Sample records for management ivm program

  1. Harnessing Integrated Vector Management for Enhanced Disease Prevention.

    PubMed

    Chanda, Emmanuel; Ameneshewa, Birkinesh; Bagayoko, Magaran; Govere, John M; Macdonald, Michael B

    2017-01-01

    The increasing global threat of emerging and re-emerging vector-borne diseases (VBDs) poses a serious health problem. The World Health Organization (WHO) recommends integrated vector management (IVM) strategy for combating VBD transmission. An IVM approach requires entomological knowledge, technical and infrastructure capacity, and systems facilitating stakeholder collaboration. In sub-Saharan Africa, successful operational IVM experience comes from relatively few countries. This article provides an update on the extent to which IVM is official national policy, the degree of IVM implementation, the level of compliance with WHO guidelines, and concordance in the understanding of IVM, and it assesses the operational impact of IVM. The future outlook encompasses rational and sustainable use of effective vector control tools and inherent improved return for investment for disease vector control. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Vector control programs in Saint Johns County, Florida and Guayas, Ecuador: successes and barriers to integrated vector management.

    PubMed

    Naranjo, Diana P; Qualls, Whitney A; Jurado, Hugo; Perez, Juan C; Xue, Rui-De; Gomez, Eduardo; Beier, John C

    2014-07-02

    Vector-borne diseases (VBDs) and mosquito control programs (MCPs) diverge in settings and countries, and lead control specialists need to be aware of the most effective control strategies. Integrated Vector Management (IVM) strategies, once implemented in MCPs, aim to reduce cost and optimize protection of the populations against VBDs. This study presents a strengths, weaknesses, opportunities, and threats (SWOT) analysis to compare IVM strategies used by MCPs in Saint Johns County, Florida and Guayas, Ecuador. This research evaluates MCPs strategies to improve vector control activities. Methods included descriptive findings of the MCP operations. Information was obtained from vector control specialists, directors, and residents through field trips, surveys, and questionnaires. Evaluations of the strategies and assets of the control programs where obtained through SWOT analysis and within an IVM approach. Organizationally, the Floridian MCP is a tax-based District able to make decisions independently from county government officials, with the oversight of an elected board of commissioners. The Guayas program is directed by the country government and assessed by non-governmental organizations like the World health Organization. Operationally, the Floridian MCP conducts entomological surveillance and the Ecuadorian MCP focuses on epidemiological monitoring of human disease cases. Strengths of both MCPs were their community participation and educational programs. Weaknesses for both MCPs included limitations in budgets and technical capabilities. Opportunities, for both MCPs, are additional funding and partnerships with private, non-governmental, and governmental organizations. Threats experienced by both MCPs included political constraints and changes in the social and ecological environment that affect mosquito densities and control efforts. IVM pillars for policy making were used to compare the information among the programs. Differences included how the Ecuadorian MCP relies heavily on the community for vector control while the American MCP relies on technologies and research. IVM based recommendations direct health policy leaders toward improving surveillance systems both entomologically and epidemiologically, improving community risk perceptions by integrating components of community participation, maximizing resources though the use of applied research, and protecting the environment by selecting low-risk pesticides. Outcomes of the research revealed that inter-sectorial and multidisciplinary interventions are critical to improve public health.

  3. Maturation capacity, morphology and morphometric assessment of human immature oocytes after vitrification and in-vitro maturation

    PubMed Central

    Nazari, Saeedeh; Khalili, Mohammad Ali; Esmaielzadeh, Forouzan; Mohsenzadeh, Mehdi

    2011-01-01

    Background: In general, 15% of oocytes collected in ART cycles are immature. These oocytes may be cryopreserved further for use in in-vitro maturation (IVM) program. Objective: The aim of this study was to determine maturation capacity, morphometric parameters and morphology of human immature oocytes in both fresh IVM (fIVM) and vitrified-IVM (vIVM) oocytes. Materials and Methods: 93 women who underwent controlled ovarian stimulation for ART were included. The immature oocytes (n=203) were divided into two groups: the first group (n=101) directly matured in vitro; and the second group (n=102) first vitrified, then matured in vitro. All oocytes underwent IVM in Ham’s F10 supplemented with LH+FSH and human follicular fluid. After 48h of incubation, the oocyte maturation rates, as well as morphometric and morphologic characteristics were assessed using cornus imaging and were compared. Results: Oocyte maturation rates were reduced in vIVM, (40.4%), in comparison with fIVM (59.4%, p<0.001). Following morphometric assessment, there was no difference in the mean oocyte diameters (µm) between fIVM and vIVM, 156.3±6.8 and 154.07±9.9, respectively. Other parameters of perimeters, egg areas, as well as oocyte and ooplasm volumes were similar in two groups. In addition, more morphologic abnormalities, such as, vacuole, and dark oocyte were observed in vIVM oocytes. Conclusion: fIVM was more successful than vIVM groups. No statistical differences were noticed in morphometry assessment in two groups. This suggests that morphometric parameters can not be applied as prognosis factor in oocyte maturation outcome in IVM program. PMID:26396566

  4. Consolidating tactical planning and implementation frameworks for integrated vector management in Uganda.

    PubMed

    Okia, Michael; Okui, Peter; Lugemwa, Myers; Govere, John M; Katamba, Vincent; Rwakimari, John B; Mpeka, Betty; Chanda, Emmanuel

    2016-04-14

    Integrated vector management (IVM) is the recommended approach for controlling some vector-borne diseases (VBD). In the face of current challenges to disease vector control, IVM is vital to achieve national targets set for VBD control. Though global efforts, especially for combating malaria, now focus on elimination and eradication, IVM remains useful for Uganda which is principally still in the control phase of the malaria continuum. This paper outlines the processes undertaken to consolidate tactical planning and implementation frameworks for IVM in Uganda. The Uganda National Malaria Control Programme with its efforts to implement an IVM approach to vector control was the 'case' for this study. Integrated management of malaria vectors in Uganda remained an underdeveloped component of malaria control policy. In 2012, knowledge and perceptions of malaria vector control policy and IVM were assessed, and recommendations for a specific IVM policy were made. In 2014, a thorough vector control needs assessment (VCNA) was conducted according to WHO recommendations. The findings of the VCNA informed the development of the national IVM strategic guidelines. Information sources for this study included all available data and accessible archived documentary records on VBD control in Uganda. The literature was reviewed and adapted to the local context and translated into the consolidated tactical framework. WHO recommends implementation of IVM as the main strategy to vector control and has encouraged member states to adopt the approach. However, many VBD-endemic countries lack IVM policy frameworks to guide implementation of the approach. In Uganda most VBD coexists and could be managed more effectively if done in tandem. In order to successfully control malaria and other VBD and move towards their elimination, the country needs to scale up proven and effective vector control interventions and also learn from the experience of other countries. The IVM strategy is important in consolidating inter-sectoral collaboration and coordination and providing the tactical direction for effective deployment of vector control interventions along the five key elements of the approach and to align them with contemporary epidemiology of VBD in the country. Uganda has successfully established an evidence-based IVM approach and consolidated strategic planning and operational frameworks for VBD control. However, operating implementation arrangements as outlined in the national strategic guidelines for IVM and managing insecticide resistance, as well as improving vector surveillance, are imperative. In addition, strengthened information, education and communication/behaviour change and communication, collaboration and coordination will be crucial in scaling up and using vector control interventions.

  5. Vector control programs in Saint Johns County, Florida and Guayas, Ecuador: successes and barriers to integrated vector management

    PubMed Central

    2014-01-01

    Background Vector-borne diseases (VBDs) and mosquito control programs (MCPs) diverge in settings and countries, and lead control specialists need to be aware of the most effective control strategies. Integrated Vector Management (IVM) strategies, once implemented in MCPs, aim to reduce cost and optimize protection of the populations against VBDs. This study presents a strengths, weaknesses, opportunities, and threats (SWOT) analysis to compare IVM strategies used by MCPs in Saint Johns County, Florida and Guayas, Ecuador. This research evaluates MCPs strategies to improve vector control activities. Methods Methods included descriptive findings of the MCP operations. Information was obtained from vector control specialists, directors, and residents through field trips, surveys, and questionnaires. Evaluations of the strategies and assets of the control programs where obtained through SWOT analysis and within an IVM approach. Results Organizationally, the Floridian MCP is a tax-based District able to make decisions independently from county government officials, with the oversight of an elected board of commissioners. The Guayas program is directed by the country government and assessed by non-governmental organizations like the World health Organization. Operationally, the Floridian MCP conducts entomological surveillance and the Ecuadorian MCP focuses on epidemiological monitoring of human disease cases. Strengths of both MCPs were their community participation and educational programs. Weaknesses for both MCPs included limitations in budgets and technical capabilities. Opportunities, for both MCPs, are additional funding and partnerships with private, non-governmental, and governmental organizations. Threats experienced by both MCPs included political constraints and changes in the social and ecological environment that affect mosquito densities and control efforts. IVM pillars for policy making were used to compare the information among the programs. Differences included how the Ecuadorian MCP relies heavily on the community for vector control while the American MCP relies on technologies and research. Conclusion IVM based recommendations direct health policy leaders toward improving surveillance systems both entomologically and epidemiologically, improving community risk perceptions by integrating components of community participation, maximizing resources though the use of applied research, and protecting the environment by selecting low-risk pesticides. Outcomes of the research revealed that inter-sectorial and multidisciplinary interventions are critical to improve public health. PMID:24990155

  6. Expanding integrated vector management to promote healthy environments

    PubMed Central

    Lizzi, Karina M.; Qualls, Whitney A.; Brown, Scott C.; Beier, John C.

    2014-01-01

    Integrated Vector Management (IVM) strategies are intended to protect communities from pathogen transmission by arthropods. These strategies target multiple vectors and different ecological and socioeconomic settings, but the aggregate benefits of IVM are limited by the narrow focus of its approach; IVM strategies only aim to control arthropod vectors. We argue that IVM should encompass environmental modifications at early stages, for instance, infrastructural development and sanitation services, to regulate not only vectors but also nuisance-biting arthropods. An additional focus on nuisance-biting arthropods will improve public health, quality of life, and minimize social disparity issues fostered by pests. Optimally, IVM could incorporate environmental awareness and promotion of control methods in order to proactively reduce threats of serious pest situations. PMID:25028090

  7. Integrated vector management: the Zambian experience.

    PubMed

    Chanda, Emmanuel; Masaninga, Fred; Coleman, Michael; Sikaala, Chadwick; Katebe, Cecilia; Macdonald, Michael; Baboo, Kumar S; Govere, John; Manga, Lucien

    2008-08-27

    The Zambian Malaria Control Programme with the Roll Back Malaria (RBM) partners have developed the current National Malaria Strategic Plan (NMSP 2006-2011) which focuses on prevention based on the Integrated Vector Management (IVM) strategy. The introduction and implementation of an IVM strategy was planned in accordance with the World Health Organization (WHO) steps towards IVM implementation namely Introduction Phase, Consolidation Phase and Expansion Phase. IVM has created commitment for Legal and Regulatory policy review, monitoring, Research and a strong stewardship by the chemical suppliers. It has also leveraged additional resources, improved inter-sectoral collaboration, capacity building and enhanced community participation which facilitated a steady scaling up in coverage and utilisation of key preventive interventions. Thus, markedly reducing malaria incidence and case fatalities in the country. Zambia has successfully introduced, consolidated and expanded IVM activities. Resulting in increased coverage and utilization of interventions and markedly reducing malaria-related morbidity and mortality while ensuring a better protection of the environment.

  8. In-vitro maturation of germinal vesicle and metaphase I eggs prior to cryopreservation optimizes reproductive potential in patients undergoing fertility preservation.

    PubMed

    Lee, Joseph A; Sekhon, Lucky; Grunfeld, Lawrence; Copperman, Alan B

    2014-06-01

    To evaluate current and previous findings related to a timely implementation of in-vitro maturation (IVM) of germinal vesicle, metaphase I and metaphase II oocytes with an optimal cryopreservation to determine whether IVM should be attempted prior to (fresh IVM) or IVM after cryopreservation (postthaw IVM). Mitochondrion, chromatin and spindle formation in both groups were interpreted from referenced studies to establish best management of all oocytes. The postthaw survival of germinal vesicle, metaphase I, fresh IVM-metaphase II and control metaphase II oocytes did not differ significantly [83.3% (n=9), 86.7% (n=12), 83% (n=57) and 86% (n=68), respectively]. Overall, combined survival and maturation were significantly higher (P<0.05) in the fresh IVM group at 63.8% (44 of 69) compared with the postthaw IVM group at 33.3% (nine of 27). Conservation of retrieved immature oocytes after vaginal oocyte retrieval has become a major concern for patients, as they strive to maximize the reproductive viability of all oocytes obtained during treatment. Oocyte cryopreservation is important for patients at risk of ovarian cancer, elective fertility preservation and potentially for ovum donation. The superior maturation rate of germinal vesicle and metaphase I oocytes in the fresh IVM vs. postthaw groups provides strong impetus to mature oocytes to the metaphase II stage prior to cryopreservation.

  9. Ivermectin reduces alcohol intake and preference in mice

    PubMed Central

    Yardley, Megan; Wyatt, Letisha; Khoja, Sheraz; Asatryan, Liana; Ramaker, Marcia J.; Finn, Deborah A.; Alkana, Ronald L.; Huynh, Nhat; Louie, Stan G.; Petasis, Nicos A.; Bortolato, Marco; Davies, Daryl L.

    2012-01-01

    The high rate of therapeutic failure in the management of alcohol use disorders (AUDs) underscores the urgent need for novel and effective strategies that can deter ethanol consumption. Recent findings from our group showed that ivermectin (IVM), a broad-spectrum anthelmintic with high tolerability and optimal safety profile in humans and animals, antagonized ethanol-mediated inhibition of P2X4 receptors (P2X4Rs) expressed in Xenopus oocytes. This finding prompted us to hypothesize that IVM may reduce alcohol consumption; thus, in the present study we investigated the effects of this agent on several models of alcohol self-administration in male and female C57BL/6 mice. Overall, IVM (1.25–10 mg/kg, intraperitoneal) significantly reduced 24-h alcohol consumption and intermittent limited access (4-h) binge drinking, and operant alcohol self-administration (1-h). The effects on alcohol intake were dose-dependent with the significant reduction in intake at 9 h after administration corresponding to peak IVM concentrations (Cmax) in the brain. IVM also produced a significant reduction in 24-h saccharin consumption, but did not alter operant sucrose self-administration. Taken together, the findings indicate that IVM reduces alcohol intake across several different models of self-administration and suggest that IVM may be useful in the treatment of AUDs. PMID:22465817

  10. Preclinical Study of Single-Dose Moxidectin, a New Oral Treatment for Scabies: Efficacy, Safety, and Pharmacokinetics Compared to Two-Dose Ivermectin in a Porcine Model.

    PubMed

    Bernigaud, Charlotte; Fang, Fang; Fischer, Katja; Lespine, Anne; Aho, Ludwig Serge; Dreau, Dominique; Kelly, Andrew; Sutra, Jean-François; Moreau, Francis; Lilin, Thomas; Botterel, Françoise; Guillot, Jacques; Chosidow, Olivier

    2016-10-01

    Scabies is one of the commonest dermatological conditions globally; however it is a largely underexplored and truly neglected infectious disease. Foremost, improvement in the management of this public health burden is imperative. Current treatments with topical agents and/or oral ivermectin (IVM) are insufficient and drug resistance is emerging. Moxidectin (MOX), with more advantageous pharmacological profiles may be a promising alternative. Using a porcine scabies model, 12 pigs were randomly assigned to receive orally either MOX (0.3 mg/kg once), IVM (0.2 mg/kg twice) or no treatment. We evaluated treatment efficacies by assessing mite count, clinical lesions, pruritus and ELISA-determined anti-S. scabiei IgG antibodies reductions. Plasma and skin pharmacokinetic profiles were determined. At day 14 post-treatment, all four MOX-treated but only two IVM-treated pigs were mite-free. MOX efficacy was 100% and remained unchanged until study-end (D47), compared to 62% (range 26-100%) for IVM, with one IVM-treated pig remaining infected until D47. Clinical scabies lesions, pruritus and anti-S. scabiei IgG antibodies had completely disappeared in all MOX-treated but only 75% of IVM-treated pigs. MOX persisted ~9 times longer than IVM in plasma and skin, thereby covering the mite's entire life cycle and enabling long-lasting efficacy. Our data demonstrate that oral single-dose MOX was more effective than two consecutive IVM-doses, supporting MOX as potential therapeutic approach for scabies.

  11. Preclinical Study of Single-Dose Moxidectin, a New Oral Treatment for Scabies: Efficacy, Safety, and Pharmacokinetics Compared to Two-Dose Ivermectin in a Porcine Model

    PubMed Central

    Bernigaud, Charlotte; Aho, Ludwig Serge; Dreau, Dominique; Kelly, Andrew; Sutra, Jean-François; Moreau, Francis; Lilin, Thomas; Botterel, Françoise; Guillot, Jacques; Chosidow, Olivier

    2016-01-01

    Background Scabies is one of the commonest dermatological conditions globally; however it is a largely underexplored and truly neglected infectious disease. Foremost, improvement in the management of this public health burden is imperative. Current treatments with topical agents and/or oral ivermectin (IVM) are insufficient and drug resistance is emerging. Moxidectin (MOX), with more advantageous pharmacological profiles may be a promising alternative. Methodology/Principal Findings Using a porcine scabies model, 12 pigs were randomly assigned to receive orally either MOX (0.3 mg/kg once), IVM (0.2 mg/kg twice) or no treatment. We evaluated treatment efficacies by assessing mite count, clinical lesions, pruritus and ELISA-determined anti-S. scabiei IgG antibodies reductions. Plasma and skin pharmacokinetic profiles were determined. At day 14 post-treatment, all four MOX-treated but only two IVM-treated pigs were mite-free. MOX efficacy was 100% and remained unchanged until study-end (D47), compared to 62% (range 26–100%) for IVM, with one IVM-treated pig remaining infected until D47. Clinical scabies lesions, pruritus and anti-S. scabiei IgG antibodies had completely disappeared in all MOX-treated but only 75% of IVM-treated pigs. MOX persisted ~9 times longer than IVM in plasma and skin, thereby covering the mite’s entire life cycle and enabling long-lasting efficacy. Conclusions/Significance Our data demonstrate that oral single-dose MOX was more effective than two consecutive IVM-doses, supporting MOX as potential therapeutic approach for scabies. PMID:27732588

  12. Quality management system and accreditation of the in vivo monitoring laboratory at Karslruhe Institute of Technology.

    PubMed

    Breustedt, B; Mohr, U; Biegard, N; Cordes, G

    2011-03-01

    The in vivo monitoring laboratory (IVM) at Karlsruhe Institute of Technology (KIT), with one whole body counter and three partial-body counters, is an approved lab for individual monitoring according to German regulation. These approved labs are required to prove their competencies by accreditation to ISO/IEC 17025:2005. In 2007 a quality management system (QMS), which was successfully audited and granted accreditation, was set up at the IVM. The system is based on the ISO 9001 certified QMS of the central safety department of the Research Centre Karlsruhe the IVM belonged to at that time. The system itself was set up to be flexible and could be adapted to the recent organisational changes (e.g. founding of KIT and an institute for radiation research) with only minor effort.

  13. Integrated vector management: a critical strategy for combating vector-borne diseases in South Sudan.

    PubMed

    Chanda, Emmanuel; Govere, John M; Macdonald, Michael B; Lako, Richard L; Haque, Ubydul; Baba, Samson P; Mnzava, Abraham

    2013-10-25

    Integrated vector management (IVM) based vector control is encouraged by the World Health Organization (WHO). However, operational experience with the IVM strategy has mostly come from countries with relatively well-established health systems and with malaria control focused programmes. Little is known about deployment of IVM for combating multiple vector-borne diseases in post-emergency settings, where delivery structures are less developed or absent. This manuscript reports on the feasibility of operational IVM for combating vector-borne diseases in South Sudan. A methodical review of published and unpublished documents on vector-borne diseases for South Sudan was conducted via systematic literature search of online electronic databases, Google Scholar, PubMed and WHO, using a combination of search terms. Additional, non-peer reviewed literature was examined for information related to the subject. South Sudan is among the heartlands of vector-borne diseases in the world, characterized by enormous infrastructure, human and financial resource constraints and a weak health system against an increasing number of refugees, returnees and internally displaced people. The presence of a multiplicity of vector-borne diseases in this post-conflict situation presents a unique opportunity to explore the potential of a rational IVM strategy for multiple disease control and optimize limited resource utilization, while maximizing the benefits and providing a model for countries in a similar situation. The potential of integrating vector-borne disease control is enormous in South Sudan. However, strengthened coordination, intersectoral collaboration and institutional and technical capacity for entomological monitoring and evaluation, including enforcement of appropriate legislation are crucial.

  14. Integrated vector management: a critical strategy for combating vector-borne diseases in South Sudan

    PubMed Central

    2013-01-01

    Background Integrated vector management (IVM) based vector control is encouraged by the World Health Organization (WHO). However, operational experience with the IVM strategy has mostly come from countries with relatively well-established health systems and with malaria control focused programmes. Little is known about deployment of IVM for combating multiple vector-borne diseases in post-emergency settings, where delivery structures are less developed or absent. This manuscript reports on the feasibility of operational IVM for combating vector-borne diseases in South Sudan. Case description A methodical review of published and unpublished documents on vector-borne diseases for South Sudan was conducted via systematic literature search of online electronic databases, Google Scholar, PubMed and WHO, using a combination of search terms. Additional, non-peer reviewed literature was examined for information related to the subject. Discussion South Sudan is among the heartlands of vector-borne diseases in the world, characterized by enormous infrastructure, human and financial resource constraints and a weak health system against an increasing number of refugees, returnees and internally displaced people. The presence of a multiplicity of vector-borne diseases in this post-conflict situation presents a unique opportunity to explore the potential of a rational IVM strategy for multiple disease control and optimize limited resource utilization, while maximizing the benefits and providing a model for countries in a similar situation. Conclusion The potential of integrating vector-borne disease control is enormous in South Sudan. However, strengthened coordination, intersectoral collaboration and institutional and technical capacity for entomological monitoring and evaluation, including enforcement of appropriate legislation are crucial. PMID:24156749

  15. Integrated vector management for malaria control

    PubMed Central

    Beier, John C; Keating, Joseph; Githure, John I; Macdonald, Michael B; Impoinvil, Daniel E; Novak, Robert J

    2008-01-01

    Integrated vector management (IVM) is defined as "a rational decision-making process for the optimal use of resources for vector control" and includes five key elements: 1) evidence-based decision-making, 2) integrated approaches 3), collaboration within the health sector and with other sectors, 4) advocacy, social mobilization, and legislation, and 5) capacity-building. In 2004, the WHO adopted IVM globally for the control of all vector-borne diseases. Important recent progress has been made in developing and promoting IVM for national malaria control programmes in Africa at a time when successful malaria control programmes are scaling-up with insecticide-treated nets (ITN) and/or indoor residual spraying (IRS) coverage. While interventions using only ITNs and/or IRS successfully reduce transmission intensity and the burden of malaria in many situations, it is not clear if these interventions alone will achieve those critical low levels that result in malaria elimination. Despite the successful employment of comprehensive integrated malaria control programmes, further strengthening of vector control components through IVM is relevant, especially during the "end-game" where control is successful and further efforts are required to go from low transmission situations to sustained local and country-wide malaria elimination. To meet this need and to ensure sustainability of control efforts, malaria control programmes should strengthen their capacity to use data for decision-making with respect to evaluation of current vector control programmes, employment of additional vector control tools in conjunction with ITN/IRS tactics, case-detection and treatment strategies, and determine how much and what types of vector control and interdisciplinary input are required to achieve malaria elimination. Similarly, on a global scale, there is a need for continued research to identify and evaluate new tools for vector control that can be integrated with existing biomedical strategies within national malaria control programmes. This review provides an overview of how IVM programmes are being implemented, and provides recommendations for further development of IVM to meet the goals of national malaria control programmes in Africa. PMID:19091038

  16. Aquatic toxicity of ivermectin in cattle dung assessed using microcosms.

    PubMed

    Mesa, Leticia M; Lindt, I; Negro, L; Gutierrez, M F; Mayora, G; Montalto, L; Ballent, M; Lifschitz, A

    2017-10-01

    Ivermectin (IVM) is a parasiticide widely used for livestock. It is a semisynthetic derivative of avermectin, a macrocyclic lactone produced by Streptomyces avermitilis. This drug is only partly metabolized by livestock; considerable amounts of parent drug are excreted mostly via feces. To simulate exposure of aquatic invertebrates and macrophytes to direct excretion of cattle dung into surface waters, a microcosm experiment with IVM spiked in cattle dung was conducted. The objectives of this study were to characterize accumulation of IVM in water, sediment+dung, roots of the floating fern Salvinia and the zooplankton Ceriodaphnia dubia, the amphipod Hyalella and the apple snail Pomacea; to determine the effect of this drug spiked in cattle dung on life-history traits of these invertebrates; and to evaluate the influence of IVM on aquatic nutrient cycling. Dung was spiked with IVM to attain concentrations of 1150, 458, 50 and 22µgkg -1 dung fresh weight, approximating those found in cattle dung at days 3, 7, 16 and 29 following subcutaneous injection. Concentrations found in dung during the first week of excretion were lethally toxic to Ceriodaphnia dubia and Hyalella, whereas no mortality was observed in Pomacea. Concentrations of IVM in roots, sediment + dung and Pomacea increased significantly from the lowest to the highest treatment level. The effect of this drug on decomposition and release of nutrients from dung would have negative consequences for nutrient cycling in water. Increasing concentrations in sediment + dung with days of the experiment suggested that toxic concentrations would persist for an extended period in the water-sediment system. IVM represents an ecological risk for aquatic ecosystems, underscoring the need for livestock management strategies to limit its entry into water bodies. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Ivermectin disposition kinetics after subcutaneous and intramuscular administration of an oil-based formulation to cattle.

    PubMed

    Lifschitz, A; Virkel, G; Pis, A; Imperiale, F; Sanchez, S; Alvarez, L; Kujanek, R; Lanusse, C

    1999-10-01

    Slight differences in formulation may change the plasma kinetics and ecto-endoparasiticide activity of endectocide compounds. This work reports on the disposition kinetics and plasma availability of ivermectin (IVM) after subcutaneous (SC) and intramuscular (IM) administration as an oil-based formulation to cattle. Parasite-free Aberdeen Angus calves (n = 24; 240-280 kg) were divided into three groups (n = 8) and treated (200 microg/kg) with either an IVM oil-based pharmaceutical preparation (IVM-TEST formulation) (Bayer Argentina S.A.) given by subcutaneous (Group A) and intramuscular (Group B) injections or the IVM-CONTROL (non-aqueous formulation) (Ivomec, MSD Agvet) subcutaneously administered (Group C). Blood samples were taken over 35 days post-treatment and the recovered plasma was extracted and analyzed by HPLC using fluorescence detection. IVM was detected in plasma between 12 h and 35 days post-administration of IVM-TEST (SC and IM injections) and IVM-CONTROL formulations. Prolonged IVM absorption half-life (p < 0.05) and delayed peak plasma concentration (p < 0.001) were obtained following the SC administration of the IVM-TEST compared to the IVM-CONTROL formulation. No differences in total plasma availability were observed among treatments. However, the plasma residence time and elimination half-life of IVM were significantly longer after injection of the IVM-TEST formulation. IVM plasma concentrations were above 0.5 ng/ml for 20.6 (CONTROL) and 27.5 days (IVM-TEST SC), respectively (p < 0.05). The modified kinetic behaviour of IVM obtained after the administration of the novel oil-based formulation examined in this trial, compared to the standard preparation, may positively impact on its strategic use in cattle.

  18. Resistant nematodes in cattle: Pharmaco-therapeutic assessment of the ivermectin- ricobendazole combination.

    PubMed

    Canton, Candela; Ceballos, Laura; Fiel, César; Moreno, Laura; Domingo Yagüez, Pablo; Bernat, Gisele; Lanusse, Carlos; Alvarez, Luis

    2017-01-30

    Nematodicidal combinations have been proposed as a valid strategy to achieve effective nematode control in the presence of drug resistance. The goals of this study were: (1) to compare the clinical efficacy (therapeutic response) of ivermectin (IVM) and ricobendazole (RBZ) given subcutaneously either by separate or combined administration to calves naturally infected with gastrointestinal nematodes resistant to IVM, and (2) to evaluate the potential pharmacokinetic (PK) and/or pharmacodynamic (PD) interactions occurring after the co-administration of both anthelmintics. Sixty male calves naturally infected with gastrointestinal nematodes resistant to IVM were randomly allocated into four groups (n=15). Untreated control: animals not receiving anthelmintic treatment; IVM alone: animals treated with IVM by subcutaneous (SC) injection (0.2mg/kg); RBZ alone: animals received RBZ by the SC route (3.75mg/kg); IVM+RBZ: animals treated with IVM and RBZ (0.2 and 3.75mg/kg, respectively), by SC injection in two separates sites. Eight animals of each treated group were randomly selected to perform the PK study. Plasma samples were taken from those animals up to 28days post-treatment. IVM and RBZ plasma concentrations were quantified by HPLC. The therapeutic response was determined by faecal egg count reduction test (FECRT). The proportions of third-stage larvae (L3) recovered from coprocultures were used to calculate the efficacy against the main parasite genera. The daily total egg deposition for each experimental group was estimated. Similar pharmacokinetic trends were obtained for both IVM and RBZ allying the single-drug and the combined treatments, which indicates the absence of PK interactions between both anthelmintics. The observed overall clinical drug efficacies were 48% (IVM alone), 94% (RBZ alone) and 98% (IVM+RBZ). Haemonchus spp. and Cooperia spp. were recovered in the coproculture after IVM treatment, suggesting that resistance to IVM includes both genera. In fact, the efficacy against Cooperia spp. was 83% (IVM), 98% (RBZ) and 98% (IVM+RBZ), while the efficacy against Haemonchus spp. was 0% (IVM), 97% (RBZ) and 100% (IVM+RBZ). The combination was the only treatment that achieved 100% clinical efficacy against IVM-resistant Haemonchus spp. The total egg excretion was reduced to 49.9% (IVM alone group), 6.3% (RBZ alone group) and 1.8% (IVM+RBZ combined group) compared to the untreated control. Although the combined treatment did not significantly increase the overall clinical efficacy in the current natural field conditions, an additive effect was achieved against IVM-resistant nematodes. In fact, the combination obtained significantly higher efficacy against IVM-resistant Haemonchus spp. than RBZ alone. Additionally, the epidemiological relevance of the reduction in the number of eggs excreted following the combined treatment is not negligible and should be taken into account in future studies. Further work is required to understand the advantages of nematodicidal combinations in different natural anthelmintic resistance scenarios. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Decreased pregnancy and live birth rates after vitrification of in vitro matured oocytes.

    PubMed

    Cohen, Yoni; St-Onge-St-Hilaire, Alexandra; Tannus, Samer; Younes, Grace; Dahan, Michael H; Buckett, William; Son, Weon-Young

    2018-06-04

    To assess effects on fertilization rate, embryo quality, pregnancy, and live birth rates of vitrification and warming of oocytes that matured in vitro (vIVM) compared to fresh in vitro maturation (fIVM) cycles. A retrospective cohort study conducted at a university hospital-affiliated IVF unit. Fifty-six cycles of vIVM cycles and 263 fIVM in women diagnosed with polycystic ovarian syndrome (PCOS) ovaries were included in the analysis. The study group included PCOS patients who failed ovulation induction with intrauterine insemination and were offered IVM cycle followed by oocyte vitrification and warming. The embryological aspects and clinical outcomes were compared to those of controls undergoing fresh IVM cycles during the same period. The main outcome measure was live birth rate. One thousand seventy oocytes were collected from 56 patients and underwent vitrification and warming. In the control group, 4781 oocytes were collected from 219 patients who had undergone a fresh IVM cycle. Oocyte maturation rates were similar between the groups (mean ± SD: 0.7 ± 0.2 vs. 0.6 ± 0.2, for vIVM and fIVM, respectively). Survival rate after warming was 59.8%. Fertilization and embryo cleavage rates per oocyte were significantly lower in the vIVM group. Clinical pregnancy (10.7 vs. 36.1%) and live birth rates (8.9 vs. 25.9%) per cycle were significantly lower in the vIVM group than those in the fIVM group (P = 0.005 and P < 0.001, respectively). Five healthy babies were born in the vIVM group. The reproductive potential of vitrified IVM oocytes is impaired. This injury likely occurs through vitrification and warming.

  20. Is the future of meat palatable? Perceptions of in vitro meat as evidenced by online news comments.

    PubMed

    Laestadius, Linnea I; Caldwell, Mark A

    2015-09-01

    To understand current public perceptions of in vitro meat (IVM) in light of its potential to be a more environmentally sustainable alternative to conventional meat. A qualitative content analysis of the comments made on online news articles highlighting the development of IVM and the world's first IVM hamburger in August 2013. News article comment sections across seven US-based online news sources (The New York Times, The Los Angeles Times, The Washington Post, The Wall Street Journal, USA Today, Cable News Network and National Public Radio). Four hundred and sixty-two commenters who made eight hundred and fourteen publicly available online comments addressing IVM. Key themes in commenter perceptions of IVM included environmental and public health benefits, but also negative themes such as IVM's status as an unnatural and unappealing food. Overall, the tone of comments was more negative than positive. Findings suggest that while the environmental and public health motivations for developing and in turn consuming IVM resonate with some segments of the population, others find that reasoning both uncompelling and problematic. Concerns about IVM as an unnatural and risky product also appear to be a significant barrier to public acceptance of IVM. Supporters of IVM may wish to begin to develop a regulatory strategy for IVM to build public trust and explore messaging strategies that cast IVM as a new technology with benefits to individuals rather than primarily a solution to global challenges. Those in the public health nutrition field can make an important contribution to the emerging public discussion about IVM.

  1. The route of administration drastically affects ivermectin activity against small strongyles in horses.

    PubMed

    Saumell, Carlos; Lifschitz, Adrián; Baroni, Renato; Fusé, Luis; Bistoletti, Mariana; Sagües, Federica; Bruno, Santiago; Alvarez, Gustavo; Lanusse, Carlos; Alvarez, Luis

    2017-03-15

    The goal of the current study was to evaluate the comparative efficacy of ivermectin (IVM) against small strongyles (cyathostomins) following its oral and intramuscular (IM) administration, in naturally parasitized horses. The parasitological data were complemented with the assessment of the plasma disposition kinetics of IVM. The trial included two different experiments. In experiment I, 40 horses naturally infected with small strongyles were randomly allocated into four experimental groups (n=10) and treated with IVM (0.2mg/kg) as follows: IVM oral paste, animals were orally treated with Eqvalan ® (IVM 1.87% paste, as the reference formulation) by the oral route; IVM oral solution, animals were orally treated with Remonta ® (IVM 2% solution, as a test formulation); IVM IM solution, animals were IM treated with the test product (Remonta ® IVM 2% solution); and control, animals were kept without treatment as untreated controls. In experiment II, 24 horses naturally parasitized with small strongyles were randomly allocated into the same four experimental groups (n=6) described for experiment I. Faecal samples were individually collected directly from the rectum of each horse prior (day -1) and at 7 and 15 (Experiment I) or 7, 15 and 21 (Experiment II) days after-treatment, to assess the eggs per gram (epg) counts and estimate the efficacy of the treatments. Additionally, the comparative plasma disposition kinetics of IVM in treated animals was assessed in experiment II. In both experiments, an excellent (100%) IVM efficacy was observed after its oral administration (test and reference formulations). However, the IM administration of IVM resulted in a low efficacy (36-64%). Similar IVM plasma concentration was observed after its oral administration as a paste or as a solution. The higher IVM plasma profiles observed after the IM administration accounted for an enhanced systemic availability. The improved IVM efficacy observed against adult cyathostomins after its oral administration can be explained by an enhanced drug exposure of the worms located at the lumen of the large intestine. These findings may have a direct impact on the practical use of macrocyclic lactones in horses. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Surveillance at the molecular level: Developing an integrated network for detecting variation in avian influenza viruses in Indonesia.

    PubMed

    Hartaningsih, Nining; Wibawa, Hendra; Pudjiatmoko; Rasa, Fadjar Sumping Tjatur; Irianingsih, Sri Handayani; Dharmawan, Rama; Azhar, Muhammad; Siregar, Elly Sawitri; McGrane, James; Wong, Frank; Selleck, Paul; Allen, John; Broz, Ivano; Torchetti, Mia Kim; Dauphin, Gwenaelle; Claes, Filip; Sastraningrat, Wiryadi; Durr, Peter A

    2015-06-01

    Since 2006, Indonesia has used vaccination as the principal means of control of H5N1-HPAI. During this time, the virus has undergone gradual antigenic drift, which has necessitated changes in seed strains for vaccine production and associated modifications to diagnostic antigens. In order to improve the system of monitoring such viral evolution, the Government of Indonesia, with the assistance of FAO/OFFLU, has developed an innovative network whereby H5N1 isolates are antigenically and genetically characterised. This molecular surveillance network ("Influenza Virus Monitoring" or "IVM") is based on the regional network of veterinary diagnostic laboratories, and is supported by a web-based data management system ("IVM Online"). The example of the Indonesian IVM network has relevance for other countries seeking to establish laboratory networks for the molecular surveillance of avian influenza and other pathogens. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Integrated vegetation management (IVM) for INDOT roadsides.

    DOT National Transportation Integrated Search

    2014-03-01

    With over 90,000 miles of road in Indiana, it is important that adjoining vegetation be maintained for safety concerns, road structure : maintenance and aesthetics. Mowing is currently the main form of vegetation management on INDOT (Indiana Departme...

  4. Integrated Vegetation Management Practices Memorandum of Understanding

    EPA Pesticide Factsheets

    Memorandum of Understanding between EPA and the Edison Electric Institute, U.S. Department of Agriculture (Forest Service), and U.S. Department of the Interior (Bureau of Land Management, Fish and Wildlife Service, and National Park Service for IVM.

  5. Relative Neurotoxicity of Ivermectin and Moxidectin in Mdr1ab (−/−) Mice and Effects on Mammalian GABA(A) Channel Activity

    PubMed Central

    Ménez, Cécile; Sutra, Jean-François; Prichard, Roger; Lespine, Anne

    2012-01-01

    The anthelmintics ivermectin (IVM) and moxidectin (MOX) display differences in toxicity in several host species. Entrance into the brain is restricted by the P-glycoprotein (P-gp) efflux transporter, while toxicity is mediated through the brain GABA(A) receptors. This study compared the toxicity of IVM and MOX in vivo and their interaction with GABA(A) receptors in vitro. Drug toxicity was assessed in Mdr1ab(−/−) mice P-gp-deficient after subcutaneous administration of increasing doses (0.11–2.0 and 0.23–12.9 µmol/kg for IVM and MOX in P-gp-deficient mice and half lethal doses (LD50) in wild-type mice). Survival was evaluated over 14-days. In Mdr1ab(−/−) mice, LD50 was 0.46 and 2.3 µmol/kg for IVM and MOX, respectively, demonstrating that MOX was less toxic than IVM. In P-gp-deficient mice, MOX had a lower brain-to-plasma concentration ratio and entered into the brain more slowly than IVM. The brain sublethal drug concentrations determined after administration of doses close to LD50 were, in Mdr1ab(−/−) and wild-type mice, respectively, 270 and 210 pmol/g for IVM and 830 and 740–1380 pmol/g for MOX, indicating that higher brain concentrations are required for MOX toxicity than IVM. In rat α1β2γ2 GABA channels expressed in Xenopus oocytes, IVM and MOX were both allosteric activators of the GABA-induced response. The Hill coefficient was 1.52±0.45 for IVM and 0.34±0.56 for MOX (p<0.001), while the maximum potentiation caused by IVM and MOX relative to GABA alone was 413.7±66.1 and 257.4±40.6%, respectively (p<0.05), showing that IVM causes a greater potentiation of GABA action on this receptor. Differences in the accumulation of IVM and MOX in the brain and in the interaction of IVM and MOX with GABA(A) receptors account for differences in neurotoxicity seen in intact and Mdr1-deficient animals. These differences in neurotoxicity of IVM and MOX are important in considering their use in humans. PMID:23133688

  6. Extending prematuration with cAMP modulators enhances the cumulus contribution to oocyte antioxidant defence and oocyte quality via gap junctions.

    PubMed

    Li, H J; Sutton-McDowall, M L; Wang, X; Sugimura, S; Thompson, J G; Gilchrist, R B

    2016-04-01

    Can bovine oocyte antioxidant defence and oocyte quality be improved by extending the duration of pre-in vitro maturation (IVM) with cyclic adenosine mono-phosphate (cAMP) modulators? Lengthening the duration of cAMP-modulated pre-IVM elevates intra-oocyte reduced glutathione (GSH) content and reduces hydrogen peroxide (H2O2) via increased cumulus cell-oocyte gap-junctional communication (GJC), associated with an improvement in subsequent embryo development and quality. Oocytes are susceptible to oxidative stress and the oocyte's most important antioxidant glutathione is supplied, at least in part, by cumulus cells. A temporary inhibition of spontaneous meiotic resumption in oocytes can be achieved by preventing a fall in cAMP, and cyclic AMP-modulated pre-IVM maintains cumulus-oocyte GJC and improves subsequent embryo development. This study consisted of a series of 10 experiments using bovine oocytes in vitro, each with multiple replicates. A range of pre-IVM durations were examined as the key study treatments which were compared with a control. The study was designed to examine if one of the oocyte's major antioxidant defences can be enhanced by pre-IVM with cAMP modulators, and to examine the contribution of cumulus-oocyte GJC on these processes. Immature bovine cumulus-oocyte complexes were treated in vitro without (control) or with the cAMP modulators; 100 µM forskolin (FSK) and 500 µM 3-isobutyl-1-methyxanthine (IBMX), for 0, 2, 4 or 6 h (pre-IVM phase) prior to IVM. Oocyte developmental competence was assessed by embryo development and quality post-IVM/IVF. Cumulus-oocyte GJC, intra-oocyte GSH and H2O2 were quantified at various time points during pre-IVM and IVM, in the presence and the absence of functional inhibitors: carbenoxolone (CBX) to block GJC and buthionine sulfoximide (BSO) to inhibit glutathione synthesis. Pre-IVM with FSK + IBMX increased subsequent blastocyst formation rate and quality compared with standard IVM (P < 0.05), regardless of pre-IVM duration. The final blastocyst yields (proportion of blastocysts/immature oocyte) were 26.3% for the control, compared with 39.2, 35.2 and 34.2%, for the 2, 4 and 6 h pre-IVM FSK + IBMX treatments, respectively. In contrast to standard IVM (control), pre-IVM with cAMP modulators maintained open gap junctions between cumulus cells and oocytes for the duration (6 h) of pre-IVM examined, and persisted for a further 8 h in the IVM phase. Cyclic AMP-modulated pre-IVM increased intra-oocyte GSH levels at the completion of both pre-IVM and IVM, in a pre-IVM duration-dependent manner (P < 0.05), which was ablated when GJC was blocked using CBX (P < 0.05). By 4 h of pre-IVM treatment with cAMP modulators, oocyte H2O2 levels were reduced compared the control (P < 0.05), although this beneficial effect was lost when oocytes were co-treated with BSO. Inhibiting glutathione synthesis with BSO during pre-IVM ablated any positive benefits of cAMP-mediated pre-IVM on oocyte developmental competence (P < 0.01). It is unclear if the improvement in oocyte antioxidant defence and developmental competence reported here is due to direct transfer of total and/or reduced glutathione from cumulus cells to the oocyte via gap junctions, or whether a GSH synthesis signal and/or amino acid substrates are supplied to the oocyte via gap junctions. Embryo transfer experiments are required to determine if the cAMP-mediated improvement in blastocyst rates leads to improved live birth rates. IVM offers significant benefits to infertile and cancer patients and has the potential to significantly alter ART practice, if IVM efficiency in embryo production could be improved closer to that of conventional IVF (using ovarian hyperstimulation). Pre-IVM with cAMP modulators is a simple and reliable means to improve IVM outcomes. This work was supported by grants and fellowships from the National Health and Medical Research Council of Australia (1007551, 627007, 1008137, 1023210) and by scholarships from the Chinese Scholarship Council (CSC) awarded to H.J.L. and the Japanese Society for the Promotion of Science Postdoctoral Fellowship for Research Abroad awarded to S.S. The Fluoview FV10i confocal microscope was purchased as part of the Sensing Technologies for Advanced Reproductive Research (STARR) facility, funded by the South Australian Premier's Science and Research Fund. We acknowledge partial support from the Australian Research Council Centre of Excellence for Nanoscale BioPhotonics (CE140100003). We declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported. © 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.

  7. Oocyte glutathione and fertilisation outcome of Macaca nemestrina and Macaca fascicularis in in vivo- and in vitro-matured oocytes

    PubMed Central

    Curnow, E. C.; Ryan, J. P.; Saunders, D. M.; Hayes, E. S.

    2010-01-01

    Fertilisation and development of IVM non-human primate oocytes is limited compared with that of in vivo-matured (IVO) oocytes. The present study describes the IVM of macaque oocytes with reference to oocyte glutathione (GSH). Timing of maturation, comparison of IVM media and cysteamine (CYS) supplementation as a modulator of GSH were investigated. A significantly greater proportion of oocytes reached MII after 30 h compared with 24 h of IVM. Following insemination, IVM oocytes had a significantly lower incidence of normal fertilisation (i.e. 2PN = two pronuclei and at least one polar body) and a higher rate of abnormal fertilisation (1PN = one pronucleus and at least one polar body) compared with IVO oocytes. Immunofluorescence of 1PN zygotes identified incomplete sperm head decondensation and failure of male pronucleus formation as the principal cause of abnormal fertilisation in IVM oocytes. The IVO oocytes had significantly higher GSH content than IVM oocytes. Cumulus-denuded oocytes had significantly lower GSH following IVM compared with immature oocytes at collection. Cysteamine supplementation of the IVM medium significantly increased the GSH level of cumulus-intact oocytes and reduced the incidence of 1PN formation, but did not improve GSH levels of the denuded oocyte. Suboptimal GSH levels in macaque IVM oocytes may be related to reduced fertilisation outcomes. PMID:20591337

  8. Oocyte glutathione and fertilisation outcome of Macaca nemestrina and Macaca fascicularis in in vivo- and in vitro-matured oocytes.

    PubMed

    Curnow, E C; Ryan, J P; Saunders, D M; Hayes, E S

    2010-01-01

    Fertilisation and development of IVM non-human primate oocytes is limited compared with that of in vivo-matured (IVO) oocytes. The present study describes the IVM of macaque oocytes with reference to oocyte glutathione (GSH). Timing of maturation, comparison of IVM media and cysteamine (CYS) supplementation as a modulator of GSH were investigated. A significantly greater proportion of oocytes reached MII after 30 h compared with 24 h of IVM. Following insemination, IVM oocytes had a significantly lower incidence of normal fertilisation (i.e. 2PN = two pronuclei and at least one polar body) and a higher rate of abnormal fertilisation (1PN = one pronucleus and at least one polar body) compared with IVO oocytes. Immunofluorescence of 1PN zygotes identified incomplete sperm head decondensation and failure of male pronucleus formation as the principal cause of abnormal fertilisation in IVM oocytes. The IVO oocytes had significantly higher GSH content than IVM oocytes. Cumulus-denuded oocytes had significantly lower GSH following IVM compared with immature oocytes at collection. Cysteamine supplementation of the IVM medium significantly increased the GSH level of cumulus-intact oocytes and reduced the incidence of 1PN formation, but did not improve GSH levels of the denuded oocyte. Suboptimal GSH levels in macaque IVM oocytes may be related to reduced fertilisation outcomes.

  9. Topical ivermectin improves allergic skin inflammation.

    PubMed

    Ventre, E; Rozières, A; Lenief, V; Albert, F; Rossio, P; Laoubi, L; Dombrowicz, D; Staels, B; Ulmann, L; Julia, V; Vial, E; Jomard, A; Hacini-Rachinel, F; Nicolas, J-F; Vocanson, M

    2017-08-01

    Ivermectin (IVM) is widely used in both human and veterinary medicine to treat parasitic infections. Recent reports have suggested that IVM could also have anti-inflammatory properties. Here, we investigated the activity of IVM in a murine model of atopic dermatitis (AD) induced by repeated exposure to the allergen Dermatophagoides farinae, and in standard cellular immunological assays. Our results show that topical IVM improved allergic skin inflammation by reducing the priming and activation of allergen-specific T cells, as well as the production of inflammatory cytokines. While IVM had no major impact on the functions of dendritic cells in vivo and in vitro, IVM impaired T-cell activation, proliferation, and cytokine production following polyclonal and antigen-specific stimulation. Altogether, our results show that IVM is endowed with topical anti-inflammatory properties that could have important applications for the treatment of T-cell-mediated skin inflammatory diseases. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Ecologists can enable communities to implement malaria vector control in Africa

    PubMed Central

    Mukabana, W Richard; Kannady, Khadija; Kiama, G Michael; Ijumba, Jasper N; Mathenge, Evan M; Kiche, Ibrahim; Nkwengulila, Gamba; Mboera, Leonard; Mtasiwa, Deo; Yamagata, Yoichi; van Schayk, Ingeborg; Knols, Bart GJ; Lindsay, Steven W; de Castro, Marcia Caldas; Mshinda, Hassan; Tanner, Marcel; Fillinger, Ulrike; Killeen, Gerry F

    2006-01-01

    Background Integrated vector management (IVM) for malaria control requires ecological skills that are very scarce and rarely applied in Africa today. Partnerships between communities and academic ecologists can address this capacity deficit, modernize the evidence base for such approaches and enable future scale up. Methods Community-based IVM programmes were initiated in two contrasting settings. On Rusinga Island, Western Kenya, community outreach to a marginalized rural community was achieved by University of Nairobi through a community-based organization. In Dar es Salaam, Tanzania, Ilala Municipality established an IVM programme at grassroots level, which was subsequently upgraded and expanded into a pilot scale Urban Malaria Control Programme with support from national academic institutes. Results Both programmes now access relevant expertise, funding and policy makers while the academic partners benefit from direct experience of community-based implementation and operational research opportunities. The communities now access up-to-date malaria-related knowledge and skills for translation into local action. Similarly, the academic partners have acquired better understanding of community needs and how to address them. Conclusion Until sufficient evidence is provided, community-based IVM remains an operational research activity. Researchers can never directly support every community in Africa so community-based IVM strategies and tactics will need to be incorporated into undergraduate teaching programmes to generate sufficient numbers of practitioners for national scale programmes. Academic ecologists at African institutions are uniquely positioned to enable the application of practical environmental and entomological skills for malaria control by communities at grassroots level and should be supported to fulfil this neglected role. PMID:16457724

  11. Prevalence of anthelmintic resistance on Lithuanian sheep farms assessed by in vitro methods.

    PubMed

    Kupčinskas, Tomas; Stadalienė, Inga; Šarkūnas, Mindaugas; Riškevičienė, Vita; Várady, Marian; Höglund, Johan; Petkevičius, Saulius

    2015-12-16

    This study examines the prevalence of drug resistance in gastrointestinal nematodes to macrocyclic lactones (ML) and benzimidazoles (BZ) in Lithuanian sheep using sensitive and precise in vitro methods. The survey was conducted from August 2013 to November 2014. Thirty-three farms with sheep previously treated with BZ and ivermectin (IVM) were included in the study. On 12 farms where only BZ were used, egg hatch discrimination dose testing (EHDDT) was conducted to detect anthelmintic resistance (AR) to BZ. On eight farms where only ML were used, micro agar larval development testing (MALDT) was conducted to detect AR to ivermectin (IVM). On the remaining 13 farms, where both classes of drugs were used, EHDDT and MALDT were both applied to detect multidrug resistance to BZ and IVM. BZ-resistant gastrointestinal nematodes were found on all 25 farms with a previous history of BZ use. High levels of resistance (>40 % of hatching) were recorded on 36 % of these farms, and low levels (<20 % of hatching) on 40 % of farms. IVM-resistant populations were found on 13 out of 21 sheep farms using this drug. Of these 13 farms with AR to IVM, low levels of resistance (<30 % development) were recorded on 84.6 % of farms and high levels (>30 % development) on 15.4 % of farms. No resistance to IVM was recorded on 38.1 % of farms. Multi-drug resistance was detected on five farms out of 13 (38.5 %) using both classes of drugs. The present study demonstrates the existence of AR to BZ and ML on Lithuanian sheep farms thus confirming results in a previous in vivo study. Cases of multi-drug resistance were recorded in the present study and require further consideration. An appropriate strategy for anthelmintic treatment, measures to prevent gastrointestinal nematode infection and a better understanding of the management practices associated with resistance may slow down further development of AR.

  12. [Comparision of in vitro maturation applied in PCOS and non-PCOS patients undergo stimulated and unstimulated protocols].

    PubMed

    Wang, Peiyu; Zhao, Junzhao; Jin, Congcong; Yu, Rong; Lin, Jia; Zhu, Ruru; Wu, Yonggen

    2014-12-01

    To compare the laboratory and clinical results between unstimulated in vitro maturation (IVM) and IVM converted from in vitro fertilization (IVF) in polycystic ovarian syndrome (PCOS) and non-PCOS patients. We divided 591 IVM cycles in the First Affiliated Hospital of Wenzhou Medical Univesity from Jan. 2008 to Dec. 2013 into 4 groups: group A1B1, PCOS patients underwent unstimulated IVM protocol, 240 cycles; group A1B2, PCOS patients underwent IVM converted from conventional stimulated IVF protocol, 153 cycles; group A2B1, non-PCOS patients underwent unstimutlated IVM protocol, 103 cycles; group A2B2, non-PCOS patient underwent IVM converted from conventional stimulated IVF protocol, 95 cycles. Multiple linear regression method and binary logistic regression method were used to assess the influence of PCOS and protocols for IVM on laboratory and clinical outcomes. The mean number of oocytes retrieved was positively related with PCOS [partial regression coefficient (B) = 3.37, P < 0.01]. The maturation rate of oocytes was positively related with hCG-prime prior to oocyte aspiration (B = 0.05, P = 0.010). High-quality embryo rate was positively related with PCOS and IVM converted from IVF (B = 0.08, P = 0.010; B = 0.09, P = 0.001), as well as implantation rate related with them (B = 0.07, P = 0.010; B = 0.10, P < 0.01). PCOS and IVM converted from IVF improved hCG positive (hCG>10 U/L) rate (OR = 1.636, 95%CI: 1.113-2.204, P < 0.05; OR = 1.861, 95%CI: 1.307-2.649, P < 0.05) and the clinical pregnancy rate (OR = 1.507, 95%CI: 1.041-2.240, P < 0.05; OR = 1.881, 95%CI: 1.312-2.696, P < 0.05). IVM converted from IVF protocol decreased the spontaneous abortion rate (OR = 0.490, 95%CI: 0.245-0.978, P < 0.05). Multiple gestation rate and ectopic pregnancy rate were not affected by PCOS condition and protocol used (P > 0.05). PCOS and IVM converted from IVF protocol improved the high-quality embryo rate, implantation rate, hCG positive rate and clinical pregnancy rate. IVM converted from IVF protocol reduced the spontaneous abortion rate. PCOS patients may be more suitable for the IVM treatment. No matter PCOS or non-PCOS patients, IVM converted from IVF protocol had better pregnancy outcome than that of unstimulated cycle.

  13. Heparin and cAMP modulators interact during pre-in vitro maturation to affect mouse and human oocyte meiosis and developmental competence.

    PubMed

    Zeng, Hai-tao; Ren, Zi; Guzman, Luis; Wang, Xiaoqian; Sutton-McDowall, Melanie L; Ritter, Lesley J; De Vos, Michel; Smitz, Johan; Thompson, Jeremy G; Gilchrist, Robert B

    2013-06-01

    Does heparin ablate the advantageous effects of cyclic adenosine mono-phosphate (cAMP) modulators during pre-in vitro maturation (IVM) and have a deleterious effect in standard oocyte IVM? Heparin interrupts energy metabolism and meiotic progression and adversely affects subsequent development of oocytes under conditions of elevated cAMP levels in cumulus-oocyte complexes (COCs) after pre-IVM treatment with forskolin. In animal IVM studies, artificial regulation of meiotic resumption by cAMP-elevating agents improves subsequent oocyte developmental competence. Heparin has no effect on spontaneous, FSH- or epidermal growth factor (EGF)-stimulated meiotic maturation. An in vitro cross-sectional study was conducted using immature mouse and human COCs. Depending on individual experimental design, COCs were treated during pre-IVM with or without heparin, in the presence or absence of forskolin and/or 3-isobutyl-1-methylxanthine (IBMX), and then COC function was assessed by various means. Forty-two women with polycystic ovaries (PCOs) or polycystic ovarian syndrome (PCOS) donated COCs after oocyte retrieval in a non-hCG-triggered IVM cycle. COCs were collected in pre-IVM treatments and then cultured for 40 h and meiotic progression was assessed. COCs from 21- to 24-day-old female CBA F1 mice were collected 46 h after stimulation with equine chorionic gonadotrophin. Following treatments, COCs were checked for meiotic progression. Effects on mouse oocyte metabolism were measured by assessing oocyte mitochondrial membrane potential using JC-1 staining and oocyte ATP content. Post-IVM mouse oocyte developmental competence was assessed by in vitro fertilization and embryo production. Blastocyst quality was evaluated by differential staining of inner cell mass (ICM) and trophectoderm (TE) layers. In the absence of heparin in pre-IVM culture, the addition of cAMP modulators did not affect human oocyte MII competence after 40 h. In standard IVM, heparin supplementation in pre-IVM did not affect MII competence; however, when heparin was combined with cAMP modulators, MII competence was significantly reduced from 65 to 15% (P < 0.05). In mouse experiments, heparin alone in pre-IVM significantly delayed germinal vesicle breakdown (GVBD) so that fewer GVBDs were observed at 0 and 1 h of IVM (P < 0.05), but not by 2 or 3 h of IVM. Combined treatment with IBMX and forskolin in the pre-IVM medium produced a large delay in GVBD such that no COCs exhibited GVBD in the first 1 h of IVM, and the addition of heparin in pre-IVM further significantly delayed the progression of GVBD (P < 0.05), in a dose-dependent manner (P < 0.01). Combined IBMX and forskolin treatment of mouse COCs during pre-IVM significantly increased mitochondrial membrane potential and ATP production in the oocyte at the end of pre-IVM (P < 0.05), and significantly improved fertilization, embryo development and quality (P < 0.05). However, heparin abolished the IBMX + forskolin-stimulated increase in mitochondrial membrane potential and ATP production (P < 0.05), and adversely affected embryonic cleavage, development rates and embryo quality (P < 0.05). This latter adverse combinational effect was negated when mouse COCs were collected in heparin and IBMX for 15 min, washed and then cultured for 45 min in IBMX and forskolin without heparin. Experiments in mice found that heparin ablation of the advantageous effects of cAMP modulators during pre-IVM was associated with altered oocyte metabolism, but the mechanism by which heparin affects metabolism remains unclear. This study has revealed a novel and unexpected interaction between heparin and cAMP modulators in pre-IVM in immature mouse and human oocytes, and established a means to collect oocytes using heparin while modulating oocyte cAMP to improve developmental potential.

  14. Long-term safety of ivermectin 1% cream vs azelaic acid 15% gel in treating inflammatory lesions of rosacea: results of two 40-week controlled, investigator-blinded trials.

    PubMed

    Stein Gold, Linda; Kircik, Leon; Fowler, Joseph; Jackson, J Mark; Tan, Jerry; Draelos, Zoe; Fleischer, Alan; Appell, Melanie; Steinhoff, Martin; Lynde, Charles; Sugarman, Jeffrey; Liu, Hong; Jacovella, Jean

    2014-11-01

    Papulopustular rosacea (PPR) is characterized by facial erythema and inflammatory lesions believed to be primarily caused by dysregulation of the innate immune system. More recent evidence also suggests that Demodex folliculorum mites may contribute to the etiology of PPR. Ivermectin (IVM) 1% cream is a novel topical treatment developed to treat PPR. Two phase 3 trials have demonstrated that IVM 1% cream was significantly better than vehicle at investigator global assessment (IGA) success rate and lesion reductions and that it was safe and well tolerated. Two 40-week extension studies of those trials were conducted to assess the long-term safety of IVM 1% cream vs azelaic acid (AzA) 15% gel. Subjects originally treated with IVM 1% continued on IVM 1% and those originally treated with vehicle switched to AzA 15% gel. IVM 1% cream was safe throughout the study with a lower incidence of related adverse events (AEs) compared to AzA 15% gel. No subjects in the IVM 1% cream group discontinued either study due to a related AE. IVM 1% also continued to be efficacious during the 40-week extension studies as the percentage of subjects with IGA scores of clear or almost clear was higher at the end of the study compared to baseline. The results of these 40-week extension studies support the use of IVM 1% cream as a long-term therapy for PPR as IVM 1% cream was shown to be safe and effective for up to 52 weeks of total treatment.

  15. Effectiveness of Ivermectin and Albendazole against Haemonchus contortus in Sheep in West Java, Indonesia.

    PubMed

    Puspitasari, Silvia; Farajallah, Achmad; Sulistiawati, Erni; Muladno

    2016-02-01

    Administering a half dose of an anthelmintic is a simple method for detecting resistance in parasites infesting small ruminants. When a single anthelmintic fails in native sheep from Indonesia, a combination of anthelmintics from different chemical classes with different modes of action are administered as an alternative parasite-control strategy. This study compared the anthelmintic efficacy of ivermectin (IVM) and albendazole (ABZ) given either separately as a single dose or half dose or co-administered to sheep naturally infected with Haemonchus contortus. Twelve sheep from Bogor, West Java, Indonesia were divided into the following six treatment groups: half-dose IVM, full-dose IVM, half-dose ABZ, full-dose ABZ, combined IVM + ABZ, and control. The treatment efficacy was determined using the faecal egg count reduction test (FECRT) at day 0 (pre-treatment) and post-treatment at days 7, 14, 21, 28, 35, and 42. The efficacies of half-dose IVM, full-dose IVM, half-dose ABZ, full-dose ABZ, and the combination treatment ranged from -1900% to 100%, 99% to 100%, -167% to 100%, -467% to 89%, and -200% to 100%, respectively. The FECRT for the half-dose IVM, half-dose ABZ, full-dose ABZ showed that H. contortus is resistant to half-dose IVM and ABZ. Full-dose IVM was effective against H. contortus. The combined treatment was more effective against H. contortus than ABZ alone.

  16. Effectiveness of Ivermectin and Albendazole against Haemonchus contortus in Sheep in West Java, Indonesia

    PubMed Central

    Puspitasari, Silvia; Farajallah, Achmad; Sulistiawati, Erni; Muladno

    2016-01-01

    Administering a half dose of an anthelmintic is a simple method for detecting resistance in parasites infesting small ruminants. When a single anthelmintic fails in native sheep from Indonesia, a combination of anthelmintics from different chemical classes with different modes of action are administered as an alternative parasite-control strategy. This study compared the anthelmintic efficacy of ivermectin (IVM) and albendazole (ABZ) given either separately as a single dose or half dose or co-administered to sheep naturally infected with Haemonchus contortus. Twelve sheep from Bogor, West Java, Indonesia were divided into the following six treatment groups: half-dose IVM, full-dose IVM, half-dose ABZ, full-dose ABZ, combined IVM + ABZ, and control. The treatment efficacy was determined using the faecal egg count reduction test (FECRT) at day 0 (pre-treatment) and post-treatment at days 7, 14, 21, 28, 35, and 42. The efficacies of half-dose IVM, full-dose IVM, half-dose ABZ, full-dose ABZ, and the combination treatment ranged from −1900% to 100%, 99% to 100%, −167% to 100%, −467% to 89%, and −200% to 100%, respectively. The FECRT for the half-dose IVM, half-dose ABZ, full-dose ABZ showed that H. contortus is resistant to half-dose IVM and ABZ. Full-dose IVM was effective against H. contortus. The combined treatment was more effective against H. contortus than ABZ alone. PMID:27019686

  17. Fate of ivermectin residues in ewes' milk and derived products.

    PubMed

    Cerkvenik, Vesna; Perko, Bogdan; Rogelj, Irena; Doganoc, Darinka Z; Skubic, Valentin; Beek, Wim M J; Keukens, Henk J

    2004-02-01

    The fate of ivermectin (IVM) residues was studied throughout the processing of daily bulk milk from 30 ewes (taken up to 33 d following subcutaneous administration of 0.2 mg IVM/kg b.w.) in the following milk products: yoghurt made from raw and pasteurized milk; cheese after pressing; 30- and 60-day ripened cheese; and whey, secondary whey and whey proteins obtained after cheese-making (albumin cheese). The concentration of the H2B1a component of IVM was analysed in these dairy products using an HPLC method with fluorescence detection. The mean recovery of the method was, depending on the matrix, between 87 and 100%. Limits of detection in the order of only 0.1 microg H2B1a/kg of product were achieved. Maximum concentrations of IVM were detected mostly at 2 d after drug administration to the ewes. The highest concentration of IVM was found on day 2 in 60-day ripened cheese (96 microg H2B1a/kg cheese). Secondary whey was the matrix with the lowest concentration of IVM (<0.6 microg H2B1a/ kg). Residue levels fell below the limits of detection between day 5 (for secondary whey) and day 25 (for all cheese samples). In the matrices investigated, linear correlations between daily concentrations of IVM, milk fat and solid content were evident. During yoghurt production, fermentation and thermal stability of IVM was observed. During cheese production, approximately 35% of the IVM, present in the raw (bulk) milk samples, was lost. From the results it was concluded that the processing of ewes' milk did not eliminate the drug residues under investigation. The consequences of IVM in the human diet were discussed. Milk from treated animals should be excluded from production of fat products like cheese for longer after treatment with IVM than for lower fat products.

  18. The definition of IVM is clear-variations need defining.

    PubMed

    De Vos, Michel; Smitz, Johan; Thompson, Jeremy G; Gilchrist, Robert B

    2016-11-01

    Oocyte in vitro maturation (IVM) is currently defined as the maturation in vitro of immature cumulus-oocyte complexes collected from antral follicles. This is the original definition as first described by Pincus and Enzmann and then by Edwards many decades ago, and this clear and unambiguous definition has served us well ever since. In an attempt to clarify apparent differences among clinicians, the following revised definition of IVM was recently proposed: 'The retrieval of oocytes from small and intermediate sized follicles in an ovary before the largest follicle has surpassed 13 mm in mean diameter'. As such, this proposed definition should encompass the use of hCG triggering. To change the clear and long-serving definition of IVM to fit varying clinical practices requires a compelling justification based on solid scientific and clinical grounds. We are of the opinion that the proposed revised definition of IVM is counterintuitive as it includes protocols that are intended to mature oocytes in vivo The proposed definitions are cumbersome and indeed further complicate the situation. It is not scientifically rational to base the definition on follicular size, and the definition ignores the vast corporate knowledge acquired from the many decades and >6000 publications in animal research that universally practices IVM as per the existing definition. Furthermore, such a definition can lead to false results in interpreting the follow-up of children conceived using IVM. Hence, we see no rationale to change the existing definition of IVM. However, we agree that variations on IVM require alternative nomenclature-these definitions need to be intuitive and need to clearly distinguish themselves from the existing long-standing definition of IVM. This would help to clarify the recent confusion within the clinical ART community as to what is and what is not, IVM. © 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.

  19. Estimation of the optimal timing of fertilization for embryo development of in vitro-matured bovine oocytes based on the times of nuclear maturation and sperm penetration.

    PubMed

    Koyama, Keisuke; Kang, Sung-Sik; Huang, Weiping; Yanagawa, Yojiro; Takahashi, Yoshiyuki; Nagano, Masashi

    2014-05-01

    The objective of this research was to estimate the optimal timing for fertilization to achieve proper embryonic development of in vitro-matured bovine oocytes. First, cumulus-oocyte complexes were subjected to in vitro maturation (IVM) for 14-22 hr. The timing when 50% of oocytes reached metaphase II stage was estimated to be 17.5 hr after IVM start. Next, using oocytes subjected to IVM for 12-30 hr, sperm penetration was examined after 4-18 hr of in vitro fertilization (IVF). A significant negative correlation between IVM duration and the timing when 50% of oocytes were penetrated by sperm after IVF start was observed (P<0.01). Finally, oocytes subjected to 12-30 hr of IVM were inseminated and cultured for 6 days to examine embryonic development. In the group with 22 hr of IVM, the percentages of cleaved embryos and blastocysts were the highest values in all groups. According to the regression equation describing the time from nuclear maturation to sperm penetration (x) and the percentage of blastocysts (y) (y=7.23x - 0.297x(2), P<0.01), the blastocyst rate peaked when sperm penetration occurred at 12.2 hr after achieving nuclear maturation. In conclusion, under the present IVM/IVF conditions, it was estimated that oocytes acquired their highest developmental competence at about 30 hr after IVM start, and thus, the optimal IVM duration was calculated to be about 21 hr.

  20. Evaluation of an in-vehicle monitoring system (IVMS) to reduce risky driving behaviors in commercial drivers: Comparison of in-cab warning lights and supervisory coaching with videos of driving behavior.

    PubMed

    Bell, Jennifer L; Taylor, Matthew A; Chen, Guang-Xiang; Kirk, Rachel D; Leatherman, Erin R

    2017-02-01

    Roadway incidents are the leading cause of work-related death in the United States. The objective of this research was to evaluate whether two types of feedback from a commercially available in-vehicle monitoring system (IVMS) would reduce the incidence of risky driving behaviors in drivers from two companies. IVMS were installed in 315 vehicles representing the industries of local truck transportation and oil and gas support operations, and data were collected over an approximate two-year period in intervention and control groups. In one period, intervention group drivers were given feedback from in-cab warning lights from an IVMS that indicated occurrence of harsh vehicle maneuvers. In another period, intervention group drivers viewed video recordings of their risky driving behaviors with supervisors, and were coached by supervisors on safe driving practices. Risky driving behaviors declined significantly more during the period with coaching plus instant feedback with lights in comparison to the period with lights-only feedback (ORadj=0.61 95% CI 0.43-0.86; Holm-adjusted p=0.035) and the control group (ORadj=0.52 95% CI 0.33-0.82; Holm-adjusted p=0.032). Lights-only feedback was not found to be significantly different than the control group's decline from baseline (ORadj=0.86 95% CI 0.51-1.43; Holm-adjusted p>0.05). The largest decline in the rate of risky driving behaviors occurred when feedback included both supervisory coaching and lights. Supervisory coaching is an effective form of feedback to improve driving habits in the workplace. The potential advantages and limitations of this IVMS-based intervention program are discussed. Published by Elsevier Ltd.

  1. Evaluation of an in-vehicle monitoring system (IVMS) to reduce risky driving behaviors in commercial drivers: Comparison of in-cab warning lights and supervisory coaching with videos of driving behavior

    PubMed Central

    Bell, Jennifer L.; Taylor, Matthew A.; Chen, Guang-Xiang; Kirk, Rachel D.; Leatherman, Erin R.

    2017-01-01

    Problem Roadway incidents are the leading cause of work-related death in the United States. Methods The objective of this research was to evaluate whether two types of feedback from a commercially available in-vehicle monitoring system (IVMS) would reduce the incidence of risky driving behaviors in drivers from two companies. IVMS were installed in 315 vehicles representing the industries of local truck transportation and oil and gas support operations, and data were collected over an approximate two-year period in intervention and control groups. In one period, intervention group drivers were given feedback from in-cab warning lights from an IVMS that indicated occurrence of harsh vehicle maneuvers. In another period, intervention group drivers viewed video recordings of their risky driving behaviors with supervisors, and were coached by supervisors on safe driving practices. Results Risky driving behaviors declined significantly more during the period with coaching plus instant feedback with lights in comparison to the period with lights-only feedback (ORadj = 0.61 95% CI 0.43–0.86; Holm-adjusted p = 0.035) and the control group (ORadj = 0.52 95% CI 0.33–0.82; Holm-adjusted p = 0.032). Lights-only feedback was not found to be significantly different than the control group's decline from baseline (ORadj = 0.86 95% CI 0.51–1.43; Holm-adjusted p > 0.05). Conclusions The largest decline in the rate of risky driving behaviors occurred when feedback included both supervisory coaching and lights. Practical applications Supervisory coaching is an effective form of feedback to improve driving habits in the workplace. The potential advantages and limitations of this IVMS-based intervention program are discussed. PMID:28160807

  2. Integrated Vegetation Management Fact Sheet

    EPA Pesticide Factsheets

    IVM is generally defined as the practice of promoting desirable, stable, low-growing plant communities that will resist invasion by tall growing tree species through the use of appropriate, environmentally-sound, and cost-effective control methods.

  3. Validation of a simple liquid chromatographic method for determination and quantitation of residual ivermectin and doramectin in pig liver.

    PubMed

    Knold, Lone; Reitov, Marianne; Mortensen, Anna Birthe; Hansen-Møller, Jens

    2002-01-01

    A rapid and quantitative method for the extraction, derivatization, and liquid chromatography with fluorescence detection of ivermectin (IVM) and doramectin (DOM) residues in porcine liver was developed and validated. IVM and DOM were extracted from the liver samples with acetonitrile, the supernatant was evaporated to dryness at 37 degrees C under nitrogen, and the residue was reconstituted in 1-methylimidazole solution. After 2 min at room temperature, IVM and DOM were converted to a fluorescent derivative and then separated on a Hypersil ODS column. The derivatives of IVM and DOM were detected and quantitated with high specificity by fluorescence (excitation: 365 nm, emission: 475 nm). Abamectin was used as an internal standard. The mean extraction efficiencies from fortified samples (15 ng/g) were 75% for IVM and 70% for DOM. The limit of detection was 0.8 ng/g for both IVM and DOM.

  4. Consolidating strategic planning and operational frameworks for integrated vector management in Eritrea.

    PubMed

    Chanda, Emmanuel; Ameneshewa, Birkinesh; Mihreteab, Selam; Berhane, Araia; Zehaie, Assefash; Ghebrat, Yohannes; Usman, Abdulmumini

    2015-12-02

    Contemporary malaria vector control relies on the use of insecticide-based, indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs). However, malaria-endemic countries, including Eritrea, have struggled to effectively deploy these tools due technical and operational challenges, including the selection of insecticide resistance in malaria vectors. This manuscript outlines the processes undertaken in consolidating strategic planning and operational frameworks for vector control to expedite malaria elimination in Eritrea. The effort to strengthen strategic frameworks for vector control in Eritrea was the 'case' for this study. The integrated vector management (IVM) strategy was developed in 2010 but was not well executed, resulting in a rise in malaria transmission, prompting a process to redefine and relaunch the IVM strategy with integration of other vector borne diseases (VBDs) as the focus. The information sources for this study included all available data and accessible archived documentary records on malaria vector control in Eritrea. Structured literature searches of published, peer-reviewed sources using online, scientific, bibliographic databases, Google Scholar, PubMed and WHO, and a combination of search terms were utilized to gather data. The literature was reviewed and adapted to the local context and translated into the consolidated strategic framework. In Eritrea, communities are grappling with the challenge of VBDs posing public health concerns, including malaria. The global fund financed the scale-up of IRS and LLIN programmes in 2014. Eritrea is transitioning towards malaria elimination and strategic frameworks for vector control have been consolidated by: developing an integrated vector management (IVM) strategy (2015-2019); updating IRS and larval source management (LSM) guidelines; developing training manuals for IRS and LSM; training of national staff in malaria entomology and vector control, including insecticide resistance monitoring techniques; initiating the global plan for insecticide resistance management; conducting needs' assessments and developing standard operating procedure for insectaries; developing a guidance document on malaria vector control based on eco-epidemiological strata, a vector surveillance plan and harmonized mapping, data collection and reporting tools. Eritrea has successfully consolidated strategic frameworks for vector control. Rational decision-making remains critical to ensure that the interventions are effective and their choice is evidence-based, and to optimize the use of resources for vector control. Implementation of effective IVM requires proper collaboration and coordination, consistent technical and financial capacity and support to offer greater benefits.

  5. A prediction model to select PCOS patients suitable for IVM treatment based on anti-Mullerian hormone and antral follicle count.

    PubMed

    Guzman, L; Ortega-Hrepich, C; Polyzos, N P; Anckaert, E; Verheyen, G; Coucke, W; Devroey, P; Tournaye, H; Smitz, J; De Vos, M

    2013-05-01

    Which baseline patient characteristics can help assisted reproductive technology practitioners to identify patients who are suitable for in-vitro maturation (IVM) treatment? In patients with polycystic ovary syndrome (PCOS) who undergo oocyte IVM in a non-hCG-triggered system, circulating anti-Müllerian hormone (AMH), antral follicle count (AFC) and total testosterone are independently related to the number of immature oocytes and hold promise as outcome predictors to guide the patient selection process for IVM. Patient selection criteria for IVM treatment have been described in normo-ovulatory patients, although patients with PCOS constitute the major target population for IVM. With this study, we assessed the independent predictive value of clinical and endocrine parameters that are related to oocyte yield in patients with PCOS undergoing IVM. Cohort study involving 124 consecutive patients with PCOS undergoing IVM whose data were prospectively collected. Enrolment took place between January 2010 and January 2012. Only data relating to the first IVM cycle of each patient were included. Patients with PCOS underwent oocyte retrieval for IVM after minimal gonadotrophin stimulation and no hCG trigger. Correlation coefficients were calculated to investigate which parameters are related to immature oocyte yield (patient's age, BMI, baseline hormonal profile and AMH, AFC). The independence of predictive parameters was tested using multivariate linear regression analysis. Finally, multivariate receiver operating characteristic (ROC) analyses for cumulus oocyte complexes (COC) yield were performed to assess the efficiency of the prediction model to select suitable candidates for IVM. Using multivariate regression analysis, circulating baseline AMH, AFC and baseline total testosterone serum concentration were incorporated into a model to predict the number of COC retrieved in an IVM cycle, with unstandardized coefficients [95% confidence interval (CI)] of 0.03 (0.02-0.03) (P < 0.001), 0.012 (0.008-0.017) (P < 0.001) and 0.37 (0.18-0.57) (P < 0.001), respectively. Logistic regression analysis shows that a prediction model based on AMH and AFC, with unstandardized coefficients (95% CI) of 0.148 (0.03-0.25) (P < 0.001) and 0.034 (-0.003-0.07) (P = 0.025), respectively, is a useful patient selection tool to predict the probability to yield at least eight COCs for IVM in patients with PCOS. In this population, patients with at least eight COC available for IVM have a statistically higher number of embryos of good morphological quality (2.9 ± 2.3; 0.9 ± 0.9; P < 0.001) and cumulative ongoing pregnancy rate [30.4% (24 out of 79); 11% (5 out of 45); P = 0.01] when compared with patients with less than eight COC. ROC curve analysis showed that this prediction model has an area under the curve of 0.7864 (95% CI = 0.6997-0.8732) for the prediction of oocyte yield in IVM. The proposed model has been constructed based on a genuine IVM system, i.e. no hCG trigger was given and none of the oocytes matured in vivo. However, other variables, such as needle type, aspiration technique and whether or not hCG-triggering is used, should be considered as confounding factors. The results of this study have to be confirmed using a second independent validation sample. The proposed model could be applied to patients with PCOS after confirmation through a further validation study. This study was supported by a research grant by the Institute for the Promotion of Innovation by Science and Technology in Flanders, Project number IWT 070719.

  6. Relative bioavailability and comparative clinical efficacy of different ivermectin oral formulations in lambs

    PubMed Central

    2013-01-01

    Background Several oral ivermectin (IVM) formulations for use in sheep are available in the pharmaceutical veterinary market in different countries. All of them are indicated at the same dose rate to treat the gastrointestinal nematodes. However, there is a lack of information on the relative systemic exposure (plasma bioavailability) and clinical efficacy among oral formulations routinely used in sheep. The main goal of the work reported here was to perform a pharmaco-parasitological assessment of three different IVM oral formulations in lambs infected with multiple resistant gastrointestinal nematodes. The comparative drug systemic exposure (IVM plasma concentrations) and nematodicidal efficacies (clinical efficacy) in lambs were determined for a reference (RF) and two different test (T1, T2) IVM oral formulations. One hundred and fifty six (n= 156) healthy Corriedale lambs, naturally infected with multiple resistant gastrointestinal nematodes were allocated into four experimental groups (n=39). Animals in each group received treatment (200 μg/kg) with either the RF, one of the test IVM formulations or were kept as untreated control. Blood samples were collected over 15 days post-treatment (n=8). The IVM plasma concentrations were measured by high performance liquid chromatography with fluorescence detection. The faecal nematode egg count reduction test (FECRT) (n=39) and evaluation of the clinical efficacy were performed at day 14 post-treatment (n=6), where a predominance of IVM highly resistant nematodes was observed. Results and conclusions Neither the overall kinetic behaviour nor the IVM systemic exposure differed among all the tested oral formulations. Equivalent efficacy results were obtained for the different preparations, with an evident therapeutic failure to control Haemonchus spp. and Teladorsagia circumcincta, which correlates with a high degree of nematode resistance to IVM. PMID:23398629

  7. In-vitro maturation versus IVF with GnRH antagonist for women with polycystic ovary syndrome: treatment outcome and rates of ovarian hyperstimulation syndrome.

    PubMed

    Das, Mausumi; Son, Weon-Young; Buckett, William; Tulandi, Togas; Holzer, Hananel

    2014-11-01

    In-vitro maturation (IVM) treatment has gained popularity for decreasing the incidence of ovarian hyperstimulation syndrome (OHSS) by eliminating or minimizing the use of gonadotrophins in women with polycystic ovary syndrome (PCOS). Studies have shown that IVF with GnRH-antagonist protocol is associated with a lower incidence of OHSS. Data comparing the relative success of these two treatments is, however, lacking. Treatment outcome and rates of OHSS were compared in patients with PCOS who underwent assisted conception with either IVM or IVF with GnRH-antagonist protocol between 2006 and 2011. The number of oocytes retrieved was higher in the IVM group, whereas the number of mature oocytes, fertilization rate and number of embryos cleaved were comparable. The implantation rate was higher in the IVF group. The clinical pregnancy rates per embryo transfer were not statistically different (IVF: 45.8% versus IVM: 32.4%). The live-birth rate was higher in the IVF group (IVF: 40.7% versus IVM: 23.5%; P = 0.04). Five women developed moderate or severe OHSS in the IVF group, whereas none did in the IVM group. Both IVM and IVF with GnRH-antagonist protocol seem to be effective treatment regimens in women with PCOS, although IVM is associated with a lower risk of OHSS. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  8. Cilostamide and forskolin treatment during pre-IVM improves preimplantation development of cloned embryos by influencing meiotic progression and gap junction communication in pigs.

    PubMed

    Park, Bola; Lee, Hanna; Lee, Yongjin; Elahi, Fazle; Lee, Joohyeong; Lee, Seung Tae; Park, Choon-Keun; Hyun, Sang-Hwan; Lee, Eunsong

    2016-08-01

    This study was conducted to evaluate the effects of treatment with the cAMP modulators cilostamide and/or forskolin during pre-IVM culture on meiotic progression, gap junction communication, intraoocyte cAMP level and glutathione content, embryonic development after parthenogenesis, and somatic cell nuclear transfer in pigs. Cumulus-oocyte complexes were cultured for 24 hours in unsupplemented medium or media containing 20 μM cilostamide and/or 50 μM forskolin. After pre-IVM, oocytes were cultured for 41 to 44 hours in a standard IVM medium to induce oocyte maturation. When the nuclear status of oocytes was examined after pre-IVM for 24 hours, a higher (P < 0.01) proportion of oocytes treated with forskolin (85.5%) and cilostamide + forskolin (92.6%) remained at the germinal vesicle stage compared with untreated (20.6%) and cilostamide-treated oocytes (54.7%). cAMP level in pre-IVM oocytes was significantly increased by combined treatment with cilostamide + forskolin (21.38 fmol/oocyte) relative to the no pre-IVM control, no treatment, cilostamide, and forskolin groups (2.85, 1.88, 1.74, and 8.95 fmol/oocyte, respectively). Forskolin with or without cilostamide significantly maintained open-gap junction communication relative to no treatment. Blastocyst formation in parthenogenesis was significantly (P < 0.01) improved by forskolin (65.3%) relative to other treatments (28.3% to 48.1%). Supplementation of pre-IVM with dibutyryl cAMP showed similar blastocyst formation as forskolin treatment (61.1% and 61.0%, respectively). In somatic cell nuclear transfer, simultaneous treatment with cilostamide + forskolin significantly (P < 0.05) increased embryonic development to the blastocyst stage (42.9%) relative to the no pre-IVM, control, and cilostamide groups (32.3, 28.6, and 32.8%, respectively). The glutathione contents in pre-IVM oocytes were increased by no treatment, forskolin, and cilostamide + forskolin (1.38, 1.39, and 1.27 pixels/oocyte, respectively) compared with no pre-IVM and cilostamide (1.00 and 0.99 pixels/oocyte, respectively; P < 0.05). Our results reported that the meiotic progression of immature pig oocytes could be reversibly attenuated by cAMP, whereas treatment with cilostamide and forskolin during pre-IVM had positive effects on developmental competence of oocytes in pigs, probably by improving cytoplasmic maturation. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. The effect of sesame and sunflower oils on the plasma disposition of ivermectin in goats.

    PubMed

    Gokbulut, C; Karademir, U; Boyacioglu, M; McKellar, Q A

    2008-10-01

    The effect of sesame oil (SSO) and sunflower oil (SFO) (the excipients) on the plasma disposition of ivermectin (IVM) following intravenous (i.v.) and subcutaneous (s.c.) administration at a dosage of 200 microg/kg was investigated in goats. Ten clinically healthy crossbred goats were used in the study. The animals were allocated by weight and sex into two groups of five animals each. Group 1 (n = 5) received the drug and excipient by the i.v. route only and group 2 received drug and excipient by the s.c. route only. The study was designed according to a two-phase crossover design protocol. In the first phase three animals in group 1 were i.v. administered IVM (0.2 mg/kg) + SSO (1 mL) and the other two animals received IVM (0.2 mg/kg) + SFO (1 mL). In the second phase animals were crossed over and received the alternate excipient with IVM at the same dosages. In group 2 during the first phase, three animals were s.c. administered IVM (0.2 mg/kg) + SSO (1 mL) and the other two animals were received IVM (0.2 mg/kg) + SFO (1 mL). In the second phase animals were crossed over and received the alternate excipient with IVM at the same dosages. A 4-week washout period was allowed between the two phases. In group 2 significantly increased dermal thickness was observed at the s.c. injection site of the all animals which received IVM during phase I regardless of the excipient. There was almost no change observed at the injection site of any animal during the second phase of the study following s.c. administration. In group 2 the plasma concentrations of IVM in the second phase for both excipient combinations were much higher than the plasma concentrations following first administration and appeared to be related with the dermal changes. The mean plasma disposition of IVM in combination with SSO or SFO was similar following i.v. administration. Longer terminal elimination half-lives and resultant longer mean resident time were observed after s.c. administration of the both combinations compared with i.v. administration.

  10. Clinical benefit of metaphase I oocytes

    PubMed Central

    Vanhoutte, Leen; De Sutter, Petra; Van der Elst, Josiane; Dhont, Marc

    2005-01-01

    Background We studied the benefit of using in vitro matured metaphase I (MI) oocytes for ICSI in patients with a maximum of 6 mature metaphase II (MII) oocytes at retrieval. Methods In 2004, 187 ICSI cycles were selected in which maximum 6 MII oocytes and at least one MI oocyte were retrieved. MI oocytes were put in culture to mature until the moment of ICSI, which was performed between 2 to 11 hours after oocyte retrieval (day 0). In exceptional cases, when the patient did not have any mature oocyte at the scheduled time of ICSI, MI oocytes were left to mature overnight and were injected between 19 to 26 hours after retrieval (day 1). Embryos from MI oocytes were chosen for transfer only when no other good quality embryos from MII oocytes were available. Outcome parameters were time period of in vitro maturation (IVM), IVM and fertilization rates, embryo development, clinical pregnancy rates, implantation rates and total MI oocyte utilization rate. Results The overall IVM rate was 43%. IVM oocytes had lower fertilization rates compared to in vivo matured sibling oocytes (52% versus 68%, P < 0.05). The proportion of poor quality embryos was significantly higher in IVM derived oocytes. One pregnancy and live birth was obtained out of 13 transfers of embryos exclusively derived from IVM oocytes. This baby originated from an oocyte that was injected after 22 hrs of IVM. Conclusion Fertilization of in vitro matured MI oocytes can result in normal embryos and pregnancy, making IVM worthwhile, particularly when few MII oocytes are obtained at retrieval. PMID:16356175

  11. Field tests demonstrating reduced activity of ivermectin and moxidectin against small strongyles in horses on 14 farms in Central Kentucky in 2007-2009.

    PubMed

    Lyons, Eugene T; Tolliver, Sharon C; Collins, Sandra S; Ionita, Mariana; Kuzmina, Tetiana A; Rossano, Mary

    2011-02-01

    Efficacy of ivermectin (IVM) and moxidectin (MOX) against small strongyles was evaluated in horses (n=363) in field tests on 14 farms in Central Kentucky between 2007 and 2009. Most of the horses were yearlings but a few were weanlings and mares. The number of horses treated with IVM was 255 and those treated with MOX was 108. Horses on six farms were allotted into two groups. One group was treated with each of the two drugs, whereas horses on the other eight farms were treated with only one of the two drugs--IVM on six farms and MOX on two farms. Strongyle eggs per gram of feces (EPGs) compared to initial use of IVM and MOX returned almost twice as quickly after treatment of horses on all of the farms. IVM has been used much more extensively in this geographical area than MOX. Reduced activity of MOX was evident even on farms with rare or no apparent previous use of MOX but with probable extensive use of IVM.

  12. Bonneville - Hood River Vegetation Management Environmental Assessment

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

    N /A

    1998-08-01

    To maintain the reliability of its electrical system, BPA, in cooperation with the U.S. Forest Service, needs to expand the range of vegetation management options used to clear unwanted vegetation on about 20 miles of BPA transmission line right-of-way between Bonneville Dam and Hood River; Oregon, within the Columbia Gorge National Scenic Area (NSA). We propose to continue controlling undesirable vegetation using a program of Integrated Vegetation Management (IVM) which includes manual, biological and chemical treatment methods. BPA has prepared an Environmental Assessment (EA) (DOE/EA-1257) evaluating the proposed project. Based on the analysis in the EA, BPA has determined thatmore » the proposed action is not a major Federal action significantly affecting the quality of the human environment, within the meaning of the National Environmental Policy Act (NEPA) of 1969. Therefore, the preparation of an Environmental Impact Statement (EIS) is not required and BPA is issuing this FONSI.« less

  13. Field trial assessment of ivermectin pharmacokinetics and efficacy against susceptible and resistant nematode populations in cattle.

    PubMed

    Canton, Candela; Canton, Lucila; Domínguez, María Paula; Moreno, Laura; Lanusse, Carlos; Alvarez, Luis; Ceballos, Laura

    2018-05-30

    The study compared the pharmacokinetic (PK) behaviour and anthelmintic efficacy against susceptible and resistant nematodes following subcutaneous (SC) and oral administration of ivermectin (IVM) to cattle. Six commercial farms were involved: Farms 1 and 2 (IVM-susceptible nematode population) and Farms 3, 4, 5 and 6 (IVM-resistant nematode population). On each farm, forty-five calves naturally infected with gastrointestinal (GI) nematodes were randomly allocated into three groups (n = 15): untreated control, IVM SC administration, and IVM oral administration (both at 0.2 mg/kg). PK assessment (plasma and faeces) was performed on Farm 1. Efficacy was determined by Faecal Egg Count Reduction Test. IVM systemic availability upon SC administration (421 ± 70.3 ng·d/mL) was higher (P < 0.05) compared to the oral treatment (132 ± 31.3 ng·d/mL). However, higher (P < 0.05) faecal IVM concentrations were observed following oral treatment (9896 ± 1931 ng·d/mL) compared to SC administration (4760 ± 924 ng·d/mL). Similar (91-93%) IVM efficacy was observed on Farms 1 and 2 by both routes. Efficacy against resistant nematodes was slightly higher on Farms 3 and 4 after the oral (63 and 82%, respectively) compared to the SC (36 and 68%, respectively) treatment. However, there was complete therapeutic failure (0% efficacy) on Farm 5 and a very low response on Farm 6 (40 and 41% for SC and oral administration, respectively). Although larger faecal concentrations following IVM oral administration may increase drug exposure of GI adult worms, this does not always improve efficacy against resistant nematodes. The potential therapeutic advantages of oral treatments should be cautiously assessed, especially in presence of anthelmintic resistance. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Effects of ivermectin on Danio rerio: a multiple endpoint approach: behaviour, weight and subcellular markers.

    PubMed

    Domingues, I; Oliveira, R; Soares, A M V M; Amorim, M J B

    2016-04-01

    Ivermectin (IVM) is a broad acting antihelmintic used in various veterinary pharmaceuticals. It has been shown that IVM enters the aquatic compartment and adversely affects organisms including fish. This study is based on the hypothesis that long term exposure to IVM affects fish and thus, the main objective was to assess the chronic effects of 0.25 and 25 µg IVM/L to zebrafish using multiple endpoints representative of several levels of biological organization: weight, behaviour (swimming and feeding) and subcellular markers including biomarkers for oestrogenicity (vitellogenin-VTG), oxidative stress (catalase-CAT and glutathione-S-transferase-GST) and neurotransmission (cholinesterase-ChE). Concentrations as low as 0.25 µg IVM/L disrupted the swimming behaviour, causing fish to spend more time at the bottom of aquaria. Such reduction of the swimming performance affected the feeding ability which is likely responsible for the weight loss. The effects on weight were gender differentiated, being more pronounced in males (0.25 µg IVM/L) than in females (25 µg IVM/L). Fish exposed to 25 µg/L exhibited darker coloration and mild curvature of the spine. No effects on VTG and AChE were observed, but a reduction on CAT and GST levels was observed in fish exposed to 25 µg IVM/L, although these alterations probably only reflect the general condition of the fish which was significantly compromised at this concentration. Despite that predicted environmental concentrations of IVM are below 0.25 µg/L, the behavioural effects may be translated into important ecological impacts, e.g. at predator-prey interactions where fish competitive advantage can be decreased. Future work should address the link between behaviour disruption and population fitness. The current study was based on a one experiment and multiple endpoint (anchored) approach, allowing the results to be integrated and linked towards a mechanistic understanding.

  15. Promise and Ontological Ambiguity in the In vitro Meat Imagescape: From Laboratory Myotubes to the Cultured Burger

    PubMed Central

    Stephens, Neil; Ruivenkamp, Martin

    2016-01-01

    Abstract In vitro meat (IVM), also known as cultured meat, involves growing cells into muscle tissue to be eaten as food. The technology had its most high-profile moment in 2013 when a cultured burger was cooked and tasted in a press conference. Images of the burger featured in the international media and were circulated across the Internet. These images—literally marks on a two-dimensional surface—do important work in establishing what IVM is and what it can do. A combination of visual semiotics and narrative analysis shows that images of IVM afford readings of their story that are co-created by the viewer. Before the cultured burger, during 2011, images of IVM fell into four distinct categories: cell images, tissue images, flowcharts, and meat in a dish images. The narrative infrastructure of each image type affords different interpretations of what IVM can accomplish and what it is. The 2013 cultured burger images both draw upon and depart from these image types in an attempt to present IVM as a normal food stuff, and as ‘matter in place’ when placed on the plate. The analysis of individual images and the collection of images about a certain object or subject—known as the imagescape—is a productive approach to understanding the ontology and promise of IVM and is applicable to other areas of social life. PMID:27695202

  16. Promise and Ontological Ambiguity in the In vitro Meat Imagescape: From Laboratory Myotubes to the Cultured Burger.

    PubMed

    Stephens, Neil; Ruivenkamp, Martin

    2016-07-02

    In vitro meat (IVM), also known as cultured meat, involves growing cells into muscle tissue to be eaten as food. The technology had its most high-profile moment in 2013 when a cultured burger was cooked and tasted in a press conference. Images of the burger featured in the international media and were circulated across the Internet. These images-literally marks on a two-dimensional surface-do important work in establishing what IVM is and what it can do. A combination of visual semiotics and narrative analysis shows that images of IVM afford readings of their story that are co-created by the viewer. Before the cultured burger, during 2011, images of IVM fell into four distinct categories: cell images, tissue images, flowcharts, and meat in a dish images. The narrative infrastructure of each image type affords different interpretations of what IVM can accomplish and what it is. The 2013 cultured burger images both draw upon and depart from these image types in an attempt to present IVM as a normal food stuff, and as 'matter in place' when placed on the plate. The analysis of individual images and the collection of images about a certain object or subject-known as the imagescape-is a productive approach to understanding the ontology and promise of IVM and is applicable to other areas of social life.

  17. What threshold values of antral follicle count and serum AMH levels should be considered for oocyte cryopreservation after in vitro maturation?

    PubMed

    Sonigo, C; Simon, C; Boubaya, M; Benoit, A; Sifer, C; Sermondade, N; Grynberg, M

    2016-07-01

    What threshold values of ultrasonographic antral follicle count (AFC) and serum anti-Müllerian hormone (AMH) levels should be considered for ensuring the cryopreservation of sufficient number of in vitro matured (IVM) oocytes, in cancer patients seeking fertility preservation (FP)? AFC and serum AMH values >20 follicles and 3.7 ng/ml, respectively, are required for obtaining at least 10 IVM oocytes for cryopreservation. IVM of cumulus oocyte complexes (COCs) followed by oocyte cryopreservation has emerged recently as an option for urgent FP. Recent data have reported that, in healthy patients, 8-20 cryopreserved oocytes after ovarian stimulation would maximize the chance of obtaining a live birth. Although both AFC and AMH have been reported as predictive factors of IVM success in infertile patients with polycystic ovary syndrome (PCOS), there is a dramatic lack of data regarding the values of these parameters in oncological patients as candidates for FP. From January 2009 to April 2015, we prospectively studied 340 cancer patients, aged 18-41 years, as candidates for oocyte cryopreservation following IVM. All patients had AFC and AMH measurements, 48-72 h before oocyte retrieval, regardless of the phase of the cycle. COCs were recovered under ultrasound guidance 36 h after hCG priming. Logistic regression allowed the determination of threshold values of AFC and AMH, for obtaining at least 8, 10 or 15 matures oocytes frozen after the IVM procedure. Similar analyses were performed for a final number of mature oocytes ≤2. Among the 340 cancer patients included, 300 were diagnosed with breast cancers, 14 had hematological malignancies and 26 underwent the procedure for others indications. Overall, the mean age of the population was 31.8 ± 4.5 years. Mean AFC and serum AMH levels were 21.7 ± 13.3 follicles and 4.4 ± 3.8 ng/ml, respectively. IVM was performed in equal proportions during the follicular or luteal phase of the cycle (49 and 51%, respectively). Statistical analysis showed that AFC and AMH values above 28 follicles and 3.9 ng/ml, 20 follicles and 3.7 ng/ml and 19 follicles and 3.5 ng/ml are required, respectively, for obtaining at least 15, 10 or 8 frozen IVM oocytes with a sensitivity ranging from 0.82 to 0.90. On the contrary, ≤2 IVM oocytes were cryopreserved when AFC and AMH were <19 follicles and 3.0 ng/ml, respectively. Although the potential of cryopreserved IVM oocytes from cancer patients remains unknown, data obtained from infertile PCOS women have shown a dramatically reduced competence of these oocytes when compared with that of oocytes recovered after ovarian stimulation. As a consequence, the optimal number of IVM oocytes frozen in candidates for FP is currently unpredictable. Cryopreservation of oocytes after IVM should be considered in the FP strategy when ovarian stimulation is unfeasible, in particular when markers of the follicular ovarian status are at a relatively high range. Further investigation is needed to objectively assess the real potential of these IVM oocytes after cryopreservation. Therefore, even when a good COCs yield is expected, we should systematically encourage IVM in combination with ovarian tissue cryopreservation. No external funding was obtained for the present study. The authors have no conflict of interest to declare. Not applicable. © 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.

  18. Doxycycline Leads to Sterility and Enhanced Killing of Female Onchocerca volvulus Worms in an Area With Persistent Microfilaridermia After Repeated Ivermectin Treatment: A Randomized, Placebo-Controlled, Double-Blind Trial

    PubMed Central

    Debrah, Alexander Yaw; Specht, Sabine; Klarmann-Schulz, Ute; Batsa, Linda; Mand, Sabine; Marfo-Debrekyei, Yeboah; Fimmers, Rolf; Dubben, Bettina; Kwarteng, Alexander; Osei-Atweneboana, Mike; Boakye, Daniel; Ricchiuto, Arcangelo; Büttner, Marcelle; Adjei, Ohene; Mackenzie, Charles D.; Hoerauf, Achim

    2015-01-01

    Background. Ivermectin (IVM) has been the drug of choice for the treatment of onchocerciasis. However, there have been reports of persistent microfilaridermia in individuals from an endemic area in Ghana after many rounds of IVM, raising concerns of suboptimal response or even the emergence of drug resistance. Because it is considered risky to continue relying only on IVM to combat this phenomenon, we assessed the effect of targeting the Onchocerca volvulus Wolbachia endosymbionts with doxycycline for these individuals with suboptimal response. Methods. One hundred sixty-seven patients, most of them with multiple rounds of IVM, were recruited in areas with IVM suboptimal response and treated with 100 mg/day doxycycline for 6 weeks. Three and 12 months after doxycycline treatment, patients took part in standard IVM treatment. Results. At 20 months after treatment, 80% of living female worms from the placebo group were Wolbachia positive, whereas only 5.1% in the doxycycline-treated group contained bacteria. Consistent with interruption of embryogenesis, none of the nodules removed from doxycycline-treated patients contained microfilariae, and 97% of those patients were without microfilaridermia, in contrast to placebo patients who remained at pretreatment levels (P < .001). Moreover, a significantly enhanced number of dead worms were observed after doxycycline. Conclusions. Targeting the Wolbachia in O. volvulus is effective in clearing microfilariae in the skin of onchocerciasis patients with persistent microfilaridermia and in enhanced killing of adult worms after repeated standard IVM treatment. Strategies can now be developed that include doxycycline to control onchocerciasis in areas where infections persist despite the frequent use of IVM. Clinical Trials Registration. ISRCTN 66649839. PMID:25948064

  19. Effect of high-fat meal intake on the pharmacokinetic profile of ivermectin in Japanese patients with scabies.

    PubMed

    Miyajima, Atsushi; Hirota, Takashi; Sugioka, Akihito; Fukuzawa, Masao; Sekine, Mari; Yamamoto, Yosuke; Yoshimasu, Takashi; Kigure, Akira; Anata, Taichi; Noguchi, Wataru; Akagi, Keita; Komoda, Masayo

    2016-09-01

    Ivermectin (IVM) is used as an anthelmintic agent in many countries. To evaluate the effect of high-fat (HF) meal intake on the pharmacokinetics of IVM, a clinical trial was conducted in Japanese patients with scabies. The patients were administrated Stromectol(®) tablets in the fasted state, and after 1 week they were also administrated it after a HF meal (fed state). After the administration, IVM concentrations in plasma and the stratum corneum were determined. The geometric mean of fed/fasted ratio of area under IVM concentration-time curve (AUC) in plasma was 1.25 (90% confidence interval, 1.09-1.43), suggesting the tendency to increased absorption after a HF meal. The fed/fasted ratio of the maximum IVM concentration in the stratum corneum was well correlated with that in plasma. In addition, no serious adverse events were observed during the trial, while a mild increase of aspartate aminotransferase and alanine aminotransferase activity in plasma was observed under the fed state in two patients. The mean AUC of IVM in plasma of those two patients were approximately threefold higher than that of the other patients at that time. On the other hand, the treatment success rate was 76.9% at 7 days after the second administration, which was comparable with the expected level. The present study not only demonstrates that HF meal intake increases the IVM concentration in plasma and the stratum corneum in Japanese patients with scabies, but also suggests the possibility that HF meals increase the risk of hepatic dysfunction by the increased exposure of IVM. © 2016 Japanese Dermatological Association.

  20. Residue depletion of ivermectin in broiler poultry.

    PubMed

    Mestorino, Nora; Buldain, Daniel; Buchamer, Andrea; Gortari, Lihuel; Daniele, Martín; Marchetti, María Laura

    2017-04-01

    Helminth infections are widespread in the poultry industry. There is evidence of extra-label use of some drugs, such as ivermectin (IVM), in broiler poultry. Pharmacokinetic and residual studies of IVM in poultry, however, are rather scarce. Our aim was to determine time restrictions for broiler chickens fed with balanced feed mixed with IVM for 21 days, and thus achieve acceptable residual levels for consumption as established by the European Union. Sixty 1-day-old chicks were fed with food supplemented with IVM at 5 mg kg -1 feed for 21 days. Groups of six treated animals were sacrificed at 0, 1, 2, 4, 8, 10, 15, 20 and 28 days after treatment. Liver, skin/fat, kidney and muscle samples were obtained. IVM were determined by liquid chromatography with fluorescence detection after automatic solid-phase extraction with SPE C 18 cartridges. The highest concentrations were measured in the liver, which is logical given that IVM is a drug that undergoes extensive hepatic metabolism. The optimal withdrawal time for edible tissues of these animals to stay within the permitted residual levels were: 12 days for liver, 8 days for skin/fat, 0 days for muscle and 10 days for kidney.

  1. Ivermectin treatment of Loa loa hyper-microfilaraemic baboons (Papio anubis): Assessment of microfilarial load reduction, haematological and biochemical parameters and histopathological changes following treatment.

    PubMed

    Wanji, Samuel; Eyong, Ebanga-Echi J; Tendongfor, Nicholas; Ngwa, Che J; Esuka, Elive N; Kengne-Ouafo, Arnaud J; Datchoua-Poutcheu, Fabrice R; Enyong, Peter; Agnew, Dalen; Eversole, Rob R; Hopkins, Adrian; Mackenzie, Charles D

    2017-07-01

    Individuals with high intensity of Loa loa are at risk of developing serious adverse events (SAEs) post treatment with ivermectin. These SAEs have remained unclear and a programmatic impediment to the advancement of community directed treatment with ivermectin. The pathogenesis of these SAEs following ivermectin has never been investigated experimentally. The Loa/baboon (Papio anubis) model can be used to investigate the pathogenesis of Loa-associated encephalopathy following ivermectin treatment in humans. 12 baboons with microfilarial loads > 8,000mf/mL of blood were randomised into four groups: Group 1 (control group receiving no drug), Group 2 receiving ivermectin (IVM) alone, Group 3 receiving ivermectin plus aspirin (IVM + ASA), and Group 4 receiving ivermectin plus prednisone (IVM + PSE). Blood samples collected before treatment and at Day 5, 7 or 10 post treatment, were analysed for parasitological, hematological and biochemical parameters using standard techniques. Clinical monitoring of animals for side effects took place every 6 hours post treatment until autopsy. At autopsy free fluids and a large number of standard organs were collected, examined and tissues fixed in 10% buffered formalin and processed for standard haematoxylin-eosin staining and specific immunocytochemical staining. Mf counts dropped significantly (p<0.05) in all animals following ivermectin treatment with reductions as high as (89.9%) recorded; while no significant drop was observed in the control animals. Apart from haemoglobin (Hb) levels which recorded a significant (p = 0.028) drop post treatment, all other haematological and biochemical parameters did not show any significant changes (p>0.05). All animals became withdrawn 48 hours after IVM administration. All treated animals recorded clinical manifestations including rashes, itching, diarrhoea, conjunctival haemorrhages, lymph node enlargement, pinkish ears, swollen face and restlessness; one animal died 5 hours after IVM administration. Macroscopic changes in post-mortem tissues observed comprised haemorrhages in the brain, lungs, heart, which seen in all groups given ivermectin but not in the untreated animals. Microscopically, the major cellular changes seen, which were present in all the ivermectin treated animals included microfilariae in varying degrees of degeneration in small vessels. These were frequently associated with fibrin deposition, endothelial changes including damage to the integrity of the blood vessel and the presence of extravascular erythrocytes (haemorrhages). There was an increased presence of eosinophils and other chronic inflammatory types in certain tissues and organs, often in large numbers and associated with microfilarial destruction. Highly vascularized organs like the brain, heart, lungs and kidneys were observed to have more microfilariae in tissue sections. The number of mf seen in the brain and kidneys of animals administered IVM alone tripled that of control animals. Co-administration of IVM + PSE caused a greater increase in mf in the brain and kidneys while the reverse was noticed with the co-administration of IVM + ASA. The treatment of Loa hyper-microfilaraemic individuals with ivermectin produces a clinical spectrum that parallels that seen in Loa hyper-microfilaraemic humans treated with ivermectin. The utilization of this experimental model can contribute to the improved management of the adverse responses in humans.

  2. Early in vitro fertilization improves development of bovine ova heat stressed during in vitro maturation.

    PubMed

    Schrock, G E; Saxton, A M; Schrick, F N; Edwards, J L

    2007-09-01

    The objectives were to examine the development of embryos derived from control (38.5 degrees C) or heat-stressed ova [41.0 degrees C during the first 12 h of in vitro maturation (hIVM)] when in vitro fertilization (IVF) was performed at 16, 18, 20, 24, or 30 hIVM. Effects of heat stress in compromising ovum development depended on when IVF was performed (in vitro maturation temperature x IVF time interaction). When IVF was performed at 24 or 30 hIVM, fewer heat-stressed ova developed to the blastocyst stage compared with the respective controls. In contrast, when IVF was performed at 16, 18, or 20 hIVM, more heat-stressed ova developed to the blastocyst stage compared with the respective controls. Performing IVF earlier than usual was beneficial, because the ability of heat-stressed ova to develop to the blastocyst stage was improved when IVF was performed at 18 or 20 vs. 24 hIVM. Blastocyst stage and quality were equivalent to non-heat-stressed controls regardless of IVF time. Control ova undergoing IVF at 20, 24, 30, or 32 hIVM and heat-stressed ova undergoing IVF at 16, 18, 20, or 24 hIVM were compared for blastocyst development by multisource regression. Although linear and quadratic slopes were similar, heat stress reduced the peak and shifted the developmental response of ova by 7.3 h. In other words, obtaining optimal blastocyst development from heat-stressed ova would depend on performing IVF at 19.5 hIVM compared with 26.7 hIVM for non-heat-stressed controls. Heat-induced reductions in peak blastocyst development significantly reduced the window of time available to perform IVF and obtain > or = 20% blastocyst development. In summary, results support an effect of heat stress to hasten developmentally important events during oocyte maturation. The inability of earlier IVF to fully restore the development of heat-stressed ova to that of non-heat-stressed controls highlights the importance of further study.

  3. Plasma dispositions and concentrations of ivermectin in eggs following treatment of laying hens.

    PubMed

    Cirak, V Y; Aksit, D; Cihan, H; Gokbulut, C

    2018-05-01

    To determine the plasma disposition and concentrations of ivermectin (IVM) in eggs produced by laying hens following S/C, oral and I/V administration. Twenty-four laying hens, aged 37 weeks and weighing 1.73 (SD 0.12) kg were allocated to three groups of eight birds. The injectable formulation of IVM was administered either orally, S/C, or I/V, at a dose of 0.2 mg/kg liveweight, following dilution (1:5, v/v) with propylene glycol. Heparinised blood samples were collected at various times between 0.25 hours and 20 days after drug administration. Eggs produced by hens were also collected daily throughout the study period. Samples of plasma and homogenised egg were analysed using HPLC. Maximum concentrations of IVM in plasma and mean residence time of IVM were lower after oral (10.2 (SD 7.2) ng/mL and 0.38 (SD 0.14) days, respectively) than after S/C (82.9 (SD 12.4) ng/mL and 1.05 (SD 0.24) days, respectively) administration (p<0.01). The time to maximum concentration and elimination half-life were shorter following oral (0.14 (SD 0.04) and 0.23 (SD 0.11) days, respectively) than S/C (0.25 (SD 0.00) and 1.45 (SD 0.45) days, respectively) administration (p<0.01). IVM was first detected in eggs 2 days after treatment in all groups and was detected until 8 days after oral and I/V administration, and until 15 days after S/C administration. Peak concentrations of IVM were 15.7, 23.3 and 1.9 µg/kg, observed 2, 5 and 4 days after I/V, S/C and oral administration, respectively. The low plasma bioavailability of IVM observed after oral administration in laying hens could result in lower efficacy or subtherapeutic plasma concentrations, which may promote the development of parasitic drug resistance. Due to high IVM residues in eggs compared to the maximum residue limits for other food-producing animal species, a withdrawal period should be necessary for eggs after IVM treatment in laying hens.

  4. Ivermectin reduces motor coordination, serum testosterone, and central neurotransmitter levels but does not affect sexual motivation in male rats.

    PubMed

    Moreira, N; Sandini, T M; Reis-Silva, T M; Navas-Suáresz, P; Auada, A V V; Lebrun, I; Flório, J C; Bernardi, M M; Spinosa, H S

    2017-12-01

    Ivermectin (IVM) is a macrocyclic lactone used for the treatment of parasitic infections and widely used in veterinary medicine as endectocide. In mammals, evidence indicates that IVM interacts with γ-aminobutyric acid (GABA)-mediated chloride channels. GABAergic system is involved in the manifestation of sexual behavior. We previously found that IVM at therapeutic doses did not alter sexual behavior in male rats, but at a higher dose, the appetitive phase of sexual behavior was impaired. Thus, we investigated whether the reduction of sexual behavior that was previously observed was a consequence of motor or motivational deficits that are induced by IVM. Data showed significant decrease in striatal dopaminergic system activity and lower testosterone levels but no effects on sexual motivation or penile erection. These findings suggest IVM may activate the GABAergic system and reduce testosterone levels, resulting in a reduction of motor coordination as consequence of the inhibition of striatal dopamine release. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Herbicide use in the management of roadside vegetation, Western Oregon, 1999-2000 : effects on the water quality of nearby streams.

    DOT National Transportation Integrated Search

    2001-01-01

    The USGS entered into a cooperative agreement with ODOT to assist the ODOT Technical Advisory Committee in evaluating the potential for impacts on water quality in nearby streams after IVM application of herbicides. This report presents the results o...

  6. Ivermectin treatment of bovine psoroptic mange: effects on serum chemistry, hematology, organ weights, and leather quality.

    PubMed

    Rehbein, S; Visser, M; Meyer, M; Lindner, T

    2016-04-01

    Psoroptic mange is a skin disease which may result in serious health and welfare problems and important economic losses. Apart from the effect on weight gain, little information is available concerning other responses of the organism consequent to the successful therapy of bovine psoroptic mange. Accordingly, serum chemistry, hematology, organ weights, and leather quality of young bulls with experimentally induced clinical Psoroptes ovis mange and treated with either ivermectin long-acting injection (IVM LAI; IVOMEC(®) GOLD, Merial) or saline (n = 16 each) were examined 8 weeks after treatment when all IVM LAI-treated bulls were free of live P. ovis mites while the saline-treated bulls maintained clinical mange. IVM LAI-treated bulls had higher (p < 0.05) alkaline phosphatase, creatinine, cholesterol, glucose, and albumin levels and lower (p < 0.01) total protein and β- and γ-globulin levels than the saline-treated bulls. Complete blood counts revealed higher leukocyte counts associated with higher eosinophil counts and higher platelet counts in the saline-treated compared to the IVM LAI-treated bulls (p < 0.01). Correlating with body weight, the warm carcass weight of the saline-treated bulls was lower than that of the IVM LAI-treated bulls (p < 0.05). Absolute and relative (organ weight divided by body weight) weights of the spleen, thymus, omental fat, and perirenal fat were higher (p < 0.01) for the IVM LAI-treated bulls than for the saline-treated bulls, while the IVM LAI-treated bulls had lower (p < 0.05) absolute and relative weights of the liver, adrenal glands, and selected lymph nodes than the saline-treated bulls. The leathers produced from the IVM LAI-treated bulls showed significantly (p < 0.001) less severe gouging or etching than leathers from the saline-treated bulls, and significantly (p < 0.05) more leather from the IVM LAI-treated bulls was of usable quality than the size of leather from the saline-treated bulls. Overall, these findings provided evidence that many changes, which are indicative of impaired protein and energy metabolism, immune system function, and performance resultant from clinical psoroptic mange, improved substantially within 8 weeks of successful treatment with injectable ivermectin.

  7. Developmental capacity of in vitro-matured human oocytes retrieved from polycystic ovary syndrome ovaries containing no follicles larger than 6 mm.

    PubMed

    Guzman, Luis; Ortega-Hrepich, Carolina; Albuz, Firas K; Verheyen, Greta; Devroey, Paul; Smitz, Johan; De Vos, Michel

    2012-08-01

    To test the developmental competence of oocytes in a nonhCG-triggered in vitro maturation (IVM) system when oocyte-cumulus complexes (OCC) are retrieved from antral follicles with a diameter of <6 mm. Prospective cohort study. Tertiary university-based referral center. From January 2010 to September 2011, 121 patients with polycystic ovaries/polycystic ovary syndrome underwent 239 IVM cycles in total. In 58 of these cycles (44 patients), all antral follicles had a diameter of <6 mm on the day of oocyte retrieval. NonhCG-triggered IVM of oocytes, fresh or vitrified/warmed embryo transfer (ET). Oocyte diameter, maturation rate, fertilization rate, embryo development and morphology, implantation rate, clinical pregnancy rate, ongoing pregnancy rate. Oocyte retrieval yielded 16.7 OCC/cycle, and 50.8% of oocytes completed IVM. The mean oocyte diameter increased from 108.8 ± 4.3 μm to 111.9 ± 4.1 μm after IVM. Mean fertilization rate was 63.7%, and 45.4% of 2-pronuclei oocytes developed into a morphologically good-quality embryo on day 3 after intracytoplasmic sperm injection. Fresh ET resulted in two ongoing pregnancies (2/37; 5.4%). Deferred vitrified-warmed ET led to an ongoing pregnancy rate of 34.6% (9/24). Three healthy babies were born and eight pregnancies were still ongoing. Oocytes retrieved from follicles with a diameter of <6 mm grow during a 40-hour IVM culture can acquire full competence in vitro, as illustrated by their development into healthy offspring. Endometrial quality appears to be a crucial determinant of pregnancy after nonhCG-triggered IVM. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  8. Avermectins differentially affect ethanol intake and receptor function: implications for developing new therapeutics for alcohol use disorders.

    PubMed

    Asatryan, Liana; Yardley, Megan M; Khoja, Sheraz; Trudell, James R; Hyunh, Nhat; Louie, Stan G; Petasis, Nicos A; Alkana, Ronald L; Davies, Daryl L

    2014-06-01

    Our laboratory is investigating ivermectin (IVM) and other members of the avermectin family as new pharmaco-therapeutics to prevent and/or treat alcohol use disorders (AUDs). Earlier work found that IVM significantly reduced ethanol intake in mice and that this effect likely reflects IVM's ability to modulate ligand-gated ion channels. We hypothesized that structural modifications that enhance IVM's effects on key receptors and/or increase its brain concentration should improve its anti-alcohol efficacy. We tested this hypothesis by comparing the abilities of IVM and two other avermectins, abamectin (ABM) and selamectin (SEL), to reduce ethanol intake in mice, to alter modulation of GABAARs and P2X4Rs expressed in Xenopus oocytes and to increase their ability to penetrate the brain. IVM and ABM significantly reduced ethanol intake and antagonized the inhibitory effects of ethanol on P2X4R function. In contrast, SEL did not affect either measure, despite achieving higher brain concentrations than IVM and ABM. All three potentiated GABAAR function. These findings suggest that chemical structure and effects on receptor function play key roles in the ability of avermectins to reduce ethanol intake and that these factors are more important than brain penetration alone. The direct relationship between the effect of these avermectins on P2X4R function and ethanol intake suggest that the ability to antagonize ethanol-mediated inhibition of P2X4R function may be a good predictor of the potential of an avermectin to reduce ethanol intake and support the use of avermectins as a platform for developing novel drugs to prevent and/or treat AUDs.

  9. Cysteamine supplementation during in vitro maturation of slaughterhouse- and opu-derived bovine oocytes improves embryonic development without affecting cryotolerance, pregnancy rate, and calf characteristics.

    PubMed

    Merton, J S; Knijn, H M; Flapper, H; Dotinga, F; Roelen, B A J; Vos, P L A M; Mullaart, E

    2013-09-01

    Optimization of ovum pick up (OPU) followed by in vitro embryo production (IVP) is strongly driven by the needs of both beef and dairy cattle breeders to enhance genetic improvement. The rapidly growing use of genomic selection in cattle has increased the interest in using OPU-IVP technology to increase the number of embryos and offspring per donor, thus allowing enhanced selection intensity for the next generation. The aim of this study was to optimize embryo production through supplementation of cysteamine during in vitro maturation (IVM) and in vitro culture (IVC) of both slaughterhouse- and OPU-derived oocytes. The effects on embryo production and on embryo cryotolerance, post-transfer embryo survival, and calf characteristics, including gestation length, birth weight, perinatal mortality, and sex ratio were studied. In study 1, immature slaughterhouse-derived cumulus-oocyte complexes (COCs) were matured in IVM medium supplemented with or without 0.1 mM cysteamine, fertilized and cultured for 7 days in 0.5 ml SOFaaBSA. In study 2, cysteamine was present during both IVM (0.1 mM) and IVC (0.01, 0.05, 0.1 mM) from Days 1 to 4. In study 3, OPU-derived COCs were matured in medium supplemented with or without 0.1 mM cysteamine in a 2 × 2 factorial design (OPU week and cysteamine treatment). Embryos were evaluated for stage and grade on Day 7 and, depending on the number of transferable embryos and recipients available, the embryos were transferred either fresh or frozen-thawed at a later date. The presence of cysteamine during IVM significantly increased the embryo production rate with slaughterhouse-derived COCs (24.0% vs. 19.4%). The higher number of embryos at Day 7 was due to an increased number of blastocysts, whereas the distribution of embryos among different quality grades and cryotolerance was not affected. Embryo production rate was negatively affected when cysteamine was present during both the processes of IVM and IVC during Days 1 to 4 of culture (13.2%-19.3% vs. 26.4%). The presence of cysteamine during IVM of OPU-derived COCs also significantly increased the embryo production rate (34.4% vs. 23.4%). The higher number of embryos was again totally due to an increased number of blastocysts, whereas cryotolerance was not affected. The relative increase in embryo production rate was higher with OPU-derived oocytes compared with slaughterhouse-derived COCs (47% vs. 24%). This improvement resulted in a mean of 1.73 transferable embryos per OPU session compared with 1.06 in the absence of cysteamine. The presence of cysteamine did not affect pregnancy rate, gestation length, birth weight, perinatal mortality, and sex of calves born from either fresh or frozen-thawed embryos. This study reported that cysteamine supplementation during IVM greatly improved the efficiency and affectivity of an OPU-IVP program. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Measuring the effect of avermectins and milbemycins on somatic muscle contraction of adult Haemonchus contortus and on motility of Ostertagia circumcincta in vitro.

    PubMed

    Demeler, Janina; VON Samson-Himmelstjerna, Georg; Sangster, Nicholas C

    2014-06-01

    The mechanism of anthelmintic resistance against the widely used macrocyclic lactones (MLs) is still not fully understood. Pharyngeal, somatic body muscles and the ovijector have been proposed as putative sites of action as well as resistance. In the present study the effects of three avermectins and three milbemycins on adult parasitic nematodes were evaluated in vitro. The Muscle Transducer system was used to investigate the effects of MLs on muscle contraction in female Haemonchus contortus and effects on motility were measured in Ostertagia (Teladorsagia) circumcincta using the Micromotility Meter. Concentration-response curves for all substances in both systems shifted to the right in the resistant isolates. Resistance was present to ivermectin (IVM) and its components IVM B1a and IVM B1b, suggesting that both components are involved in the mode of action and resistance. No consistent patterns of potency and resistance of the substances were observed except that milbemycins generally showed lower resistance ratios (RRs) than IVM. IVM and IVM B1b were the most potent inhibitors of contraction and motility in both susceptible isolates and also showed the highest RR in both species. Low RRs for milbemycins recorded in vitro for highly resistant isolates in vivo suggest that other factors such as pharmacokinetics influence drug potency in vivo.

  11. Occurrence of ovarian follicular dominance during stimulation for IVM impacts usable blastocyst yield.

    PubMed

    Romero, Sergio; Pella, Ricardo; Escudero, Francisco; Pérez, Ygor; García, Mario; Orihuela, Patricia

    2018-03-01

    To evaluate the influence of ovarian follicular dominance on the outcome of oocyte in-vitro maturation. This retrospective cohort study included 21 patients with polycystic ovaries or polycystic ovary syndrome (Rotterdam criteria, 2004) subjected to 24 invitro maturation (IVM) cycles between October 2015 and January 2017. Patients undergoing IVM received minimal gonadotropin stimulation starting on day 2 or 3 of the cycle; ovum pick-up typically occurred on days 6 to 8. No hCG-trigger shot was given. Following 30h of IVM, mature oocytes were inseminated by ICSI and the resulting embryos cultured up to the blastocyst stage. Ovarian follicular dominance was observed in nine of the 24 IVM cycles. Oocyte IVM yielded an overall maturation rate of 69.3±23.8%, and no difference was observed when the groups with or without a dominant follicle were assessed independently. The rates of fertilization and usable blastocysts per fertilized oocyte, mature oocyte (Metaphase II) or cumulus-oocyte-complex were nearly three times higher (28.7±22.5%) in the group without ovarian follicular dominance. No differences were found in the clinical pregnancy rates attained by the individuals with or without a dominant follicle after 21 vitrified-warmed blastocyst transfer cycles. Occurrence of ovarian follicular dominance during hormonal stimulation for in-vitro maturation negatively impacted embryological outcomes. Strategies devised to limit the appearance of ovarian follicular dominance must be further explored.

  12. Integrated Immunotherapy for Breast Cancer

    DTIC Science & Technology

    2014-09-01

    Figure 12). Moreover, several known inducers of autophagy (Rapamycin, Bortezomib, Resveratrol , Wortmannin) were all able to synergize with IVM in killing...ili ty 4T1.2 4h Resveratrol 0.000 0.200 0.400 0.600 0.800 1.000 1.200 Vi ab ili ty 4T1.2 4h Wortmannin Figure 13. IVM synergizes with known inducers...of autophagy. 4T1.2 cells were treated for 4h with IVM and Rapamycin, Bortezomib, Wortmannin, or Resveratrol . Cell viability was evaluated by the

  13. Production of lion (Panthera leo) blastocysts after in vitro maturation of oocytes and intracytoplasmic sperm injection.

    PubMed

    Fernandez-Gonzalez, Lorena; Hribal, Romy; Stagegaard, Julia; Zahmel, Jennifer; Jewgenow, Katarina

    2015-04-01

    Assisted reproductive techniques are becoming widely applied to the breeding of endangered species, but establishing reliable protocols for the production of embryos in vitro is challenging because of the scarcity of sample material. In our study, we applied an assisted reproductive technique protocol for IVM and intracytoplasmic sperm injection (ICSI), developed in the domestic cat, to oocytes retrieved from ovaries of four 2-year-old lionesses (Panthera leo) eight hours postmortem. In total, 68 cumulus-oocyte complexes of good quality were randomly distributed and cultured for 32 to 34 hours in two different maturation culture media, consisting of Medium 199 with Earle's salts, 3 mg/mL BSA, 0.1 mg/mL cysteine, 1.4 mg/mL sodium pyruvate, 0.6 mg/mL sodium lactate, 0.15 mg/mL l-glutamine, and 0.055 mg/mL gentamicin. Hormonal supplementation of IVM_1 was 0.02 IU/mL FSH and 0.05 IU/mL LH; IVM_2 consisted of 1.64 IU/mL FSH, 1.06 IU/mL LH, and 1 μg/mL 17ß-estradiol. Differences in hormonal supplementation did not produce significant differences in oocyte maturation rates, which were 39.4% in IVM_1 and 34.3% in IVM_2. Matured oocytes were microinjected with homologous frozen-thawed spermatozoa, and subsequent cleavage rates were 30.8% and 58.3%, respectively. Half of the embryos derived from oocytes matured in IVM_1 developed into blastocysts, whereas only 28.6% of embryos from oocytes matured in IVM_2 reached the blastocyst stage. Morula stages were present from Day 6 onward, and blastocyst stages from Day 9 on, indicating a slower developmental speed in comparison with domestic cats. This is the first report of in vitro-produced blastocysts using ICSI in the lion, and the results report that IVM and ICSI can be successfully performed with cumulus-oocyte complexes retrieved from ovaries after eight hours of shipping, obtaining competent embryos in culture. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Voltage measurements at the vacuum post-hole convolute of the Z pulsed-power accelerator

    DOE PAGES

    Waisman, E. M.; McBride, R. D.; Cuneo, M. E.; ...

    2014-12-08

    Presented are voltage measurements taken near the load region on the Z pulsed-power accelerator using an inductive voltage monitor (IVM). Specifically, the IVM was connected to, and thus monitored the voltage at, the bottom level of the accelerator’s vacuum double post-hole convolute. Additional voltage and current measurements were taken at the accelerator’s vacuum-insulator stack (at a radius of 1.6 m) by using standard D-dot and B-dot probes, respectively. During postprocessing, the measurements taken at the stack were translated to the location of the IVM measurements by using a lossless propagation model of the Z accelerator’s magnetically insulated transmission lines (MITLs)more » and a lumped inductor model of the vacuum post-hole convolute. Across a wide variety of experiments conducted on the Z accelerator, the voltage histories obtained from the IVM and the lossless propagation technique agree well in overall shape and magnitude. However, large-amplitude, high-frequency oscillations are more pronounced in the IVM records. It is unclear whether these larger oscillations represent true voltage oscillations at the convolute or if they are due to noise pickup and/or transit-time effects and other resonant modes in the IVM. Results using a transit-time-correction technique and Fourier analysis support the latter. Regardless of which interpretation is correct, both true voltage oscillations and the excitement of resonant modes could be the result of transient electrical breakdowns in the post-hole convolute, though more information is required to determine definitively if such breakdowns occurred. Despite the larger oscillations in the IVM records, the general agreement found between the lossless propagation results and the results of the IVM shows that large voltages are transmitted efficiently through the MITLs on Z. These results are complementary to previous studies [R.D. McBride et al., Phys. Rev. ST Accel. Beams 13, 120401 (2010)] that showed efficient transmission of large currents through the MITLs on Z. Taken together, the two studies demonstrate the overall efficient delivery of very large electrical powers through the MITLs on Z.« less

  15. Intravital microscopy in the study of the tumor microenvironment: from bench to human application.

    PubMed

    Gabriel, Emmanuel M; Fisher, Daniel T; Evans, Sharon; Takabe, Kazuaki; Skitzki, Joseph J

    2018-04-13

    Intravital microscopy (IVM) is a dynamic imaging modality that allows for the real time observation of biologic processes in vivo , including angiogenesis and immune cell interactions. In the setting of preclinical cancer models, IVM has facilitated an understanding of the tumor associated vasculature and the role of effector immune cells in the tumor microenvironment. Novel approaches to apply IVM to human malignancies have thus far focused on cancer diagnosis and tumor vessel characterization, but have the potential to provide advances in the field of personalized medicine by identifying individual patients who may respond to systemically delivered chemotherapeutic drugs or immunotherapeutic agents. In this review, we highlight the role that IVM has had in investigating tumor vasculature and the tumor microenvironment in preclinical studies and discuss its current and future applications to directly observe human tumors.

  16. Occurrence of ovarian follicular dominance during stimulation for IVM impacts usable blastocyst yield

    PubMed Central

    Romero, Sergio; Pella, Ricardo; Escudero, Francisco; Pérez, Ygor; García, Mario; Orihuela, Patricia

    2018-01-01

    Objective To evaluate the influence of ovarian follicular dominance on the outcome of oocyte in-vitro maturation. Methods This retrospective cohort study included 21 patients with polycystic ovaries or polycystic ovary syndrome (Rotterdam criteria, 2004) subjected to 24 in-vitro maturation (IVM) cycles between October 2015 and January 2017. Patients undergoing IVM received minimal gonadotropin stimulation starting on day 2 or 3 of the cycle; ovum pick-up typically occurred on days 6 to 8. No hCG-trigger shot was given. Following 30h of IVM, mature oocytes were inseminated by ICSI and the resulting embryos cultured up to the blastocyst stage. Results Ovarian follicular dominance was observed in nine of the 24 IVM cycles. Oocyte IVM yielded an overall maturation rate of 69.3±23.8%, and no difference was observed when the groups with or without a dominant follicle were assessed independently. The rates of fertilization and usable blastocysts per fertilized oocyte, mature oocyte (Metaphase II) or cumulus-oocyte-complex were nearly three times higher (28.7±22.5%) in the group without ovarian follicular dominance. No differences were found in the clinical pregnancy rates attained by the individuals with or without a dominant follicle after 21 vitrified-warmed blastocyst transfer cycles. Conclusion Occurrence of ovarian follicular dominance during hormonal stimulation for in-vitro maturation negatively impacted embryological outcomes. Strategies devised to limit the appearance of ovarian follicular dominance must be further explored. PMID:29338139

  17. IVF versus ICSI for the fertilization of in-vitro matured human oocytes.

    PubMed

    Walls, M; Junk, S; Ryan, J P; Hart, R

    2012-12-01

    Traditional dogma suggests that intracytoplasmic sperm injection (ICSI) should be performed to ensure successful oocyte fertilization in an in-vitro maturation (IVM) cycle. This study postulated that there would be no difference in the fertilization rate when ICSI was compared with IVF. This hypothesis was tested in a randomized trial of IVF versus ICSI in IVM. A total of 150 immature oocytes were collected in eight cycles of IVM for patients diagnosed with polycystic ovarian syndrome (PCOS). Patients were primed with minimal FSH before transvaginal oocyte aspiration. Sibling oocytes were inseminated by 50% IVF and 50% ICSI. There was no significant difference in fertilization, useable or total blastocyst development between the two insemination technique groups. Clinical pregnancy results for combined fresh and cryopreserved transfers were identical between the two insemination techniques with a total of two fresh and five cryopreserved IVF-inseminated embryos resulting in three clinical pregnancies (42.9%) and five fresh and two cryopreserved ICSI-derived embryos resulting in three clinical pregnancies (42.9%). This research has shown IVF to be a legitimate fertilization technique for IVM oocytes in PCOS patients and provides a greater awareness of the use of a fertilization method previously not utilized with IVM. In-vitro maturation (IVM) is an alternative treatment method to traditional IVF. Due to the minimal use of stimulating hormones in this treatment, IVM has a lower risk of ovarian hyperstimulation syndrome, it can be used for fertility preservation in cancer patients and it is more cost conservative. Early research into the effects of IVM showed a hardening effect on the membrane surrounding the egg (the zona pellucida). It was initially believed that, to overcome this hardening in order to allow the egg to be fertilized, spermatozoa would need to be injected into the egg using intracytoplasmic sperm injection. Due to recent advances in hormonal stimulation protocols (FSH priming) and culture conditions, we postulated that, for patients suffering from polycystic ovarian syndrome (PCOS), fertilization, embryo development and clinical pregnancy would not be superior in the injected oocytes compared with those inseminated by IVF. We found that by using the two insemination techniques on sibling oocytes from eight PCOS patients, there was no significant difference in fertilization, useable or total blastocyst development (day 5 or 6 embryos) and that clinical pregnancy results were identical. This research provides a greater awareness of a fertilization technique which is not normally utilized for IVM treatment, providing a less invasive, more cost-effective approach for the patient. Copyright © 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  18. Displacement of polarons by vibrational modes in doped conjugated polymers

    NASA Astrophysics Data System (ADS)

    Anderson, M.; Ramanan, C.; Fontanesi, C.; Frick, A.; Surana, S.; Cheyns, D.; Furno, M.; Keller, T.; Allard, S.; Scherf, U.; Beljonne, D.; D'Avino, G.; von Hauff, E.; Da Como, E.

    2017-10-01

    Organic pi-conjugated polymers are deemed to be soft materials with strong electron-phonon coupling, which results in the formation of polarons, i.e., charge carriers dressed by self-localized distortion of the nuclei. Universal signatures for polarons are optical resonances below the band gap and intense vibrational modes (IVMs), both found in the infrared (IR) spectral region. Here, we study p -doped conjugated homo- and copolymers by combining first-principles modelling and optical spectroscopy from the far-IR to the visible. Polaronic IVMs are found to feature absorption intensities comparable to purely electronic transitions and, most remarkably, show only loose resemblance to the Raman or IR-active modes of the neutral polymer. The IVM frequency is dramatically scaled down (up to 50%) compared to the backbone carbon-stretching modes in the pristine polymers. The very large intensity of IVMs is associated with displacement of the excess positive charge along the backbone driven by specific vibrational modes. We propose a quantitative picture for the identification of these polaron shifting modes that solely based on structural information, directly correlates with their IR intensity. This finding finally discloses the elusive microscopic mechanism behind the huge IR intensity of IVMs in doped polymeric semiconductors.

  19. Germline competency of parthenogenetic embryonic stem cells from immature oocytes of adult mouse ovary

    PubMed Central

    Liu, Zhong; Hu, Zhe; Pan, Xinghua; Li, Minshu; Togun, Taiwo A.; Tuck, David; Pelizzola, Mattia; Huang, Junjiu; Ye, Xiaoying; Yin, Yu; Liu, Mengyuan; Li, Chao; Chen, Zhisheng; Wang, Fang; Zhou, Lingjun; Chen, Lingyi; Keefe, David L.; Liu, Lin

    2011-01-01

    Parthenogenetic embryonic stem cells (pESCs) have been generated in several mammalian species from parthenogenetic embryos that would otherwise die around mid-gestation. However, previous reports suggest that pESCs derived from in vivo ovulated (IVO) mature oocytes show limited pluripotency, as evidenced by low chimera production, high tissue preference and especially deficiency in germline competence, a critical test for genetic integrity and pluripotency of ESCs. Here, we report efficient generation of germline-competent pESC lines (named as IVM pESCs) from parthenogenetic embryos developed from immature oocytes of adult mouse ovaries following in vitro maturation (IVM) and artificial activation. In contrast, pESCs derived from IVO oocytes show defective germline competence, consistent with previous reports. Further, IVM pESCs resemble more ESCs from fertilized embryos (fESCs) than do IVO pESCs on genome-wide DNA methylation and global protein profiles. In addition, IVM pESCs express higher levels of Blimp1, Lin28 and Stella, relative to fESCs, and in their embryoid bodies following differentiation. This may indicate differences in differentiation potentially to the germline. The mechanisms for acquisition of pluripotency and germline competency of IVM pESCs from immature oocytes remain to be determined. PMID:21239471

  20. Supplementation with nanomolar concentrations of verbascoside during in vitro maturation improves embryo development by protecting the oocyte against oxidative stress: a large animal model study.

    PubMed

    Martino, Nicola Antonio; Ariu, Federica; Bebbere, Daniela; Uranio, Manuel Filioli; Chirico, Adriana; Marzano, Giuseppina; Sardanelli, Anna Maria; Cardinali, Angela; Minervini, Fiorenza; Bogliolo, Luisa; Dell'Aquila, Maria Elena

    2016-10-01

    The effects of verbascoside (VB), added at nanomolar concentrations during in vitro maturation (IVM) of juvenile sheep oocytes, on in vitro embryo development and its mechanisms of action at the oocyte level were analyzed. Developmental rates, after IVM in the presence/absence of VB (1nM for 24h; 1nM for 2h; 10nM for 2h), were evaluated. The bioenergetic/oxidative status of oocytes matured after IVM in the presence/absence of 1nM VB for 24h was assessed by confocal analysis of mitochondria and reactive oxygen species (ROS), lipid peroxidation (LPO) assay, and quantitative PCR of bioenergy/redox-related genes. The addition of 1nM VB during 24h IVM significantly increased blastocyst formation and quality. Verbascoside reduced oocyte ROS and LPO and increased mitochondria/ROS colocalization while keeping mitochondria activity and gene expression unchanged. In conclusion, supplementation with nanomolar concentrations of VB during IVM, in the juvenile sheep model, promotes embryo development by protecting the oocyte against oxidative stress. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Bovine non-competent oocytes (BCB-) negatively impact the capacity of competent (BCB+) oocytes to undergo in vitro maturation, fertilisation and embryonic development.

    PubMed

    Salviano, M B; Collares, F J F; Becker, B S; Rodrigues, B A; Rodrigues, J L

    2016-04-01

    Competent oocyte selection remains a bottleneck in the in vitro production (IVP) of mammalian embryos. Among the vital assays described for selecting competent oocytes for IVP, the brilliant cresyl blue (BCB) test has shown consistent results. The aim of the first experiment was to observe if oocytes directly submitted to IVM show similar cleavage and blastocyst rates as those obtained with oocytes maintained under the same in vitro conditions as the oocytes that undergo the BCB test. Bovine cumulus-oocyte complexes (COCs) were recovered from slaughterhouse-derived ovaries and, after morphological evaluation, were randomised grouped into three groups: (1) directly submitted to IVM; (2) oocytes submitted to the BCB test without the addition of BCB stain (BCB control group); and (3) submitted to the BCB test. The results showed that oocytes directly submitted to IVM reached similar cleavage (48/80 - 60%) and embryonic development rates to the blastocyst stage (10/48 - 21%) as the results obtained with the BCB control group oocytes (45/77 - 58% and 08/45 - 18%, respectively). The aim of the second experiment was to determine the cleavage and blastocyst rates obtained from BCB+ oocytes undergoing IVM in the presence of BCB- oocytes at a ratio of 10:1. COCs were recovered from slaughterhouse-derived ovaries and, after morphological evaluation, were randomised into two groups that were submitted to IVM either directly (1: control group) or submitted to the BCB test prior to IVM. After the BCB test, the COCs were classified as either BCB+ (blue cytoplasm) or BCB- (colourless cytoplasm) and then divided into four experimental groups: (2) BCB+; (3) BCB-; and (4) BCB+ matured in same IVM medium drop as (5) BCB- at a ratio of 10:1. After IVM (24 h), oocytes from the different experimental groups were submitted to in vitro fertilisation (IVF) and in vitro culture (IVC) under the same culture conditions until they reached the blastocyst stage (D7). With regards to the cleavage rate (48 h after IVF), only group 3 (102/229 - 44%) differed (P < 0.05) from the other groups [1 (145/241 - 60%); 2 (150/225 - 67%); 4 (201/318 - 63%) and 5 (21/33 - 63%)]. On day 7, the embryos from group 2 (BCB+) achieved the highest blastocyst rate (46/150 - 31%) (P < 0.05) when compared with the embryo development capacity of the other experimental groups (1: 31/145 - 21%; group 3: 17/102 - 17%; group 4: 46/201 - 23%; and group 5: 2/21 - 10%). In conclusion, submitting BCB+ oocytes that were separated from BCB- oocytes to IVM increases the rate of embryonic development to the blastocyst stage when compared to the control group, BCB- oocyte group, BCB+ paracrine group and BCB- paracrine group. The presence of non-competent oocytes during IVM, even in low proportion (1:10), reduces the capacity of competent oocytes to undergo embryo development and achieve blastocyst stage during IVC.

  2. Cyclic AMP Affects Oocyte Maturation and Embryo Development in Prepubertal and Adult Cattle

    PubMed Central

    Bernal-Ulloa, Sandra Milena; Heinzmann, Julia; Herrmann, Doris; Hadeler, Klaus-Gerd; Aldag, Patrick; Winkler, Sylke; Pache, Dorit; Baulain, Ulrich; Lucas-Hahn, Andrea; Niemann, Heiner

    2016-01-01

    High cAMP levels during in vitro maturation (IVM) have been related to improved blastocyst yields. Here, we employed the cAMP/cGMP modulators, forskolin, IBMX, and cilostamide, during IVM to unravel the role of high cAMP in early embryonic development produced from prepubertal and adult bovine oocytes. Oocytes were collected via transvaginal aspiration and randomly assigned to three experimental groups: TCM24 (24h IVM/control), cAMP30 (2h pre-IVM (forskolin-IBMX), 30h IVM-cilostamide), and DMSO30 (Dimethyl Sulfoxide/vehicle control). After IVM, oocytes were fertilized in vitro and zygotes were cultured in vitro to blastocysts. Meiotic progression, cAMP levels, mRNA abundance of selected genes and DNA methylation were evaluated in oocytes. Blastocysts were used for gene expression or DNA methylation analyses. Blastocysts from the cAMP30 groups were transferred to recipients. The cAMP elevation delayed meiotic progression, but developmental rates were not increased. In immature oocytes, mRNA abundance of PRKACA was higher for cAMP30 protocol and no differences were found for PDE3A, SMAD2, ZAR1, PRDX1 and SLC2A8. EGR1 gene was up-regulated in prepubertal cAMP30 immature oocytes and down-regulated in blastocysts from all in vitro treatments. A similar gene expression profile was observed for DNMT3b, BCL2L1, PRDX1 and SLC2A8 in blastocysts. Satellite DNA methylation profiles were different between prepubertal and adult oocytes and blastocysts derived from the TCM24 and DMSO30 groups. Blastocysts obtained from prepubertal and adult oocytes in the cAMP30 treatment displayed normal methylation profiles and produced offspring. These data indicate that cAMP regulates IVM in prepubertal and adult oocytes in a similar manner, with impact on the establishment of epigenetic marks and acquisition of full developmental competency. PMID:26926596

  3. Reproductive Status of Onchocerca volvulus after Ivermectin Treatment in an Ivermectin-Naïve and a Frequently Treated Population from Cameroon

    PubMed Central

    Bopda, Jean; Kengne-Ouafo, Jonas A.; Njiokou, Flobert; Prichard, Roger K.; Wanji, Samuel; Kamgno, Joseph; Boussinesq, Michel

    2014-01-01

    Background For two decades, onchocerciasis control has been based on mass treatment with ivermectin (IVM), repeated annually or six-monthly. This drug kills Onchocerca volvulus microfilariae (mf) present in the skin and the eyes (microfilaricidal effect) and prevents for 3–4 months the release of new mf by adult female worms (embryostatic effect). In some Ghanaian communities, the long-term use of IVM was associated with a more rapid than expected skin repopulation by mf after treatment. Here, we assessed whether the embryostatic effect of IVM on O. volvulus has been altered following frequent treatment in Cameroonian patients. Methodology Onchocercal nodules were surgically removed just before (D0) and 80 days (D80) after a standard dose of IVM in two cohorts with different treatment histories: a group who had received repeated doses of IVM over 13 years, and a control group with no history of large-scale treatments. Excised nodules were digested with collagenase to isolate adult worms. Embryograms were prepared with females for the evaluation of their reproductive capacities. Principal Findings Oocyte production was not affected by IVM. The mean number of intermediate embryos (morulae and coiled mf) decreased similarly in the two groups between D0 and D80. In contrast, an accumulation of stretched mf, either viable or degenerating, was observed at D80. However, it was observed that the increase in number of degenerating mf between D0 and D80 was much lower in the frequently treated group than in the control one (Incidence Rate Ratio: 0.25; 95% CI: 0.10–0.63; p = 0.003), which may indicate a reduced sequestration of mf in the worms from the frequently treated group. Conclusion/Significance IVM still had an embryostatic effect on O. volvulus, but the effect was reduced in the frequently treated cohort compared with the control population. PMID:24762816

  4. Differential Effects of Alcohol on Memory Performance in Adolescent Men and Women with a Binge Drinking History.

    PubMed

    Vinader-Caerols, Concepción; Talk, Andrew; Montañés, Adriana; Duque, Aránzazu; Monleón, Santiago

    2017-09-01

    Binge drinking (BD) is characterized by intermittent consumption of large quantities of alcohol in short periods. This pattern of drinking is prevalent among adolescents, and has been associated with undermined learning and memory ability. This study investigates the relationships between a history of BD and the effects of acute exposure to alcohol on learning and memory performance in adolescent men and women. A high, acute dose of alcohol or control refreshment was administered to a sample of 172 adolescent undergraduate students, some of which had a history of BD and others of which had refrained from alcohol consumption. Subsequently, immediate visual memory (IVM) and working memory (WM) was measured according to the Wechsler Memory Scale in females and males with different BAC (Experiment 1) and similar BAC (Experiment 2). In both experiments, IVM was reduced after acute alcohol consumption and there was no significant main effect of Drinking Pattern. Furthermore, an effect of cognitive alcohol tolerance on IVM was observed in women but not in men. WM was not affected by alcohol, but a gender difference was evident in that performance was superior in men than in women. In adolescents, IVM is more sensitive than WM to impairment by alcohol, and women are more vulnerable to the neurotoxic effects of alcohol than men, since the cognitive tolerance effect of alcohol on IVM develops in BD women but not in BD men. These findings emphasize the need to investigate the neurotoxic effects of alcohol in adolescent women. In adolescents, immediate visual memory (IVM) is more sensitive than working memory to impairment by alcohol, and women are more vulnerable to the neurotoxic effects of alcohol than men, because the cognitive tolerance effect of alcohol on IVM develops in binge drinking (BD) women but not in BD men. © The Author 2017. Medical Council on Alcohol and Oxford University Press. All rights reserved.

  5. Birth after human chorionic gonadotropin-primed oocyte in vitro maturation and fertilization with testicular sperm in a normo-ovulatory patient.

    PubMed

    González-Ortega, Claudia; Piña-Aguilar, Raul Eduardo; Cancino-Villareal, Patricia; Gutiérrez-Gutiérrez, Antonio Martin

    2016-01-01

    In this report, we present a case of in vitro maturation (IVM) with surgical retrieved testicular sperm in a normo-ovulatory female. Human chorionic gonadotropin-primed IVM, testicular biopsy for sperm retrieval and intracytoplasmic sperm injection with fresh sperm were performed. Fourteen cumulus-oocyte complexes were obtained in germinal vesicle or metaphase I stage, eight oocytes reached metaphase II, seven presumptive zygotes were obtained, and three cleavage stages embryos in day 2 were transferred producing a singleton pregnancy. A single healthy newborn was obtained. Our results suggest that IVM may be an alternative for in vitro fertilization in normo-ovulatory women even if surgical retrieval of sperm is needed. Further research is required to depict contributing factors to the success of IVM in indications different from polycystic ovaries syndrome and the role of male gamete.

  6. A comparison of the Cook single lumen immature ovum IVM needle to the Steiner-Tan pseudo double lumen flushing needle for oocyte retrieval for IVM.

    PubMed

    Rose, B I; Laky, D

    2013-06-01

    This study compared the impact of using the Steiner-Tan pseudo double lumen needle for antral follicle oocyte retrieval to using a conventional non-flushing needle. The Steiner-Tan needle has a much smaller dead space than the needles commonly used for IVM oocyte retrievals. This was a retrospective cohort study. The patient population was determined by the time period in which a patient underwent IVM in a single physician's IVF practice. The following data was abstracted from clinical and embryology records: oocytes retrieved, oocytes matured, early maturing oocytes, oocytes fertilized, embryo quality measures, retrieval time, needle punctures, clot formation, and clinical pregnancy rate. The Steiner-Tan needle did not increase the number of oocytes retrieved. It also did not increase the time required for retrieval. However, flushing of antral follicles significantly decreased clot formation in fluid aspirates. Use of the Steiner-Tan needle also significantly decreased the number of vaginal needle punctures during each case. There was a trend toward improved embryo quality, but statistical power was inadequate to show a difference. The primary benefit of the Steiner-Tan needle was on the embryological aspects of IVM. Decreased blood and blood clots in the aspirates made an IVM retrieval more like conventional IVF for the embryologist. The patient also experienced less tissue trauma without increasing anesthesia or surgical time. There was no improvement in the number of oocytes retrieved, but based on the results, we hypothesized that oocytes were more commonly retrieved from slightly large follicles than when using a routine needle.

  7. Mass drug administration of ivermectin in south-eastern Senegal reduces the survivorship of wild-caught, blood fed malaria vectors

    PubMed Central

    2010-01-01

    Background In south-eastern Senegal, malaria and onchocerciasis are co-endemic. Onchocerciasis in this region has been controlled by once or twice yearly mass drug administration (MDA) with ivermectin (IVM) for over fifteen years. Since laboratory-raised Anopheles gambiae s.s. are susceptible to ivermectin at concentrations found in human blood post-ingestion of IVM, it is plausible that a similar effect could be quantified in the field, and that IVM might have benefits as a malaria control tool. Methods In 2008 and 2009, wild-caught blood fed An. gambiae s.l. mosquitoes were collected from huts of three pairs of Senegalese villages before and after IVM MDAs. Mosquitoes were held in an insectary to assess their survival rate, subsequently identified to species, and their blood meals were identified. Differences in mosquito survival were statistically analysed using a Glimmix model. Lastly, changes in the daily probability of mosquito survivorship surrounding IVM MDAs were calculated, and these data were inserted into a previously developed, mosquito age-structured model of malaria transmission. Results Anopheles gambiae s.s. (P < 0.0001) and Anopheles arabiensis (P = 0.0191) from the treated villages had significantly reduced survival compared to those from control villages. Furthermore, An gambiae s.s. caught 1-6 days after MDA in treated villages had significantly reduced survival compared to control village collections (P = 0.0003), as well as those caught pre-MDA (P < 0.0001) and >7 days post-MDA (P < 0.0001). The daily probability of mosquito survival dropped >10% for the six days following MDA. The mosquito age-structured model of malaria transmission demonstrated that a single IVM MDA would reduce malaria transmission (Ro) below baseline for at least eleven days, and that repeated IVM MDAs would result in a sustained reduction in malaria Ro. Conclusions Ivermectin MDA significantly reduced the survivorship of An. gambiae s.s. for six days past the date of the MDA, which is sufficient to temporarily reduce malaria transmission. Repeated IVM MDAs could be a novel and integrative malaria control tool in areas with seasonal transmission, and which would have simultaneous impacts on neglected tropical diseases in the same villages. PMID:21171970

  8. Integrative veterinary medical education and consensus guidelines for an integrative veterinary medicine curriculum within veterinary colleges

    PubMed Central

    Memon, M.A.; Shmalberg, J.; Adair, H.S.; Allweiler, S.; Bryan, J.N.; Cantwell, S.; Carr, E.; Chrisman, C.; Egger, C.M.; Greene, S.; Haussler, K.K.; Hershey, B.; Holyoak, G.R.; Johnson, M.; Jeune, S. Le; Looney, A.; McConnico, R.S.; Medina, C.; Morton, A.J.; Munsterman, A.; Nie, G.J.; Park, N.; Parsons-Doherty, M.; Perdrizet, J.A.; Peyton, J.L.; Raditic, D.; Ramirez, H.P.; Saik, J.; Robertson, S.; Sleeper, M.; Dyke, J. Van; Wakshlag, J.

    2016-01-01

    Integrative veterinary medicine (IVM) describes the combination of complementary and alternative therapies with conventional care and is guided by the best available evidence. Veterinarians frequently encounter questions about complementary and alternative veterinary medicine (CAVM) in practice, and the general public has demonstrated increased interest in these areas for both human and animal health. Consequently, veterinary students should receive adequate exposure to the principles, theories, and current knowledge supporting or refuting such techniques. A proposed curriculum guideline would broadly introduce students to the objective evaluation of new veterinary treatments while increasing their preparation for responding to questions about IVM in clinical practice. Such a course should be evidence-based, unbiased, and unaffiliated with any particular CAVM advocacy or training group. All IVM courses require routine updating as new information becomes available. Controversies regarding IVM and CAVM must be addressed within the course and throughout the entire curriculum. Instructional honesty regarding the uncertainties in this emerging field is critical. Increased training of future veterinary professionals in IVM may produce an openness to new ideas that characterizes the scientific method and a willingness to pursue and incorporate evidence-based medicine in clinical practice with all therapies, including those presently regarded as integrative, complementary, or alternative. PMID:27200270

  9. Current vector control challenges in the fight against malaria.

    PubMed

    Benelli, Giovanni; Beier, John C

    2017-10-01

    The effective and eco-friendly control of Anopheles vectors plays a key role in any malaria management program. Integrated Vector Management (IVM) suggests making use of the full range of vector control tools available. The strategies for IVM require novel technologies to control outdoor transmission of malaria. Despite the wide number of promising control tools tested against mosquitoes, current strategies for malaria vector control used in most African countries are not sufficient to achieve successful malaria control. The majority of National Malaria Control Programs in Africa still rely on indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs). These methods reduce malaria incidence but generally have little impact on malaria prevalence. In addition to outdoor transmission, growing levels of insecticide resistance in targeted vectors threaten the efficacy of LLINs and IRS. Larvicidal treatments can be useful, but are not recommended for rural areas. The research needed to improve the quality and delivery of mosquito vector control should focus on (i) optimization of processes and methods for vector control delivery; (ii) monitoring of vector populations and biting activity with reliable techniques; (iii) the development of effective and eco-friendly tools to reduce the burden or locally eliminate malaria and other mosquito-borne diseases; (iv) the careful evaluation of field suitability and efficacy of new mosquito control tools to prove their epidemiological impact; (v) the continuous monitoring of environmental changes which potentially affect malaria vector populations; (vi) the cooperation among different disciplines, with main emphasis on parasitology, tropical medicine, ecology, entomology, and ecotoxicology. A better understanding of behavioral ecology of malaria vectors is required. Key ecological obstacles that limit the effectiveness of vector control include the variation in mosquito behavior, development of insecticide resistance, presence of behavioral avoidance, high vector biodiversity, competitive and food web interactions, lack of insights on mosquito dispersal and mating behavior, and the impact of environmental changes on mosquito ecological traits. Overall, the trans-disciplinary cooperation among parasitologists and entomologists is crucial to ensure proper evaluation of the epidemiological impact triggered by novel mosquito vector control strategies. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Optimizing the conditions for in vitro maturation and artificial activation of sika deer (Cervus nippon hortulorum) oocytes.

    PubMed

    Yin, Y; Tang, L; Zhang, P; Kong, D; Wang, Z; Guan, J; Song, G; Tang, B; Li, Z

    2013-02-01

    With the goal of establishing experimental protocols for cloning sika deer, various conditions for in vitro maturation (IVM) and artificial activation of sika deer oocytes were examined. In vitro maturation was evaluated in seven different culture media. The highest rate of oocyte maturation was 75.4% in 10 μg/ml follicle-stimulating hormone (FSH), 1 μg/ml LH, 0.2 mm cysteamine and 50 ng/ml epidermal growth factor (EGF) after 24 h of IVM. The efficiency after 24 h of IVM did not differ significantly (p > 0.05) from that observed after 20 h. Cysteamine (0.2 mm) significantly increased the maturation rates after 20 h (from 59.1% to 67.2%, p < 0.05) and after 24 h (from 63.2% to 71.6%, p < 0.05) of IVM. The IVM rates of oocytes collected during the oestrous season (75.4%) and the anoestrous season (23.3%) were significantly different at 24 h. The 20 μg/ml FSH, 2 μg/ml LH, 0.4 mm cysteamine and 100 ng/ml EGF significantly increased the maturation rates (from 23.3% to 54.2%, p < 0.01) at 24 h during the anoestrous season. For the activation experiments, the most effective method was chemical activation [ionomycin + 6-dimethylaminopurine (6-DMAP)], which promoted the development of sika deer oocytes to the blastocyst stage (32.4%). Our results indicate that in vitro matured sika deer oocytes are good candidates for parthenogenetic activation and that chemical treatment is needed for relatively efficient activation of the oocytes. These optimized conditions for IVM and parthenogenetic activation may be useful for efforts to restore populations of the endangered sika deer using the somatic cell nuclear transfer technique. © 2012 Blackwell Verlag GmbH.

  11. Analysis of the mdr-1 Gene in Patients Co-Infected with Onchocerca volvulus and Loa loa Who Experienced a Post-Ivermectin Serious Adverse Event

    PubMed Central

    Bourguinat, Catherine; Kamgno, Joseph; Boussinesq, Michel; Mackenzie, Charles D.; Prichard, Roger K.; Geary, Timothy G.

    2010-01-01

    Ivermectin (IVM) is exceptionally safe in humans, and is used for mass treatment of onchocerciasis and lymphatic filariasis. However, cases of encephalopathy, sometimes fatal, have been reported in a small number of individuals who harbored large numbers of Loa loa microfilariae (mf). A loss-of-function mutation in the mdr-1 gene in some dog breeds and in mice leads to accumulation of the drug in the brain, causing coma and death. This hypothesis was tested in four individuals from Cameroon who experienced a post-IVM serious adverse event (SAE) and in nine non-SAE matched controls. No loss-of-function mutation was detected in mdr-1 in any subject. However, haplotypes, associated with altered drug disposition, were present as homozygotes in two of the SAE patients (50%), but absent as homozygotes in the controls (0%). An association of high Loa mf load and a genetic predisposition to altered IVM distribution could be involved in IVM SAEs. PMID:20595473

  12. Nebulized fentanyl vs intravenous morphine for ED patients with acute abdominal pain: a randomized double-blinded, placebo-controlled clinical trial.

    PubMed

    Deaton, Travis; Auten, Jonathan D; Darracq, Michael A

    2015-06-01

    Patients with acute abdominal pain commonly present to emergency departments. The safe and effective relief of discomfort is a concern to patients and physicians. Intravenous opioids are the traditional method used to provide pain relief in this setting, but intravenous access is time consuming and not always achievable. Alternative methods of pain control may therefore be necessary for the acute management of painful conditions without adding to the overall physical or psychological discomfort. The purpose of this study was to evaluate the feasibility of nebulized fentanyl (NF) in the alleviation of acute and undifferentiated abdominal pain. We also sought to compare NF with intravenous morphine (IVM) and to assess patient and provider satisfaction with NF. Nebulized fentanyl (2 μg/kg) was compared to IVM (0.1 mg/kg) at 10, 20, 30, and 40 minutes; and patient and physician satisfaction was recorded. The NF group experienced more rapid pain relief and more sustained and clinically significant pain relief over the 40-minute study interval. There were no adverse effects noted in the NF group. Both patient and physician satisfaction scores were higher in the NF group. Fentanyl citrate at a dose of 2 μg/kg through a breath-actuated nebulizer appears to be a feasible and safe alternative to IVM (0.1 mg/kg) in the treatment of acute abdominal pain. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Comparison of Quinn's Advantage fertilization medium and tissue culture medium 199 for in vitro maturation of oocytes.

    PubMed

    Lin, Yu-Hung; Hwang, Jiann-Loung; Huang, Lee-Wen; Seow, Kok-Min; Hsieh, Bih-Chwen; Tzeng, Chii-Ruey

    2014-03-01

    The purpose of the study was to compare the Quinn's Advantage fertilization medium (Q1) and the tissue culture medium 199 (TCM199) for in vitro maturation (IVM) of oocytes and ammonium production during IVM. The immature murine oocytes were randomly added into Q1 and TCM199. Ammonium concentrations were measured at the start and after 18 hours of IVM, and the mature oocytes were fertilized and cultured into blastocysts. The blastocysts were then stained for inner cell mass (ICM) and trophectoderm. The maturation rate was higher in Q1 than in TCM199 (85.7% vs. 76.6%, p = 0.024). The fertilization and blastocyst rates were slightly higher in Q1, but not significant. Differential staining of the blastocysts showed slightly higher ICM ratio in the blastocysts derived from Q1. Mean ammonium concentrations in Q1 and TCM199 at Time 0 were 184.9 and 339.2 μg/dL, respectively (p = 0.05), and after 18 hours of IVM were 268.7 and 443.6 μg/dL, respectively (p = 0.045). Addition of ammonium chloride into Q1 adversely affects IVM. Q1 is superior to TCM199 in terms of oocyte maturation, which may be due to lower ammonium concentration. Copyright © 2014. Published by Elsevier B.V.

  14. Pilot Study to Assess the Efficacy of Ivermectin and Fenbendazole for Treating Captive-Born Olive Baboons (Papio anubis) Coinfected with Strongyloides fülleborni and Trichuris trichiura.

    PubMed

    Reichard, Mason V; Thomas, Jennifer E; Chavez-Suarez, Maria; Cullin, Cassandra O; White, Gary L; Wydysh, Emily C; Wolf, Roman F

    2017-01-01

    In this study, we evaluated the efficacy of combined treatment with ivermectin and fenbendazole (IVM-FBZ) for treating captive olive baboons (Papio anubis) infected with Strongyloides fülleborni and Trichuris trichiura, 2 common nematode parasites of these NHP. Infected baboons were treated for a total of 9 wk with ivermectin (400 μg/kg IM twice weekly) and fenbendazole (50 mg/kg PO once daily for 3 d; 3 rounds of treatment, 21 d apart). Five baboons naturally infected with both S. fülleborni and T. trichiura (n = 4) or S. fülleborni alone (n = 1) received the combination therapy; an additional baboon infected with both parasites served as a nontreated control. The efficacy of IVM-FBZ was measured as the reduction in fecal egg counts of S. fülleborni and T. trichiura as determined by quantitative fecal flotation examination after treatment of baboons with IVM-FBZ. All baboons treated with IVM-FBZ stopped shedding S. fülleborni and T. trichiura eggs by 8 d after treatment and remained negative for at least 161 d. The nontreated control baboon shed S. fülleborni and T. trichiura eggs throughout the study period. Our results indicate that the IVM-FBZ regimen was efficacious for treating olive baboons infected with S. fülleborni and T. trichiura.

  15. Effect of Intravenous Mannitol on Intraocular Pressure in Vitrectomized Silicone-Oil-Filled Eyes.

    PubMed

    Takkar, Brijesh; Chandra, Parijat; Shah, Ritu; Bhatia, Indrish; Roy, Sangeeta; Sihota, Ramanjit

    2017-01-01

    To evaluate the effect of intravenous mannitol (IVM) on intraocular pressure (IOP) in vitrectomized eyes. Thirty-one patients with raised IOP after retinal surgery with silicone oil injection were included. Patients were administered IVM (20% solution, 1g/Kg, over 30 minutes) and IOP was noted at regular intervals. IOP reduction in vitrectomized eyes (Group 1) was compared with the normal eyes (Group 2). Percentage IOP reduction was higher in Group 1 than in Group 2 at all time intervals, 24.5% vs. 19.2% at 15 minutes (p=0.34), 22.6% vs. 9.8% at 45 minutes (p=0.003), 19.1% vs. 9.9% at two hours (p=0.023), and 16.1% vs. 7.8% at four hours (p=0.04), respectively. In Group 1, 40% eyes had an IOP reduction of 2-6 mmHg while 30% eyes had IOP reduction >6 mmHg at four hours post-IVM. IVM is useful for short-term IOP reduction in vitrectomized eyes. IOP reduction is independent of baseline IOP, and sustained and higher as compared to normal eyes.

  16. An intravital microscopy model to study early pancreatic inflammation in type 1 diabetes in NOD mice

    PubMed Central

    Lehmann, Christian; Fisher, Nicholas B.; Tugwell, Barna; Zhou, Juan

    2016-01-01

    ABSTRACT Intravital microscopy (IVM) of the pancreas has been proven to be an invaluable tool in pancreatitis, transplantation and ischemia/reperfusion research. Also in type 1 diabetes (T1D) pancreatic IVM offers unique advantages for the elucidation of the disease process. Female non-obese diabetic (NOD) mice develop T1D spontaneously by 40 weeks of age. Our goal was to establish an IVM-based method to study early pancreatic inflammation in NOD mice, which can be used to screen novel medications to prevent or delay T1D in future studies. This included evaluation of leukocyte-endothelial interactions as well as disturbances of capillary perfusion in the pancreatic microcirculation. PMID:28243521

  17. Scabies community prevalence and mass drug administration in two Fijian villages

    PubMed Central

    Haar, Karin; Romani, Lucia; Filimone, Raikanikoda; Kishore, Kamal; Tuicakau, Meciusela; Koroivueta, Josefa; Kaldor, John M; Wand, Handan; Steer, Andrew; Whitfeld, Margot

    2014-01-01

    Background Scabies has been estimated to affect approximately 300 million people worldwide each year. Scabies rates are high and pose a significant public health problem in Fiji. Community-based comparison treatment trials have not been undertaken. We estimated scabies prevalence and compared the efficacy and tolerability of mass drug administration (MDA) of benzyl benzoate lotion (BB) or oral ivermectin (IVM) in two villages in Fiji. Methods A prospective MDA trial was undertaken in two Fijian villages, comparing three daily applications of BB with single dose IVM or permethrin cream for those aged under two years. The therapies were offered to all community members regardless of the presence of scabies or its symptoms. The difference in prevalence was measured before and after the intervention and absolute risk reduction (ARR) and relative risk (RR) calculated. Results In the BB group, there were 572 eligible participants, of whom 435 (76%) enrolled and 201 (46%) returned for follow-up. In the IVM group, there were 667 eligible participants, of whom 325 (49%) enrolled and 126 (39%) returned. Scabies prevalence was lower after the intervention in both groups. It fell from 37.9 to 20.0% (ARR 18.0%; RR 0.52) in the BB group and from 23.7 to 9.5% (ARR 14.2%; RR 0.40) in the IVM group. Conclusions Our study provides proof of principle that MDA for scabies can reduce scabies prevalence at the community level, and that there was no significant difference in this trial between BB and oral IVM. PMID:24168177

  18. Ion Velocity Measurements for the Ionospheric Connections Explorer

    NASA Astrophysics Data System (ADS)

    Heelis, R. A.; Stoneback, R. A.; Perdue, M. D.; Depew, M. D.; Morgan, W. A.; Mankey, M. W.; Lippincott, C. R.; Harmon, L. L.; Holt, B. J.

    2017-10-01

    The Ionospheric Connections Explorer (ICON) payload includes an Ion Velocity Meter (IVM) to provide measurements of the ion drift motions, density, temperature and major ion composition at the satellite altitude near 575 km. The primary measurement goal for the IVM is to provide the meridional ion drift perpendicular to the magnetic field with an accuracy of 7.5 m s-1 for all daytime conditions encountered by the spacecraft within 15° of the magnetic equator. The IVM will derive this parameter utilizing two sensors, a retarding potential analyzer (RPA) and an ion drift meter (IDM) that have a robust and successful flight heritage. The IVM described here incorporates improvements in the design and operation to produce the most sensitive device that has been fielded to date. It will specify the ion drift vector, from which the component perpendicular to the magnetic field will be derived. In addition it will specify the total ion density, the ion temperature and the fractional ion composition. These data will be used in conjunction with measurements from the other ICON instruments to uncover the important connections between the dynamics of the neutral atmosphere and the ionosphere through the generation of dynamo currents perpendicular to the magnetic field and collisional forces parallel to the magnetic field. Here the configuration and operation of the IVM instrument are described, as well as the procedures by which the ion drift velocity is determined. A description of the subsystem characteristics, which allow a determination of the expected uncertainties in the derived parameters, is also given.

  19. Improved cryotolerance and developmental potential of in vitro and in vivo matured mouse oocytes by supplementing with a glutathione donor prior to vitrification.

    PubMed

    Trapphoff, Tom; Heiligentag, Martyna; Simon, Jenny; Staubach, Nora; Seidel, Thorsten; Otte, Kathrin; Fröhlich, Thomas; Arnold, Georg J; Eichenlaub-Ritter, Ursula

    2016-12-01

    Can supplementation of media with a glutathione (GSH) donor, glutathione ethyl ester (GEE), prior to vitrification protect the mouse oocyte from oxidative damage and critical changes in redox homeostasis, and thereby improve cryotolerance? GEE supplementation supported redox regulation, rapid recovery of spindle and chromosome alignment after vitrification/warming and improved preimplantation development of mouse metaphase II (MII) oocytes. Cryopreservation may affect mitochondrial functionality, induce oxidative stress, and thereby affect spindle integrity, chromosome segregation and the quality of mammalian oocytes. GEE is a membrane permeable GSH donor that promoted fertilization and early embryonic development of macaque and bovine oocytes after IVM. Two experimental groups consisted of (i) denuded mouse germinal vesicle (GV) oocytes that were matured in vitro in the presence or absence of 1 mM GEE (IVM group 1) and (ii) in vivo ovulated (IVO) MII oocytes that were isolated from the ampullae and exposed to 1 mM GEE for 1 h prior to vitrification (IVO group 2). Recovery of oocytes from both groups was followed after CryoTop vitrification/warming for up to 2 h and parthenogenetic activation. Reactive oxygen species (ROS), spindle morphology and chromosome alignment were analyzed by confocal laser scanning microscopy (CLSM) and polarization microscopy in control and GEE-supplemented MII oocytes. The relative overall intra-oocyte GSH content was assessed by analysis of monochlorobimane (MBC)-GSH adduct fluorescence in IVM MII oocytes. The GSH-dependent intra-mitochondrial redox potential (E m GSH ) of IVM MII oocytes was determined after microinjection with specific mRNA at the GV stage to express a redox-sensitive probe within mitochondria (mito-Grx1-roGFP2). The absolute negative redox capacity (in millivolts) was determined by analysis of fluorescence of the oxidized versus the reduced form of sensor by CLSM and quantification according to Nernst equation. Proteome analysis was performed by quantitative 2D saturation gel electrophoresis (2D DIGE). Since microinjection and expression of redox sensor mRNA required removal of cumulus cells, and IVM of denuded mouse oocytes in group 1 induces zona hardening, the development to blastocysts was not assessed after IVF but instead after parthenogenetic activation of vitrified/warmed MII oocytes from both experimental groups. IVM of denuded mouse oocytes in the presence of 1 mM GEE significantly increased intra-oocyte GSH content. ROS was not increased by CryoTop vitrification but was significantly lower in the IVM GEE group compared to IVM without GEE before vitrification and after recovery from vitrification/warming (P < 0.001). Vitrification alone significantly increased the GSH-dependent intra-mitochondrial redox capacity after warming (E m GSH , P < 0.001) in IVM oocytes, presumably by diffusion/uptake of cytoplasmic GSH into mitochondria. The presence of 1 mM GEE during IVM increased the redox capacity before vitrification and there was no further increase after vitrification/warming. None of the reproducibly detected 1492 spots of 2D DIGE separated proteins were significantly altered by vitrification or GEE supplementation. However, IVM of denuded oocytes significantly affected spindle integrity and chromosome alignment right after warming from vitrification (0 h) in group 1 and spindle integrity in group 2 (P < 0.05). GEE improved recovery in IVM group as numbers of oocytes with unaligned chromosomes and aberrant spindles was not significantly increased compared to unvitrified controls. The supplementation with GEE for 1 h before vitrification also supported more rapid recovery of spindle birefringence. GEE improved significantly development to the 2-cell stage for MII oocytes that were activated directly after vitrification/warming in both experimental groups, and also the blastocyst rate in the IVO GEE-supplemented group compared to the controls (P < 0.05). None LIMITATIONS, REASONS FOR CAUTION: The studies were carried out in a mouse model, in IVM denuded rather than cumulus-enclosed oocytes, and in activated rather than IVF MII oocytes. Whether the increased GSH-dependent intra-mitochondrial redox capacity also improves male pronuclear formation needs to be studied further experimentally. The influence of GEE supplementation requires also further examination and optimization in human oocytes before it can be considered for clinical ART. Although GEE supplementation did not alter the proteome at MII, the GSH donor may support cellular homeostasis and redox regulation and, thus, increase developmental competence. While human MII oocyte vitrification is an established procedure, GEE might be particularly beneficial for oocytes that suffer from oxidative stress and reduced redox capacity (e.g. aged oocytes) or possess low GSH due to a reduced supply of GSH from cumulus. It might also be of relevance for immature human oocytes that develop without cumulus to MII in vitro (e.g. in ICSI cycles) for ART. The study has been supported by the German Research Foundation (DFG FOR 1041; EI 199/3-2). There are no conflict of interests. © 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.

  20. Quality of common marmoset (Callithrix jacchus) oocytes collected after ovarian stimulation.

    PubMed

    Kanda, Akifumi; Nobukiyo, Asako; Yoshioka, Miyuki; Hatakeyama, Teruhiko; Sotomaru, Yusuke

    2018-01-15

    The common marmoset (Callithrix jacchus) is an experimental animal that is considered suitable for the creation of next-generation human disease models. It has recently been used in the reproductive technology field. Oocytes can be effectively collected from female marmosets via ovarian stimulation with injections of follicle-stimulating hormone (FSH) and human chorionic gonadotropin (hCG). The oocytes, collected about 28 h after the hCG injection, include both premature oocytes and postmature (in vivo matured; IVO) oocytes, and the premature oocytes can be matured by in vitro culture (in vitro matured; IVM). Although IVM and IVO oocytes are equivalent in appearance at the MII stage, it remains unclear whether there are differences in their properties. Therefore, we investigated their in vitro fertilization and developmental capacities and cytoskeletal statuses. Our findings revealed that the IVM and IVO oocytes had similar fertilization rates but that no IVO oocytes could develop to the blastocyst stage. Additionally, IVO oocytes showed abnormal cytoskeletal formation. It is concluded that IVM oocytes maintain normal function, whereas IVO oocytes would be affected by aging and other factors when they remain for a long time in the ovary. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Live Birth after Rescue In vitro Maturation-intracytoplasmic Sperm Injection in Type 1 Diabetes, Polycystic Ovary Syndrome Patient Using Clomiphene-antagonist Protocol.

    PubMed

    Sankari, Samundi; Elanchezhian, M; Selvamani, Divya; Nagarajan, M; Gopikrishnan, D

    2018-01-01

    Infertility in patients with polycystic ovary syndrome (PCOS) associated with diabetes leads to challenging situations seeking alternative treatments. In vitro maturation (IVM) followed by intracytoplasmic sperm injection (ICSI) could overcome the challenges with promising pregnancies in such patients. In the treatment of a 32-year-old diabetic woman who also had PCOS, single immature oocyte was retrieved. Rescue IVM followed by ICSI yielded a grade 1 day 3 embryo which on transferring resulted in pregnancy and a healthy infant was delivered. Rescue IVM-ICSI could help in achieving pregnancy and live birth. Stimulation involving clomiphene and gonadotropin-releasing hormone antagonist is an effective and patient-friendly protocol for women with PCOS and diabetes and also for poor responders.

  2. Effect of addition of FSH, LH and proteasome inhibitor MG132 to in vitro maturation medium on the developmental competence of yak (Bos grunniens) oocytes.

    PubMed

    Xiao, Xiao; Zi, Xiang-Dong; Niu, Hui-Ran; Xiong, Xian-Rong; Zhong, Jin-Cheng; Li, Jian; Wang, Li; Wang, Yong

    2014-04-22

    The competence for embryonic development after IVF is low in the yak, therefore, we investigated the effects of supplementation of FSH, LH and the proteasome inhibitor MG132 in IVM media on yak oocyte competence for development after IVF. In Experiment 1, yak cumulus-oocyte complexes (COCs) were in vitro matured (IVM) in TCM-199 with 20% fetal calf serum (FCS), 1 microg/mL estradiol-17beta, and different combinations of LH (50 or 100 IU/mL) and FSH (0, 1, 5, 10 microg/mL) at 38.6 degrees C, 5% CO2 in air for 24 h. Matured oocytes were exposed to frozen-thawed, heparin-capacitated yak sperm. Presumptive zygotes were cultured in SOF medium containing 6 mg/ml BSA, 0.5 mg/mL myoinositol, 3% (v/v) essential amino acids, 1% nonessential amino acids and 100 μg/mL L-glutamine (48 h, 38.5 degrees C, 5% CO2, 5% O2, and 90% N2). In Experiment 2, cumulus cells were collected at the end of IVM to determine FSHR and LHR mRNA expression by real-time PCR. In Experiment 3 and 4, COCs were cultured in the presence or absence of the proteasomal inhibitor MG132 from either 0-6 h or 18-24 h after initiation of maturation. The optimum concentration of FSH and LH in IVM media was 5 microg/mL FSH and 50 IU/mL LH which resulted in the greatest cleavage (79.1%) and blastocyst rates (16.1%). Both FSHR and LHR mRNA were detected in yak cumulus cells after IVM. Treatment with MG132 early in maturation reduced (P<0.05) cleavage and blastocyst rates. Conversely, treatment with MG132 late in maturation improved (P<0.05) blastocyst rate. Optimal results with MG132 were achieved at a concentration of 10 microM. An optimum concentration of FSH and LH in IVM medium, and treatment with MG132 late in maturation can improve yak oocytes competence for development after IVF.

  3. Effects of Crocin Supplementation during In Vitro Maturation of Mouse Oocytes on Glutathione Synthesis and Cytoplasmic Maturation

    PubMed Central

    Mokhber Maleki, Elham; Eimani, Hussein; Bigdeli, Mohammad Reza; Golkar Narenji, Afsane; Abedi, Reyhane

    2016-01-01

    Background Crocin is an active ingredient of saffron (Crocus sativus L.) and its antioxidant properties have been previously investigated. This carotenoid scavenges free radicals and stimulates glutathione (GSH) synthesis; consequently, it may protect cells against oxidative stress. The aim of this research is to protect oocytes from oxidative stress by the addition of a natural source antioxidant. Materials and Methods In the present in vitro experimental study, we collected cumulus oocyte complexes (COCs) from mouse ovaries of euthanized, 6-8 week-old female Naval Medical Research Institute (NMRI) mice. Oocytes were subjected to in vitro maturation (IVM) in the presence of either crocin (5 or 10 μg/ml), 5 mM buthionine-[S-R]- sulfoximine (BSO), or the combination of crocin plus BSO. Oocytes that matured in vitro in a medium without crocin or BSO supplements were considered as controls. Following 16-18 hours of IVM, matured oocytes (n=631) were fertilized by capacitated sperm from NMRI male mice, and cultured in vitro for up to 96 hours to assess preimplantation embryonic development. The levels of GSH in metaphase II (MII) oocytes after IVM (n=240) were also assessed by the 5, 5-dithio-bis (2-nitrobenzoic acid) (DTNB)-GSH reductase recycling assay. Results Supplementation of IVM media with 10 µg/ml crocin significantly (P<0.05) increased nuclear maturation, preimplantation development and GSH concentrations compared with the control group. Maturation of oocytes in IVM medium supplemented with BSO alone or the combination of 5 µg/ml crocin and BSO drastically decreased GSH concentrations and subsequently resulted in low rates of maturation, fertilization and blastocyst development. However, the combination of 10 µg/ml crocin with 5 mM BSO increased the level of nuclear maturation which was comparable to the control group. Conclusion Supplementation of IVM media with crocin can improve nuclear maturation rates and subsequent developmental potential of mouse oocytes. This may occur by its beneficial effect in increasing GSH concentrations in MII oocytes. PMID:27123201

  4. Observations of a Two Ribbon White Light Flare

    NASA Astrophysics Data System (ADS)

    Li, J.; Mickey, D.; LaBonte, B.

    2003-05-01

    On July 15 2002, an X3 flare occured within AR10030 and it was accompanied with a white light flare (WLF). The Imaging Vector Magnetograph (IVM) at Mees Solar Observatory recorded the entire event including several hours of data before and after the flare. The IVM continuum images are taken at time cadence as high as 1 seconds per image. Such observations enabled us to resolve the WLF patches in time and space. We will present (1). the initial WLF patch fell on a small sunspot located at an area surrounded with single relatively weak magnetic polarity between proceeding and following sunspot groups; (2) the energy deposited during the WLF flare; (3) the light curves of the optical continuum, the UV continuum (TRACE/1600) and microwaves (1.2 - 18 GHz from Oven's Valley Solar Array). They demonstrate the same profiles during flare impulsive phase. The observations suggest that the origin of the WLF flare was caused by accelerated particles precipitate into lower atmosphere along magnetic field lines. This work is supported by NASA grant to Mess Solar Observatory and MURI program.

  5. Avermectins differentially affect ethanol intake and receptor function: Implications for developing new therapeutics for alcohol use disorders

    PubMed Central

    Asatryan, Liana; Yardley, Megan M.; Khoja, Sheraz; Trudell, James R.; Hyunh, Nhat; Louie, Stan G.; Petasis, Nicos A.; Alkana, Ronald L.; Davies, Daryl L.

    2014-01-01

    Our laboratory is investigating ivermectin (IVM) and other members of the avermectin family as new pharmaco-therapeutics to prevent and/or treat alcohol use disorders (AUDs). Prior work found that IVM significantly reduced ethanol intake in mice and that this effect likely reflects IVM’s ability to modulate ligand-gated ion channels. We hypothesized that structural modifications that enhance IVM’s effects on key receptors and/or increase its brain concentration should improve its anti-alcohol efficacy. We tested this hypothesis by comparing the abilities of IVM and two other avermectins, abamectin (ABM) and selamectin (SEL), to reduce ethanol intake in mice, to alter modulation of GABA ARs and P2X4Rs expressed in Xenopus oocytes and to increase their ability to penetrate the brain. IVM and ABM significantly reduced ethanol intake and antagonized the inhibitory effects of ethanol on P2X4R function. In contrast, SEL did not affect either measure, despite achieving higher brain concentrations than IVM and ABM. All three potentiated GABAA receptor function. These findings suggest that chemical structure and effects on receptor function play key roles in the ability of avermectins to reduce ethanol intake and that these factors are more important than brain penetration alone. The direct relationship between the effect of these avermectins on P2X4R function and ethanol intake suggest that the ability to antagonize ethanol-mediated inhibition of P2X4R function may be a good predictor of the potential of an avermectin to reduce ethanol intake and support the use of avermectins as a platform for developing novel drugs to prevent and/or treat AUDs. PMID:24451653

  6. Insulin resistance does not affect early embryo development but lowers implantation rate in in vitro maturation-in vitro fertilization-embryo transfer cycle.

    PubMed

    Chang, Eun M; Han, Ji E; Seok, Hyun H; Lee, Dong R; Yoon, Tae K; Lee, Woo S

    2013-07-01

    Although extensive evidence indicates the hyperinsulinemia directly contributes to reproductive dysfunction in polycystic ovarian syndrome (PCOS), influence of insulin resistance (IR) on assisted reproductive technology outcomes is poorly understood. In this study we aimed to evaluate the effects of IR on in vitro maturation-in vitro fertilization-embryo transfer (IVM-IVF-ET) in patients with PCOS. Prospective observational study. Women with PCOS (n = 115) commencing IVM. IR (n = 51) and non-IR (n = 64) women with PCOS ready to commence an IVM cycle were recruited. IR was diagnosed using the glucose tolerance test (GTT) and homeostasis model assessment (HOMA) index. Patients with an abnormal GTT and/or HOMA index >2·4 were considered IR. Patients underwent 115 cycles of unstimulated hCG-primed IVM. Maturation, fertilization, cleavage rates, the number of good-quality embryo, and blastocyst formation rates were not significantly different between groups. However, implantation (11·6% vs 28·7%, P = 0·001, respectively), clinical pregnancy (23·5% vs 53·1%, P = 0·002, respectively), and ongoing pregnancy rates (21·6% vs 46·9%. P = 0·006, respectively) were significantly decreased in the IR group. The negative effect of IR on pregnancy outcomes remained after controlling for age, body mass index (BMI) and lipid profiles (OR 4·928, 95% CI 1·735-13·991, P = 0·003). Pregnancy rate after IVM is impaired in IR patients with PCOS. Oocyte development and embryo quality are not affected, suggesting that the effects of hyperinsulinemia on endometrial function and implantation process underlie the decreased pregnancy rate. © 2012 John Wiley & Sons Ltd.

  7. Bone Morphogenetic Protein 15 in the Pro-Mature Complex Form Enhances Bovine Oocyte Developmental Competence

    PubMed Central

    Sudiman, Jaqueline; Sutton-McDowall, Melanie L.; Ritter, Lesley J.; White, Melissa A.; Mottershead, David G.; Thompson, Jeremy G.; Gilchrist, Robert B.

    2014-01-01

    Developmental competence of in vitro matured (IVM) oocytes needs to be improved and this can potentially be achieved by adding recombinant bone morphogenetic protein 15 (BMP15) or growth differentiation factor (GDF9) to IVM. The aim of this study was to determine the effect of a purified pro-mature complex form of recombinant human BMP15 versus the commercially available bioactive forms of BMP15 and GDF9 (both isolated mature regions) during IVM on bovine embryo development and metabolic activity. Bovine cumulus oocyte complexes (COCs) were matured in vitro in control medium or treated with 100 ng/ml pro-mature BMP15, mature BMP15 or mature GDF9 +/− FSH. Metabolic measures of glucose uptake and lactate production from COCs and autofluorescence of NAD(P)H, FAD and GSH were measured in oocytes after IVM. Following in vitro fertilisation and embryo culture, day 8 blastocysts were stained for cell numbers. COCs matured in medium +/− FSH containing pro-mature BMP15 displayed significantly improved blastocyst development (57.7±3.9%, 43.5±4.2%) compared to controls (43.3±2.4%, 28.9±3.7%) and to mature GDF9+FSH (36.1±3.0%). The mature form of BMP15 produced intermediate levels of blastocyst development; not significantly different to control or pro-mature BMP15 levels. Pro-mature BMP15 increased intra-oocyte NAD(P)H, and reduced glutathione (GSH) levels were increased by both forms of BMP15 in the absence of FSH. Exogenous BMP15 in its pro-mature form during IVM provides a functional source of oocyte-secreted factors to improve bovine blastocyst development. This form of BMP15 may prove useful for improving cattle and human artificial reproductive technologies. PMID:25058588

  8. Bone morphogenetic protein 15 in the pro-mature complex form enhances bovine oocyte developmental competence.

    PubMed

    Sudiman, Jaqueline; Sutton-McDowall, Melanie L; Ritter, Lesley J; White, Melissa A; Mottershead, David G; Thompson, Jeremy G; Gilchrist, Robert B

    2014-01-01

    Developmental competence of in vitro matured (IVM) oocytes needs to be improved and this can potentially be achieved by adding recombinant bone morphogenetic protein 15 (BMP15) or growth differentiation factor (GDF9) to IVM. The aim of this study was to determine the effect of a purified pro-mature complex form of recombinant human BMP15 versus the commercially available bioactive forms of BMP15 and GDF9 (both isolated mature regions) during IVM on bovine embryo development and metabolic activity. Bovine cumulus oocyte complexes (COCs) were matured in vitro in control medium or treated with 100 ng/ml pro-mature BMP15, mature BMP15 or mature GDF9 +/- FSH. Metabolic measures of glucose uptake and lactate production from COCs and autofluorescence of NAD(P)H, FAD and GSH were measured in oocytes after IVM. Following in vitro fertilisation and embryo culture, day 8 blastocysts were stained for cell numbers. COCs matured in medium +/- FSH containing pro-mature BMP15 displayed significantly improved blastocyst development (57.7±3.9%, 43.5±4.2%) compared to controls (43.3±2.4%, 28.9±3.7%) and to mature GDF9+FSH (36.1±3.0%). The mature form of BMP15 produced intermediate levels of blastocyst development; not significantly different to control or pro-mature BMP15 levels. Pro-mature BMP15 increased intra-oocyte NAD(P)H, and reduced glutathione (GSH) levels were increased by both forms of BMP15 in the absence of FSH. Exogenous BMP15 in its pro-mature form during IVM provides a functional source of oocyte-secreted factors to improve bovine blastocyst development. This form of BMP15 may prove useful for improving cattle and human artificial reproductive technologies.

  9. Effect of Trans-ε-Viniferin on In Vitro Porcine Oocyte Maturation and Subsequent Developmental Competence in Preimplantation Embryos

    PubMed Central

    JEON, Yubyeol; KWAK, Seong-Sung; CHEONG, Seung-A; SEONG, Yeon Hee; HYUN, Sang-Hwan

    2013-01-01

    ABSTRACT Trans-ε-viniferin is a naturally occurring polyphenol belonging to the stilbenoid family that has been isolated from Vitis amurensis, one of the most common wild grapes in Asia. We investigated the effects of trans-ε-viniferin on in vitro maturation (IVM) and developmental competence after in vitro fertilization (IVF) or parthenogenesis (PA). We observed that trans-ε-viniferin treatment during IVM did not improve nuclear maturation rates of oocytes in any group, but significantly increased (P<0.05) intracellular glutathione (GSH) levels and reduced reactive oxygen species (ROS) levels in the 0.5 µM treatment group. Trans-ε-viniferin treatment during IVM of recipient oocytes promoted higher (P<0.05) expression of DNA methyltransferase-1 (DNMT1) mRNA in the 0.5 µM treatment group as compared with the control group. However, the expression of essential transcriptional and apoptosis-related genes did not significantly differ from that of the control. In cumulus cells, pro-apoptosis gene expressions were changed as apoptosis decreased. Oocytes treated with trans-ε-viniferin during IVM did not have significantly different cleavage rates or blastocyst formation rates after PA, but total cell numbers were significantly higher (P<0.05) in the 0.5 and 5.0 µM treatment groups compared with those in the control group. IVF embryos showed similar results. In conclusion, these results indicate that trans-ε-viniferin treatment during porcine IVM increased the total cell number of blastocysts, possibly by increasing intracellular GSH synthesis, reducing ROS levels, increasing DNMT1 gene expression of oocytes and decreasing pro-apoptosis gene expressions of cumulus cells. PMID:23698084

  10. Scabies community prevalence and mass drug administration in two Fijian villages.

    PubMed

    Haar, Karin; Romani, Lucia; Filimone, Raikanikoda; Kishore, Kamal; Tuicakau, Meciusela; Koroivueta, Josefa; Kaldor, John M; Wand, Handan; Steer, Andrew; Whitfeld, Margot

    2014-06-01

    Scabies has been estimated to affect approximately 300 million people worldwide each year. Scabies rates are high and pose a significant public health problem in Fiji. Community-based comparison treatment trials have not been undertaken. We estimated scabies prevalence and compared the efficacy and tolerability of mass drug administration (MDA) of benzyl benzoate lotion (BB) or oral ivermectin (IVM) in two villages in Fiji. A prospective MDA trial was undertaken in two Fijian villages, comparing three daily applications of BB with single dose IVM or permethrin cream for those aged under two years. The therapies were offered to all community members regardless of the presence of scabies or its symptoms. The difference in prevalence was measured before and after the intervention and absolute risk reduction (ARR) and relative risk (RR) calculated. In the BB group, there were 572 eligible participants, of whom 435 (76%) enrolled and 201 (46%) returned for follow-up. In the IVM group, there were 667 eligible participants, of whom 325 (49%) enrolled and 126 (39%) returned. Scabies prevalence was lower after the intervention in both groups. It fell from 37.9 to 20.0% (ARR 18.0%; RR 0.52) in the BB group and from 23.7 to 9.5% (ARR 14.2%; RR 0.40) in the IVM group. Our study provides proof of principle that MDA for scabies can reduce scabies prevalence at the community level, and that there was no significant difference in this trial between BB and oral IVM. © 2013 The Authors. International Journal of Dermatology published by John Wiley & Sons Ltd on behalf of The International Society of Dermatology.

  11. Impacts of 2,4-dichlorophenoxyacetic acid aquatic herbicide formulations on reproduction and development of the fathead minnow (Pimephales promelas).

    PubMed

    DeQuattro, Zachary A; Karasov, William H

    2016-06-01

    The authors studied the effects of 2 formulations of 2,4-dichlorophenoxyacetic acid, dimethylamine salt (2,4-D) herbicide on fathead minnow reproduction, embryonic development, and larval survival. Groups of reproductively mature fathead minnows were exposed for 28 d to 0.00 ppm, 0.05 ppm, 0.50 ppm, and 2.00 ppm 2,4-D (target) in a flow-through system. Weedestroy® AM40 significantly (p ≤ 0.05) depressed male tubercle presence and significantly increased female gonadosomatic index, and there were statistical trends (0.05 ≤ p ≤ 0.10) for effects on fecundity and hepatic vitellogenin mRNA expression in females and males. The herbicide DMA® 4 IVM also significantly depressed male tubercle presence. Gonads of females exposed to DMA 4 IVM exhibited significantly depressed stage of oocyte maturation, significantly increased severity of oocyte atresia, and a significant presence of an unidentified tissue type. Also, DMA 4 IVM significantly decreased larval survival. It had no impact on hepatic vitellogenin mRNA expression or gonadosomatic index. No significant effects on fertilization, hatchability, or embryonic development were observed in either trial. The formulations tested exhibited different toxicological profiles from pure 2,4-D. These data suggest that the formulations have the potential for endocrine disruption and can exert some degree of chronic toxicity. The present use of 2,4-D formulations in lake management practices and their permitting based on the toxicological profile of 2,4-D pure compound should be reconsidered. Environ Toxicol Chem 2016;35:1478-1488. © 2015 SETAC. © 2015 SETAC.

  12. Intravital microscopy of biosensor activities and intrinsic metabolic states

    PubMed Central

    Winfree, Seth; Hato, Takashi; Day, Richard N.

    2018-01-01

    Intravital microscopy (IVM) is an imaging tool that is capable of detecting subcellular signaling or metabolic events as they occur in tissues in the living animal. Imaging in highly scattering biological tissues, however, is challenging because of the attenuation of signal in images acquired at increasing depths. Depth-dependent signal attenuation is the major impediment to IVM, limiting the depth from which significant data can be obtained. Therefore, making quantitative measurements by IVM requires methods that use internal calibration, or alternatively, a completely different way of evaluating the signals. Here, we describe how ratiometric imaging of genetically encoded biosensor probes can be used to make quantitative measurements of changes in the activity of cell signaling pathways. Then, we describe how fluorescence lifetime imaging can be used for label-free measurements of the metabolic states of cells within the living animal. PMID:28434902

  13. Rapamycin treatment during in vitro maturation of oocytes improves embryonic development after parthenogenesis and somatic cell nuclear transfer in pigs.

    PubMed

    Lee, Joohyeong; Park, Jong-Im; Yun, Jung Im; Lee, Yongjin; Yong, Hwanyul; Lee, Seung Tae; Park, Choon-Keun; Hyun, Sang-Hwan; Lee, Geun-Shik; Lee, Eunsong

    2015-01-01

    This study was conducted to investigate the effects of rapamycin treatment during in vitro maturation (IVM) on oocyte maturation and embryonic development after parthenogenetic activation (PA) and somatic cell nuclear transfer (SCNT) in pigs. Morphologically good (MGCOCs) and poor oocytes (MPCOCs) were untreated or treated with 1 nM rapamycin during 0-22 h, 22-42 h, or 0-42 h of IVM. Rapamycin had no significant effects on nuclear maturation and blastocyst formation after PA of MGCOCs. Blastocyst formation after PA was significantly increased by rapamycin treatment during 22-42 h and 0-42 h (46.6% and 46.5%, respectively) relative to the control (33.3%) and 0-22 h groups (38.6%) in MPCOCs. In SCNT, blastocyst formation tended to increase in MPCOCs treated with rapamycin during 0-42 h of IVM relative to untreated oocytes (20.3% vs. 14.3%, 0.05 < p < 0.1), while no improvement was observed in MGCOCs. Gene expression analysis revealed that transcript abundance of Beclin 1 and microtubule-associated protein 1 light chain 3 mRNAs was significantly increased in MPCOCs by rapamycin relative to the control. Our results demonstrated that autophagy induction by rapamycin during IVM improved developmental competence of oocytes derived from MPCOCs.

  14. Rapamycin treatment during in vitro maturation of oocytes improves embryonic development after parthenogenesis and somatic cell nuclear transfer in pigs

    PubMed Central

    Lee, Joohyeong; Park, Jong-Im; Yun, Jung Im; Lee, Yongjin; Yong, Hwanyul; Lee, Seung Tae; Park, Choon-Keun; Hyun, Sang-Hwan; Lee, Geun-Shik

    2015-01-01

    This study was conducted to investigate the effects of rapamycin treatment during in vitro maturation (IVM) on oocyte maturation and embryonic development after parthenogenetic activation (PA) and somatic cell nuclear transfer (SCNT) in pigs. Morphologically good (MGCOCs) and poor oocytes (MPCOCs) were untreated or treated with 1 nM rapamycin during 0-22 h, 22-42 h, or 0-42 h of IVM. Rapamycin had no significant effects on nuclear maturation and blastocyst formation after PA of MGCOCs. Blastocyst formation after PA was significantly increased by rapamycin treatment during 22-42 h and 0-42 h (46.6% and 46.5%, respectively) relative to the control (33.3%) and 0-22 h groups (38.6%) in MPCOCs. In SCNT, blastocyst formation tended to increase in MPCOCs treated with rapamycin during 0-42 h of IVM relative to untreated oocytes (20.3% vs. 14.3%, 0.05 < p < 0.1), while no improvement was observed in MGCOCs. Gene expression analysis revealed that transcript abundance of Beclin 1 and microtubule-associated protein 1 light chain 3 mRNAs was significantly increased in MPCOCs by rapamycin relative to the control. Our results demonstrated that autophagy induction by rapamycin during IVM improved developmental competence of oocytes derived from MPCOCs. PMID:25797293

  15. Intraoperative intravital microscopy permits the study of human tumour vessels

    PubMed Central

    Fisher, Daniel T.; Muhitch, Jason B.; Kim, Minhyung; Doyen, Kurt C.; Bogner, Paul N.; Evans, Sharon S.; Skitzki, Joseph J.

    2016-01-01

    Tumour vessels have been studied extensively as they are critical sites for drug delivery, anti-angiogenic therapies and immunotherapy. As a preclinical tool, intravital microscopy (IVM) allows for in vivo real-time direct observation of vessels at the cellular level. However, to date there are no reports of intravital high-resolution imaging of human tumours in the clinical setting. Here we report the feasibility of IVM examinations of human malignant disease with an emphasis on tumour vasculature as the major site of tumour-host interactions. Consistent with preclinical observations, we show that patient tumour vessels are disorganized, tortuous and ∼50% do not support blood flow. Human tumour vessel diameters are larger than predicted from immunohistochemistry or preclinical IVM, and thereby have lower wall shear stress, which influences delivery of drugs and cellular immunotherapies. Thus, real-time clinical imaging of living human tumours is feasible and allows for detection of characteristics within the tumour microenvironment. PMID:26883450

  16. Influence of co-culture with denuded oocytes during in vitro maturation on fertilization and developmental competence of cumulus-enclosed porcine oocytes in a defined system.

    PubMed

    Appeltant, Ruth; Somfai, Tamás; Kikuchi, Kazuhiro; Maes, Dominiek; Van Soom, Ann

    2016-04-01

    Co-culture of cumulus-oocyte complexes (COCs) with denuded oocytes (DOs) during in vitro maturation (IVM) was reported to improve the developmental competence of oocytes via oocyte-secreted factors in cattle. The aim of the present study was to investigate if addition of DOs during IVM can improve in vitro fertilization (IVF) and in vitro culture (IVC) results for oocytes in a defined in vitro production system in pigs. The maturation medium was porcine oocyte medium supplemented with gonadotropins, dbcAMP and β-mercaptoethanol. Cumulus-oocyte complexes were matured without DOs or with DOs in different ratios (9 COC, 9 COC+16 DO and 9 COC+36 DO). Consequently; oocytes were subjected to IVF as intact COCs or after denudation to examine if DO addition during IVM would affect cumulus or oocyte properties. After fertilization, penetration and normal fertilization rates of zygotes were not different between all tested groups irrespective of denudation before IVF. When zygotes were cultured for 6 days, no difference could be observed between all treatment groups in cleavage rate, blastocyst rate and cell number per blastocyst. In conclusion, irrespective of the ratio, co-culture with DOs during IVM did not improve fertilization parameters and embryo development of cumulus-enclosed porcine oocytes in a defined system. © 2015 Japanese Society of Animal Science.

  17. Outcome of gestational surrogacy according to IVF protocol.

    PubMed

    Machtinger, Ronit; Duvdevani, Nir-Ram; Lebovitz, Oshrit; Dor, Jehoshua; Hourvitz, Ariel; Orvieto, Raoul

    2017-04-01

    Surrogacy remains the only option for having a biologic child for a unique population of women with severe medical conditions. However, no study has looked at surrogacy outcome as a result of the type of ovarian stimulation of the intended mother [controlled ovarian stimulation (COH), modified natural cycle (MNC), and in vitro maturation (IVM)] for oocyte retrieval. This is a retrospective study, including all intended mothers and gestational carriers in a tertiary, university affiliated, medical center, from 1998 to 2016. Fifty-two women underwent 252 oocyte retrieval cycles. The pregnancy outcome of 212 embryo transfer cycles (64 gestational carriers) was reviewed according to the origin of the embryo. The number of retrieved oocytes was significantly higher following COH (n = 132) compared with IVM (n = 58) and MNC cycles (n = 62) (p = 0.013 and p < 0.0001, respectively). Pregnancy rates for embryos transferred according to each protocol were similar. All pregnancies that ended in live births when oocytes from IVM cycles were used derived from transfers of retrieved mature and mixed mature and immature oocytes. Pregnancies that involved embryos derived solely from immature oocytes that further matured in vitro and were transferred to gestational carriers were unsuccessful. MNC protocol is a good option to achieve pregnancy for intended mothers using gestational surrogacy who have contraindications to COH. The yield of IVM cycles in which immature oocytes are retrieved is inconclusive.

  18. Impact of vitrification on human oocytes before and after in vitro maturation: A systematic review and meta-analysis.

    PubMed

    Mohsenzadeh, Mehdi; Salehi-Abargouei, Amin; Tabibnejad, Nasim; Karimi-Zarchi, Mojgan; Khalili, Mohammad Ali

    2018-05-21

    There are controversies regarding in vitro maturation (IVM) procedure, the time of storing frozen oocytes and maturation stage of vitrified oocytes and its impact on oocytes fertilization capability. The aim of this systematic review and meta-analysis was to evaluate the impact of vitrification on human oocytes during IVM procedure. A systematic review with meta-analysis was undertaken. Main search terms were those related key words. We searched Medline, Embase, Scopus and ISI web of science to detect English-language studies. The final search was performed on 27 January 2018. The original articles which studied laboratory outcomes after vitrification of MII or GV oocytes before or after IVM were included. Exclusion criteria were animal trials and the studies that performed cryopreservation using slow-freeze method. Oocyte maturation, survival, fertilization and cleavage rates were assessed. Bias and quality assessments were applied. 2476 articles were screened and after duplicates removing together with application of inclusion and exclusion criteria, 14 studies assessed for eligibility. Finally 5 studies included for analysis. All studies compared laboratory outcomes between oocytes that vitrified at the GV stage and those which firstly matured in vitro, and then vitrified. Meta-analysis showed that vitrification of oocytes at GV stage had a negative impact on maturation rate (RR = 1.28, 95% CI: 0.96-1.70); but not on cleavage rate (RR = 1.07, 95% CI: 0.70-1.64); fertilization rate (RR = 0.99, 95% CI: 0.85-1.14) and survival rate(RR = 1.01, 95% CI: 0.96-1.06). In general, Based on our results, oocyte vitrification decreases the maturation rate. In addition, survival, fertilization as well as cleavage rates did not significantly differ between the oocytes vitrified before IVM versus oocytes vitrified after IVM. Copyright © 2018. Published by Elsevier B.V.

  19. Prevalence of strongyles and efficacy of fenbendazole and ivermectin in working horses in El Sauce, Nicaragua.

    PubMed

    Kyvsgaard, Niels C; Lindbom, Jenny; Andreasen, Line Lundberg; Luna-Olivares, Luz Adilia; Nielsen, Martin Krarup; Monrad, Jesper

    2011-09-27

    Horses, mules and donkeys are indispensable farming and working animals in many developing countries, and their health status is important to the farmers. Strongyle parasites are ubiquitous in grazing horses world-wide and are known to constitute a threat to equine health. This study determined the prevalence of strongyle infection, the efficacy of ivermectin and fenbendazole treatment, and strongyle re-infection rates of working horses during the dry months in Nicaragua. One hundred and five horses used by farmers for transport of people and goods were randomly allocated into three treatment groups, i.e., the IVM group treated with ivermectin, the FBZ group treated with fenbendazole and the control group treated with placebo. Determined by pre-treatment faecal egg counts (FECs), horses showed a high prevalence (94%) of strongyle parasites with high intensities of infection (mean FEC of 1117 eggs per gram (EPG) with an SD of 860 EPG, n=102). Body condition scores of all horses ranged from 1.5 to 3.5 with a mean of 2.4 (scales 1-5). Fourteen days after treatment faecal egg count reductions (FECRs) were 100% and 94% in the IVM and the FBZ groups, respectively. The egg reappearance period (ERP) defined as the time until the mean FEC reached 20% of the pre-treatment level, was estimated as 42 days for the FBZ group and 60 days for the IVM group. Individual faecal cultures were set up and the larval differentiation revealed a 36% prevalence of Strongylus vulgaris before treatment (n=45). In the FBZ group, 25% of the horses were S. vulgaris-positive 70 days post treatment compared to 11% in the IVM group. Our results indicate that strongyle infection intensities in Nicaragua are high and that S. vulgaris is endemic in the area. Furthermore, efficacies and ERPs of IVM and FBZ were within the expected range with no signs of anthelmintic resistance. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Heat stress effects on the cumulus cells surrounding the bovine oocyte during maturation: altered matrix metallopeptidase 9 and progesterone production.

    PubMed

    Rispoli, L A; Payton, R R; Gondro, C; Saxton, A M; Nagle, K A; Jenkins, B W; Schrick, F N; Edwards, J L

    2013-08-01

    When the effects of heat stress are detrimental during maturation, cumulus cells are intimately associated with the oocyte. To determine the extent to which heat stress affects these cells, in this study, transcriptome profiles of the cumulus that surrounded control and heat-stressed oocytes (41 °C during the first 12 h only and then shifted back to 38.5 °C) during in vitro maturation (IVM) were compared using Affymetrix bovine microarrays. The comparison of cumulus-derived profiles revealed a number of transcripts whose levels were increased (n=11) or decreased (n=13) ≥ twofold after heat stress exposure (P<0.01), sufficient to reduce the development of blastocysts by 46.4%. In a separate study, quantitative PCR (qPCR) was used to confirm heat-induced differences in the relative abundances of the transcripts of five different genes (caveolin 1, matrix metallopeptidase 9, FSH receptor, Indian hedgehog homolog, and inducible nitric oxide synthase). Heat stress exposure resulted in >1.7-fold decrease in the protein levels of latent matrix metallopeptidase 9 (proMMP9). Heat-induced reductions in transcript levels were noted at 6 h IVM with reductions in proMMP9 protein levels at 18 h IVM (P=0.0002). Independent of temperature, proMMP9 levels at 24 h IVM were positively correlated with the development rate of blastocysts (R²=0.36; P=0.002). The production of progesterone increased during maturation; heat-induced increases were evident by 12 h IVM (P=0.002). Both MMP9 and progesterone are associated with the developmental competence of the oocyte; thus, it seems plausible for some of the negative consequences of heat stress on the cumulus-oocyte complex to be mediated through heat-induced perturbations occurring in the surrounding cumulus.

  1. Ivermectin lipid-based nanocarriers as novel formulations against head lice.

    PubMed

    Ullio-Gamboa, Gabriela; Palma, Santiago; Benoit, Jean Pierre; Allemandi, Daniel; Picollo, María Inés; Toloza, Ariel Ceferino

    2017-08-01

    The use of pyrethroids to control the human head louse, Pediculus humanus capitis De Geer (Anoplura: Pediculidae), has suffered considerable loss of efficacy due to the evolution of resistance. Thus, the development of efficiently insecticide delivery systems is imperative for the control of head lice. We studied the insecticidal activity of ivermectin-loaded lipid nanocapsules (IVM-LNC) against permethrin-resistant head lice from Argentina. The LNC, prepared by a phase inversion procedure, were characterized in terms of size, surface potential, and physical stability. These nanoparticles were nearly spherical with mean diameters of 55 nm and narrow size distribution (PI ≤ 0.2). The KT 50 mortality values of head lice after exposure to two IVM-LNC formulations (0.11 and 0.28%) were significantly smaller (5 and 3 h, respectively) compared to those exposed only to LNC control group (8 h). This investigation showed the effectiveness in the encapsulation of ivermectin (IVM) into stable LNC dispersion with a potential clinical activity against head lice.

  2. Intravital imaging by simultaneous label-free autofluorescence-multiharmonic microscopy.

    PubMed

    You, Sixian; Tu, Haohua; Chaney, Eric J; Sun, Yi; Zhao, Youbo; Bower, Andrew J; Liu, Yuan-Zhi; Marjanovic, Marina; Sinha, Saurabh; Pu, Yang; Boppart, Stephen A

    2018-05-29

    Intravital microscopy (IVM) emerged and matured as a powerful tool for elucidating pathways in biological processes. Although label-free multiphoton IVM is attractive for its non-perturbative nature, its wide application has been hindered, mostly due to the limited contrast of each imaging modality and the challenge to integrate them. Here we introduce simultaneous label-free autofluorescence-multiharmonic (SLAM) microscopy, a single-excitation source nonlinear imaging platform that uses a custom-designed excitation window at 1110 nm and shaped ultrafast pulses at 10 MHz to enable fast (2-orders-of-magnitude improvement), simultaneous, and efficient acquisition of autofluorescence (FAD and NADH) and second/third harmonic generation from a wide array of cellular and extracellular components (e.g., tumor cells, immune cells, vesicles, and vessels) in living tissue using only 14 mW for extended time-lapse investigations. Our work demonstrates the versatility and efficiency of SLAM microscopy for tracking cellular events in vivo, and is a major enabling advance in label-free IVM.

  3. Effects of oral contraceptives and metformin on the outcome of in vitro maturation in infertile women with polycystic ovary syndrome.

    PubMed

    Zhao, Jun-Zhao; Lin, Jin-Ju; Yang, Hai-Yan; Zhang, Wei; Huang, Xue-Feng; Huang, Yin-Ping

    2010-02-01

    Abstract Objective: To evaluate the effects of oral contraceptives and metformin on the outcome of in vitro maturation (IVM) in infertile women with polycystic ovary syndrome (PCOS). This is a retrospective study of 108 women with PCOS, subject to 152 cycles of IVM treatment. The study was held at the Reproductive Medicine Center of the First Affiliated Hospital of Wenzhou Medical College, People's Republic of China. Before entering IVM treatment, 54 patients who received oral contraceptive pill (marvelon, 0.15 mg desogestrel, and 0.03 mg ethinylestradiol), one tablet every day, and metformin 500 mg twice or three times per day were defined as the pretreated group, and another 64 patients who were not administered any drugs as the control group. The main outcome measures were the rates of oocyte maturation, fertilization, cleavage, miscarriage, clinical pregnancy, and live birth. There were no significant differences between the two groups in the rates of oocyte maturation, fertilization, cleavage, and clinical pregnancy (p > 0.05). A significantly lower miscarriage rate was obtained in the pretreated group than in the control group (16.13% vs 4.0%, p < 0.01). The live birth rate per embryo transfer seemed to be higher in the pretreated group than in the control group (37.70% vs 30.38%, p = 0.363), but was not statistically significant. Pretreatment with oral contraceptives and metformin improved the outcome of IVM related to the miscarriage rate and possibly also live birth rate.

  4. Preservation of primordial follicles from lions by slow freezing and xenotransplantation of ovarian cortex into an immunodeficient mouse.

    PubMed

    Wiedemann, C; Hribal, R; Ringleb, J; Bertelsen, M F; Rasmusen, K; Andersen, C Y; Kristensen, S G; Jewgenow, K

    2012-12-01

    Assisted reproductive technology (ART) is considered an important tool in the conservation of endangered species, but often the most limiting factor of ART is the availability of mature oocytes. The aim of the present study was to investigate the feasibility of preserving female germ cells from ovaries of female lions (Panthera leo). Good quality cumulus-oocyte complexes (COCs) were isolated and subjected to in vitro maturation (IVM). In addition, ovarian cortex was obtained and cut into pieces for culture and cryopreservation by slow freezing. The survival of ovarian follicles was assessed by histology. Frozen-thawed samples of ovarian cortex samples were xenotransplanted under the skin of ovariectomized immunodeficient mouse for 28 days. Overall, 178 intact COCs were obtained from 13 lions, but only 28.1% were matured in vitro indicating insufficient IVM conditions. In contrast, almost all follicles within the ovarian cortex survived culture when the original sample was from a young healthy lion collected immediately after euthanasia. Within the xenotransplants, the number of primordial follicles decreased after 28 days by 20%, but the relation between primordial and growing follicles changed in favour of follicular growth. Female gamete rescue from valuable felids may be performed by slow freeze cryopreservation of ovarian cortex. Although the IVM protocol for lions is not yet optimized, mature oocytes may be obtained after long-term xenotransplantation and IVM and could potentially represent one way of salvage of endangered felid species in the future. © 2012 Blackwell Verlag GmbH.

  5. N-3 polyunsaturated fatty acid DHA during IVM affected oocyte developmental competence in cattle.

    PubMed

    Oseikria, Mouhamad; Elis, Sébastien; Maillard, Virginie; Corbin, Emilie; Uzbekova, Svetlana

    2016-06-01

    The positive effect of n-3 polyunsaturated fatty acids (FAs) on fertility in ruminants seems to be partly mediated through direct effects on the oocyte developmental potential. We aimed to investigate whether supplementation with physiological levels of docosahexaenoic acid (DHA, C22:6 n-3 polyunsaturated fatty acids) during IVM has an effect on oocyte maturation and in vitro embryo development in cattle. We reported that DHA (0, 1, 10, or 100 μM) had no effect on oocyte viability or maturation rate after 22-hour IVM. Incubation of oocyte-cumulus complexes with 1-μM DHA during IVM significantly increased (P < 0.05) oocyte cleavage rate as compared with control (86.1% vs. 78.8%, respectively) and the greater than 4-cell embryo rate at Day 2 after parthenogenetic activation (39.1% vs. 29.7%, respectively). Supplementation with 1 μM DHA during IVM also induced a significant increase in the blastocyst rate at Day 7 after IVF as compared with control (30.6% vs. 17.6%, respectively) and tended to increase the number of cells in the blastocysts (97.1 ± 4.9 vs. 81.2 ± 5.3, respectively; P = 0.08). On the contrary, 10-μM DHA had no effects, whereas 100-μM DHA significantly decreased the cleavage rate compared with control (69.5% vs.78.8%, respectively) and the greater than 4-cell embryo rate at Day 2 after parthenogenetic activation (19.5% vs. 29.7%). As was shown by real-time polymerase chain reaction, negative effects of 100-μM DHA were associated with significant increase of progesterone synthesis by oocyte-cumulus complexes, a three-fold increase in expression level of FA transporter CD36 and a two-fold decrease of FA synthase FASN genes in cumulus cells (CCs) of corresponding oocytes. Docosahexaenoic acid at 1 and 10 μM had no effect on expression of those and other key lipid metabolism-related genes in CC. In conclusion, administration of a low physiological dose of DHA (1 μM) during IVM may have beneficial effects on oocyte developmental competence in vitro without affecting lipid metabolism gene expression in surrounding CCs, contrarily to 100 μM DHA which diminished oocyte quality associated with perturbation of lipid and steroid metabolism in CC. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Safety and clinical efficacy of tenvermectin, a novel antiparasitic 16-membered macrocyclic lactone antibiotics.

    PubMed

    Fei, Chenzhong; She, Rufeng; Li, Guiyu; Zhang, Lifang; Fan, Wushun; Xia, Suhan; Xue, Feiqun

    2018-05-30

    Tenvermectin (TVM) is a novel 16-membered macrocyclic lactone antibiotics, which contains component TVM A and TVM B. However there is not any report on safety and clinical efficacy of TVM for developing as a potential drug. In order to understand the part of safety and clinical efficacy of TVM, we conducted the acute toxicity test, the standard bacterial reverse mutation (Ames) test and the clinical deworming test. In the acute toxicity studies, TVM, TVM A and ivermectin (IVM) were administrated once by oral gavage to mice and rats. Results showed that the oral LD 50 values of TVM, TVM A and IVM in mice were 74.41, 106.95 and 53.06 mg/kg respectively. The oral LD 50 values of TVM and TVM A in rats were determined to be 164.22 and 749.34 mg/kg respectively. TVM and IVM are moderately toxic substances, meanwhile the TVM A belongs to low toxic compounds, implying that the acute toxicity is highly related to the length of side chain of TVM at position C25. In the Ames test, results showed that TVM did not induce mutagenicity in Salmonella typhimurium TA97a, TA98, TA100, TA102 and TA1535 with and without metabolic activation system, speculating that the mutagenicity is probably not related to the side chain at position C25 of 16-membered macrocyclic lactone antibiotics. In the efficacy trail of TVM against swine nematodes, growing pigs natural infection of Ascaris suum and Trichuris suis were treated with a single subcutaneous injection 0.3 mg/kg b.w.. Results showed that TVM and IVM had excellent effect in expelling Ascaris suum, and TVM had potential efficacy against Trichuris suis, however IVM had no effect on Trichuris suis. This study suggests that the side chain of TVM at position C25 may have important biological functions, which is one of the key sites of the studies on structure-activity relationship of 16-membered macrocyclic lactone compounds. TVM is a new compound exhibited some advantages worthy of developing. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Ivermectin dissipation and movement from feces to soil under field conditions.

    PubMed

    Iglesias, Lucía Emilia; Saumell, Carlos; Sagüés, Federica; Sallovitz, Juan Manuel; Lifschitz, Adrián Luis

    2018-01-02

    The aim of this work was to evaluate the fate of ivermectin (IVM) at two concentrations in cattle feces and its movement to the nearby soil and plants. Feces were spiked with IVM at two levels: 3000 ng g -1 (high group, HG) and 300 ng g -1 (low group, LG). Artificial dung pats were prepared and deposited in an experimental field area. Feces and underlying soil were sampled up to 60 days post-deposition (dpd). As an additional analysis, grasses growing around the pats were sampled at 30 and 60 dpd. Ivermectin concentrations in all matrices were determined by HPLC. Mean IVM fecal concentrations were in the range between 3901.9 ng g -1 and 2419.2 ng g -1 (high group) and 375.3 ng g -1 and 177.49 ng g -1 (low group). Mean times for 50% and 90% dissipation were 88.23 and 293.03 days (HG) and 39.1 and 129.9 days (LG). Soil concentrations ranged from 26.1 ng g -1 to 71.1 ng g -1 (HG) and 3.4 to 5.9 ng g -1 (LG); in plants, concentrations were between 71.4 and 380.8 ng g -1 and 5.40 and 51.8 ng g -1 in HG and LG, respectively. These results confirm that IVM moves from feces to the underlying soil as well as to nearby plants. The potential risk of detrimental effects on soil organisms and the impact on herbivorous animals should be further evaluated.

  8. Outcomes of in vitro fertilization cycles among patients with polycystic ovary syndrome following ovarian puncture for in vitro maturation.

    PubMed

    Lin, Jia; Wang, Peiyu; Zhao, Junzhao; Xiao, Shiquan; Yu, Rong; Jin, Congcong; Zhu, Ruru

    2016-12-01

    To investigate the effects of ovarian puncture for in vitro maturation (IVM) on subsequent in vitro fertilization (IVF) embryo transfer cycles in patients with polycystic ovary syndrome (PCOS). A retrospective study included data from patients admitted to the First Affiliated Hospital of Wenzhou Medical University, China, between January 1, 2008 and December 31, 2014. Patients with PCOS undergoing IVF cycles after having been treated with IVM unsuccessfully were included as the study group and an IVF-procedure data-matched control group of patients undergoing their first IVF cycles was included in a 1:4 ratio. Patients with reproductive anomalies were excluded. Endocrine-hormone levels and antral follicle counts were measured and fertilization-related outcomes were evaluated. There were 49 patients included in the study group and 196 included in the control group. Within the study group, basal luteal-hormone, testosterone, and antral follicle count levels were significantly lower following IVM treatment. The total gonadotropin dose was lower (P<0.001) and the duration of stimulation was shorter (P<0.001) in the study group compared with the control group. The clinical-pregnancy rate was higher in the study group (P=0.018) and no difference was observed between the groups in ovarian hyper-stimulation syndrome (P=0.633). Previous IVM resulted in improved endocrine profiles and increased clinical-pregnancy rates among patients with PCOS undergoing IVF cycles. Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  9. Tretinoin-loaded lipid-core nanocapsules decrease reactive oxygen species levels and improve bovine embryonic development during in vitro oocyte maturation.

    PubMed

    Lucas, Caroline Gomes; Remião, Mariana Härter; Komninou, Eliza Rossi; Domingues, William Borges; Haas, Cristina; Leon, Priscila Marques Moura de; Campos, Vinicius Farias; Ourique, Aline; Guterres, Silvia S; Pohlmann, Adriana R; Basso, Andrea Cristina; Seixas, Fabiana Kömmling; Beck, Ruy Carlos Ruver; Collares, Tiago

    2015-12-01

    In vitro oocyte maturation (IVM) protocols can be improved by adding chemical supplements to the culture media. Tretinoin is considered an important retinoid in embryonic development and its association with lipid-core nanocapsules (TTN-LNC) represents an innovative way of improving its solubility, and chemical stability, and reducing its toxicity. The effects of supplementing IVM medium with TTN-LNC was evaluated by analyzing production of reactive oxygen species (ROS), S36-phosphorilated-p66Shc levels and caspase activity in early embryonic development, and expression of apoptosis and pluripotency genes in blastocysts. The lowest concentration tested (0.25μM) of TTN-LNC generated higher blastocyst rate, lower ROS production and S36-p66Shc amount. Additionally, expression of BAX and SHC1 were lower in both non-encapsulated tretinoin (TTN) and TTN-LNC-treated groups. Nanoencapsulation allowed the use of smaller concentrations of tretinoin to supplement IVM medium thus reducing toxic effects related with its use, decreasing ROS levels and apoptose frequency, and improving the blastocyst rates. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Investigation of timing effects in modified composite quadrupolar echo pulse sequences by mean of average Hamiltonian theory

    NASA Astrophysics Data System (ADS)

    Mananga, Eugene Stephane

    2018-01-01

    The utility of the average Hamiltonian theory and its antecedent the Magnus expansion is presented. We assessed the concept of convergence of the Magnus expansion in quadrupolar spectroscopy of spin-1 via the square of the magnitude of the average Hamiltonian. We investigated this approach for two specific modified composite pulse sequences: COM-Im and COM-IVm. It is demonstrated that the size of the square of the magnitude of zero order average Hamiltonian obtained on the appropriated basis is a viable approach to study the convergence of the Magnus expansion. The approach turns to be efficient in studying pulse sequences in general and can be very useful to investigate coherent averaging in the development of high resolution NMR technique in solids. This approach allows comparing theoretically the two modified composite pulse sequences COM-Im and COM-IVm. We also compare theoretically the current modified composite sequences (COM-Im and COM-IVm) to the recently published modified composite pulse sequences (MCOM-I, MCOM-IV, MCOM-I_d, MCOM-IV_d).

  11. Infertility treatment for azoospermic patients with a history of infectious parotitis (mumps) using combined techniques.

    PubMed

    Zhang, Shuiwen; Li, Jianhua; Zhou, Guoping; Qin, Silong; Xin, Nan; Guo, Junhong; Xu, Ye

    2013-12-01

    The purpose of this study was to investigate the clinical efficacy of in vitro maturation-intracytoplasmic sperm injection (IVM-ICSI) technique on the treatment of azoospermic patients with a history of infectious parotitis (mumps). Spermatozoa were obtained from the testes of azoospermic patients with a history of mumps and fertilized by ICSI. Eggs were retrieved from the spouse of patients in the natural cycle. Fertilized embryos were transferred into the uterus of patients' respective spouses. Live sperm were retrieved from 16 of out of 24 (67%) azoospermic patients with a history of mumps. Using IVM-ICSI, the normal fertilization rate was 71.2%. A total of 23 treatment cycles were completed in the spouses of 16 patients and of these, 9 patients' spouses became pregnant (a pregnancy rate of 39.1%). The success rate for infertility treatment of mumps patients was equally high at 56.3% (9/16). The IVM-ICSI technique is a simple, effective and economic method for infertility treatment in azoospermic patients with a history of mumps.

  12. Investigations of oocyte in vitro maturation within a mouse model.

    PubMed

    Chin, Alexis Heng Boon; Chye, Ng Soon

    2004-02-01

    This study attempted to develop a 'less meiotically competent' murine model for oocyte in vitro maturation (IVM), which could more readily be extrapolated to human clinical assisted reproduction. Oocyte meiotic competence was drastically reduced upon shortening the standard duration of in vivo gonadotrophin stimulation from 48 h to 24 h, and by selecting only naked or partially naked germinal vesicle oocytes, instead of fully cumulus enclosed oocyte complexes. With such a less meiotically competent model, only porcine granulosa coculture significantly enhanced the oocyte maturation rate in vitro, whereas no significant enhancement was observed with macaque and murine granulosa coculture. Increased serum concentrations and the supplementation of gonadotrophins, follicular fluid and extracellular matrix gel within the culture medium did not enhance IVM under either cell-free or coculture conditions. Culture medium conditioned by porcine granulosa also enhanced the maturation rate, and this beneficial effect was not diminished upon freeze-thawing. Enhanced IVM in the presence of porcine granulosa coculture did not, however, translate into improved developmental competence, as assessed by in vitro fertilization and embryo culture to the blastocyst stage.

  13. Nose and vein, speed and pain: comparing the use of intranasal diamorphine and intravenous morphine in a Scottish paediatric emergency department.

    PubMed

    Regan, Luke; Chapman, Andrew R; Celnik, Anna; Lumsden, Lesley; Al-Soufi, Reem; McCullough, Nicola P

    2013-01-01

    Urgent analgesia is essential for all children who present in severe pain, but difficulties in obtaining venous access can delay the use of adequate opiate analgesia. Intranasal diamorphine (IND) is now in use in around 60% of emergency departments and is the preferred choice of analgesia as reported by both parents and healthcare professionals. While IND has similar efficacy to intramuscular morphine in children, no study has compared its use against the current gold standard, intravenous morphine (IVM). IND was introduced to the Royal Aberdeen Children's Hospital on 24 December 2009. A retrospective case series was constructed to compare its clinical performance with its predecessor IVM. Three unexplored factors were investigated: time to opiate analgesia, the requirement for further analgesia when still in the emergency department and the effect of simple coanalgesia (eg, paracetamol/ibuprofen) on these requirements. 297 patients were eligible for the study (147 IND, 150 IVM) over a 28-month period. There was a non-significant trend to a longer median time to administration of analgesia in patients receiving IND (p=0.170). Patients who received IND were less likely to require further analgesia (p<0.001). Both groups were less likely to require further analgesia when simple coanalgesia was given (p=0.049). The authors found no significant difference in time to administration of analgesia between agents, but a learning curve has been identified. Sustained effort should be placed on the use of simple coanalgesia. The clinical performance of IND compares favourably with IVM in children with severe pain, and it remains an appropriate preferred agent.

  14. Effects of ghrelin on activation of Akt1 and ERK1/2 pathways during in vitro maturation of bovine oocytes.

    PubMed

    Chouzouris, Thomas-Markos; Dovolou, Eleni; Krania, Fotini; Pappas, Ioannis S; Dafopoulos, Konstantinos; Messinis, Ioannis E; Anifandis, George; Amiridis, Georgios S

    2017-04-01

    The purpose of this study was to investigate the possible molecular pathways through which ghrelin accelerates in vitro oocyte maturation. Bovine cumulus-oocyte complexes (COCs), after 18 or 24 h maturation in the absence or the presence of 800 pg ml-1 of acylated ghrelin were either assessed for nuclear maturation or underwent in vitro fertilization in standard media and putative zygotes were cultured in vitro for 8 days. In a subset of COCs the levels of phosphorylated Akt1 and ERK1/2 (MAPK1/3) were assessed at the 0th, 6th, 10th, 18th and 24th hours of in vitro maturation (IVM). At 18 and 24 h no difference existed in the proportion of matured oocytes in the ghrelin-treated group, while in the control group more (P < 0.05) matured oocyte were found at 24 h. Oocyte maturation for 24 h in the presence of ghrelin resulted in substantially reduced (P < 0.05) blastocyst yield(16.3%) in comparison with that obtained after 18 h (30.0%) or to both control groups (29.3% and 26.9%, for 18 and 24 h in maturation, respectively). Ghrelin-treated oocytes expressed lower Akt1 phosphorylation rate at the 10th hour of IVM, and higher ERK1/2 at the 6th and 10th hours of IVM compared with controls. In cumulus cells, at the 18th and 24th hours of IVM Akt1 phosphorylation rate was higher in ghrelin-treated oocytes. Our results imply that ghrelin acts in a different time-dependent manner on bovine oocytes and cumulus cells modulating Akt1 and ERK1/2 phosphorylation, which brings about acceleration of the oocyte maturation process.

  15. Overexpression of hyaluronan synthase 2 and gonadotropin receptors in cumulus cells of goats subjected to one-shot eCG/FSH hormonal treatment for ovarian stimulation.

    PubMed

    Santos, Juliana D R; Batista, Ribrio I T P; Magalhães, Livia C; Paula, Alexandre R; Souza, Samara S; Salamone, Daniel F; Bhat, Maajid H; Teixeira, Dárcio I A; Freitas, Vicente J F; Melo, Luciana M

    2016-07-01

    Hormonal ovarian stimulation may affect transcripts in somatic cells of cumulus-oocyte complexes (COCs) and affect the resulting oocyte quality. Here, in parallel with morphological classification and in vitro maturation (IVM) rate analysis, we investigated the expression of hyaluronan synthase 2 (HAS2), gonadotropic receptors (FSHR and LHR) and connexin 43 (GJA1) in cumulus cells (CCs) from goat COCs after multi-dose FSH (MD) or one-shot FSH/eCG (OS) treatments, using bovine COCs as control groups. The MD treatment produced more large follicles, and the resulting COCs had a better morphology and IVM rate than were obtained with OS. The OS treatment produced COCs with increased HAS2, FSHR, LHR and GJA1 expression. This gene expression pattern was also observed in the CCs of COCs that showed poor morphological characteristics. On the other hand, the mRNA levels were more similar between groups after IVM; FSHR and LHR were the main genes that showed decreased expression. Some events that occurred in bovine CCs during IVM, such as cell expansion, increased HAS2 expression and decreased GJA1 expression, were less evident or did not occur in goat COCs. In conclusion, increasing HAS2, FSHR, LHR and GJA1 expression in goat COCs does not confer greater meiotic competence to oocytes. Instead, it may result from poor regulation of gene expression in CCs by lower quality oocytes. Finally, cumulus expansion, together with HAS2 upregulation and GJA1 downregulation, seems to be more important for bovine COCs than for goat COCs. Additional studies are needed to investigate the importance of other HAS isoforms and connexins in goat COCs. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Efficacy, Safety, and Pharmacokinetics of Coadministered Diethylcarbamazine, Albendazole, and Ivermectin for Treatment of Bancroftian Filariasis.

    PubMed

    Thomsen, Edward K; Sanuku, Nelly; Baea, Manasseh; Satofan, Samson; Maki, Elit; Lombore, Bart; Schmidt, Mark S; Siba, Peter M; Weil, Gary J; Kazura, James W; Fleckenstein, Lawrence L; King, Christopher L

    2016-02-01

    Available treatments for lymphatic filariasis (LF) are limited in their longterm clearance of microfilaria from the blood. The safety and efficacy of a single-dose triple-drug therapy of the antifilarial drugs diethylcarbamazine (DEC), ivermectin (IVM), and albendazole (ALB) for LF are unknown. We performed a pilot study to test the efficacy, safety, and pharmacokinetics of single-dose DEC, IVM, and ALB in Wuchereria bancrofti-infected Papua New Guineans. Adults were randomized into 2 treatment arms, DEC 6 mg/kg + ALB 400 mg (N = 12) or DEC 6 mg/kg + ALB 400 mg + IVM 200 μg/kg (N = 12), and monitored for microfilaria, parasite antigenemia, adverse events (AEs), and serum drug levels. Triple-drug therapy induced >2-log reductions in microfilaria levels at 36 and 168 hours after treatment compared with approximately 1-log reduction with 2 drugs. All 12 individuals who received 3 drugs were microfilaria negative 1 year after treatment, whereas 11 of 12 individuals in the 2-drug regimen were microfilaria positive. In 6 participants followed 2 years after treatment, those who received 3 drugs remained microfilaria negative. AEs, particularly fever, myalgias, pruritus, and proteinuria/hematuria, occurred in 83% vs 50% of those receiving triple-drug compared to 2-drug treatment respectively (P = .021); all resolved within 7 days after treatment. No serious AEs were observed in either group. There was no significant effect of IVM on DEC or ALB drug levels. Triple-drug therapy is safe and more effective than DEC + ALB for Bancroftian filariasis and has the potential to accelerate elimination of lymphatic filariasis. NCT01975441. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  17. Current procedures of the integrated urban vector-mosquito control as an example in Cotonou (Benin, West Africa) and Wrocław area (Poland).

    PubMed

    Rydzanicz, Katarzyna; Lonc, Elzbieta; Becker, Norbert

    2009-01-01

    Current strategy of Integrated Vector Management (IVM) comprises the general approach of environmentally friendly control measures. With regard to mosquitoes it includes first of all application of microbial insecticides based on Bacillus thuringiensis israelensis (Bti) and B. sphaericus (Bs) delta-endotoxins as well as the reduction of breeding habitats and natural enemy augmentation. It can be achieved thorough implementation of the interdisciplinary program, i. e., understanding of mosquito vector ecology, the appropriate vector-diseases (e. g., malariometric) measurements and training of local personnel responsible for mosquito abatement activities, as well as community involvement. Biocontrol methods as an alternative to chemical insecticides result from the sustainability development concept, growing awareness of environmental pollution and the development of insecticide-resistant strains of vector-mosquito populations in many parts of the world. Although sustainable trends are usually considered in terms of the monetary and training resources within countries, environmental concerns are actually more limiting factors for the duration of an otherwise successful vector control effort. In order to meet these new needs, increasing efforts have been made in search of and application of natural enemies, such as parasites, bacterial pathogens and predators which may control populations of insect vectors. The biological control agent based on the bacterial toxins Bti and Bs has been used in the Wrocław's University and Municipal Mosquito Control Programs since 1998. In West-Africa biocontrol appears to be an effective and safe tool to combat malaria in addition to bed-nets, residual indoor spraying and appropriate diagnosis and treatment of malaria parasites which are the major tools in the WHO Roll Back Malaria Program. IVM studies carried out 2005-2008 in Cotonou (Benin) as well those in Wrocław Irrigated Fields during the last years include the following major steps: 1. Mapping of all breeding sites in the project area and recording data in a geographical information system (GIS/relational database). All districts, streets and houses are numbered for quick reference during the operation; 2. Studying mosquito vector bionomics, migration and vectorial capacity in the project area, before, during and after the routine Bti treatments; 3. Assessment of the optimum for effective larvicide insecticide dosages at major breeding sites against the different target mosquito species; 4. Implementation of the microbial control agents in the integrated routine program. Adaptation of the application equipment to the local situation, training of the field staff, and routine treatments; 5. Conducting surveillance of vector-disease (e. g., malariometric) parameters in the control and experimental area before, during, and after the application of biocontrol agents.

  18. RNA-Seq transcriptome profiling of mouse oocytes after in vitro maturation and/or vitrification.

    PubMed

    Gao, Lei; Jia, Gongxue; Li, Ai; Ma, Haojia; Huang, Zhengyuan; Zhu, Shien; Hou, Yunpeng; Fu, Xiangwei

    2017-10-16

    In vitro maturation (IVM) and vitrification have been widely used to prepare oocytes before fertilization; however, potential effects of these procedures, such as expression profile changes, are poorly understood. In this study, mouse oocytes were divided into four groups and subjected to combinations of in vitro maturation and/or vitrification treatments. RNA-seq and in silico pathway analysis were used to identify differentially expressed genes (DEGs) that may be involved in oocyte viability after in vitro maturation and/or vitrification. Our results showed that 1) 69 genes were differentially expressed after IVM, 66 of which were up-regulated. Atp5e and Atp5o were enriched in the most significant gene ontology term "mitochondrial membrane part"; thus, these genes may be promising candidate biomarkers for oocyte viability after IVM. 2) The influence of vitrification on the transcriptome of oocytes was negligible, as no DEGs were found between vitrified and fresh oocytes. 3) The MII stage is more suitable for oocyte vitrification with respect to the transcriptome. This study provides a valuable new theoretical basis to further improve the efficiency of in vitro maturation and/or oocyte vitrification.

  19. Hydrostatic pressure affects in vitro maturation of oocytes and follicles and increases granulosa cell death.

    PubMed

    Rashidi, Zahra; Azadbakht, Mehri; Amini, Ali; Karimi, Isac

    2014-01-01

    This study examines the effects of hydrostatic pressure on in vitro maturation (IVM) of oocytes derived from in vitro grown follicles. In this experimental study, preantral follicles were isolated from 12-day-old female NMRI mice. Each follicle was cultured individually in Alpha Minimal Essential Medium (α-MEM) under mineral oil for 12 days. Then, follicles were induced for IVM and divided into two groups, control and experiment. In the experiment group follicles were subjected to 20 mmHg pressure for 30 minutes and cultured for 24-48 hours. We assessed for viability and IVM of the oocytes. The percentage of apoptosis in cumulus cells was determined by the TUNEL assay. A comparison between groups was made using the student's t test. The percentage of metaphase II oocytes (MII) increased in hydrostatic pressuretreated follicles compared to controls (p<0.05). Cumulus cell viability reduced in hydrostatic pressure-treated follicles compared to controls (p<0.05). Exposure of follicles to pressure increased apoptosis in cumulus cells compared to controls (p<0.05). Hydrostatic pressure, by inducing apoptosis in cumulus cells, participates in the cumulus oocyte coupled relationship with oocyte maturation.

  20. microRNAs and Their Targets in Apple (Malus domestica cv. "Fuji") Involved in Response to Infection of Pathogen Valsa mali.

    PubMed

    Feng, Hao; Xu, Ming; Zheng, Xiang; Zhu, Tongyi; Gao, Xiaoning; Huang, Lili

    2017-01-01

    miRNAs are important regulators involving in plant-pathogen interactions. However, their roles in apple tree response to Valsa canker pathogen ( Valsa mali, Vm ) infection were poorly understood. In this study, we constructed two miRNA libraries using the twig bark tissues of apple tree ( Malus domestica Borkh. cv. "Fuji") inoculated with Vm (IVm) and PDA medium (control, BMd). Among all detected miRNAs, 23 miRNAs were specifically isolated from BMd and 39 miRNAs were specifically isolated from IVm. Meanwhile, the expression of 294 miRNAs decreased; and another 172 miRNAs showed an increased expression trend in IVm compared with that in BMd. Furthermore, two degradome sequencing libraries were also constructed to identify the target genes of these miRNAs. In total, 353 differentially expressed miRNAs between IVm and BMd were detected to be able to target 1,077 unigenes with 2,251 cleavage sites. Based on GO and KEGG analysis, these genes were found to be mainly related to transcription regulation and signal transduction. In addition, we selected 17 miRNAs and 22 corresponding target genes to screen the expression profiles when apple twigs were infected by Vm . The expression trends of most miRNAs/target genes were consist with the results of deep sequencing. Many of them may involve in the apple twig- Vm interaction by inducing/reducing their expression. What's more, miRNAs and their target genes regulate the apple twig- Vm interaction by forming many complicated regulation networks rather than one to one model. It is worth that a conserved miRNAs mdm-miR482b, which was down regulated in IVm compared with BMd, has 14 potential target genes, most of which are disease resistance related genes. This indicates that mdm-miR482b may play important roles in apple twig response to Vm . More important, the feedback regulation of sRNA pathway in apple twig is also very complex, and play critical role in the interaction between apple twig and Vm based on the results of expression analysis. In all, the results will provide insights into the crucial functions of miRNAs in the woody plant, apple tree- Vm interaction.

  1. microRNAs and Their Targets in Apple (Malus domestica cv. “Fuji”) Involved in Response to Infection of Pathogen Valsa mali

    PubMed Central

    Feng, Hao; Xu, Ming; Zheng, Xiang; Zhu, Tongyi; Gao, Xiaoning; Huang, Lili

    2017-01-01

    miRNAs are important regulators involving in plant-pathogen interactions. However, their roles in apple tree response to Valsa canker pathogen (Valsa mali, Vm) infection were poorly understood. In this study, we constructed two miRNA libraries using the twig bark tissues of apple tree (Malus domestica Borkh. cv. “Fuji”) inoculated with Vm (IVm) and PDA medium (control, BMd). Among all detected miRNAs, 23 miRNAs were specifically isolated from BMd and 39 miRNAs were specifically isolated from IVm. Meanwhile, the expression of 294 miRNAs decreased; and another 172 miRNAs showed an increased expression trend in IVm compared with that in BMd. Furthermore, two degradome sequencing libraries were also constructed to identify the target genes of these miRNAs. In total, 353 differentially expressed miRNAs between IVm and BMd were detected to be able to target 1,077 unigenes with 2,251 cleavage sites. Based on GO and KEGG analysis, these genes were found to be mainly related to transcription regulation and signal transduction. In addition, we selected 17 miRNAs and 22 corresponding target genes to screen the expression profiles when apple twigs were infected by Vm. The expression trends of most miRNAs/target genes were consist with the results of deep sequencing. Many of them may involve in the apple twig-Vm interaction by inducing/reducing their expression. What's more, miRNAs and their target genes regulate the apple twig-Vm interaction by forming many complicated regulation networks rather than one to one model. It is worth that a conserved miRNAs mdm-miR482b, which was down regulated in IVm compared with BMd, has 14 potential target genes, most of which are disease resistance related genes. This indicates that mdm-miR482b may play important roles in apple twig response to Vm. More important, the feedback regulation of sRNA pathway in apple twig is also very complex, and play critical role in the interaction between apple twig and Vm based on the results of expression analysis. In all, the results will provide insights into the crucial functions of miRNAs in the woody plant, apple tree-Vm interaction. PMID:29270184

  2. Strengthening tactical planning and operational frameworks for vector control: the roadmap for malaria elimination in Namibia.

    PubMed

    Chanda, Emmanuel; Ameneshewa, Birkinesh; Angula, Hans A; Iitula, Iitula; Uusiku, Pentrina; Trune, Desta; Islam, Quazi M; Govere, John M

    2015-08-05

    Namibia has made tremendous gains in malaria control and the epidemiological trend of the disease has changed significantly over the past years. In 2010, the country reoriented from the objective of reducing disease morbidity and mortality to the goal of achieving malaria elimination by 2020. This manuscript outlines the processes undertaken in strengthening tactical planning and operational frameworks for vector control to facilitate expeditious malaria elimination in Namibia. The information sources for this study included all available data and accessible archived documentary records on malaria vector control in Namibia. A methodical assessment of published and unpublished documents was conducted via a literature search of online electronic databases, Google Scholar, PubMed and WHO, using a combination of search terms. To attain the goal of elimination in Namibia, systems are being strengthened to identify and clear all infections, and significantly reduce human-mosquito contact. Particularly, consolidating vector control for reducing transmission at the identified malaria foci will be critical for accelerated malaria elimination. Thus, guarding against potential challenges and the need for evidence-based and sustainable vector control instigated the strengthening of strategic frameworks by: adopting the integrated vector management (IVM) strategy; initiating implementation of the global plan for insecticide resistance management (GPIRM); intensifying malaria vector surveillance; improving data collection and reporting systems on DDT; updating the indoor residual spraying (IRS) data collection and reporting tool; and, improving geographical reconnaissance using geographical information system-based satellite imagery. Universal coverage with IRS and long-lasting insecticidal nets, supplemented by larval source management in the context of IVM and guided by vector surveillance coupled with rational operationalization of the GPIRM, will enable expeditious attainment of elimination in Namibia. However, national capacity to plan, implement, monitor and evaluate interventions will require adequate and sustained support for technical, physical infrastructure, and human and financial resources for entomology and vector control operations.

  3. Noninvasive assays of in vitro matured human oocytes showed insignificant correlation with fertilization and embryo development.

    PubMed

    Ashourzadeh, Sareh; Khalili, Mohammad Ali; Omidi, Marjan; Mahani, Seyed Nooraldin Nematollahi; Kalantar, Seyed Mehdi; Aflatoonian, Abbas; Habibzadeh, Victoria

    2015-08-01

    Recently, the upgrading of in vitro maturation (IVM) of human oocytes as a promising strategy has emerged in assisted reproductive technology (ART). The goal was to evaluate the correlation of the in vitro matured oocytes selected on the basis of the zona pellucida (ZP) birefringence and meiotic spindles (MS) detection with fertilization and subsequent embryo development in ICSI program. A total of 168 immature oocytes [germinal vesicle (n = 140) and metaphase I (n = 28)] obtained from patients undergoing oocytes retrieval for ICSI. After in vitro culture for 24-40 h, 112 (67 %) oocytes reached to MII stage. Using a polarized microscopy, the presence of MS and ZP birefringence were assessed in matured oocytes, followed by ICSI performance. The rates of fertilization in oocytes with spindles (51.3 %) were similar to that of the oocytes without spindles (50.7 %; P = 1.00). Moreover, the fertilization rates in high birefringence (HB) oocytes was not statistically different than oocytes with low birefringence (LB) (P = 0.44). The findings also showed that 64.9 % of the fertilized oocytes developed to embryos, in which 33.3 % were derived from spindle-detected oocytes. Regarding the ZP birefringence, 35.5 % of the embryos were derived from HB oocytes. There were insignificant relationships between the MS detection and ZP birefringence score with the rates of fertilization and embryo development in IVM oocytes.

  4. Expression stability of two housekeeping genes (18S rRNA and G3PDH) during in vitro maturation of follicular oocytes in buffalo (Bubalus bubalis).

    PubMed

    Aswal, Ajay Pal Singh; Raghav, Sarvesh; De, Sachinandan; Thakur, Manish; Goswami, Surender Lal; Datta, Tirtha Kumar

    2008-01-15

    The present study was undertaken to evaluate the expression stability of two housekeeping genes (HKGs), 18S rRNA and G3PDH during in vitro maturation (IVM) of oocytes in buffalo, which qualifies their use as internal controls for valid qRT-PCR estimation of other oocyte transcripts. A semi quantitative RT-PCR system was used with optimised qRT-PCR parameters at exponential PCR cycle for evaluation of temporal expression pattern of these genes over 24 h of IVM. 18S rRNA was found more stable in its expression pattern than G3PDH.

  5. Normal overall leakiness of microvasculature for albumin in patients with chronic obstructive lung disease (COLD).

    PubMed

    Henriksen, J H; Kok-Jensen, A

    1984-04-01

    The overall extravasation rate of albumin, TER (i.e. the fraction of the intravascular albumin mass (IVM) passing into, and during steady state returning from, the extravascular space per unit time) was determined from the disappearance of i.v. injected radioiodinated serum albumin in seven patients with severe chronic obstructive lung disease (COLD) and in seven normal controls. Arterial oxygen tension in patients with COLD was median 60 mmHg (range 47-80, normal greater than 75 mmHg), vital capacity was on the average 55% of expected normal value (median 1.80 litre, range 1.45-1.95), and forced expired volume in first sec was decreased to 21% of expected normal value (median 0.55 litre, range 0.40-0.70). Right-heart catheterization revealed pulmonary hypertension in all but one patient. TER in patients with COLD was median 6.1% IVM/h (range 3.5-10.1) as compared to that of normal controls 6.0% IVM/h (range 4.3-7.4), indicating that no significant change in microvascular leakiness to albumin could be found in patients with COLD. Thus, the results bring no support to a generally increased microvascular permeability to proteins in patients with COLD.

  6. Confocal fluorescence assessment of bioenergy/redox status of dromedary camel (Camelus dromedarius) oocytes before and after in vitro maturation.

    PubMed

    Russo, Roberto; Monaco, Davide; Rubessa, Marcello; El-Bahrawy, Khalid A; El-Sayed, Ashraf; Martino, Nicola A; Beneult, Benedicte; Ciannarella, Francesca; Dell'Aquila, Maria E; Lacalandra, Giovanni M; Filioli Uranio, Manuel

    2014-02-18

    Reproductive biotechnologies in dromedary camel (Camelus dromedarius) are less developed than in other livestock species. The in vitro maturation (IVM) technology is a fundamental step for in vitro embryo production (IVP), and its optimization could represent a way to increase the success rate of IVP. The aim of the present study was to investigate the bioenergy/oxidative status of dromedary camel oocytes before and after IVM by confocal microscopy 3D imaging. Oocytes were retrieved by slicing ovaries collected at local slaughterhouses. Recovered oocytes were examined before and after IVM culture for nuclear chromatin configuration and bioenergy/oxidative status, expressed as mitochondria (mt) distribution and activity, intracellular Reactive Oxygen Species (ROS) levels and distribution and mt/ROS colocalization. The mean recovery rate was 6 oocytes/ovary. After IVM, 61% of oocytes resumed meiosis and 36% reached the Metaphase II stage (MII). Oocyte bioenergy/redox confocal characterization revealed changes upon meiosis progression. Immature oocytes at the germinal vesicle (GV) stage were characterised by prevailing homogeneous mt distribution in small aggregates while MI and MII oocytes showed significantly higher rates of pericortical mt distribution organized in tubular networks (P<0.05). Increased mt activity in MI (P<0.001) and MII (P<0.01) oocytes compared to GV stage oocytes was also observed. At any meiotic stage, homogeneous distribution of intracellular ROS was observed. Intracellular ROS levels also increased in MI (P<0.01) and MII (P<0.05) oocytes compared to GV stage oocytes. The mt/ROS colocalization signal increased in MI oocytes (P<0.05). This study provides indications that qualitative and quantitative indicators of bioenergy and oxidative status in dromedary camel oocytes are modified in relation with oocyte meiotic stage. These data may increase the knowledge of camel oocyte physiology, in order to enhance the efficiency of IVP procedures.

  7. Royal jelly may improve the metabolism of glucose and redox state of ovine oocytes matured in vitro and embryonic development following in vitro fertilization.

    PubMed

    Eshtiyaghi, Mahbobeh; Deldar, Hamid; Pirsaraei, Zarbakht Ansari; Shohreh, Bahram

    2016-12-01

    The aim of this study was to investigate the effect of different concentrations of royal jelly (RJ) on in vitro maturation (IVM), fertilization, cleavage, blastocyst rates, glutathione (GSH) content in ovine oocyte, mRNA abundance of antioxidant enzymes in both oocyte and cumulus, and glucose metabolism-related genes in cumulus cells. In vitro maturation of oocyte was performed in the presence of control (RJ 0 ), 2.5 (RJ 2.5 ), 5 (RJ 5 ), and 10 (RJ 10 ) mg/mL of RJ. Nuclear status, intracellular GSH content in oocytes, and mRNA abundance of selected genes were evaluated following 24 hours of IVM. Following the IVM, fertilization and embryo culture were carried out in all the groups and embryonic development was examined. The addition of 10-mg/mL RJ to maturation media not only yielded a higher number of oocytes at MII stage but also showed an increased level of intracellular GSH content than did RJ 2.5 and control groups. Fertilization, cleavage, and blastocyst rate were higher in the RJ 10 treatment group in comparison to the control one. In cumulus cells, the expression of PFKM, PFKL, and G6PDH were increased following the addition of RJ to the maturation media. Supplementation of 10-mg/mL RJ to IVM medium increased the GPx mRNA abundance in both oocyte and cumulus cells and SOD expression in the cumulus cells. The CAT mRNA abundance was not influenced by the addition of RJ to the maturation media in either oocyte or cumulus cells. It seems that the improvement of oocyte maturation and its subsequent development in RJ 10 group may be associated with amelioration of redox status in the oocytes and activation of glucose metabolic pathways in their surrounding cumulus cells. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Impact of delipidated estrous sheep serum supplementation on in vitro maturation, cryotolerance and endoplasmic reticulum stress gene expression of sheep oocytes

    PubMed Central

    dos Santos Neto, Pedro C.; Cuadro, Federico; Bosolasco, Diego; Mulet, Ana P.; Crispo, Martina

    2018-01-01

    High lipid content of oocytes and embryos in domestic animals is one of the well-known factors associated with poor cryosurvival. Herein, we wanted to determine whether the use of delipidated estrous sheep serum during in vitro maturation (IVM) of ovine oocytes reduces the cytoplasmic lipid droplets content and improves embryo development and cryotolerance after vitrification. Cumulus oocytes complexes (COCs) were matured in vitro for 24 h in medium supplemented with whole or delipidated estrous sheep serum prior to vitrification. Neutral lipid present in lipid droplets of COCs, cleavage rate, embryo development rate on Day 6 and Day 8, and hatching rate on Day 8, were compared among experimental groups. Endoplasmic reticulum stress genes were evaluated in in vitro matured COCs under different lipid conditions prior to vitrification. The lipid droplets’ content (mean fluorescence intensity) of oocytes cultured with IVM media supplemented with delipidated serum was lower than COCs matured with whole serum (7.6 ± 1.7 vs. 22.8 ± 5.0 arbitrary units, respectively; P< 0.05). Despite IVM treatment, oocytes subjected to vitrification showed impaired competence compared with the non-vitrified groups (P<0.05). No significant differences in embryo production were observed in non-vitrified COCs after maturation in delipidated or whole serum (33.4±4.9 vs 31.9 ±4.2). COCs matured in delipidated serum and subjected to vitrification showed increased expression of ATF4, ATF6, GRP78, and CHOP10 genes (ER stress markers). Collectively, our results demonstrate that although supplementation of IVM medium with delipidated estrous sheep serum reduces the presence of cytoplasmic lipid droplets in oocytes after maturation, oocyte cryotolerance is not improved. Notably, the expression of genes associated with the unfolded protein response (UPR) was increased in COCs, with fewer lipid droplets subjected to vitrification, suggesting that oocyte cryopreservation is associated with ER stress and activation of adaptive responses. PMID:29912910

  9. Bovine oocyte meiotic inhibition before in vitro maturation and its value to in vitro embryo production: does it improve developmental competence?

    PubMed

    Bilodeau-Goeseels, S

    2012-08-01

    The efficiency of bovine in vitro embryo production has remained low despite extensive effort to understand the effects of culture conditions, media composition and supplementation. As bovine oocytes resume meiosis spontaneously when cultured, it was hypothesized that preventing meiosis in vitro before in vitro maturation (IVM) and in vitro fertilization (IVF) would allow more oocytes to acquire developmental competence. This article reviews some of the factors involved in meiotic arrest as well as the effects of meiotic inhibition before IVM on bovine oocytes developmental competence following IVF. Follicular components and cAMP-elevating agents can delay or inhibit meiosis in various proportions of oocytes; however, few studies have examined their effects on development following IVM and IVF because they are not practical (follicular components) or have a transient effect on meiosis (cAMP-elevating agents). Protein synthesis or phosphorylation inhibition prevented meiosis in high percentages of oocytes; however, these non-specific inhibitions led to lower developmental competence compared with non-arrested oocytes. Maturation promoting factor (MPF) inhibition with specific inhibitors has been examined in several studies. Despite faster maturation following removal from inhibition and some structural damage to the oocytes, MPF inhibition generally led to blastocyst rates similar to control, non-arrested oocytes. Future work will involve evaluating the effects on arrested oocytes of molecules that can improve developmental competence in non-arrested oocytes. It is also anticipated that new IVM systems that take into consideration new knowledge of the mechanisms involved in the control of meiosis will be developed. Moreover, global gene expression analysis studies will also provide clues to the culture conditions required for optimal expression of developmental competence. © Her Majesty the Queen in Right of Canada 2011. Reproduced with the permission of the Minister of Agriculture and Agri-Food Canada.

  10. Effect of Antioxidants (β-mercaptoethanol and Cysteamine) on Assisted Reproductive Technology In vitro.

    PubMed

    Nikseresht, Mohsen; Toori, Mehdi Akbartabar; Rahimi, Hamid Reza; Fallahzadeh, Ali Reza; Kahshani, Iraj Ragerdi; Hashemi, Seyedeh Fatemeh; Bahrami, Solmaz; Mahmoudi, Reza

    2017-02-01

    Oocyte Culture of Germinal Vesicle (GV) and its growth improves Assisted Reproductive Technology (ART) invitro and infertility. Inappropriate culture medium environment, low quality of oocytes, increase in Oxidative Stress (OS) events, Reactive Oxygen Species (ROS) and free radicals production are the main factors that result in unsuccessful Invitro Maturation (IVM) and decrease in reproduction. The present study was conducted with the aim to evaluate the effect of β-mercaptoethanol (BME) and Cysteamine (CYS) on IVM improvement, embryo fertilization and development of blastocyst of mouse immature oocyte. Oocytes were obtained from 4-6 weeks old Naval Medical Research Institute (NMRI) female mice, 48 hours after stimulation with Intraperitoneal (IP) injection of 10 IU Pregnant Mare Serum Gonadotropin (PMSG). GV oocyte with and without cumulus cells were isolated from ovaries and cultured in Tissue Culture Medium (TCM) 199 with availability of 100 μM of antioxidants (BME and CYS). After 24 hours, mature oocyte in metaphase II (MII) were fertilized with sperm in In vitro Fertilization (IVF) medium (T6) and evaluated for fetal development into blastocyst. BME and CYS could significantly (p<0.05) increase the rate of IVM and oocyte evolution, and embryo formation in medium culture. Furthermore, it is demonstrated that existence of Cumulus Oocyte Complexes (COC) significantly showed better IVM, fertilization and evolution trend as compared to oocytes without cumulus cover or Denuded Oocytes (DO), especially in TCM199 plus BME and CYS. So that the change in GV stage oocytes to MII (maturation rate), fertilization rates or 2PN formation, and two cell embryos formation or blastocyst development rate in the treatment group with addition of BME & CYS and COC was statistically significant as compared to the DO group (p-value < 0.0001). Both cellular and environmental factors could be important and involved in ART improvement.

  11. Effect of recombinant-LH and hCG in the absence of FSH on in vitro maturation (IVM) fertilization and early embryonic development of mouse germinal vesicle (GV)-stage oocytes.

    PubMed

    Dinopoulou, Vasiliki; Drakakis, Peter; Kefala, Stella; Kiapekou, Erasmia; Bletsa, Ritsa; Anagnostou, Elli; Kallianidis, Konstantinos; Loutradis, Dimitrios

    2016-06-01

    During in vitro maturation (IVM), intrinsic and extrinsic factors must co-operate properly in order to ensure cytoplasmic and nuclear maturation. We examined the possible effect of LH/hCG in the process of oocyte maturation in mice with the addition of recombinant LH (r-LH) and hCG in our IVM cultures of mouse germinal vesicle (GV)-stage oocytes. Moreover, the effects of these hormones on fertilization, early embryonic development and the expression of LH/hCG receptor were examined. Nuclear maturation of GV-stage oocytes was evaluated after culture in the presence of r-LH or hCG. Fertilization rates and embryonic development were assessed after 24h. Total RNA was isolated from oocytes of different stages of maturation and from zygotes and embryos of different stages of development in order to examine the expression of LH/hCG receptor, using RT-PCR. The in vitro nuclear maturation rate of GV-stage oocytes that received hCG was significantly higher compared to the control group. Early embryonic development was increased in the hCG and LH cultures of GV oocytes when LH was further added. The LH/hCG receptor was expressed in all stages of in vitro matured mouse oocytes and in every stage of early embryonic development. Addition of hCG in IVM cultures of mouse GV oocytes increased maturation rates significantly. LH, however, was more beneficial to early embryonic development than hCG. This suggests a promising new technique in basic science research or in clinical reproductive medicine. Copyright © 2016 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  12. Confocal fluorescence assessment of bioenergy/redox status of dromedary camel (Camelus dromedarius) oocytes before and after in vitro maturation

    PubMed Central

    2014-01-01

    Background Reproductive biotechnologies in dromedary camel (Camelus dromedarius) are less developed than in other livestock species. The in vitro maturation (IVM) technology is a fundamental step for in vitro embryo production (IVP), and its optimization could represent a way to increase the success rate of IVP. The aim of the present study was to investigate the bioenergy/oxidative status of dromedary camel oocytes before and after IVM by confocal microscopy 3D imaging. Methods Oocytes were retrieved by slicing ovaries collected at local slaughterhouses. Recovered oocytes were examined before and after IVM culture for nuclear chromatin configuration and bioenergy/oxidative status, expressed as mitochondria (mt) distribution and activity, intracellular Reactive Oxygen Species (ROS) levels and distribution and mt/ROS colocalization. Results The mean recovery rate was 6 oocytes/ovary. After IVM, 61% of oocytes resumed meiosis and 36% reached the Metaphase II stage (MII). Oocyte bioenergy/redox confocal characterization revealed changes upon meiosis progression. Immature oocytes at the germinal vesicle (GV) stage were characterised by prevailing homogeneous mt distribution in small aggregates while MI and MII oocytes showed significantly higher rates of pericortical mt distribution organized in tubular networks (P < 0.05). Increased mt activity in MI (P < 0.001) and MII (P < 0.01) oocytes compared to GV stage oocytes was also observed. At any meiotic stage, homogeneous distribution of intracellular ROS was observed. Intracellular ROS levels also increased in MI (P < 0.01) and MII (P < 0.05) oocytes compared to GV stage oocytes. The mt/ROS colocalization signal increased in MI oocytes (P < 0.05). Conclusions This study provides indications that qualitative and quantitative indicators of bioenergy and oxidative status in dromedary camel oocytes are modified in relation with oocyte meiotic stage. These data may increase the knowledge of camel oocyte physiology, in order to enhance the efficiency of IVP procedures. PMID:24548378

  13. 3D Numerical Simulation on the Rockslide Generated Tsunamis

    NASA Astrophysics Data System (ADS)

    Chuang, M.; Wu, T.; Wang, C.; Chu, C.

    2013-12-01

    The rockslide generated tsunami is one of the most devastating nature hazards. However, the involvement of the moving obstacle and dynamic free-surface movement makes the numerical simulation a difficult task. To describe both the fluid motion and solid movement at the same time, we newly developed a two-way fully-coupled moving solid algorithm with 3D LES turbulent model. The free-surface movement is tracked by volume of fluid (VOF) method. The two-step projection method is adopted to solve the Navier-Stokes type government equations. In the new moving solid algorithm, a fictitious body force is implicitly prescribed in MAC correction step to make the cell-center velocity satisfied with the obstacle velocity. We called this method the implicit velocity method (IVM). Because no extra terms are added to the pressure Poission correction, the pressure field of the fluid part is stable, which is the key of the two-way fluid-solid coupling. Because no real solid material is presented in the IVM, the time marching step is not restricted to the smallest effective grid size. Also, because the fictitious force is implicitly added to the correction step, the resulting velocity is accurate and fully coupled with the resulting pressure field. We validated the IVM by simulating a floating box moving up and down on the free-surface. We presented the time-history obstacle trajectory and compared it with the experimental data. Very accurate result can be seen in terms of the oscillating amplitude and the period (Fig. 1). We also presented the free-surface comparison with the high-speed snapshots. At the end, the IVM was used to study the rock-slide generated tsunamis (Liu et al., 2005). Good validations on the slide trajectory and the free-surface movement will be presented in the full paper. From the simulation results (Fig. 2), we observed that the rockslide generated waves are manly caused by the rebounding waves from two sides of the sliding rock after the water is dragging down by the solid downward motion. We also found that the turbulence has minor effect to the main flow field. The rock size, rock density, and the steepness of the slope were analyzed to understand their effects to the maximum runup height. The detailed algorithm of IVM, the validation, the simulation and analysis of rockslide tsunami will be presented in the full paper. Figure 1. Time-history trajectory of obstacle for the floating obstacle simulation. Figure 2. Snapshots of the free-surface elevation with streamlines for the rockslide tsunami simulation.

  14. Production of feline leukemia inhibitory factor with biological activity in Escherichia coli.

    PubMed

    Kanegi, R; Hatoya, S; Tsujimoto, Y; Takenaka, S; Nishimura, T; Wijewardana, V; Sugiura, K; Takahashi, M; Kawate, N; Tamada, H; Inaba, T

    2016-07-15

    Leukemia inhibitory factor (LIF) is a cytokine which is essential for oocyte and embryo development, embryonic stem cell, and induced pluripotent stem cell maintenance. Leukemia inhibitory factor improves the maturation of oocytes in the human and the mouse. However, feline LIF (fLIF) cloning and effects on oocytes during IVM have not been reported. Thus, we cloned complete cDNA of fLIF and examined its biological activity and effects on oocytes during IVM in the domestic cat. The aminoacid sequence of fLIF revealed a homology of 81% or 92% with that of mouse or human. The fLIF produced by pCold TF DNA in Escherichia coli was readily soluble and after purification showed bioactivity in maintaining the undifferentiated state of mouse embryonic stem cells and enhancing the proliferation of human erythrocyte leukemia cells. Furthermore, 10- and 100-ng/mL fLIF induced cumulus expansion with or without FSH and EGF (P < 0.05). The rate of metaphase II oocytes was also improved with 100-ng/mL fLIF (P < 0.05). We therefore confirmed the successful production for the first time of biologically active fLIF and revealed its effects on oocytes during IVM in the domestic cat. Feline LIF will further improve reproduction and stem cell research in the feline family. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Measurement and Analysis of Structural Integrity of Reactor Core Support Structure in Pressurized Water Reactor (PWR) Plant

    NASA Astrophysics Data System (ADS)

    Ansari, Saleem A.; Haroon, Muhammad; Rashid, Atif; Kazmi, Zafar

    2017-02-01

    Extensive calculation and measurements of flow-induced vibrations (FIV) of reactor internals were made in a PWR plant to assess the structural integrity of reactor core support structure against coolant flow. The work was done to meet the requirements of the Fukushima Response Action Plan (FRAP) for enhancement of reactor safety, and the regulatory guide RG-1.20. For the core surveillance measurements the Reactor Internals Vibration Monitoring System (IVMS) has been developed based on detailed neutron noise analysis of the flux signals from the four ex-core neutron detectors. The natural frequencies, displacement and mode shapes of the reactor core barrel (CB) motion were determined with the help of IVMS. The random pressure fluctuations in reactor coolant flow due to turbulence force have been identified as the predominant cause of beam-mode deflection of CB. The dynamic FIV calculations were also made to supplement the core surveillance measurements. The calculational package employed the computational fluid dynamics, mode shape analysis, calculation of power spectral densities of flow & pressure fields and the structural response to random flow excitation forces. The dynamic loads and stiffness of the Hold-Down Spring that keeps the core structure in position against upward coolant thrust were also determined by noise measurements. Also, the boron concentration in primary coolant at any time of the core cycle has been determined with the IVMS.

  16. In vitro embryo production in goats: Slaughterhouse and laparoscopic ovum pick up-derived oocytes have different kinetics and requirements regarding maturation media.

    PubMed

    Souza-Fabjan, Joanna Maria G; Locatelli, Yann; Duffard, Nicolas; Corbin, Emilie; Touzé, Jean-Luc; Perreau, Christine; Beckers, Jean François; Freitas, Vicente José F; Mermillod, Pascal

    2014-05-01

    A total of 3427 goat oocytes were used in this study to identify possible differences during in vitro embryo production from slaughterhouse or laparoscopic ovum pick up (LOPU) oocytes. In experiment 1, one complex, one semi-defined, and one simplified IVM media were compared using slaughterhouse oocytes. In experiment 2, we checked the effect of oocyte origin (slaughterhouse or LOPU) on the kinetics of maturation (18 vs. 22 vs. 26 hours) when submitted to semi-defined or simplified media. In experiment 3, we determined the differences in embryo development between slaughterhouse and LOPU oocytes when submitted to both media and then to IVF or parthenogenetic activation (PA). Embryos from all groups were vitrified, and their viability evaluated in vitro after thawing. In experiment 1, no difference (P > 0.05) was detected among treatments for maturation rate (metaphase II [MII]; 88% on average), cleavage (72%), blastocyst from the initial number of cumulus oocyte complexes (46%) or from the cleaved ones (63%), hatching rate (69%), and the total number of blastomeres (187). In experiment 2, there was no difference of MII rate between slaughterhouse oocytes cultured for 18 or 22 hours, whereas the MII rate increased significantly (P < 0.05) between 18 and 22 hours for LOPU oocytes in the simplified medium. Moreover, slaughterhouse oocytes cultured in simplified medium matured significantly faster than LOPU oocytes at 18 and 22 hours (P < 0.05). In experiment 3, cleavage rate was significantly greater (P < 0.001) in all four groups of embryos produced by PA than IVF. Interestingly, PA reached similar rates for slaughterhouse oocytes cultured in both media, but improved (P < 0.05) the cleavage rate of LOPU oocytes. Slaughterhouse oocytes had acceptable cleavage rate after IVF (∼67%), whereas LOPU oocytes displayed a lower one (∼38%), in contrast to cleavage after PA. The percentage of blastocysts in relation to cleaved embryos was not affected by the origin of the oocytes (P > 0.05). Therefore, slaughterhouse oocytes developed a greater proportion of blastocysts than LOPU ones, expressed as the percentage of total cumulus oocyte complexes entering to IVM. Vitrified-thawed blastocysts presented similar survival and hatching rates between the oocyte origin, media, or method of activation. In conclusion, slaughterhouse and LOPU derived oocytes may have different IVM kinetics and require different IVM and IVF conditions. Although the IVM and IVF systems still need improvements to enhance embryo yield, the in vitro development step is able to generate good quality embryos from LOPU-derived oocytes. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Comparison of intratesticular lidocaine, sacrococcygeal epidural lidocaine and intravenous methadone in cats undergoing castration: a prospective, randomized, investigator-blind clinical trial.

    PubMed

    Fernandez-Parra, Rocio; Zilberstein, Luca; Fontaine, Cyril; Adami, Chiara

    2017-03-01

    The objective of this study was to compare three analgesic protocols for feline castration. Prospective, randomized clinical study. Forty-nine client-owned cats. Cats were injected with intramuscular (IM) dexmedetomidine (15 μg kg -1 ) and alfaxalone (3 mg kg -1 ) and assigned randomly to one of three treatment groups. Group ITL (n = 15) were administered intratesticular 2% lidocaine (0.05 mL each testicle), group SCL (n = 15) a sacrococcygeal epidural injection of 2% lidocaine (0.1 mL kg -1 ) and group IVM (n = 19) intravenous (IV) methadone (0.3 mg kg -1 ), before surgery. Cardiorespiratory variables were recorded. In case of autonomic nociceptive response, IV fentanyl (2 μg kg -1 ) was administered. During recovery, time from IM atipamezole (75 μg kg -1 , administered at the end of surgery) to sternal recumbency and to active interaction was recorded. Quality of recovery was assessed using a simple descriptive scale. Postoperative analgesia was evaluated using a visual analogue scale and the UNESP-Botucatu multidimensional composite pain scale (MCPS) at return of active interaction and then 1, 2 and 3 hours later. The three analgesic protocols were comparable in terms of intraoperative fentanyl and propofol requirement. Cardiorespiratory variables stayed within normal ranges in the majority of the cases, although group IVM had the lowest intraoperative respiratory rate (p = 0.0009). No differences were detected between groups in UNESP-Botucatu MCPS scores (p = 0.21). However, group ITL showed higher visual analogue scale score than group IVM (p = 0.001). Four cats enrolled in group ITL, as well as three of group SCL and one of group IVM, required rescue analgesics before the completion of pain assessment. Intratesticular and sacrococcygeal epidural lidocaine injections could be regarded as good alternatives to systemic opioids in cats undergoing castration, although the benefits of these techniques seem to be of shorter duration than IV methadone. Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. All rights reserved.

  18. Vitrification solution containing DMSO and EG can induce parthenogenetic activation of in vitro matured ovine oocytes and decrease sperm penetration.

    PubMed

    Tian, Shu-Jun; Yan, Chang-Liang; Yang, Hui-Xin; Zhou, Guang-Bin; Yang, Zhong-Qiang; Zhu, Shi-En

    2007-10-01

    This study was designed to examine the reduced incidence of normal fertilization in vitrified ovine oocytes. After in vitro maturation for 24 h, the oocytes were randomly allocated into three groups: (1) untreated (control), (2) exposed to vitrification solution (VS) without being plunged into liquid nitrogen (toxicity), or (3) vitrified by open-pulled straw method (vitrification). In experiment 1, the treated and control oocytes were matured for another 2 h, and the oocytes were then in vitro fertilized for 12 h to examine sperm penetration. The percentage of monospermy in toxicity group (29.3%) and vitrification group (28.2%) dramatically decreased compared to the control group (45.0%) (P<0.05). To find the mechanism that the VS decreased the monospermy, some treated and control oocytes were used to test the distribution of CG and the resistance of zona pellucida (ZP) to 0.1% pronase E immediately (IVM 24 h), after another 2 h of maturation (IVM 26 h), and after 12 h of in vitro fertilization (IVF 12 h) respectively. Others were used to examine female pronucleus formation after 12 h of culture in fertilization medium with the absence of sperm. The results showed that the percentage of CG completely release in the oocytes (IVM 24 and 26 h) of toxicity group (41.2% and 39.9%) and vitrification group (41.7% and 51.7%) was significantly higher than that of control group (7.1% and 18.4%) (P<0.05). The ZP digestion duration in the oocytes (IVM 26 h) of the toxicity group (435.6 s) and vitrification group (422.3 s) was longer than that of control group (381.6 s) (P<0.05). The percentage of female pronucleus formation in toxicity group (58.7%) and vitrification group (63.9%) was higher than that (8.2%) of control group (P<0.05). The data above demonstrated that the VS containing DMSO and EG could parthenogenetically activate in vitro matured ovine oocytes, resulting in ZP hardening and decreased sperm penetration.

  19. Cumulus cell expansion and first polar body extrusion during in vitro oocyte maturation in relation to morphological and morphometric characteristics of the dromedary camel ovary.

    PubMed

    Mesbah, F; Kafi, M; Nili, H

    2016-12-01

    The morphological and morphometric characteristics of the ovary are fundamental properties for in vitro oocyte maturation. Nuclear maturation, including first polar body (1PB) extrusion, cytoplasmic maturation and cumulus cell (CC) expansion are the criteria for in vitro maturation (IVM) of oocyte. This study was designed to determine the effect of morphological and morphometric features of the ovary on CC expansion and 1PB extrusion during IVM of oocyte in the adult female dromedary camel. The weight, volume and three dimensions of ovaries from slaughtered dromedary camels and oocytes inside zona diameter and zona pellucida thickness were measured. The follicles were classified in regard to the size and oocytes according to their ooplasm appearance and CC compactness. Aspirated cumulus oocyte complexes (COCs) were incubated for 48 hr (with a 6-hr interval) in Hams-F10, and CC expansion and 1PB extrusion were assessed. Significant differences were seen in the shape, weight, volume and three dimensions of the ovaries between ≤4-year-old and >4-year-old dromedary camel (p < .5). Approximately, 95.82% of follicles were 2-4 mm in diameter. The mean (±SD) of inside zona diameter of the oocyte and zona pellucida thickness was 132.22 ± 13.8 and 14.64 ± 2.24 μm, respectively, in >4-year-old dromedary camel. The CC expansion and 1PB extrusion were seen in 86% and 21.88% of COCs, respectively. Age and sexual conditions of dromedary camel influence the morphological and morphometric characteristics of the ovary. Most COCs retrieved from 2-6 mm follicles are cultivable. The most slaughterhouse-derived COCs retrieved from 2-6 mm follicles of non-pregnant dromedary camels are excellent and good and yielding a most favourable diameter to achieve the developmental competence for IVM in an optimal time of 24-30 hr; the optimal time for CC expansion is 24-30 hr in this species. However, the CC expansion is a prerequisite process, but not sufficient for IVM. © 2016 Blackwell Verlag GmbH.

  20. Resveratrol-cyclodextrin complex affects the expression of genes associated with lipid metabolism in bovine in vitro produced embryos.

    PubMed

    Torres, V; Hamdi, M; Millán de la Blanca, M G; Urrego, R; Echeverri, J; López-Herrera, A; Rizos, D; Gutiérrez-Adán, A; Sánchez-Calabuig, M J

    2018-03-26

    Antioxidants have been widely used during in vitro production to decrease the negative effect of reactive oxygen species. It was reported that the complex resveratrol-methyl β-cyclodextrin (RV-CD) improves resveratrol's stability and bioavailability and increases its antioxidant activity. This study evaluates the effect of RV-CD during in vitro oocyte maturation (IVM) or in vitro embryo culture (IVC) on developmental competence and quantitative changes in gene expression of developmental important genes. In experiment 1, RV-CD was added to IVM media and maturation level, embryo development and oocytes, cumulus cells, and blastocysts gene expression by RT-qPCR were examined. In experiment 2, presumptive zygotes were cultured in SOF supplemented with RV-CD and embryo development and blastocysts gene expression by RT-qPCR were studied. A group without RV-CD (control - ) and a group with cyclodextrin (control + ) were included. No differences were found in cleavage rate or blastocyst yield between groups. However, the expression of LIPE was higher in blastocysts derived from oocytes treated with resveratrol compared with control groups (p < .05). Blastocysts produced by IVC with resveratrol showed that RV-CD could modify the expression of genes related to lipid metabolism (CYP51A1, PNPLA2 and MTORC1) compared with control groups (p < .05). RV-CD in the IVM and IVC media could reduce accumulated fat by increasing lipolysis and suppressing lipogenesis of blastocysts. © 2018 Blackwell Verlag GmbH.

  1. Evaluating the risk of water distribution system failure: A shared frailty model

    NASA Astrophysics Data System (ADS)

    Clark, Robert M.; Thurnau, Robert C.

    2011-12-01

    Condition assessment (CA) Modeling is drawing increasing interest as a technique that can assist in managing drinking water infrastructure. This paper develops a model based on the application of a Cox proportional hazard (PH)/shared frailty model and applies it to evaluating the risk of failure in drinking water networks using data from the Laramie Water Utility (located in Laramie, Wyoming, USA). Using the risk model a cost/ benefit analysis incorporating the inspection value method (IVM), is used to assist in making improved repair, replacement and rehabilitation decisions for selected drinking water distribution system pipes. A separate model is developed to predict failures in prestressed concrete cylinder pipe (PCCP). Various currently available inspection technologies are presented and discussed.

  2. Causal Interrogation of Neuronal Networks and Behavior through Virally Transduced Ivermectin Receptors.

    PubMed

    Obenhaus, Horst A; Rozov, Andrei; Bertocchi, Ilaria; Tang, Wannan; Kirsch, Joachim; Betz, Heinrich; Sprengel, Rolf

    2016-01-01

    The causal interrogation of neuronal networks involved in specific behaviors requires the spatially and temporally controlled modulation of neuronal activity. For long-term manipulation of neuronal activity, chemogenetic tools provide a reasonable alternative to short-term optogenetic approaches. Here we show that virus mediated gene transfer of the ivermectin (IVM) activated glycine receptor mutant GlyRα1 (AG) can be used for the selective and reversible silencing of specific neuronal networks in mice. In the striatum, dorsal hippocampus, and olfactory bulb, GlyRα1 (AG) promoted IVM dependent effects in representative behavioral assays. Moreover, GlyRα1 (AG) mediated silencing had a strong and reversible impact on neuronal ensemble activity and c-Fos activation in the olfactory bulb. Together our results demonstrate that long-term, reversible and re-inducible neuronal silencing via GlyRα1 (AG) is a promising tool for the interrogation of network mechanisms underlying the control of behavior and memory formation.

  3. Sericin Accelerates the Production of Hyaluronan and Decreases the Incidence of Polyspermy Fertilization in Bovine Oocytes During In Vitro Maturation

    PubMed Central

    HOSOE, Misa; YOSHIDA, Nao; HASHIYADA, Yutaka; TERAMOTO, Hidetoshi; TAKAHASHI, Toru; NIIMURA, Sueo

    2014-01-01

    Fetal bovine serum (FBS) has been widely used as a supplement in the maturation medium of bovine oocytes in vitro. However, serum contains many undefined factors and is potentially infectious to humans and animals. As a serum replacement, we evaluated the feasibility of using the silk protein, sericin, derived from the cocoons of silkworm. To examine the rates of oocyte maturation and fertilization, cumulus-oocyte complexes were cultured in TCM-199 supplemented with 0.01%, 0.05%, 0.1% or 0.15% sericin or 5% FBS. The sizes of the perivitelline space that might relate to polyspermy, the expressions of Has2 and CD44 mRNA, the amount of hyaluronan (hyaluronic acid: HA) contained in the oocytes and the rates of blastocyst formation following insemination were then compared between the oocytes cultured with 0.05% sericin and 5% FBS, because the polyspermy rates in oocytes cultured with 0.05% sericin were significantly lower than in those cultured with 5% FBS. After in vitro maturation (IVM), the mean size of the perivitelline space was significantly greater in oocytes cultured with sericin than in those cultured with FBS, although the rates of nuclear maturation, fertilization and blastocyst formation of oocytes under both IVM conditions were not significantly different. The expression of HAS2 and CD44 mRNA and the amount of HA in the denuded oocytes cultured with 0.05% sericin were significantly greater than in those cultured with FBS. These results indicate the feasibility of sericin as an alternative protein supplement for IVM in bovine oocytes. PMID:24748396

  4. Sericin accelerates the production of hyaluronan and decreases the incidence of polyspermy fertilization in bovine oocytes during in vitro maturation.

    PubMed

    Hosoe, Misa; Yoshida, Nao; Hashiyada, Yutaka; Teramoto, Hidetoshi; Takahashi, Toru; Niimura, Sueo

    2014-01-01

    Fetal bovine serum (FBS) has been widely used as a supplement in the maturation medium of bovine oocytes in vitro. However, serum contains many undefined factors and is potentially infectious to humans and animals. As a serum replacement, we evaluated the feasibility of using the silk protein, sericin, derived from the cocoons of silkworm. To examine the rates of oocyte maturation and fertilization, cumulus-oocyte complexes were cultured in TCM-199 supplemented with 0.01%, 0.05%, 0.1% or 0.15% sericin or 5% FBS. The sizes of the perivitelline space that might relate to polyspermy, the expressions of Has2 and CD44 mRNA, the amount of hyaluronan (hyaluronic acid: HA) contained in the oocytes and the rates of blastocyst formation following insemination were then compared between the oocytes cultured with 0.05% sericin and 5% FBS, because the polyspermy rates in oocytes cultured with 0.05% sericin were significantly lower than in those cultured with 5% FBS. After in vitro maturation (IVM), the mean size of the perivitelline space was significantly greater in oocytes cultured with sericin than in those cultured with FBS, although the rates of nuclear maturation, fertilization and blastocyst formation of oocytes under both IVM conditions were not significantly different. The expression of HAS2 and CD44 mRNA and the amount of HA in the denuded oocytes cultured with 0.05% sericin were significantly greater than in those cultured with FBS. These results indicate the feasibility of sericin as an alternative protein supplement for IVM in bovine oocytes.

  5. Fatty Acid Synthesis and Oxidation in Cumulus Cells Support Oocyte Maturation in Bovine

    PubMed Central

    Sanchez-Lazo, Laura; Brisard, Daphné; Elis, Sébastien; Maillard, Virginie; Uzbekov, Rustem; Labas, Valérie; Desmarchais, Alice; Papillier, Pascal; Monget, Philippe

    2014-01-01

    Oocyte meiotic maturation requires energy from various substrates including glucose, amino acids, and lipids. Mitochondrial fatty acid (FA) β-oxidation (FAO) in the oocyte is required for meiotic maturation, which is accompanied by differential expression of numerous genes involved in FAs metabolism in surrounding cumulus cells (CCs) in vivo. The objective was to elucidate components involved in FAs metabolism in CCs during oocyte maturation. Twenty-seven genes related to lipogenesis, lipolysis, FA transport, and FAO were chosen from comparative transcriptome analysis of bovine CCs before and after maturation in vivo. Using real-time PCR, 22 were significantly upregulated at different times of in vitro maturation (IVM) in relation to oocyte meiosis progression from germinal vesicle breakdown to metaphase-II. Proteins FA synthase, acetyl-coenzyme-A carboxylase, carnitine palmitoyltransferase, perilipin 2, and FA binding protein 3 were detected by Western blot and immunolocalized to CCs and oocyte cytoplasm, with FA binding protein 3 concentrated around oocyte chromatin. By mass spectrometry, CCs lipid profiling was shown to be different before and after IVM. FAO inhibitors etomoxir and mildronate dose-dependently decreased the oocyte maturation rate in vitro. In terms of viability, cumulus enclosed oocytes were more sensitive to etomoxir than denuded oocytes. In CCs, etomoxir (150μM) led to downregulation of lipogenesis genes and upregulated lipolysis and FAO genes. Moreover, the number of lipid droplets decreased, whereas several lipid species were more abundant compared with nontreated CCs after IVM. In conclusion, FAs metabolism in CCs is important to maintain metabolic homeostasis and may influence meiosis progression and survival of enclosed oocytes. PMID:25058602

  6. Melatonin-induced increase of lipid droplets accumulation and in vitro maturation in porcine oocytes is mediated by mitochondrial quiescence.

    PubMed

    He, Bin; Yin, Chao; Gong, Yabin; Liu, Jie; Guo, Huiduo; Zhao, Ruqian

    2018-01-01

    Melatonin, the major pineal secretory product, has a significant impact on the female reproductive system. Recently, the beneficial effects of melatonin on mammalian oocyte maturation and embryonic development have drawn increased attention. However, the exact underlying mechanisms remain to be fully elucidated. This study demonstrates that supplementing melatonin to in vitro maturation (IVM) medium enhances IVM rate, lipid droplets (LDs) accumulation as well as triglyceride content in porcine oocytes. Decrease of mitochondrial membrane potential, mitochondrial respiratory chain complex IV activity as well as mitochondrial reactive oxygen species (mROS) content indicated that melatonin induced a decrease of mitochondrial activity. The copy number of mitochondrial DNA (mtDNA) which encodes essential subunits of oxidative phosphorylation (OXPHOS), was not affected by melatonin. However, the expression of mtDNA-encoded genes was significantly down-regulated after melatonin treatment. The DNA methyltransferase DNMT1, which regulates methylation and expression of mtDNA, was increased and translocated into the mitochondria in melatonin-treated oocytes. The inhibitory effect of melatonin on the expression of mtDNA was significantly prevented by simultaneous addition of DNMT1 inhibitor, which suggests that melatonin regulates the transcription of mtDNA through up-regulation of DNMT1 and mtDNA methylation. Increase of triglyceride contents after inhibition of OXPHOS indicated that mitochondrial quiescence is crucial for LDs accumulation in oocytes. Taken together, our results suggest that melatonin-induced reduction in mROS production and increase in IVM, and LDs accumulation in porcine oocytes is mediated by mitochondrial quiescence. © 2017 Wiley Periodicals, Inc.

  7. Pharmacokinetics of butorphanol tartrate in red-tailed hawks (Buteo jamaicensis) and great horned owls (Bubo virginianus).

    PubMed

    Riggs, Shannon M; Hawkins, Michelle G; Craigmill, Arthur L; Kass, Philip H; Stanley, Scott D; Taylor, Ian T

    2008-05-01

    To determine the pharmacokinetics of butorphanol tartrate after IV and IM single-dose administration in red-tailed hawks (RTHs) and great horned owls (GHOs). 6 adult RTHs and 6 adult GHOs. Each bird received an injection of butorphanol (0.5 mg/kg) into either the right jugular vein (IVj) or the pectoral muscles in a crossover study (1-week interval between treatments). The GHOs also later received butorphanol (0.5 mg/kg) via injection into a medial metatarsal vein (IVm). During each 24-hour postinjection period, blood samples were collected from each bird; plasma butorphanol concentrations were determined via liquid chromatography-mass spectrometry. 2- and 1-compartment models best fit the IV and IM pharmacokinetic data, respectively, in both species. Terminal half-lives of butorphanol were 0.94 +/- 0.30 hours (IVj) and 0.94 +/- 0.26 hours (IM) for RTHs and 1.79 +/- 1.36 hours (IVj), 1.84 +/- 1.56 hours (IM), and 1.19 +/- 0.34 hours (IVm) for GHOs. In GHOs, area under the curve (0 to infinity) for butorphanol after IVj or IM administration exceeded values in RTHs; GHO values after IM and IVm administration were less than those after IVj administration. Plasma butorphanol clearance was significantly more rapid in the RTHs. Bioavailability of butorphanol administered IM was 97.6 +/- 33.2% (RTHs) and 88.8 +/- 4.8% (GHOs). In RTHs and GHOs, butorphanol was rapidly absorbed and distributed via all routes of administration; the drug's rapid terminal half-life indicated that published dosing intervals for birds may be inadequate in RTHs and GHOs.

  8. Effects of sorbitol on porcine oocyte maturation and embryo development in vitro.

    PubMed

    Lin, Tao; Zhang, Jin Yu; Diao, Yun Fei; Kang, Jung Won; Jin, Dong-Il

    2015-04-01

    In the present study, a porcine system was supplemented with sorbitol during in vitro maturation (IVM) or in vitro culture (IVC), and the effects of sorbitol on oocyte maturation and embryonic development following parthenogenetic activation were assessed. Porcine immature oocytes were treated with different concentrations of sorbitol during IVM, and the resultant metaphase II stage oocytes were activated and cultured in porcine zygote medium-3 (PZM-3) for 7 days. No significant difference was observed in cumulus expansion and the nuclear maturation between the control and sorbitol-treated groups, with the exception of the 100 mM group, which showed significantly decreased nuclear maturation and cumulus expansion. There was no significant difference in the intracellular reactive oxygen species (ROS) levels between oocytes matured with 10 or 20 mM sorbitol and control groups, but 50 and 100 mM groups had significantly higher ROS levels than other groups. The 20 mM group showed significant increases in intracellular glutathione and subsequent blastocyst formation rates following parthenogenetic activation compared with the other groups. During IVC, supplementation with sorbitol significantly reduced blastocyst formation and increased the apoptotic index compared with the control. The apoptotic index of blastocysts from the sorbitol-treated group for entire culture period was significantly higher than those of the partially sorbitol-exposed groups. Based on these findings, it can be concluded that the addition of a low concentration of sorbitol (20 mM) during IVM of porcine oocytes benefits subsequent blastocyst development and improves embryo quality, whereas sorbitol supplement during IVC has a negative effect on blastocyst formation.

  9. Differential expression and localization of glycosidic residues in in vitro- and in vivo-matured cumulus-oocyte complexes in equine and porcine species.

    PubMed

    Accogli, Gianluca; Douet, Cécile; Ambruosi, Barbara; Martino, Nicola Antonio; Uranio, Manuel Filioli; Deleuze, Stefan; Dell'Aquila, Maria Elena; Desantis, Salvatore; Goudet, Ghylène

    2014-12-01

    Glycoprotein oligosaccharides play major roles during reproduction, yet their function in gamete interactions is not fully elucidated. Identification and comparison of the glycan pattern in cumulus-oocyte complexes (COCs) from species with different efficiencies of in vitro spermatozoa penetration through the zona pellucida (ZP) could help clarify how oligosaccharides affect gamete interactions. We compared the expression and localization of 12 glycosidic residues in equine and porcine in vitro-matured (IVM) and preovulatory COCs by means of lectin histochemistry. The COCs glycan pattern differed between animals and COC source (IVM versus preovulatory). Among the 12 carbohydrate residues investigated, the IVM COCs from these two species shared: (a) sialo- and βN-acetylgalactosamine (GalNAc)-terminating glycans in the ZP; (b) sialylated and fucosylated glycans in cumulus cells; and (c) GalNAc and N-acetylglucosamine (GlcNAc) glycans in the ooplasm. Differences in the preovulatory COCs of the two species included: (a) sialoglycans and GlcNAc terminating glycans in the equine ZP versus terminal GalNAc and internal GlcNAc in the porcine ZP; (b) terminal galactosides in equine cumulus cells versus terminal GlcNAc and fucose in porcine cohorts; and (c) fucose in the mare ooplasm versus lactosamine and internal GlcNAc in porcine oocyte cytoplasm. Furthermore, equine and porcine cumulus cells and oocytes contributed differently to the synthesis of ZP glycoproteins. These results could be attributed to the different in vitro fertilization efficiencies between these two divergent, large-animal models. © 2014 Wiley Periodicals, Inc.

  10. Somatic cell nuclear transfer using transported in vitro-matured oocytes in cynomolgus monkey.

    PubMed

    Chen, N; Liow, S-L; Abdullah, R Bin; Embong, W Khadijah Wan; Yip, W-Y; Tan, L-G; Tong, G-Q; Ng, S-C

    2007-02-01

    Somatic cell nuclear transfer (SCNT) is not successful so far in non-human primates. The objective of this study was to investigate the effects of stimulation cycles (first and repeat) on oocyte retrieval and in vitro maturation (IVM) and to evaluate the effects of stimulation cycles and donor cell type (cumulus and fetal skin fibroblasts) on efficiency of SCNT with transported IVM oocytes. In this study, 369 immature oocytes were collected laparoscopically at 24 h following human chorionic gonadotrophin (hCG) treatment from 12 cynomolgus macaque (Macaca fascicularis) in 24 stimulation cycles, and shipped in pre-equilibrated IVM medium for a 5 h journey, placed in a dry portable incubator (37 degrees C) without CO(2) supplement. A total of 70.6% (247/350) of immature oocytes reached metaphase II (MII) stage at 36 h after hCG administration, MII spindle could be seen clearly in 80.6% (104/129) of matured IVM oocytes under polarized microscopy. A total of 50.0% (37/74) of reconstructive SCNT embryos cleaved after activation; after cleavage, 37.8% (14/37) developed to the 8-cell stage and 8.1% (3/37) developed to morula, but unfortunately none developed to the blastocyst stage. Many more oocytes could be retrieved per cycle from monkeys in the first cycle than in repeated cycles (19.1 vs. 11.7, p < 0.05). There were no significant differences in the maturation rate (70.0 vs. 71.4%, p > 0.05) and MII spindle rate under polarized microscopy (76.4 vs. 86.0%, p > 0.05) between the first and repeat cycles. There were also no significant differences in the cleavage rate, and the 4-cell, 8-cell and morula development rate of SCNT embryos between the first and repeat cycles. When fibroblast cells and cumulus cells were used as the donor cells for SCNT, first cleavage rate was not significantly different, but 4-cell (50.0 vs. 88.9%, p < 0.05) and 8-cell (0 vs. 51.9%, p < 0.01) development rate were significantly lower for the former. In conclusion, the number of stimulation cycles has a significant effect on oocyte retrieval, but has no effect on maturation and SCNT embryo development; however, different donor cell types (cumulus and fibroblast) resulted in different developmental potentials of SCNT embryos.

  11. The role of cGMP as a mediator of lipolysis in bovine oocytes and its effects on embryo development and cryopreservation.

    PubMed

    Schwarz, Kátia R L; de Castro, Fernanda C; Schefer, Letícia; Botigelli, Ramon C; Paschoal, Daniela M; Fernandes, Hugo; Leal, Cláudia L V

    2018-01-01

    This study aimed to determine the influence of cyclic guanosine 3'5'-monophosphate (cGMP) and cGMP-dependent kinase (PKG) during in vitro maturation (IVM) on lipolysis-related parameters in bovine cumulus-oocyte complexes (COCs), and on embryo development and cryosurvival. COCs were matured with cGMP/PKG modulators and assessed for metaphase II rates (MII), cGMP levels, lipid content in oocytes (OO), transcript abundance for genes involved in lipolysis (ATGL) and lipid droplets (PLIN2) in cumulus cells (CC) and OO, and presence of phosphorylated (active) hormone sensitive lipase (HSLser563) in OO. Embryo development, lipid contents and survival to vitrification were also assessed. Phosphodiesterase 5 inhibition (PDE5; cGMP-hydrolyzing enzyme) with 10-5M sildenafil (SDF) during 24 h IVM increased cGMP in COCs (56.9 vs 9.5 fMol/COC in untreated controls, p<0.05) and did not affect on maturation rate (84.3±6.4% MII). Fetal calf serum (FCS) in IVM medium decreased cGMP in COCs compared to bovine serum albumin (BSA) + SDF (19.6 vs 66.5 fMol/COC, respectively, p<0.05). FCS increased lipid content in OO (40.1 FI, p<0.05) compared to BSA (34.6 FI), while SDF decreased (29.8 and 29.6 FI, with BSA or FCS, respectively p<0.05). PKG inhibitor (KT5823) reversed this effect (38.9 FI, p<0.05). ATGL and PLIN2 transcripts were detected in CC and OO, but were affected by cGMP and PKG only in CC. HSLser563 was detected in OO matured with or without modulators. Reduced lipid content in embryos were observed only when SDF was added during IVM and IVC (27.6 FI) compared to its use in either or none of the culture periods (34.2 FI, p<0.05). Survival to vitrification was unaffected by SDF. In conclusion, cGMP and PKG are involved in lipolysis in OO and possibly in CC and embryos; serum negatively affects this pathway, contributing to lipid accumulation, and cGMP modulation may reduce lipid contents in oocytes and embryos, but without improving embryo cryotolerance.

  12. Prevalencia de alteraciones en la interfase vitreoretiniana detectadas mediante tomografía de coherencia óptica de dominio espectral.

    PubMed

    Jacob, Julie; Stalmans, Peter

    2017-07-11

    Objetivo: El objetivo principal del presente estudio consistió en determinar la prevalencia de los cambios en la interfase vitreomacular (IVM) mediante tomografía de coherencia óptica (OCT) en la población general. En segundo lugar, se describieron otros cambios de la OCT. Métodos: Las anomalías en la IVM se diagnosticaron mediante OCT y se distribuyeron de acuerdo con la clasificación del grupo International Vitreomacular Traction Study (estudio internacional de tracción vitreomacular, IVTS, por sus siglas en inglés) y se dividieron en 3 grados según John et al. [Retina 2014;34:442-446]. Resultados: La prevalencia calculada de anomalías vitreomaculares en la población belga de ≥50 años fue del 1,17% [intervalo de confianza (IC 0,38-3,62)] en el caso de tracción vitreomacular (TVM) focal de grado 1; del 0,39% (IC 0,05-2,76) en el caso de TVM focal de grado 2; del 8,17% (IC 5,33-12,53) en el caso de adhesión vitreomacular focal; y del 17,9% (IC 13,41-23,9) en el caso de adhesión vitreomacular difusa. Conclusiones: Se presentó la prevalencia de anomalías vitreomaculares en un estudio de cohortes belga. Estos resultados concuerdan en gran medida con los datos presentados previamente sobre la prevalencia de la TVM. Un conocimiento correcto sobre la epidemiología de las alteraciones en la IVM y un diagnóstico temprano permitirán una intervención satisfactoria. © 2017 S. Karger AG, Basel.

  13. Pronuclear synchronization and nuclear morphology of mature and in vitro matured oocytes in the rat: an ultrastructural study.

    PubMed

    Cincik, M; Baykal, B; Zeteroglu, S; Onalan, G; Ceyhan, S T; Ergur, R

    2005-01-01

    The objective of this study was to evaluate synchronous and asynchronous pronucleus (PN) formation and the related patterns of juxtapositional nucleolus (n) formation in immature (prophase I [PI] and metaphase I [MI]) and mature (metaphase II [MII]) oocytes after fertilization, both ultrastructurally and at the level of light microscope. A single dose of 15 IU gonadotrophin was injected subcutaneously to twenty four 26-wk-old, female Wistar rats to induce ovulation. Human chorionic gonadotrophin (4 IU) was administered 40 h later, and after 4-6 h the ovaries were dissected, and the oocytes were aspirated. A total of 214 rat oocytes were classified according to a maturation index as follows: group I, 80 PI oocytes; group II, 50 MI oocytes; and group III, 84 MII oocytes. Immature oocytes were in vitro matured for 18-36 h. Spermatozoa were acquired by microepididymal sperm aspiration and processed using swim-up technique. Intracytoplasmic sperm injection was performed on mature oocytes after 2 h of incubation and on in vitro matured (IVM) oocytes 4 h after maturation. Pronuclear synchronization [both pronucleases (PNs) centrally located, equal sized, with equal numbers and sizes of juxtapositional nucleoli (Nn)] was observed in fertilized oocytes. Asynchronous PN formation (diversity between male and female PNs, related to dimensions, localization, and the number of Nn) in groups I, II, and III was found in 75, 86, and 47% of preembryos, respectively. There was a significant difference of synchronous pronuclear formation between mature and IVM oocytes (P < 0.05). In IVM oocytes, asynchronous PN formation is high, and juxtapositional pronucleolar patterns are observed to be low by transmission electron microscope (TEM).

  14. Fibroblast Growth Factor 10 Enhances the Developmental Efficiency of Somatic Cell Nuclear Transfer Embryos by Accelerating the Kinetics of Cleavage During In Vitro Maturation.

    PubMed

    Son, Yeo-Jin; Lee, Seung-Eun; Park, Yun-Gwi; Jeong, Sang-Gi; Shin, Min-Young; Kim, Eun-Young; Park, Se-Pill

    2018-06-01

    Somatic cell nuclear transfer (SCNT) is required for the generation of transgenic animals as disease models. During the in vitro development of SCNT embryos, the quality of matured oocytes is one of the major factors regulating the developmental potential of embryos. Time-lapse monitoring systems are new tools that assess the developmental capacity of embryos for use in embryo transfer. In this study, we investigated the effect of fibroblast growth factor 10 (FGF 10) on the developmental potential of SCNT embryos. After the in vitro maturation (IVM) of oocytes in IVM medium containing 10 ng/mL FGF 10 (10 F), the polar body extrusion rate was significantly higher than in the control. However, there was no difference in the percentage of fused embryos between the groups. The cleavage and blastocyst formation rates of embryos were significantly increased in the 10 F compared with the control. In addition, the total cell number was higher and the apoptotic index was lower in the 10 F than control at day 7. The messenger RNA (mRNA) expression of genes involved in apoptosis (baculoviral inhibitor of apoptosis repeat containing 5 [BIRC5] and caspase 3 [CASP3]) and development (octamer-binding transcription factor 4 [POU5F1] and sex determining region Y box 2 [SOX2]) increased after 10 F treatment. Furthermore, the kinetics of the first cleavage was faster and the percentage of embryos at cell block was significantly lower in the 10 F group than in the control. These results demonstrate that exposure of oocytes to FGF 10 during IVM promotes developmental competence.

  15. Time-dependent effect of clonidine on microvascular permeability during endotoxemia.

    PubMed

    Schmidt, Karsten; Hernekamp, Jochen Frederick; Philipsenburg, Christoph; Zivkovic, Aleksandar R; Brenner, Thorsten; Hofer, Stefan

    2015-09-01

    Endothelial leakage with accompanying tissue edema and increased leukocyte adhesion are characteristics of the vascular inflammatory response. Tissue edema formation is a key mechanism in sepsis pathophysiology contributing to impaired tissue oxygenation and the development of shock. Sepsis mortality is directly associated with the severity of these microcirculatory alterations. Dysfunction of the sympathetic nervous system can have deleterious effects in generalized inflammation. This study evaluated the effect of the adrenergic alpha 2 agonist clonidine on microvascular permeability and leukocyte adhesion during endotoxemia. Macromolecular leakage, leukocyte adhesion, and venular wall shear rate were examined in mesenteric postcapillary venules of rats by using intravital microscopy (IVM). Lipopolysaccharide (LPS) (4mg/kg/h) or equivalent volumes of saline were continuously infused following baseline IVM at 0min. IVM was repeated after 60 and 120min in endotoxemic and nonendotoxemic animals. Clonidine (10μg/kg) was applied as an i.v. bolus. Animals received either (i) saline alone, (ii) clonidine alone, (iii) clonidine 45min prior to LPS, (iv) clonidine 10min prior to LPS, (v) clonidine 30min after LPS, or (vi) LPS alone. Due to nonparametric data distribution, Wilcoxon test and Dunn's multiple comparisons test were used for data analysis. Data were considered statistically significant at p<0.05. LPS significantly increased microvascular permeability and leukocyte adhesion and decreased venular wall shear rate. Clonidine significantly reduced microvascular permeability when applied 45min before or 30min after LPS administration. Leukocyte adhesion and venular wall shear rate were not affected by clonidine during endotoxemia. Clonidine reduces microvascular permeability in endotoxemic animals in a time-dependent manner. Adrenergic alpha 2 agonists might prove beneficial in stabilizing capillary leakage during inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. The presence of acylated ghrelin during in vitro maturation of bovine oocytes induces cumulus cell DNA damage and apoptosis, and impairs early embryo development.

    PubMed

    Sirini, Matias A; Anchordoquy, Juan Mateo; Anchordoquy, Juan Patricio; Pascua, Ana M; Nikoloff, Noelia; Carranza, Ana; Relling, Alejandro E; Furnus, Cecilia C

    2017-10-01

    The aim of this study was to investigate the effects of acylated ghrelin supplementation during in vitro maturation (IVM) of bovine oocytes. IVM medium was supplemented with 20, 40 or 60 pM acylated ghrelin concentrations. Cumulus expansion area and oocyte nuclear maturation were studied as maturation parameters. Cumulus-oocyte complexes (COC) were assessed with the comet, apoptosis and viability assays. The in vitro effects of acylated ghrelin on embryo developmental capacity and embryo quality were also evaluated. Results demonstrated that acylated ghrelin did not affect oocyte nuclear maturation and cumulus expansion area. However, it induced cumulus cell (CC) death, apoptosis and DNA damage. The damage increased as a function of the concentration employed. Additionally, the percentages of blastocyst yield, hatching and embryo quality decreased with all acylated ghrelin concentrations tested. Our study highlights the importance of acylated ghrelin in bovine reproduction, suggesting that this metabolic hormone could function as a signal that prevents the progress to reproductive processes.

  17. Effects of Mastery Learning Strategies on Community College Mathematics Students' Achievement and Success Rate.

    ERIC Educational Resources Information Center

    Abadir, Laila; And Others

    The effects of mastery learning strategies, interactive video mathematics (IVM), individualized instruction (IND), and the lecture method on mathematics achievement of community college students was studied. Interactions among instructional methods, gender, and age were examined; and the grade success rate was determined for each instructional…

  18. Talimogene Laherparepvec for Treating Metastatic Melanoma: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

    PubMed

    Fleeman, Nigel; Bagust, Adrian; Boland, Angela; Beale, Sophie; Richardson, Marty; Krishan, Ashma; Stainthorpe, Angela; Abdulla, Ahmed; Kotas, Eleanor; Banks, Lindsay; Payne, Miranda

    2017-10-01

    The National Institute for Health and Care Excellence (NICE) invited the manufacturer (Amgen) of talimogene laherparepvec (T-VEC) to submit clinical and cost-effectiveness evidence for previously untreated advanced (unresectable or metastatic) melanoma as part of the Institute's Single Technology Appraisal process. The Liverpool Reviews and Implementation Group (LRiG) at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG). This article presents a summary of the company's submission of T-VEC, the ERG review and the resulting NICE guidance (TA410), issued in September 2016. T-VEC is an oncolytic virus therapy granted a marketing authorisation by the European Commission for the treatment of adults with unresectable melanoma that is regionally or distantly metastatic (stage IIIB, IIIC and IVM1a) with no bone, brain, lung or other visceral disease. Clinical evidence for T-VEC versus granulocyte-macrophage colony-stimulating factor (GM-CSF) was derived from the multinational, open-label randomised controlled OPTiM trial [Oncovex (GM-CSF) Pivotal Trial in Melanoma]. In accordance with T-VEC's marketing authorisation, the company's submission focused primarily on 249 patients with stage IIIB to stage IV/M1a disease who constituted 57% of the overall trial population (T-VEC, n = 163 and GM-CSF, n = 86). Results from analyses of durable response rate, objective response rate, time to treatment failure and overall survival all showed marked and statistically significant improvements for patients treated with T-VEC compared with those treated with GM-CSF. However, GM-CSF is not used to treat melanoma in clinical practice. It was not possible to compare treatment with T-VEC with an appropriate comparator using conventionally accepted methods due to the absence of comparative head-to-head data or trials with sufficient common comparators. Therefore, the company compared T-VEC with ipilimumab using what it described as modified Korn and two-step Korn methods. Results from these analyses suggested that treatment with T-VEC was at least as effective as treatment with ipilimumab. Using the discounted patient access scheme (PAS) price for T-VEC and list price for ipilimumab, the company reported incremental cost-effectiveness ratios (ICERs) per quality-adjusted life-year (QALY) gained. For the comparison of treatment with T-VEC versus ipilimumab, the ICER per QALY gained was -£16,367 using the modified Korn method and -£60,271 using the two-step Korn method. The NICE Appraisal Committee (AC) agreed with the ERG that the company's methods for estimating clinical effectiveness of T-VEC versus ipilimumab were flawed and therefore produced unreliable results for modelling progression in stage IIIB to stage IVM1a melanoma. The AC concluded that the clinical and cost effectiveness of treatment with T-VEC compared with ipilimumab is unknown in patients with stage IIIB to stage IV/M1a disease. However, the AC considered that T-VEC may be a reasonable option for treating patients who are unsuitable for treatment with systemically administered immunotherapies (such as ipilimumab). T-VEC was therefore recommended by NICE as a treatment option for adults with unresectable, regionally or distantly metastatic (stage IIIB to stage IVM1a) melanoma that has not spread to bone, brain, lung or other internal organs, only if treatment with systemically administered immunotherapies is not suitable and the company provides T-VEC at the agreed discounted PAS price.

  19. Pharmacokinetic drug evaluation of talimogene laherparepvec for the treatment of advanced melanoma.

    PubMed

    Burke, Erin E; Zager, Jonathan S

    2018-04-01

    Current treatment of advanced melanoma is rapidly changing with the introduction of new and effective therapies including systemic as well as locoregional therapies. An example of one such locoregional therapy is intralesional injection with talimogene laherparepvec (T-VEC). Areas covered: T-VEC has been shown in a number of studies to be an effective treatment for patients with stage IIIB, IIIC and IVM1a melanoma. In this article the effectiveness, pharmacokinetics and safety profile of T-VEC is reviewed. Additionally, new research looking at combinations of T-VEC and systemic immunotherapies is reviewed. Expert opinion: Overall, T-VEC is an easily administered, safe, well tolerated and effective oncolytic viral therapy for the treatment of stage IIIB, IIIC, IVM1a unresectable and injectable metastatic melanoma. Recently published studies are showing promising results when T-VEC is combined with systemic therapy and this may be the way of the not too distant future in how we treat metastatic melanoma. Continued work regarding the use of T-VEC with other systemic agents will provide new and more effective treatment strategies for advanced melanoma.

  20. Toxic effects of ethylene oxide residues on bovine embryos in vitro.

    PubMed

    Holyoak, G R; Wang, S; Liu, Y; Bunch, T D

    1996-04-15

    The potential of ethylene oxide (EtO) residues in exposed plastic tissue culture dishes to adversely affect bovine oocyte maturation, fertilization and subsequent embryonic development was monitored. In experiment 1, the effects of aeration time and aeration combined with washing of EtO-gassed culture dishes on the extent of residual toxicity were investigated. There was no cleavage in any treatment in which oocytes were matured and fertilized in dishes exposed to EtO. EtO residues caused functional degeneration of oocytes even when culture dishes were aerated for more than 12 days post EtO-exposure and repeatedly washed. In experiment 2, the residual toxicity of EtO gas on in vitro maturation (IVM), in vitro fertilization (IVF) and in vitro culture (IVC) were evaluated. Cleavage rate significantly decreased and post-cleavage development was retarded in ova maintained in dishes treated with EtO either during IVM or IVF. EtO residues may be more detrimental to spermatozoa than to oocytes which may have been the primary cause of fertilization failure during IVF.

  1. Effect of sericin supplementation in maturation medium on cumulus cell expansion, oocyte nuclear maturation, and subsequent embryo development in Sanjabi ewes during the breeding season.

    PubMed

    Aghaz, F; Hajarian, H; Shabankareh, H Karami; Abdolmohammadi, A

    2015-12-01

    The purpose of this study was to evaluate the effect of sericin with different concentrations (0% [control], 0.1%, 0.5%, 1.0%, and 2.5%) added to the IVM medium on cumulus cell expansion, oocyte nuclear maturation, and subsequent embryo development in Sanjabi ewes during the breeding season. The resumption of meiosis was assessed by the frequency of germinal vesicle breakdown and the first polar body extrusion. After IVF with fresh ram semen, presumptive zygotes were cultured 8 days in potassium simplex optimization medium supplemented by amino acids, and the percentages developing to the two-cell and blastocyst stages were measured as the indicators of early embryonic developmental competence. More cumulus-oocyte complexes matured with 0.5% sericin underwent germinal vesicle breakdown and reached metaphase II stage compared with the control cumulus-oocyte complexes matured without sericin (P ≤ 0.05). The present findings indicated that supplementation with 0.5% sericin during the maturation culture may improve the nuclear maturation and the cumulus cell expansion. Furthermore, the percentage of blastocysts obtained from 0.5% and 0.1% sericin (37.8 ± 1.76% and 34.8 ± 1.09%, respectively) was higher (P ≤ 0.05) than that of the control medium (29.60 ± 1.67%). However, addition of 1% and 2.5% of sericin to the IVM medium oocytes had a negative effect on nuclear maturation and cumulus cell expansion. Furthermore, the percentage of cleavage and blastocyst rate was significantly lower in the 1% and 2.5% sericin groups than in the control group. These findings showed that supplementation of IVM medium with 0.5% sericin may improve the meiotic competence of oocytes and early embryonic development in Sanjabi ewes during the breeding season. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Fatty acid composition of porcine cumulus oocyte complexes (COC) during maturation: effect of the lipid modulators trans-10, cis-12 conjugated linoleic acid (t10,c12 CLA) and forskolin.

    PubMed

    Prates, E G; Alves, S P; Marques, C C; Baptista, M C; Horta, A E M; Bessa, R J B; Pereira, R M

    2013-05-01

    The effect of maturation and of two lipid modulators supplementation along in vitro maturation (IVM) on fatty acid (FA) and dimethylacetal (DMA) composition of porcine cumulus oocyte complexes (COC) were studied. Abattoir-derived immature COC were analyzed for FA and DMA or submitted to IVM as follows: control group; t10,c12 CLA group, t10,c12 CLA supplementation for 44 h; Forskolin group, forskolin supplementation during the initial 2 h; t10,c12 CLA + forskolin group, t10,c12 CLA for 44 h and forskolin for just 2h. Each experimental group had five replicates. FA analysis of oocytes, cumulus cells (CC), follicular fluid, and culture media were performed by gas-liquid chromatography. Oocytes and their CC had different FA composition. Oocytes were richer in saturated FA (SFA) preferentially maintaining their FA profile during maturation. Mature CC had the highest polyunsaturated FA (PUFA) content. Five individual and total SFA, and monounsaturated FA (MUFA), notably oleic acid (c9-18:1), percentages were lower (P ≤ 0.023) in mature than in immature CC. t10,c12 CLA was accumulated by COC from t10,c12 CLA and t10,c12 CLA + forskolin groups, mostly in CC where MUFA and an eicosatrienoic isomer decreased (P ≤ 0.043). Nevertheless, PUFA or FA and DMA total content were not affected. Arachidonic acid was reduced in t10,c12 CLA + forskolin CC and hexadecanal-DMA-16:0 in t10,c12 CLA CC. Forskolin alone increased (P ≤ 0.043) c9-18:1 in oocytes. In conclusion, maturation process clearly changed porcine COC FA and DMA profiles, mostly of CC, also more susceptible to modifications induced by t10,c12 CLA. This possibility of manipulating COC lipid composition during IVM could be used to improve oocyte quality/cryopreservation efficiency.

  3. Fat area and lipid droplet morphology of porcine oocytes during in vitro maturation with trans-10, cis-12 conjugated linoleic acid and forskolin.

    PubMed

    Prates, E G; Marques, C C; Baptista, M C; Vasques, M I; Carolino, N; Horta, A E M; Charneca, R; Nunes, J T; Pereira, R M

    2013-04-01

    Lipid droplets (LD) in porcine oocytes form a dark mass reaching almost all cytoplasm. Herein we investigated changes in fat areas, cytoplasmic tone and LD morphology during in vitro maturation (IVM) of porcine oocytes cultured with 100 μM trans-10, cis-12 conjugated linoleic acid (t10,c12 CLA) or 10 μM forskolin at different time periods. Four groups were constituted: control, excipient, t10,c12 CLA and forskolin, with drugs being supplemented during 44 to 48 h and the initial 22 to 24 h in Experiments 1 and 2, respectively. In Experiment 3, forskolin was supplemented for the first 2 h. Matured oocytes were inseminated with frozen-thawed boar semen and cleavage rate recorded. Before and during IVM, samples of oocytes were evaluated for LD, total and fat areas and fat gray value or for meiotic progression. Results showed that forskolin supplementation during 44 to 48 h or 22 to 24 h inhibits oocyte maturation (exp. 1: forskolin = 5.1 ± 8.0%, control = 72.6 ± 5.0%; exp. 2: forskolin = 24.3 ± 7.4%, control = 71.6 ± 5.6%) and cleavage (exp. 1: forskolin = 0.0 ± 0.0%, control = 55.4 ± 4.1%; exp. 2: forskolin = 8.3 ± 3.3%, control = 54.5 ± 3.0%). Forskolin also reduced oocyte and fat areas. In Experiment 3, forskolin negative effect on oocyte maturation and cleavage disappeared, although minor (P ⩽ 0.03) LD and oocyte fat areas were identified at 22 to 24 h of IVM. Oocytes supplemented with t10,c12 CLA during 44 to 48 h presented a lighter (P ⩽ 0.04) colour tone cytoplasm than those of control and forskolin. In conclusion, t10,c12 CLA and forskolin were capable of modifying the distribution and morphology of cytoplasmic LD during porcine oocyte maturation, thus reducing its lipid content in a time-dependent manner.

  4. Evaluation of the flipped classroom approach in a veterinary professional skills course

    PubMed Central

    Moffett, Jenny; Mill, Aileen C

    2014-01-01

    Background The flipped classroom is an educational approach that has had much recent coverage in the literature. Relatively few studies, however, use objective assessment of student performance to measure the impact of the flipped classroom on learning. The purpose of this study was to evaluate the use of a flipped classroom approach within a medical education setting to the first two levels of Kirkpatrick and Kirkpatrick’s effectiveness of training framework. Methods This study examined the use of a flipped classroom approach within a professional skills course offered to postgraduate veterinary students. A questionnaire was administered to two cohorts of students: those who had completed a traditional, lecture-based version of the course (Introduction to Veterinary Medicine [IVM]) and those who had completed a flipped classroom version (Veterinary Professional Foundations I [VPF I]). The academic performance of students within both cohorts was assessed using a set of multiple-choice items (n=24) nested within a written examination. Data obtained from the questionnaire were analyzed using Cronbach’s alpha, Kruskal–Wallis tests, and factor analysis. Data obtained from student performance in the written examination were analyzed using the nonparametric Wilcoxon rank sum test. Results A total of 133 IVM students and 64 VPF I students (n=197) agreed to take part in the study. Overall, study participants favored the flipped classroom approach over the traditional classroom approach. With respect to student academic performance, the traditional classroom students outperformed the flipped classroom students on a series of multiple-choice items (IVM mean =21.4±1.48 standard deviation; VPF I mean =20.25±2.20 standard deviation; Wilcoxon test, w=7,578; P<0.001). Conclusion This study demonstrates that learners seem to prefer a flipped classroom approach. The flipped classroom was rated more positively than the traditional classroom on many different characteristics. This preference, however, did not translate into improved student performance, as assessed by a series of multiple-choice items delivered during a written examination. PMID:25419164

  5. Evaluation of the flipped classroom approach in a veterinary professional skills course.

    PubMed

    Moffett, Jenny; Mill, Aileen C

    2014-01-01

    The flipped classroom is an educational approach that has had much recent coverage in the literature. Relatively few studies, however, use objective assessment of student performance to measure the impact of the flipped classroom on learning. The purpose of this study was to evaluate the use of a flipped classroom approach within a medical education setting to the first two levels of Kirkpatrick and Kirkpatrick's effectiveness of training framework. This study examined the use of a flipped classroom approach within a professional skills course offered to postgraduate veterinary students. A questionnaire was administered to two cohorts of students: those who had completed a traditional, lecture-based version of the course (Introduction to Veterinary Medicine [IVM]) and those who had completed a flipped classroom version (Veterinary Professional Foundations I [VPF I]). The academic performance of students within both cohorts was assessed using a set of multiple-choice items (n=24) nested within a written examination. Data obtained from the questionnaire were analyzed using Cronbach's alpha, Kruskal-Wallis tests, and factor analysis. Data obtained from student performance in the written examination were analyzed using the nonparametric Wilcoxon rank sum test. A total of 133 IVM students and 64 VPF I students (n=197) agreed to take part in the study. Overall, study participants favored the flipped classroom approach over the traditional classroom approach. With respect to student academic performance, the traditional classroom students outperformed the flipped classroom students on a series of multiple-choice items (IVM mean =21.4±1.48 standard deviation; VPF I mean =20.25±2.20 standard deviation; Wilcoxon test, w=7,578; P<0.001). This study demonstrates that learners seem to prefer a flipped classroom approach. The flipped classroom was rated more positively than the traditional classroom on many different characteristics. This preference, however, did not translate into improved student performance, as assessed by a series of multiple-choice items delivered during a written examination.

  6. Modelling studies determing the mode of action of anthelmintics inhibiting in vitro trehalose-6-phosphate phosphatase (TPP) of Anisakis simplex s.l.

    PubMed

    Łopieńska-Biernat, Elżbieta; Molcan, Tomasz; Paukszto, Łukasz; Jastrzębski, Jan Paweł; Myszczyński, Kamil

    2018-01-01

    The trehalose-6-phosphate phosphatase (TPP) enzyme is involved in the synthesis of trehalose, the main sugar in the energy metabolism of nematodes. TPP is a member of the HAD-like hydrolase superfamily and shows a robust and specific phosphatase activity for the substrate trehalose-6-phosphate. The presence of conserved active sites of TPP in closely related nematodes and its absence in humans makes it a promising target for antiparasitic drugs. In the present study, homology modeling, molecular docking and MD simulation techniques were used to explore the structure and dynamics of TPP. In the active site, a magnesium ion is stabilized by 3 coordinate bonds formed by D 189 , D 191 and D 400 . The key amino acids involved in ligand binding by the enzyme are C 198 , Y 201 ,T 357 , D 191 and Y 197 . This study relied on docking to select potential inhibitors of TPP which were tested in vitro for sensitivity to anthelmintic drugs such as levamisole and ivermectin targeting Anisakis simplex. The higher toxicity of LEV than IVM was demonstrated after 96 h, 30% of larvae were motile in cultures with 100 μg/ml of LEV and 1000 μg/ml of IVM. We identified drug combination of LEV-IVM against in vitro A. simplex as agonistic effect (CI = 1.1). Levamisole appeared to be a more effective drug which inhibited enzyme activity after 48 h and expression of mRNA after 96 h at a concentration of 10 μg/ml. This preliminary study predicted the structure of TPP, and the results of an in vitro experiment involving A. simplex will contribute to the development of effective inhibitors with potential antiparasitic activity in the future. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Pipette-tip solid-phase extraction using polypyrrole as efficient adsorbent for extraction of avermectins and milbemycins in milk.

    PubMed

    Florez, Diego Hernando Ângulo; Teixeira, Roseane Andrade; da Silva, Ricky Cássio Santos; Pires, Bruna Carneiro; Dutra, Flávia Viana Avelar; Borges, Keyller Bastos

    2018-05-01

    In this work, we developed a HPLC method for the multidetermination of avermectins (AVM) (abamectin-ABA 1b and ABA 1a, eprinomectin-EPR, and ivermectin-IVM) and milbemycins (moxidectin-MOX) in milk samples using polypyrrole (PPy) as adsorbent material in pipette-tip solid-phase extraction (PT-PPy-SPE). PPy was characterized by scanning electron microscopy, thermogravimetric analysis, Fourier transform infrared spectroscopy, and X-ray diffraction and the data agreed with the literature. The sample preparation included the clean-up of the milk by protein precipitation (PP) with acetonitrile and extraction of the analytes by PT-PPy-SPE. The chromatographic method was developed in reverse phase and isocratic mode with flow rate at 1.2 mL min -1 and ultraviolet detection at 250 nm. The mobile phase composition was acetonitrile:methanol:water (55:25:20, v/v/v). The studied parameters and the optimized conditions for the sample preparation were washing solvent (300 μL water), volume and type of eluent (500 μL methanol), volume and pH of sample (1 mL and pH 10), amount of adsorbent material (50 mg PPy), and without addition of salt (NaCl). The method was linear over the concentration range from 20 to 3000 ng mL -1 with coefficients of correlation (r) ≥ 0.99 for all analytes and recoveries around 100%. The method developed and validated was used for the analyses of real milk samples from cow treated with Ivomec ® (IVM 3.5%), in which were found 21.51 ± 2.94 ng mL -1 of IVM. Finally, the results proved that PT-PPy-SPE coupled to HPLC-UV was economical, simple, and easy-to-perform technique. Graphical abstract Pipette-tip solid phase extraction using polypirrole as adsorbent material for determination of avermectins and milbemycins in milk.

  8. Addition of insulin-like growth factor I to the maturation medium of bovine oocytes subjected to heat shock: effects on the production of reactive oxygen species, mitochondrial activity and oocyte competence.

    PubMed

    Ascari, I J; Alves, N G; Jasmin, J; Lima, R R; Quintão, C C R; Oberlender, G; Moraes, E A; Camargo, L S A

    2017-07-01

    This study was performed to investigate the effects of insulin-like growth factor-I (IGF-I) addition to in vitro maturation (IVM) medium on apoptosis, mitochondrial membrane potential, ROS production, and developmental competence of bovine oocytes subjected to heat shock. Two temperatures (conventional: 24 h at 38.5°C, or heat shock: 12 h at 41°C followed by 12 h at 38.5°C) and 3 IGF-I concentrations (0, 25, and 100 ng/mL) were tested during IVM. The oocytes were then fertilized in vitro, and the presumptive zygotes were cultured until reaching the blastocyst stage. There was no interaction between temperature and IGF-I concentration for any variable evaluated (P > 0.05). The addition of IGF-I did not alter the proportion of nuclear maturation, TUNEL-positive oocytes and caspase-3 activity, or blastocyst proportion on Days 7 and 8 post-fertilization. Furthermore, the total number of cells and the number of cells in the inner cell mass (ICM) in the blastocyst were not altered (P > 0.05). However, IGF-I increased (P < 0.05) the mitochondrial membrane potential and the production of ROS in oocytes and decreased (P < 0.05) the proportion of apoptotic cells in the ICM in blastocysts. Heat shock increased (P < 0.05) the proportion of TUNEL-positive oocytes and ROS production and reduced (P < 0.05) the mitochondrial membrane potential. Moreover, heat shock increased (P < 0.05) the apoptosis proportion in the ICM cells. In conclusion, supplementing IVM medium with IGF-I may increase the mitochondrial membrane potential and ROS production in oocytes and decrease apoptosis in the ICM in blastocysts. Heat shock for 12 h compromised oocyte developmental competence and increased apoptosis within the ICM cells of the blastocysts. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Embryo apoptosis identification: Oocyte grade or cleavage stage?

    PubMed Central

    Bakri, Noraina Mohd; Ibrahim, Siti Fatimah; Osman, Nurul Atikah; Hasan, Nurhaslina; Jaffar, Farah Hanan Fathihah; Rahman, Zulaiha Abdul; Osman, Khairul

    2015-01-01

    Apoptosis is a programed cell death that is vital for tissue homeostasis. However, embryo apoptosis had been known to be related to embryo fragmentation which should be avoided in in vitro fertilization (IVF). The purpose of this study was to evaluate the relationship of embryo apoptosis with the grade of immature oocytes and cleavage stage of in vitro produced (IVP) cattle embryos. This study consisted of 345 oocytes collected through ovary slicing. Immature oocytes were graded as A, B and C. This grading was based on cumulus cell thickness and compactness. All oocytes then underwent an in vitro maturation (IVM) procedure. An IVF was done 24 h after IVM culture. Prior to staining, stage of cleaved embryos was determined and classified as either 2, 4, 8 or >8-cell embryo stage. Apoptosis status of cleaved IVP embryos was determined by using annexin V-FITC staining technique at 48 and 72 h post insemination (hpi). Apoptosis status for each embryo was classified as either early or late. The result showed that there was no significant difference (p > 0.05) of apoptosis status among grade A, B and C embryos. All grades of oocytes showed embryo apoptosis where 1.5% late apoptosis for grade A, 4.5% and 10.4% of early and late apoptosis for grade B and grade C. Early apoptosis was not seen in grade A embryo. We also noted no significant difference (p > 0.05) of apoptosis status between 2, 4, 8 and >8-cell embryo stage. Early apoptosis was also not seen in >8-cell stage. Even though there were no differences in apoptosis expression between the three classes, the cleavage rate of grade A oocytes was significantly higher (p < 0.01) than grade B and grade C. In conclusion, the apoptosis expression in the embryo can occur regardless of the oocyte quality and the cleavage stage of the embryo produced. PMID:26858565

  10. Visualizing Viral Infection In Vivo by Multi-Photon Intravital Microscopy.

    PubMed

    Sewald, Xaver

    2018-06-20

    Viral pathogens have adapted to the host organism to exploit the cellular machinery for virus replication and to modulate the host cells for efficient systemic dissemination and immune evasion. Much of our knowledge of the effects that virus infections have on cells originates from in vitro imaging studies using experimental culture systems consisting of cell lines and primary cells. Recently, intravital microscopy using multi-photon excitation of fluorophores has been applied to observe virus dissemination and pathogenesis in real-time under physiological conditions in living organisms. Critical steps during viral infection and pathogenesis could be studied by direct visualization of fluorescent virus particles, virus-infected cells, and the immune response to viral infection. In this review, I summarize the latest research on in vivo studies of viral infections using multi-photon intravital microscopy (MP-IVM). Initially, the underlying principle of multi-photon microscopy is introduced and experimental challenges during microsurgical animal preparation and fluorescent labeling strategies for intravital imaging are discussed. I will further highlight recent studies that combine MP-IVM with optogenetic tools and transcriptional analysis as a powerful approach to extend the significance of in vivo imaging studies of viral pathogens.

  11. Quercetin improves the in vitro development of porcine oocytes by decreasing reactive oxygen species levels

    PubMed Central

    Kang, Jung-Taek; Kwon, Dae-Kee; Park, Sol-Ji; Kim, Su-Jin; Moon, Joon-Ho; Koo, Ok-Jae; Jang, Goo

    2013-01-01

    Quercetin is a plant-derived flavonoid found in fruits or vegetables that has antioxidant properties and acts as a free radical scavenger. We investigated the effects of quercetin on porcine oocyte nuclear maturation and embryonic development after parthenogenetic activation. We then evaluated the antioxidant activities of quercetin by measuring reactive oxygen species (ROS) levels in matured oocytes. Immature oocytes were untreated or treated with 1, 10, and 50 µg/mL quercetin during in vitro maturation (IVM). Quercetin treatment did not improve oocyte nuclear maturation, but significantly higher blastocyst rates (p < 0.05) of parthenogenetically activated oocytes were achieved when the IVM medium was supplemented with an adequate concentration of quercetin (1 µg/mL). However, cleavage rates and blastocyst cell numbers were not affected. Oocytes treated with 1 or 10 µg/mL quercetin had significantly lower (p < 0.05) levels of ROS than the control and group treated with the highest concentration of quercetin (50 µg/mL). Moreover, this highest concentration was detrimental to oocyte nuclear maturation and blastocyst formation. Based on our findings, we concluded that exogenous quercetin reduces ROS levels during oocyte maturation and is beneficial for subsequent embryo development. PMID:23388446

  12. Update on the distribution of Mansonella perstans in the southern part of Cameroon: influence of ecological factors and mass drug administration with ivermectin.

    PubMed

    Wanji, Samuel; Tayong, Dizzle Bita; Layland, Laura E; Datchoua Poutcheu, Fabrice R; Ndongmo, Winston Patrick Chounna; Kengne-Ouafo, Jonas Arnaud; Ritter, Manuel; Amvongo-Adjia, Nathalie; Fombad, Fanny Fri; Njeshi, Charity Nya; Nkwescheu, Armand Seraphin; Enyong, Peter A; Hoerauf, Achim

    2016-05-31

    Mansonellosis remains one of the most neglected of tropical diseases and its current distribution in the entire forest block of southern Cameroon is unknown. In order to address this issue, we have surveyed the distribution of Mansonella perstans in different bioecological zones and in addition, elucidated the influence of multiple rounds of ivermectin (IVM) based mass drug administration (MDA). A mixed design was used. Between 2000 and 2014, both cross-sectional and longitudinal surveys were carried out in 137 communities selected from 12 health districts belonging to five main bioecological zones of the southern part of Cameroon. The zones comprised of grassland savanna (GS), mosaic forest savanna (MFS), forested savanna (FS), deciduous equatorial rainforest (DERF) and the dense humid equatorial rainforest (DHERF). The survey was carried out in some areas with no treatment history as well as those currently under IVM MDA. Individuals within the participatory communities were screened for the presence of M. perstans microfilariae (mf) in peripheral blood by the calibrated thick film method to determine both prevalence and geometric mean intensities at the community level. Apart from sporadic cases in savanna areas, distribution of M. perstans was strongly linked to the equatorial rainforest zones. Before CDTI, the highest mean prevalence (70.0 %) and intensity (17,382.2 mf/ml) were obtained in communities in Mamfes' DHERF areas followed by communities in the DHERF zone of Lolodorf (53.8 % and 7,814.8 mf/ml, respectively). A longitudinal survey in Mamfe further showed that M. perstans infections had reduced by 34.5 % in DERF (P < 0.001) but not DHERF zones after ten years of IVM MDA. Further data from the cross-sectional study revealed that there was a decrease in prevalence in DHERF zones only after ten years of MDA. In DERF zones however, the infection was relatively lower after four years of MDA. The distribution of M. perstans in the southern part of Cameroon varies with bioecological zones and IVM MDA history. The zones with high prevalence and intensities lie in forested areas while those with low endemicity are in the savanna areas. MDA with ivermectin induced significant reduction in the endemicity of mansonellosis in the decidious equatorial rainforest. In contrast, the prevalence and intensity remained relatively high and stable in the dense humid equatorial rainforest zones even after a decade of mass drug administration with ivermectin. Since it is known that M. perstans down-regulates host's immune system, the findings from this work would be useful in designing studies to understand the impact of M. perstans on host immune response to vaccination and co-infection with other pathogens such as Mycobacterium spp. and Plasmodium spp. in areas of contrasting endemicities.

  13. Ovarian Tumor-Stroma Interactions in an In Vivo Orthotopic Model

    DTIC Science & Technology

    2011-08-01

    cancer cells to the novel environment. We have devised an Intravital Video Microscopy approach to this problem in which MOVCAR cells labeled with green...Ovarian cancer, gene expression, metastasis, intravital video microscopy 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER...placed in a dorsal skin-fold chamber for Intravital Video Microscopy (IVM). The minced pseudo-organ tissue revascularizes and recapitulates some of the

  14. Novel methods of treating ovarian infertility in older and POF women, testicular infertility, and other human functional diseases.

    PubMed

    Bukovsky, Antonin

    2015-02-25

    In vitro maturation (IVM) and in vitro fertilization (IVF) technologies are facing with growing demands of older women to conceive. Although ovarian stem cells (OSCs) of older women are capable of producing in vitro fresh oocyte-like cells (OLCs), such cells cannot respond to IVM and IVF due to the lack of granulosa cells required for their maturation. Follicular renewal is also dependent on support of circulating blood mononuclear cells. They induce intermediary stages of meiosis (metaphase I chromosomal duplication and crossover, anaphase, telophase, and cytokinesis) in newly emerging ovarian germ cells, as for the first time demonstrated here, induce formation of granulosa cells, and stimulate follicular growth and development. A pretreatment of OSC culture with mononuclear cells collected from blood of a young healthy fertile woman may cause differentiation of bipotential OSCs into both developing germ and granulosa cells. A small blood volume replacement may enable treatment of ovarian infertility in vivo. The transferred mononuclear cells may temporarily rejuvenate virtually all tissues, including improvement of the function of endocrine tissues. Formation of new follicles and their development may be sufficient for IVM and IVF. The novel proposed in vitro approaches may be used as a second possibility. Infertility of human males affects almost a half of the infertility cases worldwide. Small blood volume replacement from young healthy fertile men may also be easy approach for the improvement of sperm quality in older or other affected men. In addition, body rejuvenation by small blood volume replacement from young healthy individuals of the same sex could represent a decline of in vitro methodology in favor of in vivo treatment for human functional diseases. Here we propose for the first time that blood mononuclear cells are essential for rejuvenation of those tissues, where immune system components participate in an appropriate division and differentiation of tissue stem cells. If needed, small blood volume replacement from distinct young healthy individuals could be utilized in six month intervals for repair of young altered or aged reproductive and other tissue functions. Systemic and local use of honey bee propolis tincture is an alternative option for functional rejuvenation of some tissues.

  15. Competitive homing assays to study gut-tropic t cell migration.

    PubMed

    Villablanca, Eduardo J; Mora, J Rodrigo

    2011-03-01

    In order to exert their function lymphocytes need to leave the blood and migrate into different tissues in the body. Lymphocyte adhesion to endothelial cells and tissue extravasation is a multistep process controlled by different adhesion molecules (homing receptors) expressed on lymphocytes and their respective ligands (addressions) displayed on endothelial cells (1 2). Even though the function of these adhesion receptors can be partially studied ex vivo, the ultimate test for their physiological relevance is to assess their role during in vivo lymphocyte adhesion and migration. Two complementary strategies have been used for this purpose: intravital microscopy (IVM) and homing experiments. Although IVM has been essential to define the precise contribution of specific adhesion receptors during the adhesion cascade in real time and in different tissues, IVM is time consuming and labor intensive, it often requires the development of sophisticated surgical techniques, it needs prior isolation of homogeneous cell populations and it permits the analysis of only one tissue/organ at any given time. By contrast, competitive homing experiments allow the direct and simultaneous comparison in the migration of two (or even more) cell subsets in the same mouse and they also permit the analysis of many tissues and of a high number of cells in the same experiment. Here we describe the classical competitive homing protocol used to determine the advantage/disadvantage of a given cell type to home to specific tissues as compared to a control cell population. We chose to illustrate the migratory properties of gut-tropic versus non gut-tropic T cells, because the intestinal mucosa is the largest body surface in contact with the external environment and it is also the extra-lymphoid tissue with the best-defined migratory requirements. Moreover, recent work has determined that the vitamin A metabolite all-trans retinoic acid (RA) is the main molecular mechanism responsible for inducing gut-specific adhesion receptors (integrin a4b7and chemokine receptor CCR9) on lymphocytes. Thus, we can readily generate large numbers of gut-tropic and non gut-tropic lymphocytes ex vivoby activating T cells in the presence or absence of RA, respectively, which can be finally used in the competitive homing experiments described here.

  16. In Vitro Maturation in Women with vs. without Polycystic Ovarian Syndrome: A Systematic Review and Meta-Analysis

    PubMed Central

    Siristatidis, Charalampos; Sergentanis, Theodoros N.; Vogiatzi, Paraskevi; Kanavidis, Prodromos; Chrelias, Charalampos; Papantoniou, Nikolaos; Psaltopoulou, Theodora

    2015-01-01

    Objective To evaluate in vitro maturation (IVM) in sub-fertile women with polycystic ovarian syndrome (PCOS) undergoing in vitro fertilisation (IVF), by comparing outcomes with a control group of non-PCOS. Study design A search strategy was developed for PubMed and studies reporting rates of the following outcomes (live birth; clinical pregnancy; implantation; cycle cancellation; oocyte maturation; oocyte fertilization; miscarriage) between patients with PCOS, PCO and controls undergoing IVM were deemed eligible. The review was conducted in accordance to the PRISMA guidelines and included studies quality was assessed through the Newcastle-Ottawa Quality scale. ORs with their corresponding 95% CIs were calculated for the main analysis and subgroup analyses were performed for PCOS cases vs. controls and PCOS vs. PCO cases. Alternative analyses were performed for live birth and clinical pregnancy, based on cycles and on women. Subgroup analyses for FSH stimulation, hCG priming and type of procedure (IVF/ICSI) were undertaken for all meta-analyses encompassing at least four study arms. Random effects models were used to calculate pooled effect estimates. Results Eleven studies were identified. A total of 268 PCOS patients (328 cycles), 100 PCO patients (110 cycles) and 440 controls (480 cycles) were included in the meta-analysis. A borderline trend towards higher birth rates among PCOS patients emerged (pooled OR = 1.74, 95%CI: 0.99–3.04) mainly reflected at the subgroup analysis vs. controls. Clinical pregnancy (pooled OR = 2.37, 95%CI: 1.53–3.68) and implantation rates (pooled OR = 1.73, 95%CI: 1.06–2.81) were higher, while cancellation rates lower (pooled OR = 0.18, 95%CI: 0.06-0.47) among PCOS vs. non-PCOS subjects; maturation and miscarriage rates did not differ between groups, while a borderline trend towards lower fertilization rates among PCOS patients was observed. Conclusion The present meta-analysis provides preliminary evidence on the effectiveness of IVM as a treatment option when offered in sub-fertile PCOS women, as the latter present at least as high outcome rates as those in non-PCOS. PMID:26241855

  17. Effect of milrinone on the developmental competence of growing lamb oocytes identified with brilliant cresyl blue.

    PubMed

    Wang, Liqin; Jiang, Xiangjiu; Wu, Yangsheng; Lin, Jiapeng; Zhang, Li; Yang, Nan; Huang, Juncheng

    2016-11-01

    Juvenile in vitro embryo transfer is a novel technique that can be used to increase the rate of genetic gain in a population and presents an alternative to embryo technologies on the basis of adult animals. However, oocytes from prepubertal animals have a lower viability than those obtained from adult ewe oocyte donors. In this research, we aimed to determine the optimum concentration and time of treatment of oocytes from prepubertal lambs with brilliant cresyl blue (BCB) stain and milrinone during IVM. This would improve the developmental rate of lamb oocytes and embryos after IVF. First, lamb cumulus-oocyte complexes were cultured under different concentrations (13 or 26 μM) of BCB staining. Treated lamb oocytes were then divided into BCB- (colorless cytoplasm) and BCB+ (colored cytoplasm) groups on the basis of their glucose-6-phosphate dehydrogenase activity. The blastocyst efficiency rate of BCB+ oocytes treated with 13 μM BCB (37.03%) was significantly higher than that of BCB+ oocytes treated with 26 μM BCB (23.25%) and that of nontreated BCB control oocytes (15.37%), as well as that of BCB- oocytes (6.28%). Both control oocytes and BCB+ oocytes exhibited significantly higher cleavage rates (60.15% and 73.44%, respectively) than that of BCB- oocytes (36.19%). Moreover, the diameter and glutathione content of BCB+ oocytes were found to be significantly greater than those of BCB- oocytes (163.37 vs. 159.25 μm and 6.39 vs. 0.26 pM, respectively). After culturing BCB- oocytes in different concentrations of milrinone (0, 50, 75, and 100 μM) for 3, 6, or 9 hours, results reported that supplementation of IVM medium with 75 μM milrinone for 6 hours yielded a significantly higher proportion of blastocysts than the other treatments. These results show that the staining of lamb cumulus-oocyte complexes with 13 μM BCB before IVM may be used to select developmentally competent lamb oocytes. Furthermore, they suggest that milrinone can be used to promote lamb developmental competence of lamb embryos produced during IVF. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. The influence of powdered coconut water (ACP-318®) in in vitro maturation of canine oocytes.

    PubMed

    Silva, A E F; Cavalcante, L F; Rodrigues, B A; Rodrigues, J L

    2010-12-01

    The objective of this study was to determine the influence of powdered coconut water (ACP-318(®)) diluted in high glucose (11.0 mM) TCM199 in the achievement of nuclear in vitro maturation (IVM) of canine oocytes. Cumulus oocyte complexes (COCs) (n = 632) were randomly allocated into three experimental groups named as group 1 (control group), group 2 (5% powdered coconut water) and group 3 (10% powdered coconut water). The percentage of meiotic resumption (MR) (GVBD to MII) was 39.1% (81/207), 50.2% (108/215) and 46.6% (98/210) for groups 1, 2 and 3 respectively (p < 0.05). There were no differences in MR rates among groups 2 and 3. The medium with ACP-318(®) slightly enhanced the nuclear maturation of canine oocytes when a comparison was established with rates of maturation exhibited by oocytes in the experimental group 1 without ACP-318(®) (p < 0.05). The results suggest that oocytes' nuclear morphology integrity and meiosis achievement were positively influenced when exposed to high glucose TCM199 supplemented with 5% powdered coconut water. Further investigation must be performed for a better understanding of powdered coconut water influence in cellular events during IVM of dog oocytes. © 2009 Blackwell Verlag GmbH.

  19. Hanging drop monoculture for selection of optimal antioxidants during in vitro maturation of porcine oocytes.

    PubMed

    Ishikawa, S; Machida, R; Hiraga, K; Hiradate, Y; Suda, Y; Tanemura, K

    2014-04-01

    We analysed the effect of three antioxidants that have different functional mechanisms on the in vitro maturation (IVM) of porcine oocytes. Single oocyte monoculture using the hanging drop (HD) system has some advantages such as improving analysis efficiency brought by the smaller number of samples than the number of oocytes cultured in one drop. Direct effects of ligands on single oocytes could also be detected without considering the effects of paracrine factors from other oocytes. After 22 h of pre-culture, denuded oocytes were cultured for 22 h with 0.01 and 0.1 μg/ml of L-carnitine (LC), lactoferrin (LF) or sulforaphane (SF) in the presence/non-presence of oxidant stress induced by H2O2 supplementation to evaluate the reducing effects against oxidative stress on nuclear maturation. As a result, compared with LC and SF, LF showed effective reduction in oxidative stress at a lower concentration (0.01 μg/ml), suggesting that LF is a more effective antioxidant in porcine oocyte IVM. Additionally, LF also increased maturation rate even in culture without H2O2. Our results clearly suggest that the HD monoculture system is useful for screening the substances that affect porcine oocyte culture. © 2014 Blackwell Verlag GmbH.

  20. Nonparametric methods in actigraphy: An update

    PubMed Central

    Gonçalves, Bruno S.B.; Cavalcanti, Paula R.A.; Tavares, Gracilene R.; Campos, Tania F.; Araujo, John F.

    2014-01-01

    Circadian rhythmicity in humans has been well studied using actigraphy, a method of measuring gross motor movement. As actigraphic technology continues to evolve, it is important for data analysis to keep pace with new variables and features. Our objective is to study the behavior of two variables, interdaily stability and intradaily variability, to describe rest activity rhythm. Simulated data and actigraphy data of humans, rats, and marmosets were used in this study. We modified the method of calculation for IV and IS by modifying the time intervals of analysis. For each variable, we calculated the average value (IVm and ISm) results for each time interval. Simulated data showed that (1) synchronization analysis depends on sample size, and (2) fragmentation is independent of the amplitude of the generated noise. We were able to obtain a significant difference in the fragmentation patterns of stroke patients using an IVm variable, while the variable IV60 was not identified. Rhythmic synchronization of activity and rest was significantly higher in young than adults with Parkinson׳s when using the ISM variable; however, this difference was not seen using IS60. We propose an updated format to calculate rhythmic fragmentation, including two additional optional variables. These alternative methods of nonparametric analysis aim to more precisely detect sleep–wake cycle fragmentation and synchronization. PMID:26483921

  1. In vitro production of small ruminant embryos: late improvements and further research.

    PubMed

    de Souza-Fabjan, Joanna Maria Gonçalves; Panneau, Barbara; Duffard, Nicolas; Locatelli, Yann; de Figueiredo, José Ricardo; Freitas, Vicente José de Figueirêdo; Mermillod, Pascal

    2014-06-01

    Beyond the potential use of in vitro production of embryos (IVP) in breeding schemes, embryos are also required for the establishment of new biotechnologies such as cloning and transgenesis. Additionally, the knowledge of oocyte and embryo physiology acquired through IVP techniques may stimulate the further development of other techniques such as marker assisted and genomic selection of preimplantation embryos, and also benefit assisted procreation in human beings. Efficient in vitro embryo production is currently a major objective for livestock industries, including small ruminants. The heterogeneity of oocytes collected from growing follicles by laparoscopic ovum pick up or in ovaries of slaughtered females, remains an enormous challenge for IVM success, and still limits the rate of embryo development. In addition, the lower quality of the IVP embryos, compared with their in vivo-derived counterparts, translates into poor cryosurvival, which restricts the wider use of this promising technology. Therefore, many studies have been reported in an attempt to determine the most suitable conditions for IVM, IVF, and in vitro development to maximize embryo production rate and quality. This review aims to present the current panorama of IVP production in small ruminants, describing important steps for its success, reporting the recent advances and also the main obstacles identified for its improvement and dissemination. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Effect of oxygen tension and serum during IVM on developmental competence of bovine oocytes.

    PubMed

    Pereira, Michele M; Machado, Marco A; Costa, Fernanda Q; Serapiao, Raquel V; Viana, Joao H M; Camargo, Luiz S A

    2010-01-01

    With an aim to improve the in vitro production of bovine embryos, the present study investigated the effect of serum and oxygen tension during IVM on oocyte developmental competence. Four experimental groups were evaluated: G1, 10% oestrus cow serum (OCS) with 20% O(2); G2, 0.1% polyvinyl alcohol (PVA) with 20% O(2); G3, 10% OCS with 5% O(2); and G4, 0.1% PVA with 5% O(2). The proportion of MII oocytes, blastocyst rates and total cell number were not affected (P > 0.05) when the OCS was replaced with PVA under 5% O(2), whereas a higher (P < 0.05) blastocyst rate and total cell number were found with OCS compared with PVA under 20% O(2). The apoptosis index was lower in blastocysts from oocytes matured with PVA under 5% O(2) (G4) compared with other groups (G1, G2 and G3), but no differences (P > 0.05) were found in maturation and blastocyst rates. Significant differences were found in the amount of specific transcripts in oocytes matured under different conditions. In conclusion maturation with PVA and 5% O(2) provides an efficient in vitro culture condition for the maturation of bovine oocytes.

  3. Observational Investigation of Solar Interior and Atmosphere

    NASA Technical Reports Server (NTRS)

    Kuhn, Jeffrey R.

    2003-01-01

    The Imaging Vector Magnetograph (IVM) has been modified to make it easier to observe at more than one spectral line. The cell holding the blocking filter has been replaced by a four-position filter wheel, so that changing to a different line is a matter of a few minutes rather than the several hours it used to take to disassemble the cell and install a new filter. Three new filters have been obtained, for Na 1589.6 nm, Fe 1630.25 nm, and H 1656.3 nm. The new filters have better bandpass profiles than the ones they replaced: somewhat wider, with flatter tops and steeper wings. This results in a reduction of parasitic light coming from adjacent Fabry-Perot orders, from seven percent to about two percent, and flattens the apparent continuum. The Mees CCD Imaging Spectrograph (MCCD) was upgraded under this grant, with a new control computer and data system. The camera was replaced with a faster, larger-format frame-transfer camera. Final integration of the upgrades is not yet complete, but tests indicate that the system cadence will be improved by a factor of five to ten, while increasing the spatial coverage by a factor of two (depending on observation options). Synoptic observations with the IVM and MCCD continue to be conducted daily, to the extent permitted by the fact that we have a single observer responsible for the observations. The older Haleakala Stokes Polarimeter is also used to make a daily vector magnetogram, normally of the region selected by the Reuven Ramaty High Energy Solar Spectroscopic Imager (RHESSI) duty scientists. This instrument, however, is showing its age to the extent that its maintenance is becoming something of a challenge. We also run a white light full-disk imager and a video H alpha prominence camera, continuously during times of observations. Of particular interest, we obtained rapid-cadence observations of the 2003 July 15 white light flare with both the IVM and MCCD. The vector magnetograms show no obvious difference between the preflare and postflare configurations. The photospheric magnetogram sequence and H alpha spectra we obtained can be combined with spacecraft observations to construct a rather detailed picture of the events of this flare. Several papers are in preparation.

  4. Developmental competence of mature yak vitrified-warmed oocytes is enhanced by IGF-I via modulation of CIRP during in vitro maturation.

    PubMed

    Pan, Yangyang; Cui, Yan; He, Honghong; Baloch, Abdul Rasheed; Fan, Jiangfeng; Xu, Gengquan; He, Junfeng; Yang, Kun; Li, Guyue; Yu, Sijiu

    2015-12-01

    The objective of this study was to investigate whether developmental competence of mature vitrified-warmed yak (Bos grunniens) oocytes can be enhanced by supplemented insulin-like growth factor I (IGF-1) during in vitro maturation (IVM), and its relationship with the expression of cold-inducible RNA-binding protein (CIRP). In experiment 1, immature yak oocytes were divided into four groups, and IVM supplemented with 0, 50, 100 and 200 ng/mL IGF-1 was evaluated; the mRNA and protein expression levels of CIRP in mature oocytes in the four groups were evaluated using quantitative real-time PCR and western blotting analyses. In experiment 2, the mature yak oocytes in the four groups were cryopreserved using the Cryotop (CT) method, followed by chemical activation and in vitro culture for two days and eight days to determine cleavage, blastocyst rates, and total cell number in the blastocysts. Mature yak oocytes without vitrification served as a control group. The outcomes were as following: (1) the expression of CIRP in the matured oocytes was up-regulated in the IGF-1 groups and was highest expression was observed in the 100 ng/mL IGF-1 treatment group. (2) In the vitrified-warmed groups, the rates of cleavage and blastocyst were also highest in the 100 ng/mL IGF-1 treatment group (81.04 ± 1.06%% and 32.16 ± 1.01%), which were close to the rates observed in groups without vitrification (83.25 ± 0.85% and 32.54 ± 0.34%). The rates of cleavage and blastocyst in the other vitrified-warmed groups were 70.92 ± 1.32% and 27.33 ± 1.31% (0 ng/mL); 72.73 ± 0.74% and 29.41 ± 0.84% (50 ng/mL); 72.43 ± 0.61% and 27.61 ± 0.59% (200 ng/mL), respectively. There was no significant difference in the total cell number per blastocysts between the vitrified-warmed groups and group without vitrification. Thus, we conclude that the enhancement in developmental competence of mature yak vitrified-warmed oocytes after the addition of IGF-1 during IVM might result from the regulation of CIRP expression in mature yak oocytes prior to vitrification. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. JPRS Report, Science & Technology, Japan, Government and Private Sector Joint R&D Projects

    DTIC Science & Technology

    1988-08-16

    is that if this system uses exogenous genes represented by the DNA that codes for hepatitis B surface antigen, polyvaccines can be produced easily...that can express in large quantities molecular clones of genetic products is awaited. Vectors using cells of higher mammals including man have been...functions of IVM and MMD using cultured spinal nerve cells with a great advantage that the same sample can be used for both electrophysiological and

  6. Influence of herbicides and felling, fertilization, and prescribed fire on longleaf pine growth and understory vegetation through ten growing seasons and the outcome of an ensuing wildfire

    Treesearch

    James D. Haywood

    2011-01-01

    Restoring longleaf pine (Pinus palustris Mill.) over much of its original range requires artificial regeneration. In central Louisiana, USA, two fertilization levels - No (NF) or Yes (F-36 kg/ha N and 40 kg/ha P) in combination with three vegetation treatments - Check, four prescribed fires (PF), or multi-year vegetation control by herbicidal and mechanical means (IVM...

  7. Intravital microscopy for evaluating tumor perfusion of nanoparticles exposed to non-invasive radiofrequency electric fields.

    PubMed

    Lapin, Norman A; Krzykawska-Serda, Martyna; Ware, Matthew J; Curley, Steven A; Corr, Stuart J

    Poor biodistribution and accumulation of chemotherapeutics in tumors due to limitations on diffusive transport and high intra-tumoral pressures (Jain RK, Nat Med. 7(9):987-989, 2001) have prompted the investigation of adjunctive therapies to improve treatment outcomes. Hyperthermia has been widely applied in attempts to meet this need, but it is limited in its ability to reach tumors in deeply located body regions. High-intensity radiofrequency (RF) electric fields have the potential to overcome such barriers enhancing delivery and extravasation of chemotherapeutics. However, due to factors, including tumor heterogeneity and lack of kinetic information, there is insufficient understanding of time-resolved interaction between RF fields and tumor vasculature, drug molecules and nanoparticle (NP) vectors. Intravital microscopy (IVM) provides time-resolved high-definition images of specific tumor microenvironments, overcoming heterogeneity issues, and can be integrated with a portable RF device to enable detailed observation over time of the effects of the RF field on kinetics and biodistribution at the microvascular level. Herein, we provide a protocol describing the safe integration of IVM with a high-powered non-invasive RF field applied to 4T1 orthotopic breast tumors in live mice. Results show increased perfusion of NPs in microvasculature upon RF hyperthermia treatment and increased perfusion, release and spreading of injected reagents preferentially in irregular vessels during RF exposure.

  8. Imaging circulating tumor cells in freely moving awake small animals using a miniaturized intravital microscope.

    PubMed

    Sasportas, Laura Sarah; Gambhir, Sanjiv Sam

    2014-01-01

    Metastasis, the cause for 90% of cancer mortality, is a complex and poorly understood process involving the invasion of circulating tumor cells (CTCs) into blood vessels. These cells have potential prognostic value as biomarkers for early metastatic risk. But their rarity and the lack of specificity and sensitivity in measuring them render their interrogation by current techniques very challenging. How and when these cells are circulating in the blood, on their way to potentially give rise to metastasis, is a question that remains largely unanswered. In order to provide an insight into this "black box" using non-invasive imaging, we developed a novel miniature intravital microscopy (mIVM) strategy capable of real-time long-term monitoring of CTCs in awake small animals. We established an experimental 4T1-GL mouse model of metastatic breast cancer, in which tumor cells express both fluorescent and bioluminescent reporter genes to enable both single cell and whole body tumor imaging. Using mIVM, we monitored blood vessels of different diameters in awake mice in an experimental model of metastasis. Using an in-house software algorithm we developed, we demonstrated in vivo CTC enumeration and computation of CTC trajectory and speed. These data represent the first reported use we know of for a miniature mountable intravital microscopy setup for in vivo imaging of CTCs in awake animals.

  9. Imaging Circulating Tumor Cells in Freely Moving Awake Small Animals Using a Miniaturized Intravital Microscope

    PubMed Central

    Sasportas, Laura Sarah; Gambhir, Sanjiv Sam

    2014-01-01

    Metastasis, the cause for 90% of cancer mortality, is a complex and poorly understood process involving the invasion of circulating tumor cells (CTCs) into blood vessels. These cells have potential prognostic value as biomarkers for early metastatic risk. But their rarity and the lack of specificity and sensitivity in measuring them render their interrogation by current techniques very challenging. How and when these cells are circulating in the blood, on their way to potentially give rise to metastasis, is a question that remains largely unanswered. In order to provide an insight into this "black box" using non-invasive imaging, we developed a novel miniature intravital microscopy (mIVM) strategy capable of real-time long-term monitoring of CTCs in awake small animals. We established an experimental 4T1-GL mouse model of metastatic breast cancer, in which tumor cells express both fluorescent and bioluminescent reporter genes to enable both single cell and whole body tumor imaging. Using mIVM, we monitored blood vessels of different diameters in awake mice in an experimental model of metastasis. Using an in-house software algorithm we developed, we demonstrated in vivo CTC enumeration and computation of CTC trajectory and speed. These data represent the first reported use we know of for a miniature mountable intravital microscopy setup for in vivo imaging of CTCs in awake animals. PMID:24497977

  10. The Different Calcium+2 Intensity Profile and Quality of Oocyte and Goat Sperms after Cryopreservation

    NASA Astrophysics Data System (ADS)

    Ciptadi, G.; Rahayu, S.; Fatchiyah; Wahyuningsih, S.; Budiarto, A.; Nasich, M.; Putri, A. R. I.; Mudawamah, M.; Ihsan, M. N.

    2018-02-01

    This research aims were to study the effect of the oocyte and sperms cryopreservation of Indonesian local goat on the post-thawing quality and profile or characters of Calcium+2 intensity in relating with their fertility capacity. A study was conducted to test the freezing method and post-thawing viability both stock cells stored in the deep freezer and liquid nitrogen (-80°C of vs -196°C). A fertility test of sperms has been conducted through in vitro of sperm quality, while the oocytes cryopreserved test was done by in vitro maturation (IVM) rate (%). The profile of Calcium 2+ was performed and analysis by Confocal Laser Scanned Microscope (CLSM). The result showed that IVM rate of goat oocyte is considered lower when cryopreserved in -80°C than in -196°C. Meanwhile, sperm is considered having a good quality in 2 methods of cryopreservation with post-thawing motility > 40 % (SNI 2014). There is an important difference between Calcium intensity of fresh and post-thawing both for oocyte and spermatozoa. Calcium +2 profiles is varied individually on the peak of intensity, but it considered expressed the same profile of each fresh and post-thawing cell. In vitro fertilization test need to be performed to complete the viability and fertility competence of these sperm and oocyte freezing stocks.

  11. In vitro oocyte culture and somatic cell nuclear transfer used to produce a live-born cloned goat.

    PubMed

    Ohkoshi, Katsuhiro; Takahashi, Seiya; Koyama, Shin-Ichiro; Akagi, Satoshi; Adachi, Noritaka; Furusawa, Tadashi; Fujimoto, Jun-Ichiro; Takeda, Kumiko; Kubo, Masanori; Izaike, Yoshiaki; Tokunaga, Tomoyuki

    2003-01-01

    The use of an in vitro culture system was examined for production of somatic cells suitable for nuclear transfer in the goat. Goat cumulus-oocyte complexes were incubated in tissue culture medium TCM-199 supplemented with 10% fetal bovine serum (FBS) for 20 h. In vitro matured (IVM) oocytes were enucleated and used as karyoplast recipients. Donor cells obtained from the anterior pituitary of an adult male were introduced into the perivitelline space of enucleated IVM oocytes and fused by an electrical pulse. Reconstituted oocytes were cultured in chemically defined medium for 9 days. Two hundred and twenty-eight oocytes (70%) were fused with donor cells. After in vitro culture, seven somatic cell nuclear transfer (SCNT) oocytes (3%) developed to the blastocyst stage. SCNT embryos were transferred to the oviducts of recipient females (four 8-cell embryos per female) or uterine horn (two blastocysts per female). One male clone (NT1) was produced at day 153 from an SCNT blastocyst and died 16 days after birth. This study demonstrates that nuclear transferred goat oocytes produced using an in vitro culture system could develop to term and that donor anterior pituitary cells have the developmental potential to produce term offspring. In this study, it suggested that the artificial control of endocrine system in domestic animal might become possible by the genetic modification to anterior pituitary cells.

  12. Inflammation Modulates Murine Venous Thrombosis Resolution In Vivo: Assessment by Multimodal Fluorescence Molecular Imaging

    PubMed Central

    Ripplinger, Crystal M.; Kessinger, Chase W.; Li, Chunqiang; Kim, Jin Won; McCarthy, Jason R.; Weissleder, Ralph; Henke, Peter K.; Lin, Charles P.; Jaffer, Farouc A.

    2012-01-01

    Objective Assessment of thrombus inflammation in vivo could provide new insights into deep vein thrombosis (DVT) resolution. Here we develop and evaluate two integrated fluorescence molecular-structural imaging strategies to quantify DVT-related inflammation and architecture, and to assess the effect of thrombus inflammation on subsequent DVT resolution in vivo. Methods and Results Murine DVT were created with topical 5% FeCl3 application to thigh or jugular veins (n=35). On day 3, mice received macrophage and matrix metalloproteinase (MMP) activity fluorescence imaging agents. On day 4, integrated assessment of DVT inflammation and architecture was performed using confocal fluorescence intravital microscopy (IVM). Day 4 analyses showed robust relationships among in vivo thrombus macrophages, MMP activity, and FITC-dextran deposition (r>0.70, p<0.01). In a serial two-timepoint study, mice with DVT underwent IVM at day 4 and at day 6. Analyses revealed that the intensity of thrombus inflammation at day 4 predicted the magnitude of DVT resolution at day 6 (p<0.05). In a second approach, noninvasive fluorescence molecular tomography-computed tomography (FMT-CT) was employed, and detected macrophages within jugular DVT (p<0.05 vs. sham-controls). Conclusions Integrated fluorescence molecular-structural imaging demonstrates that the DVT-induced inflammatory response can be readily assessed in vivo, and can inform the magnitude of thrombus resolution. PMID:22995524

  13. A field evaluation of anthelmintics for control of cyathostomes of horses in Brazil.

    PubMed

    Pereira, M C; Kohek Júnior, I; Campos, R; Lima, S B; Foz, R P

    1991-03-01

    The anthelmintic efficacy of ivermectin (IVM), piperazine citrate (PPZ) and fenbendazole (FBZ) alone, and combinations of FBZ with varying dosages of PPZ, was evaluated for the control of strongyles of Mangalarga equids. In all cases of positive strongly egg counts per gram of faeces (EPG) before and after treatment, pure populations of cyathostome larvae with eight gut cells were consistently observed in faecal cultures. The faecal egg count reductions (FECR) were evaluated between Day 7 and Day 56 post-treatment. Significant differences (P less than or equal to 0.05) were found between Day 7 and Day 49 when comparing the mean EPG values of IVM with those of the other anthelmintics. PPZ alone and the combination of FBZ (7.5 mg kg-1) and PPZ (55 mg base kg-1) did not show significant differences during the trial; both groups exhibiting an FECR of greater than 90% between Day 7 and Day 30. Horses treated with the combinations of FBZ (7.5 mg kg-1) and PPZ at either 40 or 25 mg base kg-1, and with FBZ alone at either 7.5 or 15 mg kg-1, showed an FECR of less than 90% 2 weeks after treatment. The emergence of a degree of resistance of strongyles to FBZ and PPZ in a segment of the cyathostomes in this population is suggested.

  14. Supplementation with CTGF, SDF1, NGF, and HGF promotes ovine in vitro oocyte maturation and early embryo development.

    PubMed

    Wang, D H; Ren, J; Zhou, C J; Han, Z; Wang, L; Liang, C G

    2018-05-17

    The strategies for improving the in vitro maturation (IVM) of domestic animal oocytes focus on promoting nuclear and cytoplasmic maturation. The identification of paracrine factors and their supplementation in the culture medium represent effective approaches for oocyte maturation and embryo development. This study investigated the effects of paracrine factor supplementation including connective tissue growth factor (CTGF), nerve growth factor (NGF), hepatocyte growth factor (HGF), and stromal derived factor 1 (SDF1) on ovine oocytes and early parthenogenetic embryos using an in vitro culture system. First, we identified the optimal concentrations of CTGF (30 ng/mL), SDF1 (10 ng/mL), NGF (3 ng/mL), and HGF (100 ng/mL) for promoting oocyte maturation, which combined, induced nuclear maturation in 94.19% of oocytes. This combination also promoted cumulus cell expansion and inhibited oocyte/cumulus apoptosis, while enabling a larger proportion (33.04%) of embryos to develop into blastocysts than in the controls and prevented embryo apoptosis. These novel findings demonstrate that the paracrine factors CTGF, SDF1, NGF, and HGF facilitate ovine oocyte and early parthenogenetic embryo development in vitro. Thus, supplementation with these factors may help optimize the IVM of ovine oocytes and early parthenogenetic embryo development strategies. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Polymer Engineering: Polymeric and Molecular Electronic, Dielectric and Optical Properties for Device Applications,

    DTIC Science & Technology

    1985-01-01

    Lida ii v n I has(-* two decenerat-k:<ite ’riAJ uts lctrical codcto canan ’ 111 ’ l f organics ’w’ith rinci er jfrnp 1m sate The mca I isc diopant...mtma eim letona ta 3-ari ant i II eUl c ain g- -o,- sipstifIir~atE * ’ ivan :’ ftI~ivme ad) lifolen in2~fitif tot-- devie /ffla .flalf f.(cC rea i:-i

  16. Microbial larvicides for malaria control in The Gambia

    PubMed Central

    Majambere, Silas; Lindsay, Steven W; Green, Clare; Kandeh, Balla; Fillinger, Ulrike

    2007-01-01

    Background Mosquito larval control may prove to be an effective tool for incorporating into integrated vector management (IVM) strategies for reducing malaria transmission. Here the efficacy of microbial larvicides against Anopheles gambiae s.l. was tested in preparation for a large-scale larviciding programme in The Gambia. Methods The impact of water-dispersible (WDG) and corn granule (CG) formulations of commercial Bacillus sphaericus strain 2362 (Bs; VectoLex®) and Bacillus thuringiensis var.israelensis strain AM65-52 (Bti; VectoBac®) on larval development were tested under laboratory and field conditions to (1) identify the susceptibility of local vectors, (2) evaluate the residual effect and re-treatment intervals, (3) test the effectiveness of the microbials under operational application conditions and (4) develop a method for large-scale application. Results The major malaria vectors were highly susceptible to both microbials. The lethal concentration (LC) to kill 95% of third instar larvae of Anopheles gambiae s.s. after 24 hours was 0.023 mg/l (14.9 BsITU/l) for Bs WDG and 0.132 mg/l (396 ITU/l) for Bti WDG. In general Bs had little residual effect under field conditions even when the application rate was 200 times greater than the LC95. However, there was a residual effect up to 10 days in standardized field tests implemented during the dry season. Both microbials achieved 100% mortality of larvae 24–48 hours post-application but late instar larvae were detected 4 days after treatment. Pupae development was reduced by 94% (95% Confidence Interval = 90.8–97.5%) at weekly re-treatment intervals. Field tests showed that Bs had no residual activity against anopheline larvae. Both microbials provided complete protection when applied weekly. The basic training of personnel in identification of habitats, calibration of application equipment and active larviciding proved to be successful and achieved full coverage and control of mosquito larvae for three months under fully operational conditions. Conclusion Environmentally safe microbial larvicides can significantly reduce larval abundance in the natural habitats of The Gambia and could be a useful tool for inclusion in an IVM programme. The costs of the intervention in this setting could be reduced with formulations that provide a greater residual effect. PMID:17555570

  17. Evaluation of parasiticidal activity of fenbendazole, ivermectin, oxibendazole, and pyrantel pamoate in horse foals with emphasis on ascarids (Parascaris equorum) in field studies on five farms in Central Kentucky in 2007.

    PubMed

    Lyons, E T; Tolliver, S C; Ionita, M; Collins, S S

    2008-07-01

    Horse foals on five farms in Central Kentucky were used in field studies in 2007 evaluating activity of paste formulations of four compounds (fenbendazole-FBZ, ivermectin-IVM, oxibendazole-OBZ, and pyrantel pamoate-PRT) against internal parasites with emphasis on ascarids (Parascaris equorum). It has been well established the last few years that there is widespread resistance of P. equorum to ivermectin. The main purpose of the present research was to obtain current data on ascaridicidal activity of FBZ, OBZ, and PRT; also, to acquire further information on ascarid resistance to ivermectin. Additionally, data were documented on drug activity on small strongyles. Detection of ascarid and strongyle eggs in feces of foals was by a qualitative method (presence or absence) or a quantitative method (eggs per gram of feces). Strongyle eggs all were assumed to be from small strongyles. This is based on fecal cultures from horses on one farm and historic records from horses in this area on excellent deworming programs. A girth tape was used to estimate the body weight of each foal so that the appropriate dose rate of each drug could be given. Many of the foals were used in more than one cycle of treatments. Efficacy of the drugs, administered intraorally, was determined by calculating the average percentage reduction (% red.) of the number of foals passing eggs after vs. before treatment: (1) FBZ at 10 mg/kg was tested on four farms; 76 foals were examined, 50 with ascarid eggs (84% red.) and 62 with strongyle eggs (0% red.); (2) IVM at 200 microg/kg was tested on three farms; 58 foals were examined, 18 with ascarid eggs (0% red.) and 48 with strongyle eggs (100% red.); (3) OBZ at 10 mg/kg was tested on three farms; 181 foals were examined, 78 with ascarid eggs (94% red.) and 79 with strongyle eggs (0% red.); (4) PRT was tested on two farms, one farm at 1x (6.6 mg base/kg); 42 were foals examined, 16 with ascarid eggs (0% red.) and 33 with strongyle eggs (12% red.) and one farm at 2x (13.2 mg base/kg); 18 foals were examined, 13 with ascarid eggs (23% red.) and 15 with strongyle eggs (27% red.).

  18. Fertility preservation treatment for young women with autoimmune diseases facing treatment with gonadotoxic agents.

    PubMed

    Elizur, S E; Chian, R C; Pineau, C A; Son, W Y; Holzer, H E G; Huang, J Y J; Gidoni, Y; Levin, D; Demirtas, E; Tan, S L

    2008-10-01

    To describe a case series of seven women with SLE and other systemic autoimmune rheumatic diseases (SARDs) who required cyclophosphamide therapy and underwent fertility preservation treatments. Of the seven patients reported here, five women had SLE with nephritis, the sixth had immune thrombocytopenia purpura (ITP) and the seventh had microscopic polyangiitis (MPA) with renal involvement. All women were nulliparous and younger than 35 yrs. Patients with SLE underwent in vitro maturation (IVM) of immature oocytes aspirated during a natural menstrual cycle followed by vitrification of the matured oocytes if a male partner was not available, or vitrification of embryos if one was available. The patient with ITP and the patient with MPA underwent gonadotropin ovarian stimulation followed by oocyte or embryo vitrification. All women completed fertility preservation treatment successfully and mature oocytes or embryos (36 and 13, respectively) were vitrified. No complications were associated with this treatment and cytotoxic therapy was initiated as scheduled in all cases. Oocyte or embryo cryopreservation should be considered for fertility preservation in young women with SARDs who face imminent gonadotoxic treatment. In patients, where gonadotropin ovarian stimulation is deemed unsafe, IVM of immature oocytes, aspirated during a natural menstrual cycle, followed by vitrification or fertilization of the mature oocytes, seems to be safe and feasible. For patients in whom hormonal ovarian stimulation is not contraindicated, this method may be considered depending on the urgency to start cytotoxic therapy.

  19. In vitro embryos production after oocytes treatment with forskolin.

    PubMed

    Paschoal, Daniela Martins; Maziero, Rosiára Rosária Dias; Sudano, Mateus José; Guastali, Midyan Daroz; Vergara, Luis Eduardo; Crocomo, Letícia Ferrari; Lima-Neto, João Ferreira de; Magalhães, Luis Carlos Oña; Monteiro, Bianca Andriolo; Rascado, Tatiana da Silva; Martins, Alício; Leal, Claudia Lima Verde; Landim-Alvarenga, Fernanda da Cruz

    2016-04-01

    The inhibition of nuclear maturation allows time for the oocyte to accumulate molecules that are important for embryonic development. Thus, the objective of this work was to evaluate the effect of blocking oocyte meiosis with the addition of forskolin, an efficient inhibitor of nuclear maturation, in in vitro maturation (IVM) medium. Forskolin was added to the IVM medium for 6 h at concentrations of 0.1 mM, 0.05 mM or 0.025 mM, then the oocytes were allowed to mature in drug-free medium for 18 h. The oocytes were assessed for the stage of nuclear maturation, the activity and distribution of mitochondria, oocyte ultrastructure, the number of viable cells and the apoptosis rate. After forskolin treatment, the oocytes were fertilized in vitro and cultured for 7 days. On day 7, the blastocyst rate, the ultrastructure, the number of intact cells and the apoptosis rate of the blastocysts were measured. No differences were observed for the stage of nuclear maturation of the oocyte, the mitochondrial activity and distribution, the blastocyst rate or total number of intact cells. However, a higher rate of apoptosis was observed in the blastocysts produced from oocytes blocked for 6 h with the higher concentration of forskolin (P < 0.05). We conclude that all the experimental groups reached the MII stage after the addition of forskolin and that the highest concentration of forskolin caused cellular degeneration without harming embryo production on the 7th day.

  20. The In Vitro Effect of Ivermectin on the Activity of Trehalose Synthesis Pathway Enzymes and Their mRNA Expression in the Muscle of Adult Female Ascaris suum (Nematoda)

    PubMed Central

    Łopieńska-Biernat, Elżbieta; Zaobidna, Ewa Anna

    2014-01-01

    The in vitro effect of ivermectin lethal dose on the activity of trehalose-6-phosphate synthase (TPS) and phosphatase (TPP) and the expression of their mRNA (tps1, tps2, and tpp genes) in the muscle of adult female Ascaris suum was investigated. The presence of ivermectin in the medium caused a decrease in TPS and TPP activities during the experiment compared with the start and control groups. The exception was the group of worms grown for 8 hours in a IVM solution, in which there was a little higher TPS activity than in the control. Real-time qPCR analysis showed reduced expression of tps1 and tps2, and unchanged tpp expression after 20 hours of incubation relative to the expression at time zero. Relative to the appropriate control groups, the expression of tps2 gene was slight increased but the other two genes were reduced after 8-hours of IVM-treatment. Then the expression of all three genes was lower at the end of cultivation. The level of gene expression was positively correlated with the activity of specific enzymes. In the case of tpp gene there was only a weak correlation. Prolonged exposure to ivermectin was effective in lowering TPS and TPP activity and their mRNA expression. However, the drug did not block the pathway. PMID:25405239

  1. The in vitro effect of ivermectin on the activity of trehalose synthesis pathway enzymes and their mRNA expression in the muscle of adult female Ascaris suum (Nematoda).

    PubMed

    Dmitryjuk, Małgorzata; Łopieńska-Biernat, Elżbieta; Zaobidna, Ewa Anna

    2014-01-01

    The in vitro effect of ivermectin lethal dose on the activity of trehalose-6-phosphate synthase (TPS) and phosphatase (TPP) and the expression of their mRNA (tps1, tps2, and tpp genes) in the muscle of adult female Ascaris suum was investigated. The presence of ivermectin in the medium caused a decrease in TPS and TPP activities during the experiment compared with the start and control groups. The exception was the group of worms grown for 8 hours in a IVM solution, in which there was a little higher TPS activity than in the control. Real-time qPCR analysis showed reduced expression of tps1 and tps2, and unchanged tpp expression after 20 hours of incubation relative to the expression at time zero. Relative to the appropriate control groups, the expression of tps2 gene was slight increased but the other two genes were reduced after 8-hours of IVM-treatment. Then the expression of all three genes was lower at the end of cultivation. The level of gene expression was positively correlated with the activity of specific enzymes. In the case of tpp gene there was only a weak correlation. Prolonged exposure to ivermectin was effective in lowering TPS and TPP activity and their mRNA expression. However, the drug did not block the pathway.

  2. Goat oocyte quality and competence to undergo IVM and embryo development after parthenogenetic activation from goats fed with different levels of cashew nut bran as source of dietary lipids.

    PubMed

    Fernandes, C C L; Feltrin, C; Martins, L T; Gaudêncio Neto, S; Aguiar, L H; Silva, A M; Oliveira, C H A; Silva, L M; Silva, C M G; Bertolini, M; Rondina, D

    2014-07-15

    Lipid-rich and energy-dense diets can have significant effects on the reproductive physiology, including the ovarian function and fertility. The aim of this study was to assess the effect of cashew nut bran supplementation as a lipid source on follicle development, plasma and intrafollicular concentrations of cholesterol, and developmental competence of in vitro-matured goat oocytes. The inclusion of cashew nut bran as 24% of the goats' diet for 28 days increased the percentage and number of degenerated oocytes compared with the control (P < 0.05), and also the plasma cholesterol levels and the proportion of grade IV oocytes compared with all other treatments (P < 0.05). Moreover, a significant reduction was observed in the proportion of viable oocytes compared with the control and in the percentage of grade II oocytes compared with all other treatments (P < 0.05). Oocyte maturation, cleavage, and blastocyst rates after parthenogenetic activation of viable oocytes were not affected by the type of diet. In conclusion, the inclusion of cashew nut bran as 24% of the diet of adult goats for 28 days changed plasma cholesterol levels and reduced the proportion of viable immature oocytes; however, the 12% and 24% diet supplementations with cashew nut bran did not interfere with competence of resulting viable oocytes to reach the metaphase II stage after IVM, and to develop after parthenogenetic activation. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Visualizing the Acute Effects of Vascular-Targeted Therapy In Vivo Using Intravital Microscopy and Magnetic Resonance Imaging: Correlation with Endothelial Apoptosis, Cytokine Induction, and Treatment Outcome1

    PubMed Central

    Seshadri, Mukund; Spernyak, Joseph A; Maiery, Patricia G; Cheney, Richard T; Mazurchuk, Richard; Bellnier, David A

    2007-01-01

    Abstract The acute effects of the vascular-disrupting agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA) were investigated in vivo using intravital microscopy (IVM) and magnetic resonance imaging (MRI). Changes in vascular permeability and blood flow of syngeneic CT-26 murine colon adenocarcinomas were assessed at 4 and 24 hours after DMXAA treatment (30 mg/kg, i.p.) and correlated with induction of tumor necrosis factor-α (TNF-α), endothelial damage [CD31/terminal deoxynucleotidyl transferase (TdT)], and treatment outcome. Intravital imaging revealed a marked increase in vascular permeability 4 hours after treatment, consistent with increases in intratumoral mRNA and protein levels of TNF-α. Parallel contrast-enhanced MRI studies showed a ∼ 4-fold increase in longitudinal relaxation rates (ΔR1), indicative of increased contrast agent accumulation within the tumor. Dual immunostained tumor sections (CD31/TdT) revealed evidence of endothelial apoptosis at this time point. Twenty-four hours after treatment, extensive hemorrhage and complete disruption of vascular architecture were observed with IVM, along with a significant reduction in ΔR1; and virtual absence of CD31 immunostaining. DMXAA-induced tumor vascular damage resulted in significant long-term (60-day) cures compared to untreated controls. Multimodality imaging approaches are useful in visualizing the effects of antivascular therapy in vivo. Such approaches allow cross validation and correlation of findings with underlying molecular changes contributing to treatment outcome. PMID:17356709

  4. Environmental management through sluice gated bed-dam: a revived strategy for the control of Anopheles fluviatilis breeding in streams

    PubMed Central

    Sahu, S.S.; Gunasekaran, K.; Jambulingam, P.

    2014-01-01

    Background & objectives: Integrated vector management (IVM) emphasizes sustainable eco-friendly methods and minimal use of chemicals. In this context, the present study highlights the environmental control of breeding of Anopheles fluviatilis, the primary malaria vector, through water management in a natural stream in Koraput district, Odisha, India. Methods: The District Rural Development Agency (DRDA), Koraput, constructed two bed-dams across streams, one in Barigaon and the other in Pipalapodar village. The bed-dam in the former village was fitted with two sluice gates whereas the bed dam constructed in the latter village was without the sluice gate. The sluice gates were opened once in a week on a fixed day to flush out the water from the dam. Anopheles immatures were sampled systematically in the streams using a dipper for density measurement and species composition. Results: There was a reduction of 84.9 per cent in the proportion of positive dips for Anopheles larvae/pupae and a reduction of 98.4 per cent in immature density (number/dip) of An. fluviatilis in the experimental downstream compared to the control following opening of the sluice gates. Interpretation & conclusions: Our findins showed that opening of sluice gates of the bed-dam regularly once in a week resulted in the control of vector breeding in the downstream due to the flushing effect of the water released with a high flow from the bed-dam that stagnated water in the upstream. The outcome of the study encourages upscaling this measure to other areas, wherever feasible. PMID:25297364

  5. Mosquitocidal properties of IgG targeting the glutamate-gated chloride channel in three mosquito disease vectors (Diptera: Culicidae).

    PubMed

    Meyers, Jacob I; Gray, Meg; Foy, Brian D

    2015-05-15

    The glutamate-gated chloride channel (GluCl) is a highly sensitive insecticide target of the avermectin class of insecticides. As an alternative to using chemical insecticides to kill mosquitoes, we tested the effects of purified immunoglobulin G (IgG) targeting the extracellular domain of GluCl from Anopheles gambiae (AgGluCl) on the survivorship of three key mosquito disease vectors: Anopheles gambiae s.s., Aedes aegypti and Culex tarsalis. When administered through a single blood meal, anti-AgGluCl IgG reduced the survivorship of A. gambiae in a dose-dependent manner (LC50: 2.82 mg ml(-1), range 2.68-2.96 mg ml(-1)) but not A. aegypti or C. tarsalis. We previously demonstrated that AgGluCl is only located in tissues of the head and thorax of A. gambiae. To verify that AgGluCl IgG is affecting target antigens found outside the midgut, we injected it directly into the hemocoel via intrathoracic injection. A single, physiologically relevant concentration of anti-AgGluCl IgG injected into the hemocoel equally reduced mosquito survivorship of all three species. To test whether anti-AgGluCl IgG was entering the hemocoel of each of these mosquitoes, we fed mosquitoes a blood meal containing anti-AgGluCl IgG and subsequently extracted their hemolymph. We only detected IgG in the hemolymph of A. gambiae, suggesting that resistance of A. aegypti and C. tarsalis to anti-AgGluCl IgG found in blood meals is due to deficient IgG translocation across the midgut. We predicted that anti-AgGluCl IgG's mode of action is by antagonizing GluCl activity. To test this hypothesis, we fed A. gambiae blood meals containing anti-AgGluCl IgG and the GluCl agonist ivermectin (IVM). Anti-AgGluCl IgG attenuated the mosquitocidal effects of IVM, suggesting that anti-AgGluCl IgG antagonizes IVM-induced activation of GluCl. Lastly, we stained adult, female A. aegypti and C. tarsalis for GluCl expression. Neuronal GluCl expression in these mosquitoes was similar to previously reported A. gambiae GluCl expression; however, we also discovered GluCl staining on the basolateral surface of their midgut epithelial cells, suggesting important physiological differences in Culicine and Anopheline mosquitoes. © 2015. Published by The Company of Biologists Ltd.

  6. Mosquitocidal properties of IgG targeting the glutamate-gated chloride channel in three mosquito disease vectors (Diptera: Culicidae)

    PubMed Central

    Meyers, Jacob I.; Gray, Meg; Foy, Brian D.

    2015-01-01

    ABSTRACT The glutamate-gated chloride channel (GluCl) is a highly sensitive insecticide target of the avermectin class of insecticides. As an alternative to using chemical insecticides to kill mosquitoes, we tested the effects of purified immunoglobulin G (IgG) targeting the extracellular domain of GluCl from Anopheles gambiae (AgGluCl) on the survivorship of three key mosquito disease vectors: Anopheles gambiae s.s., Aedes aegypti and Culex tarsalis. When administered through a single blood meal, anti-AgGluCl IgG reduced the survivorship of A. gambiae in a dose-dependent manner (LC50: 2.82 mg ml−1, range 2.68–2.96 mg ml−1) but not A. aegypti or C. tarsalis. We previously demonstrated that AgGluCl is only located in tissues of the head and thorax of A. gambiae. To verify that AgGluCl IgG is affecting target antigens found outside the midgut, we injected it directly into the hemocoel via intrathoracic injection. A single, physiologically relevant concentration of anti-AgGluCl IgG injected into the hemocoel equally reduced mosquito survivorship of all three species. To test whether anti-AgGluCl IgG was entering the hemocoel of each of these mosquitoes, we fed mosquitoes a blood meal containing anti-AgGluCl IgG and subsequently extracted their hemolymph. We only detected IgG in the hemolymph of A. gambiae, suggesting that resistance of A. aegypti and C. tarsalis to anti-AgGluCl IgG found in blood meals is due to deficient IgG translocation across the midgut. We predicted that anti-AgGluCl IgG's mode of action is by antagonizing GluCl activity. To test this hypothesis, we fed A. gambiae blood meals containing anti-AgGluCl IgG and the GluCl agonist ivermectin (IVM). Anti-AgGluCl IgG attenuated the mosquitocidal effects of IVM, suggesting that anti-AgGluCl IgG antagonizes IVM-induced activation of GluCl. Lastly, we stained adult, female A. aegypti and C. tarsalis for GluCl expression. Neuronal GluCl expression in these mosquitoes was similar to previously reported A. gambiae GluCl expression; however, we also discovered GluCl staining on the basolateral surface of their midgut epithelial cells, suggesting important physiological differences in Culicine and Anopheline mosquitoes. PMID:25994632

  7. Mental Disorder Hospitalizations among Submarine Personnel in the U.S. Navy.

    DTIC Science & Technology

    1988-03-10

    hospitalization rates ( Lilienfeld , 1980). T- tests were used to assess statistical signi- ficance of differences in descriptive variables (McNemar, 1969... Lilienfeld , D. E. Foundations of epidemiology. 2nd ed. New York: Oxford University Press, 1980. McNemar, Q. Psychological statistics. 4th ed. New York: Wiley...0 5/S I milI’l 11 1 ; 𔃻 28 112.5 U-2 11112.2 II~.2.4~ 11111J.6 MICROCOPY RESOLUTION TEST CHART NADONAL BUJR[AU OF STANDARDS Ib3 A IvM Mental

  8. Ion-neutral Coupling During Deep Solar Minimum

    NASA Technical Reports Server (NTRS)

    Huang, Cheryl Y.; Roddy, Patrick A.; Sutton, Eric K.; Stoneback, Russell; Pfaff, Robert F.; Gentile, Louise C.; Delay, Susan H.

    2013-01-01

    The equatorial ionosphere under conditions of deep solar minimum exhibits structuring due to tidal forces. Data from instruments carried by the Communication Navigation Outage Forecasting System (CNOFS) which was launched in April 2008 have been analyzed for the first 2 years following launch. The Planar Langmuir Probe (PLP), Ion Velocity Meter (IVM) and Vector Electric Field Investigation (VEFI) all detect periodic structures during the 20082010 period which appear to be tides. However when the tidal features detected by these instruments are compared, there are distinctive and significant differences between the observations. Tides in neutral densities measured by the Gravity Recovery and Climate Experiment (GRACE) satellite were also observed during June 2008. In addition, Broad Plasma Decreases (BPDs) appear as a deep absolute minimum in the plasma and neutral density tidal pattern. These are co-located with regions of large downward-directed ion meridional velocities and minima in the zonal drifts, all on the nightside. The region in which BPDs occur coincides with a peak in occurrence rate of dawn depletions in plasma density observed on the Defense Meterological Satellite Program (DMSP) spacecraft, as well as a minimum in radiance detected by UV imagers on the Thermosphere Ionosphere Mesosphere Energetics and Dynamics (TIMED) and IMAGE satellites

  9. Effects of gonadotropins on in vitro maturation and of electrical stimulation on parthenogenesis of canine oocytes.

    PubMed

    Kim, B S; Lee, S R; Hyun, B H; Shin, M J; Yoo, D H; Lee, S; Park, Y S; Ha, J H; Ryoo, Z Y

    2010-02-01

    The objective of this study was to determine the effects of gonadotropins on in vitro maturation (IVM) and electrical stimulation on the parthenogenesis of canine oocytes. In experiment I, cumulus oocyte complexes were collected from ovaries at a random phase of the oestrus cycle and cultured on maturation medium treated with hCG or eCG for 48 or 72 h. There were no significant differences in the effects on the metaphase II (MII) rate between the hCG and eCG treatment groups over 48 h (5.4% vs 5.5%). The MII rate in the co-treatment group of hCG and eCG for 48 h was higher than in each hormone treated group (15.5%, p < 0.05). In experiment 2, the parthenogenetic effect on oocyte development, at various electrical field strengths (1.0, 1.5, 2.0 kV/cm DC) for 60 or 80 mus with a single DC pulse after IVM on the co-treatment of hCG and eCG, was examined. The rate of pronuclear formation (37.1%) in electrical activation at 1.5 kV/60 mus without cytochalasin B (CB) was higher than that of oocytes activated in the other groups (p < 0.05). However, we did not observe the cleavage stages. Also, CB did not influence parthenogenesis of canine oocytes. The results showed that the pronucleus formation rate, indicative of the parthenogenesis start point, could be increased by electrical stimulation. Therefore, these results can provide important data for the parthenogenesis of canine oocytes and suggest the probability of parthenogenesis in canines.

  10. Effect of Fetal Mouse Lung Tissue Co-Culture on In Vitro Maturation of Mouse Immature Oocytes.

    PubMed

    Belbasi, Masomeh; Jorsaraei, Seyed Gholam Ali; Gholamitabar Tabari, Maryam; Khanbabaei, Ramzan

    2017-10-01

    The aim of this study was to evaluate the fetal mouse lung tissue co-culture on in vitro maturation (IVM) of mouse immature oocytes. In this experimental study, germinal vesicle (GV) oocytes from ovaries of a group of 25 female mice, 6-8 weeks of age, were dissected after being stimulated by 7.5 IU pregnant mare serum gonadotropin (PMSG) through an intraperitoneal (IP) injection. The fetal lung tissues were then prepared and cultured individually. A total number of 300 oocytes were cultured in the following three groups for 24 hours: control group (n=100) containing only base medium, group I (n=100) containing base medium co-cultured with 11.5- to 12.5-day old fetal mouse lung tissues, and group II (n=100) containing base medium co-cultured with 12.5- to 13.5-day old fetal mouse lung tissues. The proportion of GV and metaphase І (MI) oocytes matured into MІІ oocytes were compared among the three groups using analysis of variance (ANOVA). Correlation test were also used to evaluate the successful rate of IVM oocytes. The proportions of GV oocytes reaching MІІ stage were 46, 65, and 56%, in control, I and II groups, respectively (P<0.05). The percentage of the oocytes remaining at the GV stage were higher in control group as compared with two treatment groups (P<0.05). This study indicated that fetal mouse lung tissue co-culture method increased the percentage of GV oocytes reaching MII stage. Copyright© by Royan Institute. All rights reserved.

  11. Milrinone treatment of bovine oocytes during in vitro maturation benefits production of nuclear transfer embryos by improving enucleation rate and developmental competence.

    PubMed

    Naruse, Kenji; Iga, Kosuke; Shimizu, Manabu; Takenouchi, Naoki; Akagi, Satoshi; Somfai, Tamas; Hirao, Yuji

    2012-01-01

    In the production of cattle nuclear transfer embryos, the production efficiency is affected by the oocyte developmental competence and successful enucleation rate. This study investigated the effect of treating oocytes with milrinone, a phosphodiesterase inhibitor, on these two characteristics. When cumulus-oocyte complexes (COCs) were cultured for 19 h with 0, 50 or 100 μM of milrinone, the enucleation rate was significantly improved by 100 μM milrinone. However, milrinone treatment during in vitro maturation (IVM) also delayed meiotic progression by at least 2 h, which would affect the examination of enucleation rate and developmental competence of oocytes. Thus, in the second experiment, meiotic resumption was temporarily inhibited with butyrolactone I (BL-I; 100 μM, 18 h) to decrease the delayed maturation caused by milrinone; this enabled a more accurate comparison of the effects of milrinone after oocyte maturation. In nuclear transfer embryo production, oocytes treated with milrinone (100 μM, 20 h) showed a significantly higher rate of enucleation compared with that of control oocytes. This improved enucleation rate was associated with a closer location of the metaphase plate to the first polar body in the treated oocytes compared with that in control oocytes. Furthermore, milrinone improved the frequency of development to the blastocyst stage in the resulting embryos. In conclusion, milrinone supplementation during IVM improved enucleation rates by rendering the metaphase plate in close proximity to the first polar body, and this treatment also improved oocyte developmental competence. These benefits additively improved the yield of cloned embryos that developed to the blastocyst stage.

  12. Current status of in vitro embryo production in sheep and goats.

    PubMed

    Paramio, M-T; Izquierdo, D

    2014-10-01

    Sheep and goat production is an important economic activity in Spain with an increasing interest in milk production. Multiovulation and Embryo Transfer (MOET) and In vitro Embryo Production (IVEP) are assisted reproductive technologies aimed at increasing the genetic diffusion of females. In vitro embryo production is a multi-step methodology comprising the following procedures: (i) In vitro Maturation (IVM) of oocytes recovered directly from the follicles, (ii) In vitro Fertilization (IVF) or co-incubation of capacitated spermatozoa with in vitro matured oocytes and (iii) In vitro culture (IVC) of zygotes up to the blastocyst stage. In vitro embryo production from oocytes recovered from prepubertal females is called JIVET (Juvenile in vitro Embryo Transfer) and allows shortened generation intervals and increased genetic gain. Embryo production together with embryo cryoconservation would allow large-scale embryo marketing, a pathogen-free genetic movement and easier and cheaper germplasm commercial transactions. Commercial Embryo activity in small ruminants is low compared to cows in the European Union (data from the European Embryo Transfer Association) and in the world (data from the International Embryo Transfer Association). There is less IVEP research in small ruminants compared to other livestock species. The aim of this review was to provide an overview of the current status of IVEP of small ruminant with an emphasis on (i) description of the main methodologies currently used for IVM, IVF and IVC of embryos (ii) comparing procedures and outputs from JIVET and IVEP of adult females and (iii) the future research perspectives of this technology. © 2014 Blackwell Verlag GmbH.

  13. The dynamic pattern of PLIN3 in pig oocytes and cumulus cells during in vitro maturation.

    PubMed

    Xu, Mingzhu; Zeng, Yaqiong; Chi, Daming; Si, Linan; Qu, Xiao; Li, Juan

    2018-02-01

    Lipid droplets (LDs) are the main energy resource for porcine preimplantation embryonic development. PLIN3 has been implicated in LD formation and regulation. Therefore, this study aimed to detect the dynamic pattern of PLIN3 in pig oocytes and cumulus cells (CC) during in vitro maturation (IVM), and to determine the relationship between PLIN3 and LD content. IVM with cumulus-enclosed oocytes (CEO), cumulus-denuded oocytes (DO) and the CCs denuded from the corresponding oocytes (DCC) was performed in porcine follicular fluid (PFF) or PFF-free optimized medium. DO and the DCC were cultured together under the same conditions as described above, while the DO was named DTO and the DCC was named DTCC in this group. Firstly, our results revealed LDs distributed widely in oocytes and CC, while the PLIN3 protein coated these LDs and spread out ubiquitously in the cytoplasm. Secondly, not only the mRNA level but also at protein level of PLIN3 in immature naked oocytes (IO) was higher than that in matured CEO, DO and DTO. Although PLIN3 was expressed at lower levels in CC from immature oocytes (ICC), the protein level of PLIN3 was comparably higher in the ECC and DCC groups. The triglyceride (TG) content in CEO and DO was significantly less abundant compared with that in IO. Therefore, our results indicated that co-culturing of oocytes and CC might affect PLIN3 expression levels in CC but not in oocytes. Lipid accumulation in pig oocytes during maturation might be affected by PLIN3 cross-talk between oocytes and CC.

  14. Monitoring the efficacy of drugs for neglected tropical diseases controlled by preventive chemotherapy

    PubMed Central

    Albonico, M.; Levecke, B.; LoVerde, P.T.; Montresor, A.; Prichard, R.; Vercruysse, J.; Webster, J.P.

    2017-01-01

    In the last decade, pharmaceutical companies, governments and global health organisations under the leadership of the World Health Organization (WHO) have pledged large-scale donations of anthelmintic drugs, including ivermectin (IVM), praziquantel (PZQ), albendazole (ALB) and mebendazole (MEB). This worldwide scale-up in drug donations calls for strong monitoring systems to detect any changes in anthelmintic drug efficacy. This review reports on the outcome of the WHO Global Working Group on Monitoring of Neglected Tropical Diseases Drug Efficacy, which consists of three subgroups: (i) soil-transmitted helminthiases (ALB and MEB); (ii) onchocerciasis and lymphatic filariasis (IVM); and (iii) schistosomiasis (PZQ). Progress of ongoing work, challenges and research needs for each of the four main drugs used in helminthic preventive chemotherapy (PC) are reported, laying the ground for appropriate implementation of drug efficacy monitoring programmes under the co-ordination and guidelines of the WHO. Best practices for monitoring drug efficacy should be made available and capacity built as an integral part of neglected tropical disease (NTD) programme monitoring. Development of a disease-specific model to predict the impact of PC programmes, to detect outliers and to solicit responses is essential. Research studies on genetic polymorphisms in relation to low-efficacy phenotypes should be carried out to identify markers of putative resistance against all NTD drugs and ultimately to develop diagnostic assays. Development of combination and co-administration of NTD drugs as well as of new drug entities to boost the armamentarium of the few drugs available for NTD control and elimination should be pursued in parallel. PMID:27842865

  15. Development of in vitro matured, in vitro fertilized domestic cat embryos following cryopreservation, culture and transfer.

    PubMed

    Gómez, Martha C; Pope, Earle; Harris, Rebecca; Mikota, Susan; Dresser, Betsy L

    2003-07-01

    The ability of embryos to successfully survive cryopreservation is dependent on both morphological and developmental characteristics. Domestic cat oocytes matured in vitro exhibit alterations in nuclear and cytoplasmic maturation that may affect developmental competence, particularly after cryopreservation. In Experiment 1, we evaluated the developmental competence of in vitro produced (IVM/IVF) cat embryos after cryopreservation on Days 2, 4 or 5 of IVC. In Experiment 2, in vivo viability was examined by transfer of cryopreserved embryos into recipient queens. Oocytes recovered from minced ovaries were cultured in TCM-199 with hCG/eCG and EGF at 38 degrees C in 5% O(2), 5% CO(2), 90% N(2) for 24h. In Experiment 1, after IVM/IVF, on Day 2 (n=56), Day 4 (n=48) and Day 5 (n=42) of IVC, embryos were equilibrated for 10 min at 22 degrees C in HEPES (15m M) Tyrode's (HeTy) with 1.4M propylene glycol (PG), 0.125 M sucrose (S), 10% dextran and 10% FBS, loaded into 0.25 ml straws, cooled at 2.0 degrees C/min to -6.0 degrees C and held for 10 min. After seeding, cooling resumed at 0.3 degrees C/min to -30 degrees C and after a 10 min hold, straws were plunged into liquid nitrogen (LN(2)). Straws were thawed in air for 2 min and cryoprotectant was removed by a five-step rinse consisting of 3 min each in HeTY with 0.95 M PG/0.25 M S; 0.95 M PG/0.125 M S; 0.45 M PG/0.125 M S; 0 PG/0.125 M S; 0 PG/0.0625 M S. Contemporary IVM/IVF embryos were used as nonfrozen controls (Day 2, n=14; Day 4, n=26; Day 5, n=35). After 8 days of IVC, the number of embryos developing to blastocysts was recorded and blastocyst cell numbers were counted after staining with Hoechst 33342. In Experiment 1, developmental stage did not affect the survival rate after thawing (Day 2=79%, Day 4=90%, Day 5=98%) and was not different from that of controls (Day 2=89%, Day 4=88%, Day 5=96%). Blastocyst development was similar among days both after cryopreservation (Day 2=59%, Day 4=54%, Day 5=63%) and in controls (Day 2=55%, Day 4=54%, Day 5=58%). Mean (+/-S.D.) cell number of blastocysts was slightly lower (NS) in cryopreserved embryos (Day 2=152+/-19, Day 4=124+/-20, Day 5=121+/-24) than in controls (Day 2=141+/-25, Day 4=169+/-21, Day 5=172+/-19). In Experiment 2, embryos frozen on Day 2 (n=68), Day 4 (n=49) or Day 5 (n=73) were thawed and cultured for 3, 1, or 0 days before transfer by laparotomy to 5 (mean=12.6+/-2.4), 4 (mean=12.2+/-3.7) and 6 (mean=12.0+/-1.6) recipients, respectively. Four recipients were pregnant on Day 21; two from embryos frozen on Day 4 and two from Day 5. Two live kittens were born at 66 days, a third kitten died during parturition at 64 days and a fourth pregnancy aborted by Day 45. In summary, we have shown that a controlled rate cryopreservation technique can be successfully applied to cat embryos produced by IVM/IVF. In vitro development to the blastocyst stage was not affected by the age of embryos at cryopreservation. The births of live kittens after ET of cryopreserved embryos is additional validation of progress toward applying assisted reproductive technology to preservation of endangered felids.

  16. Distribution of triatomine species in domestic and peridomestic environments in central coastal Ecuador

    PubMed Central

    Villacís, Anita G.; Moncayo, Ana L.; Ocaña-Mayorga, Sofia; Yumiseva, Cesar A.; Baus, Esteban G.

    2017-01-01

    Background Although the central coast of the Ecuador is considered endemic for Chagas disease, few studies have focused on determining the risk of transmission in this region. In this study we describe the triatomine household infestation in Manabí province (Central Coast region), determine the rate of Trypanosoma cruzi infection and study the risk factors associated with infestation by Rhodnius ecuadoriensis. Methodology/Principal findings An entomological survey found three triatomine species (Rhodnius ecuadoriensis, Panstrongylus rufotuberculatus and P. howardi) infesting domiciles in 47.4% of the 78 communities visited (total infestation rate of 4.5%). Four percent of domiciles were infested, and nymphs were observed in 77% of those domiciles. The three species were found in altitudes below 500 masl and in all ecological zones except cloud forest. Within the domicile, we found the three species mostly in bedrooms. Rhodnius ecuadoriensis and P. rufotuberculatus were abundant in bird nests, including chicken coops and P. howardi associated with rats in piles of bricks, in the peridomicile. Triatomine infestation was characterized by high rates of colonization, especially in peridomicile. Flagelates infection was detected in only 12% of the samples by microscopy and Trypanosoma cruzi infection in 42% of the examined triatomines by PCR (n = 372). The most important risk factors for house infestation by R. ecuadoriensis were ecological zone (w = 0.99) and presence of chickens (w = 0.96). Determinants of secondary importance were reporting no insecticide applications over the last twelve months (w = 0.86) and dirt floor (w = 0.70). On the other hand, wood as wall material was a protective factor (w = 0.85). Conclusion/Significance According the results, approximately 571,000 people would be at high risk for T. cruzi infection in Manabí province. A multidisciplinary approximation and the adhesion to a periodic integrated vector management (IVM) program are essential to guarantee sustainable preventive and control strategies for Chagas disease in this region. PMID:28968383

  17. Distribution of triatomine species in domestic and peridomestic environments in central coastal Ecuador.

    PubMed

    Grijalva, Mario J; Villacís, Anita G; Moncayo, Ana L; Ocaña-Mayorga, Sofia; Yumiseva, Cesar A; Baus, Esteban G

    2017-10-01

    Although the central coast of the Ecuador is considered endemic for Chagas disease, few studies have focused on determining the risk of transmission in this region. In this study we describe the triatomine household infestation in Manabí province (Central Coast region), determine the rate of Trypanosoma cruzi infection and study the risk factors associated with infestation by Rhodnius ecuadoriensis. An entomological survey found three triatomine species (Rhodnius ecuadoriensis, Panstrongylus rufotuberculatus and P. howardi) infesting domiciles in 47.4% of the 78 communities visited (total infestation rate of 4.5%). Four percent of domiciles were infested, and nymphs were observed in 77% of those domiciles. The three species were found in altitudes below 500 masl and in all ecological zones except cloud forest. Within the domicile, we found the three species mostly in bedrooms. Rhodnius ecuadoriensis and P. rufotuberculatus were abundant in bird nests, including chicken coops and P. howardi associated with rats in piles of bricks, in the peridomicile. Triatomine infestation was characterized by high rates of colonization, especially in peridomicile. Flagelates infection was detected in only 12% of the samples by microscopy and Trypanosoma cruzi infection in 42% of the examined triatomines by PCR (n = 372). The most important risk factors for house infestation by R. ecuadoriensis were ecological zone (w = 0.99) and presence of chickens (w = 0.96). Determinants of secondary importance were reporting no insecticide applications over the last twelve months (w = 0.86) and dirt floor (w = 0.70). On the other hand, wood as wall material was a protective factor (w = 0.85). According the results, approximately 571,000 people would be at high risk for T. cruzi infection in Manabí province. A multidisciplinary approximation and the adhesion to a periodic integrated vector management (IVM) program are essential to guarantee sustainable preventive and control strategies for Chagas disease in this region.

  18. Effect of heat stress on the survival and development of in vitro cultured bovine preantral follicles and on in vitro maturation of cumulus-oocyte complex.

    PubMed

    Paes, V M; Vieira, L A; Correia, H H V; Sa, N A R; Moura, A A A; Sales, A D; Rodrigues, A P R; Magalhães-Padilha, D M; Santos, F W; Apgar, G A; Campello, C C; Camargo, L S A; Figueiredo, J R

    2016-09-01

    The deleterious effect of heat stress (HS) on competence of oocytes from antral follicles is well recognized, but there is a lack of data regarding its impact on the viability and growth of preantral follicles. In this study, we used in vitro preantral follicle cultures to investigate the effects of HS on the following parameters: survival and development of primordial follicles after in vitro culture of ovarian fragments (experiment I); growth and antrum formation of isolated advanced secondary follicles (experiment II); and maturation rates after in vitro maturation (IVM) of cumulus-oocyte complexes (COCs) from antral follicles (>2-6 mm) grown in vivo (experiment III). Furthermore, the following end points were evaluated in all experiments: follicle/oocyte survival, reactive oxygen species (ROS), estradiol (E2) and progesterone (P4) production, as well as mRNA expression for select genes related to stress (HSP70) and apoptosis (MCL1 and BAX). In all experiments, HS consisted of exposing the structures (ovarian fragments, isolated preantral follicles and COCs) to 41 °C for 12 hours and then to 38.5 °C until the end of the culture (7 days for experiments I and II and 24 hours for experiment III). The temperature for the control group was held at 38.5 °C for the entire culture period. Heat stress increased (P < 0.05) the percentage of developing follicles (intermediate, primary, and secondary follicles) at 12 hours and increased levels of ROS at all evaluated time points (12, 24 hours, and D7), when compared to the control (experiment I). Heat stress did not affect (P > 0.05) any identified end points when preantral follicles were cultured in their isolated form (experiment II). However, in experiment III, HS decreased (P < 0.05) both the rates of metaphase II after 24 hours and E2 production at 12 hours of IVM. Moreover, HS increased (P < 0.0001) levels of P4 after IVM and ROS production at every evaluated time point, compared with the control (12 and 24 hours). In conclusion, HS caused: (1) early activation of primordial follicles; (2) an increase in ROS production by early preantral follicles enclosed in ovarian tissue and by COCs; (3) a short-term reduction of E2 production by COCs; and (4) an increase in P4 secretion from COCs. However, HS did not affect in vitro culture of advanced isolated secondary follicles. Experimental evidence indicates that preantral follicles are less sensitive to HS than COC. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Improving the cytoplasmic maturation of bovine oocytes matured in vitro with intracellular and/or extracellular antioxidants is not associated with increased rates of embryo development.

    PubMed

    Rocha-Frigoni, Nathália A S; Leão, Beatriz C S; Dall'Acqua, Priscila Chediek; Mingoti, Gisele Z

    2016-11-01

    The production of reactive oxygen species (ROS) is a normal process that occurs in the cellular mitochondrial respiratory chain. However, an increase in ROS levels during in vitro production of bovine embryos induces oxidative stress, leading to failed embryonic development. Therefore, we investigated whether supplementation of IVM medium with intracellular (cysteine and cysteamine; C + C) and/or extracellular (catalase; CAT) antioxidants improves the culture system, affects the mitochondrial membrane potential, affects the intracellular levels of ROS and glutathione (GSH) in the bovine oocytes at the end of maturation, and thereby affects the subsequent embryonic development. At the end of IVM, the metaphase II rates were unaffected by the treatments (76.7 ± 1.7% to 80.6 ± 5.2%; P > 0.05). The intracellular ROS levels, expressed in arbitrary fluorescence units, found in the oocytes treated with intracellular antioxidants (C + C and C + C + CAT groups; 1.06, averaged) were as low as those observed in immature oocytes (0 hour: 1.00 ± 0.12). Among mature oocytes, higher (P < 0.05) ROS levels were found in the control group (1.91 ± 0.10) when compared to the ROS levels found in oocytes treated with antioxidants. Intracellular GSH levels in all groups were lower (0.17 ± 0.09 to 0.51 ± 0.05; P < 0.05) than those in immature oocytes (1.00 ± 0.08), although GSH levels in the C + C group (0.51 ± 0.05) were greater (P < 0.05) than in the control, CAT, and C + C + CAT groups (0.23; averaged). The mitochondrial membrane potential in all groups was improved (1.6; averaged; P < 0.05) compared to the membrane potential observed in the immature oocytes (1.00 ± 0.05), with the exception of the C + C group (0.94 ± 0.03). There was no effect (P > 0.05) of antioxidant supplementation on embryonic development to the blastocyst stage (36.1%; averaged); however, there was an increased tendency (P = 0.0689) to obtain a higher blastocyst rate for the C + C + CAT group (47.5 ± 5.6%) compared to the control group (29.9 ± 4.8%). In conclusion, despite improvements in specific parameters of cytoplasmic maturation, the addition of intracellular and/or extracellular antioxidants during IVM did not affect embryo development. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Increasing the cAMP concentration during in vitro maturation of pig oocytes improves cumulus maturation and subsequent fertilization in vitro.

    PubMed

    Appeltant, R; Beek, J; Vandenberghe, L; Maes, D; Van Soom, A

    2015-02-01

    Porcine IVF faces various problems such as incomplete cytoplasmic maturation of the oocyte and polyspermy. Previous studies proved the importance of cAMP in regulating nuclear and cytoplasmic maturation of oocytes. This study investigated the effect of the cAMP-modulating agents 3-isobutyl-1-methylxanthine (IBMX) and dibutyryl cAMP sodium salt (dbcAMP) on several parameters during in vitro production of porcine embryos. First, we wanted to see if oocyte collection in IBMX could meiotically arrest oocytes and, as such, improve synchronization of nuclear and cytoplasmic maturation. To this end, cumulus-oocyte complexes (COCs) were collected from gilts in HEPES-buffered Tyrode balanced salt solution medium with 0.5-mM IBMX or without IBMX. At the end of oocyte collection, the effect of IBMX on chromatin configuration was evaluated. However, no differences could be observed in nuclear configuration between IBMX- and IBMX+ oocytes (P > 0.05). Second, we added dbcAMP during IVM to improve cytoplasmic maturation and evaluated cumulus expansion (lack of adhesion), a disintegrin and metalloproteinase with thrombospondin-like repeats (ADAMTS-1) levels in cumulus cells, fertilization, and blastocyst rates. Cumulus-oocyte complexes were matured in modified North Carolina State University medium 37 with or without 1-mM dbcAMP. Frozen-thawed, epididymal, boar spermatozoa were used for IVF. After IVF, presumed zygotes were cultured for 7 days in North Carolina State University medium 23. Penetration rate decreased in dbcAMP+ (57.3%) compared with dbcAMP- (67.8%), but the polyspermy rate also decreased (43.3% vs. 53.4%, respectively) leading to an increased normal fertilization rate (56.7% vs. 46.6%, respectively; P < 0.05). Only 7.2% of the COCs showed adhesion in dbcAMP+ which was lower than 15.7% in dbcAMP- (P < 0.05) probably because of an upregulation of the ADAMTS-1 protein by dbcAMP. When the adherent oocytes were removed during maturation, no difference could be detected between the blastocyst rate of dbcAMP- and dbcAMP+ (17.1% and 21.0% on Day 7, respectively; P > 0.05). In conclusion, the use of IBMX during collection did not cause a meiotic arrest. Using dbcAMP during IVM caused a greater normal fertilization rate, a lower rate of adherent COCs during IVM, higher levels of ADAMTS-1 in cumulus cells, and an equal blastocyst rate after screening out adherent COCs. These findings contribute to a better understanding of cAMP involvement in porcine oocyte maturation and provide a basis to develop an improved system with less polyspermy and higher blastocyst rates. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Monitoring the efficacy of drugs for neglected tropical diseases controlled by preventive chemotherapy.

    PubMed

    Albonico, M; Levecke, B; LoVerde, P T; Montresor, A; Prichard, R; Vercruysse, J; Webster, J P

    2015-12-01

    In the last decade, pharmaceutical companies, governments and global health organisations under the leadership of the World Health Organization (WHO) have pledged large-scale donations of anthelmintic drugs, including ivermectin (IVM), praziquantel (PZQ), albendazole (ALB) and mebendazole (MEB). This worldwide scale-up in drug donations calls for strong monitoring systems to detect any changes in anthelmintic drug efficacy. This review reports on the outcome of the WHO Global Working Group on Monitoring of Neglected Tropical Diseases Drug Efficacy, which consists of three subgroups: (i) soil-transmitted helminthiases (ALB and MEB); (ii) onchocerciasis and lymphatic filariasis (IVM); and (iii) schistosomiasis (PZQ). Progress of ongoing work, challenges and research needs for each of the four main drugs used in helminthic preventive chemotherapy (PC) are reported, laying the ground for appropriate implementation of drug efficacy monitoring programmes under the co-ordination and guidelines of the WHO. Best practices for monitoring drug efficacy should be made available and capacity built as an integral part of neglected tropical disease (NTD) programme monitoring. Development of a disease-specific model to predict the impact of PC programmes, to detect outliers and to solicit responses is essential. Research studies on genetic polymorphisms in relation to low-efficacy phenotypes should be carried out to identify markers of putative resistance against all NTD drugs and ultimately to develop diagnostic assays. Development of combination and co-administration of NTD drugs as well as of new drug entities to boost the armamentarium of the few drugs available for NTD control and elimination should be pursued in parallel. Copyright © 2015 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

  2. Effect of MEM vitamins and forskolin on embryo development and vitrification tolerance of in vitro-produced pig embryos.

    PubMed

    Cuello, C; Gomis, J; Almiñana, C; Maside, C; Sanchez-Osorio, J; Gil, M A; Sánchez, A; Parrilla, I; Vazquez, J M; Roca, J; Martinez, E A

    2013-01-30

    The aims of this study were (1) to determine the effect of in vitro maturation (IVM) medium supplementation with MEM vitamins on in vitro embryo development and sensitivity to vitrification of Day 6 blastocysts and (2) to evaluate whether the addition of forskolin to in vitro culture (IVC) medium enhances blastocyst survival following Super Open Pulled Straw (SOPS) vitrification. Cumulus-oocyte complexes (COCs; n=4000) were matured with 0.0% or 0.05% (v/v) MEM vitamins. After 44h of IVM, the oocytes were in vitro fertilized, and presumptive zygotes were cultured. At Day 5 of IVC, embryos from both experimental groups were cultured for 24h with 0 or 10μM forskolin, achieving a 2×2 factorial design. The blastocyst formation rate was assessed on Day 6, and subsets of samples from the four experimental groups were vitrified (n=469) or kept fresh (n=546). Fresh and vitrified-warmed blastocysts were cultured for 24h prior to embryo survival and total blastocyst cell number assessment. The MEM vitamins increased (P<0.001) the blastocyst formation rate at Day 6, but they did not affect embryo survival after vitrification. In contrast, the addition of forskolin to the culture medium enhanced (P<0.05) the blastocyst vitrification tolerance. The total blastocyst cell number was similar among the groups. In conclusion, supplementation with 0.05% MEM vitamins improved the blastocyst formation rate, and the addition of 10μM forskolin to the culture medium increased survival in Day 6 in vitro-produced blastocysts after SOPS vitrification. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. Mouse preantral follicle growth in 3D co-culture system using human menstrual blood mesenchymal stem cell.

    PubMed

    Rajabi, Zahra; Yazdekhasti, Hossein; Noori Mugahi, Seyed Mohammad Hossein; Abbasi, Mehdi; Kazemnejad, Somaieh; Shirazi, Abolfazl; Majidi, Masoumeh; Zarnani, Amir-Hassan

    2018-03-01

    Follicle culture provides a condition which can help investigators to evaluate various aspects of ovarian follicle growth and development and impact of different components and supplementations as well as presumably application of follicle culture approach in fertility preservation procedures. Mesenchymal Stem Cells (MSCs), particularly those isolated from menstrual blood has the potential to be used as a tool for improvement of fertility. In the current study, a 3D co-culture system with mice preantral follicles and human Menstrual Blood Mesenchymal Stem Cells (MenSCs) using either collagen or alginate beads was designed to investigate whether this system allows better preantral follicles growth and development. Results showed that MenSCs increase the indices of follicular growth including survival rate, diameter, and antrum formation as well as the rate of in vitro maturation (IVM) in both collagen and alginates beads. Although statistically not significant, alginate was found to be superior in terms of supporting survival rate and antrum formation. Hormone assay demonstrated that the amount of secreted 17 β-estradiol and progesterone in both 3D systems increased dramatically after 12 days, with the highest levels in system employing MenSCs. Data also demonstrated that relative expression of studied genes increased for Bmp15 and Gdf9 and decreased for Mater when follicles were cultured in the presence of MenSCs. Collectively, results of the present study showed that MenSCs could improve indices of follicular growth and maturation in vitro. Further studies are needed before a clinical application of MenSCs-induced IVM is considered. Copyright © 2018 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. All rights reserved.

  4. The beneficial effect of repaglinide on in vitro maturation and development ability of immature mouse oocytes.

    PubMed

    Kalehoei, Eshrat; Azadbakht, Mehri

    2017-08-01

    Repaglinide is a hypoglycemic drug, causing depolarization of the cell membrane, opening the voltage-gated calcium channels, and then increasing intracellular calcium in the pancreatic B cells by inhibition of the K-ATP-sensitive channels. Oocyte in vitro maturation (IVM) is influenced by different factors such as calcium signaling. In this study, we examined the effects of repaglinide on in vitro maturation and fertilization ability of mouse oocyte. Immature oocytes were isolated from female Naval Medical Research Institute mice which are 6-8 wk old mechanically and then cultured in 30 μl droplets of T6 medium with different concentrations of repaglinide. The control group did not receive repaglinide (R 0 ). Treatment groups received different concentrations (5, 10, and 100 nM and 1 and 10 μM) of repaglinide (R 1 , R 2 , R 3 , R 4 , and R 5 , respectively). Oocyte in vitro maturation rate was assessed after 24 h. In vitro fertilization was performed using metaphase II oocytes obtained from R 0 and R 4 treatments. Embryo cleavage rate was calculated at 48 h post-IVF. Chi-square test was used for evaluating difference between control and treatment groups (p < 0.05). Oocyte maturation rate after 24 h in treatment groups R 2 , R 3 , R 4 , and R 5 was significantly higher than that in the control (p < 0.05). Supplementation of medium with 1 μM of repaglinide (R 4 ) during IVM significantly improved outcome of embryo cleavage rate than control at 48 h post-IVF (p < 0.05). In conclusion, repaglinide can be considered as an effective agent for in vitro oocyte maturation and embryo cleavage.

  5. Melatonin influences the sonic hedgehog signaling pathway in porcine cumulus oocyte complexes.

    PubMed

    Lee, Sanghoon; Jin, Jun-Xue; Taweechaipaisankul, Anukul; Kim, Geon A; Ahn, Curie; Lee, Byeong Chun

    2017-10-01

    Melatonin, which is synthesized in the pineal gland and peripheral reproductive organs, has antioxidant properties and regulates physiological processes. It is well known that melatonin affects in vitro maturation (IVM) of oocytes and embryonic development in many species. However, beneficial effects of melatonin on IVM have been explained mainly by indirect antioxidant effects and little information is available on the underlying mechanism by which melatonin directly acts on porcine cumulus oocyte complexes (COCs). Sonic hedgehog (Shh) signaling is important for follicle development, oocyte maturation, and embryo development, and there may be a relationship between melatonin and Shh signaling. To examine this, we designed three groups: (i) control, (ii) melatonin (10 -9  mol/L), and (iii) melatonin with cyclopamine (2 μmol/L; Shh signaling inhibitor). The aim of this study was to investigate the effects of these agents on cumulus expansion, oocyte maturation, embryo development after parthenogenetic activation (PA), gene expression in cumulus cells, oocytes and blastocysts, and protein expression in COCs. Melatonin significantly increased the proportion of COCs exhibiting complete cumulus expansion (degree 4), PA blastocyst formation rates, and total cell numbers, which were inhibited by addition of cyclopamine. Simultaneously, the expression of cumulus expansion-related genes (Ptgs1, Ptgs2, and Has2) and Shh signaling-related genes (Shh, Pthc1, Smo, and Gli1) and proteins (Ptch1, Smo, and Gli1) in cumulus cells was upregulated in the melatonin-treated group, and these effects were also inhibited by cyclopamine. In conclusion, our results suggest that Shh signaling mediates effects of melatonin to improve porcine cumulus expansion and subsequent embryo development. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Effects of trehalose vitrification and artificial oocyte activation on the development competence of human immature oocytes.

    PubMed

    Zhang, Zhiguo; Wang, Tianjuan; Hao, Yan; Panhwar, Fazil; Chen, Zhongrong; Zou, Weiwei; Ji, Dongmei; Chen, Beili; Zhou, Ping; Zhao, Gang; Cao, Yunxia

    2017-02-01

    Sucrose and trehalose are conventional cryoprotectant additives for oocytes and embryos. Ethanol can artificially enhance activation of inseminated mature oocytes. This study aims to investigate whether artificial oocyte activation (AOA) with ethanol can promote the development competence of in vitro matured oocytes. A total of 810 human immature oocytes, obtained from 325 patients undergoing normal stimulated oocyte retrieval cycles, were in vitro maturated (IVM) either immediately after collection (Fresh group n = 291)) or after being vitrified as immature oocytes (Vitrified group n = 519). These groups were arbitrarily assigned. All fresh and vitrified oocytes which matured after a period of IVM then underwent intra-cytoplasmic sperm injection (ICSI). Half an hour following ICSI, they were either activated by 7% ethanol (AOA group) or left untreated (Non-AOA group). Fertilization, cleavage rate, blastocyst quality and aneuploidy rate were then evaluated. High-quality blastocysts were only obtained in both the fresh and vitrified groups which had undergone AOA after ICSI. Trehalose vitrification slightly, but not significantly, increased the formation rates of high-quality embryos (21.7% VS 15.4%, P > 0.05) and blastocysts (15.7% VS 7.69%, P > 0.05)) when compared with sucrose vitrification. Aneuploidy was observed in 12 of 24 (50%) of the AOA derived high quality blastocysts. High-quality blastocysts only developed from fresh or vitrified immature oocytes if the ICSI was followed by AOA. This information may be important for human immature oocytes commonly retrieved in normal stimulation cycles and may be particularly important for certain patient groups, such as cancer patients. AOA with an appropriate concentration of ethanol can enhance the developmental competence of embryos. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Polymyxin B in Combination with Enrofloxacin Exerts Synergistic Killing against Extensively Drug-Resistant Pseudomonas aeruginosa.

    PubMed

    Lin, Yu-Wei; Yu, Heidi H; Zhao, Jinxin; Han, Mei-Ling; Zhu, Yan; Akter, Jesmin; Wickremasinghe, Hasini; Walpola, Hasini; Wirth, Veronika; Rao, Gauri G; Forrest, Alan; Velkov, Tony; Li, Jian

    2018-06-01

    Polymyxins are increasingly used as a last-resort class of antibiotics against extensively drug-resistant (XDR) Gram-negative bacteria. However, resistance to polymyxins can emerge with monotherapy. As nephrotoxicity is the major dose-limiting factor for polymyxin monotherapy, dose escalation to suppress the emergence of polymyxin resistance is not a viable option. Therefore, novel approaches are needed to preserve this last-line class of antibiotics. This study aimed to investigate the antimicrobial synergy of polymyxin B combined with enrofloxacin against Pseudomonas aeruginosa Static time-kill studies were conducted over 24 h with polymyxin B (1 to 4 mg/liter) and enrofloxacin (1 to 4 mg/liter) alone or in combination. Additionally, in vitro one-compartment model (IVM) and hollow-fiber infection model (HFIM) experiments were performed against P. aeruginosa 12196. Polymyxin B and enrofloxacin in monotherapy were ineffective against all of the P. aeruginosa isolates examined, whereas polymyxin B-enrofloxacin in combination was synergistic against P. aeruginosa , with ≥2 to 4 log 10 kill at 24 h in the static time-kill studies. In both IVM and HFIM, the combination was synergistic, and the bacterial counting values were below the limit of quantification on day 5 in the HFIM. A population analysis profile indicated that the combination inhibited the emergence of polymyxin resistance in P. aeruginosa 12196. The mechanism-based modeling suggests that the synergistic killing is a result of the combination of mechanistic and subpopulation synergy. Overall, this is the first preclinical study to demonstrate that the polymyxin-enrofloxacin combination is of considerable utility for the treatment of XDR P. aeruginosa infections and warrants future clinical evaluations. Copyright © 2018 American Society for Microbiology.

  8. Development of an in vitro bioassay for measuring susceptibility to macrocyclic lactone anthelmintics in Dirofilaria immitis.

    PubMed

    Evans, Christopher C; Moorhead, Andrew R; Storey, Bobby E; Wolstenholme, Adrian J; Kaplan, Ray M

    2013-12-01

    For more than 20 years, anthelmintics of the macrocyclic lactone (ML) drug class have been widely and effectively used as preventives against the canine heartworm, Dirofilaria immitis. However, in recent years an increased number of lack of efficacy (LOE) cases are being reported, in which dogs develop mature heartworm infections despite receiving monthly prophylactic doses of ML drugs. While this situation is raising concerns that heartworms may be developing resistance to MLs, compelling evidence for this is still lacking. Resolution of this dilemma requires validated biological or molecular diagnostic assays, but, unfortunately, no such tests currently exist. To address this need, we developed and optimized a larval migration inhibition assay (LMIA) for use with D. immitis third-stage larvae. The LMIA was used to measure the in vitro dose-response of two ML drugs (ivermectin and eprinomectin) on a known ML-susceptible laboratory strain of D. immitis. A nonlinear regression model was fit to the dose-response data, from which IC50 values were calculated; the mean IC50 and 95% confidence interval for IVM was 4.56 μM (1.26-16.4 μM), greater than that for EPR at 2.02 μM (1.68-2.42 μM), and this difference was significant (p = 0.0428). The R (2) value for EPR assays (0.90) was also greater than that for IVM treatment (0.71). The consistency and reproducibility of the dose-response data obtained with this assay suggests that it may be a useful technique for investigating the relative susceptibilities to ML drugs in other D. immitis populations.

  9. Control of zoonotic cutaneous leishmaniasis vector, Phlebotomus papatasi, using attractive toxic sugar baits (ATSB).

    PubMed

    Saghafipour, Abedin; Vatandoost, Hassan; Zahraei-Ramazani, Ali Reza; Yaghoobi-Ershadi, Mohammad Reza; Rassi, Yavar; Karami Jooshin, Moharram; Shirzadi, Mohammad Reza; Akhavan, Amir Ahmad

    2017-01-01

    Attractive Toxic Sugar Baits (ATSB) is a new vector control method that meets Integrated Vector Management (IVM) goals. In an experimental design, this study aimed to determine effects of ATSB on control of Phlebotomus papatasi, as a main vector of Zoonotic Cutaneous Leishmaniasis (ZCL), in Qom Province, center of Iran. In a cross-sectional design, boric acid was mixed with brown sugar solution and tested as toxic baits for P. papatasi. Two methods were utilized to use the baits: (a) spraying ATSB on vegetation, bushes, and shrubs; and (b) setting ATSB-treated barrier fences in front of colonies at 500 m distance from the houses in outskirts of villages. In order to examine the residual efficacy rate of ATSB-treated barrier fences, the bioassay test was used. Density of P. papatasi sandflies was measured using sticky and light traps biweekly. For data analysis, Mann-Whitney U Test and Kruskal-Wallis were used. Results ATSB-treated barrier fences led to 3 times reduction in P. papatasi population. Besides that, ATSB spraying on plants led to more than 5 times reduction in P. papatasi population. Comparing the incidence of leishmaniasis in treated villages before and after the study showed that the incidence was statistically reduced. Therefore, ATSB is an effective method to control vectors and prevent leishmaniasis.

  10. Who Is Vulnerable to Dengue Fever? A Community Survey of the 2014 Outbreak in Guangzhou, China

    PubMed Central

    Chen, Bin; Yang, Jun; Luo, Lei; Yang, Zhicong; Liu, Qiyong

    2016-01-01

    Unprecedented dengue fever (DF) outbreaks impel China to develop useful disease control strategies. Integrated vector management (IVM) focuses on identifying vulnerable populations and interrupting human–vector contact; however, vulnerable populations have not been clearly identified in China. We conducted a case-control study during the initial stage of the 2014 DF outbreak in Guangzhou, China to assess risk factors for DF infection. Cases were randomly sampled from the National Notifiable Infectious Disease Reporting Information System (NNIDRIS). Controls were healthy individuals recruited from 17 DF infected communities through cluster sampling. A structured questionnaire on demographics, knowledge, practices, and living environment was administered to participants (165 cases; 492 controls). Logistic regression models identified characteristics of vulnerable populations. Awareness of dengue (OR = 0.08, 95% CI = 0.04–0.17), removing trash and stagnant water from around the residence (OR = 0.02, 95% CI = 0.00–0.17), and using mosquito repellent oils (OR = 0.36, 95% CI = 0.16–0.81) were protective factors. Living in an old flat or shed (OR = 2.38, 95% CI = 1.18–4.79) was a risk factor. Coils and bed nets were not protective due to incorrect knowledge of use. Using mosquito repellent oils and other protective measures can reduce vulnerability to DF infection. PMID:27428986

  11. Improved OCT imaging of lung tissue using a prototype for total liquid ventilation

    NASA Astrophysics Data System (ADS)

    Schnabel, Christian; Meissner, Sven; Koch, Edmund

    2011-06-01

    Optical coherence tomography (OCT) is used for imaging subpleural alveoli in animal models to gain information about dynamic and morphological changes of lung tissue during mechanical ventilation. The quality of OCT images can be increased if the refraction index inside the alveoli is matched to the one of tissue via liquid-filling. Thereby, scattering loss can be decreased and higher penetration depth and tissue contrast can be achieved. Until now, images of liquid-filled lungs were acquired in isolated and fixated lungs only, so that an in vivo measurement situation is not present. To use the advantages of liquid-filling for in vivo imaging of small rodent lungs, it was necessary to develop a liquid ventilator. Perfluorodecalin, a perfluorocarbon, was selected as breathing fluid because of its refraction index being similar to the one of water and the high transport capacity for carbon dioxide and oxygen. The setup is characterized by two independent syringe pumps to insert and withdraw the fluid into and from the lung and a custom-made control program for volume- or pressure-controlled ventilation modes. The presented results demonstrate the liquid-filling verified by optical coherence tomography and intravital microscopy (IVM) and the advantages of liquid-filling to OCT imaging of subpleural alveoli.

  12. Factors associated with perception of risk of contracting HIV among secondary school female learners in Mbonge subdivision of rural Cameroon.

    PubMed

    Tarkang, Elvis Enowbeyang

    2014-01-01

    Since learners in secondary schools fall within the age group hardest hit by HIV/AIDS, it is obvious that these learners might be at high risk of contracting HIV/AIDS. However, little has been explored on the perception of risk of contracting HIV among secondary school learners in Cameroon. This study aimed at examining the perception of risk of contracting HIV among secondary school learners in Mbonge subdivision of rural Cameroon using the Health Belief Model (HBM) as framework. A quantitative, correlational design was adopted, using a self-administered questionnaire to collect data from 210 female learners selected through disproportional, stratified, simple random sampling technique, from three participating senior secondary schools. Statistics were calculated using SPSS version 20 software program. Only 39.4% of the respondents perceived themselves to be at high risk of contracting HIV, though the majority, 54.0% were sexually active. Multinomial logistic regression analyses show that sexual risk behaviours (p=0.000) and the Integrated Value Mapping (IVM) of the perception components of the HBM are the most significant factors associated with perception of risk of contracting HIV at the level p<0.05. The findings of this study can play an instrumental role in the development of effective preventive and interventional messages for adolescents in Cameroon.

  13. P2X4 Receptor in Silico and Electrophysiological Approaches Reveal Insights of Ivermectin and Zinc Allosteric Modulation

    PubMed Central

    Latapiat, Verónica; Rodríguez, Felipe E.; Godoy, Francisca; Montenegro, Felipe A.; Barrera, Nelson P.; Huidobro-Toro, Juan P.

    2017-01-01

    Protein allosteric modulation is a pillar of metabolic regulatory mechanisms; this concept has been extended to include ion channel regulation. P2XRs are ligand-gated channels activated by extracellular ATP, sensitive to trace metals and other chemicals. By combining in silico calculations with electrophysiological recordings, we investigated the molecular basis of P2X4R modulation by Zn(II) and ivermectin, an antiparasite drug currently used in veterinary medicine. To this aim, docking studies, molecular dynamics simulations and non-bonded energy calculations for the P2X4R in the apo and holo states or in the presence of ivermectin and/or Zn(II) were accomplished. Based on the crystallized Danio rerio P2X4R, the rat P2X4R, P2X2R, and P2X7R structures were modeled, to determine ivermectin binding localization. Calculations revealed that its allosteric site is restricted to transmembrane domains of the P2X4R; the role of Y42 and W46 plus S341 and non-polar residues were revealed as essential, and are not present in the homologous P2X2R or P2X7R transmembrane domains. This finding was confirmed by preferential binding conformations and electrophysiological data, revealing P2X4R modulator specificity. Zn(II) acts in the P2X4R extracellular domain neighboring the SS3 bridge. Molecular dynamics in the different P2X4R states revealed allosterism-induced stability. Pore and lateral fenestration measurements of the P2X4R showed conformational changes in the presence of both modulators compatible with a larger opening of the extracellular vestibule. Electrophysiological studies demonstrated additive effects in the ATP-gated currents by joint applications of ivermectin plus Zn(II). The C132A P2X4R mutant was insensitive to Zn(II); but IVM caused a 4.9 ± 0.7-fold increase in the ATP-evoked currents. Likewise, the simultaneous application of both modulators elicited a 7.1 ± 1.7-fold increase in the ATP-gated current. Moreover, the C126A P2X4R mutant evoked similar ATP-gated currents comparable to those of wild-type P2X4R. Finally, a P2X4/2R chimera did not respond to IVM but Zn(II) elicited a 2.7 ± 0.6-fold increase in the ATP-gated current. The application of IVM plus Zn(II) evoked a 2.7 ± 0.9-fold increase in the ATP-gated currents. In summary, allosteric modulators caused additive ATP-gated currents; consistent with lateral fenestration enlargement. Energy calculations demonstrated a favorable transition of the holo receptor state following both allosteric modulators binding, as expected for allosteric interactions. PMID:29326590

  14. Is outdoor vector control needed for malaria elimination? An individual-based modelling study.

    PubMed

    Zhu, Lin; Müller, Günter C; Marshall, John M; Arheart, Kristopher L; Qualls, Whitney A; Hlaing, WayWay M; Schlein, Yosef; Traore, Sekou F; Doumbia, Seydou; Beier, John C

    2017-07-03

    Residual malaria transmission has been reported in many areas even with adequate indoor vector control coverage, such as long-lasting insecticidal nets (LLINs). The increased insecticide resistance in Anopheles mosquitoes has resulted in reduced efficacy of the widely used indoor tools and has been linked with an increase in outdoor malaria transmission. There are considerations of incorporating outdoor interventions into integrated vector management (IVM) to achieve malaria elimination; however, more information on the combination of tools for effective control is needed to determine their utilization. A spatial individual-based model was modified to simulate the environment and malaria transmission activities in a hypothetical, isolated African village setting. LLINs and outdoor attractive toxic sugar bait (ATSB) stations were used as examples of indoor and outdoor interventions, respectively. Different interventions and lengths of efficacy periods were tested. Simulations continued for 420 days, and each simulation scenario was repeated 50 times. Mosquito populations, entomologic inoculation rates (EIRs), probabilities of local mosquito extinction, and proportion of time when the annual EIR was reduced below one were compared between different intervention types and efficacy periods. In the village setting with clustered houses, the combinational intervention of 50% LLINs plus outdoor ATSBs significantly reduced mosquito population and EIR in short term, increased the probability of local mosquito extinction, and increased the time when annual EIR is less than one per person compared to 50% LLINs alone; outdoor ATSBs alone significantly reduced mosquito population in short term, increased the probability of mosquito extinction, and increased the time when annual EIR is less than one compared to 50% LLINs alone, but there was no significant difference in EIR in short term between 50% LLINs and outdoor ATSBs. In the village setting with dispersed houses, the combinational intervention of 50% LLINs plus outdoor ATSBs significantly reduced mosquito population in short term, increased the probability of mosquito extinction, and increased the time when annual EIR is less than one per person compared to 50% LLINs alone; outdoor ATSBs alone significantly reduced mosquito population in short term, but there were no significant difference in the probability of mosquito extinction and the time when annual EIR is less than one between 50% LLIN and outdoor ATSBs; and there was no significant difference in EIR between all three interventions. A minimum of 2 months of efficacy period is needed to bring out the best possible effect of the vector control tools, and to achieve long-term mosquito reduction, a minimum of 3 months of efficacy period is needed. The results highlight the value of incorporating outdoor vector control into IVM as a supplement to traditional indoor practices for malaria elimination in Africa, especially in village settings of clustered houses where LLINs alone is far from sufficient.

  15. Through-process modelling of texture and anisotropy in AA5182

    NASA Astrophysics Data System (ADS)

    Crumbach, M.; Neumann, L.; Goerdeler, M.; Aretz, H.; Gottstein, G.; Kopp, R.

    2006-07-01

    A through-process texture and anisotropy prediction for AA5182 sheet production from hot rolling through cold rolling and annealing is reported. Thermo-mechanical process data predicted by the finite element method (FEM) package T-Pack based on the software LARSTRAN were fed into a combination of physics based microstructure models for deformation texture (GIA), work hardening (3IVM), nucleation texture (ReNuc), and recrystallization texture (StaRT). The final simulated sheet texture was fed into a FEM simulation of cup drawing employing a new concept of interactively updated texture based yield locus predictions. The modelling results of texture development and anisotropy were compared to experimental data. The applicability to other alloys and processes is discussed.

  16. Identification of risk factors for malaria control by focused interventions in Ranchi district, Jharkhand, India.

    PubMed

    Saxena, Rekha; Das, M K; Nagpal, B N; Srivastava, Aruna; Gupta, Sanjeev Kumar; Kumar, Anil; Tomar, Arvind Singh; Sinha, A T S; Vidyotma, Rajkumari; Jeyaseelan, A T; Baraik, Vijay Kumar; Singh, V P

    2014-12-01

    Ranchi, the capital of Jharkhand state is endemic for malaria, particularly the Bundu Primary Health Centre (PHC) is the worst affected. Therefore, a study was initiated during 2009 using remote sensing (RS) and geographical information system (GIS) to identify risk factors responsible for high endemicity in this PHC. Bundu and Angara in Ranchi district were identified as high and low malaria endemic PHCs based on epidemiological data of three years (2007-09). The habitation, streams, other water body, landform, PHC and village boundary thematic maps were prepared using IRS-P6/LISS III-IV imageries and macro level breeding sites were identified. Digital elevation model (DEM) of the PHCs was generated using Cartosat Stereo Pair images and from DEM, slope map was derived to calculate flat area. From slope, aspect map was derived to indicate direction of water flow. Length of perennial streams, area under rocky terrain and buffer zones of 250, 500 and 750 m were constructed around streams. High resolution remote sensing imageries were used to identify micro level breeding sites. Based on macro-micro breeding sites, six villages from each PHC were selected randomly having combination of different parameters representing all ecotypes. Entomological data were collected during 2010-11 in pre- and post-monsoon seasons following standard techniques and analyzed statistically. Differential analysis was attempted to comprehend socioeconomic and other determinants associated with malaria transmission. The study identified eight risk factors responsible for higher malaria endemicity in Bundu in comparison to Angara PHC based on ecological, entomological, socioeconomic and other local parameters. Focused interventions in integrated vector management (IVM) mode are required to be carried out in the district for better management and control of disease.

  17. Management of infertility in women over 40.

    PubMed

    Cabry, Rosalie; Merviel, Philippe; Hazout, Andre; Belloc, Stephanie; Dalleac, Alain; Copin, Henri; Benkhalifa, Moncef

    2014-05-01

    Women's fertility potential is declining with age because of multiples intrinsic and extrinsic factors such as life style, oxidative stress and/or endocrine disruptors and is affecting the ability of these women to conceive naturally. This declining fertility potential and the late age of motherhood is increasing significantly the number of patients consulting infertility specialists. Different strategies of investigation and management are proposed to patients over 40 in order to overcome their infertility and improve the live birth rate in these patients. Intra Uterine Insemination (IUI) in women over 40 is associated with a low rate of ongoing pregnancy and IUI should not therefore be offered always as the first line of treatment. When the predictive factors are positive IVF/ICSI seem to be good alternatives until 43 years of age. Customized ovarian stimulation and flexible laboratory methods such as in vitro maturation (IVM), preimplantation genetic diagnosis (PGD), embryo vitrification and transfer after thawing in subsequent natural or artificial cycles can improve the success rate of ART in patients over 40. Meanwhile, oocyte and embryos donation remain good options for patient over 40 with a bad prognosis and can lead to successful ongoing pregnancies until 45 years of age. Ovarian tissue cryopreservation, oocyte vitrification at the germinal vesicle (GV) stage or metaphase II stage present a breakthrough for fertility preservation but the ideal age for starting fertility preservation is still debated as well as the minimum number of oocytes to be vitrified in order to optimize the chances of pregnancy when needed at an older age. This manuscript reports the results of our own experience from patients older than 40 in the light of the published data and discusses the different therapeutic alternatives which can be proposed to patients over 40 consulting ART centres. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Ipilimumab-induced acute severe colitis treated by infliximab.

    PubMed

    Pagès, Cecile; Gornet, Jean M; Monsel, Gentiane; Allez, Matthieu; Bertheau, Philippe; Bagot, Martine; Lebbé, Celeste; Viguier, Manuelle

    2013-06-01

    Ipilimumab (anti-CTLA-4 antibody) is a new tool for the treatment of metastatic melanoma patients that has led to an improvement in survival rates worldwide. New types of toxicities have been described with ipilimumab called 'immune-related adverse events' or irAEs. Here, we report an acute and steroid resistant case of ipilimumab-induced colitis treated with infliximab in a melanoma stage IV AJCC patient. The patient presented with acute grade 3 diarrhea after the second perfusion of ipilimumab. After the administration of intravenous steroids, the patient continued to have grade 2 diarrhea with erythematous mucous with several ulceration sites on rectosigmoidoscopy. Infliximab perfusion (5 mg/kg) was performed and resulted in resolution of symptoms within 2 days with complete healing was observed by rectal sigmoidoscopy on day 7. After failure of two further lines of chemotherapy, the patient died 10 months after the diagnosis of stage IVM1C melanoma. Treatment algorithms exist for the management of these digestive adverse events; however, some points remain unclear. No predictive marker for the occurrence of this digestive toxicity has been validated to date. Modes of administration of steroids and dosage are not clearly defined, except in cases of acute abdomen; surgery is difficult to propose for patients with a poor prognosis. Infliximab is another option for the treatment of steroid-resistant ipilimumab-induced colitis but its use in metastatic melanoma raises questions of its possible impact on the evolution of cancer. We reviewed at least 19 cases published of infliximab administration for ipilimumab-mediated colitis. Unfortunately, tolerance and cancer evolution have scarcely been reported. Thus, because more patients are being treated with CTLA-4 blockade, management of ipilimumab-induced colitis requires further studies.

  19. Tackling the malaria problem in the South-East Asia Region: need for a change in policy?

    PubMed

    Bharati, Kaushik; Ganguly, N K

    2013-01-01

    Malaria is largely neglected in the South-East Asia Region (SEAR), although it has the highest number of people susceptible to the disease. Malaria in the SEAR exhibits special epidemiological characteristics such as "forest malaria" and malaria due to migration across international borders. The Greater Mekong Subregion (GMS) has been a focal-point for the emergence of drug resistant malaria. With the recent emergence of artemisinin resistance, coupled with the limited availability of insecticides, malaria control efforts in the SEAR face a steep challenge. Indirect man-made factors such as climate change, as well as direct man-made factors such as the circulation of counterfeit drugs have added to the problem. Increased monitoring, surveillance, pharmacovigilance as well as cross-border collaboration are required to address these problems. Regional networking and data-sharing will keep all stakeholders updated about the status of various malaria control programmes in the SEAR. Cutting-edge technologies such as GIS/GPS (geographical information system/global positioning system) systems and mobile phones can provide information in "real-time". A holistic and sustained approach to malaria control by integrated vector management (IVM) is suggested, in which all the stakeholder countries work collaboratively as a consortium. This approach will address the malaria problem in a collective manner so that malaria control can be sustained over time.

  20. Tackling the malaria problem in the South-East Asia Region: Need for a change in policy?

    PubMed Central

    Bharati, Kaushik; Ganguly, N. K.

    2013-01-01

    Malaria is largely neglected in the South-East Asia Region (SEAR), although it has the highest number of people susceptible to the disease. Malaria in the SEAR exhibits special epidemiological characteristics such as “forest malaria” and malaria due to migration across international borders. The Greater Mekong Subregion (GMS) has been a focal-point for the emergence of drug resistant malaria. With the recent emergence of artemisinin resistance, coupled with the limited availability of insecticides, malaria control efforts in the SEAR face a steep challenge. Indirect man-made factors such as climate change, as well as direct man-made factors such as the circulation of counterfeit drugs have added to the problem. Increased monitoring, surveillance, pharmacovigilance as well as cross-border collaboration are required to address these problems. Regional networking and data-sharing will keep all stakeholders updated about the status of various malaria control programmes in the SEAR. Cutting-edge technologies such as GIS/GPS (geographical information system/global positioning system) systems and mobile phones can provide information in “real-time”. A holistic and sustained approach to malaria control by integrated vector management (IVM) is suggested, in which all the stakeholder countries work collaboratively as a consortium. This approach will address the malaria problem in a collective manner so that malaria control can be sustained over time. PMID:23481050

  1. Control of zoonotic cutaneous leishmaniasis vector, Phlebotomus papatasi, using attractive toxic sugar baits (ATSB)

    PubMed Central

    Saghafipour, Abedin; Vatandoost, Hassan; Zahraei-Ramazani, Ali Reza; Yaghoobi-Ershadi, Mohammad Reza; Rassi, Yavar; Karami Jooshin, Moharram; Shirzadi, Mohammad Reza; Akhavan, Amir Ahmad

    2017-01-01

    Introduction Attractive Toxic Sugar Baits (ATSB) is a new vector control method that meets Integrated Vector Management (IVM) goals. In an experimental design, this study aimed to determine effects of ATSB on control of Phlebotomus papatasi, as a main vector of Zoonotic Cutaneous Leishmaniasis (ZCL), in Qom Province, center of Iran. Methods In a cross-sectional design, boric acid was mixed with brown sugar solution and tested as toxic baits for P. papatasi. Two methods were utilized to use the baits: (a) spraying ATSB on vegetation, bushes, and shrubs; and (b) setting ATSB-treated barrier fences in front of colonies at 500 m distance from the houses in outskirts of villages. In order to examine the residual efficacy rate of ATSB-treated barrier fences, the bioassay test was used. Density of P. papatasi sandflies was measured using sticky and light traps biweekly. For data analysis, Mann-Whitney U Test and Kruskal-Wallis were used. Results ATSB-treated barrier fences led to 3 times reduction in P. papatasi population. Besides that, ATSB spraying on plants led to more than 5 times reduction in P. papatasi population. Conclusions Comparing the incidence of leishmaniasis in treated villages before and after the study showed that the incidence was statistically reduced. Therefore, ATSB is an effective method to control vectors and prevent leishmaniasis. PMID:28426679

  2. Malaria vector abundance is associated with house structures in Baringo County, Kenya.

    PubMed

    Ondiba, Isabella M; Oyieke, Florence A; Ong'amo, George O; Olumula, Macrae M; Nyamongo, Isaac K; Estambale, Benson B A

    2018-01-01

    Malaria, a major cause of morbidity and mortality, is the most prevalent vector borne disease in Baringo County; a region which has varied house designs in arid and semi-arid areas. This study investigated the association between house structures and indoor-malaria vector abundance in Baringo County. The density of malaria vectors in houses with open eaves was higher than that for houses with closed eaves. Grass thatched roof houses had higher density of malaria vectors than corrugated iron sheet roofs. Similarly, mud walled houses had higher vector density than other wall types. Houses in the riverine zone were significantly associated with malaria vector abundance (p<0.000) possibly due to more varied house structures. In Kamnarok village within riverine zone, a house made of grass thatched roof and mud wall but raised on stilts with domestic animals (sheep/goats) kept at the lower level had lower mosquito density (5.8 per collection) than ordinary houses made of same materials but at ground level (30.5 mosquitoes per collection), suggestive of a change in behavior of mosquito feeding and resting. House modifications such as screening of eaves, improvement of construction material and building stilted houses can be incorporated in the integrated vector management (IVM) strategy to complement insecticide treated bed nets and indoor residual spray to reduce indoor malaria vector density.

  3. Factors associated with perception of risk of contracting HIV among secondary school female learners in Mbonge subdivision of rural Cameroon

    PubMed Central

    Tarkang, Elvis Enowbeyang

    2014-01-01

    Introduction Since learners in secondary schools fall within the age group hardest hit by HIV/AIDS, it is obvious that these learners might be at high risk of contracting HIV/AIDS. However, little has been explored on the perception of risk of contracting HIV among secondary school learners in Cameroon. This study aimed at examining the perception of risk of contracting HIV among secondary school learners in Mbonge subdivision of rural Cameroon using the Health Belief Model (HBM) as framework. Methods A quantitative, correlational design was adopted, using a self-administered questionnaire to collect data from 210 female learners selected through disproportional, stratified, simple random sampling technique, from three participating senior secondary schools. Statistics were calculated using SPSS version 20 software program. Results Only 39.4% of the respondents perceived themselves to be at high risk of contracting HIV, though the majority, 54.0% were sexually active. Multinomial logistic regression analyses show that sexual risk behaviours (p=0.000) and the Integrated Value Mapping (IVM) of the perception components of the HBM are the most significant factors associated with perception of risk of contracting HIV at the level p<0.05. Conclusion The findings of this study can play an instrumental role in the development of effective preventive and interventional messages for adolescents in Cameroon. PMID:25309659

  4. Pig oocytes with a large perivitelline space matured in vitro show greater developmental competence after parthenogenesis and somatic cell nuclear transfer.

    PubMed

    Lee, Joohyeong; You, Jinyoung; Lee, Geun-Shik; Hyun, Sang-Hwan; Lee, Eunsong

    2013-09-01

    The objective of this study was to examine the developmental competence of pig oocytes in relation to the size of the perivitelline space (PVS) of oocytes matured in vitro. Immature oocytes were matured in medium 199 or porcine zygote medium (PZM)-3 containing 108 or 61.6 mM NaCl. In vitro-matured (IVM) oocytes were examined for intracellular glutathione (GSH) level; cyclin-dependent kinase 1 (CDK1), proliferating cell nuclear antigen (PCNA), and extracellular signal-regulated kinase 2 (ERK2) mRNA levels; and developmental competence after parthenogenesis (PA) and somatic cell nuclear transfer (SCNT). IVM oocytes with a larger PVS had higher (P < 0.05) levels of intracellular GSH (1.00 pixels/oocyte vs. 0.57 pixels/oocyte) and blastocyst formation (54.3% vs. 37.3%) after PA than oocytes with a smaller PVS. Culturing oocytes for maturation in PZM-3 with reduced (61.6 mM) NaCl increased (P < 0.05) the size of the PVS (6.4 µm vs. 2.8 µm) compared to control oocytes that were matured in normal PZM-3 containing 108 mM NaCl. Moreover, oocytes with a larger PVS showed higher CDK1, PCNA, and ERK2 mRNA and intracellular GSH levels (1.6 pixels/oocyte vs. 1.2 pixels/oocyte) and increased blastocyst formation after PA (52.1% vs. 40.6%) and SCNT (31.8% vs. 18.2%) than control oocytes. Our results demonstrate that pig oocytes with a large PVS have greater developmental competence after PA and SCNT, which is attributed to improved cytoplasmic maturation based on the enhanced GSH level and transcription factor expression. Further, enlargement of the PVS by culturing in low-NaCl medium improves the developmental competence of pig oocytes. Copyright © 2013 Wiley Periodicals, Inc.

  5. Chlorogenic acid supplementation during in vitro maturation improves maturation, fertilization and developmental competence of porcine oocytes.

    PubMed

    Nguyen, T-V; Tanihara, F; Do, Ltk; Sato, Y; Taniguchi, M; Takagi, M; Van Nguyen, T; Otoi, T

    2017-12-01

    Chlorogenic acid (CGA) is a quinic acid conjugate of caffeic acid, and a phytochemical found in many fruits and beverages that acts as an antioxidant. The present study investigated the effects of CGA supplementation during in vitro maturation (IVM), on in vitro development of porcine oocytes, to improve the porcine in vitro production (IVP) system. Oocytes were matured either without (control) or with CGA (10, 50, 100 and 200 μM). Subsequently, the matured oocytes were fertilized and cultured in vitro for 7 day. The rates of maturation, fertilization and blastocyst formation of oocytes matured with 50 μM CGA were significantly (p < .05) higher than those of the control oocytes. Hydrogen peroxide (H 2 O 2 ) is one of the reactive oxygen species and induces DNA damage in porcine oocytes. When oocytes were matured with 1 mM H 2 O 2 to assess the protective effect of CGA, 50 μM CGA supplementation improved the maturation rate and the proportion of DNA-fragmented nuclei in oocytes compared with control oocytes matured without CGA. Moreover, when oocytes were matured with either 50 μM CGA (control) or caffeic acid (10, 50 and 100 μM), the rates of maturation, fertilization and the blastocyst formation of oocytes matured with 50 μM CGA were similar to those of oocytes matured with 10 and 50 μM caffeic acid. Our results suggest that CGA has comparable effects to caffeic acid, and IVM with 50 μM CGA is particularly beneficial to IVP of porcine embryos and protects oocytes from DNA damage induced by oxidative stress. Supplementation of CGA to the maturation medium has a potential to improve porcine IVP system. © 2017 Blackwell Verlag GmbH.

  6. Developmental competence of embryos derived from reciprocal in vitro fertilization between Yak (Bos grunniens) and cattle (Bos taurus).

    PubMed

    Zi, Xiang-Dong; Yin, Rong-Hua; Chen, Shao-Wei; Liang, Guan-Nan; Zhang, Da-Wei; Guo, Chun-Hua

    2009-10-01

    The purpose of this study was to investigate fertilization ability and embryo development to the blastocyst stage after reciprocal in vitro fertilization (IVF) between yak and cattle in an attempt to clarify the problem of low conception rate after mating yak females with cattle bulls. In vitro-matured (IVM) cattle and yak oocytes were inseminated with either Holstein or yak spermatozoa, and after an 18-h of coincubation period, a proportion of the oocytes was fixed and examined for sperm penetration, polyspermy and male pronuclear formation. The remaining oocytes were cultured in vitro and evaluated for cleavage and blastocyst formation rates. The percentage of IVM oocytes penetrated by spermatozoa ranged from 78.5 to 90.5%, and the formation of one or two pronuclei and the incidence of polyspermy did not differ among the different combinations. The cleavage and blastocyst rates were not affected by the species of the sperm, but they were affected by the species of the oocytes (P<0.05), with cattle oocytes having a higher (P<0.05) cleavage and blastocyst rates (69.9 and 31.3%) than yak oocytes (62.7 and 11.5%). The blastocyst formation rate was calculated from the cleaved zygotes. The interaction between sire and oocytes species (P<0.05) influenced blastocyst formation rate, with the highest blastocyst rate occurring in cattle oocytes fertilized with yak spermatozoa (36.5%) and the lowest rate occurring in yak oocytes fertilized with yak spermatozoa (9.4%). The effect of heterosis was apparent at the blastocyst stage, but there was a large reciprocal difference in blastocyst production between crosses. It was concluded that the low conception rate that results from crossing yaks with cattle is not due to either a species-specific block of fertilization or the developmental competence of the early stage embryo.

  7. Contribution of P2X4 receptors to ethanol intake in male C57BL/6 mice

    PubMed Central

    Wyatt, Letisha R.; Finn, Deborah A.; Khoja, Sheraz; Yardley, Megan M; Asatryan, Liana; Alkana, Ronald L.; Davies, Daryl L.

    2014-01-01

    P2X receptors (P2XRs) are a family of cation-permeable ligand-gated ion channels activated by synaptically released extracellular ATP. The P2X4 subtype is abundantly expressed in the CNS and is sensitive to low intoxicating ethanol concentrations. Genetic meta-analyses identified the p2rx4 gene as a candidate gene for innate alcohol intake and/or preference. The current study used mice lacking the p2rx4 gene (knockout, KO) and wildtype (WT) C57BL/6 controls to test the hypothesis that P2X4Rs contribute to ethanol intake. The early acquisition and early maintenance phases of ethanol intake were measured with three different drinking procedures. Further, we tested the effects of ivermectin (IVM), a drug previously shown to reduce ethanol’s effects on P2X4Rs and to reduce ethanol intake and preference, for its ability to differentially alter stable ethanol intake in KO and WT mice. Depending on the procedure and the concentration of the ethanol solution, ethanol intake was transiently increased in P2X4R KO versus WT mice during the acquisition of 24-hr and limited access ethanol intake. IVM significantly reduced ethanol intake in P2X4R KO and WT mice, but the degree of reduction was 50% less in the P2X4R KO mice. Western blot analysis identified significant changes in -γ aminobutyric acidA receptor (GABAAR) α1 subunit expression in brain regions associated with the regulation of ethanol behaviors in P2X4R KO mice. These findings add to evidence that P2X4Rs contribute to ethanol intake and indicate that there is a complex interaction between P2X4Rs, ethanol, and other neurotransmitter receptor systems. PMID:24671605

  8. Blood Accessibility to Fibrin in Venous Thrombosis is Thrombus Age-Dependent and Predicts Fibrinolytic Efficacy: An In Vivo Fibrin Molecular Imaging Study

    PubMed Central

    Stein-Merlob, Ashley F.; Kessinger, Chase W.; Erdem, S. Sibel; Zelada, Henry; Hilderbrand, Scott A.; Lin, Charles P.; Tearney, Guillermo J.; Jaff, Michael R.; Reed, Guy L.; Henke, Peter K.; McCarthy, Jason R.; Jaffer, Farouc A.

    2015-01-01

    Fibrinolytic therapy of venous thromboembolism (VTE) is increasingly utilized, yet limited knowledge is available regarding in vivo mechanisms that govern fibrinolytic efficacy. In particular, it is unknown how age-dependent thrombus organization limits direct blood contact with fibrin, the target of blood-based fibrinolytic agents. Utilizing high-resolution in vivo optical molecular imaging with FTP11, a near-infrared fluorescence (NIRF) fibrin-specific reporter, here we investigated the in vivo interrelationships of blood accessibility to fibrin, thrombus age, thrombus neoendothelialization, and fibrinolysis in murine venous thrombosis (VT). In both stasis VT and non-stasis VT, NIRF microscopy showed that FTP11 fibrin binding was thrombus age-dependent. FTP11 localized to the luminal surface of early-stage VT, but only minimally to subacute VT (p<0.001). Transmission electron microscopy of early stage VT revealed direct blood cell contact with luminal fibrin-rich surfaces. In contrast, subacute VT exhibited an encasing CD31+ neoendothelial layer that limited blood cell contact with thrombus fibrin in both VT models. Next we developed a theranostic strategy to predict fibrinolytic efficacy based on the in vivo fibrin accessibility to blood NIRF signal. Mice with variably aged VT underwent FTP11 injection and intravital microscopy (IVM), followed by tissue plasminogen activator infusion to induce VT fibrinolysis. Fibrin molecular IVM revealed that early stage VT, but not subacute VT, bound FTP11 (p<0.05), and experienced higher rates of fibrinolysis and total fibrinolysis (p<0.05 vs. subacute VT). Before fibrinolysis, the baseline FTP11 NIRF signal predicted the net fibrinolysis at 60 minutes (p<0.001). Taken together, these data provide novel insights into the temporal evolution of VT and its susceptibility to therapeutic fibrinolysis. Fibrin molecular imaging may provide a theranostic strategy to identify venous thrombi amenable to fibrinolytic therapies. PMID:26516370

  9. Continuous day-time time series of E-region equatorial electric fields derived from ground magnetic observatory data

    NASA Astrophysics Data System (ADS)

    Alken, P.; Chulliat, A.; Maus, S.

    2012-12-01

    The day-time eastward equatorial electric field (EEF) in the ionospheric E-region plays an important role in equatorial ionospheric dynamics. It is responsible for driving the equatorial electrojet (EEJ) current system, equatorial vertical ion drifts, and the equatorial ionization anomaly (EIA). Due to its importance, there is much interest in accurately measuring and modeling the EEF. However, there are limited sources of direct EEF measurements with full temporal and spatial coverage of the equatorial ionosphere. In this work, we propose a method of estimating a continuous day-time time series of the EEF at any longitude, provided there is a pair of ground magnetic observatories in the region which can accurately track changes in the strength of the EEJ. First, we derive a climatological unit latitudinal current profile from direct overflights of the CHAMP satellite and use delta H measurements from the ground observatory pair to determine the magnitude of the current. The time series of current profiles is then inverted for the EEF by solving the governing electrodynamic equations. While this method has previously been applied and validated in the Peruvian sector, in this work we demonstrate the method using a pair of magnetometers in Africa (Samogossoni, SAM, 0.18 degrees magnetic latitude and Tamanrasset, TAM, 11.5 degrees magnetic latitude) and validate the resulting EEF values against the CINDI ion velocity meter (IVM) instrument on the C/NOFS satellite. We find a very good 80% correlation with C/NOFS IVM measurements and a root-mean-square difference of 9 m/s in vertical drift velocity. This technique can be extended to any pair of ground observatories which can capture the day-time strength of the EEJ. We plan to apply this work to more observatory pairs around the globe and distribute real-time equatorial electric field values to the community.

  10. Dehydroepiandrosterone Potentiates Native Ionotropic ATP Receptors Containing the P2X2 Subunit in Rat Sensory Neurones

    PubMed Central

    De Roo, Mathias; Rodeau, Jean-Luc; Schlichter, Rémy

    2003-01-01

    We have studied the modulatory effect of dehydroepiandrosterone (DHEA), the most abundant neurosteroid produced by glial cells and neurones, on membrane currents induced by the activation of ionotropic ATP (P2X) receptors in neonatal rat dorsal root ganglion neurones. ATP (1 μm) induced three types of currents/responses termed F (fast and transient), S (slowly desensitizing) and M (mixed, sum of F- and S-type responses). DHEA (10 nm to 100 μm) concentration-dependently increased the amplitude of plateau-like currents of S- and M-type responses evoked by submaximal (1 μm) but not saturating (100 μm or 1 mM) concentrations of ATP. αβ-Methylene ATP (αβme-ATP, 5 μm) also evoked F-, S- and M-type responses, the plateau phases of which were potentiated by lowering external pH (6.3) and by ivermectin (IVM, 3 μm), indicating the presence heteromeric P2X2-containing receptors and possibly of functional native P2X4/6 receptors. There was a strict correlation between the potentiating effects of low pH and DHEA on αβme-ATP responses but not between that of IVM and DHEA, suggesting that DHEA selectively modulated P2X2-containing receptors. DHEA also potentiated putative homomeric P2X2 receptor responses recorded in the continuous presence of 1 μm 2′-(or 3′)-O-(2,4,6-trinitrophenyl) adenosine 5′-triphosphate (TNP-ATP). Our results constitute the first demonstration of a fast potentiation of P2X receptors by a neurosteroid and suggest that DHEA could be an endogenous modulator of P2X2-containing receptors thereby contributing to the facilitation of the detection and/or the transmission of nociceptive messages, particularly under conditions of inflammatory pain where the P2X receptor signalling pathway appears to be upregulated. PMID:12844512

  11. Spatially targeting Culex quinquefasciatus aquatic habitats on modified land cover for implementing an Integrated Vector Management (IVM) program in three villages within the Mwea Rice Scheme, Kenya

    PubMed Central

    Jacob, Benjamin G; Shililu, Josephat; Muturi, Ephantus J; Mwangangi, Joseph M; Muriu, Simon M; Funes, Jose; Githure, John; Regens, James L; Novak, Robert J

    2006-01-01

    Background Continuous land cover modification is an important part of spatial epidemiology because it can help identify environmental factors and Culex mosquitoes associated with arbovirus transmission and thus guide control intervention. The aim of this study was to determine whether remotely sensed data could be used to identify rice-related Culex quinquefasciatus breeding habitats in three rice-villages within the Mwea Rice Scheme, Kenya. We examined whether a land use land cover (LULC) classification based on two scenes, IKONOS at 4 m and Landsat Thematic Mapper at 30 m could be used to map different land uses and rice planted at different times (cohorts), and to infer which LULC change were correlated to high density Cx. quinquefasciatus aquatic habitats. We performed a maximum likelihood unsupervised classification in Erdas Imagine V8.7® and generated three land cover classifications, rice field, fallow and built environment. Differentially corrected global positioning systems (DGPS) ground coordinates of Cx. quinquefasciatus aquatic habitats were overlaid onto the LULC maps generated in ArcInfo 9.1®. Grid cells were stratified by levels of irrigation (well-irrigated and poorly-irrigated) and varied according to size of the paddy. Results Total LULC change between 1988–2005 was 42.1 % in Kangichiri, 52.8 % in Kiuria and and 50.6 % Rurumi. The most frequent LULC changes was rice field to fallow and fallow to rice field. The proportion of aquatic habitats positive for Culex larvae in LULC change sites was 77.5% in Kangichiri, 72.9% in Kiuria and 73.7% in Rurumi. Poorly – irrigated grid cells displayed 63.3% of aquatic habitats among all LULC change sites. Conclusion We demonstrate that optical remote sensing can identify rice cultivation LULC sites associated with high Culex oviposition. We argue that the regions of higher Culex abundance based on oviposition surveillance sites reflect underlying differences in abundance of larval habitats which is where limited control resources could be concentrated to reduce vector larval abundance. PMID:16684354

  12. Impact of supplementary royal jelly on in vitro maturation of sheep oocytes: genes involved in apoptosis and embryonic development.

    PubMed

    Valiollahpoor Amiri, Mohammad; Deldar, Hamid; Ansari Pirsaraei, Zarbakht

    2016-01-01

    Optimizing culture conditions lead to the improvement of oocyte developmental competence and additives with anti-oxidative activity in culture media improved embryonic development. Royal jelly (RJ) is a product from the cephalic glands of nurse bees that has considerable health effects. The aim of this study was to investigate the effect of different concentrations of RJ on the maturation, cleavage, and blastocyst rates and gene expression in the oocyte and cumulus cells during in vitro maturation (IVM) of sheep oocyte. IVM of oocyte was performed in the presence of control (RJ0), 2.5 (RJ2.5), 5 (RJ5), 10 (RJ10), 20 (RJ20), and 40 (RJ40) mg/mL of RJ. Following the maturation period, parthenogenetic activation was carried out in two treatment groups (RJ0 and RJ10) and embryonic development was examined three and eight days thereafter. Moreover, the relative expression of BCL2 and BAX in oocyte as well as BCL2, BAX, HAS2, PTGS2, and STAR in cumulus cells were assessed. The results indicated that the addition of 10 mg/mL of RJ (90 ± 4.51%) to the maturation medium linearly increased the oocyte maturation rate compared to the control group (57 ± 2.42%), then it remained constant to the RJ40 (93 ± 3.10%) group. The higher RJ concentrations were associated with increased (p < 0.01) cleavage (53.3 ± 1.55% to 82.3 ± 2.82%) and blastocyst rate (15.5 ± 1.16% to 33.8 ± 3.09%) from the RJ0 to the RJ10 group. The relative mRNA expression of BCL2 and BAX in the oocyte was higher at RJ10. In cumulus cells, the expression of BCL2 was not affected, but that of BAX decreased, and expression of HAS2, PTGS2, and STAR were increased following the addition of RJ to the maturation media. In conclusion, the addition of 10 mg/mL of RJ to maturation medium improved blastocyst formation and decreased the apoptotic incidence in sheep cumulus cells and the oocyte during the in vitro development.

  13. Study of the Histopathologic Characteristics and Surface Morphologies of Glottic Carcinomas With Anterior Vocal Commissure Involvement.

    PubMed

    Wu, Jianhui; Zhao, Jing; Wang, Zhangfeng; Li, Zenghong; Luo, Jie; Liao, Bing; Yang, Zhiyun; Liu, Qihong; Wang, Bin; Wen, Weiping; Lei, Wenbin

    2015-07-01

    This article explores the features and the role of the anterior vocal commissure (AVC) structure and the surface morphologies of glottic carcinomas with AVC involvement to provide a reference for the selection of transoral carbon dioxide (CO2) laser surgery. A total of 31 cases of glottic carcinomas with AVC involvement from May 2012 to January 2014 were included. All patients underwent electronic laryngoscopic examinations and computed tomography scans to determine the surface morphology. After surgery, the tumor specimens were resected integrally, and axial serial sections parallel to the plane of vocal cords were taken to explore the features and possible invasion paths of the glottic carcinomas with AVC involvement. The rates of involvement of the supraglottis and subglottis were 71.4% and 14.8%, respectively, via the AVC. The involvement of the superficial layer of the unilateral or bilateral vocal cords without involvement of the vocal muscle in the AVC region (IVM) or the cartilage was present in 15 cases (48.4%). The involvement of the superficial layer of the unilateral and bilateral vocal cords occurred in 16 cases (51.6%) with the IVM in 13 cases and the involvement of the intermediate lamina of the thyroid cartilage (ITC) in 8 cases. The involvement of the ITC was associated with the involvement of the vocal muscle of the AVC region (P < 0.05). Among the pushing carcinomas, 15 of 21 (71.4%) presented with well-defined tumor mass, and 8 of 10 (80.0%) infiltrating carcinomas presented with multiple tumor nests that were often surrounded by fibrosis (P < 0.05). The AVC is an important path of invasion of subglottic in glottic carcinomas but less so for suparglottic. The Broyles' ligaments acted as a barrier against the spread of the tumors to the thyroid cartilage, but this role was obviously weaken by the involvement of the vocal muscle of the AVC region. The infiltrating carcinomas presented with multiple tumor nests in fibrous tissue. When CO2 laser microsurgery is considered as a treatment option, these facts should be kept in mind.

  14. Functional characterization of P2Y1 versus P2X receptors in RBA-2 astrocytes: elucidate the roles of ATP release and protein kinase C.

    PubMed

    Weng, Ju-Yun; Hsu, Tsan-Ting; Sun, Synthia H

    2008-05-15

    A physiological concentration of extracellular ATP stimulated biphasic Ca(2+) signal, and the Ca(2+) transient was decreased and the Ca(2+) sustain was eliminated immediately after removal of ATP and Ca(2+) in RBA-2 astrocytes. Reintroduction of Ca(2+) induced Ca(2+) sustain. Stimulation of P2Y(1) receptors with 2-methylthioadenosine 5'-diphosphate (2MeSADP) also induced a biphasic Ca(2+) signaling and the Ca(2+) sustains were eliminated using Ca(2+)-free buffer. The 2MeSADP-mediated biphasic Ca(2+) signals were inhibited by phospholipase C (PLC) inhibitor U73122, and completely blocked by P2Y(1) selective antagonist MRS2179 and protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) whereas enhanced by PKC inhibitors GF109203X and Go6979. Inhibition of capacitative Ca(2+) entry (CCE) decreased the Ca(2+)-induced Ca(2+) entry; nevertheless, ATP further enhanced the Ca(2+)-induced Ca(2+) entry in the intracellular Ca(2+) store-emptied and CCE-inhibited cells indicating that ATP stimulated Ca(2+) entry via CCE and ionotropic P2X receptors. Furthermore, the 2MeSADP-induced Ca(2+) sustain was eliminated by apyrase but potentiated by P2X(4) allosteric effector ivermectin (IVM). The agonist ADPbetaS stimulated a lesser P2Y(1)-mediated Ca(2+) signal and caused a two-fold increase in ATP release but that were not affected by IVM whereas inhibited by PMA, PLC inhibitor ET-18-OCH(3) and phospholipase D (PLD) inhibitor D609, and enhanced by removal of intra- or extracellular Ca(2+). Taken together, the P2Y(1)-mediated Ca(2+) sustain was at least in part via P2X receptors activated by the P2Y(1)-induced ATP release, and PKC played a pivotal role in desensitization of P2Y(1) receptors in RBA-2 astrocytes. Copyright 2007 Wiley-Liss, Inc.

  15. Study of the Histopathologic Characteristics and Surface Morphologies of Glottic Carcinomas With Anterior Vocal Commissure Involvement

    PubMed Central

    Wu, Jianhui; Zhao, Jing; Wang, Zhangfeng; Li, Zenghong; Luo, Jie; Liao, Bing; Yang, Zhiyun; Liu, Qihong; Wang, Bin; Wen, Weiping; Lei, Wenbin

    2015-01-01

    Abstract This article explores the features and the role of the anterior vocal commissure (AVC) structure and the surface morphologies of glottic carcinomas with AVC involvement to provide a reference for the selection of transoral carbon dioxide (CO2) laser surgery. A total of 31 cases of glottic carcinomas with AVC involvement from May 2012 to January 2014 were included. All patients underwent electronic laryngoscopic examinations and computed tomography scans to determine the surface morphology. After surgery, the tumor specimens were resected integrally, and axial serial sections parallel to the plane of vocal cords were taken to explore the features and possible invasion paths of the glottic carcinomas with AVC involvement. The rates of involvement of the supraglottis and subglottis were 71.4% and 14.8%, respectively, via the AVC. The involvement of the superficial layer of the unilateral or bilateral vocal cords without involvement of the vocal muscle in the AVC region (IVM) or the cartilage was present in 15 cases (48.4%). The involvement of the superficial layer of the unilateral and bilateral vocal cords occurred in 16 cases (51.6%) with the IVM in 13 cases and the involvement of the intermediate lamina of the thyroid cartilage (ITC) in 8 cases. The involvement of the ITC was associated with the involvement of the vocal muscle of the AVC region (P < 0.05). Among the pushing carcinomas, 15 of 21 (71.4%) presented with well-defined tumor mass, and 8 of 10 (80.0%) infiltrating carcinomas presented with multiple tumor nests that were often surrounded by fibrosis (P < 0.05). The AVC is an important path of invasion of subglottic in glottic carcinomas but less so for suparglottic. The Broyles’ ligaments acted as a barrier against the spread of the tumors to the thyroid cartilage, but this role was obviously weaken by the involvement of the vocal muscle of the AVC region. The infiltrating carcinomas presented with multiple tumor nests in fibrous tissue. When CO2 laser microsurgery is considered as a treatment option, these facts should be kept in mind. PMID:26200618

  16. Diurnal and Seasonal Statistical Characteristics of Well-formed Plasma Depletion and Enhancement Plumes under Quiet Solar Conditions

    NASA Astrophysics Data System (ADS)

    Haaser, R. A.

    2011-12-01

    The Ion Velocity Meter (IVM), a part of the Coupled Ion Neutral Dynamics Investigation (CINDI) aboard the Communication/ Navigation Outage Forecasting System (C/NOFS) satellite, is used to measure in situ ion densities and drifts at altitudes between 400 and 550 km during the nighttime hours from 2100 to 300 local time. A new approach to detecting and classifying well-formed ionospheric plasma depletion and enhancement plumes (bubbles and blobs) of scale sizes between 50 and 500 km is used to develop geophysical statistics for the summer, winter and equinox seasons of the quiet solar conditions during 2009 and 2010. Some diurnal and seasonal geomagnetic distribution characteristics confirm previous work on irregularities and scintillations, while others reveal new behaviors that require additional observations and modeling to promote full understanding.

  17. 6 CFR 29.5 - Requirements for protection.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... PCII Program Manager or the PCII Program Manager's designee; (2) The information is submitted for... information initially provided received by the PCII Program Manager or the PCII Program Manager's designee... provided, to be received by the PCII Program Manager or the PCII Program Manager's designee within a...

  18. 14 CFR 91.1017 - Amending program manager's management specifications.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... proposed amendment. (2) The Flight Standards District Office that issued the program manager's management... presented, the Flight Standards District Office that issued the program manager's management specifications... Standards District Office that issued the program manager's management specifications issues an amendment of...

  19. 14 CFR 91.1017 - Amending program manager's management specifications.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... proposed amendment. (2) The Flight Standards District Office that issued the program manager's management... presented, the Flight Standards District Office that issued the program manager's management specifications... Standards District Office that issued the program manager's management specifications issues an amendment of...

  20. The role of the case manager in a disease management program.

    PubMed

    Huston, Carol J

    2002-01-01

    Disease management programs provide new opportunities and roles for case managers to provide population-based healthcare to the chronically ill. This article identifies common components of disease management programs and examines roles assumed by case managers in disease management programs such as baseline assessment, performing economic analyses of diseases and their respective associated resource utilization, developing and/or implementing care guidelines or algorithms, educational interventions, disease management program implementation, and outcomes assessment. Areas of expertise needed to be an effective case manager in a disease management program are also identified.

  1. The role of the case manager in a disease management program.

    PubMed

    Huston, C J

    2001-01-01

    Disease management programs provide new opportunities and roles for case managers to provide population-based healthcare to the chronically ill. This article identifies common components of disease management programs and examines roles assumed by case managers in disease management programs such as baseline assessment, performing economic analyses of diseases and their respective associated resource utilization, developing and/or implementing care guidelines or algorithms, educational interventions, disease management program implementation, and outcomes assessment. Areas of expertise needed to be an effective case manager in a disease management program are also identified.

  2. 14 CFR 91.1411 - Continuous airworthiness maintenance program use by fractional ownership program manager.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... program use by fractional ownership program manager. 91.1411 Section 91.1411 Aeronautics and Space FEDERAL... airworthiness maintenance program use by fractional ownership program manager. Fractional ownership program... through 91.1443. Any program manager who elects to maintain the program aircraft using a continuous...

  3. Elucidation of monocyte/macrophage dynamics and function by intravital imaging

    PubMed Central

    Rua, Rejane; McGavern, Dorian B.

    2015-01-01

    Monocytes and macrophages are a diverse population of innate immune cells that play a critical role in homeostasis and inflammation. These cells are surveillant by nature and closely monitor the vasculature and surrounding tissue during states of health and disease. Given their abundance and strategic positioning throughout the body, myeloid cells are among the first responders to any inflammatory challenge and are active participants in most immune-mediated diseases. Recent studies have shed new light on myeloid cell dynamics and function by use of an imaging technique referred to as intravital microscopy (IVM). This powerful approach allows researchers to gain real-time insights into monocytes and macrophages performing homeostatic and inflammatory tasks in living tissues. In this review, we will present a contemporary synopsis of how intravital microscopy has revolutionized our understanding of myeloid cell contributions to vascular maintenance, microbial defense, autoimmunity, tumorigenesis, and acute/chronic inflammatory diseases. PMID:26162402

  4. 20 CFR 632.76 - Program management systems.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... NATIVE AMERICAN EMPLOYMENT AND TRAINING PROGRAMS Program Design and Management § 632.76 Program management systems. (a) All Native American grantees shall establish management information systems to... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Program management systems. 632.76 Section...

  5. 48 CFR 1301.671 - Assignment of program and project managers.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... project managers. 1301.671 Section 1301.671 Federal Acquisition Regulations System DEPARTMENT OF COMMERCE..., and Responsibilities 1301.671 Assignment of program and project managers. The Department's Program and Project Manager certification program for the assignment and certification of Program and Project Managers...

  6. KENNEDY SPACE CENTER, FLA. -- NASA and United Space Alliance (USA) Space Shuttle program managers attend a briefing, part of activities during a leadership workday. The day is intended to provide management with an in-depth, hands-on look at Shuttle processing activities at KSC. Starting third from left are NASA Deputy Associate Administrator for Space Station and Shuttle Programs Michael Kostelnik, USA Vice President and Space Shuttle Program Manager Howard DeCastro, NASA Space Shuttle Program Manager William Parsons, and USA Associate Program Manager of Ground Operations Andy Allen.

    NASA Image and Video Library

    2003-12-19

    KENNEDY SPACE CENTER, FLA. -- NASA and United Space Alliance (USA) Space Shuttle program managers attend a briefing, part of activities during a leadership workday. The day is intended to provide management with an in-depth, hands-on look at Shuttle processing activities at KSC. Starting third from left are NASA Deputy Associate Administrator for Space Station and Shuttle Programs Michael Kostelnik, USA Vice President and Space Shuttle Program Manager Howard DeCastro, NASA Space Shuttle Program Manager William Parsons, and USA Associate Program Manager of Ground Operations Andy Allen.

  7. Guide for Operational Configuration Management Program including the adjunct programs of design reconstitution and material condition and aging management. Part 1

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

    Not Available

    This standard presents program criteria and implementation guidance for an operational configuration management program for DOE nuclear and non-nuclear facilities in the operational phase. Portions of this standard are also useful for other DOE processes, activities, and programs. This Part 1 contains foreword, glossary, acronyms, bibliography, and Chapter 1 on operational configuration management program principles. Appendices are included on configuration management program interfaces, and background material and concepts for operational configuration management.

  8. 14 CFR 91.1049 - Personnel.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Management § 91.1049 Personnel. (a) Each program manager and each fractional owner must use in program... regulations. The program manager must provide oversight of those crews. (b) Each program manager must employ...) Program manager flight, duty, and rest time considerations, and in all cases within the limits set forth...

  9. Effect of holding equine oocytes in meiosis inhibitor-free medium before in vitro maturation and of holding temperature on meiotic suppression and mitochondrial energy/redox potential.

    PubMed

    Martino, Nicola A; Dell'Aquila, Maria E; Filioli Uranio, Manuel; Rutigliano, Lucia; Nicassio, Michele; Lacalandra, Giovanni M; Hinrichs, Katrin

    2014-10-11

    Evaluation of mitochondrial function offers an alternative to evaluate embryo development for assessment of oocyte viability, but little information is available on the relationship between mitochondrial and chromatin status in equine oocytes. We evaluated these parameters in immature equine oocytes either fixed immediately (IMM) or held overnight in an Earle's/Hank's' M199-based medium in the absence of meiotic inhibitors (EH treatment), and in mature oocytes. We hypothesized that EH holding may affect mitochondrial function and that holding temperature may affect the efficiency of meiotic suppression. Experiment 1 - Equine oocytes processed immediately or held in EH at uncontrolled temperature (22 to 27°C) were evaluated for initial chromatin configuration, in vitro maturation (IVM) rates and mitochondrial energy/redox potential. Experiment 2 - We then investigated the effect of holding temperature (25°C, 30°C, 38°C) on initial chromatin status of held oocytes, and subsequently repeated mitochondrial energy/redox assessment of oocytes held at 25°C vs. immediately-evaluated controls. EH holding at uncontrolled temperature was associated with advancement of germinal vesicle (GV) chromatin condensation and with meiotic resumption, as well as a lower maturation rate after IVM. Holding did not have a significant effect on mitochondrial distribution within chromatin configurations. Independent of treatment, oocytes having condensed chromatin had a significantly higher proportion of perinuclear/pericortical mitochondrial distribution than did other GV configurations. Holding did not detrimentally affect oocyte energy/redox parameters in viable GV-stage oocytes. There were no significant differences in chromatin configuration between oocytes held at 25°C and controls, whereas holding at higher temperature was associated with meiosis resumption and loss of oocytes having the condensed chromatin GV configuration. Holding at 25°C was not associated with progression of mitochondrial distribution pattern and there were no significant differences in oocyte energy/redox parameters between these oocytes and controls. Mitochondrial distribution in equine GV-stage oocytes is correlated with chromatin configuration within the GV. Progression of chromatin configuration and mitochondrial status during holding are dependent on temperature. EH holding at 25°C maintains meiotic arrest, viability and mitochondrial potential of equine oocytes. This is the first report on the effects of EH treatment on oocyte mitochondrial energy/redox potential.

  10. Scheduling Guide for Program Managers

    DTIC Science & Technology

    2001-10-01

    58 Chapter 8 TIME MANAGEMENT ....................................................................................... 59...8.1 Time Management and the Program...60 8.2 Time Management and the Program Manager

  11. Amino acid turnover by human oocytes is influenced by gamete developmental competence, patient characteristics and gonadotrophin treatment

    PubMed Central

    Hemmings, K.E.; Maruthini, D.; Vyjayanthi, S.; Hogg, J.E.; Balen, A.H.; Campbell, B.K.; Leese, H.J.; Picton, H.M.

    2013-01-01

    STUDY QUESTION Can amino acid profiling differentiate between human oocytes with differing competence to mature to metaphase II (MII) in vitro? SUMMARY ANSWER Oocytes which remained arrested at the germinal vesicle (GV) stage after 24 h of in vitro maturation (IVM) displayed differences in the depletion/appearance of amino acids compared with oocytes which progressed to MII and patient age, infertile diagnosis and ovarian stimulation regime significantly affected oocyte amino acid turnover during IVM. WHAT IS KNOWN ALREADY Amino acid profiling has been proposed as a technique which can distinguish between human pronucleate zygotes and cleavage stage embryos with the potential to develop to the blastocyst stage and implant to produce a pregnancy and those that arrest. Most recently, the amino acid turnover by individual bovine oocytes has been shown to be predictive of oocyte developmental competence as indicated by the gamete's capacity to undergo fertilization and early cleavage divisions in vitro. STUDY DESIGN, SIZE, DURATION The study was conducted between March 2005 and March 2010. A total of 216 oocytes which were at the GV or metaphase I (MI) stages at the time of ICSI were donated by 67 patients. PARTICIPANTS/MATERIALS, SETTINGS, METHODS The research was conducted in university research laboratories affiliated to a hospital-based infertility clinic. Oocytes were cultured for 24 h and the depletion/appearance of amino acids was measured during the final 6 h of IVM. Amino acid turnover was analysed in relation to oocyte meiotic progression, patient age, disease aetiology and controlled ovarian stimulation regime. MAIN RESULTS AND THE ROLE OF CHANCE The depletion/appearance of key amino acids was linked to the maturation potential of human oocytes in vitro. Oocytes which arrested at the GV stage (n = 9) depleted significantly more valine and isoleucine than those which progressed to MI (n = 32) or MII (n = 107) (P < 0.05). Glutamate, glutamine, arginine and valine depletion or appearance differed in MII versus degenerating oocytes (n = 20) (P < 0.05). Glutamine, arginine, methionine, phenylalanine, total depletion and total turnover all differed in oocytes from patients aged < 35 years versus patients ≥35 years (P < 0.05). MII oocytes obtained following ovarian stimulation with recombinant FSH depleted more isoleucine (P < 0.05) and more alanine and lysine (P < 0.05) appeared than oocytes from hMG-stimulated cycles. MII oocytes from patients with a polycystic ovary (PCO) morphology (n = 33) depleted more serine (P < 0.05) than oocytes from women with normal ovaries (n = 61). LIMITATIONS, REASONS FOR CAUTION Immature oocytes collected at the time of ICSI were used as the model for human oocyte maturation. These oocytes have therefore failed to respond to the ovulatory hCG trigger in vivo (they are meiotically incompetent), and have limited capacity to support embryo development in vitro. The lack of cumulus cells and stress of the conditions in vitro may have influenced turnover of amino acids, and owing to the small sample sizes further studies are required to confirm these findings. WIDER IMPLICATIONS OF THE FINDINGS The findings provide support for the hypothesis that oocyte metabolism reflects oocyte quality. Longitudinal studies are required to link these functional metabolic indices of human oocyte quality with embryo developmental competence. Oocyte amino acid profiling may be a useful tool to quantify the impact of new assisted reproduction technologies (ART) on oocyte quality. STUDY FUNDING/COMPETING INTERESTS This project was funded by the UK Biology and Biotechnology Research Council (BB/C007395/1) and the Medical Research Council (G 0800250). K.E.H was in receipt of a British Fertility Society/Merck Serono studentship. H.J.L. is a shareholder in Novocellus Ltd, a company which seeks to devise a non-invasive biochemical test of embryo health. PMID:23335609

  12. Sandia National Laboratories California Waste Management Program Annual Report February 2008.

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

    Brynildson, Mark E.

    The annual program report provides detailed information about all aspects of the Sandia National Laboratories, California (SNL/CA) Waste Management Program. It functions as supporting documentation to the SNL/CA Environmental Management System Program Manual. This annual program report describes the activities undertaken during the past year, and activities planned in future years to implement the Waste Management (WM) Program, one of six programs that supports environmental management at SNL/CA.

  13. The impact of middle manager affective commitment on perceived improvement program implementation success.

    PubMed

    Fryer, Ashley-Kay; Tucker, Anita L; Singer, Sara J

    Recent literature suggests that middle manager affective commitment (emotional attachment, identification, and involvement) to an improvement program may influence implementation success. However, less is known about the interplay between middle manager affective commitment and frontline worker commitment, another important driver of implementation success. We contribute to this research by surveying middle managers who directly manage frontline workers on nursing units. We assess how middle manager affective commitment is related to their perceptions of implementation success and whether their perceptions of frontline worker support mediate this relationship. We also test whether a set of organizational support factors foster middle manager affective commitment. We adapt survey measures of manager affective commitment to our research context of hospitals. We surveyed 67 nurse managers from 19 U.S. hospitals. We use hierarchical linear regression to assess relationships among middle manager affective commitment to their units' falls reduction program and their perceptions of three constructs related to the program: frontline worker support, organizational support, and implementation success. Middle manager affective commitment to their unit's falls reduction program is positively associated with their perception of implementation success. This relationship is mediated by their perception of frontline worker support for the falls program. Moreover, middle managers' affective commitment to their unit's falls program mediates the relationship between perceived organizational support for the program and perceived implementation success. We, through this research, offer an important contribution by providing empirical support of factors that may influence successful implementation of an improvement program: middle manager affective commitment, frontline worker support, and organizational support for an improvement program. Increasing levels of middle manager affective commitment to an improvement program could strengthen program implementation success by facilitating frontline worker support for the program. Furthermore, providing the organizational support items in our survey construct may bolster middle manager affective commitment.

  14. 12 CFR 1710.19 - Compliance and risk management programs; compliance with other laws.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Compliance and risk management programs... Practices and Procedures § 1710.19 Compliance and risk management programs; compliance with other laws. (a... management program. (1) An Enterprise shall establish and maintain a risk management program that is...

  15. 14 CFR 91.1003 - Management contract between owner and program manager.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Management contract between owner and... RULES Fractional Ownership Operations § 91.1003 Management contract between owner and program manager... the program manager pertaining to the operational safety of the program and those records required to...

  16. 46th Annual Targets, UAVs and Range Operations Symposium and Exhibition

    DTIC Science & Technology

    2008-10-10

    introduction  mr. Ken Hislop , QF-16 Program manager, eglin aFB, FL 1:40 Pm - 2:00 Pm U.s. navy  CaPt Pat Buckley, Usn, Program manager...Bruce Ringstad Subscale & TCS Flight Lead Mr. Jim Cornwell Program Manager Mr. Ken Hislop Program Manager Ms. Lee Neugin Program Manager & Lead...Missiles Fired / 18 Kills AAC/PA 09-26-08-429 18 QF-16 Air Superiority Target Program Manager: Mr. Ken Hislop Description Full Scale Target for Threat

  17. Repository-Based Software Engineering Program: Working Program Management Plan

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Repository-Based Software Engineering Program (RBSE) is a National Aeronautics and Space Administration (NASA) sponsored program dedicated to introducing and supporting common, effective approaches to software engineering practices. The process of conceiving, designing, building, and maintaining software systems by using existing software assets that are stored in a specialized operational reuse library or repository, accessible to system designers, is the foundation of the program. In addition to operating a software repository, RBSE promotes (1) software engineering technology transfer, (2) academic and instructional support of reuse programs, (3) the use of common software engineering standards and practices, (4) software reuse technology research, and (5) interoperability between reuse libraries. This Program Management Plan (PMP) is intended to communicate program goals and objectives, describe major work areas, and define a management report and control process. This process will assist the Program Manager, University of Houston at Clear Lake (UHCL) in tracking work progress and describing major program activities to NASA management. The goal of this PMP is to make managing the RBSE program a relatively easy process that improves the work of all team members. The PMP describes work areas addressed and work efforts being accomplished by the program; however, it is not intended as a complete description of the program. Its focus is on providing management tools and management processes for monitoring, evaluating, and administering the program; and it includes schedules for charting milestones and deliveries of program products. The PMP was developed by soliciting and obtaining guidance from appropriate program participants, analyzing program management guidance, and reviewing related program management documents.

  18. ePORT, NASA's Computer Database Program for System Safety Risk Management Oversight (Electronic Project Online Risk Tool)

    NASA Technical Reports Server (NTRS)

    Johnson, Paul W.

    2008-01-01

    ePORT (electronic Project Online Risk Tool) provides a systematic approach to using an electronic database program to manage a program/project risk management processes. This presentation will briefly cover the standard risk management procedures, then thoroughly cover NASA's Risk Management tool called ePORT. This electronic Project Online Risk Tool (ePORT) is a web-based risk management program that provides a common framework to capture and manage risks, independent of a programs/projects size and budget. It is used to thoroughly cover the risk management paradigm providing standardized evaluation criterion for common management reporting, ePORT improves Product Line, Center and Corporate Management insight, simplifies program/project manager reporting, and maintains an archive of data for historical reference.

  19. 5 CFR 10.3 - OPM authority to review personnel management programs and practices.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... management programs and practices. 10.3 Section 10.3 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT... (RULE X) § 10.3 OPM authority to review personnel management programs and practices. The Office of Personnel Management may review the human resources management programs and practices of any agency and...

  20. 12 CFR 1710.19 - Compliance and risk management programs; compliance with other laws.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... management program. (1) An Enterprise shall establish and maintain a risk management program that is reasonably designed to manage the risks of the operations of the Enterprise. (2) The risk management program... executive officer of the Enterprise. The risk management officer shall report regularly to the board of...

  1. Moxidectin and the avermectins: Consanguinity but not identity

    PubMed Central

    Prichard, Roger; Ménez, Cécile; Lespine, Anne

    2012-01-01

    The avermectins and milbemycins contain a common macrocyclic lactone (ML) ring, but are fermentation products of different organisms. The principal structural difference is that avermectins have sugar groups at C13 of the macrocyclic ring, whereas the milbemycins are protonated at C13. Moxidectin (MOX), belonging to the milbemycin family, has other differences, including a methoxime at C23. The avermectins and MOX have broad-spectrum activity against nematodes and arthropods. They have similar but not identical, spectral ranges of activity and some avermectins and MOX have diverse formulations for great user flexibility. The longer half-life of MOX and its safety profile, allow MOX to be used in long-acting formulations. Some important differences between MOX and avermectins in interaction with various invertebrate ligand-gated ion channels are known and could be the basis of different efficacy and safety profiles. Modelling of IVM interaction with glutamate-gated ion channels suggest different interactions will occur with MOX. Similarly, profound differences between MOX and the avermectins are seen in interactions with ABC transporters in mammals and nematodes. These differences are important for pharmacokinetics, toxicity in animals with defective transporter expression, and probable mechanisms of resistance. Resistance to the avermectins has become widespread in parasites of some hosts and MOX resistance also exists and is increasing. There is some degree of cross-resistance between the avermectins and MOX, but avermectin resistance and MOX resistance are not identical. In many cases when resistance to avermectins is noticed, MOX produces a higher efficacy and quite often is fully effective at recommended dose rates. These similarities and differences should be appreciated for optimal decisions about parasite control, delaying, managing or reversing resistances, and also for appropriate anthelmintic combination. PMID:24533275

  2. Guidelines to site selection for population surveillance and mosquito control trials: a case study from Mauritius.

    PubMed

    Iyaloo, Diana P; Elahee, Khouaildi B; Bheecarry, Ambicadutt; Lees, Rosemary Susan

    2014-04-01

    Many novel approaches to controlling mosquito vectors through the release of sterile and mass reared males are being developed in the face of increasing insecticide resistance and other limitations of current methods. Before full scale release programmes can be undertaken there is a need for surveillance of the target population, and investigation of parameters such as dispersal and longevity of released, as compared to wild males through mark-release-recapture (MRR) and other experiments, before small scale pilot trials can be conducted. The nature of the sites used for this field work is crucial to ensure that a trial can feasibly collect sufficient and relevant information, given the available resources and practical limitations, and having secured the correct regulatory, community and ethical approvals and support. Mauritius is considering the inclusion of the sterile insect technique (SIT), for population reduction of Aedes albopictus, as a component of the Ministry of Health and Quality of Life's 'Operational Plan for Prevention and Control of Chikungunya and Dengue'. As part of an investigation into the feasibility of integrating the SIT into the Integrated Vector Management (IVM) scheme in Mauritius a pilot trial is planned. Two potential sites have been selected for this purpose, Pointe des Lascars and Panchvati, villages in the North East of the country, and population surveillance has commenced. This case study will here be used to explore the considerations which go into determining the most appropriate sites for mosquito field research. Although each situation is unique, and an ideal site may not be available, this discussion aims to help researchers to consider and balance the important factors and select field sites that will meet their needs. Copyright © 2013 International Atomic Energy Agency 2013. Published by Elsevier B.V. All rights reserved.

  3. Sport Management Graduate Programs: Characteristics of Effectiveness.

    ERIC Educational Resources Information Center

    Li, Ming; And Others

    1994-01-01

    Reports a study that examined the characteristics that enable graduate sport management programs to achieve their objectives. Surveys of sport management educators found they agreed on 11 characteristics that indicated a sport management program's effectiveness. Respondents believed an effective program should produce sport managers, not…

  4. KENNEDY SPACE CENTER, FLA. -- From left, NASA Deputy Program Manager of the Space Shuttle Program Michael Wetmore, United Space Alliance (USA) Vice President and Space Shuttle Program Manager Howard DeCastro, NASA Deputy Associate Administrator for Space Station and Shuttle Programs Michael Kostelnik, and a USA technician examine cold plates in Orbiter Processing Facility Bay 2. NASA and USA Space Shuttle program management are participating in a leadership workday. The day is intended to provide management with an in-depth, hands-on look at Shuttle processing activities at KSC.

    NASA Image and Video Library

    2003-12-19

    KENNEDY SPACE CENTER, FLA. -- From left, NASA Deputy Program Manager of the Space Shuttle Program Michael Wetmore, United Space Alliance (USA) Vice President and Space Shuttle Program Manager Howard DeCastro, NASA Deputy Associate Administrator for Space Station and Shuttle Programs Michael Kostelnik, and a USA technician examine cold plates in Orbiter Processing Facility Bay 2. NASA and USA Space Shuttle program management are participating in a leadership workday. The day is intended to provide management with an in-depth, hands-on look at Shuttle processing activities at KSC.

  5. Emergency management training program: Guide to good practice

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

    Not Available

    1991-07-01

    The Emergency Management Training Program Guide to Good Practice is a project of the Training Resources and Data Exchange (TRADE) Emergency Management Issues Special Interest Group (EMI SIG). EMI SIG members expressed interest in a resource to assist in development of a comprehensive emergency management training program. This publication provides guidelines, methods, and materials for EMI SIG members to use, assisting in complete and effective emergency management programs. The purposes of the Emergency Management Training Program Guide to Good Practice are: Provide guidance in the development and management of Emergency Management (EM) training programs; Assist EM trainers to incorporate componentsmore » of the DOE Emergency Management System philosophy of planning, preparedness, readiness assurance, and response into EM training programs; Help EM training managers meet EM training requirements and conditions established by current regulations and policies; Supplement other TRADE EMI SIG documents and complement individual facility training documents. This program is designed for emergency management personnel who are responsible for providing or overseeing EM training but who do not necessarily possess expertise in developing training. It provides good practices from the manager`s point of view on how to produce, administer, and document facility EM training programs in the spirit of the DOE EM system philosophy. Basic guidance is also included for personnel who design, develop, deliver, and/or evaluate EM training programs or parts. This guidance includes key points of EM training programs and identifies other documents that contain useful and/or more detailed training information.« less

  6. Lightning Mapper Sensor Lens Assembly S.O. 5459: Project Management Plan

    NASA Technical Reports Server (NTRS)

    Zeidler, Janet

    1999-01-01

    Kaiser Electro-Optics, Inc. (KEO) has developed this Project Management Plan for the Lightning Mapper Sensor (LMS) program. KEO has integrated a team of experts in a structured program management organization to meet the needs of the LMS program. The project plan discusses KEO's approach to critical program elements including Program Management, Quality Assurance, Configuration Management, and Schedule.

  7. KENNEDY SPACE CENTER, FLA. -- From left, United Space Alliance (USA) Deputy Space Shuttle Program Manager of Operations Loren Shriver, USA Associate Program Manager of Ground Operations Andy Allen, NASA Deputy Associate Administrator for Space Station and Shuttle Programs Michael Kostelnik, and USA Vice President and Space Shuttle Program Manager Howard DeCastro examine a tile used in the Shuttle's Thermal Protection System (TPS) in KSC's TPS Facility. NASA and USA Space Shuttle program management are participating in a leadership workday. The day is intended to provide management with an in-depth, hands-on look at Shuttle processing activities at KSC.

    NASA Image and Video Library

    2003-12-19

    KENNEDY SPACE CENTER, FLA. -- From left, United Space Alliance (USA) Deputy Space Shuttle Program Manager of Operations Loren Shriver, USA Associate Program Manager of Ground Operations Andy Allen, NASA Deputy Associate Administrator for Space Station and Shuttle Programs Michael Kostelnik, and USA Vice President and Space Shuttle Program Manager Howard DeCastro examine a tile used in the Shuttle's Thermal Protection System (TPS) in KSC's TPS Facility. NASA and USA Space Shuttle program management are participating in a leadership workday. The day is intended to provide management with an in-depth, hands-on look at Shuttle processing activities at KSC.

  8. 75 FR 41798 - Solicitation of Letters of Interest to Participate in Biotechnology Quality Management System...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-19

    ...] Solicitation of Letters of Interest to Participate in Biotechnology Quality Management System Program AGENCY... participate in the APHIS Biotechnology Quality Management System Program. The Biotechnology Quality Management..., audit-based compliance assistance program known as the Biotechnology Quality Management System Program...

  9. 14 CFR 91.1019 - Conducting tests and inspections.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... program manager under this subpart is complying with title 49 of the United States Code, applicable regulations, and the program manager's management specifications. (b) The program manager must— (1) Make available to the Administrator at the program manager's principal base of operations, or at a place approved...

  10. 32 CFR Appendix A to Part 806 - References

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., Information Security Program Management AFI 31-501, Personnel Security Program Management AFI 31-601, Industrial Security Program Management AFI 33-129, Transmission of Information Via the Internet AFI 35-205... Management (will convert to AFPD 33-3) AFI 37-124, The Information Collections and Reports Management Program...

  11. 32 CFR Appendix A to Part 806 - References

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., Information Security Program Management AFI 31-501, Personnel Security Program Management AFI 31-601, Industrial Security Program Management AFI 33-129, Transmission of Information Via the Internet AFI 35-205... Management (will convert to AFPD 33-3) AFI 37-124, The Information Collections and Reports Management Program...

  12. 32 CFR Appendix A to Part 806 - References

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., Information Security Program Management AFI 31-501, Personnel Security Program Management AFI 31-601, Industrial Security Program Management AFI 33-129, Transmission of Information Via the Internet AFI 35-205... Management (will convert to AFPD 33-3) AFI 37-124, The Information Collections and Reports Management Program...

  13. Acute dietary zinc deficiency before conception compromises oocyte epigenetic programming and disrupts embryonic development.

    PubMed

    Tian, X; Diaz, F J

    2013-04-01

    Recent findings show that zinc is an important factor necessary for regulating the meiotic cell cycle and ovulation. However, the role of zinc in promoting oocyte quality and developmental potential is not known. Using an in vivo model of acute dietary zinc deficiency, we show that feeding a zinc deficient diet (ZDD) for 3-5 days before ovulation (preconception) dramatically disrupts oocyte chromatin methylation and preimplantation development. There was a dramatic decrease in histone H3K4 trimethylation and global DNA methylation in zinc deficient oocytes. Moreover, there was a 3-20 fold increase in transcript abundance of repetitive elements (Iap, Line1, Sineb1, Sineb2), but a decrease in Gdf9, Zp3 and Figla mRNA. Only 53% and 8% of mature eggs reached the 2-cell stage after IVF in animals receiving a 3 and 5 days ZDD, respectively, while a 5 day ZDD in vivo reduced the proportion of 2-cells to 49%. In vivo fertilized 2-cell embryos cultured in vitro formed fewer (38%) blastocysts compared to control embryos (74%). Likewise, fewer blastocyst and expanded blastocyst were collected from the reproductive tract of zinc deficient animals on day 3.5 of pregnancy. This could be due to a decrease in Igf2 and H19 mRNA in ZDD blastocyst. Supplementation with a methyl donor (SAM) during IVM restored histone H3K4me3 and doubled the IVF success rate from 17% to 43% in oocytes from zinc deficient animals. Thus, the terminal period of oocyte development is extremely sensitive to perturbation in dietary zinc availability. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. In vitro, in silico and in vivo studies of ursolic acid as an anti-filarial agent.

    PubMed

    Kalani, Komal; Kushwaha, Vikas; Sharma, Pooja; Verma, Richa; Srivastava, Mukesh; Khan, Feroz; Murthy, P K; Srivastava, Santosh Kumar

    2014-01-01

    As part of our drug discovery program for anti-filarial agents from Indian medicinal plants, leaves of Eucalyptus tereticornis were chemically investigated, which resulted in the isolation and characterization of an anti-filarial agent, ursolic acid (UA) as a major constituent. Antifilarial activity of UA against the human lymphatic filarial parasite Brugia malayi using in vitro and in vivo assays, and in silico docking search on glutathione-s-transferase (GST) parasitic enzyme were carried out. The UA was lethal to microfilariae (mf; LC100: 50; IC50: 8.84 µM) and female adult worms (LC100: 100; IC50: 35.36 µM) as observed by motility assay; it exerted 86% inhibition in MTT reduction potential of the adult parasites. The selectivity index (SI) of UA for the parasites was found safe. This was supported by the molecular docking studies, which showed adequate docking (LibDock) scores for UA (-8.6) with respect to the standard antifilarial drugs, ivermectin (IVM -8.4) and diethylcarbamazine (DEC-C -4.6) on glutathione-s-transferase enzyme. Further, in silico pharmacokinetic and drug-likeness studies showed that UA possesses drug-like properties. Furthermore, UA was evaluated in vivo in B. malayi-M. coucha model (natural infection), which showed 54% macrofilaricidal activity, 56% female worm sterility and almost unchanged microfilaraemia maintained throughout observation period with no adverse effect on the host. Thus, in conclusion in vitro, in silico and in vivo results indicate that UA is a promising, inexpensive, widely available natural lead, which can be designed and developed into a macrofilaricidal drug. To the best of our knowledge this is the first ever report on the anti-filarial potential of UA from E. tereticornis, which is in full agreement with the Thomson Reuter's 'Metadrug' tool screening predictions.

  15. 45 CFR 1304.51 - Management systems and procedures.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... control program quality, maintain program accountability, and advise governing bodies, policy groups, and... DELEGATE AGENCIES Program Design and Management § 1304.51 Management systems and procedures. (a) Program... program planning that includes consultation with the program's governing body, policy groups, and program...

  16. 22 CFR 518.20 - Purpose of financial and program management.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Purpose of financial and program management. 518... ORGANIZATIONS Post-Award Requirements Financial and Program Management § 518.20 Purpose of financial and program management. Sections 518.21 through 518.28 prescribe standards for financial management systems, methods for...

  17. 34 CFR 74.20 - Purpose of financial and program management.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Purpose of financial and program management. 74.20... Requirements Financial and Program Management § 74.20 Purpose of financial and program management. Sections 74.21 through 74.28 prescribe standards for financial management systems, methods for making payments...

  18. 22 CFR 145.20 - Purpose of financial and program management.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Purpose of financial and program management... Financial and Program Management § 145.20 Purpose of financial and program management. Sections 145.21 through 145.28 prescribe standards for financial management systems, methods for making payments and rules...

  19. 76 FR 16000 - Voluntary Protection Programs Information; Extension of the Office of Management and Budget's...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-22

    ... management programs including how the programs successfully address management leadership and employee...] Voluntary Protection Programs Information; Extension of the Office of Management and Budget's (OMB's... concerning its proposal to extend the Office of Management and Budget's (OMB's) approval of the information...

  20. 76 FR 39857 - Alaska Coastal Management Program Withdrawal From the National Coastal Management Program Under...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-07

    .... SUMMARY: By operation of Alaska State law, the federally approved Alaska Coastal Management Program... partner in the National Coastal Management Program. The ACMP expired by operation of Alaska Statutes 44.66... DEPARTMENT OF COMMERCE National Oceanic Atmospheric Administration Alaska Coastal Management...

  1. 2 CFR 215.20 - Purpose of financial and program management.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 2 Grants and Agreements 1 2010-01-01 2010-01-01 false Purpose of financial and program management... Financial and Program Management § 215.20 Purpose of financial and program management. Sections 215.21 through 215.28 prescribe standards for financial management systems, methods for making payments and rules...

  2. Developing an Information and Records Management Program.

    ERIC Educational Resources Information Center

    Rutledge, Juli G.; Kartis, Alexia M.

    1984-01-01

    The need for information controls for college records management programs and the elements of program organization, planning, and management are discussed. Conditions at institutions that indicate a flaw in information control are identified, along with the benefits of a sound records management program. The management of an information and…

  3. 5 CFR 10.3 - OPM authority to review personnel management programs and practices.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... management programs and practices. 10.3 Section 10.3 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE RULES AGENCY ACCOUNTABILITY SYSTEMS; OPM AUTHORITY TO REVIEW PERSONNEL MANAGEMENT PROGRAMS (RULE X) § 10.3 OPM authority to review personnel management programs and practices. The Office of...

  4. 30 CFR 256.20 - Consideration of coastal zone management program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 2 2011-07-01 2011-07-01 false Consideration of coastal zone management... SHELF Oil and Gas Leasing Program § 256.20 Consideration of coastal zone management program. In the development of the leasing program, consideration shall be given to the coastal zone management program being...

  5. Management of information in a research and development agency

    NASA Technical Reports Server (NTRS)

    Keene, Wallace O.

    1990-01-01

    The NASA program for managing scientific and technical information (STI) is examined, noting the technological, managerial, educational, and legal aspects of transferring and disseminating information. A definition of STI is introduced and NASA's STI-related management programs are outlined. Consideration is given to the role of STI management in NASA mission programs, research efforts supporting the management and use of STI, STI program interfaces, and the Automated Information Management Program to eliminate redundant automation efforts in common administrative functions. The infrastructure needed to manage the broad base of NASA information and the interfaces between NASA's STI management and external organizations are described.

  6. IT Workforce: Key Practices Help Ensure Strong Integrated Program Teams; Selected Departments Need to Assess Skill Gaps

    DTIC Science & Technology

    2016-11-01

    personnel, career paths for program managers, plans to strengthen program management, and use of special hiring authorities) Monitor and report...agencies with direct hiring authority for program managers and directed OPM to create a specialized career path. OMB also tasked agencies with...guidance for developing career paths for IT program managers.14 OPM’s career path guide was to build upon its IT Program Management Competency Model

  7. Emergency management training program: Guide to good practice

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

    Not Available

    1991-07-01

    The Emergency Management Training Program Guide to Good Practice is a project of the Training Resources and Data Exchange (TRADE) Emergency Management Issues Special Interest Group (EMI SIG). EMI SIG members expressed interest in a resource to assist in development of a comprehensive emergency management training program. This publication provides guidelines, methods, and materials for EMI SIG members to use, assisting in complete and effective emergency management programs. The purposes of the Emergency Management Training Program Guide to Good Practice are: Provide guidance in the development and management of Emergency Management (EM) training programs; Assist EM trainers to incorporate componentsmore » of the DOE Emergency Management System philosophy of planning, preparedness, readiness assurance, and response into EM training programs; Help EM training managers meet EM training requirements and conditions established by current regulations and policies; Supplement other TRADE EMI SIG documents and complement individual facility training documents. This program is designed for emergency management personnel who are responsible for providing or overseeing EM training but who do not necessarily possess expertise in developing training. It provides good practices from the manager's point of view on how to produce, administer, and document facility EM training programs in the spirit of the DOE EM system philosophy. Basic guidance is also included for personnel who design, develop, deliver, and/or evaluate EM training programs or parts. This guidance includes key points of EM training programs and identifies other documents that contain useful and/or more detailed training information.« less

  8. Green campus management based on conservation program in Universitas Negeri Semarang

    NASA Astrophysics Data System (ADS)

    Prihanto, Teguh

    2018-03-01

    Universitas Negeri Semarang (UNNES) has a great commitment in the development of higher education programs in line with its vision as a conservation - minded and internationally reputable university. Implementation of conservation programs with respect to the rules or conservation aspects of sustainable use, preservation, provisioning, protection, restoration and conservation of nature. In order to support the implementation of UNNES conservation program more focused, development strategies and development programs for each conservation scope are covered: (1) Biodiversity management; (2) Internal transportation management; (3) energy management; (4) Green building management; (5) Waste and water management; (6) Cultural conservation management. All related to conservation development strategies and programs are managed in the form of green campus management aimed at realizing UNNES as a green campus, characterized and reputable at the regional and global level.

  9. KENNEDY SPACE CENTER, FLA. -- From left, a United Space Alliance (USA) technician briefs NASA Deputy Program Manager of the Space Shuttle Program Michael Wetmore, USA Vice President and Space Shuttle Program Manager Howard DeCastro, and NASA Deputy Associate Administrator for Space Station and Shuttle Programs Michael Kostelnik on the use of cold plates in Orbiter Processing Facility Bay 2. NASA and USA Space Shuttle program management are participating in a leadership workday. The day is intended to provide management with an in-depth, hands-on look at Shuttle processing activities at KSC.

    NASA Image and Video Library

    2003-12-19

    KENNEDY SPACE CENTER, FLA. -- From left, a United Space Alliance (USA) technician briefs NASA Deputy Program Manager of the Space Shuttle Program Michael Wetmore, USA Vice President and Space Shuttle Program Manager Howard DeCastro, and NASA Deputy Associate Administrator for Space Station and Shuttle Programs Michael Kostelnik on the use of cold plates in Orbiter Processing Facility Bay 2. NASA and USA Space Shuttle program management are participating in a leadership workday. The day is intended to provide management with an in-depth, hands-on look at Shuttle processing activities at KSC.

  10. 14 CFR 1214.1706 - Program management.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 5 2013-01-01 2013-01-01 false Program management. 1214.1706 Section 1214... Participants § 1214.1706 Program management. The Associate Administrator for Space Flight is responsible for program management under the direction of the Committee chairperson. ...

  11. 14 CFR 1214.1706 - Program management.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 5 2012-01-01 2012-01-01 false Program management. 1214.1706 Section 1214... Participants § 1214.1706 Program management. The Associate Administrator for Space Flight is responsible for program management under the direction of the Committee chairperson. ...

  12. 14 CFR 1214.1706 - Program management.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 5 2011-01-01 2010-01-01 true Program management. 1214.1706 Section 1214... Participants § 1214.1706 Program management. The Associate Administrator for Space Flight is responsible for program management under the direction of the Committee chairperson. ...

  13. 6 CFR 29.5 - Requirements for protection.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY PROTECTED CRITICAL... PCII Program Manager or the PCII Program Manager's designee; (2) The information is submitted for... information initially provided received by the PCII Program Manager or the PCII Program Manager's designee...

  14. 6 CFR 29.5 - Requirements for protection.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY PROTECTED CRITICAL... PCII Program Manager or the PCII Program Manager's designee; (2) The information is submitted for... information initially provided received by the PCII Program Manager or the PCII Program Manager's designee...

  15. 14 CFR 1214.1706 - Program management.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Program management. 1214.1706 Section 1214... Participants § 1214.1706 Program management. The Associate Administrator for Space Flight is responsible for program management under the direction of the Committee chairperson. ...

  16. Impact of managed MediCal on California family practice programs.

    PubMed

    Zweifler, J A

    2001-05-01

    An important source of patients for California's family practice program is MediCal. During the past 5 years, MediCal has established a variety of capitated managed care plans. To assess the impact of California's managed MediCal program on the state's 38 family practice training programs. A cross-sectional, retrospective descriptive survey. A 3-page, 11-question survey was developed by family practice residency directors and staff from the California Academy of Family Physicians, San Francisco. The 38 family practice programs in existence in California in September 1997 were stratified by type of managed MediCal in their county and by type of sponsoring institution--university, county, community based, staff-model health maintenance organization, or managed care system. Of the 38 family practice programs, 27 responded; 19 of 27 programs participated in managed MediCal. The total number of family health center patients, and the percentage of MediCal patients (48%-60%) at family practice programs was similar when stratified by programs with and without managed MediCal and by type of sponsorship. Most programs reported that they were able to compete effectively, although most also reported increased administrative, nursing, and front office costs. Managed MediCal patients were directly assigned to residents in only 3 of 19 programs. The introduction of managed MediCal has not adversely affected the number of patients cared for in California's family practice programs. Continued vigilance regarding California family practice programs' involvement in managed MediCal, including collection of accurate data on the number of MediCal patients and the financial and educational implications for California's family practice programs, is warranted.

  17. IPM: Integrated Pest Management Kit for Building Managers. How To Implement an Integrated Pest Management Program in Your Building(s).

    ERIC Educational Resources Information Center

    Mitchell, Brad

    This management kit introduces building managers to the concept of Integrated Pest Management (IPM), and provides the knowledge and tools needed to implement an IPM program in their buildings. It discusses the barriers to implementing an IPM program, why such a program should be used, and the general guidelines for its implementation. Managerial…

  18. Disease Management, Case Management, Care Management, and Care Coordination: A Framework and a Brief Manual for Care Programs and Staff.

    PubMed

    Ahmed, Osman I

    2016-01-01

    With the changing landscape of health care delivery in the United States since the passage of the Patient Protection and Affordable Care Act in 2010, health care organizations have struggled to keep pace with the evolving paradigm, particularly as it pertains to population health management. New nomenclature emerged to describe components of the new environment, and familiar words were put to use in an entirely different context. This article proposes a working framework for activities performed in case management, disease management, care management, and care coordination. The author offers standard working definitions for some of the most frequently used words in the health care industry with the goal of increasing consistency for their use, especially in the backdrop of the Centers for Medicaid & Medicare Services offering a "chronic case management fee" to primary care providers for managing the sickest, high-cost Medicare patients. Health care organizations performing case management, care management, disease management, and care coordination. Road map for consistency among users, in reporting, comparison, and for success of care management/coordination programs. This article offers a working framework for disease managers, case and care managers, and care coordinators. It suggests standard definitions to use for disease management, case management, care management, and care coordination. Moreover, the use of clear terminology will facilitate comparing, contrasting, and evaluating all care programs and increase consistency. The article can improve understanding of care program components and success factors, estimate program value and effectiveness, heighten awareness of consumer engagement tools, recognize current state and challenges for care programs, understand the role of health information technology solutions in care programs, and use information and knowledge gained to assess and improve care programs to design the "next generation" of programs.

  19. 75 FR 68418 - Real-Time System Management Information Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-08

    ...-Time System Management Information Program AGENCY: Federal Highway Administration (FHWA), DOT. ACTION...) to establish a Real-Time System Management Information Program that provides, in all States, the... traveler information. The purposes of the Real-Time System Management Information Program are to: (1...

  20. 76 FR 42536 - Real-Time System Management Information Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-19

    ...-Time System Management Information Program AGENCY: Federal Highway Administration (FHWA), DOT. ACTION... Real-Time System Management Information Program and general information about current and planned... establishing requirements for the Real-Time System Management Information Program on November 8, 2010, at 75 FR...

  1. 78 FR 72747 - Meeting: RTCA Program Management Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-03

    ... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Meeting: RTCA Program Management...: Notice of RTCA Program Management Committee Meeting. SUMMARY: The FAA is issuing this notice to advise the public of a meeting of RTCA Program Management Committee. DATES: The meeting will be held December...

  2. 76 FR 74842 - RTCA Program Management Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-01

    ... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration RTCA Program Management Committee... RTCA Program Management Committee meeting. SUMMARY: The FAA is issuing this notice to advise the public of a meeting of RTCA Program Management Committee DATES: The meeting will be held December 13, 2011...

  3. 77 FR 12905 - Meeting: RTCA Program Management Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-02

    ... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Meeting: RTCA Program Management...: Notice of RTCA Program Management Committee Meeting. SUMMARY: The FAA is issuing this notice to advise the public of a meeting of the RTCA Program Management Committee. DATES: The meeting will be held...

  4. 78 FR 43962 - Meeting: RTCA Program Management Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-22

    ... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Meeting: RTCA Program Management...: Notice of RTCA Program Management Committee Meeting. SUMMARY: The FAA is issuing this notice to advise the public of a meeting of RTCA Program Management Committee. DATES: The meeting will be held August...

  5. 78 FR 57673 - RTCA Program Management Committee; Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-19

    ... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration RTCA Program Management Committee...: Notice of RTCA Program Management Committee meeting. SUMMARY: The FAA is issuing this notice to advise the public of a meeting of RTCA Program Management Committee. DATES: The meeting will be held October...

  6. Children/Youth Physical Fitness Program Management System.

    ERIC Educational Resources Information Center

    Mozzini, Lou; And Others

    Intended for physical fitness program managers, this book presents a system through which these professionals can justify, evaluate, develop, supervise, and promote a sound physical fitness program. Sections address the management stages of: (1) program assessment; (2) program commitment; (3) physical fitness program planning; (4) program…

  7. 41 CFR 102-192.150 - What are your general responsibilities as a program level mail manager?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... responsibilities as a program level mail manager? 102-192.150 Section 102-192.150 Public Contracts and Property... general responsibilities as a program level mail manager? Your responsibilities at the program level include— (a) Working closely with the agency mail manager and mail center managers who handle significant...

  8. 41 CFR 102-194.5 - What is the Standard and Optional Forms Management Program?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false What is the Standard and Optional Forms Management Program? 102-194.5 Section 102-194.5 Public Contracts and Property Management... PROGRAMS 194-STANDARD AND OPTIONAL FORMS MANAGEMENT PROGRAM § 102-194.5 What is the Standard and Optional...

  9. Project management in the Apollo program: An interdisciplinary study

    NASA Technical Reports Server (NTRS)

    Drucker, E. E.; Pooler, W. S.; Wilemon, D. L.; Wood, B. D.

    1972-01-01

    Findings concerning project management in the NASA Apollo program are presented. The Apollo program in the context of the total NASA organization is examined along with the nature of project management and the manner in which project managers functioned in the Apollo program. The utilization of the in-house technical competence in the support of the Apollo program, and the formal and informal relationships between Apollo managers and the contractors are discussed.

  10. The analysis of the program to develop the Nuclear Waste Management System: Allocated requirements for the Office of Civilian Radioactive Waste Management Program

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

    Woods, T.W.

    1991-09-01

    This report is volume 3, part B, of the program to satisfy the allocated requirements of the Office of Civilian Radioactive Waste Management Program, in the development of the nuclear waste management system. The report is divided into the following sections: regulatory compliance; external relations; international programs; strategic and contingency planning; contract business management; and administrative services. (CS)

  11. [Characteristics of case management programs and their potential for patient empowerment].

    PubMed

    Grün, Oskar; Maier, Manfred

    2008-01-01

    Different types of case management programs have been increasingly developed for health care systems. This study, therefore, aimed to identify similarities and differences of case management programs, to estimate their shaping with special emphasis on patient empowerment, and to develop an instrument for their differentiation. During an interdisciplinary seminar for students, eight different case management programs were selected and analyzed. Five characteristics of case management programs were identified: type of case, extent of functions, players involved, limits of availability and need for resources. The programs were categorized into information-, provider-, disease- or patient centred. With these characteristics the selected programs could be exactly described and their potential for patient empowerment could be assessed. This newly developed tool for describing case management programs allows for their sufficient differentiation. The potential for patient empowerment apparently is most prominent in patient centred programs.

  12. Disease management programs for CKD patients: the potential and pitfalls.

    PubMed

    Rocco, Michael V

    2009-03-01

    Disease management describes the use of a number of approaches to identify and treat patients with chronic health conditions, especially those that are expensive to treat. Disease management programs have grown rapidly in the United States in the past several years. These programs have been established for patients with chronic kidney disease (CKD), but some have been discontinued because of the high cost of the program. Disease management programs for CKD face unique challenges. Identification of patients with CKD is hampered by incomplete use of the International Classification of Diseases, Ninth Revision (ICD-9) codes for CKD by physicians and the less than universal use of estimated glomerular filtration rate from serum creatinine measurements to identify patients with an estimated glomerular filtration rate less than 60 mL/min/1.73 m(2). CKD affects multiple organ systems. Thus, a comprehensive disease management program will need to manage each of these aspects of CKD. These multiple interventions likely will make a CKD disease management program more costly than similar disease management programs designed for patients with diabetes mellitus, congestive heart failure, or other chronic diseases. The lack of data that can be used to develop effective disease management programs in CKD makes it difficult to determine goals for the management of each organ system affected by CKD. Finally, long periods of observation will be needed to determine whether a particular disease management program is effective in not only improving patient outcomes, but also decreasing both resource use and health care dollars. This long-term observation period is contrary to how most disease management contracts are written, which usually are based on meeting goals during a 1- to 3-year period. Until these challenges are resolved, it likely will be difficult to maintain effective disease management programs for CKD.

  13. Assessing the quality of cost management

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

    Fayne, V.; McAllister, A.; Weiner, S.B.

    1995-12-31

    Managing environmental programs can be effective only when good cost and cost-related management practices are developed and implemented. The Department of Energy`s Office of Environmental Management (EM), recognizing this key role of cost management, initiated several cost and cost-related management activities including the Cost Quality Management (CQM) Program. The CQM Program includes an assessment activity, Cost Quality Management Assessments (CQMAs), and a technical assistance effort to improve program/project cost effectiveness. CQMAs provide a tool for establishing a baseline of cost-management practices and for measuring improvement in those practices. The result of the CQMA program is an organization that has anmore » increasing cost-consciousness, improved cost-management skills and abilities, and a commitment to respond to the public`s concerns for both a safe environment and prudent budget outlays. The CQMA program is part of the foundation of quality management practices in DOE. The CQMA process has contributed to better cost and cost-related management practices by providing measurements and feedback; defining the components of a quality cost-management system; and helping sites develop/improve specific cost-management techniques and methods.« less

  14. Rising out-of-pocket costs in disease management programs.

    PubMed

    Chernew, Michael E; Rosen, Allison B; Fendrick, A Mark

    2006-03-01

    To document the rise in copayments for patients in disease management programs and to call attention to the inherent conflicts that exist between these 2 approaches to benefit design. Data from 2 large health plans were used to compare cost sharing in disease management programs with cost sharing outside of disease management programs. The copayments charged to participants in disease management programs usually do not differ substantially from those charged to other beneficiaries. Cost sharing and disease management result in conflicting approaches to benefit design. Increasing copayments may lead to underuse of recommended services, thereby decreasing the clinical effectiveness and increasing the overall costs of disease management programs. Policymakers and private purchasers should consider the use of targeted benefit designs when implementing disease management programs or redesigning cost-sharing provisions. Current information systems and health services research are sufficiently advanced to permit these benefit designs.

  15. 44 CFR 16.150 - Program accessibility: Existing facilities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Program accessibility: Existing facilities. 16.150 Section 16.150 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT... IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE FEDERAL EMERGENCY MANAGEMENT AGENCY § 16.150 Program...

  16. 14 CFR § 1214.1706 - Program management.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 5 2014-01-01 2014-01-01 false Program management. § 1214.1706 Section Â... Participants § 1214.1706 Program management. The Associate Administrator for Space Flight is responsible for program management under the direction of the Committee chairperson. ...

  17. 10 CFR 800.002 - Program management.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Program management. 800.002 Section 800.002 Energy DEPARTMENT OF ENERGY LOANS FOR BID OR PROPOSAL PREPARATION BY MINORITY BUSINESS ENTERPRISES SEEKING DOE CONTRACTS AND ASSISTANCE General § 800.002 Program management. Program management responsibility for...

  18. 10 CFR 800.002 - Program management.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Program management. 800.002 Section 800.002 Energy DEPARTMENT OF ENERGY LOANS FOR BID OR PROPOSAL PREPARATION BY MINORITY BUSINESS ENTERPRISES SEEKING DOE CONTRACTS AND ASSISTANCE General § 800.002 Program management. Program management responsibility for...

  19. 10 CFR 800.002 - Program management.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Program management. 800.002 Section 800.002 Energy DEPARTMENT OF ENERGY LOANS FOR BID OR PROPOSAL PREPARATION BY MINORITY BUSINESS ENTERPRISES SEEKING DOE CONTRACTS AND ASSISTANCE General § 800.002 Program management. Program management responsibility for...

  20. 10 CFR 800.002 - Program management.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Program management. 800.002 Section 800.002 Energy DEPARTMENT OF ENERGY LOANS FOR BID OR PROPOSAL PREPARATION BY MINORITY BUSINESS ENTERPRISES SEEKING DOE CONTRACTS AND ASSISTANCE General § 800.002 Program management. Program management responsibility for...

  1. 30 CFR 401.12 - Program management.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false Program management. 401.12 Section 401.12 Mineral Resources GEOLOGICAL SURVEY, DEPARTMENT OF THE INTERIOR STATE WATER RESEARCH INSTITUTE PROGRAM Application and Management Procedures § 401.12 Program management. (a) Upon approval of each fiscal year's...

  2. 30 CFR 401.12 - Program management.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 2 2012-07-01 2012-07-01 false Program management. 401.12 Section 401.12 Mineral Resources GEOLOGICAL SURVEY, DEPARTMENT OF THE INTERIOR STATE WATER RESEARCH INSTITUTE PROGRAM Application and Management Procedures § 401.12 Program management. (a) Upon approval of each fiscal year's...

  3. 30 CFR 401.12 - Program management.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 2 2013-07-01 2013-07-01 false Program management. 401.12 Section 401.12 Mineral Resources GEOLOGICAL SURVEY, DEPARTMENT OF THE INTERIOR STATE WATER RESEARCH INSTITUTE PROGRAM Application and Management Procedures § 401.12 Program management. (a) Upon approval of each fiscal year's...

  4. 30 CFR 401.12 - Program management.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 2 2011-07-01 2011-07-01 false Program management. 401.12 Section 401.12 Mineral Resources GEOLOGICAL SURVEY, DEPARTMENT OF THE INTERIOR STATE WATER RESEARCH INSTITUTE PROGRAM Application and Management Procedures § 401.12 Program management. (a) Upon approval of each fiscal year's...

  5. 30 CFR 401.12 - Program management.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 2 2014-07-01 2014-07-01 false Program management. 401.12 Section 401.12 Mineral Resources GEOLOGICAL SURVEY, DEPARTMENT OF THE INTERIOR STATE WATER RESEARCH INSTITUTE PROGRAM Application and Management Procedures § 401.12 Program management. (a) Upon approval of each fiscal year's...

  6. 78 FR 14151 - Meeting: RTCA Program Management Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-04

    ... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Meeting: RTCA Program Management...: Notice of RTCA Program Management Committee Meeting. SUMMARY: The FAA is issuing this notice to advise the public of a meeting of RTCA Program Management Committee. DATES: The meeting will be held March 20...

  7. 10 CFR 800.002 - Program management.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Program management. 800.002 Section 800.002 Energy DEPARTMENT OF ENERGY LOANS FOR BID OR PROPOSAL PREPARATION BY MINORITY BUSINESS ENTERPRISES SEEKING DOE CONTRACTS AND ASSISTANCE General § 800.002 Program management. Program management responsibility for...

  8. 77 FR 31421 - Meeting: RTCA Program Management Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-25

    ... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Meeting: RTCA Program Management...: Notice of RTCA Program Management Committee Meeting. SUMMARY: The FAA is issuing this notice to advise the public of a meeting of the RTCA Program Management Committee. DATES: The meeting will be held June...

  9. Issues in NASA Program and Project Management. Special Edition: A Collection of Papers on NASA Procedures and Guidance 7120.5A. Volume 14

    NASA Technical Reports Server (NTRS)

    Hoffman, Edward J. (Editor); Lawbaugh, William M. (Editor)

    1998-01-01

    A key aspect of NASA's new Strategic Management System is improving the way we plan, approve, execute and evaluate our programs and projects. To this end, NASA has developed the NASA Program and Project Management processes and Requirements-NASA Procedures and Guidelines (NPG) 7120.5A, which formally documents the "Provide Aerospace Products and Capabilities" crosscutting process, and defines the processes and requirements that are responsive to the Program/Project Management-NPD 7120.4A. The Program/Project Management-NPD 7120.4A, issued November 14, 1996, provides the policy for managing programs and projects in a new way that is aligned with the new NASA environment. An Agencywide team has spent thousands of hours developing the NASA Program and Project Management Processes and Requirements-NPG 7120.5A. We have created significant flexibility, authority and discretion for the program and project managers to exercise and carry out their duties, and have delegated the responsibility and the accountability for their programs and projects.

  10. 49 CFR 237.33 - Content of bridge management programs.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Content of bridge management programs. 237.33... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION BRIDGE SAFETY STANDARDS Railroad Bridge Safety Assurance § 237.33 Content of bridge management programs. Each bridge management program adopted in compliance with this part...

  11. 20 CFR 638.800 - Program management.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false Program management. 638.800 Section 638.800... TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Administrative Provisions § 638.800 Program management. (a) The Job Corps Director shall establish and use internal program management procedures sufficient...

  12. 20 CFR 638.800 - Program management.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Program management. 638.800 Section 638.800... TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Administrative Provisions § 638.800 Program management. (a) The Job Corps Director shall establish and use internal program management procedures sufficient...

  13. 77 FR 60919 - Tennessee: Final Authorization of State Hazardous Waste Management Program Revisions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-05

    ...: Final Authorization of State Hazardous Waste Management Program Revisions AGENCY: Environmental..., Division of Solid Waste Management, 5th Floor, L & C Tower, 401 Church Street, Nashville, Tennessee 37243... RCRA hazardous waste management program. We granted authorization for changes to Tennessee's program on...

  14. 14 CFR 91.1023 - Program operating manual requirements.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... manager must prepare and keep current a program operating manual setting forth procedures and policies acceptable to the Administrator. The program manager's management, flight, ground, and maintenance personnel... personnel. (b) Each program manager must maintain at least one copy of the manual at its principal base of...

  15. 20 CFR 638.800 - Program management.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Program management. 638.800 Section 638.800... TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Administrative Provisions § 638.800 Program management. (a) The Job Corps Director shall establish and use internal program management procedures sufficient...

  16. 49 CFR 237.33 - Content of bridge management programs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Content of bridge management programs. 237.33... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION BRIDGE SAFETY STANDARDS Railroad Bridge Safety Assurance § 237.33 Content of bridge management programs. Each bridge management program adopted in compliance with this part...

  17. Management Training for Directors.

    ERIC Educational Resources Information Center

    Yaptinchay, Karen

    1998-01-01

    Describes a management program for Head Start directors called the Head Start-Johnson & Johnson Management Fellows program that focuses on issues and problems encountered by directors in implementing and operating programs at the local level. Notes that the management program represents a response to increasing need for cost-effective and…

  18. 32 CFR 239.10 - Management Controls.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Systems. Headquarters, USACE has an existing information management system that manages all information related to the HAP program. (1) HAPMIS. The Homeowners Assistance Program Management Information System... to this program and the management in formation system to protect the privacy information of Expanded...

  19. 32 CFR 239.10 - Management controls.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... systems. Headquarters, USACE has an existing information management system that manages all information related to the HAP program. (1) HAPMIS. The Homeowners Assistance Program Management Information System... to this program and the management information system to protect the privacy of Expanded HAP...

  20. 32 CFR 239.10 - Management controls.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... systems. Headquarters, USACE has an existing information management system that manages all information related to the HAP program. (1) HAPMIS. The Homeowners Assistance Program Management Information System... to this program and the management information system to protect the privacy of Expanded HAP...

  1. 32 CFR 239.10 - Management controls.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... systems. Headquarters, USACE has an existing information management system that manages all information related to the HAP program. (1) HAPMIS. The Homeowners Assistance Program Management Information System... to this program and the management information system to protect the privacy of Expanded HAP...

  2. Strategies in disability management. Corporate disability management programs implemented at the work site.

    PubMed

    Kalina, C M

    1999-10-30

    Managers are challenged to demonstrate all programs as economically essential to the business, generating an appreciable return on investment. Further challenge exists to blend and integrate clinical and business objectives in program development. Disability management programs must be viewed as economically essential to the financial success of the business to assure management support for clinical interventions and return-to-work strategies essential for a successful program. This paper discusses a disability management program integrating clinical and business goals and objectives in return-to-work strategies to effect positive clinical, social-cultural, and business results. Clinical, educational, social, and economic challenges in the development, implementation, and continued management of a disability program at a large corporation with multiple global work sites are defined. Continued discussion addresses the effective clinical interventions and educational strategies utilized successfully within the workplace environment in response to each defined challenge. A multiple disciplinary team approach, clinical and business outcome measures, and quality assurance indicators are discussed as major program components. This article discusses a successful program approach focusing on business process and methodology. These parameters are used to link resources to strategy, developing a product for implementing and managing a program demonstrating economic value added through effective clinical medical case management.

  3. Issues in NASA program and project management

    NASA Technical Reports Server (NTRS)

    Hoban, Francis T. (Editor)

    1989-01-01

    This new collection of papers on aerospace management issues contains a history of NASA program and project management, some lessons learned in the areas of management and budget from the Space Shuttle Program, an analysis of tools needed to keep large multilayer programs organized and on track, and an update of resources for NASA managers. A wide variety of opinions and techniques are presented.

  4. 14 CFR 91.1431 - CAMP: Continuing analysis and surveillance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... program manager who maintains program aircraft under a CAMP must establish and maintain a system for the... program manager or by another person. (b) Whenever the Administrator finds that the programs described in... program manager must, after notification by the Administrator, make changes in those programs requested by...

  5. Major Management Challenges and Program Risks. Department of Education

    DTIC Science & Technology

    2001-01-01

    GAO United States General Accounting Office Performance and Accountability SeriesJanuary 2001 Major Management Challenges and Program Risks ...34) Title and Subtitle Major Management Challenges and Program Risks Department of Education Contract or Grant Number Program Element Number Authors...Accountability Series: Major Management Challenges and Program Risks . In that series, GAO advised the Congress that it planned to reassess the

  6. 49 CFR 237.31 - Adoption of bridge management programs.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Adoption of bridge management programs. 237.31... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION BRIDGE SAFETY STANDARDS Railroad Bridge Safety Assurance § 237.31 Adoption of bridge management programs. Each track owner shall adopt a bridge safety management program to...

  7. 45 CFR 2543.20 - Purpose of financial and program management.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Purpose of financial and program management. 2543... OTHER NON-PROFIT ORGANIZATIONS Post-Award Requirements Financial and Program Management § 2543.20 Purpose of financial and program management. Sections 2543.21 through 2543.25 prescribe standards for...

  8. 40 CFR 30.20 - Purpose of financial and program management.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Program Management § 30.20 Purpose of financial and program management. Sections 30.21 through 30.28 prescribe standards for financial management systems, methods for making payments and rules for: satisfying... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Purpose of financial and program...

  9. 30 CFR 256.20 - Consideration of coastal zone management program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false Consideration of coastal zone management....20 Consideration of coastal zone management program. In the development of the leasing program, consideration shall be given to the coastal zone management program being developed or administered by an...

  10. 24 CFR 84.20 - Purpose of financial and program management.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... and Program Management § 84.20 Purpose of financial and program management. Sections 84.21 through 84.28 prescribe standards for financial management systems, methods for making payments and rules for... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Purpose of financial and program...

  11. 75 FR 76691 - Oregon; Correction of Federal Authorization of the State's Hazardous Waste Management Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-09

    ...; Correction of Federal Authorization of the State's Hazardous Waste Management Program AGENCY: Environmental... to the State of Oregon's federally authorized RCRA hazardous waste management program. On January 7... changes the State of Oregon made to its federally authorized RCRA Hazardous Waste Management Program...

  12. 75 FR 918 - Oregon: Final Authorization of State Hazardous Waste Management Program Revision

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-07

    ... Authorization of State Hazardous Waste Management Program Revision AGENCY: Environmental Protection Agency (EPA... hazardous waste management program under the Resource Conservation and Recovery Act, as amended (RCRA). On... has decided that the revisions to the Oregon hazardous waste management program satisfy all of the...

  13. 49 CFR 237.31 - Adoption of bridge management programs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Adoption of bridge management programs. 237.31... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION BRIDGE SAFETY STANDARDS Railroad Bridge Safety Assurance § 237.31 Adoption of bridge management programs. Each track owner shall adopt a bridge safety management program to...

  14. 20 CFR 632.76 - Program management systems.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Program management systems. 632.76 Section... management systems. (a) All Native American grantees shall establish management information systems to... for the overall management of all programs including: (1) Eligibility verification systems as...

  15. [The German program for disease management guidelines--implementation with pathways and quality management].

    PubMed

    Ollenschläger, Günter; Lelgemann, Monika; Kopp, Ina

    2007-07-15

    In Germany, physicians enrolled in disease management programs are legally obliged to follow evidence-based clinical practice guidelines. That is why a Program for National Disease Management Guidelines (German DM-CPG Program) was established in 2002 aiming at implementation of best-practice evidence-based recommendations for nationwide as well as regional disease management programs. Against this background the article reviews programs, methods and tools for implementing DM-CPGs via clinical pathways as well as regional guidelines for outpatient care. Special reference is given to the institutionalized program of adapting DM-CPGs for regional use by primary-care physicians in the State of Hesse.

  16. 48 CFR 301.607-70 - General.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... General. In accordance with the Federal Acquisition Certification—Program and Project Managers (FAC-P/PM) program, HHS has established a certification program for Program or Project Managers. See HHS' Federal Acquisition Certification—Program and Project Managers Handbook (P/PM Handbook) for information on the methods...

  17. 25 CFR 170.502 - Are management systems required for the IRR Program?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... RESERVATION ROADS PROGRAM Planning, Design, and Construction of Indian Reservation Roads Program Facilities... the following systems for the IRR Program: (1) Pavement management; (2) Safety management; (3) Bridge...

  18. 25 CFR 170.502 - Are management systems required for the IRR Program?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... RESERVATION ROADS PROGRAM Planning, Design, and Construction of Indian Reservation Roads Program Facilities... the following systems for the IRR Program: (1) Pavement management; (2) Safety management; (3) Bridge...

  19. 25 CFR 170.502 - Are management systems required for the IRR Program?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... RESERVATION ROADS PROGRAM Planning, Design, and Construction of Indian Reservation Roads Program Facilities... the following systems for the IRR Program: (1) Pavement management; (2) Safety management; (3) Bridge...

  20. 25 CFR 170.502 - Are management systems required for the IRR Program?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... RESERVATION ROADS PROGRAM Planning, Design, and Construction of Indian Reservation Roads Program Facilities... the following systems for the IRR Program: (1) Pavement management; (2) Safety management; (3) Bridge...

  1. 25 CFR 170.502 - Are management systems required for the IRR Program?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... RESERVATION ROADS PROGRAM Planning, Design, and Construction of Indian Reservation Roads Program Facilities... the following systems for the IRR Program: (1) Pavement management; (2) Safety management; (3) Bridge...

  2. An evaluation of the Well at Dell health management program: health risk change and financial return on investment.

    PubMed

    Musich, Shirley; McCalister, Tre'; Wang, Sara; Hawkins, Kevin

    2015-01-01

    To investigate the effectiveness of the Well at Dell comprehensive health management program in delivering health care and productivity cost savings relative to program investment (i.e., return on investment). A quasi-experimental design was used to quantify the financial impact of the program and nonexperimental pre-post design to evaluate change in health risks. Ongoing worksite health management program implemented across multiple U.S. locations. Subjects were 24,651 employees with continuous medical enrollment in 2010-2011 who were eligible for 2011 health management programming. Incentive-driven, outcomes-based multicomponent corporate health management program including health risk appraisal (HRA)/wellness, lifestyle management, and disease management coaching programs. Medical, pharmacy, and short-term disability pre/post expenditure trends adjusted for demographics, health status, and baseline costs. Self-reported health risks from repeat HRA completers. Analysis: Propensity score-weighted and multivariate regression-adjusted comparison of baseline to post trends in health care expenditures and productivity costs for program participants and nonparticipants (i.e., difference in difference) relative to programmatic investment. The Well at Dell program achieved an overall return on investment of 2.48 in 2011. Most of the savings were realized from the HRA/wellness component of the program. Cost savings were supported with high participation and significant health risk improvement. An incentive-driven, well-managed comprehensive corporate health management program can continue to achieve significant health improvement while promoting health care and productivity cost savings in an employee population.

  3. Simplified RP-HPLC method for multi-residue analysis of abamectin, emamectin benzoate and ivermectin in rice.

    PubMed

    Xie, Xianchuan; Gong, Shu; Wang, Xiaorong; Wu, Yinxing; Zhao, Li

    2011-01-01

    A rapid, reliable and sensitive reverse-phase high-performance liquid chromatography method with fluorescence detection (RP-FLD-HPLC) was developed and validated for simultaneous analysis of the abamectin (ABA), emamectin (EMA) benzoate and ivermectin (IVM) residues in rice. After extraction with acetonitrile/water (2 : 1) with sonication, the avermectin (AVMs) residues were directly derivatised by N-methylimidazole (N-NMIM) and trifluoroacetic anhydride (TFAA) and then analysed on RP-FLD-HPLC. A good linear relationship (r(2 )> 0.99) was obtained for three AVMs ranging from 0.01 to 5 microg ml(-1), i.e. 0.01-5.0 microg g(-1) in rice matrix. The limit of detection (LOD) and the limit of quantification (LOQ) were between 0.001 and 0.002 microg g(-1) and between 0.004 and 0.006 microg g(-1), respectively. Recoveries were from 81.9% to 105.4% and precision less than 12.4%. The proposed method was successfully applied to routine analysis of the AVMs residues in rice.

  4. USAF/SCEEE Graduate Student Summer Support Program (1982). Management and Technical Report.

    DTIC Science & Technology

    1982-10-01

    AD-A130 767 USAF/SCEEE GRADUATE STUDENT SUMMER SUPPORT PROGRAM (1982) MANAGEMENT AND..(U) SOUTHEASTERN CENTER FORELECTRICAL ENGINEERING EDUCATION INC...SUMMER SUPPORT PROGRAM Conducted by Southeastern Center for Electrical Engineering Education under USAF Contract Number F49620-82-C-0035 MANAGEMENT ...UNITED STATES AIR FORCE GRADUATE STUDENT SL24MER SUPPORT PROGRAM 1982 PROGRAM MANAGEMENT AND TECHNICAL REPORT SOUTHEASTERN CENTER FOR ELECTRICAL

  5. Management Data Base Development.

    ERIC Educational Resources Information Center

    Dan, Robert L.

    1975-01-01

    A management data base is seen as essential for a management information system, program budgeting, program costing, management by objectives, program evaluation, productivity measures, and accountability in institutions of higher education. The necessity of a management data base is addressed, along with the benefits and limitations it may have…

  6. Sustaining a Mature Risk Management Process: Ensuring the International Space Station for a Vibrant Future

    NASA Technical Reports Server (NTRS)

    Raftery, Michael; Carter-Journet, Katrina

    2013-01-01

    The International Space Station (ISS) risk management methodology is an example of a mature and sustainable process. Risk management is a systematic approach used to proactively identify, analyze, plan, track, control, communicate, and document risks to help management make risk-informed decisions that increase the likelihood of achieving program objectives. The ISS has been operating in space for over 14 years and permanently crewed for over 12 years. It is the longest surviving habitable vehicle in low Earth orbit history. Without a mature and proven risk management plan, it would be increasingly difficult to achieve mission success throughout the life of the ISS Program. A successful risk management process must be able to adapt to a dynamic program. As ISS program-level decision processes have evolved, so too has the ISS risk management process continued to innovate, improve, and adapt. Constant adaptation of risk management tools and an ever-improving process is essential to the continued success of the ISS Program. Above all, sustained support from program management is vital to risk management continued effectiveness. Risk management is valued and stressed as an important process by the ISS Program.

  7. Nurse manager orientation.

    PubMed

    Hawkins, Anne; Carter, Kelly; Nugent, Mary

    2009-01-01

    On the basis of the principles of management and leadership, our organization has worked over the years to formalize the orientation program for new nurse managers. This program meets the needs of new nurse managers and responds to today's complex health care system needs. This article describes the components of a nurse manager orientation program for the novice nurse manager and methods for evaluating nurse manager effectiveness.

  8. 78 FR 25678 - Georgia: Final Authorization of State Hazardous Waste Management Program Revisions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-02

    ...: Final Authorization of State Hazardous Waste Management Program Revisions AGENCY: Environmental... of changes to its hazardous waste program under the Resource Conservation and Recovery Act (RCRA... Gwendolyn Gleaton, Permits and State Programs Section, RCRA Programs and Materials Management Branch, RCRA...

  9. 76 FR 6564 - Florida: Final Authorization of State Hazardous Waste Management Program Revisions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-07

    ...: Final Authorization of State Hazardous Waste Management Program Revisions AGENCY: Environmental... implement the RCRA hazardous waste management program. We granted authorization for changes to their program..., 06/ 62-730.185(1) F.A.C. Universal Waste Management. 29/07. State Initiated Changes to the 62-730.210...

  10. 48 CFR 301.607-78 - Contracting Officer designation of a Program/Project Manager as the Contracting Officer's...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... designation of a Program/Project Manager as the Contracting Officer's Technical Representative. 301.607-78... Contracting Officer designation of a Program/Project Manager as the Contracting Officer's Technical... acquisition. However, for those individuals serving as a Program or Project Manager under a FAC-P/PM...

  11. 48 CFR 903.104-1 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... for the purposes of the post-employment restrictions at 48 CFR 3.104-2(b)(3)— Deputy program manager means the individual within DOE who normally acts as the program manager in the absence of the program manager, and does not mean an individual who occasionally acts for the program manager or the deputy...

  12. Research of the Rio Grande Ecosystem Management Program

    Treesearch

    Deborah M. Finch

    2000-01-01

    This paper describes the mission, objectives, and preliminary results of the Middle Rio Grande Ecosystem Management Research Program managed at the Rocky Mountain Research Station's Albuquerque laboratory. This program was initiated in 1994 to address growing pressures to effectively manage the limited resources of the middle Rio Grande Basin. The program is...

  13. 32 CFR 536.154 - Claims involving tortfeasors other than nonappropriated fund employees: NAFI risk management...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... nonappropriated fund employees: NAFI risk management program (RIMP) claims. 536.154 Section 536.154 National... nonappropriated fund employees: NAFI risk management program (RIMP) claims. The risk management program (RIMP) is..., military and civilian employees, to use the family child care program and sports equipment, such claims are...

  14. 32 CFR 536.154 - Claims involving tortfeasors other than nonappropriated fund employees: NAFI risk management...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... nonappropriated fund employees: NAFI risk management program (RIMP) claims. 536.154 Section 536.154 National... nonappropriated fund employees: NAFI risk management program (RIMP) claims. The risk management program (RIMP) is..., military and civilian employees, to use the family child care program and sports equipment, such claims are...

  15. 32 CFR 536.154 - Claims involving tortfeasors other than nonappropriated fund employees: NAFI risk management...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... nonappropriated fund employees: NAFI risk management program (RIMP) claims. 536.154 Section 536.154 National... nonappropriated fund employees: NAFI risk management program (RIMP) claims. The risk management program (RIMP) is..., military and civilian employees, to use the family child care program and sports equipment, such claims are...

  16. 32 CFR 536.154 - Claims involving tortfeasors other than nonappropriated fund employees: NAFI risk management...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... nonappropriated fund employees: NAFI risk management program (RIMP) claims. 536.154 Section 536.154 National... nonappropriated fund employees: NAFI risk management program (RIMP) claims. The risk management program (RIMP) is..., military and civilian employees, to use the family child care program and sports equipment, such claims are...

  17. Integrated Pest Management: A Curriculum for Early Care and Education Programs

    ERIC Educational Resources Information Center

    California Childcare Health Program, 2011

    2011-01-01

    This "Integrated Pest Management Toolkit for Early Care and Education Programs" presents practical information about using integrated pest management (IPM) to prevent and manage pest problems in early care and education programs. This curriculum will help people in early care and education programs learn how to keep pests out of early…

  18. An Analysis of the Radio Program Manager Occupation.

    ERIC Educational Resources Information Center

    Friedberg, Jerry; Stella, Phillip.

    This occupational analysis data was assembled to help broadcasting arts teachers develop a course of study in program management for junior and senior high school students. Following a job description for a program manager, the remainder of the content in standard task analysis format presents an analysis of nine program management duties (tasks).…

  19. Management of major system programs and projects. Handbook

    NASA Technical Reports Server (NTRS)

    1993-01-01

    This Handbook establishes the detailed policies and processes for implementing NMI 7120.4, 'Management of Major System Programs and Projects'. It constitutes a comprehensive source of the specific policies and processes governing management of major development programs/projects and is intended as a resource to the entire program/project management (PPM) community.

  20. A diabetes self-management program designed for urban American Indians.

    PubMed

    Castro, Sarah; O'Toole, Mary; Brownson, Carol; Plessel, Kimberly; Schauben, Laura

    2009-10-01

    Although the American Indian population has a disproportionately high rate of type 2 diabetes, little has been written about culturally sensitive self-management programs in this population. Community and clinic partners worked together to identify barriers to diabetes self-management and to provide activities and services as part of a holistic approach to diabetes self-management, called the Full Circle Diabetes Program. The program activities and services addressed 4 components of holistic health: body, spirit, mind, and emotion. Seven types of activities or services were available to help participants improve diabetes self-management; these included exercise classes, educational classes, and talking circles. Ninety-eight percent of program enrollees participated in at least 1 activity, and two-thirds participated in 2 or more activities. Program participation resulted in a significant improvement in knowledge of resources for managing diabetes. The Full Circle Diabetes Program developed and implemented culturally relevant resources and supports for diabetes self-management in an American Indian population. Lessons learned included that a holistic approach to diabetes self-management, community participation, and stakeholder partnerships are needed for a successful program.

  1. Computer Aided Management for Information Processing Projects.

    ERIC Educational Resources Information Center

    Akman, Ibrahim; Kocamustafaogullari, Kemal

    1995-01-01

    Outlines the nature of information processing projects and discusses some project management programming packages. Describes an in-house interface program developed to utilize a selected project management package (TIMELINE) by using Oracle Data Base Management System tools and Pascal programming language for the management of information system…

  2. 75 FR 68811 - Recovery Publication, P-395, Fire Management Assistance Grant Program (FMAGP) Guide

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-09

    ... DEPARTMENT OF HOMELAND SECURITY Federal Emergency Management Agency [Docket ID FEMA-2010-0066] Recovery Publication, P-395, Fire Management Assistance Grant Program (FMAGP) Guide AGENCY: Federal... Emergency Management Agency (FEMA) is accepting comments on the Fire Management Assistance Grant Program...

  3. "I've Actually Changed How I Live"-Patients' Long-Term Perceptions of a Cognitive Behavioral Pain Management Program.

    PubMed

    Egan, Aine; Lennon, Olive; Power, Camillus K; Fullen, Brona M

    2017-02-01

    To determine patients’ perceptions regarding cognitive behavioral pain management programs, and to determine what, if any, strategies learned on the program patients continue to use long-term to manage their pain. A qualitative, focus-group based study. An outpatient multidisciplinary pain management program in a university teaching hospital. Patients with chronic pain who had previously completed a 4-week cognitive behavioral pain management program (2001–2014). Sixteen patients attended one of four focus groups. A battery of semi-structured questions explored their perceptions of the cognitive behavioral program, and which strategies they found useful and continued to use long-term to manage their pain. Six key themes emerged: 1) universal long-term positive feedback on the utility of the program; 2) the program facilitated long-term changes in daily life; 3) participants now considered themselves as the “new me”; 4) request for more updates on emerging new treatments/pain knowledge; 5) recognizing that the key to maximizing gain from the program was to be open, to listen, and accept; and 6) participants sharing pain management knowledge with others in pain. There was universal positive feedback for the pain management program. Despite the years since they participated in one, patients continue to use key strategies to effectively manage their pain (pacing, relaxation), embedding them in their daily lives to maximize their quality of life.

  4. 77 FR 59879 - Idaho: Incorporation by Reference of Approved State Hazardous Waste Management Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-01

    ...: Incorporation by Reference of Approved State Hazardous Waste Management Program AGENCY: Environmental Protection... ``Approved State Hazardous Waste Management Programs,'' Idaho's authorized hazardous waste program. The EPA... Federal Register, the EPA is codifying and incorporating by reference the State's hazardous waste program...

  5. 76 FR 6594 - Florida: Final Authorization of State Hazardous Waste Management Program Revisions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-07

    ...: Final Authorization of State Hazardous Waste Management Program Revisions AGENCY: Environmental... of the changes to its hazardous waste program under the Resource Conservation and Recovery Act (RCRA... and State Programs Section, RCRA Programs and Materials Management Branch, RCRA Division, U.S...

  6. 77 FR 60963 - Tennessee: Final Authorization of State Hazardous Waste Management Program Revisions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-05

    ...: Final Authorization of State Hazardous Waste Management Program Revisions AGENCY: Environmental... of the changes to its hazardous waste program under the Resource Conservation and Recovery Act (RCRA... Johnson, Permits and State Programs Section, RCRA Programs and Materials Management Branch, RCRA Division...

  7. Does your equipment maintenance management program measure up?

    PubMed

    Deinstadt, Deborah C

    2003-01-01

    Identifying a clear maintenance philosophy is the first step toward choosing the right program for your healthcare organization. The second step is gaining a clear understanding of how proposed savings and improvements will be delivered. The third and last step is requiring that the proposed company or manager have specific tools in place for measuring and analyzing program performance. There are three primary philosophies underlying current equipment management options. These include risk-transfer philosophy (e.g., maintenance insurance, service contracts, multi-vendor and outsource programs), asset management philosophy (e.g., programs delivering a management system based on managed time-and-materials), and internal management (in-house managed programs). The last step in selecting the right program is insisting that proper performance measurements be built into the proposed management program. A well-managed program provides results in three general areas: financial outcomes, operational improvements and process improvements. Financial outcomes are the easiest to measure. Operational and process improvements are more challenging to assess but equally important to the program's overall success. To accurately identify results in these three areas, the overall management program should measure the following eight separate components: procedures and support for department staff; equipment inventory, benchmark costs, and budget guidelines; experienced equipment support team; objective, independent analysis of maintenance events; repair documentation and reporting; vendor relations; equipment acquisition analysis; and recommendations for improvement. Do everything you reasonably can to assure that the selected company can work side-by-side with you, providing objective, measurable advice that is ultimately in your best interest. You will then know that you have been thorough in your marketplace selection and can confidently move into implementation, expecting tangible and successful results.

  8. Small Business Management Volume IV: Final Report. An Adult Education Program. Development, Demonstration and Evaluation of Management Education Programs for Small Business Entrepreneurs, Including Minorities.

    ERIC Educational Resources Information Center

    Persons, Edgar A.; Swanson, Gordon I.

    The purpose of the small business management program is to help families improve the effectiveness of their business operation and enable them to reach family and business goals. Similar to a successful program in farm management education operational in Minnesota since 1952, the program includes classroom instruction, small group instruction,…

  9. 40 CFR 130.11 - Program management.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 23 2013-07-01 2013-07-01 false Program management. 130.11 Section 130... PLANNING AND MANAGEMENT § 130.11 Program management. (a) State agencies may apply for grants under sections 106, 205(j) and 205(g) to carry out water quality planning and management activities. Interstate...

  10. 40 CFR 130.11 - Program management.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 23 2012-07-01 2012-07-01 false Program management. 130.11 Section 130... PLANNING AND MANAGEMENT § 130.11 Program management. (a) State agencies may apply for grants under sections 106, 205(j) and 205(g) to carry out water quality planning and management activities. Interstate...

  11. 40 CFR 130.11 - Program management.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 22 2014-07-01 2013-07-01 true Program management. 130.11 Section 130... PLANNING AND MANAGEMENT § 130.11 Program management. (a) State agencies may apply for grants under sections 106, 205(j) and 205(g) to carry out water quality planning and management activities. Interstate...

  12. Multimodal Self-Management for Children: An Holistic Program for Teachers.

    ERIC Educational Resources Information Center

    O'Keefe, Edward J.

    This paper describes an innovative program for teaching self-management to children in elementary and secondary schools. The background of techniques for teaching self-management is briefly reviewed, the application of self-management techniques is noted, deficits in self-management programs are considered, and Lazarus's multimodal model of…

  13. Program Manager: Journal of the Defense Systems Management College. Volume 23, Number 1, January-February 1994

    DTIC Science & Technology

    1994-02-01

    Jones, Jr. PROGRAM MANAGER Managing Editor Esther M. Farria Art Director Greg Caruth Typography and Design Paula Croisetlere Program Manager (ISSN 0199...Company bombers to implement the strategic organization - President Clayton 1. Brukner commu- bombing doctrine. This would take all brand -new cre

  14. Management Development and Training Program for Colleges and Universities. Program Handbook, May 1978.

    ERIC Educational Resources Information Center

    Higher Education Management Inst., Coconut Grove, FL.

    A Management Development and Training Program has been developed by the Higher Education Management Institute to improve the overall functioning of higher education organizations. The Institute believes management development and training can: add to individuals' knowledge and skills, increase awareness of management processes and systems;…

  15. 40 CFR 130.11 - Program management.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 21 2010-07-01 2010-07-01 false Program management. 130.11 Section 130... PLANNING AND MANAGEMENT § 130.11 Program management. (a) State agencies may apply for grants under sections 106, 205(j) and 205(g) to carry out water quality planning and management activities. Interstate...

  16. 20 CFR 632.125 - Responsibilities of Native American grantees, subgrantees and contractors for preventing fraud...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ..., subgrantees and contractors for preventing fraud and program abuse and for general program management. 632.125... and for general program management. (a) Each Native American grantee shall establish and use internal program management procedures sufficient to prevent fraud and program abuse, including subgrantee and...

  17. 20 CFR 632.125 - Responsibilities of Native American grantees, subgrantees and contractors for preventing fraud...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., subgrantees and contractors for preventing fraud and program abuse and for general program management. 632.125... and for general program management. (a) Each Native American grantee shall establish and use internal program management procedures sufficient to prevent fraud and program abuse, including subgrantee and...

  18. Dimensions and Characteristics of Personnel Manager Perceptions of Effective Drug-Testing Programs.

    ERIC Educational Resources Information Center

    Gomez-Mejia, Luis R.; Balkin, David B.

    1987-01-01

    Examined characteristics of drug-testing programs that were associated with personnel managers' judgments of the programs' effectiveness using data gathered from human resource managers (N=190). Results showed drug-testing programs considered to be effective were supported by ancillary activities (such as employee assistance programs), targeted…

  19. Amy Schwab | NREL

    Science.gov Websites

    strategic scenario planning and analysis Program portfolio analysis Program management, planning and strategic execution Change management and operational improvement Research Interests Bioenergy supply chains management, organizational improvement, and program and project management. Prior Work Experience Consultant

  20. 77 FR 8219 - Coastal Zone Management Program: Illinois

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-14

    ... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration Coastal Zone Management Program: Illinois AGENCY: Office of Ocean and Coastal Resource Management (OCRM), National Oceanic and... of Decision (ROD) for Federal Approval of the Illinois Coastal Management Program (ICMP). SUMMARY...

  1. 23 CFR 511.305 - Policy.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION TRANSPORTATION INFRASTRUCTURE MANAGEMENT REAL-TIME SYSTEM MANAGEMENT INFORMATION PROGRAM Real-Time System Management Information Program § 511.305 Policy. This part establishes the provisions and parameters for the Real-Time System Management Information Program for State DOTs...

  2. 23 CFR 511.305 - Policy.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION TRANSPORTATION INFRASTRUCTURE MANAGEMENT REAL-TIME SYSTEM MANAGEMENT INFORMATION PROGRAM Real-Time System Management Information Program § 511.305 Policy. This part establishes the provisions and parameters for the Real-Time System Management Information Program for State DOTs...

  3. 23 CFR 511.305 - Policy.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION TRANSPORTATION INFRASTRUCTURE MANAGEMENT REAL-TIME SYSTEM MANAGEMENT INFORMATION PROGRAM Real-Time System Management Information Program § 511.305 Policy. This part establishes the provisions and parameters for the Real-Time System Management Information Program for State DOTs...

  4. 23 CFR 511.305 - Policy.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION TRANSPORTATION INFRASTRUCTURE MANAGEMENT REAL-TIME SYSTEM MANAGEMENT INFORMATION PROGRAM Real-Time System Management Information Program § 511.305 Policy. This part establishes the provisions and parameters for the Real-Time System Management Information Program for State DOTs...

  5. 48 CFR 919.7011 - Developmental assistance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... limited to: (1) Management guidance relating to: (i) Financial management, (ii) Organizational management, (iii) Overall business management planning, (iv) Business development, and (v) Marketing assistance; (2... PROGRAMS SMALL BUSINESS PROGRAMS The Department of Energy Mentor-Protege Program 919.7011 Developmental...

  6. 32 CFR 239.13 - Program Performance Reviews.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... will prepare monthly program performance reviews using the Homeowners Assistance Program Management Information System; HQUSACE Annual Management Command Plan and Management Control Checklist. In addition...

  7. Management Training, Yes! Excellence?

    ERIC Educational Resources Information Center

    Davis, Gary E.

    1990-01-01

    Management training programs are a necessity for transportation supervisors. Basic and advanced training programs are available through associations for business officials and university fleet management training programs. (MLF)

  8. 15 CFR 923.131 - General.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... the requirements for review of approved State coastal zone management (CZM) programs pursuant to... approved coastal zone management program or a portion of such program; and (d) Withdrawing program approval... AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT COASTAL...

  9. 15 CFR 923.131 - General.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... the requirements for review of approved State coastal zone management (CZM) programs pursuant to... approved coastal zone management program or a portion of such program; and (d) Withdrawing program approval... AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT COASTAL...

  10. Health plans' disease management programs: extending across the medical and behavioral health spectrum?

    PubMed

    Merrick, Elizabeth Levy; Horgan, Constance M; Garnick, Deborah W; Hodgkin, Dominic; Morley, Melissa

    2008-01-01

    Although the disease management industry has expanded rapidly, there is little nationally representative data regarding medical and behavioral health disease management programs at the health plan level. National estimates from a survey of private health plans indicate that 90% of health plan products offered disease management for general medical conditions such as diabetes but only 37% had depression programs. The frequency of specific depression disease management activities varied widely. Program adoption was significantly related to product type and behavioral health contracting. In health plans, disease management has penetrated more slowly into behavioral health and depression program characteristics are highly variable.

  11. Health Plans' Disease Management Programs: Extending across the Medical and Behavioral Health Spectrum?

    PubMed Central

    Merrick, Elizabeth Levy; Horgan, Constance M.; Garnick, Deborah W.; Hodgkin, Dominic; Morley, Melissa

    2015-01-01

    While the disease management industry has expanded rapidly, there is little nationally representative data regarding medical and behavioral health disease management programs at the health plan level. National estimates from a survey of private health plans indicate that 90% of health plan products offered disease management for general medical conditions such as diabetes, but only 37% had depression programs. The frequency of specific depression disease management activities varied widely. Program adoption was significantly related to product type and behavioral health contracting. In health plans, disease management has penetrated more slowly into behavioral health, and depression program characteristics are highly variable. PMID:18806594

  12. Overview of Medicaid capitation and case-management initiatives

    PubMed Central

    Freund, Deborah A.; Neuschler, Edward

    1986-01-01

    Case-management programs have grown in number and in acceptance in the Medicaid program since 1981. In this article, we review their structure and incentives as well as what is known about their impact on cost and use. These programs also have been difficult to implement, posing myriad management challenges for prepaid program managers and State administrators. We highlight the problems in the following areas: eligibility, enrollment, rate setting, and management information systems. PMID:10311923

  13. Disease management: findings from leading state programs.

    PubMed

    Wheatley, Ben

    2002-12-01

    Disease management programs are designed to contain costs by improving health among the chronically ill. More than 20 states are now engaged in developing and implementing Medicaid disease management programs for their primary care case management and fee-for-service populations.

  14. 76 FR 18220 - Labor-Management Cooperation Grant Program Information Collection Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-01

    ... FEDERAL MEDIATION AND CONCILIATION SERVICE Labor-Management Cooperation Grant Program Information... submission of the following public information collection request (ICR) to the Office of Management and...-13). This information collection, ``Labor-Management Cooperation Grant Program Information Collection...

  15. 78 FR 7477 - Multistate Corridor Operations and Management Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-01

    ... in the Multistate Corridor Operations and Management Program authorized by the Safe, Accountable... projects to improve multimodal transportation system management and operations. This notice seeks... Multistate Corridor Operations and Management (MCOM) programs and projects. The purpose of these investments...

  16. 15 CFR 923.80 - General.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT COASTAL ZONE MANAGEMENT PROGRAM REGULATIONS Amendments to and Termination of Approved Management Programs § 923... coastal state may amend or modify a management program which it has submitted and which has been approved...

  17. 15 CFR 923.80 - General.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT COASTAL ZONE MANAGEMENT PROGRAM REGULATIONS Amendments to and Termination of Approved Management Programs § 923... coastal state may amend or modify a management program which it has submitted and which has been approved...

  18. 15 CFR 930.61 - Public participation.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ..., individual State mailings, public notice through a management program newsletter, and electronic notices, e.g... MANAGEMENT FEDERAL CONSISTENCY WITH APPROVED COASTAL MANAGEMENT PROGRAMS Consistency for Activities Requiring... consistency under the policies of the management program; (2) Provide sufficient information to serve as a...

  19. 15 CFR 930.61 - Public participation.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., individual State mailings, public notice through a management program newsletter, and electronic notices, e.g... MANAGEMENT FEDERAL CONSISTENCY WITH APPROVED COASTAL MANAGEMENT PROGRAMS Consistency for Activities Requiring... consistency under the policies of the management program; (2) Provide sufficient information to serve as a...

  20. 15 CFR 930.61 - Public participation.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ..., individual State mailings, public notice through a management program newsletter, and electronic notices, e.g... MANAGEMENT FEDERAL CONSISTENCY WITH APPROVED COASTAL MANAGEMENT PROGRAMS Consistency for Activities Requiring... consistency under the policies of the management program; (2) Provide sufficient information to serve as a...

  1. 15 CFR 930.61 - Public participation.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., individual State mailings, public notice through a management program newsletter, and electronic notices, e.g... MANAGEMENT FEDERAL CONSISTENCY WITH APPROVED COASTAL MANAGEMENT PROGRAMS Consistency for Activities Requiring... consistency under the policies of the management program; (2) Provide sufficient information to serve as a...

  2. 15 CFR 930.61 - Public participation.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ..., individual State mailings, public notice through a management program newsletter, and electronic notices, e.g... MANAGEMENT FEDERAL CONSISTENCY WITH APPROVED COASTAL MANAGEMENT PROGRAMS Consistency for Activities Requiring... consistency under the policies of the management program; (2) Provide sufficient information to serve as a...

  3. 48 CFR 1819.7205 - Mentor-protégé agreements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... in— (i) General business management, including organizational management, financial management, personnel management, marketing, business development, and overall business planning; (ii) Engineering... ADMINISTRATION SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS NASA Mentor-Protégé Program 1819.7205 Mentor...

  4. The efficacy of a combined oral formulation of derquantel-abamectin against anthelmintic resistant gastro-intestinal nematodes of sheep in the UK.

    PubMed

    Geurden, Thomas; Hodge, Andrew; Noé, Laura; Winstanley, Dana; Bartley, David J; Taylor, Mike; Morgan, Colin; Fraser, Sarah J; Maeder, Steven; Bartram, David

    2012-10-26

    The objective of the present studies was to evaluate the efficacy of a combined formulation (Startect(®) Dual Active Oral Solution for Sheep, Pfizer Animal Health) of derquantel (DQL) and abamectin (ABA) for the treatment of: (1) sheep experimentally infected with a moxidectin (MOX)-resistant isolate of Teladorsagia circumcincta, and (2) multi-drug resistant gastrointestinal nematode parasites under UK field conditions. In the first study, a total of 40 animals were allocated into 4 treatment groups, and were either left untreated or treated with DQL+ABA, MOX or ABA. Faecal samples were collected on days 1-5 and on day 7 after treatment to examine the reduction in faecal egg excretion and to evaluate the egg viability. On day 14 post treatment all animals were euthanised for abomasal worm counts. There was a 100% reduction in geometric mean worm counts for the DQL+ABA treated animals compared to the untreated control animals (P<0.0001), whereas the percentage reduction in worm counts for the MOX- (P>0.05) and ABA-treated (P=0.0004) animals was 12.4% and 71.8%, respectively. The data from the egg hatch assay (EHA) indicated that in the MOX-treated and the ABA-treated animals, the majority of the eggs hatched after treatment. In the field study, performed on four farms, animals were allocated into 6 groups of 11-15 animals each in order to conduct a faecal egg count reduction test (FECRT), based on arithmetic mean egg counts. One group of animals remained untreated, whereas the other animals were treated with DQL+ABA, MOX, fenbendazole (FBZ), levamisole (LV) or ivermectin (IVM). On each of the farms the reduction in egg excretion after treatment with FBZ, LV or IVM was below 95.0%, indicating anthelmintic resistance. The efficacy of DQL+ABA ranged from 99.1 to 100%, yielding significantly lower egg counts compared to the untreated control group (P ≤ 0.003). For MOX the egg counts were significantly (P ≤ 0.003) lower compared to the untreated group at each farm, with reductions varying from 98.2 to 100%. The post-treatment copro-cultures for larva identification indicated that T. circumcincta was the most abundant worm species after treatment (52-99% of the larvae). The results of these studies confirm the high efficacy of the DQL+ABA combination formulation against anthelmintic resistant nematodes in the UK. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. 45 CFR 74.20 - Purpose of financial and program management.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Purpose of financial and program management. 74.20... Management § 74.20 Purpose of financial and program management. Sections 74.21 through 74.28 prescribe standards for financial management systems, methods for making payments, and rules for satisfying cost...

  6. 41 CFR 105-72.300 - Purpose of financial and program management.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Purpose of financial and.../Financial and Program Management § 105-72.300 Purpose of financial and program management. Sections 105-72.301 through 105-72.308 prescribe standards for financial management systems, methods for making...

  7. Designing an Academic Project Management Program: A Collaboration between a University and a PMI Chapter

    ERIC Educational Resources Information Center

    Poston, Robin S.; Richardson, Sandra M.

    2011-01-01

    The demand for project management skills in industry is increasing resulting in a higher demand for project management educational programs. Universities are addressing industry demand by developing project management courses, degree offerings and certificate programs that focus on both technical and general project management skills. While…

  8. 44 CFR 204.25 - FEMA-State agreement for fire management assistance grant program.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... GRANT PROGRAM Declaration Process § 204.25 FEMA-State agreement for fire management assistance grant... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false FEMA-State agreement for fire management assistance grant program. 204.25 Section 204.25 Emergency Management and Assistance FEDERAL...

  9. 44 CFR 204.25 - FEMA-State agreement for fire management assistance grant program.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... GRANT PROGRAM Declaration Process § 204.25 FEMA-State agreement for fire management assistance grant... 44 Emergency Management and Assistance 1 2014-10-01 2014-10-01 false FEMA-State agreement for fire management assistance grant program. 204.25 Section 204.25 Emergency Management and Assistance FEDERAL...

  10. 44 CFR 204.25 - FEMA-State agreement for fire management assistance grant program.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... GRANT PROGRAM Declaration Process § 204.25 FEMA-State agreement for fire management assistance grant... 44 Emergency Management and Assistance 1 2011-10-01 2011-10-01 false FEMA-State agreement for fire management assistance grant program. 204.25 Section 204.25 Emergency Management and Assistance FEDERAL...

  11. 44 CFR 204.25 - FEMA-State agreement for fire management assistance grant program.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... GRANT PROGRAM Declaration Process § 204.25 FEMA-State agreement for fire management assistance grant... 44 Emergency Management and Assistance 1 2012-10-01 2011-10-01 true FEMA-State agreement for fire management assistance grant program. 204.25 Section 204.25 Emergency Management and Assistance FEDERAL...

  12. 44 CFR 204.25 - FEMA-State agreement for fire management assistance grant program.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... GRANT PROGRAM Declaration Process § 204.25 FEMA-State agreement for fire management assistance grant... 44 Emergency Management and Assistance 1 2013-10-01 2013-10-01 false FEMA-State agreement for fire management assistance grant program. 204.25 Section 204.25 Emergency Management and Assistance FEDERAL...

  13. Clinical program leadership: skill requirements for contemporary leaders.

    PubMed

    Spallina, Joseph M

    2002-01-01

    With knowledge of these leadership requirements and a shrinking base of experienced managers, healthcare organizations and professional societies have little choice in their approach to prepare for the leadership development challenges of the future. Organizations will focus leadership development, training, and continuing management education on integrating business tools and skills into clinical program management. The management requirements for clinical programs will continue to grow in complexity and the number of qualified managers will continue to diminish, New approaches to solving this shortage will evolve. Professional, forprofit companies, healthcare provider organizations, and academic programs will develop clinical program management training tracks. Organizations that create solutions to this management imperative will maintain their competitive edge in the challenging times that will greet the industry in the future.

  14. Reflections on Case Management in Youth Support Using a Program Example

    ERIC Educational Resources Information Center

    Kennedy, Rosemary; Kennedy, Barry

    2010-01-01

    Using Moxley's (1997) program development framework as an agenda for a dialogue that juxtaposes an academic perspective with that of a seasoned youth program manager, this paper focuses on the relatively unexplored terrain of case management programs. In doing so, it exposes the convergences and divergences between academic and program manager…

  15. 75 FR 136 - Privacy Act of 1974; Systems of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-04

    ..., management of students in civilian institution programs, and course management for civil engineering... civilian institution programs, and course management for civil engineering education programs. Also...

  16. 13 CFR 124.701 - What is the purpose of the 7(j) management and technical assistance program?

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...) management and technical assistance program? 124.701 Section 124.701 Business Credit and Assistance SMALL...) Business Development Management and Technical Assistance Program § 124.701 What is the purpose of the 7(j) management and technical assistance program? Section 7(j)(1) of the Small Business Act, 15 U.S.C. 636(j)(1...

  17. Impact of a disability management program on employee productivity in a petrochemical company.

    PubMed

    Skisak, Christopher M; Bhojani, Faiyaz; Tsai, Shan P

    2006-05-01

    An inhouse disability management program was implemented to reduce nonoccupational absences in a petrochemical corporation. The program was administered by full-time certified, corporate-based case managers and nine manufacturing location nurses. Employees were required to report all absences on the first day and again on the fourth workday of absence. A medical certification form was required for absences of 4 or more working days. Extended absences were actively managed. An Internet-based case management tool, Medgate, was used as a primary management tool. Results were compared with the previous year among the target population and with company business units not participating in the program. The program resulted in a 10% reduction in total absence days per employee (6.9 to 6.2) compared with the previous year, whereas business units not using the program had an 8% increase (5.5 to 5.9). This disability management program resulted in a more than four to one return on investment based on direct expenditures and cost savings in terms of reduced absence days. The inhouse disability management program was successful by absence duration, employee satisfaction, and return on investment criteria.

  18. The Air Program Information Management System (APIMS)

    DTIC Science & Technology

    2011-11-02

    Technology November 2, 2011 The Air Program Information Management System (APIMS) Frank Castaneda, III, P.E. APIMS Program Manager AFCEE/TDNQ APIMS...NOV 2011 2. REPORT TYPE 3. DATES COVERED 00-00-2011 to 00-00-2011 4. TITLE AND SUBTITLE The Air Program Information Management System (APIMS... Information   Management   System : Sustainability of  Enterprise air quality management system • Aspects and Impacts to Process • Auditing and Measurement

  19. 24 CFR 880.601 - Responsibilities of owner.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... DISABILITIES PROGRAM) SECTION 8 HOUSING ASSISTANCE PAYMENTS PROGRAM FOR NEW CONSTRUCTION Management § 880.601... units. (b) Management and maintenance. The owner is responsible for all management functions, including... financial interest and to uphold its program responsibilities where no alternative management agent is...

  20. 24 CFR 880.601 - Responsibilities of owner.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... DISABILITIES PROGRAM) SECTION 8 HOUSING ASSISTANCE PAYMENTS PROGRAM FOR NEW CONSTRUCTION Management § 880.601... units. (b) Management and maintenance. The owner is responsible for all management functions, including... financial interest and to uphold its program responsibilities where no alternative management agent is...

  1. 24 CFR 880.601 - Responsibilities of owner.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... DISABILITIES PROGRAM) SECTION 8 HOUSING ASSISTANCE PAYMENTS PROGRAM FOR NEW CONSTRUCTION Management § 880.601... units. (b) Management and maintenance. The owner is responsible for all management functions, including... financial interest and to uphold its program responsibilities where no alternative management agent is...

  2. 24 CFR 880.601 - Responsibilities of owner.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... DISABILITIES PROGRAM) SECTION 8 HOUSING ASSISTANCE PAYMENTS PROGRAM FOR NEW CONSTRUCTION Management § 880.601... units. (b) Management and maintenance. The owner is responsible for all management functions, including... financial interest and to uphold its program responsibilities where no alternative management agent is...

  3. 20 CFR 633.311 - Management information systems.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Management information systems. 633.311... AND SEASONAL FARMWORKER PROGRAMS Program Design and Administrative Procedures § 633.311 Management information systems. All grantees shall establish and maintain a program and financial management system which...

  4. 20 CFR 633.311 - Management information systems.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Management information systems. 633.311... AND SEASONAL FARMWORKER PROGRAMS Program Design and Administrative Procedures § 633.311 Management information systems. All grantees shall establish and maintain a program and financial management system which...

  5. 20 CFR 633.311 - Management information systems.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false Management information systems. 633.311... AND SEASONAL FARMWORKER PROGRAMS Program Design and Administrative Procedures § 633.311 Management information systems. All grantees shall establish and maintain a program and financial management system which...

  6. 76 FR 58077 - RTCA Program Management Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-19

    ... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration RTCA Program Management Committee AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of RTCA Program Management Committee... Management Committee. DATES: The meeting will be held September 28, 2011 from 8:30 a.m. to 1:30 p.m...

  7. 75 FR 52590 - RTCA Program Management Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-26

    ... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration RTCA Program Management Committee AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of RTCA Program Management Committee... Management Committee. DATES: The meeting will be held September 15, 2010 from 8:30 a.m. to 1:30 p.m...

  8. 76 FR 27743 - RTCA Program Management Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-12

    ... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration RTCA Program Management Committee AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of RTCA Program Management Committee... Management Committee. DATES: The meeting will be held May 26, 2011 from 12 p.m. to 1 p.m. ADDRESSES: The...

  9. Effective Program Management: A Cornerstone of Malaria Elimination

    PubMed Central

    Gosling, Jonathan; Case, Peter; Tulloch, Jim; Chandramohan, Daniel; Wegbreit, Jennifer; Newby, Gretchen; Gueye, Cara Smith; Koita, Kadiatou; Gosling, Roly

    2015-01-01

    Effective program management is essential for successful elimination of malaria. In this perspective article, evidence surrounding malaria program management is reviewed by management science and malaria experts through a literature search of published and unpublished gray documents and key informant interviews. Program management in a malaria elimination setting differs from that in a malaria control setting in a number of ways, although knowledge and understanding of these distinctions are lacking. Several core features of successful health program management are critical to achieve elimination, including effective leadership and supervision at all levels, sustained political and financial commitment, reliable supply and control of physical resources, effective management of data and information, appropriate incentives, and consistent accountability. Adding to the complexity, the requirements of an elimination program may conflict with those of a control regimen. Thus, an additional challenge is successfully managing program transitions along the continuum from control to elimination to prevention of reintroduction. This article identifies potential solutions to these challenges by exploring managerial approaches that are flexible, relevant, and sustainable in various cultural and health system contexts. PMID:26013372

  10. Guide for Operational Configuration Management Program including the adjunct programs of design reconstitution and material condition and aging management. Part 2

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

    Not Available

    This standard presents program criteria and implementation guidance for an operational configuration management program for DOE nuclear and non-nuclear facilities. This Part 2 includes chapters on implementation guidance for operational configuration management, implementation guidance for design reconstitution, and implementation guidance for material condition and aging management. Appendices are included on design control, examples of design information, conduct of walkdowns, and content of design information summaries.

  11. Cardiovascular self-management support program for preventing cardiovascular complication behaviors and clinical outcomes in the elderly with poorly controlled type 2 diabetes mellitus in Indonesia: A pilot study.

    PubMed

    Hisni, Dayan; Rukmaini, Rukmaini; Saryono, Saryono; Chinnawong, Tippamas; Thaniwattananon, Ploenpit

    2018-03-06

    The aim of the study was to determine the feasibility, and to evaluate the effect of, a cardiovascular self-management support program by applying the 5A's self-management support program on preventing cardiovascular complication behaviors and to assess the clinical outcomes in the elderly with poorly controlled type 2 diabetes mellitus (DM). This pilot study used a quasi-experimental study design. Twelve elderly persons with poorly controlled type 2 DM were assigned into either a control or experimental group, with six participants in each group. The Preventing Cardiovascular Complication Behaviors (PCCB) was measured by the Preventing Cardiovascular Complication Behaviors Questionnaire, while the clinical outcomes were measured by clinical devices that were provided. These measurements were conducted and compared at baseline and 6 weeks after the completion of the program. The self-management support program was a 6 week program with several implementation methods, based on the 5A's self-management support program. The participants who received the cardiovascular self-management support program reported a significant improvement in their PCCB and clinical outcomes, compared to those receiving the usual care. This study revealed that a cardiovascular self-management support program that applies the 5A's self-management support program is feasible for implementation. © 2018 Japan Academy of Nursing Science.

  12. Issues in NASA program and project management

    NASA Technical Reports Server (NTRS)

    Hoffman, Edward J. (Editor)

    1994-01-01

    This volume is the eighth in an ongoing series addressing current topics and lessons learned in NASA program and project management. Articles in this volume cover the following topics: (1) power sources for the Galileo and Ulysses Missions; (2) managing requirements; (3) program control of the Tropical Rainfall Measuring Mission; (4) project management method; (5) career development for project managers; and (6) resources for NASA managers.

  13. Improving Voluntary Environmental Management Programs: Facilitating Learning and Adaptation

    NASA Astrophysics Data System (ADS)

    Genskow, Kenneth D.; Wood, Danielle M.

    2011-05-01

    Environmental planners and managers face unique challenges understanding and documenting the effectiveness of programs that rely on voluntary actions by private landowners. Programs, such as those aimed at reducing nonpoint source pollution or improving habitat, intend to reach those goals by persuading landowners to adopt behaviors and management practices consistent with environmental restoration and protection. Our purpose with this paper is to identify barriers for improving voluntary environmental management programs and ways to overcome them. We first draw upon insights regarding data, learning, and adaptation from the adaptive management and performance management literatures, describing three key issues: overcoming information constraints, structural limitations, and organizational culture. Although these lessons are applicable to a variety of voluntary environmental management programs, we then present the issues in the context of on-going research for nonpoint source water quality pollution. We end the discussion by highlighting important elements for advancing voluntary program efforts.

  14. The relative effectiveness of self-management programs for type 2 diabetes.

    PubMed

    McGowan, Patrick

    2015-10-01

    The objectives of the study were to investigate the effectiveness of 2 types of peer-led self-management programs in bringing about improvements in subjects with type 2 diabetes mellitus and to determine whether there were differences in effectiveness between the 2 programs. The study used a 3-arm randomized controlled trial design with clinical measures taken at baseline and at 6 and 12 months post-program. In total, 405 persons completed baseline questionnaires and were randomly allocated to a diabetes self-management program (n=130), to a general self-management program (n=109) or to a control group (n=122). A 2-way factorial analyses of variance was employed as the primary statistical analysis. The findings showed that the self-management programs had affected 5 of the 30 measures: fatigue, cognitive symptom management, self-efficacy with regard to the disease in general, communication with physician, and the score on the Diabetes Empowerment Scale. In addition, 3 variables-social role limitations, total hospital nights and glycated hemoglobin levels-showed marginally significant interaction effects. The second analysis found similar results, with 4 of the 5 measures remaining statistically significant: fatigue, cognitive symptom management, communication with physician and diabetes empowerment, with neither program being more effective than the other. The major findings are that although both programs were effective in bringing about positive changes in the outcome measures, there was little difference in effectiveness between the Diabetes Self-Management Program and the Chronic Disease Self-Management Program. This finding is consistent with the principle that behaviour-change strategies using self-efficacy are key components in health education programs. Copyright © 2015 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

  15. German diabetes management programs improve quality of care and curb costs.

    PubMed

    Stock, Stephanie; Drabik, Anna; Büscher, Guido; Graf, Christian; Ullrich, Walter; Gerber, Andreas; Lauterbach, Karl W; Lüngen, Markus

    2010-12-01

    This paper reports the results of a large-scale analysis of a nationwide disease management program in Germany for patients with diabetes mellitus. The German program differs markedly from "classic" disease management in the United States. Although it combines important hallmarks of vendor-based disease management and the Chronic Care Model, the German program is based in primary care practices and carried out by physicians, and it draws on their personal relationships with patients to promote adherence to treatment goals and self-management. After four years of follow-up, overall mortality for patients and drug and hospital costs were all significantly lower for patients who participated in the program compared to other insured patients with similar health profiles who were not in the program. These results suggest that the German disease management program is a successful strategy for improving chronic illness care.

  16. About the Federal Energy Management Program

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

    Richard Kidd

    2009-04-23

    Richard Kidd, Program Manager for the Federal Energy Management Program (FEMP), presents a discussion on FEMP direction and its future role, federal funding trends, future financing trends, and Earth Day observations.

  17. 15 CFR 14.20 - Purpose of financial and program management.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...-PROFIT, AND COMMERCIAL ORGANIZATIONS Post-Award Requirements Financial and Program Management § 14.20 Purpose of financial and program management. Sections 14.21 through 14.28 prescribe standards for financial management systems, methods for making payments and rules for: satisfying cost sharing and...

  18. 77 FR 28854 - Proposed Information Collection; Comment Request; Coastal Zone Management Program Administration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-16

    ... federally approved coastal management programs; complete information for the Coastal Zone Management Program.... Gwellnar Banks, Management Analyst, Office of the Chief Information Officer. [FR Doc. 2012-11777 Filed 5-15... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration Proposed Information...

  19. 48 CFR 2801.603-1 - Department of Justice Acquisition Career Management Program.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Representatives, or equivalent positions. (c) The program shall include: (1) Management information system... acquisition workforce management information system. (2) Individual assessments and development plans for... Acquisition Career Management Program. 2801.603-1 Section 2801.603-1 Federal Acquisition Regulations System...

  20. 76 FR 65561 - Multistate Corridor Operations and Management Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-21

    ... participation in the Multistate Corridor Operations and Management (MCOM) Program authorized by the Safe... transportation system management and operations. This notice seeks applications for available fiscal year (FY... system management and operations. Since the MCOM program is funded by the DOT Intelligent Transportation...

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