent stromal cells (MSCs) from Callithrix jacchus in defined size alginate beads using a high voltage technique. Our results indicate that i) alginate-cell mixing procedure and cell concentration do not affect the diameter of alginate beads, ii) encapsulation of high cell numbers (up to 10×106 cells/ml) can be performed in alginate beads utilizing high voltage and iii) high voltage (15–30 kV) does not alter the viability, proliferation and differentiation capacity of MSCs post-encapsulation compared with alginate encapsulated cells produced by the traditional air-flow method. The consistent results were obtained over the period of 7 days of encapsulated MSCs culture and after cryopreservation utilizing a slow cooling procedure (1 K/min). The results of this work show that high voltage encapsulation can further be maximized to develop cell-based therapies with alginate beads in a non-human primate model towards human application. PMID:25259731

A comparative outcomes analysis evaluating clinical effectiveness in two different human placental membrane products for wound management.

PubMed

Johnson, Eric L; Marshall, James T; Michael, Georgina M

2017-01-01

Advances in tissue preservation have led to the commercialization of human placental membranes for the purposes of wound management with each product being characterized by different compositions and properties. The a priori specification of the research question in this investigator-initiated study focused on the clinical outcomes in two nonrandomized, however statistically equal and homogenous patient cohorts receiving either a viable intact cryopreserved human placental membrane (vCPM) or a dehydrated human amnion/chorion membrane (dHACM), for the management of wounds at a single center. A total of 79 patients with 101 wounds were analyzed: 40 patients with 46 wounds received vCPM and 39 patients with 55 wounds received dHACM. The proportion of wounds achieving complete wound closure was 63.0% (29/46) for vCPM and 18.2% (10/55) for dHACM (p < 0.0001) for all treated wounds combined. This is the first comparative effectiveness study to report on the clinical outcomes associated with the use of different placental wound care products once broadly implemented in the clinical setting. © 2016 The Authors. Wound Repair and Regeneration published by Wiley Periodicals, Inc. on behalf of The Wound Healing Society.

Quantitative mapping of intracellular cations in the human amniotic membrane

NASA Astrophysics Data System (ADS)

Moretto, Ph.; Llabador, Y.; Simonoff, M.; Razafindrabe, L.; Bara, M.; Guiet-Bara, A.

1993-05-01

The effect of magnesium and taurine on the permeability of cell membranes to monovalent cations has been investigated using the Bordeaux nuclear microprobe. PIXE and RBS techniques have been used to provide quantitative measurements and ion distributions in the isolated amniotic membrane. This physiological model for cellular exchanges allowed us to reveal the distribution of most elements involved in cellular pathways and the modifications under different experimental conditions of incubation in physiological fluids. The PIXE microanalysis provided an original viewpoint on these mechanisms. Following this first study, the amnion compact lamina was found to play a role which was not, up to now, taken into account in the interpretation of electrophysiological experimentations. The release of some ionic species, such as K +, from the epithelial cells, during immersion in isotonic fluids, could have been hitherto underestimated.

High-resolution imaging diagnosis of human fetal membrane by three-dimensional optical coherence tomography

NASA Astrophysics Data System (ADS)

Ren, Hugang; Avila, Cecilia; Kaplan, Cynthia; Pan, Yingtian

2011-11-01

Microscopic chorionic pseudocyst (MCP) arising in the chorion leave of the human fetal membrane (FM) is a clinical precursor for preeclampsia which may progress to fatal medical conditions (e.g., abortion) if left untreated. To examine the utility of three-dimensional (3D) optical coherence tomography (OCT) for noninvasive delineation of the morphology of human fetal membranes and early clinical detection of MCP, 60 human FM specimens were acquired from 10 different subjects undergoing term cesarean delivery for an ex vivo feasibility study. Our results showed that OCT was able to identify the four-layer architectures of human FMs consisting of high-scattering decidua vera (DV, average thickness dDV ~ 92+/-38 μm), low-scattering chorion and trophoblast (CT, dCT ~ 150+/-67 μm), high-scattering subepithelial amnion (A, dA ~ 95+/-36 μm), and low-scattering epithelium (E, dE ~ 29+/-8 μm). Importantly, 3D OCT was able to instantaneously detect MCPs (low scattering due to edema, fluid buildup, vasodilatation) and track (staging) their thicknesses dMCP ranging from 24 to 615 μm. It was also shown that high-frequency ultrasound was able to compliment OCT for detecting more advanced thicker MCPs (e.g., dMCP>615 μm) because of its increased imaging depth.

Experimental infection of pregnant goats with swine fever virus.

PubMed

Shimizu, M; Kumagai, T

1989-07-01

Thirteen pregnant goats were inoculated intravenously with the ALD strain of virulent swine fever (SF) virus on Days 64-84 of gestation. Dams showed transient and mild viremia, and produced high serum neutralizing (SN) antibody after inoculation. Six inoculated dams were reared until parturition occurred and bore six apparently normal, one apparently normal but dead, one mummified and three edematous kids. Neutralizing antibody was demonstrated in the pre-colostral sera obtained from all normal kids, but no SF virus was isolated from any of them. The other seven dams were killed on post-inoculation days (PID) 5-61, and fetuses, placenta and amnion were tested for the virus and SN antibody. All fetuses of five dams examined within PID 40 were positive for SF virus, but negative for SN antibody. SF virus was also isolated from one of three fetuses examined on PID 61. Conversely, the other two fetuses examined on PID 61 were negative for SF virus, but positive for SN antibody. Furthermore, SF virus was isolated from the placenta and amnion of all the dams.

Membrane Vesicles of Group B Streptococcus Disrupt Feto-Maternal Barrier Leading to Preterm Birth

PubMed Central

Sthanam, Lakshmi Kavitha; Srivastava, Rohit; Basu, Bhakti; Dutta, Suryendu; Sen, Shamik; Modi, Deepak

2016-01-01

Infection of the genitourinary tract with Group B Streptococcus (GBS), an opportunistic gram positive pathogen, is associated with premature rupture of amniotic membrane and preterm birth. In this work, we demonstrate that GBS produces membrane vesicles (MVs) in a serotype independent manner. These MVs are loaded with virulence factors including extracellular matrix degrading proteases and pore forming toxins. Mice chorio-decidual membranes challenged with MVs ex vivo resulted in extensive collagen degradation leading to loss of stiffness and mechanical weakening. MVs when instilled vaginally are capable of anterograde transport in mouse reproductive tract. Intra-amniotic injections of GBS MVs in mice led to upregulation of pro-inflammatory cytokines and inflammation mimicking features of chorio-amnionitis; it also led to apoptosis in the chorio-decidual tissue. Instillation of MVs in the amniotic sac also resulted in intrauterine fetal death and preterm delivery. Our findings suggest that GBS MVs can independently orchestrate events at the feto-maternal interface causing chorio-amnionitis and membrane damage leading to preterm birth or fetal death. PMID:27583406

The potential of mesenchymal stem cells derived from amniotic membrane and amniotic fluid for neuronal regenerative therapy

PubMed Central

Kim, Eun Young; Lee, Kyung-Bon; Kim, Min Kyu

2014-01-01

The mesenchymal stem cells (MSCs), which are derived from the mesoderm, are considered as a readily available source for tissue engineering. They have multipotent differentiation capacity and can be differentiated into various cell types. Many studies have demonstrated that the MSCs identified from amniotic membrane (AM-MSCs) and amniotic fluid (AF-MSCs) are shows advantages for many reasons, including the possibility of noninvasive isolation, multipotency, self-renewal, low immunogenicity, anti-inflammatory and nontumorigenicity properties, and minimal ethical problem. The AF-MSCs and AM-MSCs may be appropriate sources of mesenchymal stem cells for regenerative medicine, as an alternative to embryonic stem cells (ESCs). Recently, regenerative treatments such as tissue engineering and cell transplantation have shown potential in clinical applications for degenerative diseases. Therefore, amnion and MSCs derived from amnion can be applied to cell therapy in neuro-degeneration diseases. In this review, we will describe the potential of AM-MSCs and AF-MSCs, with particular focus on cures for neuronal degenerative diseases. [BMB Reports 2014; 47(3): 135-140] PMID:24499672

Chorionicity and Heritability Estimates from Twin Studies: The Prenatal Environment of Twins and Their Resemblance Across a Large Number of Traits.

PubMed

van Beijsterveldt, C E M; Overbeek, L I H; Rozendaal, L; McMaster, M T B; Glasner, T J; Bartels, M; Vink, J M; Martin, N G; Dolan, C V; Boomsma, D I

2016-05-01

There are three types of monozygotic (MZ) twins. MZ twins can either share one chorion and one amnion, each twin can have its own amnion, or MZ twins can-like dizygotic twins-each have their own chorion and amnion. Sharing the same chorion may create a more similar/dissimilar prenatal environment and bias heritability estimates, but most twin studies do not distinguish between these three types of MZ twin pairs. The aim of this paper is to investigate the effect of chorion sharing on the similarity within MZ twin pairs for a large number of traits. Information on chorion status was obtained for the Netherlands twin register (NTR) by linkage to the records from the database of the dutch pathological anatomy national automated archive (PALGA). Record linkage was successful for over 9000 pairs. Effect of chorion type was tested by comparing the within-pair similarity between monochorionic (MC) and dichorionic (DC) MZ twins on 66 traits including weight, height, motor milestones, child problem behaviors, cognitive function, wellbeing and personality. For only 10 traits, within-pair similarity differed between MCMZ and DCMZ pairs. For traits influenced by birth weight (e.g. weight and height in young children) we expected that MC twins would be more discordant. This was found for 5 out of 13 measures. When looking at traits where blood supply is important, we saw MCMZ twins to be more concordant than DCMZ's for 3 traits. We conclude that the influence on the MZ twin correlation of the intra-uterine prenatal environment, as measured by sharing a chorion type, is small and limited to a few phenotypes. This implies that the assumption of equal prenatal environment of mono- and DC MZ twins, which characterizes the classical twin design, is largely tenable.

Challenges in validating the sterilisation dose for processed human amniotic membranes

NASA Astrophysics Data System (ADS)

Yusof, Norimah; Hassan, Asnah; Firdaus Abd Rahman, M. N.; Hamid, Suzina A.

2007-11-01

Most of the tissue banks in the Asia Pacific region have been using ionising radiation at 25 kGy to sterilise human tissues for save clinical usage. Under tissue banking quality system, any dose employed for sterilisation has to be validated and the validation exercise has to be a part of quality document. Tissue grafts, unlike medical items, are not produced in large number per each processing batch and tissues relatively have a different microbial population. A Code of Practice established by the International Atomic Energy Agency (IAEA) in 2004 offers several validation methods using smaller number of samples compared to ISO 11137 (1995), which is meant for medical products. The methods emphasise on bioburden determination, followed by sterility test on samples after they were exposed to verification dose for attaining of sterility assurance level (SAL) of 10 -1. This paper describes our experience in using the IAEA Code of Practice in conducting the validation exercise for substantiating 25 kGy as sterilisation dose for both air-dried amnion and those preserved in 99% glycerol.

Fetal Membranes-Derived Stem Cells Microenvironment.

PubMed

Favaron, Phelipe Oliveira; Miglino, Maria Angelica

2017-01-01

Recently, the regenerative medicine has been trying to congregate different areas such as tissue engineering and cellular therapy, in order to offer effective treatments to overcome several human and veterinary medical problems. In this regard, fetal membranes have been proposed as a powerful source for obtainment of multipotent stem cells with low immunogenicity, anti-inflammatory properties and nontumorigenicity properties for the treatment of several diseases, including replacing cells lost due to tissue injuries or degenerative diseases. Morpho-physiological data have shown that fetal membranes, especially the yolk sac and amnion play different functions according to the gestational period, which are direct related to the features of the microenvironment that their cells are subject. The characteristics of the microenvironment affect or controls important cellular events involved with proliferation, division and maintenance of the undifferentiated stage or differentiation, especially acting on the extracellular matrix components. Considering the importance of the microenvironment and the diversity of embryonic and fetal membrane-derived stem cells, this chapter will addressed advances in the isolation, phenotyping, characteristics of the microenvironment, and applications of yolk sac and amniotic membrane-derived stem cells for human and veterinary regenerative medicine.

Discovery of HeLa Cell Contamination in HES Cells: Call for Cell Line Authentication in Reproductive Biology Research.

PubMed

Kniss, Douglas A; Summerfield, Taryn L

2014-08-01

Continuous cell lines are used frequently in reproductive biology research to study problems in early pregnancy events and parturition. It has been recognized for 50 years that many mammalian cell lines contain inter- or intraspecies contaminations with other cells. However, most investigators do not routinely test their culture systems for cross-contamination. The most frequent contributor to cross-contamination of cell lines is the HeLa cell isolated from an aggressive cervical adenocarcinoma. We report on the discovery of HeLa cell contamination of the human endometrial epithelial cell line HES isolated in our laboratory. Short tandem repeat analysis of 9 unique genetic loci demonstrated molecular identity between HES and HeLa cells. In addition, we verified that WISH cells, isolated originally from human amnion epithelium, were also contaminated with HeLa cells. Inasmuch as our laboratory did not culture HeLa cells at the time of HES cell derivations, the source of contamination was the WISH cell line. These data highlight the need for continued diligence in authenticating cell lines used in reproductive biology research. © The Author(s) 2014.

Intracellular Virus-Specific Structures and RNAs in Oncornavirus-Producing Human Cells

PubMed Central

Bukrinskaya, A. G.; Miller, G. G.; Lebedeva, E. N.; Zhdanov, V. M.

1974-01-01

Two kinds of virus-specific structures were isolated from the cytoplasm of Detroit-6 and human amnion cells producing oncornavirus-like particles. These structures represented A particles with the diameter of 70 to 80 nm and aggregated strands of nucleocapsids with the diameter of 3 and 6 nm. The structures were separated from cellular contaminants by isopycnic banding in linear sucrose gradients and subsequently further purified by sedimentation in velocity sucrose gradients. Their sedimentation coefficient was 250 and 150S, respectively. Both structures contain 60, 45, and 35S RNA species, and 150S structures also contained 20S RNA. The 35 and 20S RNA from the 150S structure formed hybrids with DNA enzymatically synthesized on extracellular virions. The structures displayed endogeneous polymerase activity, DNA product of the reaction being predominantly associated with 60S RNA. No 70S RNA was found in the cell structures of various densities. Also, the virions purified from tissue culture fluid contained 70S RNA. These findings are consistent with those on extracellular maturation of oncornavirus RNA. Images PMID:4810779

Fetal-to-maternal signaling to initiate parturition

PubMed Central

Reinl, Erin L.; England, Sarah K.

2015-01-01

Multiple processes are capable of activating the onset of parturition; however, the specific contributions of the mother and the fetus to this process are not fully understood. In this issue of the JCI, Gao and colleagues present evidence that steroid receptor coactivators 1 and 2 (SRC-1 and SRC-2) regulate surfactant protein-A (SP-A) and platelet-activating factor (PAF) expression, which increases in the developing fetal lung. WT dams crossed with males deficient for both SRC-1 and SRC-2 had suppressed myometrial inflammation, increased serum progesterone, and delayed parturition, which could be reconciled by injection of either SP-A or PAF into the amnion. Together, the results of this study demonstrate that the fetal lungs produce signals to initiate labor in the mouse. This work underscores the importance of the fetus as a contributor to the onset of murine, and potentially human, parturition. PMID:26098207

Catabolism of exogenous deoxyinosine in cultured epithelial amniotic cells.

PubMed

Carta, M C; Mattana, A; Camici, M; Allegrini, S; Tozzi, M G; Sgarrella, F

2001-10-03

Uptake and catabolism of purine nucleosides have been commonly considered as means to salvage the purine ring for nucleic acid synthesis, usually neglecting the destiny of the pentose moiety. With the aim to ascertain if deoxyribose derived from exogenous DNA can be utilised as a carbon and energy source, we studied the catabolism of exogenous deoxyinosine in a cell line derived from human amnion epithelium (WISH). Intact WISH cells catabolise deoxyinosine by conversion into hypoxanthine. The nucleoside enters the cell through a nitrobenzylthioinosine-insensitive equilibrative transport. Deoxyinosine undergoes a phosphorolytic cleavage inside the cell. The purine base diffuses back to the external medium, while the phosphorylated pentose moiety can be further catabolised to glycolysis and citric acid cycle intermediates. Our results indicate that the catabolism of the deoxynucleoside can be considered mainly as a means to meet the carbon and energy requirements of growing cells.

PLACENTA OF THE INDIAN ELEPHANT, ELEPHAS INDICUS.

PubMed

COOPER, R A; CONNELL, R S; WELLINGS, S R

1964-10-16

The placenta of the Indian elephant is incompletely annular and zonary macroscopically and occupies the equator of an ovoid chorioallantoic sac. The amnion is fused with the chorion over the zone. Microscopically, the placenta is labyrinthine and endotheliochorial with a rudimentary marginal hematoma. Both macroscopically and microscopically it resembles the placentas of thecarnivores, particularly the racoon, the cat, and the dog.

Infections in the tissue material and their impact on the loss of transplants in the Laboratory of in vitro Cell and Tissue Culture with Tissue Bank in the years 2011-2015.

PubMed

Kitala, D; Klama-Baryła, A; Kawecki, M; Kraut, M; Łabuś, W; Glik, J; Ples, M; Tomanek, E; Nowak, M

2017-03-01

Radiation sterilization eliminates microbiological infections but causes the degradation of the cell factor. The negative result of microbiological examination for tissue transplants is one of the conditions for approval for distribution in patients. The study attempts to verify impact of the presence of microbes onto material for transplant loss. In the 2011-2015 period, we analyzed 293 donors of skin and amnion. Microbiological sampling was performed. The total of 21 strains of bacteria, molds and fungi was identified in collected tissue. The widest spectrum of strains was found in skin (17), followed by amnia (8). The total number of positive findings was 147 and was again highest in skin (129), while the number of positive findings in amnia was 18 only. The general percentage of fungal infections was very low. The presence of fungal strains was only observed in allogeneic skin (2%). Large number of microorganisms isolated from the skin before sterilization was observed, so it seems impossible to use allogeneic intravital skin. However, the intravital application of allogeneic amnion obtained from cesarean section remains to be considered.

Sealing Penetrating Eye Injuries Using Photo-Activated Bonding

DTIC Science & Technology

2011-09-01

called PTB ) with the potential to decrease vision loss and ocular complications in warfighters sustaining penetrating eye injuries. Scope: In year 2...not competitive with PTB for sealing is amnion over penetrating cornea injuries, determined that two potential adverse effects (inhibition of...epithelial cell migration and keratocyte phototoxicity) are not significant problems, demonstrated that PTB can be used to seal lacerations in thin (e.g

Corneal Protection for Burn Patients

DTIC Science & Technology

2011-07-01

enzymatic degradation The methods used to harvest AM, to treat the amnion with proteolytic enzymes and to measure the extent of enzymatic...Multiple enzymatic cleavages of the membrane proteins degrade the AM and release peptide fragments containing free amino groups. We measured the level...appropriate modified AM for the goals of this study. Although these measurements were not part of the original proposal, we will soon be able quantify

Conditioned medium derived from rat amniotic epithelial cells confers protection against inflammation, cancer, and senescence.

PubMed

Di Germanio, Clara; Bernier, Michel; Petr, Michael; Mattioli, Mauro; Barboni, Barbara; de Cabo, Rafael

2016-06-28

Amniotic epithelial cells (AECs) are a class of fetal stem cells that derives from the epiblast and resides in the amnion until birth. AECs are suitable candidates for regenerative medicine because of the ease of collection, their low immunogenicity and inability to form tumors after transplantation. Even though human AECs have been widely investigated, the fact remains that very little is known about AECs isolated from rat, one of the most common animal models in medical testing. In this study, we showed that rat AECs retained stemness properties and plasticity, expressed the pluripotency markers Sox2, Nanog, and Oct4 and were able to differentiate toward the osteogenic lineage. The addition of conditioned medium collected from rat AECs to lipopolysaccharide-activated macrophages elicited anti-inflammatory properties through a decrease of Tnfa expression and slowed tumor cell proliferation in vitro and in vivo. The senescence-associated secretory phenotype was also significantly lower upon incubation of senescent human IMR-90 fibroblast cells with conditioned medium from rat AECs. These results confirm the potential of AECs in the modulation of inflammatory mechanisms and open new therapeutic possibilities for regenerative medicine and anti-aging therapies as well.

Sealing Penetrating Eye Injuries With Photoactivated Bonding

DTIC Science & Technology

2013-09-01

penetrating eye injuries. Scope: To establish, in ex vitro and in vivo animal models, the treatment parameters for sealing corneal and scleral...cornea surface was compared to that produced by our conventional, bare fiber system using ex vivo rabbit eyes and the standard treatment protocol...Identified the PTB treatment parameters that produce strong bonding of an amnion patch over corneal wounds in ex vivo rabbit eyes . • Determined that a

Experiences using IAEA Code of practice for radiation sterilization of tissue allografts: Validation and routine control

NASA Astrophysics Data System (ADS)

Hilmy, N.; Febrida, A.; Basril, A.

2007-11-01

Problems of tissue allografts in using International Standard (ISO) 11137 for validation of radiation sterilization dose (RSD) are limited and low numbers of uniform samples per production batch, those are products obtained from one donor. Allograft is a graft transplanted between two different individuals of the same species. The minimum number of uniform samples needed for verification dose (VD) experiment at the selected sterility assurance level (SAL) per production batch according to the IAEA Code is 20, i.e., 10 for bio-burden determination and the remaining 10 for sterilization test. Three methods of the IAEA Code have been used for validation of RSD, i.e., method A1 that is a modification of method 1 of ISO 11137:1995, method B (ISO 13409:1996), and method C (AAMI TIR 27:2001). This paper describes VD experiments using uniform products obtained from one cadaver donor, i.e., cancellous bones, demineralized bone powders and amnion grafts from one life donor. Results of the verification dose experiments show that RSD is 15.4 kGy for cancellous and demineralized bone grafts and 19.2 kGy for amnion grafts according to method A1 and 25 kGy according to methods B and C.

A "two-objective, one-area" procedure in absorption microphotometry and its application using an inverted microscope.

PubMed

Chaubal, K A

1988-08-01

A 'two-objective, one-area' method and related equations are suggested to measure absorbance of microscopic stained objects. In such work, the measuring field invariably includes an image of the object and some clear area surrounding the image. The total intensity in the two areas is measured photometrically, using two different objectives, and substituted in the equation for absorbance. The equation is independent of the term representing intensity from the clear area and hence the error in the measurement of absorbance is reduced. The limitations of the 'two-objective, one-area' method are discussed and its pragmatic operation described with an experimental setup involving an inverted microscope. The method permits measurement of intensity in a part of a stained cell while the rest of the cell remains in the field of view. The method is applied to measure absorbance in Giemsa stained ascites cells and Feulgen stained liver and Human Amnion cells.

SUBCLINICAL INFECTION OF DOGS BY CANINE-ADAPTED MEASLES VIRUS EVIDENCED BY THEIR SUBSEQUENT IMMUNITY TO CANINE DISTEMPER VIRUS

PubMed Central

Moura, Roberto A.; Warren, Joel

1961-01-01

Moura, Roberto A. (Chas. Pfizer and Company, Inc., Terre Haute, Ind.) and Joel Warren. Subclinical infection of dogs by canine-adapted measles virus evidenced by their subsequent immunity to canine distemper virus. J. Bacteriol. 82:702–705. 1961.—Young dogs were inoculated with virulent measles virus which had been adapted to canine kidney or human amnion cell culture. None of the animals showed any clinical symptoms nor could virus be isolated from the blood, although measles-neutralizing and complement-fixing antibodies developed during convalescence. All dogs failed to develop antibody to canine distemper. However, when these and normal control animals were subsequently inoculated intracerebrally with virulent distemper virus, each of the controls succumbed to typical symptoms, whereas all of the measles-immune dogs survived. These results suggest that the cross-protection conferred by measles against canine distemper virus infection involves factors other than humoral antibody. The immunity persists for a considerable length of time. PMID:14476677

Progestin treatment does not affect expression of cytokines, steroid receptors, oxytocin receptor, and cyclooxygenase 2 in fetal membranes and endometrium from pony mares at parturition.

PubMed

Palm, F; Walter, I; Nowotny, N; Budik, S; Helmreich, M; Aurich, C

2013-01-01

In most mammalian species, progestins have a major function in maintaining pregnancy. In humans, the physiologic initiation of parturition bears similarities with inflammatory processes and anti-inflammatory effects of progestins have been suggested to postpone birth until term. To examine if comparable effects exist in the horse, mares were treated with the synthetic progestin altrenogest from day 280 of gestation until parturition (N = 5) or were left untreated as controls (N = 7). Tissue from the amnion (AMN), allantochorion (AC), and endometrium (EM) was collected at foaling and mRNA expression of interleukin (IL)-6 and -8, cyclooxygenase 2 (COX2), estrogen receptor (ER) α, progesterone receptor, and oxytocin receptor (OTR) was analyzed. Leukocytes, steroid receptors, COX2, and OTR were also investigated by histology and immunohistochemistry. Expression of mRNA for IL-6 was higher in AMN and EM versus AC (P < 0.01). Expression of IL-8 was higher in AMN than AC and EM (P < 0.001). Steroid receptors and OTR were highly expressed in EM but not in AMN and AC (P < 0.001). Expression of COX2 was most pronounced in AC whereas IL expression was not upregulated in AC. No differences in mRNA expression existed between altrenogest-treated and control animals. Endometrial polymorphonuclear leukocytes were increased in altrenogest-treated mares. Epithelial cells of all tissues, except AC chorionic villi stained progesterone receptor-positive. Staining for ER was more pronounced in the amnion facing epithelium of the AC in altrenogest-treated versus control animals (P < 0.01). In conclusion, COX2 is highly expressed in the AC. The fetal membranes thus might play a role in the onset of labor in the horse. Altrenogest did not affect gene expression in the AMN, AC, and EM but had localized effects on inflammatory cells and ER expression. No anti-inflammatory effects of altrenogest in healthy, late pregnant pony mares could be detected. Copyright © 2013 Elsevier Inc. All rights reserved.

The role of inflammation in preterm birth--focus on periodontitis.

PubMed

Klebanoff, M; Searle, K

2006-12-01

It is universally accepted that acute inflammation is responsible for a substantial fraction of preterm births, particularly early cases. Much of this inflammation is caused by intrauterine infection. There is also evidence that infection and perhaps inflammation remote from the genitourinary tract can trigger preterm labour. Several studies have suggested that periodontitis during pregnancy increases the risk of preterm birth. Periodontitis may cause preterm birth by causing low-grade bacteraemia, which lodges in the decidua, chorion and amnion or by releasing endotoxin into the maternal circulation, which triggers intrauterine inflammation and preterm birth. Alternatively, it may release cytokines and other inflammatory products, which then trigger preterm labour. It is also conceivable that periodontitis might serve as a marker for other unhealthy behaviours, or immune hyperresponsiveness and that hyperresponsiveness to low-grade intrauterine infection itself might cause preterm birth. Currently, there are few data available to distinguish these possibilities. Such distinctions are important since they have clear implications for whether treatment of periodontitis might reduce the incidence of preterm birth. Several clinical trials of treatment of periodontitis are continuing, but until their results are known there is currently little evidence that treatment of periodontitis during pregnancy reduces the incidence of preterm birth.

Sealing Penetrating Eye Injuries Using Photoactivated Bonding

DTIC Science & Technology

2011-09-01

of the rabbit pushed the viscoeastic out of the eye during the laser phase of the treatment . This interfered with the bonding of the amnion...ANSI Std. Z39.18 Sealing Penetrating Eye Injuries Using Photoactivated Bonding W81XWH-09-2-0059 1 Sep 2010 - 31 Aug 2011Annual01-09-2011 Anthony...called PTB) with the potential to decrease vision loss and ocular complications in warfighters sustaining penetrating eye injuries. Scope: In

Angiogenin distribution in human term placenta, and expression by cultured trophoblastic cells

PubMed Central

Pavlov, Nadine; Hatzi, Elissavet; Bassaglia, Yann; Frendo, Jean-Louis; Evain-Brion, Danièle; Badet, Josette

2003-01-01

Human angiogenin is a 14-kDa secreted protein with angiogenic and ribonucleolytic activities. Angiogenin is associated with tumour development but is also present in normal biological fluids and tissues. To further address the physiological role of angiogenin, we studied its expression in situ and in vitro, using the human term placenta as a model of physiological angiogenesis. Angiogenin was immunodetected by light and transmission electron microscopy, and its cellular distribution was established by double immunolabelling with cell markers including von Willebrand factor, platelet/endothelial cell adhesion molecule-1 (PECAM-1), CD34, Tie-2, vascular endothelial cadherin (VE-cadherin), vascular endothelial growth factor receptor-2 (VEGF-R2), erythropoeitin receptor (Epo-R), alpha-smooth muscle actin, CD45, cytokeratin 7, and Ki-67. Angiogenin immunoreactivity was detected in villous and extravillous trophoblasts, the trophoblast basement membrane, the endothelial basal lamina, foetal blood vessels, foetal and maternal red blood cells, and amnionic cells. Its expression was confirmed by in situ hybridisation with a digoxygenin-labelled cDNA probe and reverse transcriptase-polymerase chain reaction amplification. Villous cytotrophoblasts, isolated and differentiated in vitro into a functional syncytiotrophoblast, expressed and secreted angiogenin. Given its known biological activities in vitro and its observed pattern of expression, these data suggest that, in human placenta, angiogenin has a role not only in angiogenesis but also in vascular and tissue homeostasis, maternal immune tolerance of the foetus, and host defences. PMID:15166501

Human Decidua-Derived Mesenchymal Cells Are a Promising Source for the Generation and Cell Banking of Human Induced Pluripotent Stem Cells

PubMed Central

Shofuda, Tomoko; Kanematsu, Daisuke; Fukusumi, Hayato; Yamamoto, Atsuyo; Bamba, Yohei; Yoshitatsu, Sumiko; Suemizu, Hiroshi; Nakamura, Masato; Sugimoto, Yoshikazu; Furue, Miho Kusuda; Kohara, Arihiro; Akamatsu, Wado; Okada, Yohei; Okano, Hideyuki; Yamasaki, Mami; Kanemura, Yonehiro

2013-01-01

Placental tissue is a biomaterial with remarkable potential for use in regenerative medicine. It has a three-layer structure derived from the fetus (amnion and chorion) and the mother (decidua), and it contains huge numbers of cells. Moreover, placental tissue can be collected without any physical danger to the donor and can be matched with a variety of HLA types. The decidua-derived mesenchymal cells (DMCs) are highly proliferative fibroblast-like cells that express a similar pattern of CD antigens as bone marrow-derived mesenchymal cells (BM-MSCs). Here we demonstrated that induced pluripotent stem (iPS) cells could be efficiently generated from DMCs by retroviral transfer of reprogramming factor genes. DMC-hiPS cells showed equivalent characteristics to human embryonic stem cells (hESCs) in colony morphology, global gene expression profile (including human pluripotent stem cell markers), DNA methylation status of the OCT3/4 and NANOG promoters, and ability to differentiate into components of the three germ layers in vitro and in vivo. The RNA expression of XIST and the methylation status of its promoter region suggested that DMC-iPSCs, when maintained undifferentiated and pluripotent, had three distinct states: (1) complete X-chromosome reactivation, (2) one inactive X-chromosome, or (3) an epigenetic aberration. Because DMCs are derived from the maternal portion of the placenta, they can be collected with the full consent of the adult donor and have considerable ethical advantages for cell banking and the subsequent generation of human iPS cells for regenerative applications. PMID:26858858

In Amnio MRI of Mouse Embryos

PubMed Central

Roberts, Thomas A.; Norris, Francesca C.; Carnaghan, Helen; Savery, Dawn; Wells, Jack A.; Siow, Bernard; Scambler, Peter J.; Pierro, Agostino; De Coppi, Paolo; Eaton, Simon; Lythgoe, Mark F.

2014-01-01

Mouse embryo imaging is conventionally carried out on ex vivo embryos excised from the amniotic sac, omitting vital structures and abnormalities external to the body. Here, we present an in amnio MR imaging methodology in which the mouse embryo is retained in the amniotic sac and demonstrate how important embryonic structures can be visualised in 3D with high spatial resolution (100 µm/px). To illustrate the utility of in amnio imaging, we subsequently apply the technique to examine abnormal mouse embryos with abdominal wall defects. Mouse embryos at E17.5 were imaged and compared, including three normal phenotype embryos, an abnormal embryo with a clear exomphalos defect, and one with a suspected gastroschisis phenotype. Embryos were excised from the mother ensuring the amnion remained intact and stereo microscopy was performed. Embryos were next embedded in agarose for 3D, high resolution MRI on a 9.4T scanner. Identification of the abnormal embryo phenotypes was not possible using stereo microscopy or conventional ex vivo MRI. Using in amnio MRI, we determined that the abnormal embryos had an exomphalos phenotype with varying severities. In amnio MRI is ideally suited to investigate the complex relationship between embryo and amnion, together with screening for other abnormalities located outside of the mouse embryo, providing a valuable complement to histology and existing imaging methods available to the phenotyping community. PMID:25330230

Amnion-Derived Multipotent Progenitor Cells Increase Gain of Incisional Breaking Strength and Decrease Incidence and Severity of Acute Wound Failure

PubMed Central

Xing, Liyu; Franz, Michael G.; Marcelo, Cynthia L.; Smith, Charlotte A.; Marshall, Vivienne S.; Robson, Martin C.

2007-01-01

Objective: Acute wound failure is a common complication following surgical procedures and trauma. Laparotomy wound failure leads to abdominal dehiscence and incisional hernia formation. Delayed recovery of wound-breaking strength is one mechanism for laparotomy wound failure. Early fascial wounds are relatively acellular, and there is a delay in the appearance of acute wound growth factors and cytokines. The objective of this study was to accelerate and improve laparotomy wound healing using amnion-derived multipotent cells (AMPs). AMPs' nonimmunogenic phenotype and relative abundance support its role as a cell therapy. Methods: AMPs were injected into the load-bearing layer of rat abdominal walls prior to laparotomy, and cell viability was confirmed. Wound mechanical properties were measured over 28 days. The incidence and severity of laparotomy wound failure was measured in an incisional hernia model. Results: AMP cells were viable in laparotomy wounds for at least 28 days and did not migrate to other tissues. Laparotomy wound-breaking strength was increased by postoperative day 7 following AMP therapy. AMP therapy reduced the incidence of hernia formation and the size of hernia defects. Histology suggested stimulated wound fibroplasia and angiogenesis. Conclusions: AMP cell therapy reduces the incidence of laparotomy wound failure by accelerating the recovery of wound-breaking strength. This results in fewer incisional hernias and smaller hernia defects. PMID:18091982

Human amniotic epithelial stem cells promote wound healing by facilitating migration and proliferation of keratinocytes via ERK, JNK and AKT signaling pathways.

PubMed

Zhao, Bin; Liu, Jia-Qi; Zheng, Zhao; Zhang, Jun; Wang, Shu-Yue; Han, Shi-Chao; Zhou, Qin; Guan, Hao; Li, Chao; Su, Lin-Lin; Hu, Da-Hai

2016-07-01

Wound healing is a highly orchestrated physiological process consisting in a complex interaction of cellular and biochemical events. Human amniotic epithelial stem cells (HAESCs) have been shown to be an attractive resource for wound healing because they are primitive stem cells. However, the exact effects of amnion-derived stem cells on the migration or proliferation of keratinocytes and their potential mechanism are not fully understood. We have found that HAESCs accelerate the migration of keratinocytes and induce a remarkable increase in the activity of phospho-ERK, phospho-JNK, and phospho-AKT, the blockade of which by their specific inhibitors significantly inhibits migration induced by HAESC-conditioned medium (CM). Furthermore, the co-culture of keratinocytes with HAESCs up-regulates the expression levels of cell proliferation proteins Cyclin D1, Cyclin D3 and Mdm2. In vivo animal experiments have shown that HAESC-CM improves wound healing, whereas blockade with ERK, JNK and AKT inhibitors significantly impairs wound healing. Taken together, these results reveal, for the first time, that HAESCs promote wound healing by facilitating the migration and proliferation of keratinocytes via ERK, JNK and AKT signaling pathways and might be a potential therapy in skin wound healing.

Endocrine gland-derived endothelial growth factor (EG-VEGF) is a potential novel regulator of human parturition.

PubMed

Dunand, C; Hoffmann, P; Sapin, V; Blanchon, L; Salomon, A; Sergent, F; Benharouga, M; Sabra, S; Guibourdenche, J; Lye, S J; Feige, J J; Alfaidy, N

2014-09-01

EG-VEGF is an angiogenic factor that we identified as a new placental growth factor during human pregnancy. EG-VEGF is also expressed in the mouse fetal membrane (FM) by the end of gestation, suggesting a local role for this protein in the mechanism of parturition. However, injection of EG-VEGF to gravid mice did not induce labor, suggesting a different role for EG-VEGF in parturition. Here, we searched for its role in the FM in relation to human parturition. Human pregnant sera and total FM, chorion, and amnion were collected during the second and third trimesters from preterm no labor, term no labor, and term labor patients. Primary human chorion trophoblast and FM explants cultures were also used. We demonstrate that circulating EG-VEGF increased toward term and significantly decreased at the time of labor. EG-VEGF production was higher in the FM compared to placentas matched for gestational age. Within the FM, the chorion was the main source of EG-VEGF. EG-VEGF receptors, PROKR1 and PROKR2, were differentially expressed within the FM with increased expression toward term and an abrupt decrease with the onset of labor. In chorion trophoblast and FM explants collected from nonlaboring patients, EG-VEGF decreased metalloproteinase-2 and -9 activities and increased PGDH (prostaglandin-metabolizing enzyme) expression. Altogether these data demonstrate that EG-VEGF is a new cytokine that acts locally to ensure FM protection in late pregnancy. Its fine contribution to the initiation of human labor is exhibited by the abrupt decrease in its levels as well as a reduction in its receptors. © 2014 by the Society for the Study of Reproduction, Inc.

Extraction Site Preservation Using FDBA With Bioxclude vs. FDBA With Bio-Gide: A Randomized Clinical Trial

DTIC Science & Technology

2015-06-01

neovascularization. J Surgical Res 2015; 193(2): 953-962 48. Zelen CM, Gould L, Serena TE, et al . A prospective, randomized, controlled, multi-center...tissue repair and regeneration. Tiss Eng 2002; 8(2): 295-308. 24. Niknejad H, Peirovi H, Jmjani M, et al . Properties of the amniotic membrane for...Guler R, Ercan MT, Ulutuncel M, et al . Measurement of blood flow by the 133Xe clearance technique to grafts of amnion used in vestibuloplasty. Brit J

The role of placental alpha microglobulin-1 amnisure in determining the status of the fetal membranes; its association with preterm birth. Traditions … traditions ….

PubMed

Mariona, Federico G; Roura, Lluis Cabero

2016-03-01

The integrity of the fetal amnion-chorion is an imperative for the preservation of a normal pregnancy in the human. The diagnosis of the status of the fetal membranes has traditionally been reduced to either intact or ruptured. In the last decades, evidence has accumulated demonstrating that this clinical approach may well be an over simplification. Practically, all maternal organs experienced physiologic or eventually pathologic changes during the length of the gestational period. We propose that the fetal membranes are also significantly impacted by those changes. The accurate, specific, simplified and low-cost diagnosis of the status of the fetal membranes is of critical importance for the assessment of risk to the pregnancy followed by efficient and prompt treatment. The presence of placental alpha macroglobulin-1 in the vagina specifically indicates a disruption in the integrity of the fetal membranes and may indirectly mean increased risk for preterm birth. Further research to properly characterize this marker and its importance in the care of pregnant woman at risk for preterm birth is strongly recommended.

Involvement of human decidual cell-expressed tissue factor in uterine hemostasis and abruption.

PubMed

Lockwood, C J; Paidas, M; Murk, W K; Kayisli, U A; Gopinath, A; Huang, S J; Krikun, G; Schatz, F

2009-11-01

Vascular injury increases access and binding of plasma-derived factor VII to perivascular cell membrane-bound tissue factor (TF). The resulting TF/VIIa complex promotes hemostasis by cleaving pro-thrombin to thrombin leading to the fibrin clot. In human pregnancy, decidual cell-expressed TF prevents decidual hemorrhage (abruption). During placentation, trophoblasts remodel decidual spiral arteries into high conductance vessels. Shallow trophoblast invasion impedes decidual vascular conversion, producing an inadequate uteroplacental blood flow that elicits abruption-related placental ischemia. Thrombin induces several biological effects via cell surface protease activated receptors. In first trimester human DCs thrombin increases synthesis of sFlt-1, which elicits placental ischemia by impeding angiogenesis-related decidual vascular remodeling. During pregnacy, the fibrillar collagen-rich amnion and choriodecidua extracellular matrix (ECM) provides greater than additive tensile strength and structural integrity. Thrombin acts as an autocrine/paracrine mediator that degrades these ECMs by augmenting decidual cell expression of: 1) matrix metalloproteinases and 2) interleukin-8, a key mediator of abruption-associated decidual infiltration of neutrophils, which express several ECM degrading proteases. Among the cell types at the maternal fetal interface at term, TF expression is highest in decidual cells indicating that this TF meets the hemostatic demands of labor and delivery. TF expression in cultured term decidual cells is enhanced by progestin and thrombin suggesting that the maintenance of elevated circulating progesterone provides hemostatic protection and that abruption-generated thrombin acts in an autocrine/paracrine fashion on decidual cells to promote hemostasis via enhanced TF expression.

PRODUCTION AND CHARACTERIZATION OF MULTIPLE-LAYERED POPULATIONS OF ANIMAL CELLS

PubMed Central

Kruse, Paul F.; Miedema, Ed

1965-01-01

Dense populations containing 129 x 106 Jensen sarcoma, 134 x 106 DON Chinese hamster, 28.9 x 106 WI-38 human diploid, 61.8 x 106 HEp-2 human carcinoma, and 67.4 x 106 WISH human amnion cells were produced from dilute inocula, 0.85 to 5.33 x 106, in 7 to 8 days in a perfusion system using replicate T-60 flasks. Perfusion rates as high as 560 ml medium/day/T-60 were required to maintain pH (to ca ±0.1 unit) and adequate nutrient supplies. The cell densities encountered are described by the term "monolayer equivalents" (M.E.), defined as number of cells per culture divided by number of cells in a monolayer. The M.E.'s for T-60 cultures containing unusually dense populations of 40 x 106 WI-38 and 250 x 106 DON cells (9-day perfusion) were 5 and 17, respectively, and numbers of cells in illustrations of stained cross-sections of membranes from these cultures were in excellent agreement. Threshold M.E.'s exist below which proliferation is the chief cellular activity and above which one or more cell functions may predominate even though proliferation persists. Cellular nutrition and metabolism may change with changes in M.E., as illustrated in different patterns of glutamic acid, proline, and glycine utilization or production in dense vs. dilute WI-38 cell populations. The results indicated that the role of contact inhibition phenomena in arresting cellular proliferation was diminished in perfusion system environments. PMID:5884626

The tissue bank at the national nuclear research institute in Mexico.

PubMed

Esther Martínez-Pardo, María; Lourdes Reyes-Frías, Ma

2003-01-01

The Instituto Nacional de Investigaciones Nucleares (ININ, The National Nuclear Research Institute) received during 1997-1998 strong support of the International Atomic Energy Agency (IAEA), to establish the first and only one tissue bank (BTR ININ tissue bank) in Mexico that uses ionising radiation as sterilising agent. In that time, the BTR staff was trained in different tissue banks in several countries. Basic equipment for tissue processing donated by the IAEA was received in 1998. In July, 1999 the Mexican Health Secretariat gave the Sanitary License No. 1062000001 to the BTR to operate as an official organ and tissue bank. In August, 2001 the ININ and the Hospital Materno Infantil (HMI-ISSEMYM) signed an agreement to collaborate in amnion processing. The hospital is responsible for donor selection, serology tests, tissue procurement and washing, since this hospital is the BTR amnion supplier. The tissues are collected by ININ weekly with complete documentation. The BTR is responsible for processing: cleaning, air drying, packaging, labelling, microbiological control and sterilisation by gamma irradiation. The sterilised tissue is kept under quarantine for 6 months to obtain the results of the donor second serology test. From March to June, 2002 the BTR has processed 347.86 units (50 cm(2) each), is say, 17,393 cm(2). In addition, the pig skin xenograft process has been implemented and a protocol for clinical applications of it is running at the Hospital Central Sur de Alta Especialidad (PEMEX). Also the ININ tissue bank present status and perspectives are described.

The evolution and impact of the International Atomic Energy Agency (IAEA) program on radiation and tissue banking in Asia and the Pacific region.

PubMed

Morales Pedraza, Jorge; Phillips, Glyn O

2009-05-01

The Asia and the Pacific region was within the IAEA program on radiation and tissue banking, the most active region. Most of the tissue banks in the Asia and the Pacific region were developed during the late 1980s and 1990s. The initial number of tissue banks established or supported by the IAEA program in the framework of the RCA Agreement for Asia and the Pacific region was 18. At the end of 2006, the number of tissue banks participating, in one way or another in the IAEA program was 59. Since the beginning of the implementation of the IAEA program in Asia and the Pacific region 63,537 amnion and 44,282 bone allografts were produced and 57,683 amnion and 36,388 bone allografts were used. The main impact of the IAEA program in the region was the following: the establishment or consolidation of at least 59 tissue banks in 15 countries in the region (the IAEA supported directly 16 of these banks); the improvement on the quality and safety of tissues procured and produced in the region reaching international standards; the implementation of eight national projects, two regional projects and two interregional projects; the elaboration of International Standards, a Code of Practice and a Public Awareness Strategies and, the application of quality control and quality assurances programs in all participating tissue banks.

Alpha-fetoprotein and its value for predicting pregnancy outcomes – a re-evaluation

PubMed Central

Darouich, Ayham Alhaj; Liehr, Thomas; Weise, Anja; Schlembach, Dietmar; Schleußner, Ekkehart; Kiehntopf, Michael; Schreyer, Isolde

2015-01-01

Introduction Alpha-fetoprotein (AFP) concentrations can be determined framing others from invasively acquired amnion fluid (AF-AFP). While the biological role of AFP remains unclear it is well known that AFP-levels can be altered in connection with specific clinical and/or genetic alterations of the fetus. Materials and Method here a retrospective study based on 3,119 singleton and 56 twin pregnancies is presented. The standard levels of amnion fluid derived alpha-fetoprotein level (AF-AFP) between 12th and 36th weeks of gestation were determined. Additionally, acetylcholinesterase (AChE) test results for 63 cases, ultrasonography results for 32 cases and abnormal karyotypic findings for 100 cases were available for selected cases. Results and Discussion according to the present data the AF-AFP test is reliable and provides expected test results in terms of population studies. However, individual AF-AFP test results can be subject to high individual variations. In this study AF-AFP multiple of medians (MoM) over 1.7 were indicative for neuronal tube defects and/or omphalocele in only 6.3% of the cases, while such AF-AFP values were hints on severe sonographic signs in 62% of the cases. Also, altered AF-AFP concentrations were present in 82% of cytogenetically abnormal cases. Overall, even though predicative value of the AF-AFP-test is matter of discussion it continues to be widely applied in invasive prenatal diagnostics. This study indicates that it only can be applied reliably in combination with other tests like banding cytogenetics, ultrasonography and all embedded in well-established genetic counseling. PMID:27358693

Pregnant women have increased incidence of IgE autoantibodies reactive with the skin and placental antigen BP180 (type XVII collagen)

PubMed Central

Noe, Megan H.; Messingham, Kelly A.N.; Brandt, Debra S.; Andrews, Janet I.; Fairley, Janet A.

2016-01-01

BP180 (type XVII collagen) is a transmembrane protein expressed in a variety of cell types. It is also the target of autoantibodies in cutaneous autoimmune disease including bullous pemphigoid and pemphigoid gestationis, a disease unique to pregnancy. The purpose of this study was to determine the prevalence and specificity of cutaneous autoantibodies in a cohort of pregnant women. De-identified sera were collected from pregnant women (n = 299) and from non-pregnant controls (n = 134). Sera were analyzed by ELISA for the presence of IgG and IgE autoantibodies directed against several cutaneous autoantigens. IgE antibodies against the NC16A domain of BP180 were detected in 7.7% of pregnant women, compared to 2.2% of healthy controls (p = 0.01). No increase in total or cutaneous autoantigen specific IgG was seen. Total serum IgE was within the normal range. Full-length BP180 was detected by western immunoblot in epidermal, keratinocyte, placental and cytotrophoblast (CTB) cell lysates. Furthermore, flow cytometry and indirect immunofluorescence confirmed the expression of BP180 on the surface of cultured CTBs. Finally, it was demonstrated that IgE antibodies in the pregnancy sera labeled not only cultured CTBs, but also the placental amnion and cutaneous basement membrane zone using indirect immunofluorescence. We conclude that some pregnant women develop antibodies specific for BP180, and that these autoantibodies are capable of binding both CTB and the placental amnion, potentially affecting placental function. PMID:20471095

Optimal treatment of partial thickness burns in children: a systematic review.

PubMed

Vloemans, A F P M; Hermans, M H E; van der Wal, M B A; Liebregts, J; Middelkoop, E

2014-03-01

A large part of the patient population of a burn centre consists of children, most of whom are younger than four years. The majority of these young children suffer from superficial and deep partial thickness scald burns that may easily deepen to full thickness burns. A proper wound therapy, that prevents infection and ensures a moist wound condition, might prevent the deterioration of the wound. Therefore, we performed a systematic review of wound management and dressing materials to select the best treatment option for children with burns. A search in Medline and Embase revealed 51 articles for a critical appraisal. The articles were divided into randomized controlled trials, cohort studies and a group of case-reports. Total appraisal did not differ much amongst the groups; the level of evidence was highest in the randomized controlled trials and lowest in the case-reports. In 16 out of 34 comparative studies, silver sulfadiazine or a silver sulfadiazine/chlorhexidine-gluconate combination was the standard of wound care treatment. The competitor dressing was Biobrane(®) in six studies and amnion membrane in three. Tulle gauze, or tulle gauze impregnated with an antibacterial addition were the standard of care treatment in seven studies. In general, membranous dressings like Biobrane(®) and amnion membrane performed better than the standard of care on epithelialization rate, length of hospital stay and pain for treatment of partial thickness burns in children. However, hardly any of the studies investigated long-term results like scar formation. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

FGF signalling controls anterior extraembryonic and embryonic fate in the beetle Tribolium.

PubMed

Sharma, Rahul; Beermann, Anke; Schröder, Reinhard

2013-09-01

Fibroblast growth factor (FGF) signalling plays a key role in early embryonic development and cell migration in vertebrates and in invertebrates. To gain novel insights into FGF signalling in an arthropod, we characterized the fgf1b ortholog in the beetle Tribolium that is not represented in the Drosophila genome. We found that FGF1b dependent signalling organizes the anterior to posterior axis of the early embryo. The loss of Tc-fgf1b function in Tribolium by RNA interference resulted in the reduction of the anteriormost extraembryonic fate, in an anterior shift of embryonic fate and in the loss or malformation of anterior embryonic structures. Without intact extraembryonic membranes the serosa and the amnion, Tc-fgf1b(RNAi) embryos did not undergo morphogenetic movements and remained posteriorly localized throughout embryogenesis. Only weakly affected embryos developed into a cuticle that show dorsally curved bodies with head defects and a dorsal opening. Except for the posterior dorsal amnion, the overall topology of the dorsal-ventral axis seemed unaffected. Moreover, FGF signalling was not required for the onset of mesoderm formation but for fine-tuning this tissue during later development. We also show that in affected embryos the dorsal epidermis was expanded and expressed Tc-dpp at a higher level. We conclude that in the Tribolium blastoderm embryo, FGF1-signalling organizes patterning along the AP-axis and also balances the expression level of Dpp in the dorsal epidermis, a tissue critically involved in dorsal closure. Copyright © 2013 Elsevier Inc. All rights reserved.

[The protective effect of dexpanthenol in nasal sprays. First results of cytotoxic and ciliary-toxic studies in vitro].

PubMed

Klöcker, N; Verse, T; Rudolph, P

2003-03-01

In Germany more than 60 million units of nasal decongestants are prescribed or sold over the counter. The cytotoxic and ciliary-toxic potential of alpha-sympathomimetic decongestants is well established. Furthermore, in many of the marketed products preservatives are added, predominantly benzalchonium-chloride, which can lead to a further alteration of cell- and ciliary function. Recently a protective effect of dexpanthenol was found for the human nasal mucosa. The objective of the present studies was to prove the hypothesis that dexpanthenol is able to neutralise the toxic effects of both alpha-sympathomimetic decongestants, in particular those of xylometazoline, and those of benzalconium-chloride. Therefore, systematic cytotoxic and ex vivo in vitro ciliary-toxic studies were performed. After exposition to xylometazoline in concentrations of 0.1 % and 0.05 %, the influence of dexpanthenol (5 %) and benzalconium-chloride (0,01 %) was assessed by determination of a) cell growth of FL-cells of human amnion origin, and b) ciliary beat frequency of human nasal mucosa. All tests were performed placebo-controlled. Both hypotheses were confirmed. Dexpanthenol (5 %) reduces statistically significantly the concentration-dependent toxic effects of xylometazoline, and benzalchonium-cloride regarding cell growth and ciliary beat frequency (p < 0.001). The combination of xylometazoline with dexpanthenol, while benzalconium-chloride is eliminated, resulted in a further significant increase of cell growth and ciliary beat frequency (p < 0.001), similar to control. The additive application of dexpanthenol (5 %) with nasal decongestants and/or with preserved nasal sprays seems to be able to reduce the cell- and ciliary-toxic effects of these substances.

Involvement of human decidual cell-expressed tissue factor in uterine hemostasis and abruption

PubMed Central

Lockwood, C.J.; Paidas, M.; Murk, W.K.; Kayisli, U.A.; Gopinath, A.; Krikun, G.; Huang, S.J.; Schatz, F.

2009-01-01

Vascular injury increases access and binding of plasma-derived factor VII to perivascular cell membrane-bound tissue factor (TF). The resulting TF/VIIa complex promotes hemostasis by cleaving pro-thrombin to thrombin leading to the fibrin clot. In human pregnancy, decidual cell-expressed TF prevents decidual hemorrhage (abruption). During placentation, trophoblasts remodel decidual spiral arteries into high conductance vessels. Shallow trophoblast invasion impedes decidual vascular conversion, producing an inadequate uteroplacental blood flow that elicits abruption-related placental ischemia. Thrombin induces several biological effects via cell surface protease activated receptors. In first trimester human DCs thrombin increases synthesis of sFlt-1, which elicits placental ischemia by impeding angiogenesis-related decidual vascular remodeling. During pregnacy, the fibrillar collagen-rich amnion and choriodecidua extracellular matrix (ECM) provides greater than additive tensile strength and structural integrity. Thrombin acts as an autocrine/paracrine mediator that degrades these ECMs by augmenting decidual cell expression of: 1) matrix metalloproteinases and 2) interleukin-8, a key mediator of abruption-associated decidual infiltration of neutrophils, which express several ECM degrading proteases. Our recent observations that: 1) among the cell types at the maternal fetal interface at term TF expression is highest in decidual cells indicates that this TF meets the hemostatic demands of labor and delivery; 2) TF expression in cultured term decidual cells is enhanced by progestin and thrombin suggest that maintenance of elevated circulating progesterone at term provides hemostatic protection, whereas abruption-generated thrombin can act in autocrine/paracrine fashion on DCs to promote hemostasis via enhanced TF expression. PMID:19720393

Production and characterization of multiple-layered populations of animal cells.

PubMed

Kruse, P F; Miedema, E

1965-11-01

Dense populations containing 129 x 10(6) Jensen sarcoma, 134 x 10(6) DON Chinese hamster, 28.9 x 10(6) WI-38 human diploid, 61.8 x 10(6) HEp-2 human carcinoma, and 67.4 x 10(6) WISH human amnion cells were produced from dilute inocula, 0.85 to 5.33 x 10(6), in 7 to 8 days in a perfusion system using replicate T-60 flasks. Perfusion rates as high as 560 ml medium/day/T-60 were required to maintain pH (to ca +/-0.1 unit) and adequate nutrient supplies. The cell densities encountered are described by the term "monolayer equivalents" (M.E.), defined as number of cells per culture divided by number of cells in a monolayer. The M.E.'s for T-60 cultures containing unusually dense populations of 40 x 10(6) WI-38 and 250 x 10(6) DON cells (9-day perfusion) were 5 and 17, respectively, and numbers of cells in illustrations of stained cross-sections of membranes from these cultures were in excellent agreement. Threshold M.E.'s exist below which proliferation is the chief cellular activity and above which one or more cell functions may predominate even though proliferation persists. Cellular nutrition and metabolism may change with changes in M.E., as illustrated in different patterns of glutamic acid, proline, and glycine utilization or production in dense vs. dilute WI-38 cell populations. The results indicated that the role of contact inhibition phenomena in arresting cellular proliferation was diminished in perfusion system environments.

Amniotic membranes as prosthetic material: experimental utilization data of a rat model.

PubMed

Zachariou, Z

1997-10-01

Prosthetic materials are applied for closing big tissue defects, the repair of traumatized organs, or hernias. Because nonabsorbable synthetic materials are rigid, possess a defined and unchangeable size, and foreign body reaction (FBR) may occur, biological materials may be an alternative. In experimental studies in rats the authors implanted the fetal parts of the human amniotic membranes and examined the utilization and FBR induced in a standardized model. In addition amnion (AM) was combined with vicryl-net (VN) for higher implant stability. Fifteen, 30 and 90 days after implantation, macroscopic appearance was examined, and light microscopy and immunohistology testing of the specimens were performed. Adhesions to parenchymal organs and omentum were present irrespective of the side facing the abdominal cavity. AM induced a rapid FBR, which diminished with time. Chorion (CH) and parts of the AM were resorbed within the examined period after infiltration with recipient cells and neovascularisation. The combined implant, AM, and VN showed best results because disadvantages of one material could be compensated for by the advantages of the other. The studies show that AM, in its anatomic definition, combined with VN proves to be a safe and reliable prosthetic material for the use in tissue defects.

Leprosy-associated Chronic Wound Management Using Biomaterials

PubMed Central

Sivasubramanian, Srinivasan; Mohana, Sambasivam; Maheswari, Paulraj; Victoria, Victor; Thangam, Ramar; Mahalingam, Jayashri; Chandrasekar-Janebjer, Gayathri; Savariar, Vincent; Madhan, Balaraman; Gunasekaran, Palani; Kitambi, Satish S

2018-01-01

Background: Deformities and neuropathic chronic ulcers are the common features associated with leprosy-cured individuals that impact their quality of life and impair rehabilitation efforts. The challenging aspects for treatment of chronic wounds are the factors that inhibit healing. We reasoned that limited success of various therapeutic interventions could be due to the fact that leprosy-cured individual's physiology gets acclimatized to having a chronic wound that any therapeutic intervention is counterbalanced to maintain status quo at the wound site. Therefore, an alternative strategy would be to use biomaterials that gradually alter the wound site allowing the individual's physiology to participate in the healing process. Aims: Developing the human amnion (Amn)-derived biomaterial scaffolds and evaluating its use to heal chronic wounds in leprosy-cured but deformed persons (LCDPs). Materials and Methods: Using an enzymatic protocol, we have developed a rapid method to generate biomaterial scaffolds from discarded human Amn. A clinical trial on 26 LCDPs was performed with the biomaterial, and its wound-healing potential was then compared with LCDPs undergoing standard treatment procedure. Results: Biomaterial-based treatment of chronic wounds on LCDP displayed a higher efficiency in healing when compared to standard treatment. Conclusions: This study exemplifies that biomaterial-based treatment of leprosy-wounds offers an excellent affordable alternative for wound management. This study underlines the importance of involving both local wound environment and systemic effects for healing. In addition, we highlight wound healing as a necessity for successful rehabilitation and reintegration of leprosy-cured person into the society. PMID:29910571

Leprosy-associated Chronic Wound Management Using Biomaterials.

PubMed

Sivasubramanian, Srinivasan; Mohana, Sambasivam; Maheswari, Paulraj; Victoria, Victor; Thangam, Ramar; Mahalingam, Jayashri; Chandrasekar-Janebjer, Gayathri; Savariar, Vincent; Madhan, Balaraman; Gunasekaran, Palani; Kitambi, Satish S

2018-01-01

Deformities and neuropathic chronic ulcers are the common features associated with leprosy-cured individuals that impact their quality of life and impair rehabilitation efforts. The challenging aspects for treatment of chronic wounds are the factors that inhibit healing. We reasoned that limited success of various therapeutic interventions could be due to the fact that leprosy-cured individual's physiology gets acclimatized to having a chronic wound that any therapeutic intervention is counterbalanced to maintain status quo at the wound site. Therefore, an alternative strategy would be to use biomaterials that gradually alter the wound site allowing the individual's physiology to participate in the healing process. Developing the human amnion (Amn)-derived biomaterial scaffolds and evaluating its use to heal chronic wounds in leprosy-cured but deformed persons (LCDPs). Using an enzymatic protocol, we have developed a rapid method to generate biomaterial scaffolds from discarded human Amn. A clinical trial on 26 LCDPs was performed with the biomaterial, and its wound-healing potential was then compared with LCDPs undergoing standard treatment procedure. Biomaterial-based treatment of chronic wounds on LCDP displayed a higher efficiency in healing when compared to standard treatment. This study exemplifies that biomaterial-based treatment of leprosy-wounds offers an excellent affordable alternative for wound management. This study underlines the importance of involving both local wound environment and systemic effects for healing. In addition, we highlight wound healing as a necessity for successful rehabilitation and reintegration of leprosy-cured person into the society.

Repairing Fetal Membranes with a Self-adhesive Ultrathin Polymeric Film: Evaluation in Mid-gestational Rabbit Model.

PubMed

Pensabene, Virginia; Patel, Premal P; Williams, Phillip; Cooper, Trisha L; Kirkbride, Kellye C; Giorgio, Todd D; Tulipan, Noel B

2015-08-01

Preterm premature rupture of membranes causes 40% of all preterm births, affecting 150000 women each year in the United States. Prenatal diagnostic procedures and surgical interventions increase incidence of adverse events, leading to iatrogenic membrane rupture after a fetoscopic procedure in 45% of cases. We propose an ultrathin, self-adherent, poly-L-lactic acid patch ("nanofilm") as a reparative wound closure after endoscopic/fetoscopic procedures. These nanofilms are compatible with application in wet conditions and with minimally invasive instrumentation. Ex vivo studies to evaluate the nanofilm were conducted using human chorion-amnion (CA) membranes. A custom-built inflation device was used for mechanical characterization of CA membranes and for assessment of nanofilm adhesion and sealing of membrane defects up to 3 mm in size. These ex vivo tests demonstrated the ability of the nanofilm to seal human CA defects ranging in size from 1 to 3 mm in diameter. In vivo survival studies were conducted in 25 mid-gestational rabbits, defects were created by perforating the uterus and the CA membranes and subsequently using the nanofilm to seal these wounds. These in vivo studies confirmed the successful sealing of defects smaller than 3 mm observed ex vivo. Histological analysis of whole harvested uteri 7 days after surgery showed intact uterine walls in 59% of the nanofilm repaired fetuses, along with increased uterine size and intrauterine development in 63% of the cases. In summary, we have developed an ultrathin, self-adhesive nanofilm for repair of uterine membrane defects.

RGC Neuroprotection Following Optic Nerve Trauma Mediated By Intranasal Delivery of Amnion Cell Secretome

PubMed Central

Grinblat, Gabriela A.; Khan, Reas S.; Dine, Kimberly; Wessel, Howard; Brown, Larry; Shindler, Kenneth S.

2018-01-01

Purpose Intranasally delivered ST266, the biological, proteinaceous secretome of amnion-derived multipotent progenitor cells, reduces retinal ganglion cell (RGC) loss, optic nerve inflammation, and demyelination in experimental optic neuritis. This unique therapy and novel administration route delivers numerous cytokines and growth factors to the eye and optic nerve, suggesting a potential to also treat other optic neuropathies. Thus, ST266-mediated neuroprotection was examined following traumatic optic nerve injury. Methods Optic nerve crush injury was surgically induced in C57BL/6J mice. Mice were treated daily with intranasal PBS or ST266. RGC function was assessed by optokinetic responses (OKRs), RGCs were counted, and optic nerve sections were stained with luxol fast blue and anti-neurofilament antibodies to assess myelin and RGC axon damage. Results Intranasal ST266 administered daily for 5 days, beginning at the time that a 1-second optic nerve crush was performed, significantly attenuated OKR decreases. Furthermore, ST266 treatment reduced damage to RGC axons and myelin within optic nerves, and blocked RGC loss. Following a 4-second optic nerve crush, intranasal ST266 increased RGC survival and showed a trend toward reduced RGC axon and myelin damage. Ten days following optic nerve crush, ST266 prevented myelin damage, while also inducing a trend toward increased RGC survival and visual function. Conclusions ST266 significantly attenuates traumatic optic neuropathy. Neuroprotective effects of this unique combination of biologic molecules observed here and previously in optic neuritis suggest potential broad application for preventing neuronal damage in multiple optic nerve disorders. Furthermore, results support intranasal delivery as a novel, noninvasive therapeutic modality for eyes and optic nerves. PMID:29847652

Response of human limbal epithelial cells to wounding on 3D RAFT tissue equivalents: effect of airlifting and human limbal fibroblasts.

PubMed

Massie, Isobel; Levis, Hannah J; Daniels, Julie T

2014-10-01

Limbal epithelial stem cell deficiency can cause blindness but may be treated by human limbal epithelial cell (hLE) transplantation, normally on human amniotic membrane. Clinical outcomes using amnion can be unreliable and so we have developed an alternative tissue equivalent (TE), RAFT (Real Architecture for 3D Tissue), which supports hLE expansion, and stratification when airlifted. Human limbal fibroblasts (hLF) may be incorporated into RAFT TEs, where they support overlying hLE and improve phenotype. However, the impact of neither airlifting nor hLF on hLE function has been investigated. hLE on RAFT TEs (±hLF and airlifting) were wounded using heptanol and re-epithelialisation (fluorescein diacetate staining), and percentage putative stem cell marker p63α and proliferative marker Ki67 expression (wholemount immunohistochemistry), measured. Airlifted, hLF- RAFT TEs were unable to close the wound and p63α expression was 7 ± 0.2% after wounding. Conversely, non-airlifted, hLF- RAFT TEs closed the wound within 9 days and p63α expression was higher at 22 ± 5% (p < 0.01). hLE on both hLF- and hLF+ RAFT TEs (non-airlifted) closed the wound and p63α expression was 26 ± 8% and 36 ± 3% respectively (ns). Ki67 expression by hLE increased from 1.3 ± 0.5% before wounding to 7.89 ± 2.53% post-wounding for hLF- RAFT TEs (p < 0.01), and 0.8 ± 0.08% to 17.68 ± 10.88% for hLF+ RAFT TEs (p < 0.05), suggesting that re-epithelialisation was a result of proliferation. These data suggest that neither airlifting nor hLF are necessarily required to maintain a functional epithelium on RAFT TEs, thus simplifying and shortening the production process. This is important when working towards clinical application of regenerative medicine products. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effect of Silibinin in Reducing Inflammatory Pathways in In Vitro and In Vivo Models of Infection-Induced Preterm Birth

PubMed Central

Lim, Ratana; Morwood, Carrington J.; Barker, Gillian; Lappas, Martha

2014-01-01

Infection-induced preterm birth is the largest cause of infant death and of neurological disabilities in survivors. Silibinin, from milk thistle, exerts potent anti-inflammatory activities in non-gestational tissues. The aims of this study were to determine the effect of silibinin on pro-inflammatory mediators in (i) human fetal membranes and myometrium treated with bacterial endotoxin lipopolysaccharide (LPS) or the pro-inflammatory cytokine IL-1β, and (ii) in preterm fetal membranes with active infection. The effect of silibinin on infection induced inflammation and brain injury in pregnant mice was also assessed. Fetal membranes and myometrium (tissue explants and primary cells) were treated with 200 μM silibinin in the presence or absence of 10 μg/ml LPS or 1 ng/ml IL-1β. C57BL/6 mice were injected with 70 mg/kg silibinin with or without 50 μg LPS on embryonic day 16. Fetal brains were collected after 6 h. In human fetal membranes, silibinin significantly decreased LPS-stimulated expression of IL-6 and IL-8, COX-2, and prostaglandins PGE2 and PGF2α. In primary amnion and myometrial cells, silibinin also decreased IL-1β-induced MMP-9 expression. Preterm fetal membranes with active infection treated with silibinin showed a decrease in IL-6, IL-8 and MMP-9 expression. Fetal brains from mice treated with silibinin showed a significant decrease in LPS-induced IL-8 and ninjurin, a marker of brain injury. Our study demonstrates that silibinin can reduce infection and inflammation-induced pro-labour mediators in human fetal membranes and myometrium. Excitingly, the in vivo results indicate a protective effect of silibinin on infection-induced brain injury in a mouse model of preterm birth. PMID:24647589

Escherichia coli-induced temporal and differential secretion of heat-shock protein 70 and interleukin-1β by human fetal membranes in a two-compartment culture system.

PubMed

Osorio-Caballero, M; Perdigón-Palacio, C; García-López, G; Flores-Herrera, O; Olvera-Sánchez, S; Morales-Méndez, I; Sosa-González, I; Acevedo, J F; Guzmán-Grenfell, A M; Molina-Hernández, A; Díaz, N F; Flores-Herrera, H

2015-03-01

Escherichia coli is recognized as an etiological bacteria associated with chorioamnionitis and the preterm premature rupture of fetal membranes. This pathological condition induces pro-inflammatory cytokines and degradative metalloproteinases, which are considered biological markers secreted in an acute stage of infection. Heat-shock proteins (HSPs) are an important component of the innate immunity response and are found in different pathological conditions. They have not been previously measured in human fetal membranes in response to infectious conditions. We hypothesized that the choriodecidual tissue and amniotic epithelium secreted temporal and differential Hsp-60, Hsp-70, and interleukin (IL)-1β mediated by E. coli infection. Fetal membranes were mounted in a two-compartment culture system and infected with two passes of live E. coli at different doses (10², 10⁴, 10⁵, and 10⁶ colony-forming units (CFU)/mL) and intervals of incubation (3, 6, and 24 h). The culture medium was collected, and Hsp-60, Hsp-70, and IL-1β were assessed using the enzyme-linked immunosorbent assay (ELISA) method. After 3 and 6 h of infection, E. coli induced an increase in Hsp-70 secretion in the choriodecidual tissue. However, after 24 h of incubation, Hsp-70 was downregulated and we observed an increase in IL-1β secretion. By contrast, E. coli induced a lower Hsp-60 secretion in the amnion compared to Hsp-70. Human fetal membranes responded actively to E. coli infection, with an increase in Hsp-70 during the first hours of infection. After 24 h, there was an increase in the liberation of IL-1β. Copyright © 2014 Elsevier Ltd. All rights reserved.

Role of ultrasonography in the management of twin gestation.

PubMed

Smith, Jessica; Treadwell, Marjorie C; Berman, Deborah R

2018-06-01

Twins represent 1%-2% of all pregnancies, yet continue to account for a disproportionate share of neonatal adverse events including neonatal intensive care admission, morbidity, and mortality. Ultrasonography is central to the proper diagnosis of the type of twinning. Ideally, ultrasonography is performed before 14 weeks of gestation to determine chorionicity and amnionicity. Correct identification of the chorionicity in a twin pregnancy facilitates proper counseling and management of the gestation, including ultrasonography follow-up. Herein, the different types of twinning are reviewed, together with the implications for ultrasonography monitoring of each specific type of twin gestation. © 2018 International Federation of Gynecology and Obstetrics.

Release of LHRH-activity from human fetal membranes upon exposure to PGE/sub 2/, oxytocin and isoproterenol

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

Poisner, A.M.; Poisner, R.; Becca, C.R.

1986-03-01

The authors have previously reported that superfused chorion laeve (fetal membranes) release LHRH-like immunoreactivity upon exposure to angiotensin II. They have now studied the effects of other agonists on the release of LHRH-activity and something of its chemical nature. Fetal membranes were obtained from placentas delivered by cesarean section, the amnion stripped from the chorion, and the chorion superfused in an Amicon thin-channel device with the maternal surface facing up. The whole device was submerged in a 37 C water bath and perfused with a modified Locke's solution at 0.4 - 1.0 ml/min. LHRH-activity was measured by radioimmunoassay using threemore » different antisera against LHRH. The release of LHRH-activity was stimulated by 6-10 min exposure to PGE/sub 2/, oxytocin, and isoproterenol. Extracts of chorion were studied using gel filtration on Sephacryl S-200 and ultrafiltration with Amicon PM-10 filters. The bulk of the LHRH-activity appeared as a higher molecular weight form (about 70,000 daltons). Since oxytocin has been reported to release PGE/sub 2/ from chorion, it may release LHRH-activity by virtue of liberating endogenous PGE/sub 2/. The chemical nature of the LHRH-activity is presently under investigation.« less

Mesenchymal Stem Cells from Human Amniotic Membrane and Umbilical Cord Can Diminish Immunological Response in an in vitro Allograft Model.

PubMed

Dabrowski, Filip A; Burdzinska, Anna; Kulesza, Agnieszka; Chlebus, Marcin; Kaleta, Beata; Borysowski, Jan; Zolocinska, Aleksandra; Paczek, Leszek; Wielgos, Miroslaw

2017-01-01

Mesenchymal stem cells (MSCs) are gaining rising interest in gynecology and obstetrics. MSCs immunomodulatory properties are suitable enough to reduce perinatal morbidity caused by inflammation in premature neonates. The aim of this study was to evaluate and compare the ability to inhibit allo-activated lymphocytes proliferation by MSCs derived from different sources: amniotic membrane (AM), umbilical cord (UC) and adipose tissue (AT). MSCs were isolated from AM (n = 7) and UC (n = 6) and AT (n = 6) of healthy women. Cells were characterized by flow cytometry and differentiation assay. To evaluate the potential of fetal and adult MSCs to diminish immunological response, mixed lymphocytes reaction (MLR) was performed. Amnion and UC-derived cells displayed typical MSCs characteristics. Addition of MSCs to MLR significantly inhibited the proliferation of stimulated lymphocytes. The effect was observed regardless of the MSCs type used (p < 0.01 in all groups). Comparative analysis revealed no significant differences in this action between tested MSCs types. Additionally, no type of MSCs significantly stimulated allogeneic lymphocytes. The results prove the immunosuppressive capacities of fetal-derived MSCs in vitro. In the future, they may be potentially used to treat premature newborn as well as in immunomodulation in post-transplant therapy. © 2016 S. Karger AG, Basel.

Use of hyperdry amniotic membrane in operations for cleft palate: a study in rats.

PubMed

Tsuno, Hiroaki; Noguchi, Makoto; Okabe, Motonori; Tomihara, Kei; Yoshida, Toshiko; Nikaido, Toshio

2015-04-01

The growth of maxillary bone and the development of dentition are often impaired in patients who have had pushback operations for repair of a cleft palate. There has been considerable discussion about the most suitable technique or material used in such repairs to resolve the problem. Hyperdry amniotic membrane, a new preservable material derived from human amnion, has recently been introduced in several procedures. We have evaluated its use during pushback surgery in animal studies to try to correct the inhibition of growth and development of the maxilla. Mucosal defects were created in 3-week-old rats, and then covered with hyperdry amniotic membrane or not. Healing was assessed by histological and morphological examination at 1 week and 7 weeks postoperatively. In the group treated with hyperdry amniotic membrane, submucosal tissue was reconstructed successfully during the early postoperative period. Lateral palatal growth was not inhibited as much, and medial inclination of the teeth was less, after a period of growth using this material. The results suggest that hyperdry amniotic membrane is a suitable new dressing material for use in the treatment of cleft palate. Copyright © 2015 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Human fibrin tissue adhesive for sutureless lamellar keratoplasty and scleral patch adhesion: a pilot study.

PubMed

Kaufman, Herbert E; Insler, Michael S; Ibrahim-Elzembely, Hosan A; Kaufman, Stephen C

2003-11-01

To determine whether a fibrin adhesive can facilitate the performance of sutureless lamellar keratoplasty and attachment of amnion to bare sclera. Prospective, noncomparative case series. Six patients, 5 of whom underwent lamellar keratoplasty and 1 who received an amniotic patch of the sclera and cornea. Institutional review board approval was not required for these therapeutic treatments. In 5 patients, the epithelium was removed from the corneal surface, a free cap, 200- micro m thick, was cut with a microkeratome, and a human fibrin tissue adhesive (Tisseel VH Fibrin Sealant; Baxter Healthcare Corporation, Glendale, CA) was applied to the cut surface of the corneal stroma. A 200- micro m thick, microkeratome-cut lamellar graft was placed in the stromal bed without sutures, and a bandage soft contact lens was applied. The lens was left in place for 1 week and then removed. In 1 patient, the adhesive was applied to bare sclera for attachment of amniotic membrane after removal of a conjunctival melanosis. All patients were followed up for 3 months after surgery. Tissue adhesion, corneal clarity, and visual acuity. All 5 lamellar grafts healed and remained clear, although final visual acuity varied with visual potential and astigmatism. The amniotic membrane graft also adhered well to the bare sclera. The fibrin adhesive provided satisfactory attachment without sutures for lamellar keratoplasty and amniotic patching. It should be effective for sealing of clear cornea incisions, LASIK flaps, and conjunctival and skin grafts. An adhesive that has been designed specifically for ophthalmic applications and is more convenient to use would be desirable.

Onset of human preterm and term birth is related to unique inflammatory transcriptome profiles at the maternal fetal interface.

PubMed

Bukowski, Radek; Sadovsky, Yoel; Goodarzi, Hani; Zhang, Heping; Biggio, Joseph R; Varner, Michael; Parry, Samuel; Xiao, Feifei; Esplin, Sean M; Andrews, William; Saade, George R; Ilekis, John V; Reddy, Uma M; Baldwin, Donald A

2017-01-01

Preterm birth is a main determinant of neonatal mortality and morbidity and a major contributor to the overall mortality and burden of disease. However, research of the preterm birth is hindered by the imprecise definition of the clinical phenotype and complexity of the molecular phenotype due to multiple pregnancy tissue types and molecular processes that may contribute to the preterm birth. Here we comprehensively evaluate the mRNA transcriptome that characterizes preterm and term labor in tissues comprising the pregnancy using precisely phenotyped samples. The four complementary phenotypes together provide comprehensive insight into preterm and term parturition. Samples of maternal blood, chorion, amnion, placenta, decidua, fetal blood, and myometrium from the uterine fundus and lower segment ( n  = 183) were obtained during cesarean delivery from women with four complementary phenotypes: delivering preterm with (PL) and without labor (PNL), term with (TL) and without labor (TNL). Enrolled were 35 pregnant women with four precisely and prospectively defined phenotypes: PL ( n  = 8), PNL ( n  = 10), TL ( n  = 7) and TNL ( n  = 10). Gene expression data were analyzed using shrunken centroid analysis to identify a minimal set of genes that uniquely characterizes each of the four phenotypes. Expression profiles of 73 genes and non-coding RNA sequences uniquely identified each of the four phenotypes. The shrunken centroid analysis and 10 times 10-fold cross-validation was also used to minimize false positive finings and overfitting. Identified were the pathways and molecular processes associated with and the cis-regulatory elements in gene's 5' promoter or 3'-UTR regions of the set of genes which expression uniquely characterized the four phenotypes. The largest differences in gene expression among the four groups occurred at maternal fetal interface in decidua, chorion and amnion. The gene expression profiles showed suppression of chemokines expression in TNL, withdrawal of this suppression in TL, activation of multiple pathways of inflammation in PL, and an immune rejection profile in PNL. The genes constituting expression signatures showed over-representation of three putative regulatory elements in their 5'and 3' UTR regions. The results suggest that pregnancy is maintained by downregulation of chemokines at the maternal-fetal interface. Withdrawal of this downregulation results in the term birth and its overriding by the activation of multiple pathways of the immune system in the preterm birth. Complications of the pregnancy associated with impairment of placental function, which necessitated premature delivery of the fetus in the absence of labor, show gene expression patterns associated with immune rejection.

Viable placental allograft as a biological dressing in the clinical management of full-thickness thermal occupational burns

PubMed Central

Johnson, Eric L.; Tassis, Elisabet K.; Michael, Georgina M.; Whittinghill, Susan G.

2017-01-01

Abstract Rationale: Occupational burn injuries can be detrimental and difficult to manage. The majority of complex cases are referred and managed at regional burn centers where access to specialized care is available. As an alternative to hospitalization with staged surgical procedures, placental products may be used for outpatient medical management of these common burn injuries, especially if access to a regional burn center is limited or restricted. Fresh amnion has been a treatment of choice in burns for more than 100 years. As a biological covering with a broad scope of potential uses, human placental membranes represent a dressing that is particularly advantageous for burn therapy. Recent advances in tissue-preservation technology have allowed for the commercialization of placental amnion products. Patient concerns: To address several complications associated with burn injuries—contractures, scar formation, and pain—a viable cryopreserved placental membrane (vCPM) (Grafix—PRIME, Osiris Therapeutics, Inc., MD) retaining the anti-inflammatory, anti-fibrotic, and antimicrobial properties of fresh placental tissues was chosen for clinical use in the 2 cases reported, where both patients had restricted access to the regional burn center. Diagnoses: Two cases of work-related extremity burns presented to a local rural hospital for immediate post-injury assessment. The 1st case was of a man who sustained a 55.4 cm2 full-thickness 3rd degree thermal burn with exposed bone and tendon, to the left dorsal forefoot after having an industrial pressure washer caught on his work boot. The 2nd case was of a female who sustained a 4.7 cm2 full-thickness 3rd degree crush burn to the dorsum extensor surface of her dominant hand's index finger after applying 80-pounds per square inch of heated pressure from a hydraulic press. Interventions: Both burn patients elected to continue their care at the outpatient-based wound and hyperbaric center, receiving a combination of weekly ad libitum debridement, applications of vCPM, and occupational therapy. Outcomes: Both burns reached timely wound closure, and patients regained full range of motion of the affected limb, allowing for early return to work. The average number of allograft applications was 7.5, allowing both patients to return to work in an average of 63.5 days without adverse events or post-treatment complications. Lessons: The incorporation of this product in the treatment of these complex burns prevented amputation in one patient, and skin autografting and potential index finger contracture-formation in the second patient. The incorporation of vCPM in burn management may offer a new approach to outpatient burn management and may mitigate several of the complications seen post burn injury, leading to favorable patient outcomes. PMID:29245303

Onset of human preterm and term birth is related to unique inflammatory transcriptome profiles at the maternal fetal interface

PubMed Central

Sadovsky, Yoel; Goodarzi, Hani; Zhang, Heping; Biggio, Joseph R.; Varner, Michael; Parry, Samuel; Xiao, Feifei; Esplin, Sean M.; Andrews, William; Saade, George R.; Ilekis, John V.; Reddy, Uma M.; Baldwin, Donald A.

2017-01-01

Background Preterm birth is a main determinant of neonatal mortality and morbidity and a major contributor to the overall mortality and burden of disease. However, research of the preterm birth is hindered by the imprecise definition of the clinical phenotype and complexity of the molecular phenotype due to multiple pregnancy tissue types and molecular processes that may contribute to the preterm birth. Here we comprehensively evaluate the mRNA transcriptome that characterizes preterm and term labor in tissues comprising the pregnancy using precisely phenotyped samples. The four complementary phenotypes together provide comprehensive insight into preterm and term parturition. Methods Samples of maternal blood, chorion, amnion, placenta, decidua, fetal blood, and myometrium from the uterine fundus and lower segment (n = 183) were obtained during cesarean delivery from women with four complementary phenotypes: delivering preterm with (PL) and without labor (PNL), term with (TL) and without labor (TNL). Enrolled were 35 pregnant women with four precisely and prospectively defined phenotypes: PL (n = 8), PNL (n = 10), TL (n = 7) and TNL (n = 10). Gene expression data were analyzed using shrunken centroid analysis to identify a minimal set of genes that uniquely characterizes each of the four phenotypes. Expression profiles of 73 genes and non-coding RNA sequences uniquely identified each of the four phenotypes. The shrunken centroid analysis and 10 times 10-fold cross-validation was also used to minimize false positive finings and overfitting. Identified were the pathways and molecular processes associated with and the cis-regulatory elements in gene’s 5′ promoter or 3′-UTR regions of the set of genes which expression uniquely characterized the four phenotypes. Results The largest differences in gene expression among the four groups occurred at maternal fetal interface in decidua, chorion and amnion. The gene expression profiles showed suppression of chemokines expression in TNL, withdrawal of this suppression in TL, activation of multiple pathways of inflammation in PL, and an immune rejection profile in PNL. The genes constituting expression signatures showed over-representation of three putative regulatory elements in their 5′and 3′ UTR regions. Conclusions The results suggest that pregnancy is maintained by downregulation of chemokines at the maternal-fetal interface. Withdrawal of this downregulation results in the term birth and its overriding by the activation of multiple pathways of the immune system in the preterm birth. Complications of the pregnancy associated with impairment of placental function, which necessitated premature delivery of the fetus in the absence of labor, show gene expression patterns associated with immune rejection. PMID:28879060

The impact of the International Atomic Energy Agency (IAEA) program on radiation and tissue banking in Peru.

PubMed

Gamero, Emma Castro; Morales Pedraza, Jorge

2009-05-01

The tissue bank "Rosa Guerzoni Chambergo" (RGCTB) located at the Child's Health Institute was inaugurated in 1996, with the financial and technical support of the IAEA program on radiation and tissue banking. Since 1998, the biological bandage of fresh and lyophilised pigskin, amnion and bone tissue is processed routinely in this bank. In all cases, the tissue is sterilised with the use of Cobalt-60 radiation, process carried out at the Laboratories of Irradiation of the Peruvian Institute of Nuclear Energy (IPEN). The tissue bank in the Child's Health Institute helped to save lives in an accident occurred in Lima, when a New Year's fireworks celebration ran out of control in January 2002. Nearly 300 people died in the tragic blaze and hundreds more were seriously burned and injured. Eight Lima hospitals and clinics suddenly were faced with saving the lives of severely burned men, women and children. Fortunately, authorities were ready to respond to the emergency. More than 1,600 dressings were sterilised and supplied to Lima surgeons. The efforts helped save the lives of patients who otherwise might not have survived the Lima fire. Between 1998 and September 2007, 35,012 tissue grafts were produced and irradiated. Radiation sterilised tissues are used by 20 national medical institutions as well as 17 private health institutions. The tissue bank established in Peru with the support of the IAEA is now producing the following tissues: pigskin dressings, fresh and freeze-dried; bone allografts, chips, wedges and powdered, and amnion dressings air-dried. It is also now leading the elaboration of national standards, assignment being entrusted by ONDT (Organización Nacional de Donación y Transplantes; National Organisation on Donation and Transplant). This among other will permit the accreditation of the tissue bank. In this task is also participating IPEN.

Novel concepts on pregnancy clocks and alarms: redundancy and synergy in human parturition

PubMed Central

Menon, Ramkumar; Bonney, Elizabeth A.; Condon, Jennifer; Mesiano, Sam; Taylor, Robert N.

2016-01-01

The signals and mechanisms that synchronize the timing of human parturition remain a mystery and a better understanding of these processes is essential to avert adverse pregnancy outcomes. Although our insights into human labor initiation have been informed by studies in animal models, the timing of parturition relative to fetal maturation varies among viviparous species, indicative of phylogenetically different clocks and alarms; but what is clear is that important common pathways must converge to control the birth process. For example, in all species, parturition involves the transition of the myometrium from a relaxed to a highly excitable state, where the muscle rhythmically and forcefully contracts, softening the cervical extracellular matrix to allow distensibility and dilatation and thus a shearing of the fetal membranes to facilitate their rupture. We review a number of theories promulgated to explain how a variety of different timing mechanisms, including fetal membrane cell senescence, circadian endocrine clocks, and inflammatory and mechanical factors, are coordinated as initiators and effectors of parturition. Many of these factors have been independently described with a focus on specific tissue compartments. In this review, we put forth the core hypothesis that fetal membrane (amnion and chorion) senescence is the initiator of a coordinated, redundant signal cascade leading to parturition. Whether modified by oxidative stress or other factors, this process constitutes a counting device, i.e. a clock, that measures maturation of the fetal organ systems and the production of hormones and other soluble mediators (including alarmins) and that promotes inflammation and orchestrates an immune cascade to propagate signals across different uterine compartments. This mechanism in turn sensitizes decidual responsiveness and eventually promotes functional progesterone withdrawal in the myometrium, leading to increased myometrial cell contraction and the triggering of parturition. Linkage of these processes allows convergence and integration of the gestational clocks and alarms, prompting a timely and safe birth. In summary, we provide a comprehensive synthesis of the mediators that contribute to the timing of human labor. Integrating these concepts will provide a better understanding of human parturition and ultimately improve pregnancy outcomes. PMID:27363410

Effect of Fetal Membrane-Derived Mesenchymal Stem Cell Transplantation in Rats With Acute and Chronic Pancreatitis.

PubMed

Kawakubo, Kazumichi; Ohnishi, Shunsuke; Fujita, Hirotoshi; Kuwatani, Masaki; Onishi, Reizo; Masamune, Atsushi; Takeda, Hiroshi; Sakamoto, Naoya

2016-01-01

Mesenchymal stem cells (MSCs) are a valuable cell source in regenerative medicine and can be isolated from fetal membranes (FMs), particularly amniotic membranes. We investigated the effect of rat FM-derived MSCs (rFM-MSCs) and human amnion-derived MSCs (hAMSCs) on the inflammatory reaction in vitro and therapeutic effects in rats with acute and chronic pancreatitis. Effect of rFM-MSCs or hAMSC-conditioned medium was investigated in vitro. Acute pancreatitis was induced by intraductal injection of 4% taurocholate, and rFM-MSCs were transplanted intravenously. Chronic pancreatitis was induced by intravenous injection of 5 mg/kg dibutyltin dichloride, and hAMSCs were transplanted intravenously. The inflammatory reaction of macrophages induced by lipopolysaccharide and trypsin was significantly suppressed by rFM-MSC coculture. Pancreatic acinar cell injury induced by cerulein was significantly ameliorated by hAMSC-conditioned medium. Pancreatic stellate cell activation induced by tumor necrosis factor-α was significantly decreased by hAMSC-conditioned medium. Transplantation of rFM-MSCs significantly reduced the histological score and infiltration of CD68-positive macrophages in the rat pancreas. The hAMSC transplantation significantly decreased the expression of MCP-1 and attenuated the downregulation of amylase expression in the pancreas. Transplantation of FM-MSCs and AMSCs suppressed the inflammatory reaction of acute and chronic pancreatitis in rats.

The roles of the cyclo-oxygenases types one and two in prostaglandin synthesis in human fetal membranes at term.

PubMed

Sawdy, R J; Slater, D M; Dennes, W J; Sullivan, M H; Bennett, P R

2000-01-01

The aim of this study was to determine the relative contributions of cyclo-oxygenase (COX) types 1 and 2 to prostaglandin synthesis at term. Fetal membranes were collected from 6 pregnancies after elective caesarean section at term, prior to labour. The presence of COX-1 and COX-2 protein was determined using Western analysis. The relative contributions of the two isoforms of COX to prostaglandin synthesis were determined by incubation of fetal membrane discs with either a COX-2 selective inhibitor, SC236, or a COX-1 selective inhibitor, SC560, and measurement of prostaglandin release during 24 h using enzyme-linked immuno-sorbent assay (ELISA). Both COX-1 and COX-2 protein were demonstrated in amnion and chorion-decidua. The COX-2 selective inhibitor, SC-236, significantly reduced prostaglandin synthesis, both in its COX-2 specific and higher, non-specific concentration ranges. The COX-1 selective inhibitor, SC-560, had no effect upon prostaglandin synthesis in its COX-1 specific concentration range, but did significantly reduce prostaglandin synthesis at higher, non-selective concentrations. Fetal membranes contain both COX-1 and COX-2 at term, but only COX-2 contributes towards prostaglandin synthesis. COX-2 selective NSAI drugs will be as effective as non-selective agents in inhibition of fetal membrane prostaglandin synthesis and may represent a new strategy for tocolysis. Copyright 2000 Harcourt Publishers Ltd.

A Human Amnion-Derived Extracellular Matrix-Coated Cell-Free Scaffold for Cartilage Repair: In Vitro and In Vivo Studies.

PubMed

Nogami, Makiko; Kimura, Tomoatsu; Seki, Shoji; Matsui, Yoshito; Yoshida, Toshiko; Koike-Soko, Chika; Okabe, Motonori; Motomura, Hiraku; Gejo, Ryuichi; Nikaido, Toshio

2016-04-01

Extracellular matrix (ECM) derived from human amniotic mesenchymal cells (HAMs) has various biological activities. In this study, we developed a novel HAM-derived ECM-coated polylactic-co-glycolic acid (ECM-PLGA) scaffold, examined its property on mesenchymal cells, and investigated its potential as a cell-free scaffold for cartilage repair. ECM-PLGA scaffolds were developed by inoculating HAM on a PLGA. After decellularization by irradiation, accumulated ECM was examined. Exogenous cell growth and differentiation of rat mesenchymal stem cells (MSCs) on the ECM-PLGA were analyzed in vitro by cell attachment/proliferation assay and reverse transcription-polymerase chain reaction. The cell-free ECM-PLGA scaffolds were implanted into osteochondral defects in the trochlear groove of rat knees. After 4, 12, or 24 weeks, the animals were sacrificed and the harvested tissues were examined histologically. The ECM-PLGA contained ECM that mimicked natural amniotic stroma that contains type I collagen, fibronectin, hyaluronic acid, and chondroitin sulfates. The ECM-PLGA showed excellent properties of cell attachment and proliferation. MSCs inoculated on the ECM-PLGA scaffold showed accelerated type II collagen mRNA expression after 3 weeks in culture. The ECM-PLGA implanted into an osteochondral defect in rat knees induced gradual tissue regeneration and resulted in hyaline cartilage repair, which was better than that in the empty control group. These in vitro and in vivo experiments show that the cell-free scaffold composed of HAM-derived ECM and PLGA provides a favorable growth environment for MSCs and facilitates the cartilage repair process. The ECM-PLGA may become a "ready-made" biomaterial for cartilage repair therapy.

Comparison of impact of two decontamination solutions on the viability of the cells in human amnion.

PubMed

Smeringaiova, Ingrida; Trosan, Peter; Mrstinova, Miluse Berka; Matecha, Jan; Burkert, Jan; Bednar, Jan; Jirsova, Katerina

2017-09-01

Human amniotic membrane (HAM) is used as an allograft in regenerative medicine or as a source of pluripotent cells for stem cell research. Various decontamination protocols and solutions are used to sterilize HAM before its application, but little is known about the toxicity of disinfectants on HAM cells. In this study, we tested two decontamination solutions, commercial (BASE·128) and laboratory decontamination solution (LDS), with an analogous content of antimycotic/antibiotics for their cytotoxic effect on HAM epithelial (EC) and mesenchymal stromal cells (MSC). HAM was processed in a standard way, placed on nitrocellulose scaffold, and decontaminated, following three protocols: (1) 6 h, 37 °C; (2) 24 h, room temperature; (3) 24 h, 4 °C. The viability of EC was assessed via trypan blue staining. The apoptotic cells were detected using terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL). The mean % (±SD) of dead EC (%DEC) from six fresh placentas was 12.9 ± 18.1. Decontamination increased %DEC compared to culture medium. Decontamination with BASE·128 for 6 h, 37 °C led to the highest EC viability (81.7%). Treatment with LDS at 24 h, 4 °C resulted in the lowest EC viability (55.9%) in the set. MSC were more affected by apoptosis than EC. Although the BASE·128 expresses lower toxicity compared to LDS, we present LDS as an alternative decontamination solution with a satisfactory preservation of cell viability. The basic formula of LDS will be optimised by enrichment with nutrient components, such as glucose or vitamins, to improve cell viability.

Limbal Fibroblasts Maintain Normal Phenotype in 3D RAFT Tissue Equivalents Suggesting Potential for Safe Clinical Use in Treatment of Ocular Surface Failure.

PubMed

Massie, Isobel; Dale, Sarah B; Daniels, Julie T

2015-06-01

Limbal epithelial stem cell deficiency can cause blindness, but transplantation of these cells on a carrier such as human amniotic membrane can restore vision. Unfortunately, clinical graft manufacture using amnion can be inconsistent. Therefore, we have developed an alternative substrate, Real Architecture for 3D Tissue (RAFT), which supports human limbal epithelial cells (hLE) expansion. Epithelial organization is improved when human limbal fibroblasts (hLF) are incorporated into RAFT tissue equivalent (TE). However, hLF have the potential to transdifferentiate into a pro-scarring cell type, which would be incompatible with therapeutic transplantation. The aim of this work was to assess the scarring phenotype of hLF in RAFT TEs in hLE+ and hLE- RAFT TEs and in nonairlifted and airlifted RAFT TEs. Diseased fibroblasts (dFib) isolated from the fibrotic conjunctivae of ocular mucous membrane pemphigoid (Oc-MMP) patients were used as a pro-scarring positive control against which hLF were compared using surrogate scarring parameters: matrix metalloproteinase (MMP) activity, de novo collagen synthesis, α-smooth muscle actin (α-SMA) expression, and transforming growth factor-β (TGF-β) secretion. Normal hLF and dFib maintained different phenotypes in RAFT TE. MMP-2 and -9 activity, de novo collagen synthesis, and α-SMA expression were all increased in dFib cf. normal hLF RAFT TEs, although TGF-β1 secretion did not differ between normal hLF and dFib RAFT TEs. Normal hLF do not progress toward a scarring-like phenotype during culture in RAFT TEs and, therefore, may be safe to include in therapeutic RAFT TE, where they can support hLE, although in vivo work is required to confirm this. dFib RAFT TEs (used in this study as a positive control) may be useful toward the development of an ex vivo disease model of Oc-MMP.

Limbal Fibroblasts Maintain Normal Phenotype in 3D RAFT Tissue Equivalents Suggesting Potential for Safe Clinical Use in Treatment of Ocular Surface Failure

PubMed Central

Dale, Sarah B.; Daniels, Julie T.

2015-01-01

Limbal epithelial stem cell deficiency can cause blindness, but transplantation of these cells on a carrier such as human amniotic membrane can restore vision. Unfortunately, clinical graft manufacture using amnion can be inconsistent. Therefore, we have developed an alternative substrate, Real Architecture for 3D Tissue (RAFT), which supports human limbal epithelial cells (hLE) expansion. Epithelial organization is improved when human limbal fibroblasts (hLF) are incorporated into RAFT tissue equivalent (TE). However, hLF have the potential to transdifferentiate into a pro-scarring cell type, which would be incompatible with therapeutic transplantation. The aim of this work was to assess the scarring phenotype of hLF in RAFT TEs in hLE+ and hLE− RAFT TEs and in nonairlifted and airlifted RAFT TEs. Diseased fibroblasts (dFib) isolated from the fibrotic conjunctivae of ocular mucous membrane pemphigoid (Oc-MMP) patients were used as a pro-scarring positive control against which hLF were compared using surrogate scarring parameters: matrix metalloproteinase (MMP) activity, de novo collagen synthesis, α-smooth muscle actin (α-SMA) expression, and transforming growth factor-β (TGF-β) secretion. Normal hLF and dFib maintained different phenotypes in RAFT TE. MMP-2 and -9 activity, de novo collagen synthesis, and α-SMA expression were all increased in dFib cf. normal hLF RAFT TEs, although TGF-β1 secretion did not differ between normal hLF and dFib RAFT TEs. Normal hLF do not progress toward a scarring-like phenotype during culture in RAFT TEs and, therefore, may be safe to include in therapeutic RAFT TE, where they can support hLE, although in vivo work is required to confirm this. dFib RAFT TEs (used in this study as a positive control) may be useful toward the development of an ex vivo disease model of Oc-MMP. PMID:25380529

Novel concepts on pregnancy clocks and alarms: redundancy and synergy in human parturition.

PubMed

Menon, Ramkumar; Bonney, Elizabeth A; Condon, Jennifer; Mesiano, Sam; Taylor, Robert N

2016-09-01

The signals and mechanisms that synchronize the timing of human parturition remain a mystery and a better understanding of these processes is essential to avert adverse pregnancy outcomes. Although our insights into human labor initiation have been informed by studies in animal models, the timing of parturition relative to fetal maturation varies among viviparous species, indicative of phylogenetically different clocks and alarms; but what is clear is that important common pathways must converge to control the birth process. For example, in all species, parturition involves the transition of the myometrium from a relaxed to a highly excitable state, where the muscle rhythmically and forcefully contracts, softening the cervical extracellular matrix to allow distensibility and dilatation and thus a shearing of the fetal membranes to facilitate their rupture. We review a number of theories promulgated to explain how a variety of different timing mechanisms, including fetal membrane cell senescence, circadian endocrine clocks, and inflammatory and mechanical factors, are coordinated as initiators and effectors of parturition. Many of these factors have been independently described with a focus on specific tissue compartments.In this review, we put forth the core hypothesis that fetal membrane (amnion and chorion) senescence is the initiator of a coordinated, redundant signal cascade leading to parturition. Whether modified by oxidative stress or other factors, this process constitutes a counting device, i.e. a clock, that measures maturation of the fetal organ systems and the production of hormones and other soluble mediators (including alarmins) and that promotes inflammation and orchestrates an immune cascade to propagate signals across different uterine compartments. This mechanism in turn sensitizes decidual responsiveness and eventually promotes functional progesterone withdrawal in the myometrium, leading to increased myometrial cell contraction and the triggering of parturition. Linkage of these processes allows convergence and integration of the gestational clocks and alarms, prompting a timely and safe birth. In summary, we provide a comprehensive synthesis of the mediators that contribute to the timing of human labor. Integrating these concepts will provide a better understanding of human parturition and ultimately improve pregnancy outcomes. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Placental sulfatase deficiency: maternal and fetal expression of steroid sulfatase deficiency and X-linked ichthyosis.

PubMed

Bradshaw, K D; Carr, B R

1986-07-01

PSD-X-linked ichthyosis are manifestations of a similar disorder of an inborn error of metabolism characterized by a deficiency of steroid sulfatase. The decreased enzyme activity is due to the absence of the expression of enzyme (steroid sulfatase) protein. Affected individuals with this disorder are males (X-linked inheritance) with a frequency of 1/2000 to 1/6000 births. Homozygous females from cosanguineous marriages have been reported with this disorder. The diagnosis is suspected and confirmed by: Low estriol excretion; Negative DHEAS loading test Increased DHEAS in amnionic fluid; Normal DHEAS in cord plasma; Possible delayed or abnormal labor patterns; Decreased sulfatase activity in the placenta, fibroblast, erythrocytes, lymphocytes or leukocytes of affected individuals; Development of ichthyosis in male infants at 2 to 3 months of age.

Constriction band syndrome occurring in the setting of in vitro fertilization and advanced maternal age

PubMed Central

Rinker, Brian; Vasconez, Henry C

2006-01-01

The debate as to the pathogenesis of constriction band syndrome began with Hippocrates and continues today. The exogenous theory attributes the condition to entanglement of the fetus in the amniotic remnants following premature rupture of the amnion, which is in contrast to the endogenous, or genetic, mechanism. A case of constriction band syndrome in the setting of in vitro fertilization, where the child was genetically unrelated to the birth mother, is presented. Constriction band syndrome has been reported following amniocentesis and chorionic villus sampling, but it has not heretofore been presented in the setting of in vitro fertilization. In addition, the present case presents an opportunity to separate maternal from genetic factors and, possibly, shed some light on the etiology of the condition. PMID:19554231

Using Amniotic Membrane as a Novel Method to Reduce Post-burn Hypertrophic Scar Formation: A Prospective Follow-up Study

PubMed Central

Mohammadi, Ali Akbar; Eskandari, Shima; Johari, Hamed Ghoddusi; Rajabnejad, Ata'ollah

2017-01-01

Background: Several studies have shown that the application of amniotic membrane as a biological dressing in the management of burns is accompanied by rapid re-epithelialisation. In this follow-up study, we aimed to evaluate the possible role of amniotic membrane as an adjunct to split thickness skin grafting on reducing itching and severity of hypertrophic scar formation. Materials and Methods: From October 2013 to January 2015, in a prospective follow-up study, 54 patients (108 limbs) with second and third degree burns, covering 4%–15% of total body surface area (TBSA), were included in the study. All patients needed split-thickness skin grafts for burn-wound coverage. Selected patients had symmetric burns on two (upper or lower) extremities. Then, in every patient, the extremities were randomly divided into two groups: In one limb, the skin graft was traditionally fixed with skin staples (control group) and in the other limb, the skin graft was covered with an amniotic membrane (amnion group). Therefore, in every patient, the graft was covered with an amniotic membrane in one extremity and fixed with skin staples in the other extremity. Finally, after 6 months, the degree of itching and hypertrophic scar formation was compared between the two groups. Results: The study group was composed of 108 limbs in 54 patients (27 males and 27 females) with a mean age of 23.54 ± 4.9 years and burn 9.03 ± 2.69% TBSA. The patients were divided into two groups: 54 limbs in amnion group and 54 limbs in control group. In 59.25% of the cases, patient had less itching in the extremity covered with amniotic membrane. Furthermore, in 64.81% of the cases, patients had less hypertrophic scar formation in the extremity covered with amniotic membrane. These differences were statistically significant (P < 0.001). Conclusions: Amniotic membrane used as an adjunct in split thickness skin grafting is a novel modality which significantly reduces scar formation and itching that can be greatly distressing to burn patients. However, still more prospective well designed studies are needed to prove it. PMID:28529415

Setting up a Tissue Bank in India: The Tata Memorial Hospital Experience.

PubMed

Gajiwala, A L

2003-01-01

In India, the procurement of tissues for transplantation is governed by the Transplantation of Human Organs Act, 1994. However, although this law exists, it is primarily applied to organ transplantation and rules and regulations that are specific to tissue banking have yet to be developed.The Tata Memorial Hospital (TMH) Tissue Bank was started in 1988 as part of an International Atomic Energy Agency (IAEA) programme to promote the use of ionising radiation for the sterilisation of biological tissues. It represents the Government of India within this project and was the first such facility in the country. It is registered with the Health Services Maharashtra State and provides lyophilised amnion, dura mater, skin and bone that have been terminally sterilised with exposure to 25 kGy of gamma radiation from a Cobalt 60 source. These are obtained either from cadavers or live donors.To date the TMH Tissue Bank has provided 6328 allografts for use as biological dressings or in various reconstructive procedures.The TMH Tissue Bank has helped initiate a Tissue Bank at the Defence Laboratory (DL), Jodhpur. At present these are the only two Banks in the country using radiation for terminal sterilisation of banked tissues.The availability of safe, clinically useful and cost effective grafts have resulted in changes in surgical treatment with a concomitant increase in demand for grafts and an interest in developing more tissue banks. The availability of donor tissue however, continues to be a major limitation.

Tissue banking in India: gamma-irradiated allografts.

PubMed

Lobo Gajiwala, A

2003-01-01

In India, the procurement of tissues for transplantation is governed by the Transplantation of Human Organs Act, 1994. Although this law exists, it is primarily applied to organ transplantation and rules and regulations that are specific to tissue banking which have yet to be developed. The Tata Memorial Hospital (TMH) Tissue Bank was started in 1988 as part of an International Atomic Energy Agency (IAEA) programme to promote the use of ionising radiation for the sterilisation of biological tissues. It represents the Government of India within this project and was the first facility in the country to use radiation for the sterilisation of allografts. It is registered with the Health Services Maharashtra State and provides freeze-dried, gamma irradiated amnion, dura mater, skin and bone. The tissues are obtained either from cadavers or live donors. To date the TMH Tissue Bank has provided 6328 allografts which have found use as biological dressings and in various reconstructive procedures. The TMH Tissue Bank has helped initiate a Tissue Bank at the Defence Laboratory (DL), Jodhpur. At present these are the only two Banks in the country using radiation for the terminal sterilisation of preserved tissues. The availability of safe, clinically useful and cost effective grafts has stimulated innovative approaches to surgery. There is an increased demand for banked tissues and a heightened interest in the development of tissue banks. Inadequate infrastructure for donor referral programmes and the lack of support for tissue transplant co-ordinators however, continue to limit the availability of donor tissue.

[Bile duct lesions repaired with peritoneal tube grafts].

PubMed

Lorenzana-Bautista, Ileana; Flores-Plascencia, Aníbal; Barrios-Pineda, Francisco Javier; Alderete-Vázquez, Georgia; Sánchez-Valdivieso, Enrique Alejandro

2013-01-01

A significant number of people suffer iatrogenic bile duct injury during laparoscopic cholescystectomy. Biliary-digestive bypass may be complicated by stenosis and biliary sepsis, affecting both quality of life and life expectancy. To avoid bypass synthetic grafts have been used, which are expensive. Evaluating autologous implantation of peritoneus as alternative of bile duct repair. Under general anesthesia, ten New Zealand adult rabbits were operated, common bile duct approached and sectioned underneath the cystic duct followed by a liver biopsy. An autologous graft was built of peritoneum and graft-bile duct proximal and distal end-to-end anastomosis done. Animals were followed-up by weekly bilirrubin and transferases. Rabbits were scheduled euthanized and a liver biopsy done for histological examinations. Autologous graft was easy to create and all rabbits survived. They did not develop jaundice or alterations in their normal habits. At necropsy, autologous grafts were removed and no signs of occlusion were noticed. Moderate short-term liver damage was observed but long-term damage was negligible. Bileoma and pyogenic liver abscess were observed in two animals, respectively. Our results favourably match well-known procedures used for bile duct repair, especially in cases of severe injury (Bismuth-Strasberg E1-3): it seems less complicated than biliary-digestive bypass, not as expensive as synthetic grafts, and much easier to build than human amnion graft. Interposing an autologous graft of peritoneum is an easy-to-create surgical procedure and circumferential bile duct injuries were adequately repaired.

N-methyl-N'-nitro-N-nitrosoguanidine interferes with the epidermal growth factor receptor-mediated signaling pathway.

PubMed

Gao, Zhihua; Yang, Jun; Huang, Yun; Yu, Yingnian

2005-03-01

Many environmental factors, such as ultraviolet (UV) and arsenic, can induce the clustering of cell surface receptors, including epidermal growth factor receptor (EGFR). This is accompanied by the phosphorylation of the receptors and the activation of ensuing cellular signal transduction pathways, which are implicated in the various cellular responses caused by the exposure to these factors. In this study, we have shown that N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), an alkylating agent, also induced the clustering of EGFR in human amnion FL cells, which was similar in morphology to that of epidermal growth factor treatment. However, MNNG treatment did not activate Ras, the downstream mediator in EGFR signaling pathway, as compared to EGF treatment. The autophosphorylation of tyrosine residues Y1068 and Y1173 at the intracellular domain of EGFR, which is related to Ras activation under EGF treatment, was also not observed by MNNG exposure. Interestingly, although MNNG did not affect the binding of EGF to EGFR, MNNG can interfere with EGF function. For instance, pre-incubating FL cells with MNNG inhibited the autophosphorylation of EGFR by EGF treatment, as well as the activation of Ras. In addition, the phosphorylation of Y845 on EGFR by EGF, which is mediated through c-Src or related kinases but not autophosphorylation, was also affected by MNNG. Therefore, MNNG may influence the tyrosine kinase activity as well as the phosphorylation of EGFR through its interaction with EGFR.

Influence of the antiseptic agents polyhexanide and octenidine on FL cells and on healing of experimental superficial aseptic wounds in piglets. A double-blind, randomised, stratified, controlled, parallel-group study.

PubMed

Kramer, A; Roth, B; Müller, G; Rudolph, P; Klöcker, N

2004-01-01

The main target of the combination of octenidine with phenoxyethanol (Octenisept) is the antisepsis of acute wounds, whereas polyhexanide combined with polyethylene glycol in Ringer solution (Lavasept) is the agent of choice for antisepsis of chronic wounds and burns. Because comparative data for both agents on the effects on wound healing are lacking, we investigated the influence of preparations based on polyhexanide and octenidine versus placebo (Ringer solution) in experimental superficial aseptic skin wounds (n = 108) of 20 mm diameter, using a double-blind, randomised, stratified, controlled, parallel-group design in piglets. Computerised planimetry and histopathological methods were used for the assessment of wound healing. Histologically, no significant differences could be verified at any time between the 3 groups. However, in the early phase (day 9 after wounding), the octenidine-based product retarded wound contraction to a significantly greater extent than placebo and polyhexanide, whereas in the later phase (days 18 and 28), polyhexanide promoted contraction significantly more than did placebo and octenidine. The consequence is complete wound closure after 22.9 days using polyhexanide, in comparison to the placebo after 24.1 days (p < 0.05) and octenidine after 28.3 days (no statistical difference to placebo). This may be explained by the better tolerance of polyhexanide in vitro, which was demonstrated with dose and time dependence in cytotoxicity tests on human amnion cells. Copyright 2004 S. Karger AG, Basel

Induction of Suppressor of Cytokine Signaling-3 by Herpes Simplex Virus Type 1 Contributes to Inhibition of the Interferon Signaling Pathway

PubMed Central

Yokota, Shin-ichi; Yokosawa, Noriko; Okabayashi, Tamaki; Suzutani, Tatsuo; Miura, Shunsuke; Jimbow, Kowichi; Fujii, Nobuhiro

2004-01-01

We showed previously that herpes simplex virus type 1 (HSV-1) suppresses the interferon (IFN) signaling pathway during the early infection stage in the human amnion cell line FL. HSV-1 inhibits the IFN-induced phosphorylation of Janus kinases (JAK) in infected FL cells. In the present study, we showed that the suppressor of cytokine signaling-3 (SOCS3), a host negative regulator of the JAK/STAT pathway, is rapidly induced in FL cells after HSV-1 infection. Maximal levels of SOCS3 protein were detected at around 1 to 2 h after infection. This is consistent with the occurrence of HSV-1-mediated inhibition of IFN-induced JAK phosphorylation. The HSV-1 wild-type strain VR3 induced SOCS3 more efficiently than did mutants that are defective in UL41 or UL13 and that are hyperresponsive to IFN. Induction of the IRF-7 protein and transcriptional activation of IFN-α4, which occur in a JAK/STAT pathway-dependent manner, were poorly induced by VR3 but efficiently induced by the mutant viruses. In contrast, phosphorylation of IRF-3 and transcriptional activation of IFN-β, which are JAK/STAT pathway-independent process, were equally well induced by the wild-type strain and the mutants. In conclusion, the SOCS3 protein appears to be mainly responsible for the suppression of IFN signaling and IFN production that occurs during HSV-1 infection. PMID:15163721

Placental stem cell correction of murine intermediate maple syrup urine disease.

PubMed

Skvorak, Kristen J; Dorko, Kenneth; Marongiu, Fabio; Tahan, Veysel; Hansel, Marc C; Gramignoli, Roberto; Gibson, K Michael; Strom, Stephen C

2013-03-01

There is improved survival and partial metabolic correction of a mouse intermediate maple syrup urine disease (iMSUD) model after allogenic hepatocyte transplantation, confirming that a small number of enzyme-proficient liver-engrafted cells can improve phenotype. However, clinical shortages of suitable livers for hepatocyte isolation indicate a need for alternative cell sources. Human amnion epithelial cells (hAECs) share stem cell characteristics without the latter's safety and ethical concerns and differentiate to hepatocyte-like cells. Eight direct hepatic hAEC transplantations were performed in iMSUD mice over the first 35 days beginning at birth; animals were provided a normal protein diet and sacrificed at 35 and 100 days. Treatment at the neonatal stage is clinically relevant for MSUD and may offer a donor cell engraftment advantage. Survival was significantly extended and body weight was normalized in iMSUD mice receiving hAEC transplantations compared with untreated iMSUD mice, which were severely cachectic and died ≤28 days after birth. Branched chain α-keto acid dehydrogenase enzyme activity was significantly increased in transplanted livers. The branched chain amino acids leucine, isoleucine, valine, and alloisoleucine were significantly improved in serum and brain, as were other large neutral amino acids. Placental-derived stem cell transplantation lengthened survival and corrected many amino acid imbalances in a mouse model of iMSUD. This highlights the potential for their use as a viable alternative clinical therapy for MSUD and other liver-based metabolic diseases. Copyright © 2012 American Association for the Study of Liver Diseases.

Placental Stem Cell Correction of Murine Intermediate Maple Syrup Urine Disease

PubMed Central

Skvorak, Kristen J.; Dorko, Kenneth; Marongiu, Fabio; Tahan, Veysel; Hansel, Marc C.; Gramignoli, Roberto; Gibson, K. Michael; Strom, Stephen C.

2012-01-01

We previously reported improved survival and partial metabolic correction of a mouse intermediate maple syrup urine disease (iMSUD) model post allogenic hepatocyte transplant, confirming that a small number of enzyme proficient liver-engrafted cells can improve phenotype. However, clinical shortages of suitable livers for hepatocyte isolation indicate a need for alternative cell sources. Human amnion epithelial cells (hAEC) share stem cell characteristics while lacking many safety and ethical concerns, and differentiate to hepatocyte-like cells. Eight direct hepatic hAEC transplants were administered to iMSUD mice over the first 35 days beginning at birth; animals were provided a normal protein diet and sacrificed at days 35 and 100. Treatment at the neonatal stage is clinically relevant for MSUD, and may offer a donor cell engraftment advantage. Survival was significantly extended and body weight was normalized in iMSUD mice receiving hAEC transplants compared to iMSUD (severely cachectic; dead ≤28 days). Branched chain α-keto acid dehydrogenase enzyme activity was significantly increased in transplanted livers. Branched chain amino acids leucine, isoleucine, valine, and alloisoleucine were significantly improved in the sera and brain, as were other large neutral amino acids. Conclusion: Placental-derived stem cell transplantation lengthened survival and corrected many amino acid imbalances in a mouse model of iMSUD. This highlights the potential for their use as a viable alternative clinical therapy for MSUD and other liver-based metabolic diseases. PMID:23175463

Expression of the cytokeratin endo A gene during early mouse embryogenesis.

PubMed Central

Duprey, P; Morello, D; Vasseur, M; Babinet, C; Condamine, H; Brûlet, P; Jacob, F

1985-01-01

Expression of cytokeratin endo A has been analyzed during mouse blastocyst formation and embryonal carcinoma cell differentiation. To study the regulation of endo A expression, nuclease S1 mapping experiments have been performed on RNA extracted from two-cell to 7.5-day embryos. Low levels of endo A mRNA begin to be detectable in eight-cell embryos. The amount of this mRNA increases at the blastocyst stage, suggesting that endo A expression is regulated at the mRNA level during blastocyst formation. At this stage, in situ hybridization studies show that endo A mRNA is present in the trophectoderm but not in the inner cell mass. In 7.5-day embryos, endo A mRNAs are also detectable in the endoderm layer and in the amnion. Images PMID:2417224

Significance of fibrotic bands in utero--Amniotic band sequence with limb body wall complex: A rare case of fetal autopsy.

PubMed

Devi, P Lekshmi; Cicy, P J; Thambi, Renu; Poothiode, Usha

2015-01-01

Amniotic band sequence (ABS) includes a wide spectrum of abnormalities resulting from entrapment of various fetal parts from a disrupted amnion, ranging from a mere constriction ring affecting a finger to a fatal form called limb body wall complex (LBWC). Reported cases of ABS with LBWC are very few. The spectrum of anomalies depends on which part gets entrapped and at what point of gestation. Hence, the clinical presentation can be extremely variable. Early detection of such cases using sonology is really challenging due to the small size of the fibrotic bands. Here, we present a case of amniotic band syndrome with LBWC in a fetus at 24 weeks of gestation, which was referred for an autopsy. The fetus also showed scoliosis, gastroschisis, lumbosacral meningocele, congenital talipes equinovarus, and cleft palate, thus having features of placenta cranial and placenta abdominal phenotype which is very rare.

Chorioamnionitis caused by Serratia marcescens in a non-immunocompromised host

PubMed Central

Shimizu, S; Kojima, H; Yoshida, C; Suzukawa, K; Mukai, H Y; Hasegawa, Y; Hitomi, S; Nagasawa, T

2003-01-01

A 26 year old pregnant woman with antithrombin III deficiency developed recurrent septicaemia with Serratia marcescens. In spite of the administration of antibiotics, high grade fever persisted. She subsequently manifested lower abdominal pain, and spontaneous abortion occurred. After the abortion, she became completely afebrile. The amnion was turbid, and microscopic examination of the placenta showed haemorrhage and massive infiltration of neutrophils, suggestive of infectious chorioamnionitis. Pulsed field gel electrophoresis showed that isolates from the blood, urine, and vaginal discharge were genetically identical. Intravenous pyelography revealed that she had a bilateral completed double ureter. It was thought that a urinary tract anomaly caused infection with S marcescens, and the pathogen spread to the chorioamnion via the bloodstream. This is the first report of chorioamnionitis caused by S marcescens in a non-immunocompromised host. In addition, these findings indicate that the chorioamnion can serve as a site for persistent infection in normal pregnancies. PMID:14600137

Differences in placental telomere length suggest a link between racial disparities in birth outcomes and cellular aging

PubMed Central

JONES, Christopher W.; GAMBALA, Cecilia; ESTEVES, Kyle C.; WALLACE, Maeve; SCHLESINGER, Reid; O’QUINN, Marguerite; KIDD, Laura; THEALL, Katherine P.; DRURY, Stacy S.

2017-01-01

BACKGROUND Health disparities begin early in life and persist across the life course. Despite current efforts Black women exhibit greater risk for pregnancy complications and negative perinatal outcomes compared to White women. The placenta, a complex multi-tissue organ, serves as the primary transducer of bidirectional information between the mother and fetus. Altered placental function is linked to multiple racially disparate pregnancy complications, however little is known about racial differences in molecular factors within the placenta. Several pregnancy complications, including preeclampsia and fetal growth restriction, exhibit racial disparities and are associated with shorter placental telomere length, an indicator of cellular stress and aging. Cellular senescence and telomere dynamics are linked to the molecular mechanisms associated with the onset of labor and parturition. Further, racial differences in telomere length are found in a range of different peripheral tissues. Together these factors suggest that exploration of racial differences in telomere length of the placenta may provide novel mechanistic insight into racial disparities in birth outcomes. OBJECTIVE This study examined whether telomere length measured in four distinct fetally-derived tissues were significantly different between Blacks and Whites. The study had two hypotheses: (1) that telomere length measured in different placental tissue types would be correlated and (2) that across all sampled tissues telomere length would differ by race. STUDY DESIGN In a prospective study, placental tissue samples were collected from the amnion, chorion, villus, and umbilical cord from Black and White singleton pregnancies (N=46). Telomere length was determined using monochrome multiplex quantitative real-time polymerase chain reaction in each placental tissue. Demographic and pregnancy-related data were also collected. Descriptive statistics characterized the sample overall and among Black and White women separately. The overall impact of race was assessed by multilevel mixed-effects linear regression models that included empirically relevant covariates. RESULTS Telomere length was significantly correlated across all placental tissues. Pairwise analyses of placental tissue telomere length revealed significantly longer telomere length in the amnion compared to the chorion (t=−2.06, p=0.043). Overall telomere length measured in placenta samples from Black mothers were significantly shorter than those from White mothers (β=−0.09, p=0.04). Controlling for relevant maternal and infant characteristics strengthened the significance of the observed racial differences (β=−0.12, p=0.02). Within tissue analyses revealed that the greatest difference by race was found in chorionic telomere length (t=−2.81, p=0.007). CONCLUSION These findings provide the first evidence of racial differences in placental telomere length. Telomere length was significantly shorter in placental samples derived from Black mothers compared to White. Given previous studies reporting that telomere length, cellular senescence, and telomere dynamics are molecular factors contributing to the rupture of the amniotic sac, onset of labor, and parturition, our findings of shorter telomere length in placentas from Black mothers suggests that accelerated cellular aging across placental tissues may be relevant to the increased risk of preterm delivery in Blacks. Our results suggest that racial differences in cellular aging in the placenta contribute to the earliest roots of health disparities. PMID:27865975

Tissue distribution of cells derived from the area opaca in heterospecific quail-chick blastodermal chimeras

PubMed Central

Karagenç, Levent; Sandikci, Mustafa

2010-01-01

The objective of the current study was to determine the tissue distribution of cells derived from the area opaca in heterospecific quail-chick blastodermal chimeras. Quail-chick chimeras were constructed by transferring dissociated cells from the area opaca of the stage X–XII (EG&K) quail embryo into the subgerminal cavity of the unincubated chick blastoderm. The distribution of quail cells in embryonic as well as extra-embryonic tissues of the recipient embryo were examined using the QCPN monoclonal antibody after 6 days of incubation in serial sections taken at 100-μm intervals. Data gathered in the present study demonstrated that, when introduced into the subgerminal cavity of a recipient embryo, cells of the area opaca are able to populate not only extra-embryonic structures such as the amnion and the yolk sac, but also various embryonic tissues derived from the ectoderm and less frequently the mesoderm. Ectodermal chimerism was confined mainly to the head region and was observed in tissues derived from the neural ectoderm and the surface ectoderm, including the optic cup, diencephalon and lens. Although the possibility of random incorporation of transplanted cells into these embryonic structures cannot be excluded, these results would suggest that area opaca, a peripheral ring of cells in the avian embryo destined to form the extra-embryonic ectoderm and endoderm of the yolk sac, might harbor cells that have the potential to give rise to various cell types in the recipient chick embryo, including those derived from the surface ectoderm and neural ectoderm. PMID:19900180

Anti-Inflammatory Effects of Adult Stem Cells in Sustained Lung Injury: A Comparative Study

PubMed Central

Moodley, Yuben; Vaghjiani, Vijesh; Chan, James; Baltic, Svetlana; Ryan, Marisa; Tchongue, Jorge; Samuel, Chrishan S.; Murthi, Padma; Parolini, Ornella; Manuelpillai, Ursula

2013-01-01

Lung diseases are a major cause of global morbidity and mortality that are treated with limited efficacy. Recently stem cell therapies have been shown to effectively treat animal models of lung disease. However, there are limitations to the translation of these cell therapies to clinical disease. Studies have shown that delayed treatment of animal models does not improve outcomes and that the models do not reflect the repeated injury that is present in most lung diseases. We tested the efficacy of amnion mesenchymal stem cells (AM-MSC), bone marrow MSC (BM-MSC) and human amniotic epithelial cells (hAEC) in C57BL/6 mice using a repeat dose bleomycin-induced model of lung injury that better reflects the repeat injury seen in lung diseases. The dual bleomycin dose led to significantly higher levels of inflammation and fibrosis in the mouse lung compared to a single bleomycin dose. Intravenously infused stem cells were present in the lung in similar numbers at days 7 and 21 post cell injection. In addition, stem cell injection resulted in a significant decrease in inflammatory cell infiltrate and a reduction in IL-1 (AM-MSC), IL-6 (AM-MSC, BM-MSC, hAEC) and TNF-α (AM-MSC). The only trophic factor tested that increased following stem cell injection was IL-1RA (AM-MSC). IL-1RA levels may be modulated by GM-CSF produced by AM-MSC. Furthermore, only AM-MSC reduced collagen deposition and increased MMP-9 activity in the lung although there was a reduction of the pro-fibrogenic cytokine TGF-β following BM-MSC, AM-MSC and hAEC treatment. Therefore, AM-MSC may be more effective in reducing injury following delayed injection in the setting of repeated lung injury. PMID:23936322

Comparison of cytomegalovirus (CMV)-specific neutralization capacity of hyperimmunoglobulin (HIG) versus standard intravenous immunoglobulin (IVIG) preparations: Impact of CMV IgG normalization.

PubMed

Schampera, Matthias Stefan; Schweinzer, Katrin; Abele, Harald; Kagan, Karl Oliver; Klein, Reinhild; Rettig, Ingo; Jahn, Gerhard; Hamprecht, Klaus

2017-05-01

Based on a non-randomized study of Nigro et al. (2005) the intravenous administration of hyperimmunoglobulins (HIGs) is applied frequently to women with primary CMV-infection as "off-label use" in Germany. In order to describe their CMV-specific neutralization-capacity in vitro, we analyzed the HIG preparations Cytotect ® , and Cytogam ® as well as the standard intravenous immunoglobulins (IVIG) Octagam ® , Gamunex ® , Kiovig ® . We performed short-term cell-free CMV neutralization assays (CFNT) and long-term cell-adapted neutralization-plaque-reduction assays (PRANT). Human retinal epithelial cells (ARPE-19) were used as target cells. A clinical CMV primary-isolate from amnion fluid propagated in epithelial cells without any initial fibroblast adaption was used. For calibration we previously generated serum-pools (N=100) from two cohorts of mothers at birth: seronegative and latently CMV-infected mothers. Biochemical analysis included total protein, albumin, Ig-class, and IgG-subclasses. Additionally, CMV antibody-reactivity was checked using recombinant immunoblotting. HIG and IVIG preparations showed differences in levels and patterns of protein, Ig-class and CMV-specific antibody concentrations. All IgG-preparations showed high in vitro NT-capacity and high IgG-avidity. The NT 90 -values for HIGs and IVIGs and our seropositive reference-pool showed similar NT-capacity at a dilution of (1:100) which corresponded well to 4.1 PEI-Units/ml. All HIG- and IVIG-preparations showed similar NT-capacity following CMV IgG-normalization. Our in vitro results are in strong contrast to former findings suggesting higher functional CMV NT titers in IVIG-preparations compared to HIGs. Copyright © 2017 Elsevier B.V. All rights reserved.

Differences in placental telomere length suggest a link between racial disparities in birth outcomes and cellular aging.

PubMed

Jones, Christopher W; Gambala, Cecilia; Esteves, Kyle C; Wallace, Maeve; Schlesinger, Reid; O'Quinn, Marguerite; Kidd, Laura; Theall, Katherine P; Drury, Stacy S

2017-03-01

Health disparities begin early in life and persist across the life course. Despite current efforts, black women exhibit greater risk for pregnancy complications and negative perinatal outcomes compared with white women. The placenta, which is a complex multi-tissue organ, serves as the primary transducer of bidirectional information between the mother and fetus. Altered placental function is linked to multiple racially disparate pregnancy complications; however, little is known about racial differences in molecular factors within the placenta. Several pregnancy complications, which include preeclampsia and fetal growth restriction, exhibit racial disparities and are associated with shorter placental telomere length, which is an indicator of cellular stress and aging. Cellular senescence and telomere dynamics are linked to the molecular mechanisms that are associated with the onset of labor and parturition. Further, racial differences in telomere length are found in a range of different peripheral tissues. Together these factors suggest that exploration of racial differences in telomere length of the placenta may provide novel mechanistic insight into racial disparities in birth outcomes. This study examined whether telomere length measured in 4 distinct fetally derived tissues were significantly different between black and white women. The study had 2 hypotheses: (1) that telomere length that is measured in different placental tissue types would be correlated and (2) that across all sampled tissues telomere length would differ by race. In a prospective study, placental tissue samples were collected from the amnion, chorion, villus, and umbilical cord from black and white singleton pregnancies (N=46). Telomere length was determined with the use of monochrome multiplex quantitative real-time polymerase chain reaction in each placental tissue. Demographic and pregnancy-related data were also collected. Descriptive statistics characterized the sample overall and among black and white women separately. The overall impact of race was assessed by multilevel mixed-effects linear regression models that included empirically relevant covariates. Telomere length was correlated significantly across all placental tissues. Pairwise analyses of placental tissue telomere length revealed significantly longer telomere length in the amnion compared with the chorion (t=-2.06; P=.043). Overall telomere length measured in placenta samples from black mothers were significantly shorter than those from white mothers (β=-0.09; P=.04). Controlling for relevant maternal and infant characteristics strengthened the significance of the observed racial differences (β=-0.12; P=.02). Within tissue analyses revealed that the greatest difference by race was found in chorionic telomere length (t=-2.81; P=.007). These findings provide the first evidence of racial differences in placental telomere length. Telomere length was significantly shorter in placental samples from black mothers compared with white mothers. Given previous studies that have reported that telomere length, cellular senescence, and telomere dynamics are molecular factors that contribute to the rupture of the amniotic sac, onset of labor, and parturition, our findings of shorter telomere length in placentas from black mothers suggest that accelerated cellular aging across placental tissues may be relevant to the increased risk of preterm delivery in black pregnancies. Our results suggest that racial differences in cellular aging in the placenta contribute to the earliest roots of health disparities. Copyright © 2016 Elsevier Inc. All rights reserved.

Interleukin-33 in the Human Placenta

PubMed Central

Topping, Vanessa; Romero, Roberto; Than, Nandor Gabor; Tarca, Adi L.; Xu, Zhonghui; Kim, Sun Young; Wang, Bing; Yeo, Lami; Kim, Chong Jai; Hassan, Sonia S.; Kim, Jung-Sun

2012-01-01

Objective Interleukin-33 (IL-33) is the newest member of the IL-1 cytokine family, a group of key regulators of inflammation. The purpose of this study was to determine whether IL-33 is expressed in the human placenta and to investigate its expression in the context of acute and chronic chorioamnionitis. Methods Placental tissues were obtained from five groups of patients: (1) normal pregnancy at term without labor (n=10); (2) normal pregnancy at term in labor (n=10); (3) preterm labor without inflammation (n=10); (4) preterm labor with acute chorioamnionitis (n=10); and (5) preterm labor with chronic chorioamnionitis (n=10). Immunostaining was performed to determine IL-33 protein expression patterns in the placental disk, chorioamniotic membranes, and umbilical cord. mRNA expression of IL-33 and its receptor IL1RL1 (ST2) was measured in primary amnion epithelial and mesenchymal cells (AECs and AMCs, n=4) and human umbilical vein endothelial cells (HUVECs, n=4) treated with IL-1β (1ng/ml and 10ng/ml) and CXCL10 (0.5ng/ml and 1ng/ml or 5ng/ml). Results 1) Nuclear IL-33 expression was found in endothelial and smooth muscle cells in the placenta, chorioamniotic membranes, and umbilical cord; 2) IL-33 was detected in the nucleus of CD14+ macrophages in the chorioamniotic membranes, chorionic plate, and umbilical cord, and in the cytoplasm of myofibroblasts in the Wharton’s jelly; 3) acute (but not chronic) chorioamnionitis was associated with the presence of IL-33+ macrophages in the chorioamniotic membranes and umbilical cord; 4) expression of IL-33 or IL1RL1 (ST2) mRNA in AECs was undetectable; 5) IL-33 mRNA expression increased in AMCs and HUVECs after IL-1β treatment but did not change with CXCL10 treatment; and 6) IL1RL1 (ST2) expression decreased in AMCs and increased in HUVECs after IL-1β but not CXCL10 treatment. Conclusions IL-33 is expressed in the nucleus of placental endothelial cells, CD14+ macrophages, and myofibroblasts in the Wharton’s jelly. IL-1β can induce the expression of IL-33 and its receptor. Protein expression of IL-33 is detectable in macrophages of the chorioamniotic membranes in acute (but not chronic) chorioamnionitis. PMID:23039129

Evolution and development of fetal membranes and placentation in amniote vertebrates.

PubMed

Ferner, Kirsten; Mess, Andrea

2011-08-31

We review aspects of fetal membrane evolution and patterns of placentation within amniotes, the most successful land vertebrates. Special reference is given to embryonic gas supply. The evolution of fetal membranes is a prerequisite for reproduction independent from aquatic environments. Starting from a basically similar repertoire of fetal membranes - the amnion, chorion, allantois and yolk sac, which form the cleidoic egg - different structural solutions for embryonic development have evolved. In oviparous amniotes the chorioallantoic membrane is the major site for the exchange of respiratory gases between fetus and outer environment. The richly vascularised yolk sac and allantois in concert with the chorion play an important role in the evolution of placentation in various viviparous amniotes. Highly complex placentas have evolved independently among squamate sauropsids and in marsupial and placental mammals. In conclusion, there seems to be a natural force to improve gas exchange processes in intrauterine environments by reducing the barrier between the blood systems and optimising the exchange areas. Copyright © 2011 Elsevier B.V. All rights reserved.

The earliest known reptile

NASA Astrophysics Data System (ADS)

Smithson, T. R.

1989-12-01

AMNIOTES (reptiles, birds and mammals) are distinguished from non-amniote tetrapods (amphibians) by the presence of complex embryonic membranes. One of these, the amnion, gives its name to the group. Very few skeletal characters distinguish amniotes from amphibians1, making it difficult to recognize early amniotes in the fossil record. The earliest amniote fossil identified so far is Hylonomus from the Westphalian (Upper Carboniferous) of Joggins, Nova Scotia2,3, (~300 Myr). I report here the discovery of a much earlier amniote skeleton from the Brigantian (Lower Carboniferous) of Scotland (~338 Myr) 4, which thus represents the earliest occurrence of amniotes in the fossil record. The specimen was collected from the East Kirkton Limestone, near Bathgate, West Lothian4-8, and is part of a unique terrestrial fauna that includes eurypterids, myriapods, scorpions and the earliest-known harvestman spider7,9, together with the earliest known temno-spondyls, a group that may include the ancestors of all living amphibians10. It will make an important contribution to our knowledge of early amniote morphology and the interrelationships of tetrapods.

ACR Appropriateness Criteria® Multiple Gestations.

PubMed

Glanc, Phyllis; Nyberg, David A; Khati, Nadia J; Deshmukh, Sandeep Prakash; Dudiak, Kika M; Henrichsen, Tara Lynn; Poder, Liina; Shipp, Thomas D; Simpson, Lynn; Weber, Therese M; Zelop, Carolyn M

2017-11-01

Women with twin or higher-order pregnancies will typically have more ultrasound examinations than women with a singleton pregnancy. Most women will have at minimum a first trimester scan, a nuchal translucency evaluation scan, fetal anatomy scan at 18 to 22 weeks, and one or more scans in the third trimester to evaluate growth. Multiple gestations are at higher risk for preterm delivery, congenital anomalies, fetal growth restriction, placenta previa, vasa previa, and velamentous cord insertion. Chorionicity and amnionicity should be determined as early as possible when a twin pregnancy is identified to permit triage of the monochorionic group into a closer surveillance model. Screening for congenital heart disease is warranted in monochorionic twins because they have an increased rate of congenital cardiac anomalies. In addition, monochorionic twins have a higher risk of developing cardiac abnormalities in later gestation related to right ventricular outflow obstruction, in particular the subgroups with twin-twin transfusion syndrome or selective intrauterine growth restriction. Monochorionic twins have unique complications including twin-to-twin transfusion syndrome, twin embolization syndrome, and acardius, or twin-reversed arterial perfusion sequence. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. Copyright © 2017 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Patient-centered evaluation of microsurgical management of gingival recession using coronally advanced flap with platelet-rich fibrin or amnion membrane: A comparative analysis

PubMed Central

Agarwal, Sumit Kumar; Jhingran, Rajesh; Bains, Vivek Kumar; Srivastava, Ruchi; Madan, Rohit; Rizvi, Iram

2016-01-01

Objective: To evaluate the efficacy of coronally advanced flap (CAF) procedure under microsurgical approach for the management of Miller's Class I and II gingival recession defects with the use of either platelet-rich fibrin (PRF) or amnion membrane (AM) in comparison to CAF alone. Materials and Methods: A total of 45 sites with Miller's Class I or II gingival recession defect were randomly distributed for: Experimental Group I (CAF with PRF) sites (n = 15) which were treated with the microsurgical approach using CAF along with PRF; experimental Group II (CAF with AM) sites (n = 15) were treated with the microsurgical approach using CAF along with AM; control Group III (CAF alone) sites (n = 15) were treated with the microsurgical approach using CAF alone. Vertical gingival recession (VGR), horizontal gingival recession (HGR), gingival thickness (GT) (using transgingival probing [TGP] and ultrasonography [USG]) and patients’ response and acceptance were documented at baseline, 3 months and 6 months after surgical interventions. Results: CAF alone and in combination with PRF or AM, were effective techniques for root coverage with average VGR values of 1.47 ± 0.92 mm (56%), 0.67 ± 1.23 mm (36%) and 0.60 ± 1.06 mm (33%) in Group I (CAF with PRF), Group II (CAF with AM), and Group III (CAF alone), respectively. Complete coverage (100%) was obtained in 33.3% sites of Group I (CAF with PRF), 26.6% sites of Group II (CAF with AM) and 13.3% in Group III (CAF alone). Patients’ response and acceptance for surgical treatment modality in terms of patient esthetic score and decrease in hypersensitivity score was highest for Group I (CAF with PRF), whereas patient comfort score was highest for Group II (CAF with AM). At 6 months follow-up, significant increase in GT measurements (using TGP and USG) in Group I (CAF with PRF), whereas, nonsignificant increase for Group II (CAF with AM) and no change or decrease for Group III (CAF alone) as compared to baseline was observed. Conclusion: The present study observed enhancement in root coverage when PRF or AM are used in conjunction with CAF as compared to CAF alone. These results are based on 6-month follow-up. Therefore, the long-term evaluation may be necessary to appreciate the clinical effect of autologous PRF and AM. PMID:27011751

Regulation of intramembranous absorption and amniotic fluid volume by constituents in fetal sheep urine

PubMed Central

Jonker, Sonnet S.; Louey, Samantha; Cheung, Cecilia Y.; Brace, Robert A.

2013-01-01

Our objective was to test the hypothesis that fetal urine contains a substance(s) that regulates amniotic fluid volume by altering the rate of intramembranous absorption of amniotic fluid. In late gestation ovine fetuses, amniotic fluid volumes, urine, and lung liquid production rates, swallowed volumes and intramembranous volume and solute absorption rates were measured over 2-day periods under control conditions and when urine was removed and continuously replaced at an equal rate with exogenous fluid. Intramembranous volume absorption rate decreased by 40% when urine was replaced with lactated Ringer solution or lactated Ringer solution diluted 50% with water. Amniotic fluid volume doubled under both conditions. Analysis of the intramembranous sodium and chloride fluxes suggests that the active but not passive component of intramembranous volume absorption was altered by urine replacement, whereas both active and passive components of solute fluxes were altered. We conclude that fetal urine contains an unidentified substance(s) that stimulates active intramembranous transport of amniotic fluid across the amnion into the underlying fetal vasculature and thereby functions as a regulator of amniotic fluid volume. PMID:23824958

Evidence for increased SOX3 dosage as a risk factor for X-linked hypopituitarism and neural tube defects.

PubMed

Bauters, Marijke; Frints, Suzanna G; Van Esch, Hilde; Spruijt, Liesbeth; Baldewijns, Marcella M; de Die-Smulders, Christine E M; Fryns, Jean-Pierre; Marynen, Peter; Froyen, Guy

2014-08-01

Genomic duplications of varying lengths at Xq26-q27 involving SOX3 have been described in families with X-linked hypopituitarism. Using array-CGH we detected a 1.1 Mb microduplication at Xq27 in a large family with three males suffering from X-linked hypopituitarism. The duplication was mapped from 138.7 to 139.8 Mb, harboring only two annotated genes, SOX3 and ATP11C, and was shown to be a direct tandem copy number gain. Unexpectedly, the microduplication did not fully segregate with the disease in this family suggesting that SOX3 duplications have variable penetrance for X-linked hypopituitarism. In the same family, a female fetus presenting with a neural tube defect was also shown to carry the SOX3 copy number gain. Since we also demonstrated increased SOX3 mRNA levels in amnion cells derived from an unrelated t(X;22)(q27;q11) female fetus with spina bifida, we propose that increased levels of SOX3 could be a risk factor for neural tube defects. © 2014 Wiley Periodicals, Inc.

Endoscopy, histology and electron microscopy analysis of foetal membranes in pregnant South American plains vizcacha reveal unusual excrescences on the yolk sac.

PubMed

Giacchino, Mariela; Inserra, Pablo I F; Lange, Fernando D; Gariboldi, María C; Ferraris, Sergio R; Vitullo, Alfredo D

2018-06-01

The South American hystricognathe Lagostomus maximus is a fossorial rodent whose females show unique reproductive characteristics. They have a 155-day long gestation, show massive polyovulation and a selective process of embryonic resorption in the first half of gestation. In order to explore and perform an in-situ characterization of the reproductive tract, we visualized internal structures through ultrasonography and video-endoscopy in pregnant and non-pregnant females. We describe the finding of protruding structures that lie on the yolk sac and their histological and ultrastructural characterization. The placenta was covered with whitish, small pearl-shaped structures. These structures were also seen on the extra-embryonic space, being the amnion and the umbilical cord free of them. Pearl-shaped structures were composed with loose connective tissue, lacked blood vessels, and showed collagen fibers organized in a spiral form. They were anchored by pedicles to the villous surface of the extraembryonic membrane. We discuss the biological and evolutionary meaning of the pearl-shaped structures that relate L. maximus to the African origin of the South American hystricognathe fauna.

Injectible candidate sealants for fetal membrane repair: Bonding and toxicity in vitro

PubMed Central

Bilic, Grozdana; Brubaker, Carrie; Messersmith, Phillip B.; Mallik, Ajit S.; Quinn, Thomas M.; Haller, Claudia; Done, Elisa; Gucciardo, Leonardo; Zeisberger, Steffen M.; Zimmermann, Roland; Deprest, Jan; Zisch, Andreas H.

2010-01-01

Objective This study was undertaken to test injectible surgical sealants that are biocompatible with fetal membranes, eventually for closure of iatrogenic membrane defects. Study Design Dermabond, Histoacryl, Tissucol fibrin glue, and three types of in situ forming poly(ethylene glycol)-based polymer hydrogels were tested for acute toxicity upon direct contact with fetal membranes for 24h. For determination of elution toxicity, extracts of sealants were incubated on amnion cell cultures for 72h. Bonding and toxicity was assessed through morphological and/or biochemical analysis. Results Extracts of all adhesives were non-toxic for cultured cells. However, only Tissucol and one type of poly(ethylene glycol)-based hydrogel, mussel-mimetic tissue adhesive, showed efficient, non-disruptive, non-toxic bonding to fetal membranes. Mussel-mimetic tissue adhesive applied over membrane defects created with a 3.5 mm trocar accomplished leak-proof closure that withstood membrane stretch in an in vitro model. Conclusion A synthetic hydrogel-type tissue adhesive emerged as potential sealing modality for iatrogenic membrane defects that merits further evaluation in vivo. PMID:20096254

Mechanisms leading to increased risk of preterm birth in growth-restricted guinea pig pregnancies.

PubMed

Palliser, Hannah K; Kelleher, Meredith A; Welsh, Toni N; Zakar, Tamas; Hirst, Jonathan J

2014-02-01

Intrauterine growth restriction (IUGR) is a risk factor for preterm labor; however, the mechanisms of the relationship remain unknown. Prostaglandin (PG), key stimulants of labor, availability is regulated by the synthetic enzymes, prostaglandin endoperoxidases 1 and 2 (PTGS1 and 2), and the metabolizing enzyme, 15-hydroxyprostaglandin dehydrogenase (HPGD). We hypothesized that IUGR increases susceptibility to preterm labor due to the changing balance of synthetic and metabolizing enzymes and hence greater PG availability. We have tested this hypothesis using a surgically induced IUGR model in guinea pigs, which results in significantly shorter gestation. Myometrium, amnion, chorion, and placentas were collected from sham operated or IUGR pregnancies, and PTGS1 and HPGD protein expression were quantified throughout late gestation (>62 days) and labor. The PTGS1 expression was significantly upregulated in the myometrium of IUGR animals, and chorionic HPGD expression was markedly decreased (P < .01 and P < .001, respectively). These findings suggest a shift in the balance of PG production over metabolism in IUGR pregnancies leads to a greater susceptibility to preterm birth.

Comparative Evaluation of Platelet Rich Fibrin and Dehydrated Amniotic Membrane for the Treatment of Gingival Recession- A Clinical Study

PubMed Central

Jaiswal, Gagan Rajesh; Kumathalli, Kanteshwari; Kumar, Rajesh; Singh, Alisha; Sarwan, Aakrti

2017-01-01

Introduction The main objective of any therapeutic intervention aimed at root coverage is to restore the tissue margin to the cemento-enamel junction and to regenerate the lost periodontium. Aim To compare the effectiveness of Platelet Rich Fibrin (PRF) and Amniotic Membrane (AM) in the treatment of gingival recession by Coronally Advanced Flap (CAF) Technique. Materials and Methods Thirty systemically healthy patients who met inclusion-exclusion criteria were selected. After Phase-I therapy, patients were randomly allocated to one of the groups; PRF (Group-A) and Amnion Group (Group-B). Clinical parameters like Plaque Index (PI), Recession Depth (RD) and Width of Keratinized Gingiva (WKG) were measured on the baseline day, three months and six months postoperatively. Mann-Whitney test and Wilcoxon signed ranks test were applied for intergroup and intragroup comparisons respectively. Results Intergroup comparison between platelet rich fibrin and amniotic membrane showed statistically insignificant difference in the recession depth and width of keratinized gingiva at three and six months postoperatively. Conclusion Both the membranes were equally effective in terms of recession coverage and increase in width of keratinized gingiva. PMID:28969268

Bilateral oblique facial clefts and extremity anomaly in an infant after intrauterine efavirenz exposure and review of its teratogenic risk.

PubMed

Shanske, Alan L

2012-09-10

Congenital anomalies may be caused by genetic or environmental factors or a combination of both. Oblique facial clefts are very rare congenital deformities. The occurrence of facial clefts and an extremity anomaly suggests a common underlying cause. Lateral oro-ocular clefts do not occur along normal developmental planes and may be part of the amnion disruption complex sequence. Our objective was to report a case of this very event, which also followed an unusual intrauterine exposure and review the literature on the teratogenic risk of efavirenz. We report a case of amniotic rupture sequence after fetal HIV and antiretroviral exposure. Teratogenic exposure has been rarely reported and never after antiretroviral exposure. By reporting and registering more cases, we will be able to better assess the risks such medications pose to the developing fetus. The publication of a single case report has the potential to contribute to our knowledge of the significance of prenatal exposure to antiretrovirals and other medications for common HIV-associated disorders. It also generates a hypothesis that can be tested with further clinical data, animal models and epidemiologic studies.

A tensile machine with a novel optical load cell for soft biological tissues application.

PubMed

Faturechi, Rahim; Hashemi, Ata; Abolfathi, Nabiollah

2014-11-01

The uniaxial tensile testing machine is the most common device used to measure the mechanical properties of industrial and biological materials. The need for a low-cost uniaxial tension testing device for small research centers has always been the subject of research. To address this need, a novel uniaxial tensile testing machine was designed and fabricated to measure the mechanical properties of soft biological tissues. The device is equipped with a new low-cost load cell which works based on the linear displacement/force relationship of beams. The deflection of the beam load cell is measured optically by a digital microscope with an accuracy of 1 µm. The stiffness of the designed load cell was experimentally and theoretically determined at 100 N mm(-1). The stiffness of the load cell can be easily adjusted according to the tissue's strength. The force-time behaviour of soft tissue specimens was obtained by an in-house image processing program. To demonstrate the efficiency of the fabricated device, the mechanical properties of amnion tissue was measured and compared with available data. The obtained results indicate a strong agreement with that of previous studies.

Time of initial detection of fetal and extra-fetal structures by ultrasonographic examination in Miniature Schnauzer bitches.

PubMed

Kim, Bang Sil; Son, Chang Ho

2007-09-01

Serial ultrasonographic examinations were performed daily on 9 Miniature Schnauzer bitches from the 15th day of gestation until parturition to determine the time the gestational structures were first detected. The gestational age was timed from the day of ovulation (day 0), which was estimated to occur when the plasma progesterone concentration was >4.0 ng/ml. The gestational length in 9 Miniature Schnauzer bitches was found to be 63.0 +/- 1.7 (range 61-65) days. The initial detection of the fetal and extra-fetal structures were as follows: gestational sac at day 18.0 +/- 0.9 (17-19); zonary placenta in the uterine wall at day 24.9 +/- 1.1 (23-26); yolk sac membrane at day 25.0 +/- 0.9 (24-26); amnionic membrane at day 27.7 +/- 1.0 (26- 29); embryo initial detection at day 22.6 +/- 0.5 (22-23); heartbeat at day 23.4 +/- 0.5 (23-24); fetal movement at day 32.5 +/- 0.8 (32-34); stomach at day 31.2 +/- 1.6 (29-33); urinary bladder at day 32.6 +/- 1.8 (31-35); skeleton at day 34.9 +/- 1.6 (34-38) and kidney at day 42.2 +/- 0.7 (41-43).

Chorioamnionitis: a comparative histologic, bacteriologic, and clinical study.

PubMed

Zhang, J M; Kraus, F T; Aquino, T I

1985-01-01

Using morphologic and bacteriologic techniques, we examined placentas from 224 deliveries considered potentially complicated by infection. The severity of the chorioamnionitis was graded histologically according to the intensity of the inflammatory infiltrate. Chorioamnionitis or funisitis occurred in 111 placentas. Neonatal morbidity in this group was 48 (43%) as compared with 14 (12%) in those without chorioamnionitis. Pathogens were cultured from 49 of the 111 placentas with chorioamnionitis. Neonatal morbidity or mortality occurred in 28 (58%) of the group with positive cultures but occurred also in 20 (32%) of the 63 with chorioamnionitis from which no pathogens were cultured. Perinatal mortality was especially high (64%) among premature infants (less than 30 weeks) with infection. A comparison of culture techniques (surface swab versus swab of subchorionic fibrin after searing amnionic surface) showed similar rates of recovery but less contamination using the deep culture technique. Neonatal morbidity and mortality with severe chorioamnionitis (grades II and III; 62% and 82%) were significantly greater than with little or no chorioamnionitis (grades I and 0; 43% and 36%). Higher grades of histologically demonstrable chorioamnionitis are associated significantly with the highest rates of neonatal morbidity or mortality. In many instances, pathogens are not recovered by conventional aerobic and anaerobic bacteriologic study. A search for other infectious agents (viruses, mycoplasmas, chlamydiae) deserves attention.

Effects of in ovo feeding of carbohydrates and arginine on hatchability, body weight, energy metabolism and perinatal growth in duck embryos and neonates.

PubMed

Tangara, M; Chen, W; Xu, J; Huang, F R; Peng, J

2010-10-01

1. The objective of this study was to test the hypothesis that in ovo feeding of carbohydrates and arginine into the duck amnion may improve the glycogen store and perinatal growth. At 23 d of incubation, fertile eggs were injected with 1·2 ml of sodium chloride (NaCl), sucrose + maltose (CHO), arginine (Arg) or sucrose + maltose + arginine (CHO + Arg), with controls not injected. Body weight, liver and muscle glycogen levels, and hepatic glucose-6-phosphatase activity were determined at 25 d of incubation, at hatch, and at 3 and 7 d posthatch. 2. At hatch and 7 d of age, the body weights were greater in the in ovo-feeding treatments than the controls. Arg and CHO + Arg significantly enhanced liver glycogen level at hatch compared with controls. CHO and CHO + Arg significantly increased muscle glycogen level at 25 d of incubation over controls. CHO and Arg decreased glucose-6-phosphatase at 25 d of incubation, whereas NaCl and CHO + Arg increased glucose-6-phosphatase at hatch relative to controls. 3. In ovo feeding of carbohydrates and arginine at 23 d of incubation may improve glycogen reserves, which may, in turn, provide the energy needed for perinatal growth.

The Evolutionary Economics of Embryonic-Sac Fluids in Squamate Reptiles.

PubMed

Bonnet, Xavier; Naulleau, Guy; Shine, Richard

2017-03-01

The parchment-shelled eggs of squamate reptiles take up substantial water from the nest environment, enabling the conversion of yolk into neonatal tissue and buffering the embryo against the possibility of subsequent dry weather. During development, increasing amounts of water are stored in the embryonic sacs (i.e., membranes around the embryo: amnion, allantois, and chorion). The evolution of viviparity (prolonged uterine retention of developing embryos) means that embryonic-sac fluid storage now imposes a cost (increased maternal burdening), confers less benefit (because the mother buffers fetal water balance), and introduces a potential conflict among uterine siblings (for access to finite water supplies). Our data on nine species of squamate reptiles and published information on three species show that the embryonic-sac fluids comprise around 33% of neonatal mass in viviparous species versus 94% in full-term eggs of oviparous squamates. Data on parturition in 149 vipers (Vipera aspis, a viviparous species) show that larger offspring store more fluids in their fetal sacs and that an increase in litter size is associated with a decrease in fluid-sac mass per offspring. Overall, the evolutionary transition from oviparity to viviparity may have substantially altered selective forces on offspring packaging and created competition among offspring for access to water reserves during embryonic development.

A prospective, randomised, controlled, multi-centre comparative effectiveness study of healing using dehydrated human amnion/chorion membrane allograft, bioengineered skin substitute or standard of care for treatment of chronic lower extremity diabetic ulcers.

PubMed

Zelen, Charles M; Gould, Lisa; Serena, Thomas E; Carter, Marissa J; Keller, Jennifer; Li, William W

2015-12-01

A prospective, randomised, controlled, parallel group, multi-centre clinical trial was conducted at three sites to compare the healing effectiveness of treatment of chronic lower extremity diabetic ulcers with either weekly applications of Apligraf(®) (Organogenesis, Inc., Canton, MA), EpiFix(®) (MiMedx Group, Inc., Marietta, GA), or standard wound care with collagen-alginate dressing. The primary study outcome was the percent change in complete wound healing after 4 and 6 weeks of treatment. Secondary outcomes included percent change in wound area per week, velocity of wound closure and a calculation of the amount and cost of Apligraf or EpiFix used. A total of 65 subjects entered the 2-week run-in period and 60 were randomised (20 per group). The proportion of patients in the EpiFix group achieving complete wound closure within 4 and 6 weeks was 85% and 95%, significantly higher (all adjusted P-values ≤ 0·003) than for patients receiving Apligraf (35% and 45%), or standard care (30% and 35%). After 1 week, wounds treated with EpiFix had reduced in area by 83·5% compared with 53·1% for wounds treated with Apligraf. Median time to healing was significantly faster (all adjusted P-values ≤0·001) with EpiFix (13 days) compared to Apligraf (49 days) or standard care (49 days). The mean number of grafts used and the graft cost per patient were lower in the EpiFix group campared to the Apligraf group, at 2·15 grafts at a cost of $1669 versus 6·2 grafts at a cost of $9216, respectively. The results of this study demonstrate the clinical and resource utilisation superiority of EpiFix compared to Apligraf or standard of care, for the treatment of diabetic ulcers of the lower extremities. © 2014 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Damage-associated molecular patterns (DAMPs) in preterm labor with intact membranes and preterm PROM: a study of the alarmin HMGB1

PubMed Central

Romero, Roberto; Chaiworapongsa, Tinnakorn; Savasan, Zeynep Alpay; Xu, Yi; Hussein, Youssef; Dong, Zhong; Kusanovic, Juan Pedro; Kim, Chong Jai; Hassan, Sonia S

2012-01-01

Objective Preterm parturition is a syndrome caused by multiple etiologies. Although intra-amniotic infection is causally linked with intrauterine inflammation and the onset of preterm labor, other patients have preterm labor in the absence of demonstrable infection. It is now clear that inflammation may be elicited by activation of the Damage-Associated Molecular Patterns (DAMPs), which include pathogen-associated molecular patterns (PAMPs) as well as “alarmins” (endogenous molecules that signal tissue and cellular damage). A prototypic alarmin is high-mobility group box-1 (HMGB1) protein, capable of inducing inflammation and tissue repair when it reaches the extracellular environment. HMGB1 is a late-mediator of sepsis, and blockade of HMGB1 activity reduces mortality in an animal model of endotoxemia, even if administered late during the course of the disorder. The objectives of this study were to: 1) determine whether intra-amniotic infection/inflammation (IAI) is associated with changes in amniotic fluid concentrations of HMGB1; and 2) localize immunoreactivity of HMGB1 in the fetal membranes and umbilical cord of patients with chorioamnionitis. Methods Amniotic fluid samples were collected from the following groups: 1) preterm labor with intact membranes (PTL) with (n=42) and without IAI (n=84); and 2) preterm prelabor rupture of membranes (PROM) with (n=38) and without IAI (n=35). IAI was defined as either a positive amniotic fluid culture or amniotic fluid concentration of interleukin-6 (IL-6) ≥2.6 ng/mL. HMGB1 concentrations in amniotic fluid were determined by ELISA. Immunofluorescence staining for HMGB1 was performed in the fetal membranes and umbilical cord of pregnancies with acute chorioamnionitis. Results Amniotic fluid HMGB1 concentrations were higher in patients with IAI than in those without IAI in both the PTL and preterm PROM groups (PTL IAI: median 3.1 ng/mL vs. without IAI; median 0.98 ng/mL; p<0.001; and preterm PROM with IAI median 7.3 ng/mL vs. without IAI median 2.6 ng/mL; p=0.002); patients with preterm PROM without IAI had a higher median amniotic fluid HMGB1 concentration than those with PTL and intact membranes without IAI (p<0.001); and HMGB1 was immunolocalized to amnion epithelial cells and stromal cells in the Wharton’s jelly (prominent in the nuclei and cytoplasm). Myofibroblasts and macrophages of the chorioamniotic connective tissue layer and infiltrating neutrophils showed diffuse cytoplasmic HMGB1 immunoreactivity. Conclusions Intra-amniotic infection/inflammation is associated with elevated amniotic fluid HMGB1 concentrations regardless of membrane status; preterm PROM was associated with a higher amniotic fluid HMGB1 concentration than PTL with intact membranes, suggesting that rupture of membranes is associated with an elevation of alarmins; immunoreactive HMGB1 was localized to amnion epithelial cells, Wharton’s jelly and cells involved in the innate immune response; and we propose that HMGB1 released from stress or injured cells into amniotic fluid may be responsible, in part, for intra-amniotic inflammation due to non-microbial insults. PMID:21958433

The epidemiologic evidence linking prenatal and postnatal exposure to endocrine disrupting chemicals with male reproductive disorders: a systematic review and meta-analysis.

PubMed

Bonde, Jens Peter; Flachs, Esben Meulengracht; Rimborg, Susie; Glazer, Clara Helene; Giwercman, Aleksander; Ramlau-Hansen, Cecilia Høst; Hougaard, Karin Sørig; Høyer, Birgit Bjerre; Hærvig, Katia Keglberg; Petersen, Sesilje Bondo; Rylander, Lars; Specht, Ina Olmer; Toft, Gunnar; Bräuner, Elvira Vaclavik

2016-12-01

More than 20 years ago, it was hypothesized that exposure to prenatal and early postnatal environmental xenobiotics with the potential to disrupt endogenous hormone signaling might be on the causal path to cryptorchidism, hypospadias, low sperm count and testicular cancer. Several consensus statements and narrative reviews in recent years have divided the scientific community and have elicited a call for systematic transparent reviews. We aimed to fill this gap in knowledge in the field of male reproductive disorders. The aim of this study was to systematically synthesize published data on the risk of cryptorchidism, hypospadias, low sperm counts and testicular cancer following in utero or infant exposure to chemicals that have been included on the European Commission's list of Category 1 endocrine disrupting chemicals defined as having documented adverse effects due to endocrine disruption in at least one intact organism. A systematic literature search for original peer reviewed papers was performed in the databases PubMed and Embase to identify epidemiological studies reporting associations between the outcomes of interest and exposures documented by biochemical analyses of biospecimens including maternal blood or urine, placenta or fat tissue as well as amnion fluid, cord blood or breast milk; this was followed by meta-analysis of quantitative data. The literature search resulted in 1314 references among which we identified 33 papers(28 study populations) fulfilling the eligibility criteria. These provided 85 risk estimates of links between persistent organic pollutants and rapidly metabolized compounds (phthalates and Bisphenol A) and male reproductive disorders. The overall odds ratio (OR) across all exposures and outcomes was 1.11 (95% CI 0.91-1.35). When assessing four specific chemical subgroups with sufficient data for meta-analysis for all outcomes, we found that exposure to one of the four compounds, p,p'-DDE, was related to an elevated risk: OR 1.35 (95% CI 1.04-1.74). The data did not indicate that this increased risk was driven by any specific disorder. The current epidemiological evidence is compatible with a small increased risk of male reproductive disorders following prenatal and postnatal exposure to some persistent environmental chemicals classified as endocrine disruptors but the evidence is limited. Future epidemiological studies may change the weight of the evidence in either direction. No evidence of distortion due to publication bias was found, but exposure-response relationships are not evident. There are insufficient data on rapidly metabolized endocrine disruptors and on specific exposure-outcome relations. A particular data gap is evident with respect to delayed effects on semen quality and testicular cancer. Although high quality epidemiological studies are still sparse, future systematic and transparent reviews may provide pieces of evidence contributing to the narrative and weight of the evidence assessments in the field. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.

A portable meter for measuring low frequency currents in the human body.

PubMed

Niple, J C; Daigle, J P; Zaffanella, L E; Sullivan, T; Kavet, R

2004-07-01

A portable meter has been developed for measuring low frequency currents that flow in the human body. Although the present version of the meter was specifically designed to measure 50/60 Hz "contact currents," the principles involved can be used with other low frequency body currents. Contact currents flow when the human body provides a conductive path between objects in the environment with different electrical potentials. The range of currents the meter detects is approximately 0.4-800 microA. This provides measurements of currents from the threshold of human perception (approximately 500 microA(RMS)) down to single microampere levels. The meter has a unique design, which utilizes the human subject's body impedance as the sensing element. Some of the advantages of this approach are high sensitivity, the ability to measure current flow in the majority of the body, and relative insensitivity to the current path connection points. Current measurement accuracy varies with the accuracy of the body impedance (resistance) measurement and different techniques can be used to obtain a desired level of accuracy. Techniques are available to achieve an estimated +/-20% accuracy. Copyright 2004 Wiley-Liss, Inc.

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2015-05-01

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

What exactly is an exact copy? And why it matters when trying to ban human reproductive cloning in Australia.

PubMed

Gogarty, B

2003-04-01

This paper examines the current Australian regulatory response to human reproductive cloning. The central consideration is the capacity of the current regulatory regime to effectively deter human cloning efforts. A legislative prohibition on human cloning must be both effective and clear enough to allow researchers to know what practices are acceptable. This paper asks whether the current Australian regime evinces these qualities and suggests that Australia should follow the example set in the UK by the enactment of the Human Reproductive Cloning Act 2001.

Amnioinfusion for preterm rupture of membranes.

PubMed

Hofmeyr, G J

2000-01-01

Preterm rupture of membranes places a fetus at risk of cord compression and amnionitis. Amnioinfusion aims to prevent or relieve umbilical cord compression by infusing a solution into the uterine cavity. The objective of this review was to assess the effects of amnioinfusion for preterm rupture of membranes on maternal and perinatal outcomes. The Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Controlled Trials Register were searched. Randomised trials of amnioinfusion compared to no amnioinfusion in women with preterm rupture of membranes. Eligibility and trial quality were assessed by the reviewer. One trial of 66 women was included. It had some methodological flaws. No significant differences between amnioinfusion and no amnioinfusion were detected for caesarean section (relative risk 0.32, 95% confidence interval 0.07 to 1.40); low Apgar scores (relative risk 0.28, 95% confidence interval 0.03 to 2.33) or neonatal death (relative risk 0.55, 95% confidence interval 0.05 to 5.77). In the amnioinfusion group, the number of severe fetal heart rate decelerations per hour during the first stage of labour were reduced (weighted mean difference -1.20, 95% confidence interval -1.83 to -0.57). These outcomes are consistent with those found in the Cochrane review on amnioinfusion for cord compression. There is not enough evidence concerning the use of amnioinfusion for preterm rupture of membranes.

Time of initial detection of fetal and extra-fetal structures by ultrasonographic examination in Miniature Schnauzer bitches

PubMed Central

Kim, Bang-Sil

2007-01-01

Serial ultrasonographic examinations were performed daily on 9 Miniature Schnauzer bitches from the 15th day of gestation until parturition to determine the time the gestational structures were first detected. The gestational age was timed from the day of ovulation (day 0), which was estimated to occur when the plasma progesterone concentration was >4.0 ng/ml. The gestational length in 9 Miniature Schnauzer bitches was found to be 63.0 ± 1.7 (range 61-65) days. The initial detection of the fetal and extra-fetal structures were as follows: gestational sac at day 18.0 ± 0.9 (17-19); zonary placenta in the uterine wall at day 24.9 ± 1.1 (23-26); yolk sac membrane at day 25.0 ± 0.9 (24-26); amnionic membrane at day 27.7 ± 1.0 (26-29); embryo initial detection at day 22.6 ± 0.5 (22-23); heartbeat at day 23.4 ± 0.5 (23-24); fetal movement at day 32.5 ± 0.8 (32-34); stomach at day 31.2 ± 1.6 (29-33); urinary bladder at day 32.6 ± 1.8 (31-35); skeleton at day 34.9 ± 1.6 (34-38) and kidney at day 42.2 ± 0.7 (41-43). PMID:17679777

Cell Therapy From Bench to Bedside Translation in CNS Neurorestoratology Era

PubMed Central

Huang, Hongyun; Chen, Lin; Sanberg, Paul

2010-01-01

Recent advances in cell biology, neural injury and repair, and the progress towards development of neurorestorative interventions are the basis for increased optimism. Based on the complexity of the processes of demyelination and remyelination, degeneration and regeneration, damage and repair, functional loss and recovery, it would be expected that effective therapeutic approaches will require a combination of strategies encompassing neuroplasticity, immunomodulation, neuroprotection, neurorepair, neuroreplacement, and neuromodulation. Cell-based restorative treatment has become a new trend, and increasing data worldwide have strongly proven that it has a pivotal therapeutic value in CNS disease. Moreover, functional neurorestoration has been achieved to a certain extent in the CNS clinically. Up to now, the cells successfully used in preclinical experiments and/or clinical trial/treatment include fetal/embryonic brain and spinal cord tissue, stem cells (embryonic stem cells, neural stem/progenitor cells, hematopoietic stem cells, adipose-derived adult stem/precursor cells, skin-derived precursor, induced pluripotent stem cells), glial cells (Schwann cells, oligodendrocyte, olfactory ensheathing cells, astrocytes, microglia, tanycytes), neuronal cells (various phenotypic neurons and Purkinje cells), mesenchymal stromal cells originating from bone marrow, umbilical cord, and umbilical cord blood, epithelial cells derived from the layer of retina and amnion, menstrual blood-derived stem cells, Sertoli cells, and active macrophages, etc. Proof-of-concept indicates that we have now entered a new era in neurorestoratology. PMID:21359168

Human Infrastructure Detection and Exploitation (HIDE)

DTIC Science & Technology

2009-11-01

Finding human infrastructure elements such as machinery, chemicals, radiofrequency emissions, electrical currents, or other evidence of human ... activity in confined enclosed spaces is a deficiency in current intelligence, surveillance, and reconnaissance (ISR) systems. In addition, operations in

21 CFR 110.5 - Current good manufacturing practice.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Current good manufacturing practice. 110.5 Section...) FOOD FOR HUMAN CONSUMPTION CURRENT GOOD MANUFACTURING PRACTICE IN MANUFACTURING, PACKING, OR HOLDING HUMAN FOOD General Provisions § 110.5 Current good manufacturing practice. (a) The criteria and...

What exactly is an exact copy? And why it matters when trying to ban human reproductive cloning in Australia

PubMed Central

Gogarty, B

2003-01-01

This paper examines the current Australian regulatory response to human reproductive cloning. The central consideration is the capacity of the current regulatory regime to effectively deter human cloning efforts. A legislative prohibition on human cloning must be both effective and clear enough to allow researchers to know what practices are acceptable. This paper asks whether the current Australian regime evinces these qualities and suggests that Australia should follow the example set in the UK by the enactment of the Human Reproductive Cloning Act 2001. PMID:12672887

The Rated Voltage Determination of DC Building Power Supply System Considering Human Beings Safety

NASA Astrophysics Data System (ADS)

Wang, Zhicheng; Yu, Kansheng; Xie, Guoqiang; Zou, Jin

2018-01-01

Generally two-level voltages are adopted for DC building power supply system. From the point of view of human beings safety, only the lower level voltage which may be contacted barehanded is discussed in this paper based on the related safety thresholds of human beings current effect. For several voltage levels below 100V recommended by IEC, the body current and current density of human electric shock under device normal work condition, as well as effect of unidirectional single impulse currents of short durations are calculated and analyzed respectively. Finally, DC 60V is recommended as the lower level rating voltage through the comprehensive consideration of technical condition and cost of safety criteria.

The ultimate intrinsic signal-to-noise ratio of loop- and dipole-like current patterns in a realistic human head model.

PubMed

Pfrommer, Andreas; Henning, Anke

2018-03-13

The ultimate intrinsic signal-to-noise ratio (UISNR) represents an upper bound for the achievable SNR of any receive coil. To reach this threshold a complete basis set of equivalent surface currents is required. This study systematically investigated to what extent either loop- or dipole-like current patterns are able to reach the UISNR threshold in a realistic human head model between 1.5 T and 11.7 T. Based on this analysis, we derived guidelines for coil designers to choose the best array element at a given field strength. Moreover, we present ideal current patterns yielding the UISNR in a realistic body model. We distributed generic current patterns on a cylindrical and helmet-shaped surface around a realistic human head model. We excited electromagnetic fields in the human head by using eigenfunctions of the spherical and cylindrical Helmholtz operator. The electromagnetic field problem was solved by a fast volume integral equation solver. At 7 T and above, adding curl-free current patterns to divergence-free current patterns substantially increased the SNR in the human head (locally >20%). This was true for the helmet-shaped and the cylindrical surface. On the cylindrical surface, dipole-like current patterns had high SNR performance in central regions at ultra-high field strength. The UISNR increased superlinearly with B0 in most parts of the cerebrum but only sublinearly in the periphery of the human head. The combination of loop and dipole elements could enhance the SNR performance in the human head at ultra-high field strength. © 2018 International Society for Magnetic Resonance in Medicine.

Modulating endogenous electric currents in human corneal wounds--a novel approach of bioelectric stimulation without electrodes.

PubMed

Reid, Brian; Graue-Hernandez, Enrique O; Mannis, Mark J; Zhao, Min

2011-03-01

To measure electric current in human corneal wounds and test the feasibility of pharmacologically enhancing the current to promote corneal wound healing. Using a noninvasive vibrating probe, corneal electric current was measured before and after wounding of the epithelium of donated postmortem human corneas. The effects of drug aminophylline and chloride-free solution on wound current were also tested. Unwounded cornea had small outward currents (0.07 μA/cm²). Wounding increased the current more than 5 fold (0.41 μA/cm²). Monitoring the wound current over time showed that it seemed to be actively regulated and maintained above normal unwounded levels for at least 6 hours. The time course was similar to that previously measured in rat cornea. Drug treatment or chloride-free solution more than doubled the size of wound currents. Electric current at human corneal wounds can be significantly increased with aminophylline or chloride-free solution. Because corneal wound current directly correlates with wound healing rate, our results suggest a role for chloride-free and/or aminophylline eyedrops to enhance healing of damaged cornea in patients with reduced wound healing such as the elderly or diabetic patient. This novel approach offers bioelectric stimulation without electrodes and can be readily tested in patients.

The Challenge of Human Spermatozoa Proteome: A Systematic Review.

PubMed

Gilany, Kambiz; Minai-Tehrani, Arash; Amini, Mehdi; Agharezaee, Niloofar; Arjmand, Babak

2017-01-01

Currently, there are 20,197 human protein-coding genes in the most expertly curated database (UniProtKB/Swiss-Pro). Big efforts have been made by the international consortium, the Chromosome-Centric Human Proteome Project (C-HPP) and independent researchers, to map human proteome. In brief, anno 2017 the human proteome was outlined. The male factor contributes to 50% of infertility in couples. However, there are limited human spermatozoa proteomic studies. Firstly, the development of the mapping of the human spermatozoa was analyzed. The human spermatozoa have been used as a model for missing proteins. It has been shown that human spermatozoa are excellent sources for finding missing proteins. Y chromosome proteome mapping is led by Iran. However, it seems that it is extremely challenging to map the human spermatozoa Y chromosome proteins based on current mass spectrometry-based proteomics technology. Post-translation modifications (PTMs) of human spermatozoa proteome are the most unexplored area and currently the exact role of PTMs in male infertility is unknown. Additionally, the clinical human spermatozoa proteomic analysis, anno 2017 was done in this study.

Low-density lipoproteins modulate endothelial cells to secrete endothelin-1 in a polarized pattern: a study using a culture model system simulating arterial intima.

PubMed

Unoki, H; Fan, J; Watanabe, T

1999-01-01

We investigated the structural and functional properties of human umbilical vein endothelial cells (HUVECs) cultured on a two-chamber culture model system using an amnion membrane. Compared to HUVECs cultured on a plastic dish, HUVECs cultured on the model system exhibited several features similar to those of in vivo vessels, including formation of the intercellular junctional devices and expression of tight junction-associated protein ZO-1 and adherence junction-associated protein alpha-catenin. Furthermore, we found that HUVECs had a property of polar secretion of endothelin-1 (ET-1). About 90% of the total amount of synthesized ET-1 was found in the lower well, designated as the basal side. When HUVECs were incubated with either native low-density lipoproteins (nLDLs) or oxidized LDLs (oxLDLs) at a concentration of 100 microgram/ml, ET-1 secretion was significantly increased, dependent on the cell side (apical vs basal) on which the nLDLs or oxLDLs were loaded. When the LDLs were loaded on the apical side, the secretion of ET-1 from HUVECs on the apical side was increased by 48% (nLDL) and 61% (oxLDL), whereas it was accompanied by a concomitant decrease of ET-1 on the basal side (45% by nLDLs and 38% by oxLDLs). When loaded on the basal side, however, ET-1 was increased by 23% (nLDLs) and 53% (oxLDLs) on the basal side, with a 26% simultaneous decrease of ET-1 on the opposite side for both nLDLs and oxLDLs. On the contrary, high-density lipoproteins (HDLs) inhibited ET-1 secretion from HUVECs on the opposite side of the well on which HDLs were loaded; there was a 57% decrease on the basal side when HDLs were loaded on the apical side, and a 46% decrease on the apical side when loaded on the basal side. These results indicate that modulation of ET-1 secretion from ECs by lipoproteins is virtually dependent on the place (apical vs basal) where these proteins are present. The finding that nLDLs and oxLDLs enhance ET-1 secretion by ECs in a polarized pattern suggests that ET-1 may be involved in pathophysiological processes such as atherogenesis.

NASA Space Flight Human-System Standard Human Factors, Habitability, and Environmental Health

NASA Technical Reports Server (NTRS)

Holubec, Keith; Connolly, Janis

2010-01-01

This slide presentation reviews the history, and development of NASA-STD-3001, NASA Space Flight Human-System Standard Human Factors, Habitability, and Environmental Health, and the related Human Integration Design Handbook. Currently being developed from NASA-STD-3000, this project standard currently in review will be available in two volumes, (i.e., Volume 1 -- VCrew Health and Volume 2 -- Human Factors, Habitability, and Environmental Health) and the handbook will be both available as a pdf file and as a interactive website.

Transient interaction model of electromagnetic field generated by lightning current pulses and human body

NASA Astrophysics Data System (ADS)

Iváncsy, T.; Kiss, I.; Szücs, L.; Tamus, Z. Á.

2015-10-01

The lightning current generates time-varying magnetic field near the down- conductor and the down-conductors are mounted on the wall of the buildings where residential places might be situated. It is well known that the rapidly changing magnetic fields can generate dangerous eddy currents in the human body.The higher duration and gradient of the magnetic field can cause potentially life threatening cardiac stimulation. The coupling mechanism between the electromagnetic field and the human body is based on a well-known physical phenomena (e.g. Faradays law of induction). However, the calculation of the induced current is very complicated because the shape of the organs is complex and the determination of the material properties of living tissues is difficult, as well. Our previous study revealed that the cardiac stimulation is independent of the rising time of the lightning current and only the peak of the current counts. In this study, the authors introduce an improved model of the interaction of electromagnetic fields of lighting current near down-conductor and human body. Our previous models are based on the quasi stationer field calculations, the new improved model is a transient model. This is because the magnetic field around the down-conductor and in the human body can be determined more precisely, therefore the dangerous currents in the body can be estimated.

[Effects of human amniotic epithelial stem cells-derived exosomes on healing of wound with full-thickness skin defect in rats].

PubMed

Zhao, B; Wu, G F; Zhang, Y J; Zhang, W; Yang, F F; Xiao, D; Zeng, K X; Shi, J H; Su, L L; Hu, D H

2017-01-20

Objective: To investigate the effects of human amniotic epithelial stem cells-derived exosomes on healing of wound with full-thickness skin defect in rats. Methods: (1) Human amniotic epithelial stem cells were isolated from the amnion tissue of 5 full-term pregnant women in Department of Obstetrics of our hospital by the method of trypsin digestion, and their morphology was observed. The third passage of cells were stained with rhodamine-phalloidin for cytoskeleton observation. The third passage of cells were identified with flow cytometry through the detection of expressions of cell surface markers CD29, CD31, CD34, CD90, CD105, SSEA3, SSEA4 and immunity-related marker human leukocyte antigen-D related site (HLA-DR). The third passage of cells were also assessed the ability of adipogenic and osteogenic differentiation. (2) The third passage of human amniotic epithelial stem cells were cultured in DMEM medium supplemented with 10% exosome-free fetal bovine serum. Exosomes were isolated from culture supernatant by the method of ultracentrifugation and represented with scanning electron microscope for morphologic observation. (3) Six adult SD rats were anesthetized, and four 1 cm×1 cm sized wounds with full-thickness skin defect were made on the back of each rat. The wounds on the back of each rat were divided into control group, 25 μg/mL exosomes group, 50 μg/mL exosomes group, and 100 μg/mL exosomes group according to the random number table (with 6 wounds in each group), and a total volume of 100 μL phosphate buffered saline, 25 μg/mL exosomes, 50 μg/mL exosomes, and 100 μg/mL exosomes were evenly injected around the wound through multiple subcutaneous sites, respectively. The wound healing rate was calculated based on measurement on post injury day (PID) 7, 14, and 21. On PID 21, the healed wound tissue of each group was collected and stained with HE to observe and count skin accessories, and the arrangement of collagen fibers was observed with Masson staining. Data were processed with analysis of variance for repeated measurement, analysis of variance of randomized block design, one-way analysis of variance, and Bonferroni test. Results: (1) The cells, which were isolated and cultured, displayed typical cobblestone morphology with many microvilli on cell surface. Among the cells, the positive expression rates of CD29, CD90, SSEA3, and SSEA4 were above 50.0%, and the rate of CD105 was 8.0%, while the rates of CD31, CD34, and HLA-DR were almost 0. The cells could differentiate into adipocytes and osteoblasts. The above results revealed that the cells cultured were human amniotic epithelial stem cells. (2) Human amniotic epithelial stem cells-derived exosomes were round or oval vesicles with diameter from 50 to 150 nm. (3) On PID 7 and 21, wound healing rates of the four groups were close (with P values above 0.05). On PID 14, wound healing rates of 50 and 100 μg/mL exosomes groups were (89.8±4.3)% and (92.0±4.6)% respectively, significantly higher than the wound healing rate of control group [(80.3±6.4)%, P <0.05 or P <0.01]. Moreover, the wound healing rate of 100 μg/mL exosomes group was significantly higher than that of 25 μg/mL exosomes group [(83.3±5.1)%, P <0.05]. On PID 21, the numbers of skin accessories in 50 and 100 μg/mL exosomes groups were 4.3±1.4 and 5.1±1.6 respectively, obviously more than those of control group and 25 μg/mL exosomes group (respectively 1.4±0.5 and 1.8±0.6, with P values below 0.01). Well reorganized collagen fibers were observed just in the healed wound tissue of 50 and 100 μg/mL exosomes groups. Conclusions: Human amniotic epithelial stem cells-derived exosomes can promote healing of wound with full-thickness skin defect in rats.

Liver Biopsy

MedlinePlus

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Regulation of amniotic fluid volume: mathematical model based on intramembranous transport mechanisms

PubMed Central

Anderson, Debra F.; Cheung, Cecilia Y.

2014-01-01

Experimentation in late-gestation fetal sheep has suggested that regulation of amniotic fluid (AF) volume occurs primarily by modulating the rate of intramembranous transport of water and solutes across the amnion into underlying fetal blood vessels. In order to gain insight into intramembranous transport mechanisms, we developed a computer model that allows simulation of experimentally measured changes in AF volume and composition over time. The model included fetal urine excretion and lung liquid secretion as inflows into the amniotic compartment plus fetal swallowing and intramembranous absorption as outflows. By using experimental flows and solute concentrations for urine, lung liquid, and swallowed fluid in combination with the passive and active transport mechanisms of the intramembranous pathway, we simulated AF responses to basal conditions, intra-amniotic fluid infusions, fetal intravascular infusions, urine replacement, and tracheoesophageal occlusion. The experimental data are consistent with four intramembranous transport mechanisms acting in concert: 1) an active unidirectional bulk transport of AF with all dissolved solutes out of AF into fetal blood presumably by vesicles; 2) passive bidirectional diffusion of solutes, such as sodium and chloride, between fetal blood and AF; 3) passive bidirectional water movement between AF and fetal blood; and 4) unidirectional transport of lactate into the AF. Further, only unidirectional bulk transport is dynamically regulated. The simulations also identified areas for future study: 1) identifying intramembranous stimulators and inhibitors, 2) determining the semipermeability characteristics of the intramembranous pathway, and 3) characterizing the vesicles that are the primary mediators of intramembranous transport. PMID:25186112

Simple estimation of induced electric fields in nervous system tissues for human exposure to non-uniform electric fields at power frequency

NASA Astrophysics Data System (ADS)

Tarao, Hiroo; Miyamoto, Hironobu; Korpinen, Leena; Hayashi, Noriyuki; Isaka, Katsuo

2016-06-01

Most results regarding induced current in the human body related to electric field dosimetry have been calculated under uniform field conditions. We have found in previous work that a contact current is a more suitable way to evaluate induced electric fields, even in the case of exposure to non-uniform fields. If the relationship between induced currents and external non-uniform fields can be understood, induced electric fields in nervous system tissues may be able to be estimated from measurements of ambient non-uniform fields. In the present paper, we numerically calculated the induced electric fields and currents in a human model by considering non-uniform fields based on distortion by a cubic conductor under an unperturbed electric field of 1 kV m-1 at 60 Hz. We investigated the relationship between a non-uniform external electric field with no human present and the induced current through the neck, and the relationship between the current through the neck and the induced electric fields in nervous system tissues such as the brain, heart, and spinal cord. The results showed that the current through the neck can be formulated by means of an external electric field at the central position of the human head, and the distance between the conductor and the human model. As expected, there is a strong correlation between the current through the neck and the induced electric fields in the nervous system tissues. The combination of these relationships indicates that induced electric fields in these tissues can be estimated solely by measurements of the external field at a point and the distance from the conductor.

3D Miniaturization of Human Organs for Drug Discovery.

PubMed

Park, Joseph; Wetzel, Isaac; Dréau, Didier; Cho, Hansang

2018-01-01

"Engineered human organs" hold promises for predicting the effectiveness and accuracy of drug responses while reducing cost, time, and failure rates in clinical trials. Multiorgan human models utilize many aspects of currently available technologies including self-organized spherical 3D human organoids, microfabricated 3D human organ chips, and 3D bioprinted human organ constructs to mimic key structural and functional properties of human organs. They enable precise control of multicellular activities, extracellular matrix (ECM) compositions, spatial distributions of cells, architectural organizations of ECM, and environmental cues. Thus, engineered human organs can provide the microstructures and biological functions of target organs and advantageously substitute multiscaled drug-testing platforms including the current in vitro molecular assays, cell platforms, and in vivo models. This review provides an overview of advanced innovative designs based on the three main technologies used for organ construction leading to single and multiorgan systems useable for drug development. Current technological challenges and future perspectives are also discussed. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Electrical signal analysis to assess the physical condition of a human or animal

DOEpatents

Cox, Daryl F.; Hochanadel, Charles D.; Haynes, Howard D.

2010-06-15

The invention is a human and animal performance data acquisition, analysis, and diagnostic system for fitness and therapy devices having an interface box removably disposed on incoming power wiring to a fitness and therapy device, at least one current transducer removably disposed on said interface box for sensing current signals to said fitness and therapy device, and a means for analyzing, displaying, and reporting said current signals to determine human and animal performance on said device using measurable parameters.

Education for Sustainability: The Need for a New Human Perspective.

ERIC Educational Resources Information Center

Cortese, Anthony

Disturbing global trends show that human activity continues to threaten our ability to meet current human needs without compromising the ability of future generations to meet their own needs. Sustainability will become more inaccessible without a dramatic change in our current mindset and behavior. As the primary centers of teaching, research, and…

Impact of ionic current variability on human ventricular cellular electrophysiology.

PubMed

Romero, Lucía; Pueyo, Esther; Fink, Martin; Rodríguez, Blanca

2009-10-01

Abnormalities in repolarization and its rate dependence are known to be related to increased proarrhythmic risk. A number of repolarization-related electrophysiological properties are commonly used as preclinical biomarkers of arrhythmic risk. However, the variability and complexity of repolarization mechanisms make the use of cellular biomarkers to predict arrhythmic risk preclinically challenging. Our goal is to investigate the role of ionic current properties and their variability in modulating cellular biomarkers of arrhythmic risk to improve risk stratification and identification in humans. A systematic investigation into the sensitivity of the main preclinical biomarkers of arrhythmic risk to changes in ionic current conductances and kinetics was performed using computer simulations. Four stimulation protocols were applied to the ten Tusscher and Panfilov human ventricular model to quantify the impact of +/-15 and +/-30% variations in key model parameters on action potential (AP) properties, Ca(2+) and Na(+) dynamics, and their rate dependence. Simulations show that, in humans, AP duration is moderately sensitive to changes in all repolarization current conductances and in L-type Ca(2+) current (I(CaL)) and slow component of the delayed rectifier current (I(Ks)) inactivation kinetics. AP triangulation, however, is strongly dependent only on inward rectifier K(+) current (I(K1)) and delayed rectifier current (I(Kr)) conductances. Furthermore, AP rate dependence (i.e., AP duration rate adaptation and restitution properties) and intracellular Ca(2+) and Na(+) levels are highly sensitive to both I(CaL) and Na(+)/K(+) pump current (I(NaK)) properties. This study provides quantitative insights into the sensitivity of preclinical biomarkers of arrhythmic risk to variations in ionic current properties in humans. The results show the importance of sensitivity analysis as a powerful method for the in-depth validation of mathematical models in cardiac electrophysiology.

Inhibitory effects of hesperetin on Kv1.5 potassium channels stably expressed in HEK 293 cells and ultra-rapid delayed rectifier K(+) current in human atrial myocytes.

PubMed

Wang, Huan; Wang, Hong-Fei; Wang, Chen; Chen, Yu-Fang; Ma, Rong; Xiang, Ji-Zhou; Du, Xin-Ling; Tang, Qiang

2016-10-15

In the present study, the inhibitory effects of hesperetin (HSP) on human cardiac Kv1.5 channels expressed in HEK 293 cells and the ultra-rapid delayed rectifier K(+) current (Ikur) in human atrial myocytes were examined by using the whole-cell configuration of the patch-clamp techniques. We found that hesperetin rapidly and reversibly suppressed human Kv1.5 current in a concentration dependent manner with a half-maximal inhibition (IC50) of 23.15 μΜ with a Hill coefficient of 0.89. The current was maximally diminished about 71.36% at a concentration of 300μM hesperetin. Hesperetin significantly positive shifted the steady-state activation curve of Kv1.5, while negative shifted the steady-state inactivation curve. Hesperetin also accelerated the inactivation and markedly slowed the recovery from the inactivation of Kv1.5 currents. Block of Kv1.5 currents by hesperetin was in a frequency dependent manner. However, inclusion of 30μM hesperetin in pipette solution produced no effect on Kv1.5 channel current, while the current were remarkable and reversibly inhibited by extracellular application of 30μM hesperetin. We also found that hesperetin potently and reversibly inhibited the ultra-repaid delayed K(+) current (Ikur) in human atrial myocytes, which is in consistent with the effects of hesperetin on Kv1.5 currents in HEK 293 cells. In conclusion, hesperetin is a potent inhibitor of Ikur (which is encoded by Kv1.5), with blockade probably due to blocking of both open state and inactivated state channels from outside of the cell. Copyright © 2016 Elsevier B.V. All rights reserved.

Analysis of the charge exchange between the human body and ground: evaluation of "earthing" from an electrical perspective.

PubMed

Chamberlin, Kent; Smith, Wayne; Chirgwin, Christopher; Appasani, Seshank; Rioux, Paul

2014-12-01

The purpose of this study was to investigate "earthing" from an electrical perspective through measurement and analysis of the naturally occurring electron flow between the human body or a control and ground as this relates to the magnitude of the charge exchange, the relationship between the charge exchange and body functions (respiration and heart rate), and the detection of other information that might be contained in the charge exchange. Sensitive, low-noise instrumentation was designed and fabricated to measure low-level current flow at low frequencies. This instrumentation was used to record current flow between human subjects or a control and ground, and these measurements were performed approximately 40 times under varied circumstances. The results of these measurements were analyzed to determine if information was contained in the current exchange. The currents flowing between the human body and ground were small (nanoamperes), and they correlated with subject motion. There did not appear to be any information contained in this exchange except for information about subject motion. This study showed that currents flow between the environment (earth) and a grounded human body; however, these currents are small (nanoamperes) and do not appear to contain information other than information about subject motion.

Analysis of the Charge Exchange Between the Human Body and Ground: Evaluation of “Earthing” From an Electrical Perspective

PubMed Central

Chamberlin, Kent; Smith, Wayne; Chirgwin, Christopher; Appasani, Seshank; Rioux, Paul

2014-01-01

Objective The purpose of this study was to investigate “earthing” from an electrical perspective through measurement and analysis of the naturally occurring electron flow between the human body or a control and ground as this relates to the magnitude of the charge exchange, the relationship between the charge exchange and body functions (respiration and heart rate), and the detection of other information that might be contained in the charge exchange. Methods Sensitive, low-noise instrumentation was designed and fabricated to measure low-level current flow at low frequencies. This instrumentation was used to record current flow between human subjects or a control and ground, and these measurements were performed approximately 40 times under varied circumstances. The results of these measurements were analyzed to determine if information was contained in the current exchange. Results The currents flowing between the human body and ground were small (nanoamperes), and they correlated with subject motion. There did not appear to be any information contained in this exchange except for information about subject motion. Conclusions This study showed that currents flow between the environment (earth) and a grounded human body; however, these currents are small (nanoamperes) and do not appear to contain information other than information about subject motion. PMID:25435837

The Na+/K+ pump is an important modulator of refractoriness and rotor dynamics in human atrial tissue.

PubMed

Sánchez, Carlos; Corrias, Alberto; Bueno-Orovio, Alfonso; Davies, Mark; Swinton, Jonathan; Jacobson, Ingemar; Laguna, Pablo; Pueyo, Esther; Rodríguez, Blanca

2012-03-01

Pharmacological treatment of atrial fibrillation (AF) exhibits limited efficacy. Further developments require a comprehensive characterization of ionic modulators of electrophysiology in human atria. Our aim is to systematically investigate the relative importance of ionic properties in modulating excitability, refractoriness, and rotor dynamics in human atria before and after AF-related electrical remodeling (AFER). Computer simulations of single cell and tissue atrial electrophysiology were conducted using two human atrial action potential (AP) models. Changes in AP, refractory period (RP), conduction velocity (CV), and rotor dynamics caused by alterations in key properties of all atrial ionic currents were characterized before and after AFER. Results show that the investigated human atrial electrophysiological properties are primarily modulated by maximal value of Na(+)/K(+) pump current (G(NaK)) as well as conductances of inward rectifier potassium current (G(K1)) and fast inward sodium current (G(Na)). G(NaK) plays a fundamental role through both electrogenic and homeostatic modulation of AP duration (APD), APD restitution, RP, and reentrant dominant frequency (DF). G(K1) controls DF through modulation of AP, APD restitution, RP, and CV. G(Na) is key in determining DF through alteration of CV and RP, particularly in AFER. Changes in ionic currents have qualitatively similar effects in control and AFER, but effects are smaller in AFER. The systematic analysis conducted in this study unravels the important role of the Na(+)/K(+) pump current in determining human atrial electrophysiology.

Terminal Area Productivity Program: Dynamic Spacing Human Factors

NASA Technical Reports Server (NTRS)

Kanki, Barbara G.

1997-01-01

Dynamic spacing human factors deals with the following human factors issues: define controller limits to incorporating dynamic changes in separation standards; identify timing, planning, and coordination strategies; and consider consistency with current practices, policies, and regulations. The AVOSS technologies will make it possible to reduce separation standards in the terminal area under certain meteorological conditions. This paper contains the following sections: Dynamic space human factors overview, Preliminary tests, and current research status & plans.

Human spermatozoa possess a calcium-dependent chloride channel that may participate in the acrosomal reaction

PubMed Central

Orta, Gerardo; Ferreira, Gonzalo; José, Omar; Treviño, Claudia L; Beltrán, Carmen; Darszon, Alberto

2012-01-01

Motility, maturation and the acrosome reaction (AR) are fundamental functions of mammalian spermatozoa. While travelling through the female reproductive tract, spermatozoa must mature through a process named capacitation, so that they can reach the egg and undergo the AR, an exocytotic event necessary to fertilize the egg. Though Cl− is important for sperm capacitation and for the AR, not much is known about the molecular identity of the Cl− transporters involved in these processes. We implemented a modified perforated patch-clamp strategy to obtain whole cell recordings sealing on the head of mature human spermatozoa. Our whole cell recordings revealed the presence of a Ca2+-dependent Cl− current. The biophysical characteristics of this current and its sensitivity to niflumic acid (NFA) and 4,4′-diisothiocyano-2,2′-stilbene disulphonic acid (DIDIS) are consistent with those displayed by the Ca2+-dependent Cl− channel from the anoctamin family (TMEM16). Whole cell patch clamp recordings in the cytoplasmic droplet of human spermatozoa corroborated the presence of these currents, which were sensitive to NFA and to a small molecule TMEM16A inhibitor (TMEM16Ainh, an aminophenylthiazole). Importantly, the human sperm AR induced by a recombinant human glycoprotein from the zona pellucida, rhZP3, displayed a similar sensitivity to NFA, DIDS and TMEM16Ainh as the sperm Ca2+-dependent Cl− currents. Our findings indicate the presence of Ca2+-dependent Cl− currents in human spermatozoa, that TMEM16A may contribute to these currents and also that sperm Ca2+-dependent Cl− currents may participate in the rhZP3-induced AR. PMID:22473777

Electrical signature analysis to quantify human and animal performance on fitness and therapy equipment such as a treadmill

DOEpatents

Cox, Daryl F.; Hochanadel, Charles D.; Haynes, Howard D.

2010-05-18

The invention is a human and animal performance data acquisition, analysis, and diagnostic system for fitness and therapy devices having an interface box removably disposed on incoming power wiring to a fitness and therapy device, at least one current transducer removably disposed on said interface box for sensing current signals to said fitness and therapy device, and a means for analyzing, displaying, and reporting said current signals to determine human and animal performance on said device using measurable parameters.

Space Mission Human Reliability Analysis (HRA) Project

NASA Technical Reports Server (NTRS)

Boyer, Roger

2014-01-01

The purpose of the Space Mission Human Reliability Analysis (HRA) Project is to extend current ground-based HRA risk prediction techniques to a long-duration, space-based tool. Ground-based HRA methodology has been shown to be a reasonable tool for short-duration space missions, such as Space Shuttle and lunar fly-bys. However, longer-duration deep-space missions, such as asteroid and Mars missions, will require the crew to be in space for as long as 400 to 900 day missions with periods of extended autonomy and self-sufficiency. Current indications show higher risk due to fatigue, physiological effects due to extended low gravity environments, and others, may impact HRA predictions. For this project, Safety & Mission Assurance (S&MA) will work with Human Health & Performance (HH&P) to establish what is currently used to assess human reliabiilty for human space programs, identify human performance factors that may be sensitive to long duration space flight, collect available historical data, and update current tools to account for performance shaping factors believed to be important to such missions. This effort will also contribute data to the Human Performance Data Repository and influence the Space Human Factors Engineering research risks and gaps (part of the HRP Program). An accurate risk predictor mitigates Loss of Crew (LOC) and Loss of Mission (LOM).The end result will be an updated HRA model that can effectively predict risk on long-duration missions.

In-vivo Imaging of Magnetic Fields Induced by Transcranial Direct Current Stimulation (tDCS) in Human Brain using MRI

NASA Astrophysics Data System (ADS)

Jog, Mayank V.; Smith, Robert X.; Jann, Kay; Dunn, Walter; Lafon, Belen; Truong, Dennis; Wu, Allan; Parra, Lucas; Bikson, Marom; Wang, Danny J. J.

2016-10-01

Transcranial direct current stimulation (tDCS) is an emerging non-invasive neuromodulation technique that applies mA currents at the scalp to modulate cortical excitability. Here, we present a novel magnetic resonance imaging (MRI) technique, which detects magnetic fields induced by tDCS currents. This technique is based on Ampere’s law and exploits the linear relationship between direct current and induced magnetic fields. Following validation on a phantom with a known path of electric current and induced magnetic field, the proposed MRI technique was applied to a human limb (to demonstrate in-vivo feasibility using simple biological tissue) and human heads (to demonstrate feasibility in standard tDCS applications). The results show that the proposed technique detects tDCS induced magnetic fields as small as a nanotesla at millimeter spatial resolution. Through measurements of magnetic fields linearly proportional to the applied tDCS current, our approach opens a new avenue for direct in-vivo visualization of tDCS target engagement.

Computational dosimetry for grounded and ungrounded human models due to contact current

NASA Astrophysics Data System (ADS)

Chan, Kwok Hung; Hattori, Junya; Laakso, Ilkka; Hirata, Akimasa; Taki, Masao

2013-08-01

This study presents the computational dosimetry of contact currents for grounded and ungrounded human models. The uncertainty of the quasi-static (QS) approximation of the in situ electric field induced in a grounded/ungrounded human body due to the contact current is first estimated. Different scenarios of cylindrical and anatomical human body models are considered, and the results are compared with the full-wave analysis. In the QS analysis, the induced field in the grounded cylindrical model is calculated by the QS finite-difference time-domain (QS-FDTD) method, and compared with the analytical solution. Because no analytical solution is available for the grounded/ungrounded anatomical human body model, the results of the QS-FDTD method are then compared with those of the conventional FDTD method. The upper frequency limit for the QS approximation in the contact current dosimetry is found to be 3 MHz, with a relative local error of less than 10%. The error increases above this frequency, which can be attributed to the neglect of the displacement current. The QS or conventional FDTD method is used for the dosimetry of induced electric field and/or specific absorption rate (SAR) for a contact current injected into the index finger of a human body model in the frequency range from 10 Hz to 100 MHz. The in situ electric fields or SAR are compared with the basic restrictions in the international guidelines/standards. The maximum electric field or the 99th percentile value of the electric fields appear not only in the fat and muscle tissues of the finger, but also around the wrist, forearm, and the upper arm. Some discrepancies are observed between the basic restrictions for the electric field and SAR and the reference levels for the contact current, especially in the extremities. These discrepancies are shown by an equation that relates the current density, tissue conductivity, and induced electric field in the finger with a cross-sectional area of 1 cm2.

Involuntary Euthanasia and Current Attempts to Define Persons with Mental Retardation as Less Than Human.

ERIC Educational Resources Information Center

Lusthaus, Evelyn W.

1985-01-01

The author examines current attempts to define mentally retarded persons as less than human and suggests that these ideologies are being used to justify euthanasia practices and to formulate euthanasia policies. (CL)

Welfare of apes in captive environments: comments on, and by, a specific group of apes.

PubMed

Savage-Rumbaugh, Sue; Wamba, Kanzi; Wamba, Panbanisha; Wamba, Nyota

2007-01-01

Accurately determining the proper captive environment for apes requires adequately assessing the psychological similarities between apes and humans. Scientists currently believe apes lack mental complexity (Millikan, 2006), raising questions concerning the evolution of human culture from ape-like societies (Tomasello, 1999). A long-term cultural study with bonobos suggests less intellectual divergence from humans than currently postulated (Savage-Rumbaugh, 2005). Because humans view apes as mentally limited, some current captive environments may appear idyllic while offering only an illusion of appropriate care, derived from a simplistic view of what apes are, rather than what they might be. This perception of apes determines their handling, which determines their mental development, which perpetuates the prevailing perception. Only breaking this cycle will allow the current perception of apes to change. Their usual captive environment limits any demonstration of culture. However, the bonobo study reveals what ape culture can become, which should affect future welfare considerations for at least those species genetically close to humans (bonobos and chimpanzees). Development of a languaged bonobo culture allows these nonhuman animals to provide their own responses regarding adequate ape welfare.

In vitro and in vivo comparisons of constant resistance AC iontophoresis and DC iontophoresis.

PubMed

Li, S Kevin; Higuchi, William I; Zhu, Honggang; Kern, Steven E; Miller, David J; Hastings, Matthew S

2003-09-04

A previous in vitro constant electrical resistance alternating current (AC) iontophoresis study with human epidermal membrane (HEM) and a model neutral permeant has shown less inter- and intra-sample variability in iontophoretic transport relative to conventional constant direct current (DC) iontophoresis. The objectives of the present study were to address the following questions. (1) Can the skin electrical resistance be maintained at a constant level by AC in humans in vivo? (2) Are the in vitro data with HEM representative of those in vivo? (3) Does constant skin resistance AC iontophoresis have less inter- and intra-sample variability than conventional constant current DC iontophoresis in vivo? (4) What are the electrical and the barrier properties of skin during iontophoresis in vivo? In the present study, in vitro HEM experiments were carried out with the constant resistance AC and the conventional constant current DC methods using mannitol and glucose as the neutral model permeants. In vivo human experiments were performed using glucose as the permeant with a constant skin resistance AC only protocol and two conventional constant current DC methods (continuous constant current DC and constant current DC with its polarity alternated every 10 min with a 3:7 on:off duty cycle). Constant current DC iontophoresis was conducted with commercial constant current DC devices, and constant resistance AC iontophoresis was carried out by reducing and maintaining the skin resistance at a constant target value with AC supplied from a function generator. This study shows that (1) skin electrical resistance can be maintained at a constant level during AC iontophoresis in vivo; (2) HEM in vitro and human skin in vivo demonstrate similar electrical and barrier properties, and these properties are consistent with our previous findings; (3) there is general qualitative and semi-quantitative agreement between the HEM data in vitro and human skin data in vivo; and (4) constant skin resistance AC iontophoresis generally provides less inter- and intra-subject variability than conventional constant current DC.

Human Hemato-Lymphoid System Mice: Current Use and Future Potential for Medicine

PubMed Central

Rongvaux, Anthony; Takizawa, Hitoshi; Strowig, Till; Willinger, Tim; Eynon, Elizabeth E.

2014-01-01

To directly study complex human hemato-lymphoid system physiology and respective system-associated diseases in vivo, human-to-mouse xenotransplantation models for human blood and blood-forming cells and organs have been developed over the past three decades. We here review the fundamental requirements and the remarkable progress made over the past few years in improving these systems, the current major achievements reached by use of these models, and the future challenges to more closely model and study human health and disease and to achieve predictive preclinical testing of both prevention measures and potential new therapies. PMID:23330956

HIV Disease: Current Concepts.

ERIC Educational Resources Information Center

Keeling, Richard P.

1993-01-01

Describes human immunodeficiency virus (HIV), newly characterized human retrovirus which causes chronic, progressive, immune deficiency disease, the most severe phase of which is Acquired Immune Deficiency Syndrome (AIDS). Reviews most important current epidemiologic, clinical, and virologic information about HIV and HIV disease and provides…

Simulation study on transient electric shock characteristics of human body under high voltage ac transmission lines

NASA Astrophysics Data System (ADS)

Huang, Tao; Zou, Yanhui; Lv, Jianhong; Yang, Jinchun; Tao, Li; Zhou, Jianfei

2017-09-01

Human body under high-voltage AC transmission lines will produce a certain induced voltage due to the electrostatic induction. When the human body contacts with some grounded objects, the charges transfer from the body to the ground and produce contact current which may cause transient electric shock. Using CDEGS and ATP/EMTP, the paper proposes a method for quantitatively calculating the transient electric shock characteristics. It calculates the human body voltage, discharge current and discharge energy under certain 500kV compact-type transmission lines and predicts the corresponding human feelings. The results show that the average root value of discharge current is less than 10mA when the human body is under the 500kV compact-type transmission lines and the human body is overall safe if the transmission lines satisfy the relevant design specifications. It concludes that the electric field strength above the ground should be limited to 4kV/m through the residential area for the purpose of reducing the electromagnetic impact.

A meta-analysis of human-system interfaces in unmanned aerial vehicle (UAV) swarm management.

PubMed

Hocraffer, Amy; Nam, Chang S

2017-01-01

A meta-analysis was conducted to systematically evaluate the current state of research on human-system interfaces for users controlling semi-autonomous swarms composed of groups of drones or unmanned aerial vehicles (UAVs). UAV swarms pose several human factors challenges, such as high cognitive demands, non-intuitive behavior, and serious consequences for errors. This article presents findings from a meta-analysis of 27 UAV swarm management papers focused on the human-system interface and human factors concerns, providing an overview of the advantages, challenges, and limitations of current UAV management interfaces, as well as information on how these interfaces are currently evaluated. In general allowing user and mission-specific customization to user interfaces and raising the swarm's level of autonomy to reduce operator cognitive workload are beneficial and improve situation awareness (SA). It is clear more research is needed in this rapidly evolving field. Copyright © 2016 Elsevier Ltd. All rights reserved.

Animal rights, animal minds, and human mindreading.

PubMed

Mameli, M; Bortolotti, L

2006-02-01

Do non-human animals have rights? The answer to this question depends on whether animals have morally relevant mental properties. Mindreading is the human activity of ascribing mental states to other organisms. Current knowledge about the evolution and cognitive structure of mindreading indicates that human ascriptions of mental states to non-human animals are very inaccurate. The accuracy of human mindreading can be improved with the help of scientific studies of animal minds. However, the scientific studies do not by themselves solve the problem of how to map psychological similarities (and differences) between humans and animals onto a distinction between morally relevant and morally irrelevant mental properties. The current limitations of human mindreading-whether scientifically aided or not-have practical consequences for the rational justification of claims about which rights (if any) non-human animals should be accorded.

Modeling Sustainability: Population, Inequality, Consumption, and Bidirectional Coupling of the Earth and Human Systems

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

Motesharrei, Safa; Rivas, Jorge; Kalnay, Eugenia

Over the last two centuries, the impact of the Human System has grown dramatically, becoming strongly dominant within the Earth System in many different ways. Consumption, inequality, and population have increased extremely fast, especially since about 1950, threatening to overwhelm the many critical functions and ecosystems of the Earth System. Changes in the Earth System, in turn, have important feedback effects on the Human System, with costly and potentially serious consequences. However, current models do not incorporate these critical feedbacks. Here, we argue that in order to understand the dynamics of either system, Earth System Models must be coupled withmore » Human System Models through bidirectional couplings representing the positive, negative, and delayed feedbacks that exist in the real systems. In particular, key Human System variables, such as demographics, inequality, economic growth, and migration, are not coupled with the Earth System but are instead driven by exogenous estimates, such as United Nations population projections.This makes current models likely to miss important feedbacks in the real Earth–Human system, especially those that may result in unexpected or counterintuitive outcomes, and thus requiring different policy interventions from current models. Lastly, the importance and imminence of sustainability challenges, the dominant role of the Human System in the Earth System, and the essential roles the Earth System plays for the Human System, all call for collaboration of natural scientists, social scientists, and engineers in multidisciplinary research and modeling to develop coupled Earth–Human system models for devising effective science-based policies and measures to benefit current and future generations.« less

Modeling Sustainability: Population, Inequality, Consumption, and Bidirectional Coupling of the Earth and Human Systems

NASA Technical Reports Server (NTRS)

Motesharrei, Safa; Rivas, Jorge; Kalnay, Eugenia; Asrar, Ghassem R.; Busalacchi, Antonio J.; Cahalan, Robert F.; Cane, Mark A.; Colwell, Rita R.; Feng, Kuishuang; Franklin, Rachel S.;

Modeling Sustainability: Population, Inequality, Consumption, and Bidirectional Coupling of the Earth and Human Systems

DOE PAGES

Motesharrei, Safa; Rivas, Jorge; Kalnay, Eugenia; ...

2016-12-11

Over the last two centuries, the impact of the Human System has grown dramatically, becoming strongly dominant within the Earth System in many different ways. Consumption, inequality, and population have increased extremely fast, especially since about 1950, threatening to overwhelm the many critical functions and ecosystems of the Earth System. Changes in the Earth System, in turn, have important feedback effects on the Human System, with costly and potentially serious consequences. However, current models do not incorporate these critical feedbacks. Here, we argue that in order to understand the dynamics of either system, Earth System Models must be coupled withmore » Human System Models through bidirectional couplings representing the positive, negative, and delayed feedbacks that exist in the real systems. In particular, key Human System variables, such as demographics, inequality, economic growth, and migration, are not coupled with the Earth System but are instead driven by exogenous estimates, such as United Nations population projections.This makes current models likely to miss important feedbacks in the real Earth–Human system, especially those that may result in unexpected or counterintuitive outcomes, and thus requiring different policy interventions from current models. Lastly, the importance and imminence of sustainability challenges, the dominant role of the Human System in the Earth System, and the essential roles the Earth System plays for the Human System, all call for collaboration of natural scientists, social scientists, and engineers in multidisciplinary research and modeling to develop coupled Earth–Human system models for devising effective science-based policies and measures to benefit current and future generations.« less

Early afterdepolarizations promote transmural reentry in ischemic human ventricles with reduced repolarization reserve

PubMed Central

Dutta, Sara; Mincholé, Ana; Zacur, Ernesto; Quinn, T. Alexander; Taggart, Peter; Rodriguez, Blanca

2016-01-01

Aims Acute ischemia is a major cause of sudden arrhythmic death, further promoted by potassium current blockers. Macro-reentry around the ischemic region and early afterdepolarizations (EADs) caused by electrotonic current have been suggested as potential mechanisms in animal and isolated cell studies. However, ventricular and human-specific arrhythmia mechanisms and their modulation by repolarization reserve remain unclear. The goal of this paper is to unravel multiscale mechanisms underlying the modulation of arrhythmic risk by potassium current (IKr) block in human ventricles with acute regional ischemia. Methods and results A human ventricular biophysically-detailed model, with acute regional ischemia is constructed by integrating experimental knowledge on the electrophysiological ionic alterations caused by coronary occlusion. Arrhythmic risk is evaluated by determining the vulnerable window (VW) for reentry following ectopy at the ischemic border zone. Macro-reentry around the ischemic region is the main reentrant mechanism in the ischemic human ventricle with increased repolarization reserve due to the ATP-sensitive potassium current (IK(ATP)) activation. Prolongation of refractoriness by 4% caused by 30% IKr reduction counteracts the establishment of macro-reentry and reduces the VW for reentry (by 23.5%). However, a further decrease in repolarization reserve (50% IKr reduction) is less anti-arrhythmic despite further prolongation of refractoriness. This is due to the establishment of transmural reentry enabled by electrotonically-triggered EADs in the ischemic border zone. EADs are produced by L-type calcium current (ICaL) reactivation due to prolonged low amplitude electrotonic current injected during the repolarization phase. Conclusions Electrotonically-triggered EADs are identified as a potential mechanism facilitating intramural reentry in a regionally-ischemic human ventricles model with reduced repolarization reserve. PMID:26850675

Basally activated nonselective cation currents regulate the resting membrane potential in human and monkey colonic smooth muscle

PubMed Central

Dwyer, Laura; Rhee, Poong-Lyul; Lowe, Vanessa; Zheng, Haifeng; Peri, Lauren; Ro, Seungil; Sanders, Kenton M.

2011-01-01

Resting membrane potential (RMP) plays an important role in determining the basal excitability of gastrointestinal smooth muscle. The RMP in colonic muscles is significantly less negative than the equilibrium potential of K+, suggesting that it is regulated not only by K+ conductances but by inward conductances such as Na+ and/or Ca2+. We investigated the contribution of nonselective cation channels (NSCC) to the RMP in human and monkey colonic smooth muscle cells (SMC) using voltage- and current-clamp techniques. Qualitative reverse transcriptase-polymerase chain reaction was performed to examine potential molecular candidates for these channels among the transient receptor potential (TRP) channel superfamily. Spontaneous transient inward currents and holding currents were recorded in human and monkey SMC. Replacement of extracellular Na+ with equimolar tetraethylammonium or Ca2+ with Mn2+ inhibited basally activated nonselective cation currents. Trivalent cations inhibited these channels. Under current clamp, replacement of extracellular Na+ with N-methyl-d-glucamine or addition of trivalent cations caused hyperpolarization. Three unitary conductances of NSCC were observed in human and monkey colonic SMC. Molecular candidates for basally active NSCC were TRPC1, C3, C4, C7, M2, M4, M6, M7, V1, and V2 in human and monkey SMC. Comparison of the biophysical properties of these TRP channels with basally active NSCC (bINSCC) suggests that TRPM4 and specific TRPC heteromultimer combinations may underlie the three single-channel conductances of bINSCC. In conclusion, these findings suggest that basally activated NSCC contribute to the RMP in human and monkey colonic SMC and therefore may play an important role in determining basal excitability of colonic smooth muscle. PMID:21566016

[How to integrate humanization and technology in nursing training].

PubMed

Meyer, Dagmar Estermann

2002-01-01

This paper discusses the current incorporation of the subject of humanization of care in the current context of Brazilian nursing. The relation between nursing and technology is approached, in this study, from a historical perspective. The study also develops the proposition of "human re-signification", having as reference the concept of Cyborg, considering the way this concept has been employed in the contemporary cultural and feminist theoretical framework.

A Novel Yeast Genomics Method for Identifying New Breast Cancer Susceptibility Genes

DTIC Science & Technology

2007-05-01

find new candidate genes for breast cancer susceptibility in women and identifying these human genes can further improve monitoring and treatment...breast cancer susceptibility genes in humans that are currently unknown and not deducible from current methodologies. It is a fundamental...template to faithfully repair the broken strand. In human cancer it is loss of HR, rather than NHEJ, that is more important in increasing cancer

Effect of Human Model Height and Sex on Induced Current Dosimetry in Household Induction Heater Users

NASA Astrophysics Data System (ADS)

Tarao, Hiroo; Hayashi, Noriyuki; Isaka, Katsuo

Induced currents in the high-resolution, anatomical human models are numerically calculated by the impedance method. The human models are supposed to be exposed to highly inhomogeneous 20.9 kHz magnetic fields from a household induction heater (IH). In the case of the adult models, the currents ranging from 5 to 19 mA/m2 are induced for between the shoulder and lower abdomen. Meanwhile, in the case of the child models, the currents ranging from 5 to 21 mA/m2 are induced for between the head and abdomen. In particular, the induced currents near the brain tissue are almost the same as those near the abdomen. When the induced currents in the central nervous system tissues are considered, the induced currents in the child model are 2.1 to 6.9 times as large as those in the adult model under the same B-field exposure environment. These results suggest the importance of further investigation intended for a pregnant female who uses the IH as well as for a child (or the IH users of small standing height).

The Case for the Humanities.

ERIC Educational Resources Information Center

Cary, Michael S.

1981-01-01

Describes the current impoverishment of the humanities and the gulf separating the humanities from the sciences. Discusses the need for adequate humanities instruction at the elementary-secondary level. Suggests that humanities teachers rediscover the Italian Renaissance spirit to improve their teaching. (SB)

Issues around radiological protection of the environment and its integration with protection of humans: promoting debate on the way forward.

PubMed

Brownless, G P

2007-12-01

This paper explores issues to consider around integrating direct, explicit protection of the environment into the current system of radiological protection, which is focused on the protection of humans. Many issues around environmental radiological protection have been discussed, and ready-to-use toolboxes have been constructed for assessing harm to non-human biota, but it is not clear how (or even if) these should be fitted into the current system of protection. Starting from the position that the current approach to protecting the environment (namely that it follows from adequately protecting humans) is generally effective, this paper considers how explicit radiological protection of the environment can be integrated with the current system, through developing a 'worked example' of how this could be done and highlighting issues peculiar to protection of the environment. The aim of the paper is to promote debate on this topic, with the ultimate aim of ensuring that any changes to the system are consensual and robust.

Fate of egg proteins during the development of Columba livia domestica embryo.

PubMed

Shbailat, Seba Jamal; Aslan, Ibtisam Omar

2018-01-01

The transfer of egg white into the yolk and consumption of yolk proteins by the embryo are largely unexplored in the pigeon Columba livia domestica. Here, we investigated the route of egg white transfer as well as the degradation and uptake of yolk proteins by the pigeon embryo. Initially, we tested the electrophoretic patterns of proteins in different egg compartments throughout development. Then, we used lysozyme as a reference protein to follow the egg white transfer, and we measured its activity using Micrococcus lysodeikticus as a substrate. Moreover, we determined the general protease activity during different developmental stages in the yolk using casein. Finally, we examined the expression of aminopeptidase-N (APN) and oligopeptide transporter PepT1 genes in the yolk sac membrane (YSM) from incubation day 8 until day 17. Several electrophoretic bands of presumptive egg white proteins appeared in different egg compartments. Also, lysozyme activity was detected chronologically in the egg compartments. It appeared on day 12 in the amniotic and intestinal fluids and on day 14 in the yolk. Moreover, protease activity in the yolk increased significantly on day 14 and thereafter. APN expression was largest on day 8 and reduced generally afterward, whereas PepT1 expression peaked between days 13 and 15 but then reduced substantially. Our results suggest that the egg white proteins move through the amnion and intestine into the yolk where they undergo degradation by the activated proteases. Furthermore, the YSM appears to have a role in protein consumption, and this role decreases toward hatch. © 2018 Wiley Periodicals, Inc.

Retinoic Acid Engineered Amniotic Membrane Used as Graft or Homogenate: Positive Effects on Corneal Alkali Burns.

PubMed

Joubert, Romain; Daniel, Estelle; Bonnin, Nicolas; Comptour, Aurélie; Gross, Christelle; Belville, Corinne; Chiambaretta, Frédéric; Blanchon, Loïc; Sapin, Vincent

2017-07-01

Alkali burns are the most common, severe chemical ocular injuries, their functional prognosis depending on corneal wound healing efficiency. The purpose of our study was to compare the benefits of amniotic membrane (AM) grafts and homogenates for wound healing in the presence or absence of previous all-trans retinoic acid (atRA) treatment. Fifty male CD1 mice with reproducible corneal chemical burn were divided into five groups, as follows: group 1 was treated with saline solution; groups 2 and 3 received untreated AM grafts or grafts treated with atRA, respectively; and groups 4 and 5 received untreated AM homogenates or homogenates treated with atRA, respectively. After 7 days of treatment, ulcer area and depth were measured, and vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP-9) were quantified. AM induction by atRA was confirmed via quantification of retinoic acid receptor β (RARβ), a well-established retinoic acid-induced gene. Significant improvements of corneal wound healing in terms of ulcer area and depth were obtained with both strategies. No major differences were found between the efficiency of AM homogenates and grafts. This positive action was increased when AM was pretreated with atRA. Furthermore, AM induced a decrease in VEGF and MMP-9 levels during the wound healing process. The atRA treatment led to an even greater decrease in the expression of both proteins. Amnion homogenate is as effective as AM grafts in promoting corneal wound healing in a mouse model. A higher positive effect was obtained with atRA treatment.

Regulation of amniotic fluid volume: mathematical model based on intramembranous transport mechanisms.

PubMed

Brace, Robert A; Anderson, Debra F; Cheung, Cecilia Y

2014-11-15

Experimentation in late-gestation fetal sheep has suggested that regulation of amniotic fluid (AF) volume occurs primarily by modulating the rate of intramembranous transport of water and solutes across the amnion into underlying fetal blood vessels. In order to gain insight into intramembranous transport mechanisms, we developed a computer model that allows simulation of experimentally measured changes in AF volume and composition over time. The model included fetal urine excretion and lung liquid secretion as inflows into the amniotic compartment plus fetal swallowing and intramembranous absorption as outflows. By using experimental flows and solute concentrations for urine, lung liquid, and swallowed fluid in combination with the passive and active transport mechanisms of the intramembranous pathway, we simulated AF responses to basal conditions, intra-amniotic fluid infusions, fetal intravascular infusions, urine replacement, and tracheoesophageal occlusion. The experimental data are consistent with four intramembranous transport mechanisms acting in concert: 1) an active unidirectional bulk transport of AF with all dissolved solutes out of AF into fetal blood presumably by vesicles; 2) passive bidirectional diffusion of solutes, such as sodium and chloride, between fetal blood and AF; 3) passive bidirectional water movement between AF and fetal blood; and 4) unidirectional transport of lactate into the AF. Further, only unidirectional bulk transport is dynamically regulated. The simulations also identified areas for future study: 1) identifying intramembranous stimulators and inhibitors, 2) determining the semipermeability characteristics of the intramembranous pathway, and 3) characterizing the vesicles that are the primary mediators of intramembranous transport. Copyright © 2014 the American Physiological Society.

Dystocia following prolonged retention of a dead fetus in an Asian elephant (Elephas maximus).

PubMed

Thitaram, Chatchote; Pongsopawijit, Pornsawan; Thongtip, Nikorn; Angkavanich, Taweepoke; Chansittivej, Sarun; Wongkalasin, Waroot; Somgird, Chalermchart; Suwankong, Niyada; Prachsilpchai, Worapat; Suchit, Kittiphat; Clausen, Bjarne; Boonthong, Pinich; Nimtrakul, Kannika; Niponkit, Charawee; Siritepsongklod, Somchai; Roongsri, Ronnachit; Mahasavankul, Sittidet

2006-09-15

A 32-year-old nulliparous female Asian elephant (Elephas maximus) showed signs of parturition 8 months later than predicted from the breeding records. However, while serosanguineous fluid, necrotic tissue and pieces of amnion were expelled, second-stage labor did not progress. Since the fetus was not found during an endoscopic examination of the vestibule, it was assumed that the elephant had calved unseen and she was returned to the forest to recuperate. Twelve months later, the elephant showed clear signs of second-stage labor accompanied by a bulge in the perineum and passage of keratinized nail through the vulva. A 35 cm episiotomy incision was made in the perineum just below the anus, via which chains were attached to the forelimbs of the fetus. Traction on the forelimbs alone proved insufficient to achieve delivery because the fetal head kept rotating and impacting in the pelvis. However, traction applied via a hook inserted behind the mandibular symphysis allowed the head to be elevated and extended, and the fetus to be delivered. The episiotomy wound was sutured in two layers and although the skin did not heal during primary closure it subsequently healed uneventfully by second intention. Retrospective evaluation of the elephant's serum progestagens profile demonstrated a fall to baseline at the suspected onset of parturition, supporting the supposition that the fetus was retained in the uterus for 12 months after parturition began. It is suggested that serum progestagens concentrations should be monitored regularly in mated elephant cows to verify the establishment of pregnancy and to better estimate the expected timing, and the onset of calving.

Synthesis of a smart pH-responsive magnetic nanocomposite as high loading carrier of pharmaceutical agents.

PubMed

Berah, Razieh; Ghorbani, Mohsen; Moghadamnia, Ali Akbar

2017-06-01

To create facile external controlled drug delivery system, a magnetic porous carrier based on Tin oxide nanoparticles was synthesized by an inexpensive and versatile hydrothermal strategy and used for in-vitro process. Magnetic nanocomposites were qualified by Fourier Transform Infrared (FTIR), Scanning Electron Microscopy (SEM), X-Ray Diffraction (XRD), Vibrational Sample Magnetometer (VSM) and Transmission Electron Microscopy (TEM). Results showed that nanoparticles were synthesized successfully with good dispersion of magnetic nanoparticles in cavity, uniform particle size distribution with average size of 65nm and high magnetization of 33.75 emu/mg. Furthermore, the nano-porosity and magnetism allowed high efficiency and remote controlled drug release. In this study, anti-migraine Sumatriptan was used as drug sample and the effect of drug concentration, Fe/Sn ratio and loading time on drug absorption were investigated. The best result was checked for stability at body temperature and different body pH. The sample with drug concentration of 0.25(mg/ml), Fe/Sn=0.22 and loading time of 1.5h had the highest drug efficiency (70%). Finally, in order to simulate the in vivo process for in-vitro step, Amnion was used and drug diffusion rate was measured in different intervals and different pH values. The result illustrated that after 25h, diffusion reached 65% at pH=2 and 56% at pH=7, and then became constant. Based on the above mentioned results, the carrier has an acceptable in vitro yield and therefore could be chosen for future in vivo researches. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparative gene expression analysis of Dtg, a novel target gene of Dpp signaling pathway in the early Drosophila melanogaster embryo.

PubMed

Hodar, Christian; Zuñiga, Alejandro; Pulgar, Rodrigo; Travisany, Dante; Chacon, Carlos; Pino, Michael; Maass, Alejandro; Cambiazo, Verónica

2014-02-10

In the early Drosophila melanogaster embryo, Dpp, a secreted molecule that belongs to the TGF-β superfamily of growth factors, activates a set of downstream genes to subdivide the dorsal region into amnioserosa and dorsal epidermis. Here, we examined the expression pattern and transcriptional regulation of Dtg, a new target gene of Dpp signaling pathway that is required for proper amnioserosa differentiation. We showed that the expression of Dtg was controlled by Dpp and characterized a 524-bp enhancer that mediated expression in the dorsal midline, as well as, in the differentiated amnioserosa in transgenic reporter embryos. This enhancer contained a highly conserved region of 48-bp in which bioinformatic predictions and in vitro assays identified three Mad binding motifs. Mutational analysis revealed that these three motifs were necessary for proper expression of a reporter gene in transgenic embryos, suggesting that short and highly conserved genomic sequences may be indicative of functional regulatory regions in D. melanogaster genes. Dtg orthologs were not detected in basal lineages of Dipterans, which unlike D. melanogaster develop two extra-embryonic membranes, amnion and serosa, nevertheless Dtg orthologs were identified in the transcriptome of Musca domestica, in which dorsal ectoderm patterning leads to the formation of a single extra-embryonic membrane. These results suggest that Dtg was recruited as a new component of the network that controls dorsal ectoderm patterning in the lineage leading to higher Cyclorrhaphan flies, such as D. melanogaster and M. domestica. Copyright © 2013 Elsevier B.V. All rights reserved.

Dispersive FDTD analysis of induced electric field in human models due to electrostatic discharge.

PubMed

Hirata, Akimasa; Nagai, Toshihiro; Koyama, Teruyoshi; Hattori, Junya; Chan, Kwok Hung; Kavet, Robert

2012-07-07

Contact currents flow from/into a charged human body when touching a grounded conductive object. An electrostatic discharge (ESD) or spark may occur just before contact or upon release. The current may stimulate muscles and peripheral nerves. In order to clarify the difference in the induced electric field between different sized human models, the in-situ electric fields were computed in anatomically based models of adults and a child for a contact current in a human body following ESD. A dispersive finite-difference time-domain method was used, in which biological tissue is assumed to obey a four-pole Debye model. From our computational results, the first peak of the discharge current was almost identical across adult and child models. The decay of the induced current in the child was also faster due mainly to its smaller body capacitance compared to the adult models. The induced electric fields in the forefingers were comparable across different models. However, the electric field induced in the arm of the child model was found to be greater than that in the adult models primarily because of its smaller cross-sectional area. The tendency for greater doses in the child has also been reported for power frequency sinusoidal contact current exposures as reported by other investigators.

Integrating autonomous distributed control into a human-centric C4ISR environment

NASA Astrophysics Data System (ADS)

Straub, Jeremy

2017-05-01

This paper considers incorporating autonomy into human-centric Command, Control, Communications, Computers, Intelligence, Surveillance and Reconnaissance (C4ISR) environments. Specifically, it focuses on identifying ways that current autonomy technologies can augment human control and the challenges presented by additive autonomy. Three approaches to this challenge are considered, stemming from prior work in two converging areas. In the first, the problem is approached as augmenting what humans currently do with automation. In the alternate approach, the problem is approached as treating humans as actors within a cyber-physical system-of-systems (stemming from robotic distributed computing). A third approach, combines elements of both of the aforementioned.

Debris Motion and Injury Relationships in All Hazard Environments

DTIC Science & Technology

1976-07-01

reaction, limit of voluntary tolerance, injury threshold, LD5 0 value, limit of survival, etc. Our current state of knowledge concerning human impact...of-the-art review of "Human Impact Tolerance" up to approximately August 1970. Snyder concludes that current knowledge on human tolerance to impact...children and adults, suicides, high divers, skiers etc. have occurred and are reported in the literature (Refs. 19, 20, 21). With the objective of

Modeling Sustainability: Population, Inequality, Consumption, and Bidirectional Coupling of the Earth and Human Systems

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

Motesharrei, Safa; Rivas, Jorge; Kalnay, Eugenia

Over the last two centuries, the impact of the Human System has grown dramatically, becoming strongly dominant within the Earth System in many different ways. Consumption, inequality, and population have increased extremely fast, especially since about 1950, threatening to overwhelm the many critical functions and ecosystems of the Earth System. Changes in the Earth System, in turn, have important feedback effects on the Human System, with costly and potentially serious consequences. However, current models do not incorporate these critical feedbacks. We argue that in order to understand the dynamics of either system, Earth System Models must be coupled with Humanmore » System Models through bidirectional couplings representing the positive, negative, and delayed feedbacks that exist in the real systems. In particular, key Human System variables, such as demographics, inequality, economic growth, and migration, are not coupled with the Earth System but are instead driven by exogenous estimates, such as United Nations population projections. This makes current models likely to miss important feedbacks in the real Earth–Human system, especially those that may result in unexpected or counterintuitive outcomes, and thus requiring different policy interventions from current models. The importance and imminence of sustainability challenges, the dominant role of the Human System in the Earth System, and the essential roles the Earth System plays for the Human System, all call for collaboration of natural scientists, social scientists, and engineers in multidisciplinary research and modeling to develop coupled Earth–Human system models for devising effective science-based policies and measures to benefit current and future generations.« less

In vitro exposure to 0.57-MHz electric currents exerts cytostatic effects in HepG2 human hepatocarcinoma cells.

PubMed

Hernández-Bule, María Luisa; Trillo, María Angeles; Cid, María Antonia; Leal, Jocelyne; Ubeda, Alejandro

2007-03-01

Capacitive-resistive electric transfer (CRET) therapy is a non-invasive technique currently applied to the treatment of skin, muscle and tendon injuries that uses 0.45-0.6 MHz electric currents to transdermically and focally increase the internal temperature of targeted tissues. Because CRET electrothermal treatment has been reported to be more effective than other thermal therapies, it has been proposed that the electric stimulus could induce responses in exposed tissues that are cooperative or synergic with the thermal effects of the treatment. Previous studies by our group, investigating the nature of the alleged electric response, have shown that short, repeated stimuli with 0.57-MHz currents at subthermal levels could provoke partial, cytotoxic effects on human neuroblastoma cells in vitro. The aim of the present study was to investigate the response from another human cell type, the human hepatocarcinoma HepG2 line, during and after the exposure to 0.57-MHz CRET currents at subthermal densities. The electric stimuli provoked a decrease in the proliferation rate of the cultures, possibly due to an electrically-induced blocking of the cell cycle in a fraction of the cellular population.

New Paradigms for Human-Robotic Collaboration During Human Planetary Exploration

NASA Astrophysics Data System (ADS)

Parrish, J. C.; Beaty, D. W.; Bleacher, J. E.

2017-02-01

Human exploration missions to other planetary bodies offer new paradigms for collaboration (control, interaction) between humans and robots beyond the methods currently used to control robots from Earth and robots in Earth orbit.

Current Ebola vaccines

PubMed Central

Hoenen, Thomas; Groseth, Allison; Feldmann, Heinz

2012-01-01

Introduction Ebolaviruses cause severe viral hemorrhagic fever in humans and non-human primates, with case fatality rates of up to 90%. Currently, neither a specific treatment nor a vaccine licensed for use in humans is available. However, a number of vaccine candidates have been developed in the last decade that are highly protective in non-human primates, the gold standard animal model for Ebola hemorrhagic fever. Areas covered This review analyzes a number of scenarios for the use of ebolavirus vaccines, discusses the requirements for ebolavirus vaccines in these scenarios, and describes current ebolavirus vaccines. Among these vaccines are recombinant Adenoviruses, recombinant Vesicular Stomatitis viruses, recombinant Human Parainfluenza viruses and virus-like particles. Interestingly, one of these vaccine platforms, based on recombinant Vesicular Stomatitis viruses, has also demonstrated post-exposure protection in non-human primates. Expert opinion The most pressing remaining challenge is now to move these vaccine candidates forward into human trials and towards licensure. In order to achieve this, it will be necessary to establish the mechanisms and correlates of protection for these vaccines, and to continue to demonstrate their safety, particularly in potentially immunocompromised populations. However, already now there is sufficient evidence that, from a scientific perspective, a vaccine protective against ebolaviruses is possible. PMID:22559078

CELLPEDIA: a repository for human cell information for cell studies and differentiation analyses.

PubMed

Hatano, Akiko; Chiba, Hirokazu; Moesa, Harry Amri; Taniguchi, Takeaki; Nagaie, Satoshi; Yamanegi, Koji; Takai-Igarashi, Takako; Tanaka, Hiroshi; Fujibuchi, Wataru

2011-01-01

CELLPEDIA is a repository database for current knowledge about human cells. It contains various types of information, such as cell morphologies, gene expression and literature references. The major role of CELLPEDIA is to provide a digital dictionary of human cells for the biomedical field, including support for the characterization of artificially generated cells in regenerative medicine. CELLPEDIA features (i) its own cell classification scheme, in which whole human cells are classified by their physical locations in addition to conventional taxonomy; and (ii) cell differentiation pathways compiled from biomedical textbooks and journal papers. Currently, human differentiated cells and stem cells are classified into 2260 and 66 cell taxonomy keys, respectively, from which 934 parent-child relationships reported in cell differentiation or transdifferentiation pathways are retrievable. As far as we know, this is the first attempt to develop a digital cell bank to function as a public resource for the accumulation of current knowledge about human cells. The CELLPEDIA homepage is freely accessible except for the data submission pages that require authentication (please send a password request to cell-info@cbrc.jp). Database URL: http://cellpedia.cbrc.jp/

Human and biophysical legacies shape contemporary urban forests: A literature synthesis

Treesearch

Lara A. Roman; Hamil Pearsall; Theodore S. Eisenman; Tenley M. Conway; Robert T. Fahey; Shawn Landry; Jess Vogt; Natalie S. van Doorn; J. Morgan Grove; Dexter H. Locke; Adrina C. Bardekjian; John J. Battles; Mary L. Cadenasso; Cecil C. Konijnendijk van den Bosch; Meghan Avolio; Adam Berland; G. Darrel Jenerette; Sarah K. Mincey; Diane E. Pataki; Christina Staudhammer

2018-01-01

Understanding how urban forests developed their current patterns of tree canopy cover, species composition, and diversity requires an appreciation of historical legacy effects. However, analyses of current urban forest characteristics are often limited to contemporary socioeconomic factors, overlooking the role of history. The institutions, human communities, and...

21 CFR 113.5 - Current good manufacturing practice.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Current good manufacturing practice. 113.5 Section 113.5 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION THERMALLY PROCESSED LOW-ACID FOODS PACKAGED IN HERMETICALLY SEALED...

21 CFR 113.5 - Current good manufacturing practice.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 2 2013-04-01 2013-04-01 false Current good manufacturing practice. 113.5 Section 113.5 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION THERMALLY PROCESSED LOW-ACID FOODS PACKAGED IN HERMETICALLY SEALED...

21 CFR 113.5 - Current good manufacturing practice.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 2 2012-04-01 2012-04-01 false Current good manufacturing practice. 113.5 Section 113.5 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION THERMALLY PROCESSED LOW-ACID FOODS PACKAGED IN HERMETICALLY SEALED...

21 CFR 113.5 - Current good manufacturing practice.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 2 2014-04-01 2014-04-01 false Current good manufacturing practice. 113.5 Section 113.5 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION THERMALLY PROCESSED LOW-ACID FOODS PACKAGED IN HERMETICALLY SEALED...

21 CFR 1271.150 - Current good tissue practice requirements.

Code of Federal Regulations, 2011 CFR

2011-04-01

....150 Section 1271.150 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... HUMAN CELLS, TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS Current Good Tissue Practice § 1271.150... implemented for reproductive HCT/Ps described in § 1271.10 and regulated solely under section 361 of the...

21 CFR 1271.150 - Current good tissue practice requirements.

Code of Federal Regulations, 2012 CFR

2012-04-01

....150 Section 1271.150 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... HUMAN CELLS, TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS Current Good Tissue Practice § 1271.150... implemented for reproductive HCT/Ps described in § 1271.10 and regulated solely under section 361 of the...

21 CFR 1271.150 - Current good tissue practice requirements.

Code of Federal Regulations, 2013 CFR

2013-04-01

....150 Section 1271.150 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... HUMAN CELLS, TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS Current Good Tissue Practice § 1271.150... implemented for reproductive HCT/Ps described in § 1271.10 and regulated solely under section 361 of the...

21 CFR 1271.150 - Current good tissue practice requirements.

Code of Federal Regulations, 2014 CFR

2014-04-01

....150 Section 1271.150 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... HUMAN CELLS, TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS Current Good Tissue Practice § 1271.150... implemented for reproductive HCT/Ps described in § 1271.10 and regulated solely under section 361 of the...

21 CFR 120.5 - Current good manufacturing practice.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Current good manufacturing practice. 120.5 Section 120.5 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION HAZARD ANALYSIS AND CRITICAL CONTROL POINT (HACCP) SYSTEMS General...

21 CFR 120.5 - Current good manufacturing practice.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 2 2013-04-01 2013-04-01 false Current good manufacturing practice. 120.5 Section 120.5 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION HAZARD ANALYSIS AND CRITICAL CONTROL POINT (HACCP) SYSTEMS General...

21 CFR 120.5 - Current good manufacturing practice.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 2 2012-04-01 2012-04-01 false Current good manufacturing practice. 120.5 Section 120.5 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION HAZARD ANALYSIS AND CRITICAL CONTROL POINT (HACCP) SYSTEMS General...

21 CFR 120.5 - Current good manufacturing practice.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Current good manufacturing practice. 120.5 Section 120.5 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION HAZARD ANALYSIS AND CRITICAL CONTROL POINT (HACCP) SYSTEMS General...

21 CFR 120.5 - Current good manufacturing practice.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 2 2014-04-01 2014-04-01 false Current good manufacturing practice. 120.5 Section 120.5 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION HAZARD ANALYSIS AND CRITICAL CONTROL POINT (HACCP) SYSTEMS General...

Managing the HRD Function. Symposium 32. [AHRD Conference, 2001].

ERIC Educational Resources Information Center

2001

This document contains three papers on managing the human resource development (HRD) function. "The Relationship between Factors Impacted by the Current Economic Crisis and Human Resource Development Roles and Functions in Thailand" (Chiraprapha Tan Akaraborworn, Gary N. McLean) presents data indicating that the current economic crisis…

Sodium leak channel, non-selective contributes to the leak current in human myometrial smooth muscle cells from pregnant women.

PubMed

Reinl, Erin L; Cabeza, Rafael; Gregory, Ismail A; Cahill, Alison G; England, Sarah K

2015-10-01

Uterine contractions are tightly regulated by the electrical activity of myometrial smooth muscle cells (MSMCs). These cells require a depolarizing current to initiate Ca(2+) influx and induce contraction. Cationic leak channels, which permit a steady flow of cations into a cell, are known to cause membrane depolarization in many tissue types. Previously, a Gd(3+)-sensitive, Na(+)-dependent leak current was identified in the rat myometrium, but the presence of such a current in human MSMCs and the specific ion channel conducting this current was unknown. Here, we report the presence of a Na(+)-dependent leak current in human myometrium and demonstrate that the Na(+)-leak channel, NALCN, contributes to this current. We performed whole-cell voltage-clamp on fresh and cultured MSMCs from uterine biopsies of term, non-laboring women and isolated the leak currents by using Ca(2+) and K(+) channel blockers in the bath solution. Ohmic leak currents were identified in freshly isolated and cultured MSMCs with normalized conductances of 14.6 pS/pF and 10.0 pS/pF, respectively. The myometrial leak current was significantly reduced (P < 0.01) by treating cells with 10 μM Gd(3+) or by superfusing the cells with a Na(+)-free extracellular solution. Reverse transcriptase PCR and immunoblot analysis of uterine biopsies from term, non-laboring women revealed NALCN messenger RNA and protein expression in the myometrium. Notably, ∼90% knockdown of NALCN protein expression with lentivirus-delivered shRNA reduced the Gd(3+)-sensitive leak current density by 42% (P < 0.05). Our results reveal that NALCN, in part, generates the leak current in MSMCs and provide the basis for future research assessing NALCN as a potential molecular target for modulating uterine excitability. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

[Current problems in the data acquisition of digitized virtual human and the countermeasures].

PubMed

Zhong, Shi-zhen; Yuan, Lin

2003-06-01

As a relatively new field of medical science research that has attracted the attention from worldwide researchers, study of digitized virtual human still awaits long-term dedicated effort for its full development. In the full array of research projects of the integrated Virtual Chinese Human project, virtual visible human, virtual physical human, virtual physiome, and intellectualized virtual human must be included as the four essential constitutional opponents. The primary importance should be given to solving the problems concerning the data acquisition for the dataset of this immense project. Currently 9 virtual human datasets have been established worldwide, which are subjected to critical analyses in the paper with special attention given to the problems in the data storage and the techniques employed, for instance, in these datasets. On the basis of current research status of Virtual Chinese Human project, the authors propose some countermeasures for solving the problems in the data acquisition for the dataset, which include (1) giving the priority to the quality control instead of merely racing for quantity and speed, and (2) improving the setting up of the markers specific for the tissues and organs to meet the requirement from information technology, (3) with also attention to the development potential of the dataset which should have explicit pertinence to specific actual applications.

Aquinas's account of human embryogenesis and recent interpretations.

PubMed

Eberl, Jason T

2005-08-01

In addressing bioethical issues at the beginning of human life, such as abortion, in vitro fertilization, and embryonic stem cell research, one primary concern regards establishing when a developing human embryo or fetus can be considered a person. Thomas Aquinas argues that an embryo or fetus is not a human person until its body is informed by a rational soul. Aquinas's explicit account of human embryogenesis has been generally rejected by contemporary scholars due to its dependence upon medieval biological data, which has been far surpassed by current scientific research. A number of scholars, however, have attempted to combine Aquinas's basic metaphysical account of human nature with current embryological data to develop a contemporary Thomistic account of a human person's beginning. In this article, I discuss two recent interpretations in which it is argued that a human person does not begin to exist until a fetus has developed a functioning cerebral cortex.

Inter-professional collaboration as a health human resources strategy: moving forward with a western provinces research agenda.

PubMed

Mickelson, Grace; Suter, Esther; Deutschlander, Siegrid; Bainbridge, Lesley; Harrison, Liz; Grymonpre, Ruby; Hepp, Shelanne

2012-01-01

The current gap in research on inter-professional collaboration and health human resources outcomes is explored by the Western Canadian Interprofessional Health Collaborative (WCIHC). In a recent research planning workshop with the four western provinces, 82 stakeholders from various sectors including health, provincial governments, research and education engaged with WCIHC to consider aligning their respective research agendas relevant to inter-professional collaboration and health human resources. Key research recommendations from a recent knowledge synthesis on inter-professional collaboration and health human resources as well as current provincial health priorities framed the discussions at the workshop. This knowledge exchange has helped to consolidate a shared current understanding of inter-professional education and practice and health workforce planning and management among the participating stakeholders. Ultimately, through a focused research program, a well-aligned approach between sectors to finding health human resources solutions will result in sustainable health systems reform. Copyright © 2013 Longwoods Publishing.

Man’s best friend: what can pet dogs teach us about non-Hodgkin lymphoma?

PubMed Central

Richards, Kristy L.; Suter, Steven E.

2014-01-01

Summary Animal models are essential for understanding lymphoma biology and testing new treatments prior to human studies. Spontaneously arising lymphomas in pet dogs represent an underutilized resource that could be used to complement current mouse lymphoma models, which do not adequately represent all aspects of the human disease. Canine lymphoma resembles human lymphoma in many important ways, including characteristic translocations and molecular abnormalities and similar therapeutic responses to chemotherapy, radiation, and newer targeted therapies (e.g. ibrutinib). Given the large number of pet dogs and high incidence of lymphoma, particularly in susceptible breeds, dogs represent a largely untapped resource for advancing the understanding and treatment of human lymphoma. This review highlights similarities in molecular biology, diagnosis, treatment, and outcomes between human and canine lymphoma. It also describes resources that are currently available to study canine lymphoma, advantages to be gained by exploiting the genetic breed structure in dogs, and current and future challenges and opportunities to take full advantage of this resource for lymphoma studies. PMID:25510277

Achieving competitive advantage through strategic human resource management.

PubMed

Fottler, M D; Phillips, R L; Blair, J D; Duran, C A

1990-01-01

The framework presented here challenges health care executives to manage human resources strategically as an integral part of the strategic planning process. Health care executives should consciously formulate human resource strategies and practices that are linked to and reinforce the broader strategic posture of the organization. This article provides a framework for (1) determining and focusing on desired strategic outcomes, (2) identifying and implementing essential human resource management actions, and (3) maintaining or enhancing competitive advantage. The strategic approach to human resource management includes assessing the organization's environment and mission; formulating the organization's business strategy; assessing the human resources requirements based on the intended strategy; comparing the current inventory of human resources in terms of numbers, characteristics, and human resource management practices with respect to the strategic requirements of the organization and its services or product lines; formulating the human resource strategy based on the differences between the assessed requirements and the current inventory; and implementing the appropriate human resource practices to reinforce the strategy and attain competitive advantage.

New perspectives on evolutionary medicine: the relevance of microevolution for human health and disease.

PubMed

Rühli, Frank Jakobus; Henneberg, Maciej

2013-04-29

Evolutionary medicine (EM) is a growing field focusing on the evolutionary basis of human diseases and their changes through time. To date, the majority of EM studies have used pure theories of hominin macroevolution to explain the present-day state of human health. Here, we propose a different approach by addressing more empirical and health-oriented research concerning past, current and future microevolutionary changes of human structure, functions and pathologies. Studying generation-to-generation changes of human morphology that occurred in historical times, and still occur in present-day populations under the forces of evolution, helps to explain medical conditions and warns clinicians that their current practices may influence future humans. Also, analyzing historic tissue specimens such as mummies is crucial in order to address the molecular evolution of pathogens, of the human genome, and their coadaptations.

Using an instrumented manikin for Space Station Freedom analysis

NASA Technical Reports Server (NTRS)

Orr, Linda; Hill, Richard

1989-01-01

One of the most intriguing and complex areas of current computer graphics research is animating human figures to behave in a realistic manner. Believable, accurate human models are desirable for many everyday uses including industrial and architectural design, medical applications, and human factors evaluations. For zero-gravity (0-g) spacecraft design and mission planning scenarios, they are particularly valuable since 0-g conditions are difficult to simulate in a one-gravity Earth environment. At NASA/JSC, an in-house human modeling package called PLAID is currently being used to produce animations for human factors evaluation of Space Station Freedom design issues. Presented here is an introductory background discussion of problems encountered in existing techniques for animating human models and how an instrumented manikin can help improve the realism of these models.

Social Bots: Human-Like by Means of Human Control?

PubMed

Grimme, Christian; Preuss, Mike; Adam, Lena; Trautmann, Heike

2017-12-01

Social bots are currently regarded an influential but also somewhat mysterious factor in public discourse and opinion making. They are considered to be capable of massively distributing propaganda in social and online media, and their application is even suspected to be partly responsible for recent election results. Astonishingly, the term social bot is not well defined and different scientific disciplines use divergent definitions. This work starts with a balanced definition attempt, before providing an overview of how social bots actually work (taking the example of Twitter) and what their current technical limitations are. Despite recent research progress in Deep Learning and Big Data, there are many activities bots cannot handle well. We then discuss how bot capabilities can be extended and controlled by integrating humans into the process and reason that this is currently the most promising way to realize meaningful interactions with other humans. This finally leads to the conclusion that hybridization is a challenge for current detection mechanisms and has to be handled with more sophisticated approaches to identify political propaganda distributed with social bots.

Scaling a Human Body Finite Element Model with Radial Basis Function Interpolation

DTIC Science & Technology

Human body models are currently used to evaluate the body’s response to a variety of threats to the Soldier. The ability to adjust the size of human...body models is currently limited because of the complex shape changes that are required. Here, a radial basis function interpolation method is used to...morph the shape on an existing finite element mesh. Tools are developed and integrated into the Blender computer graphics software to assist with

Mesenchymal Stem Cells for Osteochondral Tissue Engineering

PubMed Central

Ng, Johnathan; Bernhard, Jonathan; Vunjak-Novakovic, Gordana

2017-01-01

Summary Mesenchymal stem cells (MSC) are of major interest to regenerative medicine, because of the ease of harvesting from a variety of sources (including bone marrow and fat aspirates) and ability to form a range of mesenchymal tissues, in vitro and in vivo. We focus here on the use of MSCs for engineering of cartilage, bone, and complex osteochondral tissue constructs, using protocols that replicate some aspects of the natural mesodermal development. For engineering of human bone, we discuss some of the current advances, and highlight the use of perfusion bioreactors for supporting anatomically exact human bone grafts. For engineering of human cartilage, we discuss limitations of current approaches, and highlight engineering of stratified, mechanically functional human cartilage interfaced with bone by mesenchymal condensation of MSCs. Taken together, the current advances enable engineering physiologically relevant bone, cartilage and osteochondral composites, and physiologically relevant studies of osteochondral development and disease. PMID:27236665

Parabens and their effects on the endocrine system.

PubMed

Nowak, Karolina; Ratajczak-Wrona, Wioletta; Górska, Maria; Jabłońska, Ewa

2018-03-27

Preservatives (ingredients which inhibit growth of microorganisms) are used to prolong shelf life of various foods, cosmetics, and pharmaceutical products. Parabens are one of the most popular preservatives used in the aforementioned products and is currently being used worldwide. Parabens are easily absorbed by the human body. Thus, it is important to discuss about their safety with respect to human physiology. In view of the current literature, which classifies parabens as a group of endocrine disrupting chemicals (EDCs), it seems that the precise assessment of their influence on the human endocrine system is particularly important. Disruption of the endocrine homoeostasis might lead to multidirectional implications causing disruption of fitness and functions of the body. Therefore, in this review article, we aimed to summarize the current literature on properties, occurrence, and metabolism of parabens as well as to present recent progress in knowledge about their influence on the human endocrine system. Copyright © 2018 Elsevier B.V. All rights reserved.

Genistein and tyrphostin AG556 decrease ultra-rapidly activating delayed rectifier K+ current of human atria by inhibiting EGF receptor tyrosine kinase.

PubMed

Xiao, Guo-Sheng; Zhang, Yan-Hui; Wu, Wei; Sun, Hai-Ying; Wang, Yan; Li, Gui-Rong

2017-03-01

The ultra-rapidly activating delayed rectifier K + current I Kur (encoded by K v 1.5 or KCNA5) plays an important role in human atrial repolarization. The present study investigates the regulation of this current by protein tyrosine kinases (PTKs). Whole-cell patch voltage clamp technique and immunoprecipitation and Western blotting analysis were used to investigate whether the PTK inhibitors genistein, tyrphostin AG556 (AG556) and PP2 regulate human atrial I Kur and hKv1.5 channels stably expressed in HEK 293 cells. Human atrial I Kur was decreased by genistein (a broad-spectrum PTK inhibitor) and AG556 (a highly selective EGFR TK inhibitor) in a concentration-dependent manner. Inhibition of I Kur induced by 30 μM genistein or 10 μM AG556 was significantly reversed by 1 mM orthovanadate (a protein tyrosine phosphatase inhibitor). Similar results were observed in HEK 293 cells stably expressing hK v 1.5 channels. On the other hand, the Src family kinase inhibitor PP2 (1 μM) slightly enhanced I Kur and hK v 1.5 current, and the current increase was also reversed by orthovanadate. Immunoprecipitation and Western blotting analysis showed that genistein, AG556, and PP2 decreased tyrosine phosphorylation of hK v 1.5 channels and that the decrease was countered by orthovanadate. The PTK inhibitors genistein and AG556 decrease human atrial I Kur and cloned hK v 1.5 channels by inhibiting EGFR TK, whereas the Src kinase inhibitor PP2 increases I Kur and hK v 1.5 current. These results imply that EGFR TK and the soluble Src kinases may have opposite effects on human atrial I Kur . © 2017 The British Pharmacological Society.

Block of Na(+)/Ca(2+) exchanger by SEA0400 in human right atrial preparations from patients in sinus rhythm and in atrial fibrillation.

PubMed

Christ, Torsten; Kovács, Peter P; Acsai, Karoly; Knaut, Michael; Eschenhagen, Thomas; Jost, Norbert; Varró, András; Wettwer, Erich; Ravens, Ursula

2016-10-05

The Na(+)/Ca(2+) exchanger (NCX) plays a major role in myocardial Ca(2+) homoeostasis, but is also considered to contribute to the electrical instability and contractile dysfunction in chronic atrial fibrillation (AF). Here we have investigated the effects of the selective NCX blocker SEA0400 in human right atrial cardiomyocytes from patients in sinus rhythm (SR) and AF in order to obtain electrophysiological evidence for putative antiarrhythmic activity of this new class of drugs. Action potentials were measured in right atrial trabeculae using conventional microelectrodes. Human myocytes were enzymatically isolated. Rat atrial and ventricular cardiomyocytes were used for comparison. Using perforated-patch, NCX was measured as Ni(2+)-sensitive current during ramp pulses. In ruptured-patch experiments, NCX current was activated by changing the extracellular Ca(2+) concentration from 0 to 1mM in Na(+)-free bath solution (100mM Na(+) intracellular, "Hilgemann protocol"). Although SEA0400 was effective in rat cardiomyocytes, 10µM did not influence action potentials and contractility, neither in SR nor AF. SEA0400 (10μM) also failed to affect human atrial NCX current measured with perforated patch. With the "Hilgemann protocol" SEA0400 concentration-dependently suppressed human atrial NCX current, and its amplitude was larger in AF than in SR cardiomyocytes. Our results confirm higher NCX activity in AF than SR. SEA0400 fails to block Ni(2+)-sensitive current in human atrial cells unless unphysiological conditions are used. We speculate that block of NCX with SEA0400 depends on intracellular Na(+) concentration. Copyright © 2016 Elsevier B.V. All rights reserved.

Development of a head-phantom and measurement setup for lightning effects.

PubMed

Machts, Rene; Hunold, Alexander; Leu, Carsten; Haueisen, Jens; Rock, Michael

2016-08-01

Direct lightning strikes to human heads lead to various effects ranging from Lichtenberg figures, over loss of consciousness to death. The evolution of the induced current distribution in the head is of great interest to understand the effect mechanisms. This work describes a technique to model a simplified head-phantom to investigate effects during direct lightning strike. The head-phantom geometry, conductive and dielectric parameters were chosen similar to that of a human head. Three layers (brain, skull, and scalp) were created for the phantom using agarose hydrogel doped with sodium chloride and carbon. The head-phantom was tested on two different impulse generators, which reproduce approximate lightning impulses. The effective current and the current distribution in each layer were analyzed. The biggest part of the current flowed through the brain layer, approx. 70 % in cases without external flashover. Approx. 23 % of the current flowed through skull layer and 6 % through the scalp layer. However, the current decreased within the head-phantom to almost zero after a complete flashover on the phantom occurred. The flashover formed faster with a higher impulse current level. Exposition time of current through the head decreases with a higher current level of the lightning impulse. This mechanism might explain the fact that people can survive a lightning strike. The experiments help to understand lightning effects on humans.

PROOF OF CONCEPT FOR A HUMAN RELIABILITY ANALYSIS METHOD FOR HEURISTIC USABILITY EVALUATION OF SOFTWARE

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

Ronald L. Boring; David I. Gertman; Jeffrey C. Joe

2005-09-01

An ongoing issue within human-computer interaction (HCI) is the need for simplified or “discount” methods. The current economic slowdown has necessitated innovative methods that are results driven and cost effective. The myriad methods of design and usability are currently being cost-justified, and new techniques are actively being explored that meet current budgets and needs. Recent efforts in human reliability analysis (HRA) are highlighted by the ten-year development of the Standardized Plant Analysis Risk HRA (SPAR-H) method. The SPAR-H method has been used primarily for determining humancentered risk at nuclear power plants. The SPAR-H method, however, shares task analysis underpinnings withmore » HCI. Despite this methodological overlap, there is currently no HRA approach deployed in heuristic usability evaluation. This paper presents an extension of the existing SPAR-H method to be used as part of heuristic usability evaluation in HCI.« less

Human factors dimensions in the evolution of increasingly automated control rooms for near-earth satellites

NASA Technical Reports Server (NTRS)

Mitchell, C. M.

1982-01-01

The NASA-Goddard Space Flight Center is responsible for the control and ground support for all of NASA's unmanned near-earth satellites. Traditionally, each satellite had its own dedicated mission operations room. In the mid-seventies, an integration of some of these dedicated facilities was begun with the primary objective to reduce costs. In this connection, the Multi-Satellite Operations Control Center (MSOCC) was designed. MSOCC represents currently a labor intensive operation. Recently, Goddard has become increasingly aware of human factors and human-machine interface issues. A summary is provided of some of the attempts to apply human factors considerations in the design of command and control environments. Current and future activities with respect to human factors and systems design are discussed, giving attention to the allocation of tasks between human and computer, and the interface for the human-computer dialogue.

HEDD: Human Enhancer Disease Database

PubMed Central

Wang, Zhen; Zhang, Quanwei; Zhang, Wen; Lin, Jhih-Rong; Cai, Ying; Mitra, Joydeep

2018-01-01

Abstract Enhancers, as specialized genomic cis-regulatory elements, activate transcription of their target genes and play an important role in pathogenesis of many human complex diseases. Despite recent systematic identification of them in the human genome, currently there is an urgent need for comprehensive annotation databases of human enhancers with a focus on their disease connections. In response, we built the Human Enhancer Disease Database (HEDD) to facilitate studies of enhancers and their potential roles in human complex diseases. HEDD currently provides comprehensive genomic information for ∼2.8 million human enhancers identified by ENCODE, FANTOM5 and RoadMap with disease association scores based on enhancer–gene and gene–disease connections. It also provides Web-based analytical tools to visualize enhancer networks and score enhancers given a set of selected genes in a specific gene network. HEDD is freely accessible at http://zdzlab.einstein.yu.edu/1/hedd.php. PMID:29077884

New perspectives on evolutionary medicine: the relevance of microevolution for human health and disease

PubMed Central

2013-01-01

Evolutionary medicine (EM) is a growing field focusing on the evolutionary basis of human diseases and their changes through time. To date, the majority of EM studies have used pure theories of hominin macroevolution to explain the present-day state of human health. Here, we propose a different approach by addressing more empirical and health-oriented research concerning past, current and future microevolutionary changes of human structure, functions and pathologies. Studying generation-to-generation changes of human morphology that occurred in historical times, and still occur in present-day populations under the forces of evolution, helps to explain medical conditions and warns clinicians that their current practices may influence future humans. Also, analyzing historic tissue specimens such as mummies is crucial in order to address the molecular evolution of pathogens, of the human genome, and their coadaptations. PMID:23627943

Effects of a 3D segmental prosthetic system for tricuspid valve annulus remodelling on the right coronary artery: a human cadaveric coronary angiography study.

PubMed

Riki-Marishani, Mohsen; Gholoobi, Arash; Sazegar, Ghasem; Aazami, Mathias H; Hedjazi, Aria; Sajjadian, Maryam; Ebrahimi, Mahmoud; Aghaii-Zade Torabi, Ahmad

2017-09-01

A prosthetic system to repair secondary tricuspid valve regurgitation was developed. The conceptual engineering of the current device is based on 3D segmental remodelling of the tricuspid valve annulus in lieu of reductive annuloplasty. This study was designed to investigate the operational safety of the current prosthetic system with regard to the anatomical integrity of the right coronary artery (RCA) in fresh cadaveric human hearts. During the study period, from January to April 2016, the current prosthetic system was implanted on the tricuspid valve annulus in fresh cadaveric human hearts that met the study's inclusion criteria. The prepared specimens were investigated via selective coronary angiography of the RCA in the catheterization laboratory. The RCA angiographic anatomies were categorized as normal, distorted, kinked or occluded. Sixteen specimens underwent implantation of the current prosthetic system. The mean age of the cadaveric human hearts was 43.24 ± 15.79 years, with vehicle accident being the primary cause of death (59%). A dominant RCA was noticed in 62.5% of the specimens. None of the specimens displayed any injury, distortion, kinking or occlusion in the RCA due to the implantation of the prostheses. In light of the results of the present study, undertaken on fresh cadaveric human heart specimens, the current segmental prosthetic system for 3D remodelling of the tricuspid valve annulus seems to be safe vis-à-vis the anatomical integrity of the RCA. Further in vivo studies are needed to investigate the functional features of the current prosthetic system with a view to addressing the complex pathophysiology of secondary tricuspid valve regurgitation. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Human-induced pluripotent stem cell-derived cardiomyocytes from cardiac progenitor cells: effects of selective ion channel blockade.

PubMed

Altomare, Claudia; Pianezzi, Enea; Cervio, Elisabetta; Bolis, Sara; Biemmi, Vanessa; Benzoni, Patrizia; Camici, Giovanni G; Moccetti, Tiziano; Barile, Lucio; Vassalli, Giuseppe

2016-12-01

Human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes are likely to revolutionize electrophysiological approaches to arrhythmias. Recent evidence suggests the somatic cell origin of hiPSCs may influence their differentiation potential. Owing to their cardiomyogenic potential, cardiac-stromal progenitor cells (CPCs) are an interesting cellular source for generation of hiPSC-derived cardiomyocytes. The effect of ionic current blockade in hiPSC-derived cardiomyocytes generated from CPCs has not been characterized yet. Human-induced pluripotent stem cell-derived cardiomyocytes were generated from adult CPCs and skin fibroblasts from the same individuals. The effect of selective ionic current blockade on spontaneously beating hiPSC-derived cardiomyocytes was assessed using multi-electrode arrays. Cardiac-stromal progenitor cells could be reprogrammed into hiPSCs, then differentiated into hiPSC-derived cardiomyocytes. Human-induced pluripotent stem cell-derived cardiomyocytes of cardiac origin showed higher upregulation of cardiac-specific genes compared with those of fibroblastic origin. Human-induced pluripotent stem cell-derived cardiomyocytes of both somatic cell origins exhibited sensitivity to tetrodotoxin, a blocker of Na +  current (I Na ), nifedipine, a blocker of L-type Ca 2+  current (I CaL ), and E4031, a blocker of the rapid component of delayed rectifier K +  current (I Kr ). Human-induced pluripotent stem cell-derived cardiomyocytes of cardiac origin exhibited sensitivity to JNJ303, a blocker of the slow component of delayed rectifier K +  current (I Ks ). In hiPSC-derived cardiomyocytes of cardiac origin, I Na , I CaL , I Kr , and I Ks were present as tetrodotoxin-, nifedipine-, E4031-, and JNJ303-sensitive currents, respectively. Although cardiac differentiation efficiency was improved in hiPSCs of cardiac vs. non-cardiac origin, no major functional differences were observed between hiPSC-derived cardiomyocytes of different somatic cell origins. Further studies are warranted to characterize electrophysiological properties of hiPSC-derived cardiomyocytes generated from CPCs. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For Permissions, please email: journals.permissions@oup.com.

Quantitative detection of caffeine in human skin by confocal Raman spectroscopy--A systematic in vitro validation study.

PubMed

Franzen, Lutz; Anderski, Juliane; Windbergs, Maike

2015-09-01

For rational development and evaluation of dermal drug delivery, the knowledge of rate and extent of substance penetration into the human skin is essential. However, current analytical procedures are destructive, labor intense and lack a defined spatial resolution. In this context, confocal Raman microscopy bares the potential to overcome current limitations in drug depth profiling. Confocal Raman microscopy already proved its suitability for the acquisition of qualitative penetration profiles, but a comprehensive investigation regarding its suitability for quantitative measurements inside the human skin is still missing. In this work, we present a systematic validation study to deploy confocal Raman microscopy for quantitative drug depth profiling in human skin. After we validated our Raman microscopic setup, we successfully established an experimental procedure that allows correlating the Raman signal of a model drug with its controlled concentration in human skin. To overcome current drawbacks in drug depth profiling, we evaluated different modes of peak correlation for quantitative Raman measurements and offer a suitable operating procedure for quantitative drug depth profiling in human skin. In conclusion, we successfully demonstrate the potential of confocal Raman microscopy for quantitative drug depth profiling in human skin as valuable alternative to destructive state-of-the-art techniques. Copyright © 2015 Elsevier B.V. All rights reserved.

Working across the veterinary and human health sectors.

PubMed

Garcia-Alvarez, Laura; Dawson, Susan; Cookson, Barry; Hawkey, Peter

2012-07-01

Antibiotics are widely used in human and veterinary medicine for the prevention and treatment of infectious diseases. This practice has led to the emergence of antimicrobial-resistant bacteria in both humans and animals. The potential role that animals, particularly livestock, might play as potential reservoirs of antibiotic resistance genes has been recognized, and it is currently a cause of public health concern. The impact of animal and human antibiotic usage on the emergence and persistence of resistant bacteria and the precise transfer pathways for resistance genes between humans and animals are not currently fully understood. As part of the remit of the UK Advisory Committee on Antimicrobial Resistance and Healthcare-Associated Infection (ARHAI), two main areas were addressed, namely methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Gram-negative bacteria, where both the human and veterinary health sectors share interests. We review the current knowledge of MRSA and resistant Gram-negative bacteria, and provide guidance on occupational risks for veterinary healthcare workers relating to animals infected or colonized with MRSA. Findings and recommendations for further work across disciplines and future research in multidrug-resistant Gram-negative bacteria are also presented. Working collaboratively across disciplines is essential in order to better understand and challenge an important human and animal health problem: antimicrobial resistance.

Biomedical wellness challenges and opportunities

NASA Astrophysics Data System (ADS)

Tangney, John F.

2012-06-01

The mission of ONR's Human and Bioengineered Systems Division is to direct, plan, foster, and encourage Science and Technology in cognitive science, computational neuroscience, bioscience and bio-mimetic technology, social/organizational science, training, human factors, and decision making as related to future Naval needs. This paper highlights current programs that contribute to future biomedical wellness needs in context of humanitarian assistance and disaster relief. ONR supports fundamental research and related technology demonstrations in several related areas, including biometrics and human activity recognition; cognitive sciences; computational neurosciences and bio-robotics; human factors, organizational design and decision research; social, cultural and behavioral modeling; and training, education and human performance. In context of a possible future with automated casualty evacuation, elements of current science and technology programs are illustrated.

NASA's Flexible Path for the Human Exploration

NASA Technical Reports Server (NTRS)

Soeder, James F.

2016-01-01

The idea of human exploration of Mars has been a topic in science fiction for close to a century. For the past 50 years it has been a major thrust in NASAs space mission planning. Currently, NASA is pursuing a flexible development path with the final goal to have humans on Mars. To reach Mars, new hardware will have to be developed and many technology hurdles will have to be overcome. This presentation discusses Mars and its Moons; the flexible path currently being followed; the hardware under development to support exploration; and the technical and organizational challenges that must be overcome to realize the age old dream of humans traveling to Mars.

Report on the COSPAR Workshop on Refining Planetary Protection Requirements for Human Missions

NASA Astrophysics Data System (ADS)

Spry, James Andrew; Rummel, John; Conley, Catharine; Race, Margaret; Kminek, Gerhard; Siegel, Bette

2016-07-01

A human mission to Mars has been the driving long-term goal for the development of the Global Exploration Roadmap by the International Space Exploration Coordination Group. Additionally, multiple national space agencies and commercial organizations have published similar plans and aspirations for human missions beyond LEO. The current COSPAR planetary protection "Guidelines for Human Missions to Mars" were developed in a series of workshops in the early 2000s and adopted into COSPAR policy at the Montreal Assembly in 2008. With changes and maturation in mission architecture concepts and hardware capabilities, the holding of a workshop provided an opportunity for timely review of these guidelines and their interpretation within current frameworks provided by ISECG and others. The COSPAR Workshop on Refining Planetary Protection Requirements for Human Missions was held in the US in spring 2016 to evaluate recent efforts and activities in the context of current COSPAR policy, as well as collect inputs from the various organizations considering crewed exploration missions to Mars and precursor robotic missions focused on surface material properties and environmental challenges. The workshop also considered potential updates to the COSPAR policy for human missions across a range of planetary destinations. This paper will report on those deliberations.

Evidence for a genetic discontinuity between Neandertals and 24,000-year-old anatomically modern Europeans.

PubMed

Caramelli, David; Lalueza-Fox, Carles; Vernesi, Cristiano; Lari, Martina; Casoli, Antonella; Mallegni, Francesco; Chiarelli, Brunetto; Dupanloup, Isabelle; Bertranpetit, Jaume; Barbujani, Guido; Bertorelle, Giorgio

2003-05-27

During the late Pleistocene, early anatomically modern humans coexisted in Europe with the anatomically archaic Neandertals for some thousand years. Under the recent variants of the multiregional model of human evolution, modern and archaic forms were different but related populations within a single evolving species, and both have contributed to the gene pool of current humans. Conversely, the Out-of-Africa model considers the transition between Neandertals and anatomically modern humans as the result of a demographic replacement, and hence it predicts a genetic discontinuity between them. Following the most stringent current standards for validation of ancient DNA sequences, we typed the mtDNA hypervariable region I of two anatomically modern Homo sapiens sapiens individuals of the Cro-Magnon type dated at about 23 and 25 thousand years ago. Here we show that the mtDNAs of these individuals fall well within the range of variation of today's humans, but differ sharply from the available sequences of the chronologically closer Neandertals. This discontinuity is difficult to reconcile with the hypothesis that both Neandertals and early anatomically modern humans contributed to the current European gene pool.

The Relationship between Robot's Nonverbal Behaviour and Human's Likability Based on Human's Personality.

PubMed

Thepsoonthorn, Chidchanok; Ogawa, Ken-Ichiro; Miyake, Yoshihiro

2018-05-30

At current state, although robotics technology has been immensely developed, the uncertainty to completely engage in human-robot interaction is still growing among people. Many current studies then started to concern about human factors that might influence human's likability like human's personality, and found that compatibility between human's and robot's personality (expressions of personality characteristics) can enhance human's likability. However, it is still unclear whether specific means and strategy of robot's nonverbal behaviours enhances likability from human with different personality traits and whether there is a relationship between robot's nonverbal behaviours and human's likability based on human's personality. In this study, we investigated and focused on the interaction via gaze and head nodding behaviours (mutual gaze convergence and head nodding synchrony) between introvert/extravert participants and robot in two communication strategies (Backchanneling and Turn-taking). Our findings reveal that the introvert participants are positively affected by backchanneling in robot's head nodding behaviour, which results in substantial head nodding synchrony whereas the extravert participants are positively influenced by turn-taking in gaze behaviour, which leads to significant mutual gaze convergence. This study demonstrates that there is a relationship between robot's nonverbal behaviour and human's likability based on human's personality.

Smart Distributed Sensor Fields: Algorithms for Tactical Sensors

DTIC Science & Technology

2013-12-23

ranging from detecting, identifying, localizing/tracking interesting events, discarding irrelevant data, to providing actionable intelligence currently...tracking interesting events, discarding irrelevant data, to providing actionable intelligence currently requires significant human super- vision. Human...view of the overall system. The main idea is to reduce the problem to the relevant data, and then reason intelligently over that data. This process

The Factors and Conditions for National Human Resource Development in Brazil

ERIC Educational Resources Information Center

Sparkman, Torrence E.

2015-01-01

Purpose: The purpose of this paper is to understand the factors and conditions that influence national human resource development (NHRD) in Brazil. In this paper, the transitioning nature of the political, economic, social and educational conditions; the current challenges and trends that may impact NHRD; and the current status of NHRD research in…

On Certain Similarities between Mainstream Psychology and the Writings of B. F. Skinner

ERIC Educational Resources Information Center

Goddard, Murray

2012-01-01

Selected writings of B. F. Skinner are compared to 5 current topics in mainstream psychology, including the role of the unconscious, human language, the role of dispositions in psychology, human perceptions of conformity and bias, and mindfulness. The striking similarities between Skinner's work and these 5 current topics support Richelle's (1993)…

Novel regulatory mechanism in human urinary bladder: central role of transient receptor potential melastatin 4 channels in detrusor smooth muscle function

PubMed Central

Hristov, Kiril L.; Smith, Amy C.; Parajuli, Shankar P.; Malysz, John; Rovner, Eric S.

2016-01-01

Transient receptor potential melastatin 4 (TRPM4) channels are Ca2+-activated nonselective cation channels that have been recently identified as regulators of detrusor smooth muscle (DSM) function in rodents. However, their expression and function in human DSM remain unexplored. We provide insights into the functional role of TRPM4 channels in human DSM under physiological conditions. We used a multidisciplinary experimental approach, including RT-PCR, Western blotting, immunohistochemistry and immunocytochemistry, patch-clamp electrophysiology, and functional studies of DSM contractility. DSM samples were obtained from patients without preoperative overactive bladder symptoms. RT-PCR detected mRNA transcripts for TRPM4 channels in human DSM whole tissue and freshly isolated single cells. Western blotting and immunohistochemistry with confocal microscopy revealed TRPM4 protein expression in human DSM. Immunocytochemistry further detected TRPM4 protein expression in DSM single cells. Patch-clamp experiments showed that 9-phenanthrol, a selective TRPM4 channel inhibitor, significantly decreased the transient inward cation currents and voltage step-induced whole cell currents in freshly isolated human DSM cells. In current-clamp mode, 9-phenanthrol hyperpolarized the human DSM cell membrane potential. Furthermore, 9-phenanthrol attenuated the spontaneous phasic, carbachol-induced and nerve-evoked contractions in human DSM isolated strips. Significant species-related differences in TRPM4 channel activity between human, rat, and guinea pig DSM were revealed, suggesting a more prominent physiological role for the TRPM4 channel in the regulation of DSM function in humans than in rodents. In conclusion, TRPM4 channels regulate human DSM excitability and contractility and are critical determinants of human urinary bladder function. Thus, TRPM4 channels could represent promising novel targets for the pharmacological or genetic control of overactive bladder. PMID:26791488

Bioelectric effect and bacterial biofilms. A systematic review

PubMed Central

DEL POZO, J. L.; ROUSE, M. S.; PATEL, R.

2014-01-01

Bacteria growing in biofilms cause a wide range of human infections. Biofilm bacteria are resistant to antimicrobics at levels 500 to 5,000 times higher than those needed to kill non-biofilm bacteria. In vitro experiments have shown that electric current can enhance the activity of some antimicrobial agents against certain bacteria in biofilms; this has been termed the “bioelectric effect”. Direct electrical current has already been safely used in humans for fracture healing. Application of direct electric current with antimicrobial chemotherapy in humans could theoretically abrogate the need to remove the device in device-related infections, a procedure associated with substantial morbidity and cost. In this article, we review what has been described in the literature with regards to the bioelectric effect. PMID:18924090

Human influenza A (H5N1): a brief review and recommendations for travelers.

PubMed

Hurtado, Timothy R

2006-01-01

Although avian influenza A (H5N1) is common in birds worldwide, it has only recently led to disease in humans. Humans who are infected with the disease (referred to as human influenza A [H5N1]) have a greater than 50% mortality rate. Currently there has not been documented sustained human-to-human transmission; however, should the virus mutate and make this possible, the world could experience an influenza pandemic. Probable risk factors for infection include slaughtering, defeathering, and butchering fowl; close contact with wild birds or caged poultry; ingestion of undercooked poultry products; direct contact with surfaces contaminated with poultry feces; and close contact with infected humans. Possible risk factors include swimming in or ingesting water contaminated with bird feces or dead birds and the use of unprocessed poultry feces as fertilizer. Clinically, early human influenza A (H5N1) resembles typical influenza illnesses, with fever and a preponderance of lower respiratory tract symptoms. Often, patients develop rapidly progressive respiratory failure and require ventilatory support. Treatment is primarily supportive care with the addition of antiviral medications. Currently, travelers to countries with both human and avian influenza A (H5N1) have a low risk of developing the disease. There are no current recommended travel restrictions. Travelers are advised to avoid contact with all birds, especially poultry; avoid surfaces contaminated with poultry feces; and avoid undercooked poultry products. The use of prophylactic antiviral medications is not recommended.

The Human Side of Information's Converging Technology.

ERIC Educational Resources Information Center

Williams, Berney

1982-01-01

Discusses current issues in the design of information systems, noting contributions from three professions--computer science, human factors engineering, and information science. The eclectic nature of human factors engineering and the difficulty of drawing together studies with human engineering or software psychological components from diverse…

Singularity now: using the ventricular assist device as a model for future human-robotic physiology.

PubMed

Martin, Archer K

2016-04-01

In our 21 st century world, human-robotic interactions are far more complicated than Asimov predicted in 1942. The future of human-robotic interactions includes human-robotic machine hybrids with an integrated physiology, working together to achieve an enhanced level of baseline human physiological performance. This achievement can be described as a biological Singularity. I argue that this time of Singularity cannot be met by current biological technologies, and that human-robotic physiology must be integrated for the Singularity to occur. In order to conquer the challenges we face regarding human-robotic physiology, we first need to identify a working model in today's world. Once identified, this model can form the basis for the study, creation, expansion, and optimization of human-robotic hybrid physiology. In this paper, I present and defend the line of argument that currently this kind of model (proposed to be named "IshBot") can best be studied in ventricular assist devices - VAD.

Singularity now: using the ventricular assist device as a model for future human-robotic physiology

PubMed Central

Martin, Archer K.

2016-01-01

In our 21st century world, human-robotic interactions are far more complicated than Asimov predicted in 1942. The future of human-robotic interactions includes human-robotic machine hybrids with an integrated physiology, working together to achieve an enhanced level of baseline human physiological performance. This achievement can be described as a biological Singularity. I argue that this time of Singularity cannot be met by current biological technologies, and that human-robotic physiology must be integrated for the Singularity to occur. In order to conquer the challenges we face regarding human-robotic physiology, we first need to identify a working model in today’s world. Once identified, this model can form the basis for the study, creation, expansion, and optimization of human-robotic hybrid physiology. In this paper, I present and defend the line of argument that currently this kind of model (proposed to be named “IshBot”) can best be studied in ventricular assist devices – VAD. PMID:28913480

IRBs, conflict and liability: will we see IRBs in court? Or is it when?

PubMed

Icenogle, Daniel L

2003-01-01

The entire human research infrastructure is under intense and increasing financial pressure. These pressures may have been responsible for several errors in judgment by those responsible for managing human research and protecting human subjects. The result of these errors has been some terrible accidents, some of which have cost the lives of human research volunteers. This, in turn, is producing both increased liability risk for those who manage the various aspects of human research and increasing scrutiny as to the capability of the human research protection structure as currently constituted. It is the author's contention that the current structure is fully capable of offering sufficient protection for participants in human research-if Institutional Review Board (IRB) staff and members are given sufficient resources and perform their tasks with sufficient responsibility. The status quo alternative is that IRBs and their members will find themselves at great risk of becoming defendants in lawsuits seeking compensation for damages resulting from human experimentation gone awry.

Emergence Potential of Sylvatic Dengue Virus Type 4 in the Urban Transmission Cycle is Restrained by Vaccination and Homotypic Immunity

PubMed Central

Durbin, Anna P.; Mayer, Sandra V.; Rossi, Shannan L.; Amaya-Larios, Irma Y.; Ramos-Castaneda, Jose; Ooi, Eng Eong; Cardosa, M. Jane; Munoz-Jordan, Jorge L.; Tesh, Robert B.; Messer, William B.; Weaver, Scott C.; Vasilakis, Nikos

2013-01-01

Sylvatic dengue viruses (DENV) are both evolutionarily and ecologically distinct from human DENV and are maintained in an enzootic transmission cycle. Evidence of sylvatic human infections from West Africa and Southeast Asia suggests that sylvatic DENV come into regular contact with humans. Thus, this potential of emergence into the human transmission cycle could limit the potential for eradicating this cycle with vaccines currently in late stages of development. We assessed the likelihood of sylvatic DENV-4 emergence in the face of natural immunity to current human strains and vaccination with two DENV-4 vaccine candidates. Our data indicate homotypic neutralization of sylvatic and human DENV-4 strains by human primary convalescent and vaccinee sera but limited heterotypic immunity. These results suggest that emergence of sylvatic strains into the human cycle would be limited by homotypic immunity mediated by virus neutralizing antibodies produced by natural infection or vaccination. PMID:23485373

Non-pharmacological treatment options for refractory epilepsy: an overview of human treatment modalities and their potential utility in dogs.

PubMed

Martlé, Valentine; Van Ham, Luc; Raedt, Robrecht; Vonck, Kristl; Boon, Paul; Bhatti, Sofie

2014-03-01

Refractory epilepsy is a common disorder both in humans and dogs and treatment protocols are difficult to optimise. In humans, different non-pharmacological treatment modalities currently available include surgery, the ketogenic diet and neurostimulation. Surgery leads to freedom from seizures in 50-75% of patients, but requires strict patient selection. The ketogenic diet is indicated in severe childhood epilepsies, but efficacy is limited and long-term compliance can be problematic. In the past decade, various types of neurostimulation have emerged as promising treatment modalities for humans with refractory epilepsy. Currently, none of these treatment options are used in routine daily clinical practice to treat dogs with the condition. Since many dogs with poorly controlled seizures do not survive, the search for alternative treatment options for canine refractory epilepsy should be prioritised. This review provides an overview of non-pharmacological treatment options for human refractory epilepsy. The current knowledge and limitations of these treatments in canine refractory epilepsy is also discussed. Copyright © 2013 Elsevier Ltd. All rights reserved.

Human occupational and nonoccupational exposure to fibers.

PubMed Central

Esmen, N A; Erdal, S

1990-01-01

Human exposure to fibers in occupational and nonoccupational environments has been a health concern for nearly a century. In this review, selected results from the literature are presented to highlight the availability, limitations, and interpretive difficulties associated with the past and current human fiber exposure data sets. In the traditionally defined asbestos fibers, large amounts of the data available suffer from the diversity of sample collection and analysis methods. Two simple generalizations suggest that occupational exposures are several orders of magnitude higher than that of environmental exposures; and currently extant data and the current routine measurement practices present significant difficulties in the consistent interpretation of the data with respect to health effects. The data on the human exposures to man-made vitreous fibers are much more complete than the data on asbestos exposure, while exposure data on other man-made fibrous materials are lacking. The human exposure data to many minerals which, at times, exist in fibrous habit, are very scanty, and in view of the biological activity of some of these fibers, this lack may be of significant concern. PMID:2272324

Human-Robot Interaction: Status and Challenges.

PubMed

Sheridan, Thomas B

2016-06-01

The current status of human-robot interaction (HRI) is reviewed, and key current research challenges for the human factors community are described. Robots have evolved from continuous human-controlled master-slave servomechanisms for handling nuclear waste to a broad range of robots incorporating artificial intelligence for many applications and under human supervisory control. This mini-review describes HRI developments in four application areas and what are the challenges for human factors research. In addition to a plethora of research papers, evidence of success is manifest in live demonstrations of robot capability under various forms of human control. HRI is a rapidly evolving field. Specialized robots under human teleoperation have proven successful in hazardous environments and medical application, as have specialized telerobots under human supervisory control for space and repetitive industrial tasks. Research in areas of self-driving cars, intimate collaboration with humans in manipulation tasks, human control of humanoid robots for hazardous environments, and social interaction with robots is at initial stages. The efficacy of humanoid general-purpose robots has yet to be proven. HRI is now applied in almost all robot tasks, including manufacturing, space, aviation, undersea, surgery, rehabilitation, agriculture, education, package fetch and delivery, policing, and military operations. © 2016, Human Factors and Ergonomics Society.

Translating chimpanzee personality to humans: Investigating the transportability of chimpanzee-derived personality scales to humans.

PubMed

Latzman, Robert D; Sauvigné, Katheryn C; Hopkins, William D

2016-06-01

There is a growing interest in the study of personality in chimpanzees with repeated findings of a similar structure of personality in apes to that found in humans. To date, however, the direct translational value of instruments used to assess chimpanzee personality to humans has yet to be explicitly tested. As such, in the current study we sought to determine the transportability of factor analytically-derived chimpanzee personality scales to humans in a large human sample (N = 301). Human informants reporting on target individuals they knew well completed chimpanzee-derived and human-derived measures of personality from the two most widely studied models of human personality: Big Five and Big Three. The correspondence between informant-reported chimpanzee- and human-derived personality scales was then investigated. Results indicated high convergence for corresponding scales across most chimpanzee- and human-derived personality scales. Findings from the current study provide evidence that chimpanzee-derived scales translate well to humans and operate quite similarly to the established human-derived personality scales in a human sample. This evidence of transportability lends support to the translational nature of chimpanzee personality research suggesting clear relevance of this growing literature to humans. Am. J. Primatol. 78:601-609, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Glenn Research Center Human Research Program: Overview

NASA Technical Reports Server (NTRS)

Nall, Marsha M.; Myers, Jerry G.

2013-01-01

The NASA-Glenn Research Centers Human Research Program office supports a wide range of technology development efforts aimed at enabling extended human presence in space. This presentation provides a brief overview of the historical successes, current 2013 activities and future projects of NASA-GRCs Human Research Program.

A Prelinguistic Gestural Universal of Human Communication

ERIC Educational Resources Information Center

Liszkowski, Ulf; Brown, Penny; Callaghan, Tara; Takada, Akira; de Vos, Conny

2012-01-01

Several cognitive accounts of human communication argue for a language-independent, prelinguistic basis of human communication and language. The current study provides evidence for the universality of a prelinguistic gestural basis for human communication. We used a standardized, semi-natural elicitation procedure in seven very different cultures…

When Humanoid Robots Become Human-Like Interaction Partners: Corepresentation of Robotic Actions

ERIC Educational Resources Information Center

Stenzel, Anna; Chinellato, Eris; Bou, Maria A. Tirado; del Pobil, Angel P.; Lappe, Markus; Liepelt, Roman

2012-01-01

In human-human interactions, corepresenting a partner's actions is crucial to successfully adjust and coordinate actions with others. Current research suggests that action corepresentation is restricted to interactions between human agents facilitating social interaction with conspecifics. In this study, we investigated whether action…

Mars Surface Systems Common Capabilities and Challenges for Human Missions

NASA Technical Reports Server (NTRS)

Toups, Larry; Hoffman, Stephen J.; Watts, Kevin

2016-01-01

This paper describes the current status of common systems and operations as they are applied to actual locations on Mars that are representative of Exploration Zones (EZ) - NASA's term for candidate locations where humans could land, live and work on the martian surface. Given NASA's current concepts for human missions to Mars, an EZ is a collection of Regions of Interest (ROIs) located within approximately 100 kilometers of a centralized landing site. ROIs are areas that are relevant for scientific investigation and/or development/maturation of capabilities and resources necessary for a sustainable human presence. An EZ also contains a habitation site that will be used by multiple human crews during missions to explore and utilize the ROIs within the EZ. The Evolvable Mars Campaign (EMC), a description of NASA's current approach to these human Mars missions, assumes that a single EZ will be identified within which NASA will establish a substantial and durable surface infrastructure that will be used by multiple human crews. The process of identifying and eventually selecting this single EZ will likely take many years to finalized. Because of this extended EZ selection process it becomes important to evaluate the current suite of surface systems and operations being evaluated for the EMC as they are likely to perform at a variety of proposed EZ locations and for the types of operations - both scientific and development - that are proposed for these candidate EZs. It is also important to evaluate proposed EZs for their suitability to be explored or developed given the range of capabilities and constraints for the types of surface systems and operations being considered within the EMC.

Conversational Scholarship in Cyberspace: The Evolution and Activities of H-Net, the Online Network for the Humanities.

ERIC Educational Resources Information Center

Turnbull, Paul

1996-01-01

The origins and current use of H-Net, an online humanities network on the World Wide Web, are examined. H-Net currently sponsors 73 electronic discussion lists that reach subscribers in 68 countries. Discussion groups have not met expectations for scholarly exchange, possibly because of plagiarism and copyright concerns. New ventures include book…

The Current State of Human Performance Technology: A Citation Network Analysis of "Performance Improvement Quarterly," 1988-2010

ERIC Educational Resources Information Center

Cho, Yonjoo; Jo, Sung Jun; Park, Sunyoung; Kang, Ingu; Chen, Zengguan

2011-01-01

This study conducted a citation network analysis (CNA) of human performance technology (HPT) to examine its current state of the field. Previous reviews of the field have used traditional research methods, such as content analysis, survey, Delphi, and citation analysis. The distinctive features of CNA come from using a social network analysis…

Human Modeling for Ground Processing Human Factors Engineering Analysis

NASA Technical Reports Server (NTRS)

Stambolian, Damon B.; Lawrence, Brad A.; Stelges, Katrine S.; Steady, Marie-Jeanne O.; Ridgwell, Lora C.; Mills, Robert E.; Henderson, Gena; Tran, Donald; Barth, Tim

2011-01-01

There have been many advancements and accomplishments over the last few years using human modeling for human factors engineering analysis for design of spacecraft. The key methods used for this are motion capture and computer generated human models. The focus of this paper is to explain the human modeling currently used at Kennedy Space Center (KSC), and to explain the future plans for human modeling for future spacecraft designs

Effects of in ovo feeding of creatine pyruvate on the hatchability, growth performance and energy status in embryos and broiler chickens.

PubMed

Zhao, M M; Gao, T; Zhang, L; Li, J L; Lv, P A; Yu, L L; Gao, F; Zhou, G H

2017-10-01

The effects of in ovo feeding (IOF) of creatine pyruvate (CrPyr) on the hatchability, growth performance and energy status of embryos and broilers (Arbor Acres) were investigated. Five treatments were arranged as non-injected treatment (Control), 0.6 ml physiological saline (0.75%) injected treatment (Saline), and IOF treatments injected with 0.6 ml physiological saline (0.75%) containing 3, 6 or 12 mg CrPyr (CrPyr3, CrPyr6 or CrPyr12) into the amnion per fertile egg on day 17.5 of incubation. After hatching, 80 male chicks from each treatment with similar weight close to the average BW of their pooled group were selected and randomly assigned into eight replicates of 10 chicks each. The results showed that the hatchability was not affected among groups, whereas the hatching weight of broilers in CrPyr12 was significantly higher than the control and saline groups (P0.05). Irrespective of dosage, the concentrations of creatine and phosphocreatine, and activities of creatine kinase in embryos were enhanced in CrPyr treatments at 19 E when compared with the control and saline groups (P<0.05). The activities of glucose-6-phosphatase in liver in CrPyr6 and CrPyr12 treatments were higher than the control and saline groups at 19 E (P<0.05). In conclusion, these results indicated that IOF of CrPyr, especially at the level of 12 mg/egg, could improve energy status of embryos and hatchlings, which was useful for enhancing hatching weight, BW and pectoral muscle weight until the end of the experiments at 21 days post-hatch in broilers.

Effects of endocrine disruptors on imprinted gene expression in the mouse embryo

PubMed Central

Tran, Diana A; Rivas, Guillermo E; Singh, Purnima; Pfeifer, Gerd P

2011-01-01

Environmental endocrine disruptors (EDs) are synthetic chemicals that resemble natural hormones and are known to cause epigenetic perturbations. EDs have profound effects on development and fertility. Imprinted genes had been identified as candidate susceptibility loci to environmental insults because they are functionally haploid, and because the imprints undergo epigenetic resetting between generations. To screen for possible epigenetic perturbations caused by EDs at imprinted loci, we treated pregnant mice daily between 8.5 and 12.5 days post coitum (dpc) with di-(2-ethylhexyl)-phthalate (DEHP), bisphenol A (BPA), vinclozolin (VZ) or control oil vehicle. After isolating RNA from the placenta, yolk sac, amnion, head, body, heart, liver, lung, stomach and intestines of 13.5 dpc embryos we measured the allele-specific expression of 39 imprinted transcripts using multiplex single nucleotide primer extension (SNuPE) assays. In this representative data set we identified only a small number of transcripts that exhibited a substantial relaxation of imprinted expression with statistical significance: Slc22a18 with 10% relaxation in the embryo after BPA treatment; Rtl1as with 11 and 16% relaxation in the lung and placenta, respectively after BPA treatment; and Rtl1 with 12% relaxation in the yolk sac after DEHP treatment. Additionally, the standard deviation of allele-specificity increased in various organs after ED treatment for several transcripts including Igf2r, Rasgrf1, Usp29, Slc38a4 and Xist. Our data suggest that the maintenance of strongly biased monoallelic expression of imprinted genes is generally insensitive to EDs in the 13.5 dpc embryo and extra-embryonic organs, but is not immune to those effects. PMID:21636974

Amnioinfusion for umbilical cord compression in labour.

PubMed

Hofmeyr, G J

2000-01-01

Amnioinfusion aims to prevent or relieve umbilical cord compression during labour by infusing a solution into the uterine cavity. The objective of this review was to assess the effects of amnioinfusion on maternal and perinatal outcome for potential or suspected umbilical cord compression or potential amnionitis. The Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Controlled Trials Register were searched. Randomised trials of amnioinfusion compared with no amnioinfusion in women with babies at risk of umbilical cord compression; and women at risk of intrauterine infection. Eligibility and trial quality were assessed by the reviewer. Twelve studies were included. Transcervical amnioinfusion for potential or suspected umbilical cord compression was associated with the following reductions: fetal heart rate decelerations (relative risk 0.54, 95% confidence interval 0.43 to 0.68); caesarean section for suspected fetal distress (relative risk 0.35, 95% confidence interval 0.24 to 0.52); neonatal hospital stay greater than 3 days (relative risk 0.40, 95% confidence interval 0. 26 to 0.62); maternal hospital stay greater than 3 days (relative risk 0.46, 95% 0.29 to 0.74). Transabdominal amnioinfusion showed similar results. Transcervical amnioinfusion to prevent infection in women with membranes ruptured for more than 6 hours was associated with a reduction in puerperal infection (relative risk 0.50, 95% confidence interval 0.26 to 0.97). Amnioinfusion appears to reduce the occurrence of variable heart rate decelerations and lower the use of caesarean section. However the studies were done in settings where fetal distress was not confirmed by fetal blood sampling. The results may therefore only be relevant where caesarean sections are commonly done for abnormal fetal heart rate alone. The trials reviewed are too small to address the possibility of rare but serious maternal adverse effects of amnioinfusion.

Ultrasound-guided microinjection into the mouse forebrain in utero at E9.5.

PubMed

Pierfelice, Tarran J; Gaiano, Nicholas

2010-11-13

In utero survival surgery in mice permits the molecular manipulation of gene expression during development. However, because the uterine wall is opaque during early embryogenesis, the ability to target specific parts of the embryo for microinjection is greatly limited. Fortunately, high-frequency ultrasound imaging permits the generation of images that can be used in real time to guide a microinjection needle into the embryonic region of interest. Here we describe the use of such imaging to guide the injection of retroviral vectors into the ventricular system of the mouse forebrain at embryonic day (E) 9.5. This method uses a laparotomy to permit access to the uterine horns, and a specially designed plate that permits host embryos to be bathed in saline while they are imaged and injected. Successful surgeries often result in most or all of the injected embryos surviving to any subsequent time point of interest (embryonically or postnatally). The principles described here can be used with slight modifications to perform injections into the amnionic fluid of E8.5 embryos (thereby permitting infection along the anterior posterior extent of the neural tube, which has not yet closed), or into the ventricular system of the brain at E10.5/11.5. Furthermore, at mid-neurogenic ages (~E13.5), ultrasound imaging can be used direct injection into specific brain regions for viral infection or cell transplantation. The use of ultrasound imaging to guide in utero injections in mice is a very powerful technique that permits the molecular and cellular manipulation of mouse embryos in ways that would otherwise be exceptionally difficult if not impossible.

Amniotic Fluid Cells Show Higher Pluripotency-Related Gene Expression Than Allantoic Fluid Cells.

PubMed

Kehl, Debora; Generali, Melanie; Görtz, Sabrina; Geering, Diego; Slamecka, Jaroslav; Hoerstrup, Simon P; Bleul, Ulrich; Weber, Benedikt

2017-10-01

Amniotic fluid represents an abundant source of multipotent stem cells, referred as broadly multipotent given their differentiation potential and expression of pluripotency-related genes. However, the origin of this broadly multipotent cellular fraction is not fully understood. Several sources have been proposed so far, including embryonic and extraembryonic tissues. In this regard, the ovine developmental model uniquely allows for direct comparison of fetal fluid-derived cells from two separate fetal fluid cavities, the allantois and the amnion, over the entire duration of gestation. As allantoic fluid mainly collects fetal urine, cells originating from the efferent urinary tract can directly be compared with cells deriving from the extraembryonic amniotic tissues and the fetus. This study shows isolation of cells from the amniotic [ovine amniotic fluid cells (oAFCs)] and allantoic fluid [ovine allantoic fluid cells (oALCs)] in a strictly paired fashion with oAFCs and oALCs derived from the same fetus. Both cell types showed cellular phenotypes comparable to standard mesenchymal stem cells (MSCs), with trilineage differentiation potential, and expression of common ovine MSC markers. However, the expression of MSC markers per single cell was higher in oAFCs as measured by flow cytometry. oAFCs exhibited higher proliferative capacities and showed significantly higher expression of pluripotency-related genes OCT4, STAT3, NANOG, and REX1 by quantitative real-time polymerase chain reaction compared with paired oALCs. No significant decrease of pluripotency-related gene expression was noted over gestation, implying that cells with high differentiation potential may be isolated at the end of pregnancy. In conclusion, this study suggests that cells with highest stem cell characteristics may originate from the fetus itself or the amniotic fetal adnexa rather than from the efferent urinary tract or the allantoic fetal adnexa.

Interleukin 18 messenger RNA and proIL-18 protein expression in chorioamniotic membranes from pregnant women with preterm prelabor rupture of membranes.

PubMed

Polettini, Jossimara; Vieira, Eliane Passarelli; Santos, Mariana Perlati dos; Peraçoli, José Carlos; Witkin, Steven S; da Silva, Márcia Guimarães

2012-04-01

To quantify the expression of IL-18 mRNA and protein in the chorioamniotic membranes of pregnant women with PPROM and correlate expression with histological chorioamnionitis. A case control study that included 42 pregnant women not in labor in the following groups: PPROM (n=28) and controls with intact membranes submitted to selective cesarean section at term (n=14). Expression of IL-18 mRNA in chorioamniotic membranes was determined by real-time polymerase chain reaction, and IL-18 protein expression was measured by western blot. Histopathological analyses and immunolocalization of IL-18 by immunohistochemistry were also performed. Analyses were performed using the Mann-Whitney or Fisher's exact tests and the group effect was considered significant if the adjusted p-values were <0.05 and the magnitude of change was greater than 2-fold for mRNA expression. IL-18 mRNA was present in 100% of samples and no difference in expression was observed between term vs. PPROM membranes (fold-change 0.12; p=0.88). In the PPROM group, no difference was observed in IL-18 mRNA regarding gestational age (fold-change 0.11; p=0.42) or the presence of histological chorioamnionitis (fold-change 0.26; p=0.15). ProIL-18 was present in all samples. IL-18 was immunolocalized to amnion, chorion and decidua cells, with intense immunohistochemical staining at the choriodecidual junction. Chorioamniotic membranes are sources of IL-18 mRNA and proIL-18, and their expression is unrelated to PPROM or histological chorioamnionitis. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

The current biodiversity extinction event: scenarios for mitigation and recovery.

PubMed

Novacek, M J; Cleland, E E

2001-05-08

The current massive degradation of habitat and extinction of species is taking place on a catastrophically short timescale, and their effects will fundamentally reset the future evolution of the planet's biota. The fossil record suggests that recovery of global ecosystems has required millions or even tens of millions of years. Thus, intervention by humans, the very agents of the current environmental crisis, is required for any possibility of short-term recovery or maintenance of the biota. Many current recovery efforts have deficiencies, including insufficient information on the diversity and distribution of species, ecological processes, and magnitude and interaction of threats to biodiversity (pollution, overharvesting, climate change, disruption of biogeochemical cycles, introduced or invasive species, habitat loss and fragmentation through land use, disruption of community structure in habitats, and others). A much greater and more urgently applied investment to address these deficiencies is obviously warranted. Conservation and restoration in human-dominated ecosystems must strengthen connections between human activities, such as agricultural or harvesting practices, and relevant research generated in the biological, earth, and atmospheric sciences. Certain threats to biodiversity require intensive international cooperation and input from the scientific community to mitigate their harmful effects, including climate change and alteration of global biogeochemical cycles. In a world already transformed by human activity, the connection between humans and the ecosystems they depend on must frame any strategy for the recovery of the biota.

Extending breath analysis to the cellular level: current thoughts on the human microbiome and the expression of organic compounds in the human exposome

EPA Science Inventory

Human biomarkers are comprised of compounds from cellular metabolism, oxidative stress, and the microbiome of bacteria in the gut, genitourinary, and pulmonary tracts. When we examine patterns in human biomarkers to discern human health state or diagnose specific diseases, it is...

Growth is similar in premature infants fed human milk fortified with a human milk or bovine milk-based fortifier

USDA-ARS?s Scientific Manuscript database

Preterm infants require fortification of human milk (HM) to provide adequate nutrients for growth. A human milk fortifier (HMF) made from donor human milk has recently been introduced. However, limited data are available comparing the growth outcomes of this product with current fortifiers. We evalu...

Human-human reliance in the context of automation.

PubMed

Lyons, Joseph B; Stokes, Charlene K

2012-02-01

The current study examined human-human reliance during a computer-based scenario where participants interacted with a human aid and an automated tool simultaneously. Reliance on others is complex, and few studies have examined human-human reliance in the context of automation. Past research found that humans are biased in their perceived utility of automated tools such that they view them as more accurate than humans. Prior reviews have postulated differences in human-human versus human-machine reliance, yet few studies have examined such reliance when individuals are presented with divergent information from different sources. Participants (N = 40) engaged in the Convoy Leader experiment.They selected a convoy route based on explicit guidance from a human aid and information from an automated map. Subjective and behavioral human-human reliance indices were assessed. Perceptions of risk were manipulated by creating three scenarios (low, moderate, and high) that varied in the amount of vulnerability (i.e., potential for attack) associated with the convoy routes. Results indicated that participants reduced their behavioral reliance on the human aid when faced with higher risk decisions (suggesting increased reliance on the automation); however, there were no reported differences in intentions to rely on the human aid relative to the automation. The current study demonstrated that when individuals are provided information from both a human aid and automation,their reliance on the human aid decreased during high-risk decisions. This study adds to a growing understanding of the biases and preferences that exist during complex human-human and human-machine interactions.

Human-Robot Control Strategies for the NASA/DARPA Robonaut

NASA Technical Reports Server (NTRS)

Diftler, M. A.; Culbert, Chris J.; Ambrose, Robert O.; Huber, E.; Bluethmann, W. J.

2003-01-01

The Robotic Systems Technology Branch at the NASA Johnson Space Center (JSC) is currently developing robot systems to reduce the Extra-Vehicular Activity (EVA) and planetary exploration burden on astronauts. One such system, Robonaut, is capable of interfacing with external Space Station systems that currently have only human interfaces. Robonaut is human scale, anthropomorphic, and designed to approach the dexterity of a space-suited astronaut. Robonaut can perform numerous human rated tasks, including actuating tether hooks, manipulating flexible materials, soldering wires, grasping handrails to move along space station mockups, and mating connectors. More recently, developments in autonomous control and perception for Robonaut have enabled dexterous, real-time man-machine interaction. Robonaut is now capable of acting as a practical autonomous assistant to the human, providing and accepting tools by reacting to body language. A versatile, vision-based algorithm for matching range silhouettes is used for monitoring human activity as well as estimating tool pose.

Site, Sector, Scope: Mapping the Epistemological Landscape of Health Humanities.

PubMed

Charise, Andrea

2017-12-01

This essay presents a critical appraisal of the current state of baccalaureate Health Humanities, with a special focus on the contextual differences currently influencing the implementation of this field in Canada and, to a lesser extent, the United States and United Kingdom. I argue that the epistemological bedrock of Health Humanities goes beyond that generated by its written texts to include three external factors that are especially pertinent to undergraduate education: site (the setting of Health Humanities education), sector (the disciplinary eligibility for funding) and scope (the critical engagement with a program's local context alongside an emergent "core" of Health Humanities knowledge, learning, and practice). Drawing largely from the Canadian context, I discuss how these differences can inform or obstruct this field's development, and offer preliminary recommendations for encouraging the growth of baccalaureate Health Humanities-in Canada and elsewhere-in light of these factors.

A review of human factors principles for the design and implementation of medication safety alerts in clinical information systems.

PubMed

Phansalkar, Shobha; Edworthy, Judy; Hellier, Elizabeth; Seger, Diane L; Schedlbauer, Angela; Avery, Anthony J; Bates, David W

2010-01-01

The objective of this review is to describe the implementation of human factors principles for the design of alerts in clinical information systems. First, we conduct a review of alarm systems to identify human factors principles that are employed in the design and implementation of alerts. Second, we review the medical informatics literature to provide examples of the implementation of human factors principles in current clinical information systems using alerts to provide medication decision support. Last, we suggest actionable recommendations for delivering effective clinical decision support using alerts. A review of studies from the medical informatics literature suggests that many basic human factors principles are not followed, possibly contributing to the lack of acceptance of alerts in clinical information systems. We evaluate the limitations of current alerting philosophies and provide recommendations for improving acceptance of alerts by incorporating human factors principles in their design.

Current knowledge and pending challenges in zoonosis caused by Mycobacterium bovis: a review.

PubMed

Pérez-Lago, Laura; Navarro, Yurena; García-de-Viedma, Darío

2014-10-01

Mycobacterium bovis is both the causative agent of bovine tuberculosis (TB) and a zoonotic pathogen. In humans, considerably fewer cases of TB are caused by M. bovis than M. tuberculosis; nevertheless, diagnostic limitations mean that currently available data on prevalence grossly underestimate the true dimension of the problem. The routes of transmission from animals to humans are well known and include direct exposure to infected animals or consumption of contaminated animal products. Application of fingerprinting tools facilitates analysis of the molecular epidemiology of M. bovis in animal-to-human and human-to-human transmission. Apart from cattle and M. bovis, other animal species and members within the M. tuberculosis complex can contribute to the zoonosis. Improvements in diagnostic techniques, application of more advanced discriminatory genotyping tools, and collaboration between veterinary and human health care researchers are key to our understanding of this zoonosis. Copyright © 2013 Elsevier Ltd. All rights reserved.

The use of fire and human distribution

PubMed Central

MacDonald, Katharine

2017-01-01

ABSTRACT Humans today live in a wide range of environments from the iciest to the hottest, thanks to diverse cultural solutions that buffer temperature extremes. The prehistory of this relationship between human distribution, cultural solutions and temperature conditions may help us to understand the evolution of human biological adaptations to cold temperature. Fire has long been seen as an important factor in human evolution and range expansion, particularly into temperate latitudes. Nevertheless, the earliest evidence for hominin presence in Eurasia, and middle latitudes in northern Europe, substantially predates convincing evidence for fire use in these regions. This review outlines the current state of knowledge of the chronology of hominin dispersal into temperate latitudes, from the earliest occupants to our own species, and the archeological evidence for fire use. Given continuing disagreement about this chronology and limitations to the archeological evidence, new, complementary approaches are worthwhile and would benefit from information from studies of current human temperature regulation. PMID:28680931

A Touch Sensing Technique Using the Effects of Extremely Low Frequency Fields on the Human Body

PubMed Central

Elfekey, Hatem; Bastawrous, Hany Ayad; Okamoto, Shogo

2016-01-01

Touch sensing is a fundamental approach in human-to-machine interfaces, and is currently under widespread use. Many current applications use active touch sensing technologies. Passive touch sensing technologies are, however, more adequate to implement low power or energy harvesting touch sensing interfaces. This paper presents a passive touch sensing technique based on the fact that the human body is affected by the surrounding extremely low frequency (ELF) electromagnetic fields, such as those of AC power lines. These external ELF fields induce electric potentials on the human body—because human tissues exhibit some conductivity at these frequencies—resulting in what is called AC hum. We therefore propose a passive touch sensing system that detects this hum noise when a human touch occurs, thus distinguishing between touch and non-touch events. The effectiveness of the proposed technique is validated by designing and implementing a flexible touch sensing keyboard. PMID:27918416

A Touch Sensing Technique Using the Effects of Extremely Low Frequency Fields on the Human Body.

PubMed

Elfekey, Hatem; Bastawrous, Hany Ayad; Okamoto, Shogo

2016-12-02

Touch sensing is a fundamental approach in human-to-machine interfaces, and is currently under widespread use. Many current applications use active touch sensing technologies. Passive touch sensing technologies are, however, more adequate to implement low power or energy harvesting touch sensing interfaces. This paper presents a passive touch sensing technique based on the fact that the human body is affected by the surrounding extremely low frequency (ELF) electromagnetic fields, such as those of AC power lines. These external ELF fields induce electric potentials on the human body-because human tissues exhibit some conductivity at these frequencies-resulting in what is called AC hum. We therefore propose a passive touch sensing system that detects this hum noise when a human touch occurs, thus distinguishing between touch and non-touch events. The effectiveness of the proposed technique is validated by designing and implementing a flexible touch sensing keyboard.

Current status of prediction of drug disposition and toxicity in humans using chimeric mice with humanized liver.

PubMed

Kitamura, Shigeyuki; Sugihara, Kazumi

2014-01-01

1. Human-chimeric mice with humanized liver have been constructed by transplantation of human hepatocytes into several types of mice having genetic modifications that injure endogenous liver cells. Here, we focus on liver urokinase-type plasminogen activator-transgenic severe combined immunodeficiency (uPA/SCID) mice, which are the most widely used human-chimeric mice. Studies so far indicate that drug metabolism, drug transport, pharmacological effects and toxicological action in these mice are broadly similar to those in humans. 2. Expression of various drug-metabolizing enzymes is known to be different between humans and rodents. However, the expression pattern of cytochrome P450, aldehyde oxidase and phase II enzymes in the liver of human-chimeric mice resembles that in humans, not that in the host mice. 3. Metabolism of various drugs, including S-warfarin, zaleplon, ibuprofen, naproxen, coumarin, troglitazone and midazolam, in human-chimeric mice is mediated by human drug-metabolizing enzymes, not by host mouse enzymes, and thus resembles that in humans. 4. Pharmacological and toxicological effects of various drugs in human-chimeric mice are also similar to those in humans. 5. The current consensus is that chimeric mice with humanized liver are useful to predict drug metabolism catalyzed by cytochrome P450, aldehyde oxidase and phase II enzymes in humans in vivo and in vitro. Some remaining issues are discussed in this review.

45 CFR 1179.3 - Applicability.

Code of Federal Regulations, 2010 CFR

2010-10-01

... HUMANITIES NATIONAL ENDOWMENT FOR THE HUMANITIES SALARY OFFSET § 1179.3 Applicability. (a) These regulations are to be followed when: (1) The National Endowment for the Humanities is owed a debt by an individual currently employed by another Federal agency; (2) The National Endowment for the Humanities is owed a debt...

45 CFR 1179.3 - Applicability.

Code of Federal Regulations, 2011 CFR

2011-10-01

... HUMANITIES NATIONAL ENDOWMENT FOR THE HUMANITIES SALARY OFFSET § 1179.3 Applicability. (a) These regulations are to be followed when: (1) The National Endowment for the Humanities is owed a debt by an individual currently employed by another Federal agency; (2) The National Endowment for the Humanities is owed a debt...

45 CFR 1179.1 - Purpose and scope.

Code of Federal Regulations, 2011 CFR

2011-10-01

... HUMANITIES NATIONAL ENDOWMENT FOR THE HUMANITIES SALARY OFFSET § 1179.1 Purpose and scope. (a) This... to all Federal employees who owe debts to the National Endowment for the Humanities (NEH) and to current employees of the National Endowment for the Humanities who owe debts to other Federal agencies...

45 CFR 1179.1 - Purpose and scope.

Code of Federal Regulations, 2010 CFR

2010-10-01

... HUMANITIES NATIONAL ENDOWMENT FOR THE HUMANITIES SALARY OFFSET § 1179.1 Purpose and scope. (a) This... to all Federal employees who owe debts to the National Endowment for the Humanities (NEH) and to current employees of the National Endowment for the Humanities who owe debts to other Federal agencies...

76 FR 39399 - Chlorpyrifos Registration Review; Preliminary Human Health Risk Assessment; Notice of Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-06

... Review; Preliminary Human Health Risk Assessment; Notice of Availability AGENCY: Environmental Protection... perform its intended function without unreasonable adverse effects on human health or the environment. As... pesticide's registration is based on current scientific and other knowledge, including its effects on human...

Ethical Considerations in Human Movement Research.

ERIC Educational Resources Information Center

Olivier, Steve

1995-01-01

Highlights ethical issues for human subject research, identifying principles that form the construct of a code of research ethics and evaluating against this construct past human experimentation and current research in human movement studies. The efficacy of legislation and self-regulation is examined. Particular attention is given to the context…

Overload and Boredom: When the Humanities Turn to Noise.

ERIC Educational Resources Information Center

Walter, James A.

This paper argues that the current debate over humanities curricula has failed to articulate a vision for humanities education because it has turned on a liberal/conservative axis. It also contends that educators must stop debating elite versus democratic values or traditional versus contemporary problems in humanities education, and start…

Human Factors and Robotics: Current Status and Future Prospects.

ERIC Educational Resources Information Center

Parsons, H. McIlvaine; Kearsley, Greg P.

The principal human factors engineering issue in robotics is the division of labor between automation (robots) and human beings. This issue reflects a prime human factors engineering consideration in systems design--what equipment should do and what operators and maintainers should do. Understanding of capabilities and limitations of robots and…

78 FR 43258 - Privacy Act; System of Records: Human Resources Records, State-31

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-19

... DEPARTMENT OF STATE [Public Notice 8384] Privacy Act; System of Records: Human Resources Records... system of records, Human Resources Records, State- 31, pursuant to the provisions of the Privacy Act of... State proposes that the current system will retain the name ``Human Resources Records'' (previously...

Decolonizing Education: A Critical Discourse Analysis of Post-Secondary Humanities Textbooks

ERIC Educational Resources Information Center

Harper, Kimberly C.

2012-01-01

This dissertation examines nine post-secondary humanities textbooks published between 2001 and 2011 using an approach that includes both qualitative and quantitative methodology to analyze the written and visual content of humanities textbooks. This dissertation engages in current debates that address bias in humanities textbooks and contributes…

Voltage-gated Na+ currents in human dorsal root ganglion neurons

PubMed Central

Zhang, Xiulin; Priest, Birgit T; Belfer, Inna; Gold, Michael S

2017-01-01

Available evidence indicates voltage-gated Na+ channels (VGSCs) in peripheral sensory neurons are essential for the pain and hypersensitivity associated with tissue injury. However, our understanding of the biophysical and pharmacological properties of the channels in sensory neurons is largely based on the study of heterologous systems or rodent tissue, despite evidence that both expression systems and species differences influence these properties. Therefore, we sought to determine the extent to which the biophysical and pharmacological properties of VGSCs were comparable in rat and human sensory neurons. Whole cell patch clamp techniques were used to study Na+ currents in acutely dissociated neurons from human and rat. Our results indicate that while the two major current types, generally referred to as tetrodotoxin (TTX)-sensitive and TTX-resistant were qualitatively similar in neurons from rats and humans, there were several differences that have important implications for drug development as well as our understanding of pain mechanisms. DOI: http://dx.doi.org/10.7554/eLife.23235.001 PMID:28508747

The Non-Human Primate Experimental Glaucoma Model

PubMed Central

Burgoyne, Claude F.

2015-01-01

The purpose of this report is to summarize the current strengths and weaknesses of the non-human primate (NHP) experimental glaucoma (EG) model through sections devoted to its history, methods, important findings, alternative optic neuropathy models and future directions. NHP EG has become well established for studying human glaucoma in part because the NHP optic nerve head (ONH) shares a close anatomic association with the human ONH and because it provides the only means of systematically studying the very earliest visual system responses to chronic IOP elevation, i.e. the conversion from ocular hypertension to glaucomatous damage. However, NHPs are impractical for studies that require large animal numbers, demonstrate spontaneous glaucoma only rarely, do not currently provide a model of the neuropathy at normal levels of IOP, and cannot easily be genetically manipulated, except through tissue-specific, viral vectors. The goal of this summary is to direct NHP EG and non-NHP EG investigators to the previous, current and future accomplishment of clinically relevant knowledge in this model. PMID:26070984

Plastic and Human Health: A Micro Issue?

PubMed

Wright, Stephanie L; Kelly, Frank J

2017-06-20

Microplastics are a pollutant of environmental concern. Their presence in food destined for human consumption and in air samples has been reported. Thus, microplastic exposure via diet or inhalation could occur, the human health effects of which are unknown. The current review article draws upon cross-disciplinary scientific literature to discuss and evaluate the potential human health impacts of microplastics and outlines urgent areas for future research. Key literature up to September 2016 relating to accumulation, particle toxicity, and chemical and microbial contaminants was critically examined. Although microplastics and human health is an emerging field, complementary existing fields indicate potential particle, chemical and microbial hazards. If inhaled or ingested, microplastics may accumulate and exert localized particle toxicity by inducing or enhancing an immune response. Chemical toxicity could occur due to the localized leaching of component monomers, endogenous additives, and adsorbed environmental pollutants. Chronic exposure is anticipated to be of greater concern due to the accumulative effect that could occur. This is expected to be dose-dependent, and a robust evidence-base of exposure levels is currently lacking. Although there is potential for microplastics to impact human health, assessing current exposure levels and burdens is key. This information will guide future research into the potential mechanisms of toxicity and hence therein possible health effects.

Monitoring the outcomes of interventions against Taenia solium: options and suggestions.

PubMed

Lightowlers, M W; Garcia, H H; Gauci, C G; Donadeu, M; Abela-Ridder, B

2016-03-01

There is an increasing interest in reducing the incidence of human neurocysticercosis, caused by infection with the larval stage of Taenia solium. Several intervention trials are currently assessing various options for control of T. solium transmission. A critical aspect of these trials will be the evaluation of whether the interventions have been successful. However, there is no consensus about the most appropriate or valuable methods that should be used. Here, we undertake a critical assessment of the diagnostic tests which are currently available for human T. solium taeniasis and human and porcine cysticercosis, as well as their suitability for evaluation of intervention trial outcomes. Suggestions are made about which of the measures that are available for evaluation of T. solium interventions would be most suitable, and which methodologies are the most appropriate given currently available technologies. Suggestions are also made in relation to the most urgent research needs in order to address deficiencies in current diagnostic methods. © 2015 The Authors. Parasite Immunology Published by John Wiley & Sons Ltd.

Human Factors in the Design of the Crew Exploration Vehicle (CEV)

NASA Technical Reports Server (NTRS)

Whitmore, Mihriban; Byrne, Vicky; Holden, Kritina

2007-01-01

NASA s Space Exploration vision for humans to venture to the moon and beyond provides interesting human factors opportunities and challenges. The Human Engineering group at NASA has been involved in the initial phases of development of the Crew Exploration Vehicle (CEV), Orion. Getting involved at the ground level, Human Factors engineers are beginning to influence design; this involvement is expected to continue throughout the development lifecycle. The information presented here describes what has been done to date, what is currently going on, and what is expected in the future. During Phase 1, prior to the contract award to Lockheed Martin, the Human Engineering group was involved in generating requirements, conducting preliminary task analyses based on interviews with subject matter experts in all vehicle systems areas, and developing preliminary concepts of operations based on the task analysis results. In addition, some early evaluations to look at CEV net habitable volume were also conducted. The program is currently in Phase 2, which is broken down into design cycles, including System Readiness Review, Preliminary Design Review, and Critical Design Review. Currently, there are ongoing Human Engineering Technical Interchange Meetings being held with both NASA and Lockheed Martin in order to establish processes, desired products, and schedules. Multiple design trades and quick-look evaluations (e.g. display device layout and external window size) are also in progress. Future Human Engineering activities include requirement verification assessments and crew/stakeholder evaluations of increasing fidelity. During actual flights of the CEV, the Human Engineering group is expected to be involved in in-situ testing and lessons learned reporting, in order to benefit human space flight beyond the initial CEV program.

The Role of Experience in the Behavioral Development of Human Infants: Current Status and Recommendations.

ERIC Educational Resources Information Center

White, Burton L.

This paper is designed as an information guide for those persons responsible for rearing human infants from birth to 18 months. The author provides an extensive review of the literature and trends of research in this area noting that the current volumes of knowledge in this area are not yet dependable enough to provide reliable bases for practice.…

Human responses to electricity: A literature review

NASA Technical Reports Server (NTRS)

Turner, H. S.

1972-01-01

An extensive review of literature on research concerning biomedical sensors is presented for establishing standards for current limiting devices. The physiological and pathological responses of the human, when exposed to electricity are reported including the thresholds: for perception of electricity, pain by electric current, induction of muscular contraction by electric shock, and ventricular fibrillation. The passive electrical properties of cells and tissues are also reported.

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016.

PubMed

Bikson, Marom; Grossman, Pnina; Thomas, Chris; Zannou, Adantchede Louis; Jiang, Jimmy; Adnan, Tatheer; Mourdoukoutas, Antonios P; Kronberg, Greg; Truong, Dennis; Boggio, Paulo; Brunoni, André R; Charvet, Leigh; Fregni, Felipe; Fritsch, Brita; Gillick, Bernadette; Hamilton, Roy H; Hampstead, Benjamin M; Jankord, Ryan; Kirton, Adam; Knotkova, Helena; Liebetanz, David; Liu, Anli; Loo, Colleen; Nitsche, Michael A; Reis, Janine; Richardson, Jessica D; Rotenberg, Alexander; Turkeltaub, Peter E; Woods, Adam J

2016-01-01

This review updates and consolidates evidence on the safety of transcranial Direct Current Stimulation (tDCS). Safety is here operationally defined by, and limited to, the absence of evidence for a Serious Adverse Effect, the criteria for which are rigorously defined. This review adopts an evidence-based approach, based on an aggregation of experience from human trials, taking care not to confuse speculation on potential hazards or lack of data to refute such speculation with evidence for risk. Safety data from animal tests for tissue damage are reviewed with systematic consideration of translation to humans. Arbitrary safety considerations are avoided. Computational models are used to relate dose to brain exposure in humans and animals. We review relevant dose-response curves and dose metrics (e.g. current, duration, current density, charge, charge density) for meaningful safety standards. Special consideration is given to theoretically vulnerable populations including children and the elderly, subjects with mood disorders, epilepsy, stroke, implants, and home users. Evidence from relevant animal models indicates that brain injury by Direct Current Stimulation (DCS) occurs at predicted brain current densities (6.3-13 A/m(2)) that are over an order of magnitude above those produced by conventional tDCS. To date, the use of conventional tDCS protocols in human trials (≤40 min, ≤4 milliamperes, ≤7.2 Coulombs) has not produced any reports of a Serious Adverse Effect or irreversible injury across over 33,200 sessions and 1000 subjects with repeated sessions. This includes a wide variety of subjects, including persons from potentially vulnerable populations. Copyright © 2016 Elsevier Inc. All rights reserved.

Safety of transcranial Direct Current Stimulation: Evidence Based Update 2016

PubMed Central

Bikson, Marom; Grossman, Pnina; Thomas, Chris; Zannou, Adantchede Louis; Jiang, Jimmy; Adnan, Tatheer; Mourdoukoutas, Antonios P; Kronberg, Greg; Truong, Dennis; Boggio, Paulo; Brunoni, André R.; Charvet, Leigh; Fregni, Felipe; Fritsch, Brita; Gillick, Bernadette; Hamilton, Roy H.; Hampstead, Benjamin M.; Jankord, Ryan; Kirton, Adam; Knotkova, Helena; Liebetanz, David; Liu, Anli; Loo, Colleen; Nitsche, Michael A.; Reis, Janine; Richardson, Jessica D.; Rotenberg, Alexander; Turkeltaub, Peter E.; Woods, Adam J.

2016-01-01

This review updates and consolidates evidence on the safety of transcranial Direct Current Stimulation (tDCS). Safety is here operationally defined by, and limited to, the absence of evidence for a Serious Adverse Effect, the criteria for which are rigorously defined. This review adopts an evidence-based approach, based on an aggregation of experience from human trials, taking care not to confuse speculation on potential hazards or lack of data to refute such speculation with evidence for risk. Safety data from animal tests for tissue damage are reviewed with systematic consideration of translation to humans. Arbitrary safety considerations are avoided. Computational models are used to relate dose to brain exposure in humans and animals. We review relevant dose-response curves and dose metrics (e.g. current, duration, current density, charge, charge density) for meaningful safety standards. Special consideration is given to theoretically vulnerable populations including children and the elderly, subjects with mood disorders, epilepsy, stroke, implants, and home users. Evidence from relevant animal models indicates that brain injury by Direct Current Stimulation (DCS) occurs at predicted brain current densities (6.3–13 A/m2) that are over an order of magnitude above those produced by conventional tDCS. To date, the use of conventional tDCS protocols in human trials (≤40 min, ≤4 mA, ≤7.2 Coulombs) has not produced any reports of a Serious Adverse Effect or irreversible injury across over 33,200 sessions and 1,000 subjects with repeated sessions. This includes a wide variety of subjects, including persons from potentially vulnerable populations. PMID:27372845

21 CFR 210.2 - Applicability of current good manufacturing practice regulations.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Applicability of current good manufacturing... AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE IN MANUFACTURING, PROCESSING, PACKING, OR HOLDING OF DRUGS; GENERAL § 210.2 Applicability of current good manufacturing...

Generating trunk neural crest from human pluripotent stem cells

PubMed Central

Huang, Miller; Miller, Matthew L.; McHenry, Lauren K.; Zheng, Tina; Zhen, Qiqi; Ilkhanizadeh, Shirin; Conklin, Bruce R.; Bronner, Marianne E.; Weiss, William A.

2016-01-01

Neural crest cells (NCC) are stem cells that generate different lineages, including neuroendocrine, melanocytic, cartilage, and bone. The differentiation potential of NCC varies according to the level from which cells emerge along the neural tube. For example, only anterior “cranial” NCC form craniofacial bone, whereas solely posterior “trunk” NCC contribute to sympathoadrenal cells. Importantly, the isolation of human fetal NCC carries ethical and scientific challenges, as NCC induction typically occur before pregnancy is detectable. As a result, current knowledge of NCC biology derives primarily from non-human organisms. Important differences between human and non-human NCC, such as expression of HNK1 in human but not mouse NCC, suggest a need to study human NCC directly. Here, we demonstrate that current protocols to differentiate human pluripotent stem cells (PSC) to NCC are biased toward cranial NCC. Addition of retinoic acid drove trunk-related markers and HOX genes characteristic of a posterior identity. Subsequent treatment with bone morphogenetic proteins (BMPs) enhanced differentiation to sympathoadrenal cells. Our approach provides methodology for detailed studies of human NCC, and clarifies roles for retinoids and BMPs in the differentiation of human PSC to trunk NCC and to sympathoadrenal lineages. PMID:26812940

On the Modeling of Electrical Effects Experienced by Space Explorers During Extra Vehicular Activities: Intracorporal Currents, Resistances, and Electric Fields

NASA Technical Reports Server (NTRS)

Cela, Carlos J.; Loizos, Kyle; Lazzi, Gianluca; Hamilton, Douglas; Lee, Raphael C.

2011-01-01

Recent research has shown that space explorers engaged in Extra Vehicular Activities (EVAs) may be exposed, under certain conditions, to undesired electrical currents. This work focuses on determining whether these undesired induced electrical currents could be responsible for involuntary neuromuscular activity in the subjects, possibly caused by either large diameter peripheral nerve activation or reflex activity from cutaneous afferent stimulation. An efficient multiresolution variant of the admittance method along with a millimeter-resolution model of a male human body were used to calculate induced electric fields, resistance between contact electrodes used to simulate the potential exposure condition, and currents induced in the human body model. Results show that, under realistic exposure conditions using a 15V source, current density magnitudes and total current injected are well above previously reported startle reaction thresholds. This indicates that, under the considered conditions, the subjects could experience involuntary motor response.

Domestic dogs comprehend human communication with iconic signs.

PubMed

Kaminski, Juliane; Tempelmann, Sebastian; Call, Josep; Tomasello, Michael

2009-11-01

A key skill in early human development is the ability to comprehend communicative intentions as expressed in both nonlinguistic gestures and language. In the current studies, we confronted domestic dogs (some of whom knew many human 'words') with a task in which they had to infer the intended referent of a human's communicative act via iconic signs--specifically, replicas and photographs. Both trained and untrained dogs successfully used iconic replicas to fetch the desired item, with many doing so from the first trial. Dogs' ability to use photographs in this same situation was less consistent. Because simple matching to sample in experimental contexts typically takes hundreds of trials (and because similarity between iconic sign and target item did not predict success), we propose that dogs' skillful performance in the current task reflects important aspects of the comprehension of human communicative intentions.

Are evolving human rights harmless? An examination of English legislation, prostitution and its effect on human relatedness.

PubMed

Westin, Anna

2014-01-01

This paper addresses key philosophical and social questions that shape the contemporary discourse on prostitution. The initial section outlines the contemporary challenges facing legislative practice on prostitution in England. This involves analysing moral and legal framework surrounding prostitution that has made the current legislative dilemma surrounding prostitution practice possible. The second part of the paper then outlines the history of the philosophy of human rights from Aquinas to the Universal Declaration of Human Rights (1948). The paper concludes by analysing whether the current ontology employed by human rights theory is effective in creating a system of just relatedness between agents, made visible in concrete legislative guidance. I argue that legislation guided by a fragmented teleology and ontological anthropology enables asymmetrical patterns of relatedness that can cause genuine physical and psychological harm to individuals.

When Humans Become Animals: Development of the Animal Category in Early Childhood

ERIC Educational Resources Information Center

Herrmann, Patricia A.; Medin, Douglas L.; Waxman, Sandra R.

2012-01-01

The current study examines 3- and 5-year-olds' representation of the concept we label "animal" and its two nested concepts--"animal"[subscript contrastive] (including only non-human animals) and "animal"[subscript inclusive] (including both humans and non-human animals). Building upon evidence that naming promotes object categorization, we…

75 FR 53577 - Choline hydroxide; Exemption from the Requirement of a Tolerance

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-01

... endogenously in the human body. Humans are currently exposed to choline on a daily basis through commonly eaten... dietary consumption of choline, choline is made endogenously in the human body. Choline is a precursor to... human health. In order to determine the risks from aggregate exposure to pesticide inert ingredients...

Swine Brucellosis: Current Perspectives

USDA-ARS?s Scientific Manuscript database

Brucella suis is a significant zoonosis that is present in domestic livestock and wildlife in many countries worldwide. Transmission from animal reservoirs is the source of human infection as human to human transmission is very rare. Although swine brucellosis causes economic losses in domestic liv...

Current applications of human pluripotent stem cells: possibilities and challenges.

PubMed

Ho, Pai-Jiun; Yen, Men-Luh; Yet, Shaw-Fang; Yen, B Linju

2012-01-01

Stem cells are self-renewable cells with the differentiation capacity to develop into somatic cells with biological functions. This ability to sustain a renewable source of multi- and/or pluripotential differentiation has brought new hope to the field of regenerative medicine in terms of cell therapy and tissue engineering. Moreover, stem cells are invaluable tools as in vitro models for studying diverse fields, from basic scientific questions such as developmental processes and lineage commitment, to practical application including drug screening and testing. The stem cells with widest differentiation potential are pluripotent stem cells (PSCs), which are rare cells with the ability to generate somatic cells from all three germ layers. PSCs are considered the most optimal choice for therapeutic potential of stem cells, bringing new impetus to the field of regenerative medicine. In this article, we discuss the therapeutic potential of human PSCs (hPSCs) including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), reviewing the current preclinical and clinical data using these stem cells. We describe the classification of different sources of hPSCs, ongoing research, and currently encountered clinical obstacles of these novel and versatile human stem cells.

Current ebola vaccines.

PubMed

Hoenen, Thomas; Groseth, Allison; Feldmann, Heinz

2012-07-01

Ebolaviruses cause severe viral hemorrhagic fever in humans and non-human primates (NHPs), with case fatality rates of up to 90%. Currently, neither a specific treatment nor a vaccine licensed for use in humans is available. However, a number of vaccine candidates have been developed in the last decade that are highly protective in NHPs, the gold standard animal model for ebola hemorrhagic fever. This review analyzes a number of scenarios for the use of ebolavirus vaccines, discusses the requirements for ebolavirus vaccines in these scenarios and describes current ebolavirus vaccines. Among these vaccines are recombinant adenoviruses, recombinant vesicular stomatitis viruses (VSVs), recombinant human parainfluenza viruses and virus-like particles. Interestingly, one of these vaccine platforms, based on recombinant VSVs, has also demonstrated post-exposure protection in NHPs. The most pressing remaining challenge is now to move these vaccine candidates forward into human trials and toward licensure. In order to achieve this, it will be necessary to establish the mechanisms and correlates of protection for these vaccines, and to continue to demonstrate their safety, particularly in potentially immunocompromised populations. However, already now there is sufficient evidence that, from a scientific perspective, a vaccine protective against ebolaviruses is possible.

Experimental primates and non-human primate (NHP) models of human diseases in China: current status and progress.

PubMed

Zhang, Xiao-Liang; Pang, Wei; Hu, Xin-Tian; Li, Jia-Li; Yao, Yong-Gang; Zheng, Yong-Tang

2014-11-18

Non-human primates (NHPs) are phylogenetically close to humans, with many similarities in terms of physiology, anatomy, immunology, as well as neurology, all of which make them excellent experimental models for biomedical research. Compared with developed countries in America and Europe, China has relatively rich primate resources and has continually aimed to develop NHPs resources. Currently, China is a leading producer and a major supplier of NHPs on the international market. However, there are some deficiencies in feeding and management that have hampered China's growth in NHP research and materials. Nonetheless, China has recently established a number of primate animal models for human diseases and achieved marked scientific progress on infectious diseases, cardiovascular diseases, endocrine diseases, reproductive diseases, neurological diseases, and ophthalmic diseases, etc. Advances in these fields via NHP models will undoubtedly further promote the development of China's life sciences and pharmaceutical industry, and enhance China's position as a leader in NHP research. This review covers the current status of NHPs in China and other areas, highlighting the latest developments in disease models using NHPs, as well as outlining basic problems and proposing effective countermeasures to better utilize NHP resources and further foster NHP research in China.

Humanized mouse models: Application to human diseases.

PubMed

Ito, Ryoji; Takahashi, Takeshi; Ito, Mamoru

2018-05-01

Humanized mice are superior to rodents for preclinical evaluation of the efficacy and safety of drug candidates using human cells or tissues. During the past decade, humanized mouse technology has been greatly advanced by the establishment of novel platforms of genetically modified immunodeficient mice. Several human diseases can be recapitulated using humanized mice due to the improved engraftment and differentiation capacity of human cells or tissues. In this review, we discuss current advanced humanized mouse models that recapitulate human diseases including cancer, allergy, and graft-versus-host disease. © 2017 Wiley Periodicals, Inc.

Human Missions to Near-Earth Asteroids: An Update on NASA's Current Status and Proposed Activities for Small Body Exploration

NASA Technical Reports Server (NTRS)

Abell, P. A.; Mazanek, D. D.; Barbee, B. W.; Mink, R. G.; Landis, R. R.; Adamo, D. R.; Johnson, L. N.; Yeomans, D. K.; Reeves, D. M.; Larman, K. T.;

The aspiration for holism in the medical humanities: Some historical and philosophical sources of reflection.

PubMed

Pilgrim, David

2016-07-01

The relationship between the arts and health is now of interest to policy makers, patients, professionals and health researchers. This article historicises the potential for holism, a current aspiration within the medical humanities. This contemporary debate in the research community reflects philosophical positions about idealism and realism, with their traceable historical roots. This article summarises those roots and draws attention to their current relevance for health researchers. Starting with the recognition within the medical humanities that biomedical reductionism now attracts criticism, it moves to exploring the history of ideas in philosophy, the arts and science about holism and the challenge of researching health and illness within the complexity of being fully human. © The Author(s) 2015.

[Nutritional epigenetics and epigenetic effects of human breast milk].

PubMed

Lukoyanova, O L; Borovik, T E

The article provides an overview of the current literature on nutritional epigenetics. There are currently actively studied hypothesis that nutrition especially in early life or in critical periods of the development, may have a role in modulating gene expression, and, therefore, have later effects on health in adults. Nutritional epigenetics concerns knowledge about the possible effects of nutrients on gene expression. Human breast milk is well-known for its ability in preventing necrotizing enterocolitis, infectious diseases, and also non-communicable diseases, such as obesity and related disorders. This paper discusses about presumed epigenetic effects of human breast milk and some its components. While evidence suggests that a direct relationship may exist of some components of human breast milk with epigenetic changes, the mechanisms involved are stillunclear.

Therapeutic options for diseases due to potential viral agents of bioterrorism.

PubMed

Bronze, Michael S; Greenfield, Ronald A

2003-02-01

The etiologic agents of smallpox and viral hemorrhagic fever have emerged as potential agents of bioterrorism due to their virulence, potential for human to human dissemination and limited strategies for treatment and prevention. Cidofovir has shown significant promise in animal models, and limited case reports in humans are encouraging. Ribavirin is the treatment of choice for certain hemorrhagic fever viral infections, but has no current application to Ebola and Marburg infections. Current vaccine strategies for smallpox are effective, but carry significant risk for complications. Licensed vaccines for hemorrhagic fever viruses are limited to yellow fever, but animal studies are promising. Genomic analysis of the viral pathogen and the animal model response to infection may provide valuable information enabling the development of novel treatment and prevention strategies. Current knowledge of these strategies is reviewed.

Some inadequacies of the current human factors certification process of advanced aircraft technologies

NASA Technical Reports Server (NTRS)

Paries, Jean

1994-01-01

Automation related accidents or serious incidents are not limited to advanced technology aircraft. There is a full history of such accidents with conventional technology aircraft. However, this type of occurrence is far from sparing the newest 'glass cockpit' generation, and it even seems to be a growing contributor to its accident rate. Nevertheless, all these aircraft have been properly certificated according to the relevant airworthiness regulations. Therefore, there is a growing concern that with the technological advancement of air transport aircraft cockpits, the current airworthiness regulations addressing cockpit design and human factors may have reached some level of inadequacy. This paper reviews some aspects of the current airworthiness regulations and certification process related to human factors of cockpit design and focuses on questioning their ability to guarantee the intended safety objectives.

A Critical Assessment of Research on Neurotransmitters in Alzheimer's Disease.

PubMed

Reddy, P Hemachandra

2017-01-01

The purpose of this mini-forum, "Neurotransmitters and Alzheimer's Disease", is to critically assess the current status of neurotransmitters in Alzheimer's disease. Neurotransmitters are essential neurochemicals that maintain synaptic and cognitive functions in mammals, including humans, by sending signals across pre- to post-synaptic neurons. Authorities in the fields of synapses and neurotransmitters of Alzheimer's disease summarize the current status of basic biology of synapses and neurotransmitters, and also update the current status of clinical trials of neurotransmitters in Alzheimer's disease. This article discusses the prevalence, economic impact, and stages of Alzheimer's dementia in humans.

Human Missions to Near-Earth Asteroids: An Update on NASA's Current Status and Proposed Activities for Small Body Exploration

NASA Technical Reports Server (NTRS)

Abell, P. A.; Mazanek, D. D.; Barbee, B. W.; Mink, R. G.; Landis, R. R.; Adamo, D. R.; Johnson, L. N.; Yeomans, D. K.; Reeves, D. M.; Larman, K. T.;

Introduction to human factors

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

Winters, J.M.

Some background is given on the field of human factors. The nature of problems with current human/computer interfaces is discussed, some costs are identified, ideal attributes of graceful system interfaces are outlined, and some reasons are indicated why it's not easy to fix the problems. (LEW)

Report: EPA’s Distribution of Superfund Human Resources Does Not Support Current Regional Workload

EPA Pesticide Factsheets

Report #17-P-0397, September 19, 2017. Due to insufficient human resources to cover all Superfund site work, some regions have had to slow down or discontinue their efforts to protect human health and the environment.

The estimated impact of human papillomavirus vaccine coverage on the lifetime cervical cancer burden among girls currently aged 12 years and younger in the United States.

PubMed

Chesson, Harrell W; Ekwueme, Donatus U; Saraiya, Mona; Dunne, Eileen F; Markowitz, Lauri E

2014-11-01

Using a previously published dynamic model, we illustrate the potential benefits of human papillomavirus vaccination among girls currently 12 years or younger in the United States. Increasing vaccine coverage of young girls to 80% would avert 53,300 lifetime cervical cancer cases versus 30% coverage and 28,800 cases versus 50% coverage.

A review of current methods using bacteriophages in live animals, food and animal products intended for human consumption.

PubMed

Cooper, Ian R

2016-11-01

Bacteriophages are utilised in the food industry as biocontrol agents to reduce the load of bacteria, and thus reduce potential for human infection. This review focuses on current methods using bacteriophages within the food chain. Limitations of research will be discussed, and the potential for future food-based bacteriophage research. Copyright © 2016 Elsevier B.V. All rights reserved.

Overview of the HFM-181 Symposium Programme, Medical Technology Repurposed to Enhance Human Performance

DTIC Science & Technology

2009-10-01

BIO -INSPIRED HUMAN PERFORMANCE ENHANCEMENT 3.1 Biological performance currently outside of the bounds of the human species HPE opportunities may...strategies to preferentially burn fat in weight reduction (85). 3.2 Bio -inspired opportunities for human performance There are many interesting...solutions to assist human performance Nonmedical applications of bio -inspired engineering and computing technologies are a recognized priority in

Human Factors Engineering as a System in the Vision for Exploration

NASA Technical Reports Server (NTRS)

Whitmore, Mihriban; Smith, Danielle; Holden, Kritina

2006-01-01

In order to accomplish NASA's Vision for Exploration, while assuring crew safety and productivity, human performance issues must be well integrated into system design from mission conception. To that end, a two-year Technology Development Project (TDP) was funded by NASA Headquarters to develop a systematic method for including the human as a system in NASA's Vision for Exploration. The specific goals of this project are to review current Human Systems Integration (HSI) standards (i.e., industry, military, NASA) and tailor them to selected NASA Exploration activities. Once the methods are proven in the selected domains, a plan will be developed to expand the effort to a wider scope of Exploration activities. The methods will be documented for inclusion in NASA-specific documents (such as the Human Systems Integration Standards, NASA-STD-3000) to be used in future space systems. The current project builds on a previous TDP dealing with Human Factors Engineering processes. That project identified the key phases of the current NASA design lifecycle, and outlined the recommended HFE activities that should be incorporated at each phase. The project also resulted in a prototype of a webbased HFE process tool that could be used to support an ideal HFE development process at NASA. This will help to augment the limited human factors resources available by providing a web-based tool that explains the importance of human factors, teaches a recommended process, and then provides the instructions, templates and examples to carry out the process steps. The HFE activities identified by the previous TDP are being tested in situ for the current effort through support to a specific NASA Exploration activity. Currently, HFE personnel are working with systems engineering personnel to identify HSI impacts for lunar exploration by facilitating the generation of systemlevel Concepts of Operations (ConOps). For example, medical operations scenarios have been generated for lunar habitation in order to identify HSI requirements for the lunar communications architecture. Throughout these ConOps exercises, HFE personnel are testing various tools and methodologies that have been identified in the literature. A key part of the effort is the identification of optimal processes, methods, and tools for these early development phase activities, such as ConOps, requirements development, and early conceptual design. An overview of the activities completed thus far, as well as the tools and methods investigated will be presented.

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

PubMed

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

2012-06-01

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

Basolateral K+ channel involvement in forskolin-activated chloride secretion in human colon

PubMed Central

McNamara, Brian; Winter, Desmond C; Cuffe, John E; O'Sullivan, Gerald C; Harvey, Brian J

1999-01-01

In this study we investigated the role of basolateral potassium transport in maintaining cAMP-activated chloride secretion in human colonic epithelium. Ion transport was quantified in isolated human colonic epithelium using the short-circuit current technique. Basolateral potassium transport was studied using nystatin permeabilization. Intracellular calcium measurements were obtained from isolated human colonic crypts using fura-2 spectrofluorescence imaging. In intact isolated colonic strips, forskolin and prostaglandin E2 (PGE2) activated an inward transmembrane current (ISC) consistent with anion secretion (for forskolin ΔISC = 63.8 ± 6.2 μA cm−2, n = 6; for PGE2 ΔISC = 34.3 ± 5.2 μA cm−2, n = 6). This current was inhibited in chloride-free Krebs solution or by inhibiting basolateral chloride uptake with bumetanide and 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS). The forskolin- and PGE2-induced chloride secretion was inhibited by basolateral exposure to barium (5 mM), tetrapentylammonium (10 μM) and tetraethylammonium (10 mM). The transepithelial current produced under an apical to serosal K+ gradient in nystatin-perforated colon is generated at the basolateral membrane by K+ transport. Forskolin failed to activate this current under conditions of high or low calcium and failed to increase the levels of intracellular calcium in isolated crypts In conclusion, we propose that potassium recycling through basolateral K+ channels is essential for cAMP-activated chloride secretion. PMID:10432355

Semantic Likelihood Models for Bayesian Inference in Human-Robot Interaction

NASA Astrophysics Data System (ADS)

Sweet, Nicholas

Autonomous systems, particularly unmanned aerial systems (UAS), remain limited in au- tonomous capabilities largely due to a poor understanding of their environment. Current sensors simply do not match human perceptive capabilities, impeding progress towards full autonomy. Recent work has shown the value of humans as sources of information within a human-robot team; in target applications, communicating human-generated 'soft data' to autonomous systems enables higher levels of autonomy through large, efficient information gains. This requires development of a 'human sensor model' that allows soft data fusion through Bayesian inference to update the probabilistic belief representations maintained by autonomous systems. Current human sensor models that capture linguistic inputs as semantic information are limited in their ability to generalize likelihood functions for semantic statements: they may be learned from dense data; they do not exploit the contextual information embedded within groundings; and they often limit human input to restrictive and simplistic interfaces. This work provides mechanisms to synthesize human sensor models from constraints based on easily attainable a priori knowledge, develops compression techniques to capture information-dense semantics, and investigates the problem of capturing and fusing semantic information contained within unstructured natural language. A robotic experimental testbed is also developed to validate the above contributions.

Commentary: A Historical Review of Centers for Disease Control and Prevention Antiviral Treatment and Postexposure Chemoprophylaxis Guidance for Human Infections With Novel Influenza A Viruses Associated With Severe Human Disease.

PubMed

Havers, Fiona P; Campbell, Angela P; Uyeki, Timothy M; Fry, Alicia M

2017-09-15

Human infections with novel influenza A viruses are of global public health concern, and antiviral medications have a potentially important role in treatment and prevention of human illness. Initial guidance was developed by the U.S. Centers for Disease Control and Prevention after the emergence of human infections with avian influenza A(H5N1) and has evolved over time, with identification of influenza A(H7N9) virus infections in humans, as well as detection of avian influenza viruses in birds in the United States. This commentary describes the historical context and current guidance for the use of influenza antiviral medications for treatment and post-exposure chemoprophylaxis of human infections with novel influenza A viruses associated with severe human illness, or with the potential to cause severe human disease, and provides the scientific rationale behind current recommendations. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Application of postured human model for SAR measurements

NASA Astrophysics Data System (ADS)

Vuchkovikj, M.; Munteanu, I.; Weiland, T.

2013-07-01

In the last two decades, the increasing number of electronic devices used in day-to-day life led to a growing interest in the study of the electromagnetic field interaction with biological tissues. The design of medical devices and wireless communication devices such as mobile phones benefits a lot from the bio-electromagnetic simulations in which digital human models are used. The digital human models currently available have an upright position which limits the research activities in realistic scenarios, where postured human bodies must be considered. For this reason, a software application called "BodyFlex for CST STUDIO SUITE" was developed. In its current version, this application can deform the voxel-based human model named HUGO (Dipp GmbH, 2010) to allow the generation of common postures that people use in normal life, ensuring the continuity of tissues and conserving the mass to an acceptable level. This paper describes the enhancement of the "BodyFlex" application, which is related to the movements of the forearm and the wrist of a digital human model. One of the electromagnetic applications in which the forearm and the wrist movement of a voxel based human model has a significant meaning is the measurement of the specific absorption rate (SAR) when a model is exposed to a radio frequency electromagnetic field produced by a mobile phone. Current SAR measurements of the exposure from mobile phones are performed with the SAM (Specific Anthropomorphic Mannequin) phantom which is filled with a dispersive but homogeneous material. We are interested what happens with the SAR values if a realistic inhomogeneous human model is used. To this aim, two human models, a homogeneous and an inhomogeneous one, in two simulation scenarios are used, in order to examine and observe the differences in the results for the SAR values.

Surveillance of Human Rabies by National Authorities--A Global Survey.

PubMed

Taylor, L H; Knopf, L

2015-11-01

Effective prevention of deaths due to human rabies is currently hampered by a lack of understanding of the scale of the problem, and the distribution of both animal and human cases across countries, regions and continents. Unfortunately, despite the severity of the disease, accurate data on which to assess these questions and to prioritize and direct public health interventions are not available for many parts of the world. This survey sought to understand the current global situation regarding the surveillance of human rabies. Data were collected from 91 countries across all continents and all categories of human rabies risk, generating the most complete and representative global data set currently available. Respondents were asked key questions about whether human rabies was a notifiable disease, how the surveillance system for human rabies operated and whether the respondent considered that the surveillance system was working effectively. Across the 91 countries from which data were collated, human rabies was a notifiable disease in all but eight. Despite international guidance, surveillance systems were very varied. Even where rabies is a notifiable disease, many countries had surveillance system judged to be ineffective, almost all of these being high and moderate rabies risk countries in Africa and Asia. Overall, 41% of the population covered by this survey (around 2.5 billion people) live in countries where there is no or ineffective rabies surveillance. The lack of robust surveillance is hindering rabies control efforts. However, whilst worldwide rabies surveillance would be improved if rabies were notifiable in all countries, many other challenges to the implementation of effective global human rabies surveillance systems remain. © 2015 Blackwell Verlag GmbH.

Aviation Safety: Modeling and Analyzing Complex Interactions between Humans and Automated Systems

NASA Technical Reports Server (NTRS)

Rungta, Neha; Brat, Guillaume; Clancey, William J.; Linde, Charlotte; Raimondi, Franco; Seah, Chin; Shafto, Michael

2013-01-01

The on-going transformation from the current US Air Traffic System (ATS) to the Next Generation Air Traffic System (NextGen) will force the introduction of new automated systems and most likely will cause automation to migrate from ground to air. This will yield new function allocations between humans and automation and therefore change the roles and responsibilities in the ATS. Yet, safety in NextGen is required to be at least as good as in the current system. We therefore need techniques to evaluate the safety of the interactions between humans and automation. We think that current human factor studies and simulation-based techniques will fall short in front of the ATS complexity, and that we need to add more automated techniques to simulations, such as model checking, which offers exhaustive coverage of the non-deterministic behaviors in nominal and off-nominal scenarios. In this work, we present a verification approach based both on simulations and on model checking for evaluating the roles and responsibilities of humans and automation. Models are created using Brahms (a multi-agent framework) and we show that the traditional Brahms simulations can be integrated with automated exploration techniques based on model checking, thus offering a complete exploration of the behavioral space of the scenario. Our formal analysis supports the notion of beliefs and probabilities to reason about human behavior. We demonstrate the technique with the Ueberligen accident since it exemplifies authority problems when receiving conflicting advices from human and automated systems.

Avian Influenza Virus Infection of Immortalized Human Respiratory Epithelial Cells Depends upon a Delicate Balance between Hemagglutinin Acid Stability and Endosomal pH*

PubMed Central

Daidoji, Tomo; Watanabe, Yohei; Ibrahim, Madiha S.; Yasugi, Mayo; Maruyama, Hisataka; Masuda, Taisuke; Arai, Fumihito; Ohba, Tomoyuki; Honda, Ayae; Ikuta, Kazuyoshi; Nakaya, Takaaki

2015-01-01

The highly pathogenic avian influenza (AI) virus, H5N1, is a serious threat to public health worldwide. Both the currently circulating H5N1 and previously circulating AI viruses recognize avian-type receptors; however, only the H5N1 is highly infectious and virulent in humans. The mechanism(s) underlying this difference in infectivity remains unclear. The aim of this study was to clarify the mechanisms responsible for the difference in infectivity between the current and previously circulating strains. Primary human small airway epithelial cells (SAECs) were transformed with the SV40 large T-antigen to establish a series of clones (SAEC-Ts). These clones were then used to test the infectivity of AI strains. Human SAEC-Ts could be broadly categorized into two different types based on their susceptibility (high or low) to the viruses. SAEC-T clones were poorly susceptible to previously circulating AI but were completely susceptible to the currently circulating H5N1. The hemagglutinin (HA) of the current H5N1 virus showed greater membrane fusion activity at higher pH levels than that of previous AI viruses, resulting in broader cell tropism. Moreover, the endosomal pH was lower in high susceptibility SAEC-T clones than that in low susceptibility SAEC-T clones. Taken together, the results of this study suggest that the infectivity of AI viruses, including H5N1, depends upon a delicate balance between the acid sensitivity of the viral HA and the pH within the endosomes of the target cell. Thus, one of the mechanisms underlying H5N1 pathogenesis in humans relies on its ability to fuse efficiently with the endosomes in human airway epithelial cells. PMID:25673693

Visualizing the Anthropocene: Human Land Use History and Environmental Management

Treesearch

Richard D. Periman

2006-01-01

The term “Anthropocene” defines the current, human-dominated, geological epoch of human-caused environmental influences. Some researchers believe that the beginning of this epoch coincides with the inception of the Industrial Revolution (Crutzen and Stoermer 2000). Research is revealing that humans have affected environments on global and local scales for millennia....

78 FR 78838 - Grant of Interim Extension of the Term of U.S. Patent No. 5,496,801; Recombinant Human...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-27

... Hormone AGENCY: United States Patent and Trademark Office, Commerce. ACTION: Notice of interim patent term... No. 5,496,801. The patent claims the human biological product recombinant human parathyroid hormone... human parathyroid hormone, was filed on October 24, 2013, and is currently undergoing regulatory review...

Update: What Nurses Need to Know about Human Trafficking.

PubMed

Washburn, Joy

Nurses are key people who interact with victims of human trafficking in healthcare and other settings. This article provides a current overview of human trafficking, explains legal definitions, elements for protocols in healthcare settings when trafficking is suspected, nursing roles and responses, interview tools, resources, public health recommendations, and nursing education approaches to address human trafficking.

Reducing the Complexity Gap: Expanding the Period of Human Nurturance

ERIC Educational Resources Information Center

Kiel, L. Douglas

2014-01-01

Socio-techno-cultural reality, in the current historical era, evolves at a faster rate than do human brain or human institutions. This reality creates a "complexity gap" that reduces human and institutional capacities to adapt to the challenges of late modernity. New insights from the neurosciences may help to reduce the complexity gap.…

Domestic Dogs Comprehend Human Communication with Iconic Signs

ERIC Educational Resources Information Center

Kaminski, Juliane; Tempelmann, Sebastian; Call, Josep; Tomasello, Michael

2009-01-01

A key skill in early human development is the ability to comprehend communicative intentions as expressed in both nonlinguistic gestures and language. In the current studies, we confronted domestic dogs (some of whom knew many human "words") with a task in which they had to infer the intended referent of a human's communicative act via iconic…

Robots and Humans in Planetary Exploration: Working Together?

NASA Technical Reports Server (NTRS)

Landis, Geoffrey A.; Lyons, Valerie (Technical Monitor)

2002-01-01

Today's approach to human-robotic cooperation in planetary exploration focuses on using robotic probes as precursors to human exploration. A large portion of current NASA planetary surface exploration is focussed on Mars, and robotic probes are seen as precursors to human exploration in: Learning about operation and mobility on Mars; Learning about the environment of Mars; Mapping the planet and selecting landing sites for human mission; Demonstration of critical technology; Manufacture fuel before human presence, and emplace elements of human-support infrastructure

The origins of non-human primates' manual gestures

PubMed Central

Liebal, Katja; Call, Josep

2012-01-01

The increasing body of research into human and non-human primates' gestural communication reflects the interest in a comparative approach to human communication, particularly possible scenarios of language evolution. One of the central challenges of this field of research is to identify appropriate criteria to differentiate a gesture from other non-communicative actions. After an introduction to the criteria currently used to define non-human primates' gestures and an overview of ongoing research, we discuss different pathways of how manual actions are transformed into manual gestures in both phylogeny and ontogeny. Currently, the relationship between actions and gestures is not only investigated on a behavioural, but also on a neural level. Here, we focus on recent evidence concerning the differential laterality of manual actions and gestures in apes in the framework of a functional asymmetry of the brain for both hand use and language. PMID:22106431

Zoonotic viral diseases and the frontier of early diagnosis, control and prevention.

PubMed

Heeney, J L

2006-11-01

Public awareness of the human health risks of zoonotic infections has grown in recent years. Currently, concern of H5N1 flu transmission from migratory bird populations has increased with foci of fatal human cases. This comes on the heels of other major zoonotic viral epidemics in the last decade. These include other acute emerging or re-emerging viral diseases such as severe acute respiratory syndrome (SARS), West-Nile virus, Ebola virus, monkeypox, as well as the more inapparent insidious slow viral and prion diseases. Virus infections with zoonotic potential can become serious killers once they are able to establish the necessary adaptations for efficient human-to-human transmission under circumstances sufficient to reach epidemic proportions. The monitoring and early diagnosis of these potential risks are overlapping frontiers of human and veterinary medicine. Here, current viral zoonotics and evolving threats are reviewed.

Completion of the swine genome will simplify the production of swine as a large animal biomedical model

PubMed Central

2012-01-01

Background Anatomic and physiological similarities to the human make swine an excellent large animal model for human health and disease. Methods Cloning from a modified somatic cell, which can be determined in cells prior to making the animal, is the only method available for the production of targeted modifications in swine. Results Since some strains of swine are similar in size to humans, technologies that have been developed for swine can be readily adapted to humans and vice versa. Here the importance of swine as a biomedical model, current technologies to produce genetically enhanced swine, current biomedical models, and how the completion of the swine genome will promote swine as a biomedical model are discussed. Conclusions The completion of the swine genome will enhance the continued use and development of swine as models of human health, syndromes and conditions. PMID:23151353

Three Human Attributes

ERIC Educational Resources Information Center

Eaves, Ronald C.; Williams, Thomas O., Jr.

2004-01-01

This study represents a beginning step in research that may ultimately show that the multitudes of human behavior that educators currently encounter may be reduced to three broad human attributes: arousal, affect, and cognition. The resulting simplicity should lead to improved understanding and better decision making by practitioners. Four…

21 CFR 110.19 - Exclusions.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Exclusions. 110.19 Section 110.19 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION CURRENT GOOD MANUFACTURING PRACTICE IN MANUFACTURING, PACKING, OR HOLDING HUMAN FOOD General...

21 CFR 110.19 - Exclusions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Exclusions. 110.19 Section 110.19 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION CURRENT GOOD MANUFACTURING PRACTICE IN MANUFACTURING, PACKING, OR HOLDING HUMAN FOOD General...

in vitro Models if Human Embryonic Mesenchymal Transitions in Morphogenesis

EPA Science Inventory

Our ability to predict human developmental consequences produced by exposure to environmental chemicals is limited by the current experimental and computational models.Human heart defects are among the most common type of birth defects and affect 1% of children (~40,000 children)...

Information Structure, Information Technology, and the Human Services Organizational Environment.

ERIC Educational Resources Information Center

Semke, Jeanette I.; Nurius, Paula S.

1991-01-01

Examines current trends in data collection and information use in human services organizations. Describes issues for managers who are planning information systems, including practitioner resistance to automation. Proposes that conceptual integration of agendas for human services automation, practice evaluation, and service effectiveness enables…

Human Resource Management. Third Edition.

ERIC Educational Resources Information Center

Fisher, Cynthia D.; And Others

This book offers students, practicing managers, and human resource professionals a comprehensive, current, research-based introduction to the human resource management (HRM) function. It is organized in eight sections, logically following the progression of individuals into, through, and out of the organization. Part 1, overview and introduction,…

From Network Analysis to Functional Metabolic Modeling of the Human Gut Microbiota.

PubMed

Bauer, Eugen; Thiele, Ines

2018-01-01

An important hallmark of the human gut microbiota is its species diversity and complexity. Various diseases have been associated with a decreased diversity leading to reduced metabolic functionalities. Common approaches to investigate the human microbiota include high-throughput sequencing with subsequent correlative analyses. However, to understand the ecology of the human gut microbiota and consequently design novel treatments for diseases, it is important to represent the different interactions between microbes with their associated metabolites. Computational systems biology approaches can give further mechanistic insights by constructing data- or knowledge-driven networks that represent microbe interactions. In this minireview, we will discuss current approaches in systems biology to analyze the human gut microbiota, with a particular focus on constraint-based modeling. We will discuss various community modeling techniques with their advantages and differences, as well as their application to predict the metabolic mechanisms of intestinal microbial communities. Finally, we will discuss future perspectives and current challenges of simulating realistic and comprehensive models of the human gut microbiota.

hPSC-derived lung and intestinal organoids as models of human fetal tissue

PubMed Central

Aurora, Megan; Spence, Jason R.

2016-01-01

In vitro human pluripotent stem cell (hPSC) derived tissues are excellent models to study certain aspects of normal human development. Current research in the field of hPSC derived tissues reveals these models to be inherently fetal-like on both a morphological and gene expression level. In this review we briefly discuss current methods for differentiating lung and intestinal tissue from hPSCs into individual 3-dimensional units called organoids. We discuss how these methods mirror what is known about in vivo signaling pathways of the developing embryo. Additionally, we will review how the inherent immaturity of these models lends them to be particularly valuable in the study of immature human tissues in the clinical setting of premature birth. Human lung organoids (HLOs) and human intestinal organoids (HIOs) not only model normal development, but can also be utilized to study several important diseases of prematurity such as respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), and necrotizing enterocolitis (NEC). PMID:27287882

Still Human: A Call for Increased Focus on Ethical Standards in Cadaver Research.

PubMed

Bach, Michelle C

2016-12-01

Research on human cadavers is an important mechanism of scientific progress and comprises a large industry in the United States. However, despite its importance and influence, there is little ethical or regulatory oversight of cadaver-based research. This lack of transparency raises important ethical questions. Thus, this paper serves as a call for ethicists and regulators to pay increased attention to cadaver research. I argue that cadaver research ought to be considered a subset of human subjects research and held accountable to higher ethical standards. After describing current practices, I argue that oversight of cadaver research as a form of human subjects research is appropriate because cadaver research is similar to other types of human research, participants in cadaver research incur risks of harm, and a current lack of oversight has allowed the cadaver industry to entice research participation through ethically questionable practices. This paper urges greater dialogue among human subjects research ethicists and regulators about what constitutes appropriate protections for participants in cadaver research.

21 CFR 212.2 - What is current good manufacturing practice for PET drugs?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 4 2010-04-01 2010-04-01 false What is current good manufacturing practice for... HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR POSITRON EMISSION TOMOGRAPHY DRUGS (Eff. 12-12-2011) General Provisions § 212.2 What is current good manufacturing practice for...

21 CFR 1271.150 - Current good tissue practice requirements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Current good tissue practice requirements. 1271... HUMAN CELLS, TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS Current Good Tissue Practice § 1271.150 Current good tissue practice requirements. (a) General. This subpart D and subpart C of this part set...

21 CFR 110.40 - Equipment and utensils.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HUMAN CONSUMPTION CURRENT GOOD MANUFACTURING PRACTICE IN MANUFACTURING, PACKING, OR HOLDING HUMAN FOOD... manufacturing systems, including gravimetric, pneumatic, closed, and automated systems, shall be of a design and...

21 CFR 110.40 - Equipment and utensils.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HUMAN CONSUMPTION CURRENT GOOD MANUFACTURING PRACTICE IN MANUFACTURING, PACKING, OR HOLDING HUMAN FOOD... manufacturing systems, including gravimetric, pneumatic, closed, and automated systems, shall be of a design and...

21 CFR 110.40 - Equipment and utensils.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HUMAN CONSUMPTION CURRENT GOOD MANUFACTURING PRACTICE IN MANUFACTURING, PACKING, OR HOLDING HUMAN FOOD... manufacturing systems, including gravimetric, pneumatic, closed, and automated systems, shall be of a design and...

21 CFR 110.40 - Equipment and utensils.

Code of Federal Regulations, 2014 CFR

2014-04-01

... HUMAN CONSUMPTION CURRENT GOOD MANUFACTURING PRACTICE IN MANUFACTURING, PACKING, OR HOLDING HUMAN FOOD... manufacturing systems, including gravimetric, pneumatic, closed, and automated systems, shall be of a design and...

21 CFR 110.40 - Equipment and utensils.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HUMAN CONSUMPTION CURRENT GOOD MANUFACTURING PRACTICE IN MANUFACTURING, PACKING, OR HOLDING HUMAN FOOD... manufacturing systems, including gravimetric, pneumatic, closed, and automated systems, shall be of a design and...

Mechanisms of pro-arrhythmic abnormalities in ventricular repolarisation and anti-arrhythmic therapies in human hypertrophic cardiomyopathy.

PubMed

Passini, Elisa; Mincholé, Ana; Coppini, Raffaele; Cerbai, Elisabetta; Rodriguez, Blanca; Severi, Stefano; Bueno-Orovio, Alfonso

2016-07-01

Hypertrophic cardiomyopathy (HCM) is a cause of sudden arrhythmic death, but the understanding of its pro-arrhythmic mechanisms and an effective pharmacological treatment are lacking. HCM electrophysiological remodelling includes both increased inward and reduced outward currents, but their role in promoting repolarisation abnormalities remains unknown. The goal of this study is to identify key ionic mechanisms driving repolarisation abnormalities in human HCM, and to evaluate anti-arrhythmic effects of single and multichannel inward current blocks. Experimental ionic current, action potential (AP) and Ca(2+)-transient (CaT) recordings were used to construct populations of human non-diseased and HCM AP models (n=9118), accounting for inter-subject variability. Simulations were conducted for several degrees of selective and combined inward current block. Simulated HCM cardiomyocytes exhibited prolonged AP and CaT, diastolic Ca(2+) overload and decreased CaT amplitude, in agreement with experiments. Repolarisation abnormalities in HCM models were consistently driven by L-type Ca(2+) current (ICaL) re-activation, and ICaL block was the most effective intervention to normalise repolarisation and diastolic Ca(2+), but compromised CaT amplitude. Late Na(+) current (INaL) block partially abolished repolarisation abnormalities, with small impact on CaT. Na(+)/Ca(2+) exchanger (INCX) block effectively restored repolarisation and CaT amplitude, but increased Ca(2+) overload. Multichannel block increased efficacy in normalising repolarisation, AP biomarkers and CaT amplitude compared to selective block. Experimentally-calibrated populations of human AP models identify ICaL re-activation as the key mechanism for repolarisation abnormalities in HCM, and combined INCX, INaL and ICaL block as effective anti-arrhythmic therapies also able to partially reverse the HCM electrophysiological phenotype. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

An interdisciplinary review of current and future approaches to improving human-predator relations.

PubMed

Pooley, S; Barua, M; Beinart, W; Dickman, A; Holmes, G; Lorimer, J; Loveridge, A J; Macdonald, D W; Marvin, G; Redpath, S; Sillero-Zubiri, C; Zimmermann, A; Milner-Gulland, E J

2017-06-01

In a world of shrinking habitats and increasing competition for natural resources, potentially dangerous predators bring the challenges of coexisting with wildlife sharply into focus. Through interdisciplinary collaboration among authors trained in the humanities, social sciences, and natural sciences, we reviewed current approaches to mitigating adverse human-predator encounters and devised a vision for future approaches to understanding and mitigating such encounters. Limitations to current approaches to mitigation include too much focus on negative impacts; oversimplified equating of levels of damage with levels of conflict; and unsuccessful technical fixes resulting from failure to engage locals, address hidden costs, or understand cultural (nonscientific) explanations of the causality of attacks. An emerging interdisciplinary literature suggests that to better frame and successfully mitigate negative human-predator relations conservation professionals need to consider dispensing with conflict as the dominant framework for thinking about human-predator encounters; work out what conflicts are really about (they may be human-human conflicts); unravel the historical contexts of particular conflicts; and explore different cultural ways of thinking about animals. The idea of cosmopolitan natures may help conservation professionals think more clearly about human-predator relations in both local and global context. These new perspectives for future research practice include a recommendation for focused interdisciplinary research and the use of new approaches, including human-animal geography, multispecies ethnography, and approaches from the environmental humanities notably environmental history. Managers should think carefully about how they engage with local cultural beliefs about wildlife, work with all parties to agree on what constitutes good evidence, develop processes and methods to mitigate conflicts, and decide how to monitor and evaluate these. Demand for immediate solutions that benefit both conservation and development favors dispute resolution and technical fixes, which obscures important underlying drivers of conflicts. If these drivers are not considered, well-intentioned efforts focused on human-wildlife conflicts will fail. © 2016 The Authors. Conservation Biology published by Wiley Periodicals, Inc. on behalf of Society for Conservation Biology.

Targeting the human genome-microbiome axis for drug discovery: inspirations from global systems biology and traditional Chinese medicine.

PubMed

Zhao, Liping; Nicholson, Jeremy K; Lu, Aiping; Wang, Zhengtao; Tang, Huiru; Holmes, Elaine; Shen, Jian; Zhang, Xu; Li, Jia V; Lindon, John C

2012-07-06

Most chronic diseases impairing current human public health involve not only the human genome but also gene-environment interactions, and in the latter case the gut microbiome is an important factor. This makes the classical single drug-receptor target drug discovery paradigm much less applicable. There is widespread and increasing international interest in understanding the properties of traditional Chinese medicines (TCMs) for their potential utilization as a source of new drugs for Western markets as emerging evidence indicates that most TCM drugs are actually targeting both the host and its symbiotic microbes. In this review, we explore the challenges of and opportunities for harmonizing Eastern-Western drug discovery paradigms by focusing on emergent functions at the whole body level of humans as superorganisms. This could lead to new drug candidate compounds for chronic diseases targeting receptors outside the currently accepted "druggable genome" and shed light on current high interest issues in Western medicine such as drug-drug and drug-diet-gut microbial interactions that will be crucial in the development and delivery of future therapeutic regimes optimized for the individual patient.

The genus Shewanella: from the briny depths below to human pathogen.

PubMed

Janda, J Michael; Abbott, Sharon L

2014-11-01

The genus Shewanella is currently composed of more than 50 species that inhabit a range of marine environs and ecosystems. Several members of this genus, including S. oneidensis, have been identified that could potentially play key roles in environmental processes such as bioremediation of toxic elements and heavy metals and serving as microbial fuel cells. In contrast to this beneficial role, shewanellae are increasingly being implicated as human pathogens in persons exposed through occupational or recreational activities to marine niches containing shewanellae. Documented illnesses linked to Shewanella include skin and soft tissue infections, bacteremia, and otitis media. At present, it is unclear exactly how many Shewanella species are truly bona fide human pathogens. Recent advances in the taxonomy and phylogenetic relatedness of members of this genus, however, support the concept that most human infections are caused by a single species, S. algae. Some phylogenetic data further suggest that some current members of the genus are not true Shewanella species sensu stricto. The current review summarizes our present knowledge of the distribution, epidemiology, disease spectrum, and identification of microbial species focusing on a clinical perspective.

Apparatus for measuring high frequency currents

NASA Technical Reports Server (NTRS)

Hagmann, Mark J. (Inventor); Sutton, John F. (Inventor)

2003-01-01

An apparatus for measuring high frequency currents includes a non-ferrous core current probe that is coupled to a wide-band transimpedance amplifier. The current probe has a secondary winding with a winding resistance that is substantially smaller than the reactance of the winding. The sensitivity of the current probe is substantially flat over a wide band of frequencies. The apparatus is particularly useful for measuring exposure of humans to radio frequency currents.

Human epithelial hair follicle stem cells and their progeny: current state of knowledge, the widening gap in translational research and future challenges.

PubMed

Purba, Talveen S; Haslam, Iain S; Poblet, Enrique; Jiménez, Francisco; Gandarillas, Alberto; Izeta, Ander; Paus, Ralf

2014-05-01

Epithelial hair follicle stem cells (eHFSCs) are required to generate, maintain and renew the continuously cycling hair follicle (HF), supply cells that produce the keratinized hair shaft and aid in the reepithelialization of injured skin. Therefore, their study is biologically and clinically important, from alopecia to carcinogenesis and regenerative medicine. However, human eHFSCs remain ill defined compared to their murine counterparts, and it is unclear which murine eHFSC markers really apply to the human HF. We address this by reviewing current concepts on human eHFSC biology, their immediate progeny and their molecular markers, focusing on Keratin 15 and 19, CD200, CD34, PHLDA1, and EpCAM/Ber-EP4. After delineating how human eHFSCs may be selectively targeted experimentally, we close by defining as yet unmet key challenges in human eHFSC research. The ultimate goal is to transfer emerging concepts from murine epithelial stem cell biology to human HF physiology and pathology. © 2014 WILEY Periodicals, Inc.

Review of Significant Incidents and Close Calls in Human Spaceflight from a Human Factors Perspective

NASA Technical Reports Server (NTRS)

Silva-Martinez, Jackelynne; Ellenberger, Richard; Dory, Jonathan

2017-01-01

This project aims to identify poor human factors design decisions that led to error-prone systems, or did not facilitate the flight crew making the right choices; and to verify that NASA is effectively preventing similar incidents from occurring again. This analysis was performed by reviewing significant incidents and close calls in human spaceflight identified by the NASA Johnson Space Center Safety and Mission Assurance Flight Safety Office. The review of incidents shows whether the identified human errors were due to the operational phase (flight crew and ground control) or if they initiated at the design phase (includes manufacturing and test). This classification was performed with the aid of the NASA Human Systems Integration domains. This in-depth analysis resulted in a tool that helps with the human factors classification of significant incidents and close calls in human spaceflight, which can be used to identify human errors at the operational level, and how they were or should be minimized. Current governing documents on human systems integration for both government and commercial crew were reviewed to see if current requirements, processes, training, and standard operating procedures protect the crew and ground control against these issues occurring in the future. Based on the findings, recommendations to target those areas are provided.

Medical Humanities in Nepal: Present Scenario.

PubMed

Dhakal, Ajaya Kumar; Shankar, P Ravi; Dhakal, Sanjaya; Shrestha, Devendra; Piryani, Rano Mal

2014-01-01

Humanities have an essential role in medical education. The current gap between the humanities and medicine has to be bridged and there should be continuous and vigorous debate about the theory and practice of medical humanities. Medical humanities is a relatively new concept even in developed countries, and is at infancy stage in developing countries. In Nepal, modules on medical humanities have been initiated in certain medical schools by enthusiastic faculties and it requires further debates for inclusion in curriculum.

The historical, ethical, and legal background of human-subjects research.

PubMed

Rice, Todd W

2008-10-01

The current system of human-subject-research oversight and protections has developed over the last 5 decades. The principles of conducting human research were first developed as the Nuremberg code to try Nazi war criminals. The 3 basic elements of the Nuremberg Code (voluntary informed consent, favorable risk/benefit analysis, and right to withdraw without repercussions) became the foundation for subsequent ethical codes and research regulations. In 1964 the World Medical Association released the Declaration of Helsinki, which built on the principles of the Nuremberg Code. Numerous research improprieties between 1950 and 1974 in the United States prompted Congressional deliberations about human-subject-research oversight. Congress's first legislation to protect the rights and welfare of human subjects was the National Research Act of 1974, which created the National Commission for Protection of Human Subjects of Biomedical and Behavioral Research, which issued the Belmont Report. The Belmont Report stated 3 fundamental principles for conducting human-subjects research: respect for persons, beneficence, and justice. The Office of Human Research Protections oversees Title 45, Part 46 of the Code for Federal Regulations, which pertains to human-subjects research. That office indirectly oversees human-subjects research through local institutional review boards (IRB). Since their inception, the principles of conducting human research, IRBs, and the Code for Federal Regulations have all advanced substantially. This paper describes the history and current status of human-subjects-research regulations.

Current Issues in Mental Retardation and Human Development: Selected Papers from the 1970 Staff Development Conferences of the President's Committee on Mental Retardation (Washington, D.C., 1971).

ERIC Educational Resources Information Center

Stedman, Donald J., Ed.

Six papers discuss some of the current issues in the field of mental retardation and human development. Epidemiology of mental retardation from a sociological and clinical point of view is analyzed by Jane R. Mercer, based on studies of mental retardation in the community in Pomona, California. The role of genetics and intra-uterine diagnosis of…

Future Performance Trend Indicators: A Current Value Approach to Human Resources Accounting. Report I. Internal Consistencies and Relationships to Performance By Site. Final Report.

ERIC Educational Resources Information Center

Pecorella, Patricia A.; Bowers, David G.

Analyses preparatory to construction of a suitable file for generating a system of future performance trend indicators are described. Such a system falls into the category of a current value approach to human resources accounting. It requires that there be a substantial body of data which: (1) uses the work group or unit, not the individual, as…

Teaching Assessment for Teacher Human Capital Management: Learning from the Current State of the Art. WCER Working Paper No. 2011-2

ERIC Educational Resources Information Center

Milanowski, Anthony T.; Heneman, Herbert G., III; Kimball, Steven M.

2011-01-01

This paper reports on a study of the current state of the art in teaching assessment. The major goal of the study was to examine a sample of assessment systems and then develop a specification for a state-of the art performance assessment system to be used for human capital management functions. The authors hope was that this specification would…

Current Applications of Chromatographic Methods in the Study of Human Body Fluids for Diagnosing Disorders.

PubMed

Jóźwik, Jagoda; Kałużna-Czaplińska, Joanna

2016-01-01

Currently, analysis of various human body fluids is one of the most essential and promising approaches to enable the discovery of biomarkers or pathophysiological mechanisms for disorders and diseases. Analysis of these fluids is challenging due to their complex composition and unique characteristics. Development of new analytical methods in this field has made it possible to analyze body fluids with higher selectivity, sensitivity, and precision. The composition and concentration of analytes in body fluids are most often determined by chromatography-based techniques. There is no doubt that proper use of knowledge that comes from a better understanding of the role of body fluids requires the cooperation of scientists of diverse specializations, including analytical chemists, biologists, and physicians. This article summarizes current knowledge about the application of different chromatographic methods in analyses of a wide range of compounds in human body fluids in order to diagnose certain diseases and disorders.

Current advances in the cognitive neuroscience of music.

PubMed

Levitin, Daniel J; Tirovolas, Anna K

2009-03-01

The study of music perception and cognition is one of the oldest topics in experimental psychology. The last 20 years have seen an increased interest in understanding the functional neuroanatomy of music processing in humans, using a variety of technologies including fMRI, PET, ERP, MEG, and lesion studies. We review current findings in the context of a rich intellectual history of research, organized by the cognitive systems underlying different aspects of human musical behavior. We pay special attention to the perception of components of musical processing, musical structure, laterality effects, cultural issues, links between music and movement, emotional processing, expertise, and the amusias. Current trends are noted, such as the increased interest in evolutionary origins of music and comparisons of music and language. The review serves to demonstrate the important role that music can play in informing broad theories of higher order cognitive processes such as music in humans.

The life-cycle research productivity of mathematicians and scientists.

PubMed

Diamond, A M

1986-07-01

Declining research productivity with age is implied by economic models of life-cycle human capital investment but is denied by some recent empirical studies. The purpose of the present study is to provide new evidence on whether a scientist's output generally declines with advancing age. A longitudinal data set has been compiled for scientists and mathematicians at six major departments, including data on age, salaries, annual citations (stock of human capital), citations to current output (flow of human capital), and quantity of current output measured both in number of articles and in number of pages. Analysis of the data indicates that salaries peak from the early to mid-60s, whereas annual citations appear to peak from age 39 to 89 for different departments with a mean age of 59 for the 6 departments. The quantity and quality of current research output appear to decline continuously with age.

Alzheimer’s in 3D culture: Challenges and perspectives

PubMed Central

D'Avanzo, Carla; Aronson, Jenna; Kim, Young Hye; Choi, Se Hoon; Tanzi, Rudolph E.; Kim, Doo Yeon

2015-01-01

Summary Alzheimer’s disease (AD) is the most common cause of dementia, and there is currently no cure. The “β-amyloid cascade hypothesis” of AD is the basis of current understanding of AD pathogenesis and drug discovery. However, no AD models have fully validated this hypothesis. We recently developed a human stem cell culture model of AD by cultivating genetically modified human neural stem cells in a three-dimensional (3D) cell culture system. These cells were able to recapitulate key events of AD pathology including β-amyloid plaques and neurofibrillary tangles. In this review, we will discuss the progress and current limitations of AD mouse models and human stem cell models as well as explore the breakthroughs of 3D cell culture systems. We will also share our perspective on the potential of dish models of neurodegenerative diseases for studying pathogenic cascades and therapeutic drug discovery. PMID:26252541

The Rhetorical Primate

ERIC Educational Resources Information Center

Dance, Frank E. X.

1977-01-01

Reviews various current experimental attempts to induce a form of human language in chimpanzees and concludes that research results indicate that only Homo Sapiens are capable of mastering human forms of communication. (MH)

The effects of amiloride and age on oxygen consumption coupled to electrogenic sodium transport in the human sigmoid colon.

PubMed

Carra, Graciela E; Matus, Daniel; Ibáñez, Jorge E; Saraví, Fernando D

2015-01-01

Aerobic metabolism is necessary for ion transport in many transporting epithelia, including the human colonic epithelium. We assessed the effects of the epithelial sodium channel blocker, amiloride, on oxygen consumption and short-circuit current of the human sigmoid epithelium to determine whether these effects were influenced by the age of the subject. Segments of the sigmoid colon were obtained from the safety margin of resections performed in patients of 62-77 years of age. Isolated mucosa preparations were obtained and mounted in airtight Ussing chambers, fit for simultaneous measurement of short-circuit current and oxygen concentration, before and after blocking epithelial sodium channels with amiloride (0.1 mmol/L). Regression analyses were performed to assess the associations between short-circuit current, oxygen consumption, and age of the subject as well as to define the relationship between the decreases in short-circuit current and oxygen consumption after blockade. Epithelial sodium channel blockade caused an 80% reduction in short-circuit current and a 26% reduction in oxygen consumption. Regression analysis indicated that both changes were significantly related (r = 0.884;P = 0.0007). Oxygen consumption decreased by 1 m mol/h/cm2 for each 25 m A/cm2 decrease in short-circuit current. Neither short-circuit current nor oxygen consumption had any significant relationship with the age of the subjects. The decrease in epithelial oxygen consumption caused by amiloride is proportional to the decrease in short-circuit current and independent of the age of the subject.

Electric fence standards comport with human data and AC limits.

PubMed

Kroll, Mark W; Perkins, Peter E; Panescu, Dorin

2015-08-01

The ubiquitous electric fence is essential to modern agriculture and has saved lives by reducing the number of livestock automobile collisions. Modern safety standards such as IEC 60335-2-76 and UL 69 have played a role in this positive result. However, these standards are essentially based on energy and power (RMS current), which have limited direct relationship to cardiac effects. We compared these standards to bioelectrically more relevant units of charge and average current in view of recent work on VF (ventricular fibrillation) induction and to existing IEC AC current limits. There are 3 limits for normal (low) pulsing rate: IEC energy limit, IEC current limit, and UL current limit. We then calculated the delivered charge allowed for each pulse duration for these limits and then compared them to a charge-based safety model derived from published human ventricular-fibrillation induction data. Both the IEC and UL also allow for rapid pulsing for up to 3 minutes. We calculated maximum outputs for various pulse durations assuming pulsing at 10, 20, and 30 pulses per second. These were then compared to standard utility power safety (AC) limits via the conversion factor of 7.4 to convert average current to RMS current for VF risk. The outputs of TASER electrical weapons (typically < 100 μC and ~100 μs duration) were also compared. The IEC and UL electric fence energizer normal rate standards are conservative in comparison with actual human laboratory experiments. The IEC and UL electric fence energizer rapid-pulsing standards are consistent with accepted IEC AC current limits for commercially used pulse durations.

The brain and the law.

PubMed Central

Chorvat, Terrence; McCabe, Kevin

2004-01-01

Much has been written about how law as an institution has developed to solve many problems that human societies face. Inherent in all of these explanations are models of how humans make decisions. This article discusses what current neuroscience research tells us about the mechanisms of human decision making of particular relevance to law. This research indicates that humans are both more capable of solving many problems than standard economic models predict, but also limited in ways those models ignore. This article discusses how law is both shaped by our cognitive processes and also shapes them. The article considers some of the implications of this research for improving our understanding of how our current legal regimes operate and how the law can be structured to take advantage of our neural mechanisms to improve social welfare. PMID:15590613

The dual loop model: its relation to language and other modalities

PubMed Central

Rijntjes, Michel; Weiller, Cornelius; Bormann, Tobias; Musso, Mariacristina

2012-01-01

The current neurobiological consensus of a general dual loop system scaffolding human and primate brains gives evidence that the dorsal and ventral connections subserve similar functions, independent of the modality and species. However, most current commentators agree that although bees dance and chimpanzees grunt, these systems of communication differ qualitatively from human language. So why is language unique to humans? We discuss anatomical differences between humans and other animals, the meaning of lesion studies in patients, the role of inner speech, and compare functional imaging studies in language with other modalities in respect to the dual loop model. These aspects might be helpful for understanding what kind of biological system the language faculty is, and how it relates to other systems in our own species and others. PMID:22783188

Los Alamos National Laboratory Human and Intellectual Capital for Sustaining Nuclear Deterrence

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

McAlpine, Bradley

2015-04-01

This paper provides an overview of the current human and intellectual capital at Los Alamos National Laboratory, through specific research into the statistics and demographics as well as numerous personal interviews at all levels of personnel. Based on this information, a series of recommendations are provided to assist Los Alamos National Laboratory in ensuring the future of the human and intellectual capital for the nuclear deterrence mission. While the current human and intellectual capital is strong it stands on the precipice and action must be taken to ensure Los Alamos National Laboratory maintains leadership in developing and sustaining national nuclearmore » capabilities. These recommendations may be applicable to other areas of the nuclear enterprise, including the Air Force, after further research and study.« less

Intermittent fasting and cardiovascular disease: current evidence and unresolved questions.

PubMed

Tinsley, Grant M; Horne, Benjamin D

2018-01-01

Intermittent fasting has produced a variety of beneficial health effects in animal models, although high-quality research in humans has been limited. This special report examines current evidences for intermittent fasting in humans, discusses issues that require further examination, and recommends new research that can improve the knowledge base in this emerging research area. While potentially useful for health improvement, intermittent fasting requires further study prior to widespread implementation for health purposes. Randomized, longer-term studies are needed to determine whether using intermittent fasting as a lifestyle rather than a diet is feasible and beneficial for the health of some members of the human population.

Aeroassist Technology Planning for Exploration

NASA Technical Reports Server (NTRS)

Munk, Michelle M.; Powell, Richard W.

2000-01-01

Now that the International Space Station is undergoing assembly, NASA is strategizing about the next logical exploration strategy for robotic missions and the next destination for humans. NASA's current efforts are in developing technologies that will both aid the robotic exploration strategy and make human flight to other celestial bodies both safe and affordable. One of these enabling technologies for future robotic and human exploration missions is aeroassist. This paper will (1) define aeroassist, (2) explain the benefits and uses of aeroassist, and (3) describe a method, currently used by the NASA Aeroassist Working Group, by which widely geographically distributed teams can assemble, present, use, and archive technology information.

Potential Vaccines and Post-Exposure Treatments for Filovirus Infections

PubMed Central

Friedrich, Brian M.; Trefry, John C.; Biggins, Julia E.; Hensley, Lisa E.; Honko, Anna N.; Smith, Darci R.; Olinger, Gene G.

2012-01-01

Viruses of the family Filoviridae represent significant health risks as emerging infectious diseases as well as potentially engineered biothreats. While many research efforts have been published offering possibilities toward the mitigation of filoviral infection, there remain no sanctioned therapeutic or vaccine strategies. Current progress in the development of filovirus therapeutics and vaccines is outlined herein with respect to their current level of testing, evaluation, and proximity toward human implementation, specifically with regard to human clinical trials, nonhuman primate studies, small animal studies, and in vitro development. Contemporary methods of supportive care and previous treatment approaches for human patients are also discussed. PMID:23170176

Intelligent Systems For Aerospace Engineering: An Overview

NASA Technical Reports Server (NTRS)

KrishnaKumar, K.

2003-01-01

Intelligent systems are nature-inspired, mathematically sound, computationally intensive problem solving tools and methodologies that have become extremely important for advancing the current trends in information technology. Artificially intelligent systems currently utilize computers to emulate various faculties of human intelligence and biological metaphors. They use a combination of symbolic and sub-symbolic systems capable of evolving human cognitive skills and intelligence, not just systems capable of doing things humans do not do well. Intelligent systems are ideally suited for tasks such as search and optimization, pattern recognition and matching, planning, uncertainty management, control, and adaptation. In this paper, the intelligent system technologies and their application potential are highlighted via several examples.

Donor human milk banking and the emergence of milk sharing.

PubMed

Landers, Susan; Hartmann, Ben T

2013-02-01

Donor human milk has emerged as the preferred substrate to feed extremely preterm infants, when mother's own milk is unavailable. This article summarizes the clinical data demonstrating the safety, efficacy, and cost-effectiveness of feeding donor human milk to premature babies. It describes the current state of milk banking in North America, as well as other parts of the world, and the differing criteria for donor selection, current pasteurization techniques, and quality control measures. A risk assessment methodology is proposed, which would allow milk banks globally to assess the safety of their process and respond appropriately to differing risk environments. Copyright © 2013. Published by Elsevier Inc.

Overview of EPA Superfund human health research program.

PubMed

Kowalski, Lorelei; Denne, Jane; Dyer, Robert; Garrahan, Kevin; Wentsel, Randall S

2002-03-01

This paper presents major research needs for the Superfund program, and provides an overview of the EPA Office of Research and Development's (ORDs) current human health research program designed to fill some of those data gaps. Research is presented in terms of the risk paradigm and covers exposure, effects, and assessment activities directly funded by Superfund, as well as research not funded by Superfund but directly applicable to Superfund research needs. Research on risk management is not covered. Current research activities conducted by the Superfund program office are also included to provide a full picture of Superfund human health research activities being conducted by EPA.

Intelligent Systems for Aerospace Engineering: An Overview

NASA Technical Reports Server (NTRS)

Krishnakumar, Kalmanje

2002-01-01

Intelligent systems are nature-inspired, mathematically sound, computationally intensive problem solving tools and methodologies that have become extremely important for advancing the current trends in information technology. Artificially intelligent systems currently utilize computers to emulate various faculties of human intelligence and biological metaphors. They use a combination of symbolic and sub-symbolic systems capable of evolving human cognitive skills and intelligence, not just systems capable of doing things humans do not do well. Intelligent systems are ideally suited for tasks such as search and optimization, pattern recognition and matching, planning, uncertainty management, control, and adaptation. In this paper, the intelligent system technologies and their application potential are highlighted via several examples.

A REVIEW OF HUMAN STUDIES ON THE REPRODUCTIVE AND DEVELOPMENTAL EFFECTS OF PESTICIDE EXPOSURE

EPA Science Inventory

Many pesticides cxause reproductive or developmental toxicity at high doses in animal models, but effects in humans at environmental exposure levels are difficult to assess. Human data on reproductive and developmental outcomes for currently used pesticides may help to define ris...

Where Are the People? The Human Viewpoint Approach for Architecting and Acquisition

DTIC Science & Technology

2014-10-01

however, systems engineers currently do not have sufficient tools to quantitatively integrate human considerations into systems development ( Hardman ...Engineering, 13(1), 72–79. Hardman , N., & Colombi, J. (2012). An empirical methodology for human integration in the SE technical processes. Journal of Systems

Swine as a model for influenza A virus infection

USDA-ARS?s Scientific Manuscript database

Influenza A viruses (IAV) infect a variety of hosts, including humans, swine, and various avian species. The annual influenza disease burden in the human population remains significant even with current vaccine usage and much about the pathogenesis and transmission of influenza viruses in human rema...

The Current MEPAG Representation of Potential Dust-related Hazards as They May Relate to the Human Exploration of Mars

NASA Astrophysics Data System (ADS)

Ashley, J. W.; Banfield, D.; Beaty, D. W.; Bleacher, J. E.; Carrier, B. L.; Hamilton, V. E.; Whitley, R. J.; Zurek, R. W.

2017-06-01

The MEPAG Goals Document presents investigations that may correlate with dust risk to humans and human operations in potential future Mars missions. We list these here, together with their respective priority rankings, and invite community input.

Estimation of Tetrabromobisphenol A (TBBPA)percutaneous uptake in humans using the parallelogram method.

EPA Science Inventory

Tetrabromobisphenol A (Tl3BPA) is currently the world's highest production volumebrominated flame retardant. Humans are frequently exposed to TBBPA by the dermal route. In the present study., a parallelogram approach was used to make predictions of internal dose in exposed humans...

A Chemogenetic Receptor That Enhances the Magnitude and Frequency of Glycinergic Inhibitory Postsynaptic Currents without Inducing a Tonic Chloride Flux.

PubMed

Islam, Robiul; Zhang, Yan; Xu, Li; Sah, Pankaj; Lynch, Joseph W

2017-03-15

The gene transfer-mediated expression of inhibitory ion channels in nociceptive neurons holds promise for treating intractable pain. Chemogenetics, which involves expressing constructs activated by biologically inert molecules, is of particular interest as it permits tunable neuromodulation. However, current chloride-permeable chemogenetic constructs are problematic as they mediate a tonic chloride influx which over time would deplete the chloride electrochemical gradient and reduce inhibitory efficacy. Inflammatory pain sensitization can be caused by prostaglandin E2-mediated inhibition of glycinergic inhibitory postsynaptic currents in spinal nociceptive neurons. We developed a highly conducting (100 pS) inhibitory chemogenetic construct based on a human glycine receptor (α1 Y279F,A288G ) with high ivermectin sensitivity. When virally infected into spinal neurons, 10 nM ivermectin increased the magnitude and frequency of glycinergic postsynaptic currents without activating a tonic chloride flux. The construct should thus produce analgesia. Its human origin and the well-established biocompatibility of its ligand suggest it may be suited to human use.

21 CFR 110.110 - Natural or unavoidable defects in food for human use that present no health hazard.

Code of Federal Regulations, 2011 CFR

2011-04-01

... use that present no health hazard. 110.110 Section 110.110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION CURRENT GOOD MANUFACTURING... unavoidable defects in food for human use that present no health hazard. (a) Some foods, even when produced...

Does Reconsolidation Occur in Humans?

PubMed Central

Schiller, Daniela; Phelps, Elizabeth A.

2011-01-01

Evidence for reconsolidation in non-human animals has accumulated rapidly in the last decade, providing compelling` demonstration for this phenomenon across species and memory paradigms. In vast contrast, scant evidence exists for human reconsolidation to date. A major reason for this discrepancy is the invasive nature of current techniques used to investigate reconsolidation, which are difficult to apply in humans. Pharmacological blockade of reconsolidation, for example, has been typically used in animals as a proof of concept. However, most compounds used in these studies are toxic for humans, and those compounds that are safe target related, but not direct mechanisms of reconsolidation. Thus, although human reconsolidation has been hypothesized, there is limited evidence it actually exists. The best evidence for human reconsolidation emerges from non-invasive techniques that “update” memory during reconsolidation rather than block it, a technique only rarely used in animal research. Here we discuss the current state of human reconsolidation and the challenges ahead. We review findings on reconsolidation of emotional associative, episodic, and procedural memories, using invasive and non-invasive techniques. We discuss the possible interpretation of these results, attempt to reconcile some inconsistencies, and suggest a conceptual framework for future research. PMID:21629821

Current status of Mycobacterium avium subspecies paratuberculosis infection in animals & humans in India: What needs to be done?

PubMed

Singh, Ajay Vir; Chauhan, Devendra Singh; Singh, Shoor Vir; Kumar, Vijay; Singh, Abhinendra; Yadav, Anjali; Yadav, Virendra Singh

2016-11-01

Mycobacterium avium subspecies paratuberculosis (MAP) has emerged as a major health problem for domestic livestock and human beings. Reduced per animal productivity of domestic livestock seriously impacts the economics of dairy farming globally. High to very high bioload of MAP in domestic livestock and also in the human population has been reported from north India. Presence of live MAP bacilli in commercial supplies of raw and pasteurized milk and milk products indicates its public health significance. MAP is not inactivated during pasteurization, therefore, entering into human food chain daily. Recovery of MAP from patients with inflammatory bowel disease or Crohn's disease and animal healthcare workers suffering with chronic gastrointestinal problems indicate a close association of MAP with a number of chronic and other diseases affecting human health. Higher bioload of MAP in the animals increases the risk of exposure to the human population with MAP. This review summarizes the current status of MAP infection in animals as well as in human beings and also highlights the prospects of effective management and control of disease in animals to reduce the risk of exposure to human population.

Health effects of indoor odorants.

PubMed Central

Cone, J E; Shusterman, D

1991-01-01

People assess the quality of the air indoors primarily on the basis of its odors and on their perception of associated health risk. The major current contributors to indoor odorants are human occupant odors (body odor), environmental tobacco smoke, volatile building materials, bio-odorants (particularly mold and animal-derived materials), air fresheners, deodorants, and perfumes. These are most often present as complex mixtures, making measurement of the total odorant problem difficult. There is no current method of measuring human body odor, other than by human panel studies of expert judges of air quality. Human body odors have been quantitated in terms of the "olf" which is the amount of air pollution produced by the average person. Another quantitative unit of odorants is the "decipol," which is the perceived level of pollution produced by the average human ventilated by 10 L/sec of unpolluted air or its equivalent level of dissatisfaction from nonhuman air pollutants. The standard regulatory approach, focusing on individual constituents or chemicals, is not likely to be successful in adequately controlling odorants in indoor air. Besides the current approach of setting minimum ventilation standards to prevent health effects due to indoor air pollution, a standard based on the olf or decipol unit might be more efficacious as well as simpler to measure. PMID:1821378

Experimental primates and non-human primate (NHP) models of human diseases in China: current status and progress

PubMed Central

ZHANG, Xiao-Liang; PANG, Wei; HU, Xin-Tian; LI, Jia-Li; YAO, Yong-Gang; ZHENG, Yong-Tang

2014-01-01

Non-human primates (NHPs) are phylogenetically close to humans, with many similarities in terms of physiology, anatomy, immunology, as well as neurology, all of which make them excellent experimental models for biomedical research. Compared with developed countries in America and Europe, China has relatively rich primate resources and has continually aimed to develop NHPs resources. Currently, China is a leading producer and a major supplier of NHPs on the international market. However, there are some deficiencies in feeding and management that have hampered China’s growth in NHP research and materials. Nonetheless, China has recently established a number of primate animal models for human diseases and achieved marked scientific progress on infectious diseases, cardiovascular diseases, endocrine diseases, reproductive diseases, neurological diseases, and ophthalmic diseases, etc. Advances in these fields via NHP models will undoubtedly further promote the development of China’s life sciences and pharmaceutical industry, and enhance China’s position as a leader in NHP research. This review covers the current status of NHPs in China and other areas, highlighting the latest developments in disease models using NHPs, as well as outlining basic problems and proposing effective countermeasures to better utilize NHP resources and further foster NHP research in China. PMID:25465081

Electrocardiographic Biomarkers for Detection of Drug-Induced Late Sodium Current Block

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

Vicente, Jose; Johannesen, Lars; Hosseini, Meisam

Drugs that prolong the heart rate corrected QT interval (QTc) on the electrocardiogram (ECG) by blocking the hERG potassium channel and also block inward currents (late sodium or L-type calcium) are not associated with torsade de pointes (e.g. ranolazine and verapamil). Furthermore, identifying ECG signs of late sodium current block could aid in the determination of proarrhythmic risk for new drugs. A new cardiac safety paradigm for drug development (the "CiPA" initiative) will involve the preclinical assessment of multiple human cardiac ion channels and ECG biomarkers are needed to determine if there are unexpected ion channel effects in humans.

Electrocardiographic Biomarkers for Detection of Drug-Induced Late Sodium Current Block

DOE PAGES

Vicente, Jose; Johannesen, Lars; Hosseini, Meisam; ...

2016-12-30

Drugs that prolong the heart rate corrected QT interval (QTc) on the electrocardiogram (ECG) by blocking the hERG potassium channel and also block inward currents (late sodium or L-type calcium) are not associated with torsade de pointes (e.g. ranolazine and verapamil). Furthermore, identifying ECG signs of late sodium current block could aid in the determination of proarrhythmic risk for new drugs. A new cardiac safety paradigm for drug development (the "CiPA" initiative) will involve the preclinical assessment of multiple human cardiac ion channels and ECG biomarkers are needed to determine if there are unexpected ion channel effects in humans.

Analytical methods for human biomonitoring of pesticides. A review.

PubMed

Yusa, Vicent; Millet, Maurice; Coscolla, Clara; Roca, Marta

2015-09-03

Biomonitoring of both currently-used and banned-persistent pesticides is a very useful tool for assessing human exposure to these chemicals. In this review, we present current approaches and recent advances in the analytical methods for determining the biomarkers of exposure to pesticides in the most commonly used specimens, such as blood, urine, and breast milk, and in emerging non-invasive matrices such as hair and meconium. We critically discuss the main applications for sample treatment, and the instrumental techniques currently used to determine the most relevant pesticide biomarkers. We finally look at the future trends in this field. Copyright © 2015 Elsevier B.V. All rights reserved.

Psycholinguistics.

ERIC Educational Resources Information Center

Fillenbaum, Samuel

This article provides a discussion of current topics in psycholinguistics and of the current research on these problems. The author discusses current thought on the biological foundations of language and the problem of universals. If human language is a species-particular achievement contingent upon a biological endowment, there should be certain…

Interaction of pyroclastic density currents with human settlements: Evidence from ancient Pompeii

NASA Astrophysics Data System (ADS)

Gurioli, Lucia; Pareschi, M. Teresa; Zanella, Elena; Lanza, Roberto; Deluca, Enrico; Bisson, Marina

2005-06-01

Integrating field observations and rock-magnetic measurements, we report how a turbulent pyroclastic density current interacted with and moved through an urban area. The data are from the most energetic, turbulent pyroclastic density current of the A.D. 79 eruption of Vesuvius, Italy, which partially destroyed the Roman city of Pompeii. Our results show that the urban fabric was able to divide the lower portion of the current into several streams that followed the city walls and the intracity roads. Vortices, revealed by upstream particle orientations and decreases in deposit temperature, formed downflow of obstacles or inside cavities. Although these perturbations affected only the lower part of the current and were localized, they could represent, in certain cases, cooler zones within which chances of human survival are increased. Our integrated field data for pyroclastic density current temperature and flow direction, collected for the first time across an urban environment, enable verification of coupled thermodynamic numerical models and their hazard simulation abilities.

Transcranial Direct Current Stimulation in Epilepsy.

PubMed

San-Juan, Daniel; Morales-Quezada, León; Orozco Garduño, Adolfo Josué; Alonso-Vanegas, Mario; González-Aragón, Maricarmen Fernández; Espinoza López, Dulce Anabel; Vázquez Gregorio, Rafael; Anschel, David J; Fregni, Felipe

2015-01-01

Transcranial direct current stimulation (tDCS) is an emerging non-invasive neuromodulation therapy in epilepsy with conflicting results in terms of efficacy and safety. Review the literature about the efficacy and safety of tDCS in epilepsy in humans and animals. We searched studies in PubMed, MedLine, Scopus, Web of Science and Google Scholar (January 1969 to October 2013) using the keywords 'transcranial direct current stimulation' or 'tDCS' or 'brain polarization' or 'galvanic stimulation' and 'epilepsy' in animals and humans. Original articles that reported tDCS safety and efficacy in epileptic animals or humans were included. Four review authors independently selected the studies, extracted data and assessed the methodological quality of the studies using the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions, PRISMA guidelines and Jadad Scale. A meta-analysis was not possible due to methodological, clinical and statistical heterogeneity of included studies. We analyzed 9 articles with different methodologies (3 animals/6 humans) with a total of 174 stimulated individuals; 109 animals and 65 humans. In vivo and in vitro animal studies showed that direct current stimulation can successfully induce suppression of epileptiform activity without neurological injury and 4/6 (67%) clinical studies showed an effective decrease in epileptic seizures and 5/6 (83%) reduction of inter-ictal epileptiform activity. All patients tolerated tDCS well. tDCS trials have demonstrated preliminary safety and efficacy in animals and patients with epilepsy. Further larger studies are needed to define the best stimulation protocols and long-term follow-up. Copyright © 2015 Elsevier Inc. All rights reserved.

The Humanities in English Primary Schools: Struggling to Survive

ERIC Educational Resources Information Center

Barnes, Jonathan; Scoffham, Stephen

2017-01-01

This article surveys the state of the humanities in English primary schools drawing on evidence from serving head teachers, current literature and policy documents. The findings suggest that whilst the humanities are highly valued in schools, there are serious challenges which threaten the "broad and balanced" curriculum. It is suggested…

Nitrous oxide as a humane method for piglet euthanasia: behavior and electroencephalography

USDA-ARS?s Scientific Manuscript database

The search for humane methods to euthanize piglets is critical to address public concern that current methods are not optimal. Blunt force trauma is considered humane but aesthetically objectionable. Carbon dioxide (CO2) is used but criticized as aversive. This research sought to: 1) evaluate the av...

76 FR 34984 - Propetamphos Registration Review Final Decision; Notice of Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-15

... on human health or the environment. Through this program, EPA is ensuring that each pesticide's registration is based on current scientific and other knowledge, including its effects on human health and the..., human health, farm worker, and agricultural advocates; the chemical industry; pesticide users; and...

76 FR 17646 - Registration Review; Pesticide Dockets Opened for Review and Comment and Other Docket Actions...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-30

... without unreasonable adverse effects on human health or the environment. A pesticide's registration review... adverse effects on human health or the environment. Registration review dockets contain information that... pesticide's registration is based on current scientific and other knowledge, including its effects on human...

76 FR 25340 - Fenoxycarb, Sodium Tetrathiocarbonate, and Temephos; Registration Review Proposed Decisions...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-04

... effects on human health or the environment. Through this program, EPA is ensuring that each pesticide's registration is based on current scientific and other knowledge, including its effects on human health and the... stakeholders including environmental, human health, farm worker, and agricultural advocates; the chemical...

75 FR 12746 - Difenzoquat; Registration Review Case Closure; Notice of Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-17

... on human health or the environment. Through this program, EPA is ensuring that each pesticide's registration is based on current scientific and other knowledge, including its effects on human health and the..., human health, farm worker, and agricultural advocates; the chemical industry; pesticide users; and...

75 FR 6655 - Disulfoton Registration Review Decision; Notice of Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-10

... pesticide can perform its intended function without causing unreasonable adverse effects on human health or... current scientific and other knowledge, including its effects on human health and the environment. FOR... general, and may be of interest to a wide range of stakeholders including environmental, human health...

75 FR 51055 - Propionic Acid and Salts, and Urea Sulfate; Registration Review Proposed Decisions; Notice of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-18

... human health or the environment. Through this program, EPA is ensuring that each pesticide's registration is based on current scientific and other knowledge, including its effects on human health and the... range of stakeholders including environmental, human health, farm worker, and agricultural advocates...

75 FR 57782 - Clofencet; Registration Review Case Closure; Notice of Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-22

... on human health or the environment. Through this program, EPA is ensuring that each pesticide's registration is based on current scientific and other knowledge, including its effects on human health and the..., human health, farm worker, and agricultural advocates; the chemical industry; pesticide users; and...

75 FR 16113 - Bacillus subtilis; Registration Review Final Decision; Notice of Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-31

... on human health or the environment. Through this program, EPA is ensuring that each pesticide's registration is based on current scientific and other knowledge, including its effects on human health and the... environmental, human health, farm worker, and agricultural advocates; the chemical industry; pesticide users...

75 FR 64725 - Methamidophos Registration Review Final Decision; Notice of Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-20

... on human health or the environment. Through this program, EPA is ensuring that each pesticide's registration is based on current scientific and other knowledge, including its effects on human health and the..., human health, farm worker, and agricultural advocates; the chemical industry; pesticide users; and...