Budget impact analysis of darbepoetin alfa every 3 weeks versus epoetin alfa every week for the treatment of chemotherapy-induced anaemia from a US payer's perspective.

PubMed

Rubin, Robert J; Glaspy, John A; Adams, John L; Mafilios, Michael S; Wang, Sharon M; Viswanathan, Hema N; Kallich, Joel D

2008-01-01

This analysis was conducted to compare the direct medical costs of treatment with darbepoetin alfa every 3 weeks (Q3W) and epoetin alfa every week (QW) in patients with chemotherapy-induced anaemia (CIA) from the payer's perspective. An analysis was conducted from a US health plan perspective to compare the annual budget impact for CIA with darbepoetin alfa Q3W and epoetin alfa QW over a 16-week treatment period. Dosing regimens were obtained from registration clinical trials. Mean doses, including dose adjustments, were 375.6 microg Q3W for darbepoetin alfa and 43,187 U QW for epoetin alfa. Costs of medical resources included drug acquisition and administration costs. The base case analysis resulted in a per-patient budget impact of $8,544 and $8,667 for darbepoetin alfa and epoetin alfa, respectively. Per member per month cost was $0.90 for darbepoetin alfa and $0.91 for epoetin alfa, based on an estimate of 2,735 CIA patients in a health plan population of 2.17 million. The analysis was most sensitive to drug dose, treatment period and drug price. Results suggest that per-patient direct medical costs of CIA treatment, when initiated at labelled starting doses, are comparable for darbepoetin alfa Q3W and epoetin alfa QW.

Middle East Economics and Development, Spring 2008 - Project 08-02

DTIC Science & Technology

2008-05-01

a Proportional Representation Electoral System .................................. 145 Table 10: Iran’s Macroeconomic Indicators ( Source : CIA World...Fact Book) ........................... 165 Table 11: Iran’s Trading Partners ( Source : CIA World Fact Book... Sources of Electricity in Afghanistan – 2007................................................................ 29 Figure 3: Ethno-linguistic Groups in

Collagen-induced arthritis as an animal model of rheumatoid cachexia.

PubMed

Alabarse, Paulo V G; Lora, Priscila S; Silva, Jordana M S; Santo, Rafaela C E; Freitas, Eduarda C; de Oliveira, Mayara S; Almeida, Andrelise S; Immig, Mônica; Teixeira, Vivian O N; Filippin, Lidiane I; Xavier, Ricardo M

2018-03-25

Rheumatoid arthritis is characterized by chronic polyarticular synovitis and presents systemic changes that impact quality of life, such as impaired muscle function, seen in up to 66% of the patients. This can progress to severely debilitating state known as rheumatoid cachexia-without loss of fat mass and body weight-for which there is little consensus in terms of diagnosis or treatment. This study aims to evaluate whether the collagen-induced arthritis (CIA) animal model also develops clinical and functional features characteristic of rheumatoid cachexia. Male DBA1/J mice were randomly divided into 2 groups: healthy animals (CO, n = 11) and CIA animals (n = 13). The clinical score and edema size, animal weight and food intake, free exploratory locomotion, grip strength, and endurance exercise performance were tested 0, 18, 35, 45, 55, and 65 days after disease induction. After euthanasia, several organs, visceral and brown fat, and muscles were dissected and weighed. Muscles were used to assess myofiber diameter. Ankle joint was used to assess arthritis severity by histological score. Statistical analysis were performed using one-way and two-way analyses of variance followed by Tukey's and Bonferroni's test or t-test of Pearson and statistical difference were assumed for a P value under 0.05. The CIA had significantly higher arthritis scores and larger hind paw edema volumes than CO. The CIA had decreased endurance exercise performance total time (fatigue; 23, 22, 24, and 21% at 35, 45, 55, and 65 days, respectively), grip strength (27, 55, 63, 60, and 66% at 25, 35, 45, 55, and 65 days, respectively), free locomotion (43, 57, 59, and 66% at 35, 45, 55, and 65 days, respectively), and tibialis anterior and gastrocnemius muscle weight (25 and 24%, respectively) compared with CO. Sarcoplasmic ratios were also reduced in CIA (TA: 23 and GA: 22% less sarcoplasmic ratio), confirming the atrophy of skeletal muscle mass in these animals than in CO. Myofiber diameter was also reduced 45% in TA and 41% in GA in CIA when compared with the CO. Visceral and brown fat were lighter in CIA (54 and 39%, respectively) than CO group. The CIA model is a valid experimental model for rheumatoid cachexia given that the clinical changes observed were similar to those described in patients with rheumatoid arthritis. © 2018 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.

Eating Disorder Examination Questionnaire (EDE-Q) and Clinical Impairment Assessment (CIA): clinical norms and functional impairment in male and female adults with eating disorders.

PubMed

Dahlgren, Camilla Lindvall; Stedal, Kristin; Rø, Øyvind

2017-05-01

The aim of the current study was to collect clinical normative data for the Clinical Impairment Assessment questionnaire (CIA) and the Eating Disorder Examination Questionnaire (EDE-Q) from adult patients with eating disorders (EDs). This study also examined unique contributions of eating disorder (ED) symptoms on levels of ED-related impairment. A sample of 667 patients, 620 females and 47 males, was recruited from six specialist centres across Norway. The majority of the sample (40.3%) was diagnosed with eating disorder not otherwise specified (EDNOS), 34.5% had bulimia nervosa (BN), and 25.2% were diagnosed with anorexia nervosa (AN). There were significant differences for global EDE-Q and CIA scores between females and males. In the female sample, significant differences were found on several EDE-Q sub-scales between the AN and BN group, and between the AN and EDNOS group. No significant differences were found between the diagnostic groups on the CIA. In the male sample, no significant differences were found between diagnostic groups on the EDE-Q or CIA. A multiple regression analysis revealed that 46.8% of the variance in impairment as measured by the CIA was accounted for by ED symptoms. Body mass index, Eating Concern, Shape/Weight Concern, and binge eating served as significant, unique predictors of impairment. The results from the present study contribute to the interpretation of EDE-Q and CIA scores in ED samples.

Potent Antiarthritic Properties of Phloretin in Murine Collagen-Induced Arthritis.

PubMed

Wang, Shun-Ping; Lin, Shih-Chao; Li, Shiming; Chao, Ya-Hsuan; Hwang, Guang-Yuh; Lin, Chi-Chen

2016-01-01

In the exploration of potential therapeutic agents for rheumatoid arthritis (RA), DBA/1J mice are used as the RA model of collagen-induced arthritis (CIA). Phloretin, a flavonoid compound extracted from Prunus mandshurica , has been found to exhibit anti-inflammatory activity, making it a potential candidate for treatment of RA. The objective of this study was to evaluate the therapeutic effects of phloretin on CIA mice. CIA mice were dosed daily with phloretin at either 50 or 100 mg/kg among two treatment groups. CIA treated mice showed mitigation of clinical symptoms of RA in addition to reduced inflammation of hind-limbs compared to mice who did not receive phloretin. Histological analysis showed that phloretin suppressed the severity of RA and effectively mitigated joint inflammation and cartilage- and bone-destruction via reducing proinflammatory cytokine productions (TNF- α , IL-6, IL-1 β , and IL-17). This was at least partially mediated by causing inadequate splenocyte activation and proliferation. Moreover, phloretin-treated CIA mice showed decreased oxidative stress and diminished levels of malondialdehyde (MDA) and hydrogen peroxide (H 2 O 2 ) in paw tissues as well as reduced productivity of anti-collagen antibodies in serum. We have concluded that phloretin could be a potent and effective antiarthritis agent, demonstrating anti-inflammatory, antioxidative, and immunomodulatory effects in CIA mice.

Low-cost and eco-friendly nebulizer spray coated CuInAlS2 counter electrode for dye-sensitized solar cells

NASA Astrophysics Data System (ADS)

Dhas, C. Ravi; Christy, A. Jennifer; Venkatesh, R.; Esther Santhoshi Monica, S.; Panda, Subhendu K.; Subramanian, B.; Ravichandran, K.; Sudhagar, P.; Raj, A. Moses Ezhil

2018-05-01

CuInAlS2 thin films for different substrate temperatures were deposited by a novel nebulizer spray technique. The polycrystalline CIAS thin film exhibited tetragonal structure with the preferential orientation of (1 1 2) plane. Nanoflakes were observed from the surface morphology of CIAS film. The peak position of core level spectra confirms the presence of CuInAlS2 from XPS analysis. The absorbance spectra and optical band gap were observed from the optical property. The activation energy, carrier concentration, hole mobility and resistivity were determined by linear four probe and Hall effect measurements. The CIAS film was used as a counter electrode (CE) in dye-sensitized solar cells (DSSCs) and is characterized by cyclic voltammetry, electrochemical impedance spectroscopy and Tafel measurements. DSSC fabricated with the CIAS CE achieved the photo conversion efficiency of about 2.55%.

Farmácia Popular Program: pharmaceutical market analysis of antihypertensive acting on the renin-angiotensin system medicines.

PubMed

Silva, Rondineli Mendes da; Chaves, Gabriela Costa; Chaves, Luisa Arueira; Campos, Mônica Rodrigues; Luiza, Vera Lucia; Bertoldi, Andréa Dâmaso; Ross-Degnan, Dennis; Emmerick, Isabel Cristina Martins

2017-08-01

This paper aims to analyse changes in the retail pharmaceutical market following policy changes in the Farmácia Popular Program (FP), a medicines subsidy program in Brazil. The retrospective longitudinal analyses focus on therapeutic class of agents acting on the renin-angiotensin system. Data obtained from QuintilesIMS (formerly IMS Health) included private retail pharmacy sales volume (pharmaceutical units) and sales values from 2002 to 2013. Analyses evaluated changes in market share following key FP policy changes. The therapeutic class was selected due to its relevance to hypertension treatment. Market share was analysed by therapeutic sub-classes and by individual company. Losartan as a single product accounted for the highest market share among angiotensin II antagonists. National companies had higher sales volume during the study period, while multinational companies had higher sales value. Changes in pharmaceutical market share coincided with the inclusion of specific products in the list of medicines covered by FP and with increases in or exemption from patient copayment.

Command Interface ASIC - Analog Interface ASIC Chip Set

NASA Technical Reports Server (NTRS)

Ruiz, Baldes; Jaffe, Burton; Burke, Gary; Lung, Gerald; Pixler, Gregory; Plummer, Joe; Katanyoutanant,, Sunant; Whitaker, William

2003-01-01

A command interface application-specific integrated circuit (ASIC) and an analog interface ASIC have been developed as a chip set for remote actuation and monitoring of a collection of switches, which can be used to control generic loads, pyrotechnic devices, and valves in a high-radiation environment. The command interface ASIC (CIA) can be used alone or in combination with the analog interface ASIC (AIA). Designed primarily for incorporation into spacecraft control systems, they are also suitable for use in high-radiation terrestrial environments (e.g., in nuclear power plants and facilities that process radioactive materials). The primary role of the CIA within a spacecraft or other power system is to provide a reconfigurable means of regulating the power bus, actuating all valves, firing all pyrotechnic devices, and controlling the switching of power to all switchable loads. The CIA is a mixed-signal (analog and digital) ASIC that includes an embedded microcontroller with supporting fault-tolerant switch control and monitoring circuitry that is capable of connecting to a redundant set of interintegrated circuit (I(sup 2)C) buses. Commands and telemetry requests are communicated to the CIA. Adherence to the I(sup 2)C bus standard helps to reduce development costs by facilitating the use of previously developed, commercially available components. The AIA is a mixed-signal ASIC that includes the analog circuitry needed to connect the CIA to a custom higher powered version of the I(sup 2)C bus. The higher-powered version is designed to enable operation with bus cables longer than those contemplated in the I(sup 2)C standard. If there are multiple higher-power I(sup 2)C-like buses, then there must an AIA between the CIA and each such bus. The AIA includes two identical interface blocks: one for the side-A I(sup 2)C clock and data buses and the other for the side B buses. All the AIAs on each side are powered from a common power converter module (PCM). Sides A and B of the I(sup 2)C buses are electrically isolated from each other (see figure). They are also isolated from the CIA by use of transformer coupling of signals between the AIA blocks and the CIA.

Collagen-induced arthritis increases inducible nitric oxide synthase not only in aorta but also in the cardiac and renal microcirculation of mice.

PubMed

Palma Zochio Tozzato, G; Taipeiro, E F; Spadella, M A; Marabini Filho, P; de Assis, M R; Carlos, C P; Girol, A P; Chies, A B

2016-03-01

Rheumatoid arthritis (RA) may promote endothelial dysfunction. This phenomenon requires further investigation, especially in collagen-induced arthritis (CIA), as it is considered the experimental model most similar to RA. The objectives of this study were to identify CIA-induced changes in noradrenaline (NE) and acetylcholine (ACh) responses in mice aortas that may suggest endothelial dysfunction in these animals. Moreover, we characterize CIA-induced modifications in inducible nitric oxide synthase (iNOS) expression in the aortas and cardiac and renal tissues taken from these mice that may be related to possible endothelial dysfunction. Male DBA/1J mice were immunized with 100 μg of emulsified bovine collagen type II (CII) plus complete Freund's adjuvant. Twenty-one days later, these animals received a boost of an additional 100 μg plus incomplete Freund's adjuvant. Fifteen days after the onset of the disease, aortic rings from CIA and control mice were challenged with NE and ACh in an organ bath. In these animals, iNOS was detected through immunohistochemical analysis of aorta, heart and kidneys. Plasma nitrite concentration was determined using the Griess reaction. CIA did not change NE or ACh responses in mice aorta but apparently increased the iNOS expression not only in aorta, but also in cardiac and renal microcirculation. In parallel, CIA reduced nitrite plasma concentration. In mice, CIA appears to increase the presence of iNOS in aorta, as well as in heart and in kidney microcirculation. This iNOS increase occurs apparently in parallel to a reduction of the bioavailability of NO. This phenomenon does not appear to change NE or ACh responses in aorta. © 2015 British Society for Immunology, Clinical and Experimental Immunology.

Prognostic Effects of Adjuvant Chemotherapy-Induced Amenorrhea and Subsequent Resumption of Menstruation for Premenopausal Breast Cancer Patients.

PubMed

Jeon, Se Jeong; Lee, Jae Il; Jeon, Myung Jae; Lee, Maria

2016-04-01

Chemotherapy-induced amenorrhea (CIA) is a side effect that occurs in patients with breast cancer (BC) as a result of chemotherapy. These patients require special treatments to avoid infertility and menopause. However, the factors controlling CIA, resumption of menstruation (RM), and persistence of menstruation after chemotherapy are unknown. The long-term prognosis for premenopausal patients with BC and the prognostic factors associated with CIA and RM are subject to debate. We performed a retrospective study by reviewing the medical records of 249 patients with BC (stage I to stage III) who were treated with cytotoxic chemotherapy. The median patient age was 43 (range, 26-55 years) and the median duration of follow-up was 64 months (range, 28-100 months). The medical records indicated that 219 patients (88.0%) scored as positive for the hormone receptor (HR); the majority of these patients completed chemotherapy and then received additional therapy of tamoxifen. Our analyses revealed that 88.0% (n = 219) of patients experienced CIA, and the percentage of RM during follow-up was 48.6% (n = 121). A total of 30 patients (12.0%) did not experience CIA. Disease-free survival (DFS) was affected by several factors, including tumour size ≥2 cm, node positivity, HR negative status, and body mass index ≥23 kg/m. Multivariate analysis indicated that tumour size ≥2 cm remained as a significant factor for DFS (hazard ratio = 3.3, P = 0.034). In summary, this study finds that the majority of premenopausal patients with BC (stage I to stage III) who receive chemotherapy experience CIA and subsequent RM. Although tumour size ≥2 cm is negatively associated with DFS, RM after CIA is not associated with poor prognosis.

New Aspects of the Interplay between Penicillin Binding Proteins, murM, and the Two-Component System CiaRH of Penicillin-Resistant Streptococcus pneumoniae Serotype 19A Isolates from Hungary

PubMed Central

Schweizer, Inga; Blättner, Sebastian; Maurer, Patrick; Peters, Katharina; Vollmer, Daniela; Vollmer, Waldemar; Hakenbeck, Regine

2017-01-01

ABSTRACT The Streptococcus pneumoniae clone Hungary19A-6 expresses unusually high levels of β-lactam resistance, which is in part due to mutations in the MurM gene, encoding a transferase involved in the synthesis of branched peptidoglycan. Moreover, it contains the allele ciaH232, encoding the histidine kinase CiaH (M. Müller, P. Marx, R. Hakenbeck, and R. Brückner, Microbiology 157:3104–3112, 2011, https://doi.org/10.1099/mic.0.053157-0). High-level penicillin resistance primarily requires the presence of low-affinity (mosaic) penicillin binding protein (PBP) genes, as, for example, in strain Hu17, a closely related member of the Hungary19A-6 lineage. Interestingly, strain Hu15 is β-lactam sensitive due to the absence of mosaic PBPs. This unique situation prompted us to investigate the development of cefotaxime resistance in transformation experiments with genes known to play a role in this phenotype, pbp2x, pbp1a, murM, and ciaH, and penicillin-sensitive recipient strains R6 and Hu15. Characterization of phenotypes, peptidoglycan composition, and CiaR-mediated gene expression revealed several novel aspects of penicillin resistance. The murM gene of strain Hu17 (murMHu17), which is highly similar to murM of Streptococcus mitis, induced morphological changes which were partly reversed by ciaH232. murMHu17 conferred cefotaxime resistance only in the presence of the pbp2x of strain Hu17 (pbp2xHu17). The ciaH232 allele contributed to a remarkable increase in cefotaxime resistance in combination with pbp2xHu17 and pbp1a of strain Hu17 (pbp1aHu17), accompanied by higher levels of expression of CiaR-regulated genes, documenting that ciaH232 responds to PBP1aHu17-mediated changes in cell wall synthesis. Most importantly, the proportion of branched peptides relative to the proportion of linear muropeptides increased in cells containing mosaic PBPs, suggesting an altered enzymatic activity of these proteins. PMID:28483958

Significance of isolated reactive treponemal chemiluminescence immunoassay results.

PubMed

Hunter, Michael G; Robertson, Peter W; Post, Jeffrey J

2013-05-01

Isolated reactive serum treponemal chemiluminescence immunoassay (CIA) specimens cause clinical uncertainty. Sera were screened by CIA, and reactive samples underwent reflex testing with rapid plasma reagin (RPR), Treponema pallidum particle agglutination (TPPA), and fluorescent treponemal antibody absorption (FTA Abs) assays. Samples reactive only on the CIA were deemed "isolated" reactive CIA samples. We undertook detailed review of a subset of subjects with isolated reactive CIA specimens. Of 28 261 specimens, 1171 (4.1%) were reactive on CIA, of which 133 (11.3%) had isolated CIA reactivity. Most subjects (66 of 82 [80.5%]) with isolated reactive CIA specimens were from high-prevalence populations. We found evidence of CIA, TPPA, and FTA Abs seroreversion. The median chemiluminescent signal-to-cutoff ratio was similar for isolated reactive CIA sera and sera that were reactive on either FTA Abs or TPPA assays (2.19 vs 2.32; P = .15) but lower than for sera reactive on both FTA Abs and TPPA assays (12.37; P < .001) or for sera reactive on RPR assays (25.53; P < .001). A total of 11 of 20 patients (55%) with an isolated reactive CIA specimen who underwent medical record review had previous or subsequent evidence of syphilis infection. Isolated reactive CIA specimens may represent true T. pallidum infection and may be found after seroreversion of traditional treponemal assays.

Discordant Syphilis Immunoassays in Pregnancy: Perinatal Outcomes and Implications for Clinical Management.

PubMed

Mmeje, Okeoma; Chow, Joan M; Davidson, Lisette; Shieh, Jennifer; Schapiro, Jeffrey M; Park, Ina U

2015-10-01

The reverse sequence algorithm is often used for prenatal syphilis screening by high-volume laboratories, beginning with a treponemal test such as the chemiluminescence immunoassay (CIA), followed by testing of CIA-positive (CIA(+)) specimens with the rapid plasma reagin test (RPR). The clinical significance of discordant serology (CIA(+)/RPR(-)) for maternal and neonatal outcomes is unknown. From August 2007 to August 2010, all pregnant women at Kaiser Permanente Northern California with discordant treponemal serology underwent reflexive testing with Treponema pallidum particle agglutination assay (TP-PA) and were categorized as "TP-PA confirmed" (CIA(+)/RPR(-)/TP-PA(+)) or "isolated CIA positive" (CIA(+)/RPR(-)/TP-PA(-)). Demographic variables and clinical data were abstracted from the medical record and compared by TP-PA status. Of 194 pregnant women, 156 (80%) were CIA(+)/RPR(-)/TP-PA(-) and 38 (20%) were CIA(+)/RPR(-)/TP-PA(+). Among the 77 (49%) CIA(+)/RPR(-)/TP-PA(-) women who were retested, 53% became CIA(-). CIA(+)/RPR(-)/TP-PA(+) (n = 38) women were more likely to be older, have a prior history of sexually transmitted infections, and receive treatment for syphilis during pregnancy than women who were CIA(+)/RPR(-)/TP-PA(-) (all P < .005). Most pregnancies (189/194 [97.5%]) resulted in a live birth; there was no difference in birth outcomes according to TP-PA status and no stillbirths attributable to syphilis. Most pregnant women with discordant serology were CIA(+)/RPR(-)/TP-PA(-); more than half who were retested became CIA(-). CIA(+)/RPR(-)/TP-PA(-) serology in pregnancy is likely to be falsely positive. Reflexive testing of discordant specimens with TP-PA is important to stratify risk given the likelihood of false-positive results in this population. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Measurement invariance across Genders on the Childhood Illness Attitude Scales (CIAS).

PubMed

Thorisdottir, Audur S; Villadsen, Anna; LeBouthillier, Daniel M; Rask, Charlotte Ulrikka; Wright, Kristi D; Walker, John R; Feldgaier, Steven; Asmundson, Gordon J G

2017-07-01

The Childhood Illness Attitude Scales (CIAS) were created as a developmentally appropriate measure for symptoms of health anxiety (HA) in school-aged children. Despite overall sound psychometric properties reported in previous studies, more comprehensive examination of the latent structure and potential response bias in the CIAS is needed. The purpose of the present study was to cross-validate the latent structure of the CIAS across genders and to examine gender-specific variations in CIAS scores. The sample comprised data from 602 Canadian and Danish school-aged children (M age =10.54, SD=0.99; 52.5% girls). Confirmatory factor analyses were conducted to test 3-, modified 3-, and 4-factor models in both samples. Multigroup confirmatory factor analysis was performed to test factor structure invariance across boys and girls in a combined sample. Differential Item Functioning (DIF) was assessed using test characteristic curves. A modified 3-factor solution (i.e., fears=11 items, help-seeking=6 items, and symptom effects=4 items) provided the best fit to the data (χ 2 (364, N=602)=681.7, p<0.001; χ 2 /df=1.803; RMSEA=0.037; CFI=0.926). The factor structure was stable, well-fitting, and indicated measurement invariance across groups. DIF analyses revealed no gender-based response bias at the scale level. Results support a revised 3-factor version of the CIAS that can be used with confidence to assess symptoms of HA in school-aged boys and girls. Copyright © 2017 Elsevier Inc. All rights reserved.

Some Good Practices for Integration and Outreach and their Implementation in the Community Integrated Assessment System (CIAS) and its associated web portal CLIMASCOPE

NASA Astrophysics Data System (ADS)

Warren, R. F.; Price, J. T.; Goswami, S.

2010-12-01

Successful communication of knowledge to climate change policy makers requires the careful integration of scientific knowledge in an integrated assessment that can be clearly communicated to stakeholders, and which encapsulates the uncertainties in the analysis and conveys the need for using a risk assessment approach. It is important that (i) the system is co-designed with the users (ii) relevant disciplines are included (iii) assumptions made are clear (iv) the robustness of outputs to uncertainties is demonstrated (v) the system is flexible so that it can keep up with changing stakeholder needs and (vi) the results are communicated clearly and are readily accessible. The “Community Integrated Assessment System” (CIAS) is a unique multi-institutional, modular, and flexible integrated assessment system for modeling climate change which fulfils the above six criteria. It differs from other integrated models in being a flexible system allowing various combinations of component modules, to be connected together into alternative integrated assessment models. These modules may be written at different institutions in different computer languages and/or based on different operating systems. Scientists are able determine which particular CIAS coupled model they wish to use through a web portal. This includes the facility to implement Latin hypercube experimental design facilitating formal uncertainty analysis. Further exploration of robustness is possible through the ability to select, for example, alternative hyrdrological or climate models to address the same questions. It has been applied to study future scenarios of climate change mitigation, through for example the AVOIDing dangerous climate change project for DEFRA, in which the avoided impacts (benefits) of alternative climate policies were compared to no-policy baselines. These highlight the potential for mitigation to remove a substantial fraction of the climate change impacts that would otherwise occur; but also show that is not possible to avoid all the impacts, and hence that adaptation will still be required. For example, this has been shown for projections of future European drought. CIAS has also been used for analyses used in the IPCC 4AR and the Stern review. Recent applications include a study of the role of avoided deforestation in climate mitigation, and a study of the impacts of climate change on biodiversity. A second web portal, CLIMASCOPE, is being developed for use by stakeholders, currently focusing on the needs of adaptation planners. This will benefit communication by allowing a wide range of users free access to regional climate change projections in simple manner, yet one which encourages risk assessment through encapsulation of the uncertainties in climate change projection. Examples of CLIMASCOPE output that is being made available to stakeholders will be shown.

Does the type of CIA policy significantly affect bar and restaurant employment in Minnesota cities?

PubMed Central

Klein, Elizabeth G.; Forster, Jean L.; Erickson, Darin J.; Lytle, Leslie A.; Schillo, Barbara

2009-01-01

Background Clean indoor air (CIA) policies that include free-standing bars and restaurants have been adopted by communities to protect employees in all workplaces from exposure to environmental tobacco smoke, most notably employees working in restaurants and free-standing bars. However, due to the perception of negative economic effects on alcohol-licensed hospitality businesses, partial CIA policies (those that provide an exemption for free-standing bars) have been proposed as a means to reduce the risk of economic effects of comprehensive CIA policies applied to all worksites. Objective To determine if partial CIA produce differential economic effects compared to comprehensive CIA policies using bar and restaurant employment per capita. Design, setting, and subjects Ten cities in the state of Minnesota were studied from 2003 to 2006. Economic data were drawn from monthly employment in bars and restaurants, and a pooled time-series was completed to evaluate three types of local CIA policies: Comprehensive, partial, or none beyond the state law. Results Communities with a comprehensive CIA policy had a decrease of 9 employees per 10,000 residents compared with communities with a partial CIA policies (p=0.10). Communities with any type of CIA policy (partial or comprehensive) had an increase of 3 employees per 10,000 residents compared to communities without any CIA policies (p=0.36). Conclusion There were no significant differential economic effects by CIA policy type in Minnesota cities. These findings support the adoption of comprehensive CIA policies to provide all employees protection from environmental tobacco smoke exposure. PMID:19184432

Rheumatoid arthritis exacerbates the severity of osteonecrosis of the jaws (ONJ) in mice. A randomized, prospective, controlled animal study

PubMed Central

de Molon, Rafael Scaf; Hsu, Chingyun; Bezouglaia, Olga; Dry, Sarah M.; Pirih, Flavia Q.; Soundia, Akrivoula; Cunha, Fernando Queiroz; Cirelli, Joni Augusto; Aghaloo, Tara L.; Tetradis, Sotirios

2016-01-01

Rheumatoid arthritis (RA), an autoimmune inflammatory disorder, results in persistent synovitis with severe bone and cartilage destruction. Bisphosphonates (BPs) are often utilized in RA patients to reduce bone destruction and manage osteoporosis. However, BPs, especially at high doses, are associated with osteonecrosis of the jaw (ONJ). Here, utilizing previously published ONJ animal models, we are exploring interactions between RA and ONJ incidence and severity. DBA1/J-mice were divided in 4 groups: control, zoledronic acid (ZA), collagen induced arthritis (CIA), and CIA-ZA. Animals were pre-treated with vehicle or ZA. Bovine collagen II emulsified in Freund’s adjuvant was injected to induce arthritis (CIA) and the mandibular molar crowns were drilled to induce periapical disease. Vehicle or ZA treatment continued for 8-weeks. ONJ indices were measured by micro-CT and histological examination of maxillae and mandibles. Arthritis development was assessed by visual scoring of paw swelling, and by micro-CT and histology of interphalangeal and knee joints. Maxillae and mandibles of control and CIA mice showed bone loss, PDL space widening, lamina dura loss and cortex thinning. ZA prevented theses changes in both ZA and CIA-ZA groups. Epithelial to alveolar crest distance was increased in the control and CIA mice. This distance was preserved in ZA and CIA-ZA animals. Empty osteocytic lacunae and areas of osteonecrosis were present in ZA and CIA-ZA but more extensively in CIA-ZA animals, indicating more severe ONJ. CIA and CIA-ZA groups developed severe arthritis in the paws and knees. Interphalangeal and knee joints of CIA mice showed advanced bone destruction with cortical erosions and trabecular bone loss, and ZA treatment reduced these effects. Importantly, no osteonecrosis was noted adjacent to areas of articular inflammation in CIA-ZA mice. Our data suggest that ONJ burden was more pronounced in ZA treated CIA mice and that RA could be a risk factor for ONJ development. PMID:26950411

New Aspects of the Interplay between Penicillin Binding Proteins, murM, and the Two-Component System CiaRH of Penicillin-Resistant Streptococcus pneumoniae Serotype 19A Isolates from Hungary.

PubMed

Schweizer, Inga; Blättner, Sebastian; Maurer, Patrick; Peters, Katharina; Vollmer, Daniela; Vollmer, Waldemar; Hakenbeck, Regine; Denapaite, Dalia

2017-07-01

The Streptococcus pneumoniae clone Hungary 19A -6 expresses unusually high levels of β-lactam resistance, which is in part due to mutations in the MurM gene, encoding a transferase involved in the synthesis of branched peptidoglycan. Moreover, it contains the allele ciaH232 , encoding the histidine kinase CiaH (M. Müller, P. Marx, R. Hakenbeck, and R. Brückner, Microbiology 157:3104-3112, 2011, https://doi.org/10.1099/mic.0.053157-0). High-level penicillin resistance primarily requires the presence of low-affinity (mosaic) penicillin binding protein (PBP) genes, as, for example, in strain Hu17, a closely related member of the Hungary 19A -6 lineage. Interestingly, strain Hu15 is β-lactam sensitive due to the absence of mosaic PBPs. This unique situation prompted us to investigate the development of cefotaxime resistance in transformation experiments with genes known to play a role in this phenotype, pbp2x , pbp1a , murM , and ciaH , and penicillin-sensitive recipient strains R6 and Hu15. Characterization of phenotypes, peptidoglycan composition, and CiaR-mediated gene expression revealed several novel aspects of penicillin resistance. The murM gene of strain Hu17 ( murM Hu17 ), which is highly similar to murM of Streptococcus mitis , induced morphological changes which were partly reversed by ciaH232. murM Hu17 conferred cefotaxime resistance only in the presence of the pbp2x o f strain Hu17 ( pbp2x Hu17 ). The ciaH232 allele contributed to a remarkable increase in cefotaxime resistance in combination with pbp2x Hu17 and pbp1a of strain Hu17 ( pbp1a Hu17 ), accompanied by higher levels of expression of CiaR-regulated genes, documenting that ciaH232 responds to PBP1a Hu17 -mediated changes in cell wall synthesis. Most importantly, the proportion of branched peptides relative to the proportion of linear muropeptides increased in cells containing mosaic PBPs, suggesting an altered enzymatic activity of these proteins. Copyright © 2017 Schweizer et al.

Prognostic Effects of Adjuvant Chemotherapy-Induced Amenorrhea and Subsequent Resumption of Menstruation for Premenopausal Breast Cancer Patients

PubMed Central

Jeon, Se Jeong; Lee, Jae Il; Jeon, Myung Jae; Lee, Maria

2016-01-01

Abstract Chemotherapy-induced amenorrhea (CIA) is a side effect that occurs in patients with breast cancer (BC) as a result of chemotherapy. These patients require special treatments to avoid infertility and menopause. However, the factors controlling CIA, resumption of menstruation (RM), and persistence of menstruation after chemotherapy are unknown. The long-term prognosis for premenopausal patients with BC and the prognostic factors associated with CIA and RM are subject to debate. We performed a retrospective study by reviewing the medical records of 249 patients with BC (stage I to stage III) who were treated with cytotoxic chemotherapy. The median patient age was 43 (range, 26–55 years) and the median duration of follow-up was 64 months (range, 28–100 months). The medical records indicated that 219 patients (88.0%) scored as positive for the hormone receptor (HR); the majority of these patients completed chemotherapy and then received additional therapy of tamoxifen. Our analyses revealed that 88.0% (n = 219) of patients experienced CIA, and the percentage of RM during follow-up was 48.6% (n = 121). A total of 30 patients (12.0%) did not experience CIA. Disease-free survival (DFS) was affected by several factors, including tumour size ≥2 cm, node positivity, HR negative status, and body mass index ≥23 kg/m2. Multivariate analysis indicated that tumour size ≥2 cm remained as a significant factor for DFS (hazard ratio = 3.3, P = 0.034). In summary, this study finds that the majority of premenopausal patients with BC (stage I to stage III) who receive chemotherapy experience CIA and subsequent RM. Although tumour size ≥2 cm is negatively associated with DFS, RM after CIA is not associated with poor prognosis. PMID:27057900

Fifty Years of Silent Service: A Peek Inside the CIA Library.

ERIC Educational Resources Information Center

Newlen, Robert R.

1998-01-01

Describes the CIA (Central Intelligence Agency) library. Highlights include security measures, a day in the life of two CIA librarians, sample reference questions, collection development, the Historical Intelligence Collection, the CIA Web site, and library modernization. (JAK)

[Clinical study of induced abortion of early-early pregnancy: an analysis of 10, 404 cases].

PubMed

Kang, Jian; Wang, Xue-fen; Zhang, Li; Liu, Jian-hua

2012-01-03

To evaluate the advantages and disadvantages of early-early pregnancy induced abortion (EPIA). A total of 10 404 cases of EPIA performed at our hospital from January 1993 to December 2003 were retrospectively analyzed and compared with 9434 cases of common induced abortion (CIA). The amount of hemorrhage and operative duration, degree of pain, rate of induced-abortion syndrome, rate of incomplete abortion, menstrual changes and post-operative onset of Asherman's syndrome were observed and compared between 2 groups. The average age, ratio of parous cases, ratio of the cases of first-pregnancy induced abortion were not different between 2 groups (P > 0.05). The amount of hemorrhage bleeding ((4.9 ± 3.2) ml), operative duration ((90.3 ± 12.4) s), degree of pain, rate of induced-abortion syndrome, menstrual changes and the rate of Asherman's syndrome in the EPIA group were all significantly less than those in the CIA group (P < 0.05). However, the rate of incomplete abortion (0.44%) in the EPIA group was significantly higher than that (0.21%) in the CIA group (P < 0.05). EPIA has the advantages of lesser hemorrhage, less pain, shorter operative duration and fewer complications over CIA. Therefore the recovery of EPIA cases is earlier than that of CIA cases. While the risk of incomplete abortion stays high.

Traditional Chinese medicine formula Bi-Qi capsule alleviates rheumatoid arthritis-induced inflammation, synovial hyperplasia, and cartilage destruction in rats.

PubMed

Wang, Kai; Zhang, Dongmei; Liu, Yan; Wang, Xuan; Zhao, Jiantong; Sun, Tingting; Jin, Tingting; Li, Baoli; Pathak, Janak L

2018-03-14

Traditional Chinese medicine (TCM) formula Bi-Qi capsule (Bi-Qi) is a commonly prescribed drug to treat rheumatoid arthritis (RA). However, the mechanism of Bi-Qi-mediated amelioration of RA pathogenesis is still a mystery. Collagen induced arthritis (CIA) in rats is an established model that shares many similarities with RA in humans. In this study we investigated the effect of Bi-Qi on the pathogenesis of CIA in rats. CIA was developed in Sprague-Dawley (S.D) rats (n = 60, female) and used as a model resembling RA in humans. Rats were treated with a high or moderate dose of Bi-Qi, or methotrexate (MTX). Effects of the treatment on local joint and systemic inflammation, synovial hyperplasia, cartilage destruction, and other main features in the pathogenesis of CIA were analyzed. Inflamed and swollen ankles and joints were observed in arthritic rats, while Bi-Qi or MTX treatment alleviated these symptoms. Only the Bi-Qi moderate dose decreased RA-induced serum levels of tumor necrosis factor-alpha (TNF-α). Both Bi-Qi and MTX reduced the interleukin (IL)-18 serum level. Protein levels of cartilage oligomeric matrix protein and osteopontin in serum, synovium, and cartilage were elevated in arthritic rats, while Bi-Qi alleviated these effects. Synovial hyperplasia, inflammatory cell infiltration in synovium and a high degree of cartilage degradation was observed in RA, and Bi-Qi or MTX alleviated this effect. Bi-Qi at the moderate dose was the most effective in mitigating CIA-related clinical complications. Our findings showed that Bi-Qi alleviates CIA-induced inflammation, synovial hyperplasia, cartilage destruction, and the other main features in the pathogenesis of CIA. This provides fundamental evidence for the anti-arthritic properties of Bi-Qi and corroborates the use of Bi-Qi TCM formula for the treatment of RA.

Rheumatoid Arthritis Exacerbates the Severity of Osteonecrosis of the Jaws (ONJ) in Mice. A Randomized, Prospective, Controlled Animal Study.

PubMed

de Molon, Rafael Scaf; Hsu, Chingyun; Bezouglaia, Olga; Dry, Sarah M; Pirih, Flavia Q; Soundia, Akrivoula; Cunha, Fernando Queiroz; Cirelli, Joni Augusto; Aghaloo, Tara L; Tetradis, Sotirios

2016-08-01

Rheumatoid arthritis (RA), an autoimmune inflammatory disorder, results in persistent synovitis with severe bone and cartilage destruction. Bisphosphonates (BPs) are often utilized in RA patients to reduce bone destruction and manage osteoporosis. However, BPs, especially at high doses, are associated with osteonecrosis of the jaw (ONJ). Here, utilizing previously published ONJ animal models, we are exploring interactions between RA and ONJ incidence and severity. DBA1/J mice were divided into four groups: control, zoledronic acid (ZA), collagen-induced arthritis (CIA), and CIA-ZA. Animals were pretreated with vehicle or ZA. Bovine collagen II emulsified in Freund's adjuvant was injected to induce arthritis (CIA) and the mandibular molar crowns were drilled to induce periapical disease. Vehicle or ZA treatment continued for 8 weeks. ONJ indices were measured by micro-CT (µCT) and histological examination of maxillae and mandibles. Arthritis development was assessed by visual scoring of paw swelling, and by µCT and histology of interphalangeal and knee joints. Maxillae and mandibles of control and CIA mice showed bone loss, periodontal ligament (PDL) space widening, lamina dura loss, and cortex thinning. ZA prevented these changes in both ZA and CIA-ZA groups. Epithelial to alveolar crest distance was increased in the control and CIA mice. This distance was preserved in ZA and CIA-ZA animals. Empty osteocytic lacunae and areas of osteonecrosis were present in ZA and CIA-ZA but more extensively in CIA-ZA animals, indicating more severe ONJ. CIA and CIA-ZA groups developed severe arthritis in the paws and knees. Interphalangeal and knee joints of CIA mice showed advanced bone destruction with cortical erosions and trabecular bone loss, and ZA treatment reduced these effects. Importantly, no osteonecrosis was noted adjacent to areas of articular inflammation in CIA-ZA mice. Our data suggest that ONJ burden was more pronounced in ZA treated CIA mice and that RA could be a risk factor for ONJ development. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

A randomized phase 2 study of idarubicin and cytarabine with clofarabine or fludarabine in patients with newly diagnosed acute myeloid leukemia.

PubMed

Jabbour, Elias; Short, Nicholas J; Ravandi, Farhad; Huang, Xuelin; Xiao, Lianchun; Garcia-Manero, Guillermo; Plunkett, William; Gandhi, Varsha; Sasaki, Koji; Pemmaraju, Naveen; Daver, Naval G; Borthakur, Gautam; Jain, Nitin; Konopleva, Marina; Estrov, Zeev; Kadia, Tapan M; Wierda, William G; DiNardo, Courtney D; Brandt, Mark; O'Brien, Susan M; Cortes, Jorge E; Kantarjian, Hagop

2017-11-15

Fludarabine and clofarabine are purine nucleoside analogues with established clinical activity in patients with acute myeloid leukemia (AML). Herein, the authors evaluated the efficacy and safety of idarubicin and cytarabine with either clofarabine (CIA) or fludarabine (FIA) in adults with newly diagnosed AML. Adults with newly diagnosed AML who were deemed suitable for intensive chemotherapy were randomized using a Bayesian adaptive design to receive CIA (106 patients) or FIA (76 patients). Patients received induction with idarubicin and cytarabine, plus either clofarabine or fludarabine. Responding patients could receive up to 6 cycles of consolidation therapy. Outcomes were compared with a historical cohort of patients who received idarubicin and cytarabine. The complete remission/complete remission without platelet recovery rate was similar among patients in the CIA and FIA arms (80% and 82%, respectively). The median event-free survival was 13 months and 12 months, respectively (P = .91), and the median overall survival was 24 months and not reached, respectively (P = .23), in the 2 treatment arms. CIA was associated with more adverse events, particularly transaminase elevation, hyperbilirubinemia, and rash. Early mortality was similar in the 2 arms (60-day mortality rate of 4% for CIA vs 1% for FIA; P = .32). In an exploratory analysis of patients aged <50 years, FIA was found to be associated with improved survival compared with idarubicin and cytarabine (2-year event-free survival rate: 58% vs 30% [P = .05] and 2-year overall survival rate: 72% vs 36% [P = .009]). CIA and FIA have similar efficacy in younger patients with newly diagnosed AML, although FIA is associated with a better toxicity profile. Cancer 2017;123:4430-9. © 2017 American Cancer Society. © 2017 American Cancer Society.

A Randomized Phase 2 Study of Idarubicin and Cytarabine With Clofarabine or Fludarabine in Patients With Newly Diagnosed Acute Myeloid Leukemia

PubMed Central

Jabbour, Elias; Short, Nicholas J.; Ravandi, Farhad; Huang, Xuelin; Xiao, Lianchun; Garcia-Manero, Guillermo; Plunkett, William; Gandhi, Varsha; Sasaki, Koji; Pemmaraju, Naveen; Daver, Naval G.; Borthakur, Gautam; Jain, Nitin; Konopleva, Marina; Estrov, Zeev; Kadia, Tapan M.; Wierda, William G.; DiNardo, Courtney D.; Brandt, Mark; O’Brien, Susan M.; Cortes, Jorge E.; Kantarjian, Hagop

2017-01-01

BACKGROUND Fludarabine and clofarabine are purine nucleoside analogues with established clinical activity in patients with acute myeloid leukemia (AML). METHODS Herein, the authors evaluated the efficacy and safety of idarubicin and cytarabine with either clofarabine (CIA) or fludarabine (FIA) in adults with newly diagnosed AML. Adults with newly diagnosed AML who were deemed suitable for intensive chemotherapy were randomized using a Bayesian adaptive design to receive CIA (106 patients) or FIA (76 patients). Patients received induction with idarubicin and cytarabine, plus either clofarabine or fludarabine. Responding patients could receive up to 6 cycles of consolidation therapy. Outcomes were compared with a historical cohort of patients who received idarubicin and cytarabine. RESULTS The complete remission/complete remission without platelet recovery rate was similar among patients in the CIA and FIA arms (80% and 82%, respectively). The median event-free survival was 13 months and 12 months, respectively (P = .91), and the median overall survival was 24 months and not reached, respectively (P = .23), in the 2 treatment arms. CIA was associated with more adverse events, particularly transaminase elevation, hyperbilirubinemia, and rash. Early mortality was similar in the 2 arms (60-day mortality rate of 4% for CIA vs 1% for FIA; P = .32). In an exploratory analysis of patients aged <50 years, FIA was found to be associated with improved survival compared with idarubicin and cytarabine (2-year event-free survival rate: 58% vs 30% [P = .05] and 2-year overall survival rate: 72% vs 36% [P = .009]). CONCLUSIONS CIA and FIA have similar efficacy in younger patients with newly diagnosed AML, although FIA is associated with a better toxicity profile. PMID:28708931

Formularity: Software for Automated Formula Assignment of Natural and Other Organic Matter from Ultrahigh-Resolution Mass Spectra.

PubMed

Tolić, Nikola; Liu, Yina; Liyu, Andrey; Shen, Yufeng; Tfaily, Malak M; Kujawinski, Elizabeth B; Longnecker, Krista; Kuo, Li-Jung; Robinson, Errol W; Paša-Tolić, Ljiljana; Hess, Nancy J

2017-12-05

Ultrahigh resolution mass spectrometry, such as Fourier transform ion cyclotron resonance mass spectrometry (FT ICR MS), can resolve thousands of molecular ions in complex organic matrices. A Compound Identification Algorithm (CIA) was previously developed for automated elemental formula assignment for natural organic matter (NOM). In this work, we describe software Formularity with a user-friendly interface for CIA function and newly developed search function Isotopic Pattern Algorithm (IPA). While CIA assigns elemental formulas for compounds containing C, H, O, N, S, and P, IPA is capable of assigning formulas for compounds containing other elements. We used halogenated organic compounds (HOC), a chemical class that is ubiquitous in nature as well as anthropogenic systems, as an example to demonstrate the capability of Formularity with IPA. A HOC standard mix was used to evaluate the identification confidence of IPA. Tap water and HOC spike in Suwannee River NOM were used to assess HOC identification in complex environmental samples. Strategies for reconciliation of CIA and IPA assignments were discussed. Software and sample databases with documentation are freely available.

The Mammalian Proteins MMS19, MIP18, and ANT2 Are Involved in Cytoplasmic Iron-Sulfur Cluster Protein Assembly*

PubMed Central

van Wietmarschen, Niek; Moradian, Annie; Morin, Gregg B.; Lansdorp, Peter M.; Uringa, Evert-Jan

2012-01-01

Iron-sulfur (Fe-S) clusters are essential cofactors of proteins with a wide range of biological functions. A dedicated cytosolic Fe-S cluster assembly (CIA) system is required to assemble Fe-S clusters into cytosolic and nuclear proteins. Here, we show that the mammalian nucleotide excision repair protein homolog MMS19 can simultaneously bind probable cytosolic iron-sulfur protein assembly protein CIAO1 and Fe-S proteins, confirming that MMS19 is a central protein of the CIA machinery that brings Fe-S cluster donor proteins and the receiving apoproteins into proximity. In addition, we show that mitotic spindle-associated MMXD complex subunit MIP18 also interacts with both CIAO1 and Fe-S proteins. Specifically, it binds the Fe-S cluster coordinating regions in Fe-S proteins. Furthermore, we show that ADP/ATP translocase 2 (ANT2) interacts with Fe-S apoproteins and MMS19 in the CIA complex but not with the individual proteins. Together, these results elucidate the composition and interactions within the late CIA complex. PMID:23150669

Cryopyrin-associated periodic syndrome: a case report and review of the Japanese literature.

PubMed

Aoyama, Kumi; Amano, Hiroo; Takaoka, Yuki; Nishikomori, Ryuta; Ishikawa, Osamu

2012-07-01

Cryopyrin-associated periodic syndrome is an autoinflammatory syndrome caused by mutations of the CIAS1 gene (currently named NLRP3), and is characterized by periodic attacks of an urticaria-like rash, fever, head-ache, conjunctivitis and arthralgia. We report here a case of a 1-year-old boy with cryopyrin-associated periodic syndrome, which manifested as a recurrent skin rash in the postnatal period. Genetic analysis revealed a missense mutation of the CIAS1 gene in the mother and infant.

A NEW SENSITIVE ASSAY FOR ANTIBODY AGAINST CELL SURFACE ANTIGENS BASED ON INHIBITION OF CELL-DEPENDENT ANTIBODY-MEDIATED CYTOTOXICITY

PubMed Central

Halloran, Phil; Schirrmacher, Volker; Festenstein, Hilliard

1974-01-01

Inhibition of cell-dependent antibody-mediated cytotoxicity has been investigated as a new assay for antibody against cell surface antigens. The cytotoxicity system consisted of effector cells (normal mouse spleen cells), target cells (61Cr-labeled chicken erythrocytes), and antitarget cell antibody. Addition of antibody against cell surface antigens in the effector cell population regularly inhibited the cytotoxicity measured in this system. This cytotoxicity inhibition assay (CIA) detected antibody with a variety of specificities: anti-H-2, anti-Thy 1.2, anti-immunoglobulin, and antimouse bone marrow-derived lymphocyte antigen. When the inhibition by anti-H-2 sera was analyzed using effector cells from congenic mice, the activity was found to be directed against specificities mapping in the H-2K, H-2D, and I regions of the H-2 complex, correlating well with the specificities characterized by complement-dependent assays. A comparison between the sensitivity of the CIA and complement-dependent lysis revealed that the CIA was 2–11 times more sensitive for anti-H-2 antisera and 20–780 times more sensitive for certain antisera against subpopulations of the spleen cells (i.e., T cells or B cells). The CIA proved to be precise, sensitive, and reliable. It may become a very useful antibody assay in various species including man. PMID:4547657

Young adult support for clean indoor air laws in restaurants and bars.

PubMed

Bernat, Debra H; Klein, Elizabeth G; Fabian, Lindsey E A; Forster, Jean L

2009-07-01

This study examined support for clean indoor air (CIA) laws among 2044 young adults in Minnesota during 2006 and 2007. Two-thirds of young adult participants supported restaurant CIA laws and 40% supported bar/club CIA laws. A higher proportion of young adults living with CIA laws supported the laws compared with young adults living without them. Nonsmokers, college students, those with nonsmoking friends, and those living with home smoking bans were consistently more supportive of both CIA laws.

Young Adult Support for Clean Indoor Air Laws in Restaurants and Bars

PubMed Central

Bernat, Debra H.; Klein, Elizabeth; Fabian, Lindsey; Forster, Jean L.

2009-01-01

This study examined support for clean indoor air (CIA) laws among 2,044 young adults in Minnesota during 2006 and 2007. Two-thirds of young adult participants supported restaurant CIA laws and 40% supported bar/club CIA laws. A higher proportion of young adults living with CIA laws supported the laws, compared to young adults living without them. Nonsmokers, college students, those with nonsmoking friends, and those living with home smoking bans were consistently more supportive of both CIA laws. PMID:19541258

Chromatic Image Analysis For Quantitative Thermal Mapping

NASA Technical Reports Server (NTRS)

Buck, Gregory M.

1995-01-01

Chromatic image analysis system (CIAS) developed for use in noncontact measurements of temperatures on aerothermodynamic models in hypersonic wind tunnels. Based on concept of temperature coupled to shift in color spectrum for optical measurement. Video camera images fluorescence emitted by phosphor-coated model at two wavelengths. Temperature map of model then computed from relative brightnesses in video images of model at those wavelengths. Eliminates need for intrusive, time-consuming, contact temperature measurements by gauges, making it possible to map temperatures on complex surfaces in timely manner and at reduced cost.

Chemotherapy-Induced Amenorrhea – An Update

PubMed Central

Liedtke, C.; Kiesel, L.

2012-01-01

Because of the heterogeneity in the definition of chemotherapy-induced amenorrhea (CIA) there are distinct differences in the literature with regard to its incidence as well as its dependence on various influencing factors. The occurrence of CIA varies greatly depending on the applied chemotherapy. The pathogenesis of CIA is especially based on a reduction of ovarian reserves. Various sonographic and biochemical factors can be used to exclude or confirm CIA. This is particularly important when an endocrine therapy with tamoxifen is not possible and the use of aromatase inhibitors is under consideration. CIA and especially the frequently thereby resulting early menopause can lead to pronounced restrictions in the quality of life of the affected patients, not least due to the resulting infertility. On the other hand, various studies have shown that CIA may have a positive prognostic significance. Thus, the identification of measures to prevent CIA (for example, through the use of GnRH analogues) is of particular importance. PMID:26640289

32 CFR 1905.4 - Procedure for production.

Code of Federal Regulations, 2014 CFR

2014-07-01

... procedures set forth in this section. (b) The General Counsel of CIA and Deputy Directors or Heads of... available to CIA prior to the start of any search for information responsive to the demand. CIA may, in its... non-appealable disposition of any such defenses and objections raised by CIA has been made by the...

32 CFR 1905.4 - Procedure for production.

Code of Federal Regulations, 2010 CFR

2010-07-01

... procedures set forth in this section. (b) The General Counsel of CIA and Deputy Directors or Heads of... available to CIA prior to the start of any search for information responsive to the demand. CIA may, in its... non-appealable disposition of any such defenses and objections raised by CIA has been made by the...

32 CFR 1905.4 - Procedure for production.

Code of Federal Regulations, 2011 CFR

2011-07-01

... procedures set forth in this section. (b) The General Counsel of CIA and Deputy Directors or Heads of... available to CIA prior to the start of any search for information responsive to the demand. CIA may, in its... non-appealable disposition of any such defenses and objections raised by CIA has been made by the...

32 CFR 1905.4 - Procedure for production.

Code of Federal Regulations, 2012 CFR

2012-07-01

... procedures set forth in this section. (b) The General Counsel of CIA and Deputy Directors or Heads of... available to CIA prior to the start of any search for information responsive to the demand. CIA may, in its... non-appealable disposition of any such defenses and objections raised by CIA has been made by the...

32 CFR 1905.4 - Procedure for production.

Code of Federal Regulations, 2013 CFR

2013-07-01

... procedures set forth in this section. (b) The General Counsel of CIA and Deputy Directors or Heads of... available to CIA prior to the start of any search for information responsive to the demand. CIA may, in its... non-appealable disposition of any such defenses and objections raised by CIA has been made by the...

32 CFR Appendix A to Part 154 - Investigative Scope

Code of Federal Regulations, 2010 CFR

2010-07-01

... verification of citizenship. g. Central Intelligence Agency (CIA). The files of CIA contain information on.... Investigation Criteria for CIA Checks NAC, DNACI or ENTNAC Residence anywhere outside of the U.S. for a year or... files shall also be checked if subject has been an employee of CIA or when other sources indicate that...

32 CFR Appendix A to Part 154 - Investigative Scope

Code of Federal Regulations, 2011 CFR

2011-07-01

... verification of citizenship. g. Central Intelligence Agency (CIA). The files of CIA contain information on.... Investigation Criteria for CIA Checks NAC, DNACI or ENTNAC Residence anywhere outside of the U.S. for a year or... files shall also be checked if subject has been an employee of CIA or when other sources indicate that...

32 CFR Appendix A to Part 154 - Investigative Scope

Code of Federal Regulations, 2012 CFR

2012-07-01

... verification of citizenship. g. Central Intelligence Agency (CIA). The files of CIA contain information on.... Investigation Criteria for CIA Checks NAC, DNACI or ENTNAC Residence anywhere outside of the U.S. for a year or... files shall also be checked if subject has been an employee of CIA or when other sources indicate that...

32 CFR Appendix A to Part 154 - Investigative Scope

Code of Federal Regulations, 2014 CFR

2014-07-01

... verification of citizenship. g. Central Intelligence Agency (CIA). The files of CIA contain information on.... Investigation Criteria for CIA Checks NAC, DNACI or ENTNAC Residence anywhere outside of the U.S. for a year or... files shall also be checked if subject has been an employee of CIA or when other sources indicate that...

32 CFR Appendix A to Part 154 - Investigative Scope

Code of Federal Regulations, 2013 CFR

2013-07-01

... verification of citizenship. g. Central Intelligence Agency (CIA). The files of CIA contain information on.... Investigation Criteria for CIA Checks NAC, DNACI or ENTNAC Residence anywhere outside of the U.S. for a year or... files shall also be checked if subject has been an employee of CIA or when other sources indicate that...

Common iliac artery aneurysms in patients with abdominal aortic aneurysms.

PubMed

Armon, M P; Wenham, P W; Whitaker, S C; Gregson, R H; Hopkinson, B R

1998-03-01

To determine the incidence of common iliac artery (CIA) aneurysms in patients with abdominal aortic aneurysms (AAA) and to evaluate the relationship between AAA and CIA diameter. Spiral CT angiography was used to measure the maximum diameters of the abdominal aorta and the common iliac arteries of 215 patients with AAA. The median CIA diameter was 1.7 cm--significantly greater than the published mean of 1.25 (2 S.D. = 0.85-1.65) cm of an age-matched, non-vascular population. Thirty-four patients (16%) had unilateral and 26 patients (12%) bilateral CIA aneurysms > or = 2.4 cm diameter. Eight-six vessels (20%) were affected. Right CIA diameters were wider than left CIA diameters (p < 0.0001, Wilcoxon matched-pairs signed rank test). The correlation between AAA size and CIA diameter was weak. The AAA population has abnormally dilated common iliac arteries. In this population, common iliac artery aneurysms should be defined as those greater than 2.4 cm diameter. 20% of CIAs in patients with AAA are aneurysmal according to this definition.

Mesenchymal Stem Cells Promote the Osteogenesis in Collagen-Induced Arthritic Mice through the Inhibition of TNF-α

PubMed Central

Liu, Chang; Tang, Xiaojun; Feng, Ruihai; Yao, Genhong; Chen, Weiwei; Li, Wenchao; Liang, Jun; Feng, Xuebing

2018-01-01

Objective To investigate the effects of umbilical cord mesenchymal stem cell (UC-MSC) transplantation on joint damage and osteoporosis in collagen-induced arthritis (CIA) mice and to explore the mechanisms by which UC-MSCs modulate the osteogenic differentiation. Methods CIA mice were divided into the following treated groups: UC-MSC transplantation group, antitumor necrosis factor- (TNF-) α group, and zoledronic acid (ZA) group. Microcomputed tomography (micro-CT) was used to analyze the bone morphology parameters. Osteogenic differentiation of treated CIA mice was determined. Bone marrow mesenchymal stem cells (BM-MSCs) from CIA mice were treated with TNF-α in vitro to explore their effects on osteogenesis. Results The arthritis score was significantly reduced in the UC-MSC transplantation and anti-TNF-α-treated CIA groups, compared with control mice (P < 0.001). Micro-CT showed that CIA mice developed osteoporosis at 12 weeks after immunization. The bone morphology parameters were partially improved in UC-MSC-treated CIA mice. Impaired osteogenic differentiation functions were indicated by decreased ALP activity (P < 0.001) and reduced mRNA and protein levels of osteogenic marker genes (P < 0.05) in CIA mice compared with DBA/1 mice. UC-MSC treatment significantly upregulated the impaired osteogenic differentiation ability in CIA mice. Meanwhile, the serum TNF-α level was decreased significantly in the UC-MSC group. The osteogenesis was reduced with the addition of TNF-α in vitro. Conclusion This study demonstrated that UC-MSC transplantation not only significantly improved the joint damage but also played a beneficial role in osteoporosis in CIA mice. Mechanistically, the improved osteogenic differentiation of CIA under UC-MSC treatment may be achieved by inhibition of TNF-α. PMID:29853911

Obesity aggravates the joint inflammation in a collagen-induced arthritis model through deviation to Th17 differentiation

PubMed Central

Jhun, Joo-Yeon; Yoon, Bo-Young; Park, Mi-Kyung; Oh, Hye-Joa; Byun, Jae-Kyeong; Lee, Seon-Young; Min, Jun-Ki; Park, Sung-Hwan; Kim, Ho-Youn

2012-01-01

White fat cells secrete adipokines that induce inflammation and obesity has been reported to be characterized by high serum levels of inflammatory cytokines such as IL-6 and TNF-α. Rheumatoid arthritis (RA) is a prototype of inflammatory arthritis, but the relationship between RA and obesity is controversial. We made an obese inflammatory arthritis model: obese collagen-induced arthritis (CIA). C57BL/6 mice were fed a 60-kcal high fat diet (HFD) from the age of 4 weeks and they were immunized twice with type II collagen (CII). After immunization, the obese CIA mice showed higher arthritis index scores and histology scores and a more increased incidence of developing arthritis than did the lean CIA mice. After treatment with CII, mixed lymphocyte reaction also showed CII-specific response more intensely in the obese CIA mice than lean CIA. The anti-CII IgG and anti-CII IgG2a levels in the sera of the obese CIA mice were higher than those of the lean CIA mice. The number of Th17 cells was higher and the IL-17 mRNA expression of the splenocytes in the obese CIA mice was higher than that of the lean CIA mice. Obese CIA mice also showed high IL-17 expression on synovium in immunohistochemistry. Although obesity may not play a pathogenic role in initiating arthritis, it could play an important role in amplifying the inflammation of arthritis through the Th1/Th17 response. The obese CIA murine model will be an important tool when we investigate the effect of several therapeutic target molecules to treat RA. PMID:22513335

Epidemiology and molecular characterization of chicken anaemia virus from commercial and native chickens in Taiwan.

PubMed

Ou, S-C; Lin, H-L; Liu, P-C; Huang, H-J; Lee, M-S; Lien, Y-Y; Tsai, Y-L

2018-04-25

Chicken infectious anaemia (CIA) is a disease with a highly economic impact in the poultry industry. The infected chickens are characterized by aplastic anaemia and extreme immunosuppression, followed by the increased susceptibility to secondary infectious pathogens and suboptimal immune responses for vaccination. Commercially available CIA vaccines are routinely used in the breeders in Taiwan to protect their progeny with maternal-derived antibodies. However, CIA cases still occur in the field and little is known about the genetic characteristics of Taiwanese chicken anaemia viruses (CAVs). In this study, CAV DNA was detected in 72 of 137 flocks collected during 2010-2015. Among the PCR-positive samples, the coding regions of 51 CAVs were sequenced. Phylogenetic analysis of the VP1 gene revealed that, although most of Taiwanese CAVs belonged to genotypes II and III, some isolates were clustered into a novel genotype (genotype IV). Moreover, a Taiwanese isolate in this novel genotype IV appeared to be derived from a recombination event between genotypes II and III viruses. Five Taiwanese CAV isolates were highly similar to the vaccine strains, 26P4 or Del-Ros. Taken together, these results indicate that the sequences of CAVs in Taiwan are variable, and inter-genotypic recombination had occurred between viruses of different genotypes. Moreover, vaccine-like strains might induce clinical signs of CIA in chickens. Our findings could be useful for understanding the evolution of CAVs and development of a better control strategy for CIA. © 2018 Blackwell Verlag GmbH.

Chemotherapy-induced amenorrhea and the resumption of menstruation in premenopausal women with hormone receptor-positive early breast cancer.

PubMed

Koga, Chinami; Akiyoshi, Sayuri; Ishida, Mayumi; Nakamura, Yoshiaki; Ohno, Shinji; Tokunaga, Eriko

2017-09-01

For premenopausal women with breast cancer, information on the effects of chemotherapy and the risk of infertility is important. In this study, the effect of chemotherapy on the ovarian function in premenopausal women with hormone receptor-positive breast cancer was investigated, with an age-stratified analysis of the appearance of amenorrhea and the resumption of menstruation after the use of chemotherapy with anthracyclines or taxanes. Premenopausal women diagnosed with operable Stage I-III hormone receptor-positive breast cancer and underwent neoadjuvant or adjuvant chemotherapy with the standard regimen of anthracyclines and/or taxanes were included. The patients were classified into age groups in 5-year increments, and the rates of chemotherapy-induced amenorrhea (CIA), resumption of menstruation, and duration of CIA after chemotherapy were analyzed. The subjects consisted of 101 patients (median age 45 years). CIA occurred in 97 (96%) patients and 40 patients resumed menstruation. In all patients aged ≤39 years menstruation restarted, whereas in all patients aged ≥50 years, menstruation did not restart. For the patients who resumed menstruation, the younger the patients, the sooner menstruation tended to restart. The resumption of menstruation occurred within 1 year for younger patients aged around 30 years, but for those aged ≥35 years, 60% of cases took around 2-3 years for resumption. The incidence of CIA, the resumption of menstruation and duration of CIA after chemotherapy depend greatly on the patient's age.

The Effect of Endovascular Revascularization of Common Iliac Artery Occlusions on Erectile Function

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

Gur, Serkan, E-mail: mserkangur@yahoo.com; Ozkan, Ugur; Onder, Hakan

To determine the incidence of erectile dysfunction in patients with common iliac artery (CIA) occlusive disease and the effect of revascularization on erectile function using the sexual health inventory for males (SHIM) questionnaire. All patients (35 men; mean age 57 {+-} 5 years; range 42-67 years) were asked to recall their sexual function before and 1 month after iliac recanalization. Univariate and multivariate analyses were performed to determine variables effecting improvement of impotence. The incidence of impotence in patients with CIA occlusion was 74% (26 of 35) preoperatively. Overall 16 (46%) of 35 patients reported improved erectile function after iliacmore » recanalization. The rate of improvement of impotence was 61.5% (16 of 26 impotent patients). Sixteen patients (46%), including seven with normal erectile function before the procedure, had no change. Three patients (8%) reported deterioration of their sexual function, two of whom (6%) had normal erectile function before the procedure. The median SHIM score increased from 14 (range 4-25) before the procedure to 20 (range 1-25) after the procedure (P = 0.005). The type of recanalization, the age of the patients, and the length of occlusion were related to erectile function improvement in univariate analysis. However, these factors were not independent factors for improvement of erectile dysfunction in multivariate analysis (P > 0.05). Endovascular recanalization of CIA occlusions clearly improves sexual function. More than half of the patients with erectile dysfunction who underwent endovascular recanalization of the CIA experienced improvement.« less

Patency of the Internal Iliac Artery after Placement of Common and External Iliac Artery Stents.

PubMed

Vinogradova, Margie; Lee, Hye Joon; Armstrong, Ehrin J; Laird, John; Humphries, Misty D

2017-01-01

Treatment of severe aortoiliac occlusive disease (AIOD) frequently requires long-segment stenting of the common and external iliac arteries (CIA and EIA, respectively). This study aims to analyze the patency of the internal iliac artery (IIA) after placement of a CIA and EIA stents across the orifice. A retrospective analysis of all patients who underwent de novo ipsilateral stent placement in the CIA and EIA between 2006 and 2013 was performed. Kaplan-Meier analysis was used to analyze patency of the IIA, and Cox proportional hazard models were used to identify characteristics associated with occlusion. We identified 77 patients and 93 limbs where ipsilateral CIA and EIA stents were placed. Preintervention angiographic review found 52 cases of a patent ipsilateral IIA where stents were placed across the origin of the IIA in 31 cases and staggered across the orifice in 20 limbs. Kaplan-Meier analysis demonstrated a 37% patency in limbs where the stent covered the IIA orifice compared to 78% patency in uncovered arteries (P = 0.04). New-onset buttock claudication developed in 4 patients, 2 with patent IIAs and 2 with occluded. New-onset impotence also developed in 3 patients with occluded IIA and 5 patients with patent IIAs. Placement of stents across the origin of the IIA may not result in immediate occlusion, but long-term patency of covered IIAs is decreased compared to uncovered IIAs. This study is limited by a small sample size, but when treating AIOD, coverage of the internal iliac origin should be avoided to maintain patency of the pelvic circulation. Copyright © 2016 Elsevier Inc. All rights reserved.

Descriptive Quantitative Analysis of Rearfoot Alignment Radiographic Parameters.

PubMed

Meyr, Andrew J; Wagoner, Matthew R

2015-01-01

Although the radiographic parameters of the transverse talocalcaneal angle (tTCA), calcaneocuboid angle (CCA), talar head uncovering (THU), calcaneal inclination angle (CIA), talar declination angle (TDA), lateral talar-first metatarsal angle (lTFA), and lateral talocalcaneal angle (lTCA) form the basis of the preoperative evaluation and procedure selection for pes planovalgus deformity, the so-called normal values of these measurements are not well-established. The objectives of the present study were to retrospectively evaluate the descriptive statistics of these radiographic parameters (tTCA, CCA, THU, CIA, TDA, lTFA, and lTCA) in a large population, and, second, to determine an objective basis for defining "normal" versus "abnormal" measurements. As a secondary outcome, the relationship of these variables to the body mass index was assessed. Anteroposterior and lateral foot radiographs from 250 consecutive patients without a history of previous foot and ankle surgery and/or trauma were evaluated. The results revealed a mean measurement of 24.12°, 13.20°, 74.32%, 16.41°, 26.64°, 8.37°, and 43.41° for the tTCA, CCA, THU, CIA, TDA, lTFA, and lTCA, respectively. These were generally in line with the reported historical normal values. Descriptive statistical analysis demonstrated that the tTCA, THU, and TDA met the standards to be considered normally distributed but that the CCA, CIA, lTFA, and lTCA demonstrated data characteristics of both parametric and nonparametric distributions. Furthermore, only the CIA (R = -0.2428) and lTCA (R = -0.2449) demonstrated substantial correlation with the body mass index. No differentiations in deformity progression were observed when the radiographic parameters were plotted against each other to lead to a quantitative basis for defining "normal" versus "abnormal" measurements. Copyright © 2015 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Making the best of corporate integrity agreements.

PubMed

Henderson, W M; Imperato, G L

2001-07-01

Corporate integrity agreements (CIAs) imposed by the Office of Inspector General (OIG) of HHS have increased dramatically in the past five years. Healthcare organizations that enter into a CIA face burdensome monitoring and reporting requirements. However, it may be possible to lessen these burdens by negotiating modifications to the CIA's requirements. Organizations that have compliance programs in place can negotiate with the OIG to integrate elements of their existing compliance programs into the CIA. The organization also should attempt to negotiate limiting the scope of the monitoring to include only the area that was originally investigated. In addition, it may be valuable to negotiate insertion of a clause in the CIA allowing the organization to request renegotiation of the terms and duration of certain elements of the agreement after the first year, if conditions are met. An organized CIA negotiation process may be valuable in obtaining a reduced scope of the procedures required by the CIA and preparing the organization to meet its obligations.

Curcumin attenuates collagen-induced inflammatory response through the "gut-brain axis".

PubMed

Dou, Yannong; Luo, Jinque; Wu, Xin; Wei, Zhifeng; Tong, Bei; Yu, Juntao; Wang, Ting; Zhang, Xinyu; Yang, Yan; Yuan, Xusheng; Zhao, Peng; Xia, Yufeng; Hu, Huijuan; Dai, Yue

2018-01-06

Previous studies have demonstrated that oral administration of curcumin exhibited an anti-arthritic effect despite its poor bioavailability. The present study aimed to explore whether the gut-brain axis is involved in the therapeutic effect of curcumin. The collagen-induced arthritis (CIA) rat model was induced by immunization with an emulsion of collagen II and complete Freund's adjuvant. Sympathetic and parasympathetic tones were measured by electrocardiographic recordings. Unilateral cervical vagotomy (VGX) was performed before the induction of CIA. The ChAT, AChE activities, and serum cytokine levels were determined by ELISA. The expression of the high-affinity choline transporter 1 (CHT1), ChAT, and vesicular acetylcholine transporter (VAChT) were determined by real-time PCR and immunohistochemical staining. The neuronal excitability of the vagus nerve was determined by whole-cell patch clamp recording. Oral administration of curcumin restored the imbalance between the sympathetic and parasympathetic tones in CIA rats and increased ChAT activity and expression of ChAT and VAChT in the gut, brain, and synovium. Additionally, VGX eliminated the effects of curcumin on arthritis and ACh biosynthesis and transport. Electrophysiological data showed that curcumin markedly increased neuronal excitability of the vagus nerve. Furthermore, selective α7 nAChR antagonists abolished the effects of curcumin on CIA. Our results demonstrate that curcumin attenuates CIA through the "gut-brain axis" by modulating the function of the cholinergic system. These findings provide a novel approach for mechanistic studies of anti-arthritic compounds with low oral absorption and bioavailability.

Mangiferin suppresses CIA by suppressing the expression of TNF-α, IL-6, IL-1β, and RANKL through inhibiting the activation of NF-κB and ERK1/2.

PubMed

Tsubaki, Masanobu; Takeda, Tomoya; Kino, Toshiki; Itoh, Tatsuki; Imano, Motohiro; Tanabe, Genzo; Muraoka, Osamu; Satou, Takao; Nishida, Shozo

2015-01-01

Rheumatoid arthritis is a systemic autoimmune disease characterized by chronic inflammation of synovial joints, ultimately leading to a progressive and irreversible joint destruction. Activation of nuclear factor-kappa B (NF-κB) promotes production of proinflammatory cytokines in various inflammatory diseases including rheumatoid arthritis. Mangiferin, 1,3,6,7-tetrahydroxyxanthone-C2-β-D-glucoside (C-glucosyl xanthone), is a naturally occurring polyphenol. Our previous results showed that mangiferin suppressed NF-κB activation. However, it is unclear, whether mangiferin can prevent rheumatoid arthritis through suppression of NF-κB activation and expression of various cytokines, such as tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6), which play a critical role in the pathogenesis of rheumatoid arthritis. In the present study, we found that mangiferin suppressed the progression and incidence of CIA in DBA1/J mice. In CIA mice, mangiferin inhibited the mRNA expression of cytokine genes in thymus and spleen of CIA mie and led to decreased serum levels of IL-1β, IL-6, TNF-α, and receptor activator NF-κB ligand (RANKL) via inhibition of NF-κB and activation of extracellular signal-regulated kinase 1/2 (ERK1/2). In addition, mangiferin markedly inhibited not only developing but also clinically evident CIA. These findings suggest that mangiferin has potential clinical applications for the treatment of rheumatoid arthritis.

Formularity: Software for Automated Formula Assignment of Natural and Other Organic Matter from Ultrahigh-Resolution Mass Spectra

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

Tolić, Nikola; Liu, Yina; Liyu, Andrey

Ultrahigh-resolution mass spectrometry, such as Fourier transform ion-cyclotron resonance mass spectrometry (FT-ICR MS), can resolve thousands of molecular ions in complex organic matrices. A Compound Identification Algorithm (CIA) was previously developed for automated elemental formula assignment for natural organic matter (NOM). In this work we describe a user friendly interface for CIA, titled Formularity, which includes an additional functionality to perform search of formulas based on an Isotopic Pattern Algorithm (IPA). While CIA assigns elemental formulas for compounds containing C, H, O, N, S, and P, IPA is capable of assigning formulas for compounds containing other elements. We used halogenatedmore » organic compounds (HOC), a chemical class that is ubiquitous in nature as well as anthropogenic systems, as an example to demonstrate the capability of Formularity with IPA. A HOC standard mix was used to evaluate the identification confidence of IPA. The HOC spike in NOM and tap water were used to assess HOC identification in natural and anthropogenic matrices. Strategies for reconciliation of CIA and IPA assignments are discussed. Software and sample databases with documentation are freely available from the PNNL OMICS software repository https://omics.pnl.gov/software/formularity.« less

Characterization of CIA-1, an Ambler class A extended-spectrum β-lactamase from Chryseobacterium indologenes.

PubMed

Matsumoto, Takehisa; Nagata, Mika; Ishimine, Nau; Kawasaki, Kenji; Yamauchi, Kazuyoshi; Hidaka, Eiko; Kasuga, Eriko; Horiuchi, Kazuki; Oana, Kozue; Kawakami, Yoshiyuki; Honda, Takayuki

2012-01-01

An Ambler class A β-lactamase gene, bla(CIA-1), was cloned from the reference strain Chryseobacterium indologenes ATCC 29897 and expressed in Escherichia coli BL21. The bla(CIA-1) gene encodes a novel extended-spectrum β-lactamase (ESBL) that shared 68% and 60% identities with the CGA-1 and CME-1 β-lactamases, respectively. bla(CIA-1)-like genes were detected from clinical isolates. In addition to the metallo-β-lactamase IND of Ambler class B, C. indologenes has a class A ESBL gene, bla(CIA-1), located on the chromosome.

Increased long-term immunity to Bacillus anthracis protective antigen in mice immunized with a CIA06B-adjuvanted anthrax vaccine.

PubMed

Wui, Seo Ri; Han, Ji Eun; Kim, Yeon Hee; Rhie, Gi-eun; Lee, Na Gyong

2013-04-01

Anthrax is an acute infectious disease caused by Bacillus anthracis. We previously reported that the adjuvant CIA06B, which consists of TLR4 agonist CIA05 and aluminum hydroxide (alum), enhanced the immune response to anthrax protective antigen (PA) in mice. This study was carried out to determine whether CIA06B can enhance long-term immune responses to PA in mice. BALB/c mice were immunized intramuscularly three times at 2-week intervals with recombinant PA alone or PA combined with alum or CIA06B. At 8 and 24 weeks post-immunization, the immunological responses including serum anti-PA IgG antibody titer, toxin-neutralizing antibody titer, splenic cytokine secretion and the frequency of PA-specific memory B cells were assessed. Compared with mice injected with PA alone or PA plus alum, mice injected with PA plus CIA06B had higher titers of serum anti-PA IgG antibodies, and higher frequencies of PA-specific memory B cells and interferon-γ secreting cells. Furthermore, anti-PA antibodies induced by CIA06B were more effective in neutralizing anthrax toxin. These results demonstrated that CIA06B is capable of providing long-term immunity when used as an adjuvant in a PA-based anthrax vaccine.

Studies in Intelligence. Volume 52, Number 3, 2008

DTIC Science & Technology

2008-09-01

September 2008) Center for the Study of Intelligence In Memory of Thomas Francis Troy, CIA Teacher, Historian, 1919–2008 Amnesia to Anamnesis ...CIA Teacher, Historian, 1919–2008 1 By Hayden Peake and Nicholas Dujmovic Amnesia to Anamnesis Commemoration of the Dead at CIA 3 Nicholas Dujmovic...Intelligence Vol. 52, No. 3 Amnesia to Anamnesis Commemoration of the Dead at CIA Nicholas Dujmovic “History—as it is learned and remembered— ” shapes

A novel rat model for chemotherapy-induced alopecia.

PubMed

Wikramanayake, T C; Amini, S; Simon, J; Mauro, L M; Elgart, G; Schachner, L A; Jimenez, J J

2012-04-01

More than half of all people diagnosed with cancer receive chemotherapy, and approximately 65% of these develop chemotherapy-induced alopecia (CIA), a side-effect that can have considerable negative psychological repercussions. Currently, there are very few animal models available to study the mechanism and prevention of CIA. To develop a clinically relevant adult rat model for CIA. We first tested whether neonatal pigmented Long-Evans (LE) rats developed alopecia in response to the chemotherapeutic agents etoposide and cyclophosphamide. We then determined whether the rats developed CIA as adults. In the latter experiment, rat dorsal hair was clipped during the early telogen stage to synchronize the hair cycle, and starting 15 days later, the rats were treated with etoposide for 3 days. Neonatal LE pups developed CIA in response to etoposide and cyclophosphamide, similar to other murine models for CIA. Clipping of the hair shaft during early telogen resulted in synchronized anagen induction and subsequent alopecia after etoposide treatment in the clipped areas only. Hair follicles in the clipped areas had the typical chemotherapy-induced follicular dystrophy (dystrophic catagen). When the hair in the pigmented alopecic areas regrew, it had normal pigmentation. A novel, pigmented adult rat model has been established for CIA. By hair-shaft clipping during early telogen, synchronized anagen entry was induced, which resulted in alopecia in response to chemotherapy. This is the first clinically relevant adult rat model for CIA, and will be a useful tool to test agents for the prevention and treatment of CIA. © The Author(s). CED © 2012 British Association of Dermatologists.

Adaptation and Evaluation of the Clinical Impairment Assessment to Assess Disordered Eating Related Distress in an Adolescent Female Ethnic Fijian Population

PubMed Central

Becker, Anne E; Thomas, Jennifer J; Bainivualiku, Asenaca; Richards, Lauren; Navara, Kesaia; Roberts, Andrea L; Gilman, Stephen E; Striegel-Moore, Ruth H

2010-01-01

Objective: Measurement of disease-related impairment and distress is central to diagnostic, therapeutic, and health policy considerations for eating disorders across diverse populations. This study evaluates psychometric properties of a translated and adapted version of the Clinical Impairment Assessment (CIA) in an ethnic Fijian population. Method: The adapted CIA was administered to ethnic Fijian adolescent schoolgirls (N = 215). We calculated Cronbach's α to assess the internal consistency, examined the association between indicators of eating disorder symptom severity and the CIA to assess construct and criterion validity, and compared the strength of relation between the CIA and measures of disordered eating versus with measures of generalized distress. Results: The Fijian version of the CIA is feasible to administer as an investigator-based interview. It has excellent internal consistency (α = 0.93). Both construct and criterion validity were supported by the data, and regression models indicated that the CIA predicts eating disorder severity, even when controlling for generalized distress and psychopathology. Discussion: The adapted CIA has excellent psychometric properties in this Fijian study population. Findings suggest that the CIA can be successfully adapted for use in a non-Western study population and that at least some associated distress and impairment transcends cultural differences. © 2009 by Wiley Periodicals, Inc. Int J Eat Disord, 2010 PMID:19308992

Exercise and chemotherapy-induced amenorrhea.

PubMed

Mathis, Katlynn M; Sturgeon, Kathleen M; Winkels, Renate M; Wiskemann, Joachim; Williams, Nancy I; Schmitz, Kathryn

2018-07-01

Chemotherapy-induced amenorrhea (CIA) is the temporary or permanent loss of menses experienced by premenopausal women undergoing chemotherapy treatment for cancer. Two possible mechanisms through which chemotherapy induces CIA have been identified: systemic endothelial dysfunction, resulting in decreased blood flow to the ovaries, and increased oxidative stress within the ovaries, both of which are proposed to lead to apoptosis of follicles. Endothelial dysfunction in ovarian arteries in women undergoing or who have undergone chemotherapy treatment is characterized by prothrombotic changes and thickening of the vascular wall. These changes result in occlusion of the blood vessels. Oxidative stress is increased and antioxidants decreased in the ovaries secondary to chemotherapy drugs, specifically cyclophosphamide. It is hypothesized that low to moderate intensity aerobic exercise during chemotherapy may prevent these changes and lessen the risk for developing CIA in premenopausal women. Low to moderate intensity aerobic exercise has been shown to improve endothelial function and blood flow in patients with cardiovascular disease-a disease state characterized by endothelial dysfunction and for which patients who have undergone chemotherapy are at increased risk. In mice, moderate intensity aerobic exercise has been shown to decrease the amount of oxidative stress within the ovaries, and in humans, chronic aerobic exercise has been shown to increase antioxidant production systemically. This hypothesis should be tested in both a mouse model, using sedentary and exercising mice treated with chemotherapy drugs that commonly result in CIA, as well as a human model to determine the effects of low to moderate intensity aerobic exercise on ovarian function in premenopausal women undergoing chemotherapy. Copyright © 2018 Elsevier Ltd. All rights reserved.

CIAS detection of Fasciola hepatica/F. gigantica intermediate forms in bovines from Bangladesh.

PubMed

Ahasan, Syed Ali; Valero, M Adela; Chowdhury, Emdadul Haque; Islam, Mohammad Taohidul; Islam, Mohammad Rafiqul; Hussain Mondal, Mohammad Motahar; Peixoto, Raquel V; Berinde, Lavinia; Panova, Miroslava; Mas-Coma, Santiago

2016-03-01

Fascioliasis is an important food-borne parasitic zoonosis caused by two trematode species, Fasciola hepatica and Fasciola gigantica. The characterisation and differentiation of Fasciola populations is crucial to control the disease, given the different transmission, epidemiology and pathology characteristics of the two species. Lineal biometric features of adult liver flukes infecting livestock have been studied to characterise and discriminate fasciolids from Bangladesh. An accurate analysis was conducted to phenotypically discriminate between fasciolids from naturally infected bovines (cattle, buffaloes) throughout the country. Morphometric analyses were made with a computer image analysis system (CIAS) applied on the basis of standardised measurements and the logistic model of the body growth and development of fasciolids in the different host groups. Since it is the first ever comprehensive study of this kind undertaken in Bangladesh, the results are compared to pure fasciolid populations of F. hepatica from the European Mediterranean area and F. gigantica from Burkina Faso, geographical areas where both species do not co-exist. Principal component analysis showed that the biometric characteristics of fasciolids from Bangladesh are situated between F. hepatica and F. gigantica standard populations, indicating the presence of phenotypes of intermediate forms in Bangladesh. These results are analysed by considering the present emergence of animal fascioliasis, the local lymnaeid fauna, the impact of climate change, and the risk of human infection in the country.

An analytical platform for cumulative impact assessment based on multiple futures: the impact of petroleum drilling and forest harvesting on moose (Alces alces) and marten (Martes americana) habitats in northeastern British Columbia.

PubMed

Strimbu, Bogdan; Innes, John

2011-07-01

The combined influence on the environment of all projects occurring in a single area is evaluated through cumulative impact assessments (CIA), which consider the consequences of multiple projects, each insignificant on its own, yet important when evaluated collectively. Traditionally, future human activities are included in CIA using an analytical platform, commonly based on complex models that supply precise predictions but with reduced accuracy. To compensate for the lack of accuracy in current CIA approaches, we propose a shift in the paradigm governing CIA. The paradigm shift involves a change in the focus of CIA investigations from the detailed analysis of one unlikely future to the identification of the patterns describing multiple potential future changes in the environment. To illustrate the approach, a set of 144 possible and equally likely futures were developed that aimed to identify the potential impacts of forest harvesting and petroleum drilling on the habitat suitability of moose and marten in northeast British Columbia, Canada. The evolution of two measures of habitat suitability (average habitat suitability index and surface of the stands with habitat suitability index >0.5) revealed that the human activities could induce cycles in the habitat dynamics of moose and marten. The planning period of 100 years was separated into three distinct periods following a sinusoidal pattern (i.e., increase - constant - decrease in the habitat suitability measures). The attributes that could induce significant changes in the assessment of environment are the choice of harvesting age and species. Copyright © 2011 Elsevier Ltd. All rights reserved.

Transcriptome-Wide Changes in Chlamydomonas reinhardtii Gene Expression Regulated by Carbon Dioxide and the CO2-Concentrating Mechanism Regulator CIA5/CCM1[W][OA

PubMed Central

Fang, Wei; Si, Yaqing; Douglass, Stephen; Casero, David; Merchant, Sabeeha S.; Pellegrini, Matteo; Ladunga, Istvan; Liu, Peng; Spalding, Martin H.

2012-01-01

We used RNA sequencing to query the Chlamydomonas reinhardtii transcriptome for regulation by CO2 and by the transcription regulator CIA5 (CCM1). Both CO2 and CIA5 are known to play roles in acclimation to low CO2 and in induction of an essential CO2-concentrating mechanism (CCM), but less is known about their interaction and impact on the whole transcriptome. Our comparison of the transcriptome of a wild type versus a cia5 mutant strain under three different CO2 conditions, high CO2 (5%), low CO2 (0.03 to 0.05%), and very low CO2 (<0.02%), provided an entry into global changes in the gene expression patterns occurring in response to the interaction between CO2 and CIA5. We observed a massive impact of CIA5 and CO2 on the transcriptome, affecting almost 25% of all Chlamydomonas genes, and we discovered an array of gene clusters with distinctive expression patterns that provide insight into the regulatory interaction between CIA5 and CO2. Several individual clusters respond primarily to either CIA5 or CO2, providing access to genes regulated by one factor but decoupled from the other. Three distinct clusters clearly associated with CCM-related genes may represent a rich source of candidates for new CCM components, including a small cluster of genes encoding putative inorganic carbon transporters. PMID:22634760

Security Analysis of Selected AMI Failure Scenarios Using Agent Based Game Theoretic Simulation

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

Abercrombie, Robert K; Schlicher, Bob G; Sheldon, Frederick T

Information security analysis can be performed using game theory implemented in dynamic Agent Based Game Theoretic (ABGT) simulations. Such simulations can be verified with the results from game theory analysis and further used to explore larger scale, real world scenarios involving multiple attackers, defenders, and information assets. We concentrated our analysis on the Advanced Metering Infrastructure (AMI) functional domain which the National Electric Sector Cyber security Organization Resource (NESCOR) working group has currently documented 29 failure scenarios. The strategy for the game was developed by analyzing five electric sector representative failure scenarios contained in the AMI functional domain. From thesemore » five selected scenarios, we characterize them into three specific threat categories affecting confidentiality, integrity and availability (CIA). The analysis using our ABGT simulation demonstrates how to model the AMI functional domain using a set of rationalized game theoretic rules decomposed from the failure scenarios in terms of how those scenarios might impact the AMI network with respect to CIA.« less

The Adaptor Molecule Signaling Lymphocytic Activation Molecule (SLAM)-associated Protein (SAP) Is Essential in Mechanisms Involving the Fyn Tyrosine Kinase for Induction and Progression of Collagen-induced Arthritis

PubMed Central

Zhong, Ming-Chao; Veillette, André

2013-01-01

Signaling lymphocytic activation molecule-associated protein (SAP) is an Src homology 2 domain-only adaptor involved in multiple immune cell functions. It has also been linked to immunodeficiencies and autoimmune diseases, such as systemic lupus erythematosus. Here, we examined the role and mechanism of action of SAP in autoimmunity using a mouse model of autoimmune arthritis, collagen-induced arthritis (CIA). We found that SAP was essential for development of CIA in response to collagen immunization. It was also required for production of collagen-specific antibodies, which play a key role in disease pathogenesis. These effects required SAP expression in T cells, not in B cells. In mice immunized with a high dose of collagen, the activity of SAP was nearly independent of its ability to bind the protein tyrosine kinase Fyn and correlated with the capacity of SAP to promote full differentiation of follicular T helper (TFH) cells. However, with a lower dose of collagen, the role of SAP was more dependent on Fyn binding, suggesting that additional mechanisms other than TFH cell differentiation were involved. Further studies suggested that this might be due to a role of the SAP-Fyn interaction in natural killer T cell development through the ability of SAP-Fyn to promote Vav-1 activation. We also found that removal of SAP expression during progression of CIA attenuated disease severity. However, it had no effect on disease when CIA was clinically established. Together, these results indicate that SAP plays an essential role in CIA because of Fyn-independent and Fyn-dependent effects on TFH cells and, possibly, other T cell types. PMID:24045941

The adaptor molecule signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) is essential in mechanisms involving the Fyn tyrosine kinase for induction and progression of collagen-induced arthritis.

PubMed

Zhong, Ming-Chao; Veillette, André

2013-11-01

Signaling lymphocytic activation molecule-associated protein (SAP) is an Src homology 2 domain-only adaptor involved in multiple immune cell functions. It has also been linked to immunodeficiencies and autoimmune diseases, such as systemic lupus erythematosus. Here, we examined the role and mechanism of action of SAP in autoimmunity using a mouse model of autoimmune arthritis, collagen-induced arthritis (CIA). We found that SAP was essential for development of CIA in response to collagen immunization. It was also required for production of collagen-specific antibodies, which play a key role in disease pathogenesis. These effects required SAP expression in T cells, not in B cells. In mice immunized with a high dose of collagen, the activity of SAP was nearly independent of its ability to bind the protein tyrosine kinase Fyn and correlated with the capacity of SAP to promote full differentiation of follicular T helper (TFH) cells. However, with a lower dose of collagen, the role of SAP was more dependent on Fyn binding, suggesting that additional mechanisms other than TFH cell differentiation were involved. Further studies suggested that this might be due to a role of the SAP-Fyn interaction in natural killer T cell development through the ability of SAP-Fyn to promote Vav-1 activation. We also found that removal of SAP expression during progression of CIA attenuated disease severity. However, it had no effect on disease when CIA was clinically established. Together, these results indicate that SAP plays an essential role in CIA because of Fyn-independent and Fyn-dependent effects on TFH cells and, possibly, other T cell types.

Sirt2 suppresses inflammatory responses in collagen-induced arthritis

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

Lin, Jiangtao; Department of Orthopaedics, Yantaishan Hospital, 91 Jiefang Road, Yantai, Shandong 264001; Sun, Bing

Highlights: •Sirt2 expression decreases in collagen-induced arthritis (CIA). •Sirt2 knockout aggravates severity of arthritis in mice with CIA. •Sirt2 knockout increases levels of pro-inflammatory factors in the serum. •Sirt2 deacetylates p65 and inhibits pro-inflammatory factors expression. •Sirt2 rescue abates severity of arthritis in mice with CIA. -- Abstract: Arthritis is a common autoimmune disease that is associated with progressive disability, systemic complications and early death. However, the underling mechanisms of arthritis are still unclear. Sirtuins are a NAD{sup +}-dependent class III deacetylase family, and regulate cellular stress, inflammation, genomic stability, carcinogenesis, and energy metabolism. Among the sirtuin family members, Sirt1more » and Sirt6 are critically involved in the development of arthritis. It remains unknown whether other sirtuin family members participate in arthritis. Here in this study, we demonstrate that Sirt2 inhibits collagen-induced arthritis (CIA) using in vivo and in vitro evidence. The protein and mRNA levels of Sirt2 significantly decreased in joint tissues of mice with CIA. When immunized with collagen, Sirt2-KO mice showed aggravated severity of arthritis based on clinical scores, hind paw thickness, and radiological and molecular findings. Mechanically, Sirt2 deacetylated p65 subunit of nuclear factor-kappa B (NF-κB) at lysine 310, resulting in reduced expression of NF-κB-dependent genes, including interleukin 1β (IL-1β), IL-6, monocyte chemoattractant protein 1(MCP-1), RANTES, matrix metalloproteinase 9 (MMP-9) and MMP-13. Importantly, our rescue experiment showed that Sirt2 re-expression abated the severity of arthritis in Sirt2-KO mice. Those findings strongly indicate Sirt2 as a considerably inhibitor of the development of arthritis.« less

Economic evaluation of the Programs Rede Farmácia de Minas do SUS versus Farmácia Popular do Brasil.

PubMed

Garcia, Marina Morgado; Guerra, Augusto Afonso; Acúrcio, Francisco de Assis

2017-01-01

We conducted an economic assessment of the Pharmaceutical Assistance - Rede Farmácia de Minas Gerais-RFMG and Farmácia Popular do Brasil-FPB to ascertain which of the two models stands out as the most efficient. To do this, a model, which consisted of a study of incurred costs in both programs, up to the dispensing of medicine to citizens, was developed. The uncertainties of the proposed model were tested using the Monte Carlo method. If the entire population initially estimated in the RFMG were attended in the FPB, there would be an additional cost of R$ 139,324,050.19. The sensitivity analysis appeared to be favorable to the RFMG. A total of 10000 simulations were carried out, resulting in a median value of R$ 114,053,709.99 for the RFMG and R$ 254,106,120.65 for the FPB. The current National Drug Policy emphasizes the need to strengthen pharmaceutical services beyond the mere acquisition and delivery of pharmaceutical products. The public healthcare service model, consistent with the principles and guidelines of the SUS, seems to be more appropriate in ensuring complete and universal quality healthcare services to the citizens. The economic study conducted reinforces this fact, as it appears to be a more efficient alternative of the direct use of resources in the public health network.

32 CFR 1904.4 - Notification to CIA Office of General Counsel.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 6 2013-07-01 2013-07-01 false Notification to CIA Office of General Counsel. 1904.4 Section 1904.4 National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY PROCEDURES GOVERNING ACCEPTANCE OF SERVICE OF PROCESS § 1904.4 Notification to CIA Office...

32 CFR 1904.4 - Notification to CIA Office of General Counsel.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 6 2010-07-01 2010-07-01 false Notification to CIA Office of General Counsel. 1904.4 Section 1904.4 National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY PROCEDURES GOVERNING ACCEPTANCE OF SERVICE OF PROCESS § 1904.4 Notification to CIA Office...

32 CFR 1904.4 - Notification to CIA Office of General Counsel.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 6 2011-07-01 2011-07-01 false Notification to CIA Office of General Counsel. 1904.4 Section 1904.4 National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY PROCEDURES GOVERNING ACCEPTANCE OF SERVICE OF PROCESS § 1904.4 Notification to CIA Office...

32 CFR 1904.4 - Notification to CIA Office of General Counsel.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 6 2014-07-01 2014-07-01 false Notification to CIA Office of General Counsel. 1904.4 Section 1904.4 National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY PROCEDURES GOVERNING ACCEPTANCE OF SERVICE OF PROCESS § 1904.4 Notification to CIA Office...

32 CFR 1904.4 - Notification to CIA Office of General Counsel.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 6 2012-07-01 2012-07-01 false Notification to CIA Office of General Counsel. 1904.4 Section 1904.4 National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY PROCEDURES GOVERNING ACCEPTANCE OF SERVICE OF PROCESS § 1904.4 Notification to CIA Office...

Osteoarticular Expression of Musashi-1 in an Experimental Model of Arthritis

PubMed Central

O'Valle, Francisco; Peregrina, Magdalena; Crespo-Lora, Vicente; Galindo-Moreno, Pablo; Roman, Maria; Aneiros-Fernandez, Jose; Aguilar, David; Gonzalez-Rey, Elena; Delgado, Mario; Hernandez-Cortes, Pedro

2015-01-01

Background. Collagen-induced arthritis (CIA), a murine experimental disease model induced by immunization with type II collagen (CII), is used to evaluate novel therapeutic strategies for rheumatoid arthritis. Adult stem cell marker Musashi-1 (Msi1) plays an important role in regulating the maintenance and differentiation of stem/precursor cells. The objectives of this investigation were to perform a morphological study of the experimental CIA model, evaluate the effect of TNFα-blocker (etanercept) treatment, and determine the immunohistochemical expression of Msi1 protein. Methods. CIA was induced in 50 male DBA1/J mice for analyses of tissue and serum cytokine; clinical and morphological lesions in limbs; and immunohistochemical expression of Msi1. Results. Clinically, TNFα-blocker treatment attenuated CIA on day 32 after immunization (P < 0.001). Msi1 protein expression was significantly higher in joints damaged by CIA than in those with no lesions (P < 0.0001) and was related to the severity of the lesions (Spearman's rho = 0.775, P = 0.0001). Conclusions. Treatment with etanercept attenuates osteoarticular lesions in the murine CIA model. Osteoarticular expression of Msi1 protein is increased in joints with CIA-induced lesion and absent in nonlesioned joints, suggesting that this protein is expressed when the lesion is produced in order to favor tissue repair. PMID:26064941

Polymorphism of the MHC class II Eb gene determines the protection against collagen-induced arthritis

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

Gonzalez-Gay, M.A.; Zanelli, E.; Krco, C.J.

1995-05-01

Collagen-induced arthritis (CIA) is an animal model of auto immune polyarthritis, sharing similarities with rheumatoid arthritis (RA). Paradoxally, susceptibility to mouse CIA is controlled by the H2A loci (DQ homologous) while RA is linked to HLA.DR genes (H2E homologous). We recently showed that the E{beta}{sup d} molecule prevents CIA development in susceptible H2{sup q} mice. We addressed the question of whether H2Eb polymorphism will influence CIA incidence as HLA.DRB1 polymorphism does in RA. In F{sub 1} mice, only H2Eb{sup d} and H2Eb{sup s} molecules showed protection. Using recombinant B10.RDD (Eb{sup d/b}) mice, we found that CIA protection was mediated bymore » the first domain of the E{beta}{sup d} molecule. Using peptides covering the third hypervariable region of the E{beta} chain, we found a perfect correlation between presentation of E{beta} peptides by the H2A{sup q} molecule and protection on CIA. Therefore, the mechanism by which H2Eb protects against CIA seems to rely on the affinity of E{beta} peptides for the H2A{sup q} molecule. 35 refs., 2 figs., 3 tabs.« less

Computer-aided analysis with Image J for quantitatively assessing psoriatic lesion area.

PubMed

Sun, Z; Wang, Y; Ji, S; Wang, K; Zhao, Y

2015-11-01

Body surface area is important in determining the severity of psoriasis. However, objective, reliable, and practical method is still in need for this purpose. We performed a computer image analysis (CIA) of psoriatic area using the image J freeware to determine whether this method could be used for objective evaluation of psoriatic area. Fifteen psoriasis patients were randomized to be treated with adalimumab or placebo in a clinical trial. At each visit, the psoriasis area of each body site was estimated by two physicians (E-method), and standard photographs were taken. The psoriasis area in the pictures was assessed with CIA using semi-automatic threshold selection (T-method), or manual selection (M-method, gold standard). The results assessed by the three methods were analyzed with reliability and affecting factors evaluated. Both T- and E-method correlated strongly with M-method, and T-method had a slightly stronger correlation with M-method. Both T- and E-methods had a good consistency between the evaluators. All the three methods were able to detect the change in the psoriatic area after treatment, while the E-method tends to overestimate. The CIA with image J freeware is reliable and practicable in quantitatively assessing the lesional of psoriasis area. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Costs of Public Pharmaceutical Services in Rio de Janeiro Compared to Farmácia Popular Program

PubMed Central

da Silva, Rondineli Mendes; Caetano, Rosângela

2016-01-01

ABSTRACT OBJECTIVE To analyze the costs of public pharmaceutical services compared to Farmácia Popular Program (Popular Pharmacy Program). METHODS Comparison between prices paid by Aqui Tem Farmácia Popular Program (Farmácia Popular is available here) with the full costs of medicine provision by the Municipal Health Department of Rio de Janeiro. The comparison comprised 25 medicines supplied by both the municipal pharmaceutical service and Aqui Tem Farmácia Popular Program. Calculating the cost per pharmaceutical unit of each medicine included expenditure by Municipal Health Department of Rio de Janeiro with procurement (price), logistics, and local dispensation. The reference price of medicines paid by Aqui Tem Farmácia Popular was taken from the Brazilian Ministry of Health standard in force in 2012. Comparisons included full reference price; reference price minus 10.0% copayment by users; and maximum reference paid by the Ministry of Health (minus copayment and taxes). Simulations were carried out of the differences between the costs of Municipal Health Department of Rio de Janeiro with the common medicines and those potentially incurred based on the reference price of Aqui Tem Farmácia Popular. RESULTS The Municipal Health Department of Rio de Janeiro spent R$28,526,526.57 with 25 medicines of the common list in 2012; 58.7% accounted for direct procurement costs. The estimated costs of the Health Department were generally lower than the reference prices of the Aqui Tem Farmácia Popular Program for 20 medicines, regardless of reference prices. The potential costs incurred by Health Department if expenditure of its consumption pattern were based on the reference prices of Aqui Tem Farmácia Popular would be R$124,170,777.76, considering the best scenario of payment by the Brazilian Ministry of Health (90.0% of the reference price, minus taxes). CONCLUSIONS The difference in costs between public provision by Municipal Health Department of Rio de Janeiro and Farmácia Popular Program indicates that some reference prices could be reviewed aiming at their reduction. PMID:28099664

Culinary School Gives Latinos a Taste of the Top

ERIC Educational Resources Information Center

Gardner, Lee

2012-01-01

With scholarships and other special programs, the Culinary Institute of America's (CIA) Texas campus hopes to make its Latino students into industry leaders. CIA is considered as the most august culinary school in the United States. CIA San Antonio dispatches chefs to study and document traditional cuisines throughout Latin America for its Center…

32 CFR 1901.22 - Action and determination(s) by originator(s) or any interested party.

Code of Federal Regulations, 2012 CFR

2012-07-01

... for access. CIA components tasked pursuant to a Privacy Act access request shall search all relevant... any). (b) Initial action for amendment. CIA components tasked pursuant to a Privacy Act amendment... amendment request. If the CIA component records manager declines to make the requested amendment or declines...

32 CFR 1901.22 - Action and determination(s) by originator(s) or any interested party.

Code of Federal Regulations, 2014 CFR

2014-07-01

... for access. CIA components tasked pursuant to a Privacy Act access request shall search all relevant... any). (b) Initial action for amendment. CIA components tasked pursuant to a Privacy Act amendment... amendment request. If the CIA component records manager declines to make the requested amendment or declines...

32 CFR 1901.22 - Action and determination(s) by originator(s) or any interested party.

Code of Federal Regulations, 2010 CFR

2010-07-01

... for access. CIA components tasked pursuant to a Privacy Act access request shall search all relevant... any). (b) Initial action for amendment. CIA components tasked pursuant to a Privacy Act amendment... amendment request. If the CIA component records manager declines to make the requested amendment or declines...

Bosentan, an endothelin receptor antagonist, ameliorates collagen-induced arthritis: the role of TNF-α in the induction of endothelin system genes.

PubMed

Donate, Paula B; Cunha, Thiago M; Verri, Waldiceu A; Junta, Cristina M; Lima, Flavia O; Vieira, Silvio M; Peres, Rafael S; Bombonato-Prado, Karina F; Louzada, Paulo; Ferreira, Sergio H; Donadi, Eduardo A; Passos, Geraldo A S; Cunha, Fernando Q

2012-04-01

Endothelins (ETs) are involved in several inflammatory events. The present study investigated the efficacy of bosentan, a dual ETA/ETB receptor antagonist, in collagen-induced arthritis (CIA) in mice. CIA was induced in DBA/1J mice. Arthritic mice were treated with bosentan (100 mg/kg) once a day, starting from the day when arthritis was clinically detectable. CIA progression was assessed by measurements of visual clinical score, paw swelling and hypernociception. Histological changes, neutrophil infiltration and pro-inflammatory cytokines were evaluated in the joints. Gene expression in the lymph nodes of arthritic mice was evaluated by microarray technology. PreproET-1 mRNA expression in the lymph nodes of mice and in peripheral blood mononuclear cells (PBMCs) was evaluated by real-time PCR. The differences were evaluated by one-way ANOVA or Student's t test. Oral treatment with bosentan markedly ameliorated the clinical aspects of CIA (visual clinical score, paw swelling and hyperalgesia). Bosentan treatment also reduced joint damage, leukocyte infiltration and pro-inflammatory cytokine levels (IL-1β, TNFα and IL-17) in the joint tissues. Changes in gene expression in the lymph nodes of arthritic mice returned to the levels of the control mice after bosentan treatment. PreproET mRNA expression increased in PBMCs from rheumatoid arthritis (RA) patients but returned to basal level in PBMCs from patients under anti-TNF therapy. In-vitro treatment of PBMCs with TNFα upregulated ET system genes. These findings indicate that ET receptor antagonists, such as bosentan, might be useful in controlling RA. Moreover, it seems that ET mediation of arthritis is triggered by TNFα.

Prevalence of anti-DFS70 antibodies in patients with and without systemic autoimmune rheumatic diseases.

PubMed

Shovman, Ora; Gilburd, Boris; Chayat, Chen; Amital, Howard; Langevitz, Pnina; Watad, Abdulla; Guy, Adi; Perez, Dolores; Azoulay, Danielle; Blank, Miri; Segal, Yael; Bentow, Chelsea; Mahler, Michael; Shoenfeld, Yehuda

2018-01-01

Autoantibodies to the dense fine speckled 70 (DFS70) antigen are common among antinuclear antibodies (ANA) positive healthy individuals (HI). We assessed the prevalence of anti-DFS70 antibodies in patients with and without ANA-associated rheumatic diseases (AARDs) by two methods: chemiluminescent immunoassay (CIA) and an indirect immunofluorescence (IIF) assay based on immunoadsorption for DFS70. Fifty-one ANA-positive sera samples from patients with confirmed clinical diagnosis of AARD, 92 samples from HI and 85 samples submitted to a reference laboratory for routine ANA testing were evaluated for the presence of anti-DFS70 antibodies. The samples were evaluated by QUANTA Flash DFS70 CIA using BIO-FLASH instrument and by NOVA Lite selected HEp-2 kit on NOVA View - an automated IIF system. Sera with DFS positive pattern were pre-absorbed with highly purified human DFS70 antigen, and then tested again. Twenty-four samples (10.5%) tested by QUANTA Flash DFS70 CIA were positive for anti-DFS70 antibodies. The prevalence of monospecific anti-DFS70 antibodies was significantly higher in healthy subjects than in patients with AARDs (10.9% vs. 1.9%, p=0.02). The frequency of anti-DFS70 antibodies in samples submitted for routine ANA testing was 15.2%. A very good agreement was found between CIA and the DFS pattern identified by the automated HEp-2 IIF (kappa=0.97). In 80% of the samples obtained from patients without AARDs, immunoadsorption effectively inhibited the anti-DFS70 antibodies. The data confirm that mono-specific anti-DFS70 antibodies are a strong discriminator between ANA positive HI and AARD patients, and their evaluation should be included in ANA testing algorithms.

Multiple two-component systems modulate alkali generation in Streptococcus gordonii in response to environmental stresses.

PubMed

Liu, Yaling; Burne, Robert A

2009-12-01

The oral commensal Streptococcus gordonii must adapt to constantly fluctuating and often hostile environmental conditions to persist in the oral cavity. The arginine deiminase system (ADS) of S. gordonii enables cells to produce, ornithine, ammonia, CO(2), and ATP from arginine hydrolysis, augmenting the acid tolerance of the organism. The ADS genes are substrate inducible and sensitive to catabolite repression, mediated through ArcR and CcpA, respectively, but the system also requires low pH and anaerobic conditions for optimal activation. Here, we demonstrate that the CiaRH and ComDE two-component systems (TCS) are required for low-pH-dependent expression of ADS genes in S. gordonii. Further, the VicRK TCS is required for optimal ADS gene expression under anaerobic conditions and enhances the sensitivity of the operon to repression by oxygen. The known anaerobic activator of the ADS, Fnr-like protein (Flp), appeared to act independently of the Vic TCS. Mutants of S. gordonii lacking components of the CiaRH, ComDE, or VicRK grew more slowly in acidified media and were more sensitive to killing at lethal pH values and to agents that induce oxidative stress. This study provides the first evidence that TCS can regulate the ADS of bacteria in response to specific environmental signals and reveals some notable differences in the contribution of CiaRH, ComDE, and VicRK to viability and stress tolerance between the oral commensal S. gordonii and the oral pathogen Streptococcus mutans.

Blocking of p38 and transforming growth factor β receptor pathways impairs the ability of tolerogenic dendritic cells to suppress murine arthritis.

PubMed

Gárate, David; Rojas-Colonelli, Nicole; Peña, Corina; Salazar, Lorena; Abello, Paula; Pesce, Bárbara; Aravena, Octavio; García-González, Paulina; Ribeiro, Carolina H; Molina, María C; Catalán, Diego; Aguillón, Juan C

2013-01-01

Dendritic cells (DCs) modulated with lipopolysaccharide (LPS) are able to reduce inflammation when therapeutically administered into mice with collagen-induced arthritis (CIA). The aim of this study was to uncover the mechanisms that define the tolerogenic effect of short-term LPS-modulated DCs on CIA. Bone marrow-derived DCs were stimulated for 4 hours with LPS and characterized for their expression of maturation markers and their cytokine secretion profiles. Stimulated cells were treated with SB203580 or SB431542 to inhibit the p38 or transforming growth factor β (TGFβ) receptor pathway, respectively, or were left unmodified and, on day 35 after CIA induction, were used to inoculate mice. Disease severity was evaluated clinically. CD4+ T cell populations were counted in the spleen and lymph nodes from inoculated or untreated mice with CIA. CD4+ splenic T cells were transferred from mice with CIA treated with LPS-stimulated DCs or from untreated mice with CIA into other mice with CIA on day 35 of arthritis. Treatment with LPS-stimulated DCs increased the numbers of interleukin-10 (IL-10)-secreting and TGFβ-secreting CD4+ T cells, but decreased the numbers of Th17 cells. Adoptive transfer of CD4+ T cells from treated mice with CIA reproduced the inhibition of active CIA accomplished with LPS-stimulated DCs. The therapeutic effect of LPS-stimulated DCs and their influence on T cell populations were abolished when the p38 and the TGFβ receptor pathways were inhibited. DCs modulated short-term (4 hours) with LPS are able to confer a sustained cure in mice with established arthritis by re-educating the CD4+ T cell populations. This effect is dependent on the p38 and the TGFβ receptor signaling pathways, which suggests the participation of IL-10 and TGFβ in the recovery of tolerance. Copyright © 2013 by the American College of Rheumatology.

Effect of nutritional support on mitochondrial complex I activity in malnourished patients with anorexia nervosa.

PubMed

De-Mateo-Silleras, Beatriz; Alonso-Torre, Sara R; Redondo-del-Río, Paz; Jeejeebhoy, Khursheed; Miján-de-la-Torre, Alberto

2013-11-01

Previous studies have shown a reduction in lymphocyte mitochondrial complex I activity (CIA) in malnourished patients, which is restored after refeeding. Our aim was to evaluate the usefulness of CIA as an indicator of nutritional status in anorexia nervosa patients. Twelve malnourished anorexia nervosa females (mean age, 24.5 years) were admitted to the Eating Disorders Unit. Basal and weekly anthropometrics, bioelectric impedance (BIA), body composition, and CIA were performed until discharge. Patients were matched to 25 healthy females and refeeding was adjusted according to the Unit's protocol. Statistics were used as appropriated and significance was reached at p < 0.05. Patients showed a significant reduction in body mass index, fat mass and fat free mass (FFM), triceps skinfold, and waist circumference on admission as compared with the control group. Parameters improved during hospitalization, but they failed to reach normal values at discharge. Compared with controls, CIA was significantly lower in patients on admission (2.16 vs. 5.68 nmol·min(-1)·mg protein(-1)). Refeeding and weight gain did not restore CIA. A positive association (r(2) = 0.69) was found between FFM and CIA in patients at discharge. Malnourished females with anorexia nervosa have lower CIA than controls that is not recovered after refeeding. This could be because of a low FFM exacerbated by physical inactivity while in hospital.

Suppressing effect of low-dose gamma-ray irradiation on collagen-induced arthritis.

PubMed

Nakatsukasa, Hiroko; Tsukimoto, Mitsutoshi; Ohshima, Yasuhiro; Tago, Fumitoshi; Masada, Ayako; Kojima, Shuji

2008-07-01

We previously reported attenuation of autoimmune disease by low-dose gamma-ray irradiation in MRL-lpr/lpr mice. Here, we studied the effect of low-dose gamma-ray irradiation on collagen-induced arthritis (CIA) in DBA/1J mice. Mice were immunized with type II collagen, and exposed to low-dose gamma-rays (0.5 Gy per week for 5 weeks). Paw swelling, redness, and bone degradation were suppressed by irradiation, which also delayed the onset of pathological change and reduced the severity of the arthritis. Production of tumor necrosis factor-alpha, interferon-gamma, and interleukin-6, which play important roles in the onset of CIA, was suppressed by the irradiation. The level of anti-type II collagen antibody, which is essential for the onset of CIA, was also lower in irradiated CIA mice. The population of plasma cells was increased in CIA mice, but irradiation blocked this increase. Since regulatory T cells are known to be involved in suppression of autoimmune disease, the population of CD4(+)CD25(+)Foxp3(+) regulatory T cells was measured. Intriguingly, a significant increase of these regulatory T cells was found in irradiated CIA mice. Overall, our data suggest that low-dose gamma-ray irradiation could attenuate CIA through suppression of pro-inflammatory cytokines and autoantibody production, and induction of regulatory T cells.

76 FR 11561 - Additional Designations, Foreign Narcotics Kingpin Designation Act

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-02

....A., Cali, Colombia; c/o INVERSIONES CIFUENTES Y CIA. S. EN C., Medellin, Colombia; c/o PARQUES...., Mexico City, Distrito Federal, Mexico; c/o INVERSIONES CIFUENTES Y CIA. S. EN C., Medellin, Colombia; c/o..., Colombia; c/o INVERSIONES CIFUENTES Y CIA. S. EN C., Medellin, Colombia; c/o LE CLAUDE, S.A. DE C.V...

Microsurgical Bypass Training Rat Model: Part 2-Anastomosis Configurations.

PubMed

Tayebi Meybodi, Ali; Lawton, Michael T; Yousef, Sonia; Mokhtari, Pooneh; Gandhi, Sirin; Benet, Arnau

2017-11-01

Mastery of microsurgical anastomosis is key to achieving good outcomes in cerebrovascular bypass procedures. Animal models (especially rodents) provide an optimal preclinical bypass training platform. However, the existing models for practicing different anastomosis configurations have several limitations. We sought to optimize the use of the rat's abdominal aorta and common iliac arteries (CIA) for practicing the 3 main anastomosis configurations commonly used in cerebrovascular surgery. Thirteen male Sprague-Dawley rats underwent inhalant anesthesia. The abdominal aorta and the CIAs were exposed. The distances between the major branches of the aorta were measured to find the optimal location for an end-to-end anastomosis. Also, the feasibility of performing side-to-side and end-to-side anastomoses between the CIAs was assessed. All bypass configurations could be performed between the left renal artery and the CIA bifurcation. The longest segments of the aorta without major branches were 1) between the left renal and left iliolumbar arteries (16.9 mm ± 4.6), and 2) between the right iliolumbar artery and the aortic bifurcation (9.7 mm ± 4.7). The CIAs could be juxtaposed for an average length of 7.6 mm ± 1.3, for a side-to-side anastomosis. The left CIA could be successfully reimplanted on to the right CIA at an average distance of 9.1 mm ± 1.6 from the aortic bifurcation. Our results show that rat's abdominal aorta and CIAs may be effectively used for all the anastomosis configurations used in cerebral revascularization procedures. We also provide technical nuances and anatomic descriptions to plan for practicing each bypass configuration. Copyright © 2017 Elsevier Inc. All rights reserved.

Extracts of Bauhinia championii (Benth.) Benth. attenuate the inflammatory response in a rat model of collagen-induced arthritis.

PubMed

Xu, Wei; Huang, Mingqing; Zhang, Yuqin; Li, Huang; Zheng, Haiyin; Yu, Lishuang; Chu, Kedan; Lin, Yu; Chen, Lidian

2016-05-01

Rheumatoid arthritis is considered a serious public health problem, which is commonly treated with traditional Chinese or herbal medicine. The present study evaluated the effects of Bauhinia championii (Benth.) Benth. extraction (BCBE) on a type II collagen-induced arthritis (CIA) rat model. Wistar rats with CIA received either 125 or 500 mg/kg BCBE, after which, paw swelling was markedly suppressed compared with in the model group. In addition, BCBE significantly ameliorated pathological joint alterations, including synovial hyperplasia, and cartilage and bone destruction. The protein and mRNA expression levels of interleukin (IL)‑6, IL‑8, tumor necrosis factor‑α and nuclear factor‑κB in synovial tissue were determined by immunohistochemical staining, western blot analysis and reverse transcription‑polymerase chain reaction. The results demonstrated that the expression levels of these factors were significantly downregulated in the BCBE‑treated group compared with in the model group. These results indicated that BCBE may exert an inhibitory effect on the CIA rat model, and its therapeutic potential is associated with its anti-inflammatory action.

Extracts of Bauhinia championii (Benth.) Benth. attenuate the inflammatory response in a rat model of collagen-induced arthritis

PubMed Central

XU, WEI; HUANG, MINGQING; ZHANG, YUQIN; LI, HUANG; ZHENG, HAIYIN; YU, LISHUANG; CHU, KEDAN; LIN, YU; CHEN, LIDIAN

2016-01-01

Rheumatoid arthritis is considered a serious public health problem, which is commonly treated with traditional Chinese or herbal medicine. The present study evaluated the effects of Bauhinia championii (Benth.) Benth. extraction (BCBE) on a type II collagen-induced arthritis (CIA) rat model. Wistar rats with CIA received either 125 or 500 mg/kg BCBE, after which, paw swelling was markedly suppressed compared with in the model group. In addition, BCBE significantly ameliorated pathological joint alterations, including synovial hyperplasia, and cartilage and bone destruction. The protein and mRNA expression levels of interleukin (IL)-6, IL-8, tumor necrosis factor-α and nuclear factor-κB in synovial tissue were determined by immunohistochemical staining, western blot analysis and reverse transcription-polymerase chain reaction. The results demonstrated that the expression levels of these factors were significantly downregulated in the BCBE-treated group compared with in the model group. These results indicated that BCBE may exert an inhibitory effect on the CIA rat model, and its therapeutic potential is associated with its anti-inflammatory action. PMID:27035125

Collison-Induced Absorption of Oxygen Molecule as Studied by High Sensitivity Spectroscopy

NASA Astrophysics Data System (ADS)

Kashihara, Wataru; Shoji, Atsushi; Kawai, Akio

2017-06-01

Oxygen dimol is transiently generated when two oxygen molecules collide. At this short period, the electron clouds of molecules are distorted and some forbidden transition electronic transitions become partially allowed. This transition is called CIA (Collision-induced absorption). There are several CIA bands appearing in the spectral region from UV to near IR. Absorption of solar radiation by oxygen dimol is a small but significant part of the total budget of incoming shortwave radiation. However, a theory predicting the lineshape of CIA is still under developing. In this study, we measured CIA band around 630 nm that is assigned to optical transition, a^{1}Δ_{g}(v=0):a^{1}Δ_{g}(v=0)-X^{3}Σ_{g}^{-}(v=0):X^{3}Σ_{g}^{-}(v=0) of oxygen dimol. CRDS(Cavity Ring-down Spectroscopy) was employed to measure weak absorption CIA band of oxygen. Laser beam around 630 nm was generated by a dye laser that was pumped by a YAG Laser. Multiple reflection of the probe light was performed within a vacuum chamber that was equipped with two high reflective mirrors. We discuss the measured line shape of CIA on the basis of collision pair model.

Oral administration of curcumin suppresses production of matrix metalloproteinase (MMP)-1 and MMP-3 to ameliorate collagen-induced arthritis: inhibition of the PKCdelta/JNK/c-Jun pathway.

PubMed

Mun, Se Hwan; Kim, Hyuk Soon; Kim, Jie Wan; Ko, Na Young; Kim, Do Kyun; Lee, Beob Yi; Kim, Bokyung; Won, Hyung Sik; Shin, Hwa-Sup; Han, Jeung-Whan; Lee, Hoi Young; Kim, Young Mi; Choi, Wahn Soo

2009-09-01

We investigated whether oral administration of curcumin suppressed type II collagen-induced arthritis (CIA) in mice and its effect and mechanism on matrix metalloproteinase (MMP)-1 and MMP-3 production in CIA mice, RA fibroblast-like synoviocytes (FLS), and chondrocytes. CIA in mice was suppressed by oral administration of curcumin in a dose-dependent manner. Macroscopic observations were confirmed by histological examinations. Histological changes including infiltration of immune cells, synovial hyperplasia, cartilage destruction, and bone erosion in the hind paw sections were extensively suppressed by curcumin. The histological scores were consistent with clinical arthritis indexes. Production of MMP-1 and MMP-3 were inhibited by curcumin in CIA hind paw sections and tumor necrosis factor (TNF)-alpha-stimulated FLS and chondrocytes in a dose-dependent manner. As for the mechanism, curcumin inhibited activating phosphorylation of protein kinase Cdelta (PKCdelta) in CIA, FLS, and chondrocytes. Curcumin also suppressed the JNK and c-Jun activation in those cells. This study suggests that the suppression of MMP-1 and MMP-3 production by curcumin in CIA is mediated through the inhibition of PKCdelta and the JNK/c-Jun signaling pathway.

Investigation into low-level anti-rubella virus IgG results reported by commercial immunoassays.

PubMed

Dimech, Wayne; Arachchi, Nilukshi; Cai, Jingjing; Sahin, Terri; Wilson, Kim

2013-02-01

Since the 1980s, commercial anti-rubella virus IgG assays have been calibrated against a WHO International Standard and results have been reported in international units per milliliter (IU/ml). Laboratories testing routine patients' samples collected 100 samples that gave anti-rubella virus IgG results of 40 IU/ml or less from each of five different commercial immunoassays (CIA). The total of 500 quantitative results obtained from 100 samples from each CIA were compared with results obtained from an in-house enzyme immunoassay (IH-EIA) calibrated using the WHO standard. All 500 samples were screened using a hemagglutination inhibition assay (HAI). Any sample having an HAI titer of 1:8 or less was assigned a negative anti-rubella virus antibody status. If the HAI titer was greater than 1:8, the sample was tested in an immunoblot (IB) assay. If the IB result was negative, the sample was assigned a negative anti-rubella virus IgG status; otherwise, the sample was assigned a positive status. Concordance between the CIA qualitative results and the assigned negative status ranged from 50.0 to 93.8% and 74.5 to 97.8% for the assigned positive status. Using a receiver operating characteristic analysis with the cutoff set at 10 IU/ml, the estimated sensitivity and specificity ranged from 70.2 to 91.2% and 65.9 to 100%, respectively. There was poor correlation between the quantitative CIA results and those obtained by the IH-EIA, with the coefficient of determination (R(2)) ranging from 0.002 to 0.413. Although CIAs have been calibrated with the same international standard for more than 2 decades, the level of standardization continues to be poor. It may be time for the scientific community to reevaluate the relevance of quantification of anti-rubella virus IgG.

Investigation into Low-Level Anti-Rubella Virus IgG Results Reported by Commercial Immunoassays

PubMed Central

Arachchi, Nilukshi; Cai, Jingjing; Sahin, Terri; Wilson, Kim

2013-01-01

Since the 1980s, commercial anti-rubella virus IgG assays have been calibrated against a WHO International Standard and results have been reported in international units per milliliter (IU/ml). Laboratories testing routine patients' samples collected 100 samples that gave anti-rubella virus IgG results of 40 IU/ml or less from each of five different commercial immunoassays (CIA). The total of 500 quantitative results obtained from 100 samples from each CIA were compared with results obtained from an in-house enzyme immunoassay (IH-EIA) calibrated using the WHO standard. All 500 samples were screened using a hemagglutination inhibition assay (HAI). Any sample having an HAI titer of 1:8 or less was assigned a negative anti-rubella virus antibody status. If the HAI titer was greater than 1:8, the sample was tested in an immunoblot (IB) assay. If the IB result was negative, the sample was assigned a negative anti-rubella virus IgG status; otherwise, the sample was assigned a positive status. Concordance between the CIA qualitative results and the assigned negative status ranged from 50.0 to 93.8% and 74.5 to 97.8% for the assigned positive status. Using a receiver operating characteristic analysis with the cutoff set at 10 IU/ml, the estimated sensitivity and specificity ranged from 70.2 to 91.2% and 65.9 to 100%, respectively. There was poor correlation between the quantitative CIA results and those obtained by the IH-EIA, with the coefficient of determination (R2) ranging from 0.002 to 0.413. Although CIAs have been calibrated with the same international standard for more than 2 decades, the level of standardization continues to be poor. It may be time for the scientific community to reevaluate the relevance of quantification of anti-rubella virus IgG. PMID:23254301

Zebrafish CiA interneurons are late-born primary neurons.

PubMed

Yeo, Sang-Yeob

2009-12-11

Pax2 is a neural-related transcription factor downstream of Notch signaling and is expressed in the developing spinal cord of zebrafish, including in CiA interneurons. However, the characteristics of pax2-positive neurons are largely unknown. The goal of this study was to characterize Pax2-positive neurons by examining their expression in embryos in which Notch function had been knocked down by mutation or injection of a morpholino or mRNA. I found that Pax2-positive CiA interneurons were late-differentiating primary neurons. pax2.1 was expressed in CoPA commissural neurons and CiA interneurons at 26 hpf. The number of pax2.1-positive cells increased in mind bomb mutant embryos or embryos injected with Su(H)1-MO, but not in cells injected with Xenopus Delta or Delta(stu) mRNA. These observations imply that Notch signaling plays a role in regulating the number of CiA neurons by preventing uncommitted precursors from acquiring a neuronal fate during vertebrate development.

Cancer-Related NEET Proteins Transfer 2Fe-2S Clusters to Anamorsin, a Protein Required for Cytosolic Iron-Sulfur Cluster Biogenesis.

PubMed

Lipper, Colin H; Paddock, Mark L; Onuchic, José N; Mittler, Ron; Nechushtai, Rachel; Jennings, Patricia A

2015-01-01

Iron-sulfur cluster biogenesis is executed by distinct protein assembly systems. Mammals have two systems, the mitochondrial Fe-S cluster assembly system (ISC) and the cytosolic assembly system (CIA), that are connected by an unknown mechanism. The human members of the NEET family of 2Fe-2S proteins, nutrient-deprivation autophagy factor-1 (NAF-1) and mitoNEET (mNT), are located at the interface between the mitochondria and the cytosol. These proteins have been implicated in cancer cell proliferation, and they can transfer their 2Fe-2S clusters to a standard apo-acceptor protein. Here we report the first physiological 2Fe-2S cluster acceptor for both NEET proteins as human Anamorsin (also known as cytokine induced apoptosis inhibitor-1; CIAPIN-1). Anamorsin is an electron transfer protein containing two iron-sulfur cluster-binding sites that is required for cytosolic Fe-S cluster assembly. We show, using UV-Vis spectroscopy, that both NAF-1 and mNT can transfer their 2Fe-2S clusters to apo-Anamorsin with second order rate constants similar to those of other known human 2Fe-2S transfer proteins. A direct protein-protein interaction of the NEET proteins with apo-Anamorsin was detected using biolayer interferometry. Furthermore, electrospray mass spectrometry of holo-Anamorsin prepared by cluster transfer shows that it receives both of its 2Fe-2S clusters from the NEETs. We propose that mNT and NAF-1 can provide parallel routes connecting the mitochondrial ISC system and the CIA. 2Fe-2S clusters assembled in the mitochondria are received by NEET proteins and when needed transferred to Anamorsin, activating the CIA.

Anti-inflammatory effects of oxymatrine on rheumatoid arthritis in rats via regulating the imbalance between Treg and Th17 cells

PubMed Central

Ma, Ailing; Yang, Yongya; Wang, Qiuyang; Wang, Yin; Wen, Jing; Zhang, Yanli

2017-01-01

Oxymatrine (OMT), a monosomic alkaloid extracted from the Chinese herb, Sophora flavescens Ait, has long been used as a traditional Chinese medicine for the treatment of inflammatory diseases. The aim of the present study was to investigate the potential anti-inflammatory effect of OMT, and its modulation on imbalance between regulatory T (Treg) cells and T helper (Th) 17 cells in rats with collagen-induced arthritis (CIA). Sprague-Dawley rats were immunized with type II collagen and following a second collagen immunization, the rats were treated with OMT or dexamethasone (DXM) intraperitoneally once a day for 43 days. Paw swelling, arthritic score and joint histopathology were evaluated. The Treg/Th17-mediated autoreactive response was assessed by determining serum levels of inflammatory response cytokines, including tumor necrosis factor (TNF)-α and interleukin (IL)-17, using an enzyme-linked immunosorbent assay. The mRNA levels of forkhead box P3 (FOXP3) and retinoic acid-related orphan receptor (ROR)γt in spleen cells stimulated with type II collagen were determined using reverse transcription-quantitative polymerase chain reaction analysis. In addition, the protein expression levels of FOXP3 and RORγt were measured using western blot analysis. The results showed that OMT treatment significantly reduced the severity of CIA, markedly abrogating paw swelling, arthritic scores and synovial hyperplasia, and the increased loss in body weight. OMT significantly reduced the production of TNF-α and IL-17A, upregulated FOXP3 and downregulated RORγt in rats with CIA. In conclusion, the present study demonstrated that OMT exhibited a protective effect on rheumatoid arthritis (RA) through the inhibition of inflammation and regulation of Treg/Th17 in the CIA rats, suggesting that OMT may be used as an immune suppressive and cartilage protective medicine in human RA. PMID:28440447

A pair of novel Cd(II) enantiomers based on lactate derivatives: Synthesis, crystal structures and properties

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

Xu, Zhong-Xuan, E-mail: xuzhongxuan1974@163.com; State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, the Chinese Academy of Sciences, Fuzhou, Fujian 350002; Ao, Ke-Hou

A pair of novel 3D homochiral metal−organic frameworks (HMOFs), namely [Cd{sub 2.5}((R)-CIA){sub 6}(1,4-DIB)(H{sub 2}O){sub 2}]·((CH{sub 3}){sub 2}NH{sub 2})·H{sub 2}O (1-D), [Cd{sub 2.5}((S)-CIA){sub 6}(1,4-DIB)(H{sub 2}O){sub 2}]·((CH{sub 3}){sub 2}NH{sub 2})·H{sub 2}O (1-L), have been synthesized using lactic acid derivative ligands ((R)-H{sub 3}CIA and (S)-H{sub 3}CIA) and 1,4-DIB. Crystallographic analyses indicate that the complexes 1-D and 1-L are packed by cage substructures. Some physical characteristics, such as solid-state circular dichroism (CD), thermal stabilities and photoluminescent properties are also investigated. Our results highlight the effective method to apply lactic acid derivative ligands to form interesting HMOFs. - Graphical abstract: Using lactic acid derivative ligandsmore » ((R)-H{sub 3}CIA and (S)-H{sub 3}CIA) and 1,4-DIB to assemble with Cd{sup 2+} ions, a pair of novel 3D homochiral metal-organic frameworks (HMOFs) with cage substructures have been synthesized. Display Omitted - Highlights: • Lactic acid derivative ligands • Cage substructure • Enantiomers.« less

Fe-S cluster coordination of the chromokinesin KIF4A alters its sub-cellular localization during mitosis.

PubMed

Ben-Shimon, Lilach; Paul, Viktoria D; David-Kadoch, Galit; Volpe, Marina; Stümpfig, Martin; Bill, Eckhard; Mühlenhoff, Ulrich; Lill, Roland; Ben-Aroya, Shay

2018-05-30

Fe-S clusters act as co-factors of proteins with diverse functions, e.g. in DNA repair. Down-regulation of the cytosolic iron-sulfur protein assembly (CIA) machinery promotes genomic instability by the inactivation of multiple DNA repair pathways. Furthermore, CIA deficiencies are associated with so far unexplained mitotic defects. Here, we show that CIA2B and MMS19, constituents of the CIA targeting complex involved in facilitating Fe-S cluster insertion into cytosolic and nuclear target proteins, co-localize with components of the mitotic machinery. Down-regulation of CIA2B and MMS19 impairs the mitotic cycle. We identify the chromokinesin KIF4A as a mitotic component involved in these effects. KIF4A binds a Fe-S cluster in vitro through its conserved cysteine-rich domain. We demonstrate in vivo that this domain is required for the mitosis-related KIF4A localization and for the mitotic defects associated with KIF4A knockout. KIF4A is the first identified mitotic component carrying such a post-translational modification. These findings suggest that the lack of Fe-S clusters in KIF4A upon down-regulation of the CIA targeting complex contributes to the mitotic defects. © 2018. Published by The Company of Biologists Ltd.

Palmitoylethanolamide and luteolin ameliorate development of arthritis caused by injection of collagen type II in mice.

PubMed

Impellizzeri, Daniela; Esposito, Emanuela; Di Paola, Rosanna; Ahmad, Akbar; Campolo, Michela; Peli, Angelo; Morittu, Valeria Maria; Britti, Domenico; Cuzzocrea, Salvatore

2013-01-01

N-palmitoylethanolamine (PEA) is an endogenous fatty acid amide belonging to the family of the N-acylethanolamines (NAEs). Recently, several studies demonstrated that PEA is an important analgesic, antiinflammatory, and neuroprotective mediator. The aim of this study was to investigate the effect of co-ultramicronized PEA + luteolin formulation on the modulation of the inflammatory response in mice subjected to collagen-induced arthritis (CIA). CIA was induced by an intradermally injection of 100 μl of the emulsion (containing 100 μg of bovine type II collagen (CII)) and complete Freund adjuvant (CFA) at the base of the tail. On day 21, a second injection of CII in CFA was administered. Mice subjected to CIA were administered PEA (10 mg/kg 10% ethanol, intraperitoneally (i.p.)) or co-ultramicronized PEA + luteolin (1 mg/kg, i.p.) every 24 hours, starting from day 25 to 35. Mice developed erosive hind-paw arthritis when immunized with CII in CFA. Macroscopic clinical evidence of CIA first appeared as periarticular erythema and edema in the hindpaws. The incidence of CIA was 100% by day 28 in the CII-challenged mice, and the severity of CIA progressed over a 35-day period with a resorption of bone. The histopathology of CIA included erosion of the cartilage at the joint. Treatment with PEA or PEA + luteolin ameliorated the clinical signs at days 26 to 35 and improved histologic status in the joint and paw. The degree of oxidative and nitrosative damage was significantly reduced in PEA + luteolin-treated mice, as indicated by nitrotyrosine and malondialdehyde (MDA) levels. Plasma levels of the proinflammatory cytokines and chemokines were significantly reduced by PEA + luteolin treatment. We demonstrated that PEA co-ultramicronized with luteolin exerts an antiinflammatory effect during chronic inflammation and ameliorates CIA.

Palmitoylethanolamide and luteolin ameliorate development of arthritis caused by injection of collagen type II in mice

PubMed Central

2013-01-01

Introduction N-palmitoylethanolamine (PEA) is an endogenous fatty acid amide belonging to the family of the N-acylethanolamines (NAEs). Recently, several studies demonstrated that PEA is an important analgesic, antiinflammatory, and neuroprotective mediator. The aim of this study was to investigate the effect of co-ultramicronized PEA + luteolin formulation on the modulation of the inflammatory response in mice subjected to collagen-induced arthritis (CIA). Methods CIA was induced by an intradermally injection of 100 μl of the emulsion (containing 100 μg of bovine type II collagen (CII)) and complete Freund adjuvant (CFA) at the base of the tail. On day 21, a second injection of CII in CFA was administered. Mice subjected to CIA were administered PEA (10 mg/kg 10% ethanol, intraperitoneally (i.p.)) or co-ultramicronized PEA + luteolin (1 mg/kg, i.p.) every 24 hours, starting from day 25 to 35. Results Mice developed erosive hind-paw arthritis when immunized with CII in CFA. Macroscopic clinical evidence of CIA first appeared as periarticular erythema and edema in the hindpaws. The incidence of CIA was 100% by day 28 in the CII-challenged mice, and the severity of CIA progressed over a 35-day period with a resorption of bone. The histopathology of CIA included erosion of the cartilage at the joint. Treatment with PEA or PEA + luteolin ameliorated the clinical signs at days 26 to 35 and improved histologic status in the joint and paw. The degree of oxidative and nitrosative damage was significantly reduced in PEA + luteolin-treated mice, as indicated by nitrotyrosine and malondialdehyde (MDA) levels. Plasma levels of the proinflammatory cytokines and chemokines were significantly reduced by PEA + luteolin treatment. Conclusions We demonstrated that PEA co-ultramicronized with luteolin exerts an antiinflammatory effect during chronic inflammation and ameliorates CIA. PMID:24246048

Achilles tenodesis for calcaneal insufficiency avulsion fractures associated with diabetes mellitus.

PubMed

Choi, Youngrak; Kwon, Young-Woo; Sim, Young-Suk; Kim, Taeho; Song, Dayoung; Lee, Soohyun

2017-12-13

Calcaneal insufficiency avulsion (CIA) fractures often present with neuropathic etiology, such as Charcot neuroarthropathy (CN). Under the same surgical procedures, the outcomes of CIA fractures are less desirable, compared to the outcomes of the traumatic calcaneal avulsion fractures. Here, the study suggests Achilles tenodesis technique using suture anchor after resection of the CIA fracture fragments could provide satisfactory clinical results in the cases of surgically indicated CIA fractures. This retrospective study included seven patients of calcaneal avulsion fracture who had underlying diabetes mellitus (DM) and no specific traumatic event. The patients were treated with Achilles tenodesis techniques for their CIA fractures. Achilles tenodesis was performed using suture anchor with removal of the fracture fragments. The patients were evaluated with the Foot and Ankle Outcome Score (FAOS), visual analogue scale (VAS), single-heel rise test, and X-ray images on their final follow-ups. Initially, three of the CIA fracture cases treated with traditional open reduction and internal fixation reported pullout failure. Consequently, all patients received Achilles tenodesis using suture anchor after bone fragment resection and had good clinical outcomes. Only one subject with low compliance reported poor outcome. The FAOS of each patient were obtained at a mean of 16.3 months after surgery. The results are as follows: pain 80.6 (SD = 6.2), symptom 83.8 (SD = 4.9), activities of daily living 80.5 (SD = 8.0), sport and recreation function 75.6 (SD = 11.93), and foot- and ankle-related quality of life 77.9 (SD = 6.7). On their final follow-ups, the average VAS was 2.6 (range, 1 to 4). Achilles tenodesis using suture anchor after bone fragment resection achieved competent clinical results in the patients with CIA fractures. The study proposes that this surgical procedure could be an appropriate treatment option for patients with CIA fractures. The study was approved by the institutional review board (IRB) of our medical center (IRB File No. 2016-07-043), retrospectively registered.

Costs of Public Pharmaceutical Services in Rio de Janeiro Compared to Farmácia Popular Program.

PubMed

Silva, Rondineli Mendes da; Caetano, Rosângela

2016-12-22

To analyze the costs of public pharmaceutical services compared to Farmácia Popular Program (Popular Pharmacy Program). Comparison between prices paid by Aqui Tem Farmácia Popular Program (Farmácia Popular is available here) with the full costs of medicine provision by the Municipal Health Department of Rio de Janeiro. The comparison comprised 25 medicines supplied by both the municipal pharmaceutical service and Aqui Tem Farmácia Popular Program. Calculating the cost per pharmaceutical unit of each medicine included expenditure by Municipal Health Department of Rio de Janeiro with procurement (price), logistics, and local dispensation. The reference price of medicines paid by Aqui Tem Farmácia Popular was taken from the Brazilian Ministry of Health standard in force in 2012. Comparisons included full reference price; reference price minus 10.0% copayment by users; and maximum reference paid by the Ministry of Health (minus copayment and taxes). Simulations were carried out of the differences between the costs of Municipal Health Department of Rio de Janeiro with the common medicines and those potentially incurred based on the reference price of Aqui Tem Farmácia Popular. The Municipal Health Department of Rio de Janeiro spent R$28,526,526.57 with 25 medicines of the common list in 2012; 58.7% accounted for direct procurement costs. The estimated costs of the Health Department were generally lower than the reference prices of the Aqui Tem Farmácia Popular Program for 20 medicines, regardless of reference prices. The potential costs incurred by Health Department if expenditure of its consumption pattern were based on the reference prices of Aqui Tem Farmácia Popular would be R$124,170,777.76, considering the best scenario of payment by the Brazilian Ministry of Health (90.0% of the reference price, minus taxes). The difference in costs between public provision by Municipal Health Department of Rio de Janeiro and Farmácia Popular Program indicates that some reference prices could be reviewed aiming at their reduction. Analisar custos da assistência farmacêutica pública frente ao Programa Farmácia Popular. Comparação entre os valores pagos pelo Programa Aqui Tem Farmácia Popular com os custos integrais relativos à provisão de medicamentos pela Secretaria Municipal de Saúde do Rio de Janeiro. A comparação compreendeu 25 medicamentos, comuns tanto à provisão pela assistência farmacêutica pública municipal quanto pelo Programa Aqui Tem Farmácia Popular. O cálculo do custo unitário por unidade farmacotécnica de cada medicamento envolveu os gastos da Secretaria Municipal de Saúde com custos de aquisição (preço), logísticos e com a dispensação em nível local. O valor de referência dos medicamentos pago pelo Aqui Tem Farmácia Popular foi extraído da norma ministerial em vigor em 2012. As comparações envolveram o valor de referência pleno; valor de referência com desconto dos 10,0% pagos de contrapartida pelos usuários; e valor de referência máximo pago pelo Ministério da Saúde (descontados contrapartida e sem impostos).Foram realizadas simulações das diferenças entre os gastos da Secretaria Municipal de Saúde do Rio de Janeiro com os medicamentos do elenco comum e os que seriam incorridos se esses tivessem sido executados com base no valor de referência do Aqui Tem Farmácia Popular. A Secretaria Municipal de Saúde do Rio de Janeiro gastou R$28.526.526,57 com 25 medicamentos do rol comum em 2012; 58,7% corresponderam a custos diretos com a aquisição dos produtos. Os custos estimados da Secretaria Municipal de Saúde do Rio de Janeiro foram, em geral, menores que os valores de referência do Programa Aqui Tem Farmácia Popular em 20 medicamentos, independentemente dos valores de referência. Os custos que seriam incorridos pela Secretaria Municipal de Saúde do Rio de Janeiro, caso seu padrão de consumo tivesse como valor de pagamento os valores de referência do Aqui Tem Farmácia Popular seriam de R$124.170.777,76 considerando a melhor situação de pagamento pelo Ministério da Saúde (90,0% do valor de referência, com impostos descontados). A diferença de custos entre a provisão pública pela Secretaria Municipal de Saúde do Rio de Janeiro e o Programa Aqui Tem Farmácia Popular sinaliza que alguns valores de referência poderiam ser objetos de exame para sua redução.

Why UW: Factoring in the Decision Point for Unconventional Warfare

DTIC Science & Technology

2012-12-01

political, economic, ideological, and technological elements into the concept of strategy has existed since ancient times. See Edward Mead Earle...declassified CIA records. Irene Gendzier, states that “Known CIA agents Miles Copeland and Stephen Meade were directly involved in the Syria coup of 1947...State Herbert Hoover Jr. gave full approval.98 The only note of caution came later from the CIA operations chief, Frank Wisner, who insisted that no

Assessment of Caregiver Inventory for Rett Syndrome

PubMed Central

Lane, Jane B.; Salter, Amber R.; Jones, Nancy E.; Cutter, Gary; Horrigan, Joseph; Skinner, Steve A.; Kaufmann, Walter E.; Glaze, Daniel G.; Neul, Jeffrey L.; Percy, Alan K.

2017-01-01

Rett syndrome (RTT) requires total caregiver attention and leads to potential difficulties throughout life. The Caregiver Burden Inventory, designed for Alzheimer disease, was modified to a RTT Caregiver Inventory Assessment (RTT CIA). Reliability and face, construct, and concurrent validity were assessed in caregivers of individuals with RTT. Chi-square or Fisher’s exact test for categorical variables and t-tests or Wilcoxon two-sample tests for continuous variables were utilized. Survey completed by 198 caregivers; 70 caregivers completed follow-up assessment. Exploratory factor analysis revealed good agreement for Physical Burden, Emotional Burden, and Social Burden. Internal reliability was high (Cronbach’s alpha: 0.898). RTT CIA represents a reliable and valid measure, providing a needed metric of caregiver burden in this disorder. PMID:28132121

Intraosseous anesthesia using a computer-controlled system during non-surgical periodontal therapy (root planing): Two case reports.

PubMed

Han, Keumah; Kim, Jongbin

2018-02-01

Local anesthesia is administered to control pain, but it may induce fear and anxiety. Root planing is a non-surgical periodontal therapy; however, when it is performed in an extensive manner, some tissue removal is inevitable. Notably, this removal may be so painful that local anesthesia is required to be administered to the area scheduled for the treatment. Although patients tend to accept root planing easily, they frequently express a fear of local anesthesia. Intraosseous anesthesia (IA) is an intraosseous injection technique, whereby local anesthetic is injected into the cancellous bone supporting the teeth. A computer-controlled IA system (CIAS) exhibits multiple benefits, such as less painful anesthesia, reduced soft tissue numbness, and the provision of palatal or lingual, as well as buccal, anesthesia via single needle penetration. In this report, we present two cases of root planing that were performed under local anesthesia, using a CIAS.

Intraosseous anesthesia using a computer-controlled system during non-surgical periodontal therapy (root planing): Two case reports

PubMed Central

2018-01-01

Local anesthesia is administered to control pain, but it may induce fear and anxiety. Root planing is a non-surgical periodontal therapy; however, when it is performed in an extensive manner, some tissue removal is inevitable. Notably, this removal may be so painful that local anesthesia is required to be administered to the area scheduled for the treatment. Although patients tend to accept root planing easily, they frequently express a fear of local anesthesia. Intraosseous anesthesia (IA) is an intraosseous injection technique, whereby local anesthetic is injected into the cancellous bone supporting the teeth. A computer-controlled IA system (CIAS) exhibits multiple benefits, such as less painful anesthesia, reduced soft tissue numbness, and the provision of palatal or lingual, as well as buccal, anesthesia via single needle penetration. In this report, we present two cases of root planing that were performed under local anesthesia, using a CIAS. PMID:29556561

Assessing Immunity to Rubella Virus: a Plea for Standardization of IgG (Immuno)assays

PubMed Central

Bouthry, Elise; Huzly, Daniela; Ogee-Nwankwo, Adaeze; Hao, LiJuan; Adebayo, Adebola; Icenogle, Joseph; Sarasini, Antonella; Revello, Maria Grazia; Grangeot-Keros, Liliane

2016-01-01

Immunity to rubella virus (RV) is commonly determined by measuring specific immunoglobulin G (RV IgG). However, RV IgG results and their interpretation may vary, depending on the immunoassay, even though most commercial immunoassays (CIAs) have been calibrated against an international standard and results are reported in international units per milliliter. A panel of 322 sera collected from pregnant women that tested negative or equivocal for RV IgG in a prior test (routine screening) was selected. This panel was tested with two reference tests, immunoblotting (IB) and neutralization (Nt), and with 8 CIAs widely used in Europe. IB and Nt gave concordant results on 267/322 (82.9%) sera. Of these, 85 (26.4%) sera were negative and 182 (56.5%) sera were positive for both tests. All 85 IB/Nt-negative samples were classified as negative with all CIAs. Of the 182 IB/Nt-positive samples, 25.3 to 61.5% were classified as equivocal and 6 to 64.8% were classified as positive with the CIAs. Wide variations in titers in international units per milliliter were observed. In our series, more than half of the women considered susceptible to RV based on CIA results tested positive for RV antibodies by IB/Nt. Our data suggest that (i) sensitivity of CIAs could be increased by considering equivocal results as positive and (ii) the definition of immunity to RV as the 10-IU/ml usual cutoff as well as the use of quantitative results for clinical decisions may warrant reconsideration. A better standardization of CIAs for RV IgG determination is needed. PMID:27147722

Interleukin-35 upregulates OPG and inhibits RANKL in mice with collagen-induced arthritis and fibroblast-like synoviocytes.

PubMed

Li, Y; Li, D; Li, Y; Wu, S; Jiang, S; Lin, T; Xia, L; Shen, H; Lu, J

2016-04-01

IL-35 is a novel anti-inflammatory cytokine, but the exact role of IL-35 in the progression of RA remains unclear, especially associated with osteoporosis and bone erosion. The present research has not been reported. Our purpose is to study how IL-35 affects RA bone destruction. This study investigated the effect of interleukin-35 (IL-35) on OPG and RANKL expression in collagen-induced arthritis (CIA) in rats and in cultured fibroblast-like synoviocytes (FLS). Thirty DBA/1J mice were randomly assigned to three groups (n = 10 per group): the control group, the CIA group, and the CIA + IL-35 group. Collagen-induced arthritis was induced by immunization with collagen. IL-35 was intraperitoneally injected daily for 10 days, starting from the 24(th) day after immunization. FLS cells were isolated and cultured from CIA. The expression of IL-17, RANKL, and OPG was determined by RT-PCR and Western blot. Each experiment was repeated three times. CIA mice exhibited arthritis symptoms on day 24, followed by a rapid progression of arthritis. The expression of IL-17 and RANKL was increased and the expression of OPG was decreased in CIA mice compared with control mice. IL-35 treatment inhibited the development of arthritis in CIA mice, accompanied by a decrease in the expression of IL-17 and RANKL and an increase in the expression of OPG. Furthermore, IL-35 dose-dependently inhibited the expression of RANKL and increased the expression of OPG in cultured FLS cells. IL-35 inhibits RANKL expression and increases OPG expression in CIA mice. IL-35 may be used for treating rheumatoid arthritis.

Assessing Immunity to Rubella Virus: a Plea for Standardization of IgG (Immuno)assays.

PubMed

Bouthry, Elise; Furione, Milena; Huzly, Daniela; Ogee-Nwankwo, Adaeze; Hao, LiJuan; Adebayo, Adebola; Icenogle, Joseph; Sarasini, Antonella; Revello, Maria Grazia; Grangeot-Keros, Liliane; Vauloup-Fellous, Christelle

2016-07-01

Immunity to rubella virus (RV) is commonly determined by measuring specific immunoglobulin G (RV IgG). However, RV IgG results and their interpretation may vary, depending on the immunoassay, even though most commercial immunoassays (CIAs) have been calibrated against an international standard and results are reported in international units per milliliter. A panel of 322 sera collected from pregnant women that tested negative or equivocal for RV IgG in a prior test (routine screening) was selected. This panel was tested with two reference tests, immunoblotting (IB) and neutralization (Nt), and with 8 CIAs widely used in Europe. IB and Nt gave concordant results on 267/322 (82.9%) sera. Of these, 85 (26.4%) sera were negative and 182 (56.5%) sera were positive for both tests. All 85 IB/Nt-negative samples were classified as negative with all CIAs. Of the 182 IB/Nt-positive samples, 25.3 to 61.5% were classified as equivocal and 6 to 64.8% were classified as positive with the CIAs. Wide variations in titers in international units per milliliter were observed. In our series, more than half of the women considered susceptible to RV based on CIA results tested positive for RV antibodies by IB/Nt. Our data suggest that (i) sensitivity of CIAs could be increased by considering equivocal results as positive and (ii) the definition of immunity to RV as the 10-IU/ml usual cutoff as well as the use of quantitative results for clinical decisions may warrant reconsideration. A better standardization of CIAs for RV IgG determination is needed. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Identification of a Novel Gene, CIA6, Required for Normal Pyrenoid Formation in Chlamydomonas reinhardtii1[C][W][OA

PubMed Central

Ma, Yunbing; Pollock, Steve V.; Xiao, Ying; Cunnusamy, Khrishen; Moroney, James V.

2011-01-01

Chlamydomonas reinhardtii possesses a CO2-concentrating mechanism (CCM) that allows the alga to grow at low CO2 concentrations. One common feature seen in photosynthetic organisms possessing a CCM is the tight packaging of Rubisco within the cell. In many eukaryotic algae, Rubisco is localized to the pyrenoid, an electron-dense structure within the chloroplast. In order to identify genes required for a functional CCM, insertional Bleomycin resistance (BleR) mutants were generated and screened for growth on minimal medium under high CO2 conditions (5% CO2 in air) but only slow or no growth under very low CO2 conditions (0.01% CO2 in air). One mutant identified from this screen was named cia6. Physiological studies established that cia6 grows poorly on low levels of CO2 and has an impaired ability to accumulate inorganic carbon. The inserted BleR disrupted a gene encoding a protein with sequence similarity to proteins containing SET domain methyltransferase, although experiments using overexpressed CIA6 failed to demonstrate the methyltransferase activity. Electron microscopy revealed that the pyrenoid of cia6 mutant cells is highly disorganized. Complementation of the mutant restored the pyrenoid, the ability to grow under low-CO2 conditions, and the ability to concentrate inorganic carbon. Quantitative reverse transcription-polymerase chain reaction data from a low-CO2 induction time-course experiment demonstrated that the up-regulation of several CCM components is slower in cia6 compared with the wild type. This slow induction was further confirmed at the protein level using western blots. These results indicated that CIA6 is required for the formation of the pyrenoid and further supported the notion that the pyrenoid is required for a functional CCM in C. reinhardtii. PMID:21527423

Does Military Culture Adequately Prepare Senior Leaders to Provide Clear Objective, and Useful Strategic Advice?

DTIC Science & Technology

2012-05-17

of Gross Domestic Product (GDP). The CIA World Factbook estimates the 2010 GDP of the ROK at just over $1 trillion and the 2009 DPRK GDP at around...3 Central Intelligence Agency, “The World Fact Book,” cia.gov. https://www.cia.gov/library...publications/the- world -factbook/fields/2195.html#ks (accessed online on 9 January 2012). 4 George C.Herring, America’s Longest War: The United States and

The role of lipopolysaccharide injected systemically in the reactivation of collagen-induced arthritis in mice

PubMed Central

Yoshino, Shin; Ohsawa, Motoyasu

2000-01-01

We investigated the role of bacterial lipopolysaccharide (LPS) in the reactivation of autoimmune disease by using collagen-induced arthritis (CIA) in mice in which autoimmunity to the joint cartilage component type II collagen (CII) was involved.CIA was induced by immunization with CII emulsified with complete Freund's adjuvant at the base of the tail (day 0) followed by a booster injection on day 21. Varying doses of LPS from E. coli were i.p. injected on day 50.Arthritis began to develop on day 25 after immunization with CII and reached a peak on day 35. Thereafter, arthritis subsided gradually but moderate joint inflammation was still observed on day 50. An i.p. injection of LPS on day 50 markedly reactivated arthritis on a dose-related fashion. Histologically, on day 55, there were marked oedema of synovium which had proliferated by the day of LPS injection, new formation of fibrin, and intense infiltration of neutrophils accompanied with a large number of mononuclear cells. The reactivation of CIA by LPS was associated with increases in anti-CII IgG and IgG2a antibodies as well as various cytokines including IL-12, IFN-γ, IL-1β, and TNF-α. LPS from S. enteritidis, S. typhimurium, and K. neumoniae and its component, lipid A from E. coli also reactivated the disease. Polymyxin B sulphate suppressed LPS- or lipid A-induced reactivation of CIA.These results suggest that LPS may play an important role in the reactivation of autoimmune joint inflammatory diseases such as rheumatoid arthritis in humans. PMID:10742285

Performance evaluation of a novel chemiluminescence assay for detection of anti-GBM antibodies: an international multicenter study.

PubMed

Mahler, Michael; Radice, Antonella; Sinico, Renato A; Damoiseaux, Jan; Seaman, Andrea; Buckmelter, Kristen; Vizjak, Alenka; Buchner, Carol; Binder, Walter L; Fritzler, Marvin J; Cui, Zhao

2012-01-01

Autoantibodies to the non-collagen region (NC1) of the alpha-3 subunit of collagen IV represent a serological hallmark in the diagnosis of Goodpasture's syndrome (GPS). The objective of our study was to carefully analyze the performance characteristics of a novel anti-glomerular basement membrane (GBM) chemiluminescence immunoassay (CIA). Sera from patients with GPS (n = 90) were collected from four clinical centers. Samples from different disease groups (n = 397) and healthy individuals (n = 400) were used as controls. All samples were tested for anti-GBM antibodies by a rapid, random access CIA (QUANTA Flash™ GBM). Most of the samples were also tested using other methods including different commercial anti-GBM IgG assays and research assays for anti-GBM IgA and IgM. The sensitivity and specificity of the novel CIA was 95.6% [95% confidence interval (CI) 89.0-98.8%] and 99.6% (95% CI 98.9-99.9%), respectively. Receiver operating characteristic analysis showed good discrimination between GPS patients and controls. The area under the curve was 0.98 (CI 0.96-1.0). The three anti-GBM antibody-positive samples from the control group were from two healthy individuals and one human immunodeficiency virus (HIV)-infected patient. All three individuals had low levels of anti-GBM antibodies [20, 24 and 25 chemiluminescent unit (CU), cutoff 20 CU]. When the results of the new CIA were compared to other methods, good agreement was observed: 95.8% (kappa = 0.92) versus EliA™ GBM, 97.4% (kappa = 0.95) versus both BINDAZYME™ Anti-GBM and QUANTA Lite® GBM. Anti-GBM IgA was detectable in low concentrations in patients with GPS and was associated with anti-GBM IgG but was less useful in discriminating GPS patients and controls. No discrimination was found for anti-GBM IgM. The novel QUANTA Flash™ GBM CIA demonstrated good sensitivity and specificity and had good agreement with other methods. Our data confirm that ∼5% of patients with GPS do not have detectable levels of anti-GBM antibodies.

Wu-Tou Decoction in Rheumatoid Arthritis: Integrating Network Pharmacology and In Vivo Pharmacological Evaluation

PubMed Central

Guo, Qingqing; Zheng, Kang; Fan, Danping; Zhao, Yukun; Li, Li; Bian, Yanqin; Qiu, Xuemei; Liu, Xue; Zhang, Ge; Ma, Chaoying; He, Xiaojuan; Lu, Aiping

2017-01-01

Purpose: This study aimed to explore underlying action mechanism of Wu-Tou decoction (WTD) in rheumatoid arthritis (RA) through network pharmacology prediction and experimental verification. Methods: Chemical compounds and human target proteins of WTD as well as RA-related human genes were obtained from TCM Database @ Taiwan, PubChem and GenBank, respectively. Subsequently, molecular networks and canonical pathways presumably involved in the treatment of WTD on RA were generated by ingenuity pathway analysis (IPA) software. Furthermore, experimental validation was carried out with MIP-1β-induced U937 cell model and collagen induced arthritis (CIA) rat model. Results: CCR5 signaling pathway in macrophages was shown to be the top one shared signaling pathway associated with both cell immune response and cytokine signaling. In addition, protein kinase C (PKC) δ and p38 in this pathway were treated as target proteins of WTD in RA. In vitro experiments indicated that WTD inhibited MIP-1β-induced production of TNF-α, MIP-1α, and RANTES as well as phosphorylation of CCR5, PKC δ, and p38 in U937 cells. WTD treatment maintained the inhibitory effects on production of TNF-α and RANTES in MIP-1β-induced U937 cells after CCR5 knockdown. In vivo experiments demonstrated that WTD ameliorated symptoms in CIA rats, decreased the levels of IL-1β, IL-2, IL-6, TNF-α, MIP-1α, MIP-2, RANTES, and IP-10 in serum of CIA rats, as well as mRNA levels of MIP-1α, MIP-2, RANTES, and IP-10 in ankle joints of CIA rats. Furthermore, WTD also lowered the phosphorylation levels of CCR5, PKC δ and p38 in both ankle joints and macrophages in ankle joints from CIA rats. Conclusion: It was demonstrated in this research that WTD played a role in inhibiting inflammatory response in RA which was closely connected with the modulation effect of WTD on CCR5 signaling pathway in macrophages. PMID:28515692

High-Performance Liquid Chromatography (HPLC) Quantification of Liposome-Delivered Doxorubicin in Arthritic Joints of Collagen-Induced Arthritis Rats.

PubMed

Niu, Hongqing; Xu, Menghua; Li, Shuangtian; Chen, Junwei; Luo, Jing; Zhao, Xiangcong; Gao, Chong; Li, Xiaofeng

2017-04-14

BACKGROUND Neoangiogenesis occurring in inflamed articular synovium in early rheumatoid arthritis (RA) is characterized by enhanced vascular permeability that allows nanoparticle agents, including liposomes, to deliver encapsulated drugs to arthritic joints and subsequently improve therapeutic efficacy and reduce adverse effects. However, the targeting distribution of liposomes in arthritic joints during RA has not been quantitatively demonstrated. We performed this study to evaluate the targeting distribution of PEGylated doxorubicin liposomes in the arthritic joints of collagen-induced arthritis (CIA) rats by high-performance liquid chromatography (HPLC). MATERIAL AND METHODS Two doxorubicin formulations were administered to CIA rats via tail intravenous injection at a single dose (50 mg/m²). CIA rats were sacrificed and the tissues of the inflamed ankle joints were collected. The content of doxorubicin in the arthritic joints was analyzed by a validated and reproducible HPLC method. A two-way ANOVA for 2×5 factorial design was used for statistical analysis. RESULTS The developed HPLC method was sensitive, precise, and reproducible. The method was successfully applied to quantify doxorubicin content in arthritic tissues. At each time point (6, 12, 24, 48, and 72 h), doxorubicin content in the arthritic joints of the doxorubicin liposome group (DOX-LIP group) was higher than in the free doxorubicin group (DOX group) (P<0.05). In the DOX-LIP group, doxorubicin levels in the arthritic joints increased gradually and significantly in the interval of 6-72 h post-administration. CONCLUSIONS PEGylated doxorubicin liposomes were targeted to, accumulated, and retained in the arthritic joints of CIA rats. The present study indicates that liposome encapsulation increases the therapeutic efficacy of antirheumatic drugs, presenting a promising therapeutic strategy for RA.

OX40 signaling is involved in the autoactivation of CD4+CD28- T cells and contributes to the pathogenesis of autoimmune arthritis.

PubMed

Jiang, Juean; Liu, Cuiping; Liu, Mi; Shen, Yu; Hu, Xiaohan; Wang, Qin; Wu, Jian; Wu, Min; Fang, Qi; Zhang, Xueguang

2017-03-21

CD4 + CD28 - T cells exhibit autoreactive potential in autoimmune disorders, including rheumatoid arthritis (RA). It is not well known which costimulator functions as an alternative second signal in the activation of this subset after CD28 expression is downregulated. Tumor necrosis factor receptor superfamily member OX40 is a key costimulator in the activation of T cells. The aim of this study was to investigate the costimulatory effects of OX40 on CD4 + CD28 - T cells in autoimmune arthritis. Clinical samples were collected from patients with RA and control subjects. Collagen-induced arthritis (CIA) was induced with collagen type II (CII) in DBA/1 mice. The CD4 + CD28 - OX40 + T-cell subset and its cytokine production were detected by flow cytometry. After T-cell purification, adoptive transfer was performed in CIA mice. The regulatory role of OX40 was determined by blocking experiments in vitro and in vivo. OX40 and OX40L were abnormally expressed in patients with RA and CIA mice. Further analysis showed that CD4 + CD28 - OX40 + T cells accumulated in patients with RA and in animal models. These cells produced higher levels of proinflammatory cytokines and were closely correlated with the clinicopathological features of the affected individuals. Adoptive transfer of CII-specific CD4 + CD28 - OX40 + T cells remarkably aggravated arthritic development and joint pathology in CIA mice. Moreover, OX40 blockade significantly reduced the proinflammatory responses and ameliorated arthritis development. OX40 acts as an alternative costimulator of CD4 + CD28 - T cells and plays a pathogenic role in autoimmune arthritic development, suggesting that it is a potential target for immunomodulatory therapy of RA.

Methotrexate, combined with cyclophosphamide attenuates murine collagen induced arthritis by modulating the expression level of Breg and DCs.

PubMed

Fan, Jinnan; Luo, Jing; Yan, Caiping; Hao, Runxi; Zhao, Xiangcong; Jia, Ruihuan; He, Jiaojiao; Xu, Dan; Miao, Miao; Li, Xiaofeng

2017-10-01

To explore the mechanism of methotrexate (MTX) and its combination with cyclophosphamide (CTX) in collagen-induced arthritis (CIA), we investigated the levels of several immune cells and cytokines in mice with different treatments. CIA was induced in DBA/1 mice at the age of 7 weeks by primary immunization with 100μl emulsion containing 2mg/ml bovine type II collagen which was mixed with complete Freund's adjuvant (CFA). The booster immunization was performed with 50-100μl emulsion containing 2mg/ml bovine type II collagen (CII) mixed with incomplete Freund's adjuvant (IFA). MTX, CTX or both were administrated after the booster immunization. Therapeutic effect was evaluated by arthritic scores, X-rays and assessment of histopathological joint destruction. The expression of TNF-α, IL-6, IL-23, IL-10 were also measured. The frequencies of different immune cell subsets in the lymph node, spleen and bone marrow were determined by flow cytometry analysis. Our results showed that CTX and MTX treatment attenuated the severity of arthritis of CIA mice and reduced the levels of several cytokines. CTX and MTX treated mice showed a lower frequency of B cells in bone marrow. Also, when treated the CIA mice with MTX, alone or together with CTX, the lymph nodes and spleen exhibited a decrease in regulatory B cells (Breg) and dendritic cells (DCs). Notably, the combination of MTX and CTX had a more pronounced effect. By measuring the levels of different immune cells those participated in the development of rheumatoid arthritis (RA), our experiment may help to evaluate the therapeutic effects and prognosis of arthritic diseases. Copyright © 2017. Published by Elsevier Ltd.

Petrography and chemistry of the bed sediments of the Red River in China and Vietnam: Provenance and chemical weathering

NASA Astrophysics Data System (ADS)

Borges, Joniell; Huh, Youngsook

2007-02-01

The Red (Hong) River straddles southwestern China and northern Vietnam and drains the eastern Indo-Asian collision zone. We collected bed sediments from its tributaries and main channel and report the petrographic point counts of framework grains and major oxide compositions as well as organic and inorganic carbon contents. The Q:F:Rf ratios and Q:F:(L-L c) ratios of the bed-load indicate quartz-poor, mineralogically immature sediments of recycled orogen provenance. The weathering indices based on major oxides — the chemical index of alteration (CIA) and the weathering index of Parker — are also consistent with the recycled sedimentary nature of the bed sediments. Using geographic information system (GIS) we calculated for each sample basin such parameters as temperature, precipitation, potential evapotranspiration, runoff, basin length, area, relief, and areal exposure of igneous, metamorphic and sedimentary rocks. Statistically meaningful correlations are obtained between the two weathering indices, between CIA and sedimentary to metamorphic rock fragments ratio, S / (S + M), and between CIA and sedimentary rock cover, but otherwise correlations are poor. The bed sediments preserve signatures of their provenance, but the effect of weathering is not clearly seen. Subtle differences in the bed sediments are observed between the Red and the Himalayan rivers (Indus, Ganges, and Brahmaputra) as well as between sub-basins within the Red River system and are attributed mainly to differences in lithology.

Enhancing student performance: Linking the geography curriculum, instruction, and assessment in the English-speaking Caribbean

NASA Astrophysics Data System (ADS)

Collymore, Jennifer C.

In a 21st century knowledge society individuals are expected to use their knowledge and skills to think critically, problem solve, make decisions, comprehend new ideas, communicate, and collaborate effectively with others. Helping students achieve this level of performance is no easy task and it brings into focus the fact that the effectiveness of any education system rests on the systemic coordination or alignment of three crucial components: curriculum, instruction and assessment (referred to as the CIA). These components must work in concert to facilitate and enhance student performance. However, educational reform typically targets these components in isolation, often treating only one component, rather than the system as a whole. The misalignment of these components can adversely affect student performance in any discipline. When the CIA components are out of alignment, it is difficult to evaluate student and system performance and achieve improvement in an educational system. Therefore, using geography education in Trinidad & Tobago as a case study, this study examined the nature of the alignment among the CIA components in the advanced geography system in the English- Speaking Caribbean and the extent to which the alignment may be affecting student performance. The study sought to determine the possible sources and causes of misalignment, the challenges to achieving alignment, and ways of achieving greater coordination among the CIA components of the system. The methodology employed in the study involved the use of classroom observations, interviews, and the Surveys of Enacted Curriculum Alignment Model which uses content analyses and surveys. The results showed that there were varying degrees of alignment among the components. There was acceptable alignment (Alignment Index ≥ 0.25) between the curriculum and assessment. However, the alignment between curriculum and instruction or assessment and instruction was poor (Alignment Index ≤ 0.12). The baseline threshold for acceptable alignment was 0.25. The misalignment between the curriculum and assessment stemmed from the fact that there were items tested in the assessment that were not identified in the examination syllabus. In terms of the misalignment between the curriculum/assessment and instruction, teachers were misallocating their teaching time and efforts; spending too much time teaching the skills and practices of the discipline rather than the core content areas and they were spending too much time teaching the content at the lower order cognitive level of recall. In addition, while research promotes student-centered approaches, cooperative learning, dialogic discourse, open informal questioning and discursive forms of writing, teachers still primarily use teacher-centered approaches, individualize instruction, monologic discourse and closed recall questions. The teachers' instructional practices are not affording students the opportunity to acquire and display their knowledge at the higher levels of cognition. The cause of the misalignment was attributed to a vague, overloaded syllabus and limited teaching time; vague evaluative criteria and feedback from the Examination Council; inadequate and insufficient teacher training and professional development; a lack of administrative support and mentorship for inexperienced teachers; and teacher frustration. Subsequently, the study offers a number of evidence based recommendations that range from the modification and refinement of the geography CIA triad to professional development programs and the design of interventions that can advance the teaching and learning of the discipline. Though the study is undertaken in a specific context, the educational issues addressed in the study transcend time, scale, and geographic boundaries and the results can inform the decision-making and practices of educators and education policy-makers everywhere.

Cell source-dependent in vivo immunosuppressive properties of mesenchymal stem cells derived from the bone marrow and synovial fluid of minipigs

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

Lee, Won-Jae; Hah, Young-Sool; Ock, Sun-A.

The in vitro differentiation and immunosuppressive capacity of mesenchymal stem cells (MSCs) derived from synovial fluid (SF-MSCs) and bone marrow extract (BM-MSCs) in an isogenic background of minipigs were comparatively analyzed in a collagen-induced arthritis (CIA) mouse model of rheumatoid arthritis (RA). The proliferation capacity and expression of pluripotent transcription factors (Oct3/4 and Sox2) were significantly (P<0.05) higher in SF-MSCs than in BM-MSCs. The differentiation capacity of SF-MSCs into adipocytes, osteocytes and neurocytes was significantly (P<0.05) lower than that of BM-MSCs, and the differentiation capacity of SF-MSCs into chondrocytes was significantly (P<0.05) higher than that of BM-MSCs. Systemic injection ofmore » BM- and SF-MSCs significantly (P<0.05) ameliorated the clinical symptoms of CIA mice, with SF-MSCs having significantly (P<0.05) higher clinical and histopathological recovery scores than BM-MSCs. Furthermore, the immunosuppressive properties of SF-MSCs in CIA mice were associated with increased levels of the anti-inflammatory cytokine interleukin (IL)-10, and decreased levels of the pro-inflammatory cytokine IL-1β and osteoclast-related sRANKL. In conclusion, SF-MSCs exhibited eminent pluripotency and differentiation capacity into chondrocytes, addition to substantial in vivo immunosuppressive capacity by elevating IL-10 and reducing IL-1β levels in CIA mice. - Highlights: • Immunosuppressive capacity of BM-, SM-, and SF-MSCs was evaluated in an RA model. • Proliferation, pluripotency and chondrogenic differentiation capacity were higher in SF-MSCs. • SF-MSCs exhibited improved therapeutic effects than BM-MSCs. • SF-MSCs may have applications as immunosuppressive therapy in autoimmune diseases.« less

32 CFR 1901.02 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY PUBLIC RIGHTS UNDER THE... meanings indicated: (a) Agency or CIA means the United States Central Intelligence Agency acting through... individual that is maintained by the Central Intelligence Agency in a system of records; (k) Requester or...

32 CFR 1901.02 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY PUBLIC RIGHTS UNDER THE... meanings indicated: (a) Agency or CIA means the United States Central Intelligence Agency acting through... individual that is maintained by the Central Intelligence Agency in a system of records; (k) Requester or...

Foot mobility and plantar fascia elasticity in patients with plantar fasciitis.

PubMed

Sahin, Namık; Oztürk, Alpaslan; Atıcı, Teoman

2010-01-01

In this study, we investigated the radiologic changes of feet in sagittal plane under weightbearing either with or without plantar fasciitis. The study includes 64 feet of the 42 subjects with heel pain (Group 1: 32 women, 10 men, mean age 48 years, range 33-57 years) and 80 feet of the 40 patients (Group 2: 30 women, 10 men, mean age 47.2 years, range 35-56 years) without heel pain. Calcaneal inclination angle (CIA), calcaneal-first metatarsal angle (CMA), and plantar fascia length (PFL) were measured in the lateral radiographs of the weightbearing and non-weightbearing foot. The values of Group 1 and Group 2 were compared. The mean CIA was 26° (range 18-35°), CMA was 121° (range 115-133°), and PFL was 131 mm (range 110-158 mm) in non-weightbearing position for Group 1. The mean CIA was 27° (range 17-38°), CMA was 122° (range 110-135°), and PFL was 136 mm (range 120-155 mm) in non-weightbearing position for Group 2. The mean CIA was 13.6° (range 5-25°), CMA was 138° (range 130-153°), and PFU was 143.8 mm (range 118-158 mm) in weightbearing position for Group 1. The mean CIA was 9.9° (range 4-25°), CMA was 145° (range 130-155°), and PFU was 151.4 mm (range 137-167 mm) in weightbearing position for Group 2. The difference between CIA, CMA, and PFL values were -13°, 17°, and 12 mm under condition of weightbearing and nonweightbearing position values for Group 1; and -17°, 23°, and 15 mm for Group 2. The differences were significant between weightbearing and non-weightbearing position values (p<0.05). The reduced CIA, CMA, and PFL changes during weight bearing might show reduced foot mobility and plantar fascia elasticity, which may lead to posterior heel pain syndrome.

Assessment of Collagen-Induced Arthritis Using Cyanine 5.5 Conjugated with Hydrophobically Modified Glycol Chitosan Nanoparticles: Correlation with 18F-Fluorodeoxyglucose Positron Emission Tomography Data

PubMed Central

Cha, Ji Hyeon; Lee, Sheen-Woo; Park, Kyeongsoon; Moon, Dae Hyuk; Kim, Kwangmeyung; Biswal, Sandip

2012-01-01

Objective To evaluate the potential and correlation between near-infrared fluorescence (NIRF) imaging using cyanine 5.5 conjugated with hydrophobically modified glycol chitosan nanoparticles (HGC-Cy5.5) and 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) imaging of collagen-induced arthritis (CIA). Materials and Methods We used 10 CIA and 3 normal mice. Nine days after the injecting collagen twice, microPET imaging was performed 40 minutes after the intravenous injection of 9.3 MBq 18F-FDG in 200 µL PBS. One day later, NIRF imaging was performed two hours after the intravenous injection of HGC-cy5.5 (5 mg/kg). We assessed the correlation between these two modalities in the knees and ankles of CIA mice. Results The mean standardized uptake values of 18F-FDG for knees and ankles were 1.68 ± 0.76 and 0.79 ± 0.71, respectively, for CIA mice; and 0.57 ± 0.17 and 0.54 ± 0.20 respectively for control mice. From the NIRF images, the total photon counts per 30 mm2 for knees and ankles were 2.32 ± 1.54 × 105 and 2.75 ± 1.51 × 105, respectively, for CIA mice, and 1.22 ± 0.27 × 105 and 0.88 ± 0.24 × 105, respectively, for control mice. These two modalities showed a moderate correlation for knees (r = 0.604, p = 0.005) and ankles (r = 0.464, p = 0.039). Moreover, both HGC-Cy5.5 (p = 0.002) and 18F-FDG-PET (p = 0.005) imaging also showed statistically significant differences between CIA and normal mice. Conclusion NIRF imaging using HGC-Cy5.5 was moderately correlated with 18F-FDG-PET imaging in the CIA model. As such, HGC-Cy5.5 imaging can be used for the early detection of rheumatoid arthritis. PMID:22778567

Persistent Adaptation by Chronic Alcohol is Facilitated by Neuroimmune Activation Linked to Stress and CRF

PubMed Central

Breese, George R.; Knapp, Darin J.

2016-01-01

This review updates the conceptual basis for the association of alcohol abuse with an insidious adaptation that facilitates negative affect during withdrawal from chronic intermittent alcohol (CIA) exposure – a change that later supports sensitization of stress-induced anxiety following alcohol abstinence. The finding that a CRF1-receptor antagonist (CRF1RA) minimized CIA withdrawal-induced negative affect supported an association of alcohol withdrawal with a stress mechanism. The finding that repeated stresses or multiple CRF injections into selected brain sites prior to a single 5-day chronic alcohol (CA) exposure induced anxiety during withdrawal provided critical support for a linkage of CIA withdrawal with stress. The determination that CRF1RA injection into positive CRF-sensitive brain sites prevented CIA withdrawal-induced anxiety provided support that neural path integration maintains the persistent CIA adaptation. Based upon reports that stress increases neuroimmune function, an effort was undertaken to test whether cytokines would support the adaptation induced by stress/CA exposure. Twenty-four hours after withdrawal from CIA, cytokine mRNAs were found to be increased in cortex as well as other sites in brain. Further, repeated cytokine injections into previously identified brain sites substituted for stress and CRF induction of anxiety during CA withdrawal. Discovery that a CRF1RA prevented the brain cytokine mRNA increase induced by CA withdrawal provided critical evidence for CRF involvement in this neuroimmune induction after CA withdrawal. However, the CRF1RA did not block the stress increase in cytokine mRNA increases in controls. The latter data supported the hypothesis that distinct mechanisms linked to stress and CA withdrawal can support common neuroimmune functions within a brain site. As evidence evolves concerning neural involvement in brain neuroimmune function, a better understanding of the progressive adaptation associated with CIA exposure will advance new knowledge that could possibly lead to strategies to combat alcohol abuse. PMID:27139233

Segregated Regulatory CD39+ CD4+ T Cell Function: TGF-β-Producing FoxP3− and IL-10-Producing FoxP3+ Cells Are Interdependent for Protection Against Collagen-Induced Arthritis1

PubMed Central

Kochetkova, Irina; Thornburg, Theresa; Callis, Gayle; Pascual, David W.

2011-01-01

Oral immunization with a Salmonella vaccine vector expressing enterotoxigenic E. coli colonization factor antigen I (CFA/I) can protect against collagen-induced arthritis (CIA) by dampening IL-17 and IFN-γ via enhanced IL-4, IL-10, and TGF-β. To identify the responsible regulatory CD4+ T cells making the host refractory to CIA, Salmonella-CFA/I induced CD39+CD4+ T cells with enhanced apyrase activity relative to Salmonella vector-immunized mice. Adoptive transfer of vaccine-induced CD39+CD4+ T cells into CIA mice conferred complete protection, while CD39−CD4+ T cells did not. Subsequent analysis of vaccinated FoxP3-GFP mice revealed the CD39+ T cells were composed of FoxP3-GFP− and FoxP3-GFP+ subpopulations. Although each adoptively transferred Salmonella-CFA/I-induced FoxP3− and FoxP3+CD39+CD4+ T cells could protect against CIA, each subset was not as efficacious as total CD39+CD4+ T cells, suggesting their interdependence for optimal protection. Cytokine analysis revealed FoxP3− CD39+CD4+ T cells produced TGF-β, and FoxP3+CD39+CD4+ T cells produced IL-10, showing a segregation of function. Moreover, donor FoxP3-GFP− CD4+ T cells converted to FoxP3-GFP+ CD39+CD4+ T cells in the recipients, showing plasticity of these regulatory T cells. TGF-β was found to be essential for protection since in vivo TGF-β neutralization reversed activation of cAMP-response element-binding protein (CREB) and reduced the development of CD39+CD4+ T cells. Thus, CD39 apyrase-expressing CD4+ T cells stimulated by Salmonella-CFA/I are composed of TGF-β-producing FoxP3− CD39+CD4+ T cells and support the stimulation of IL-10-producing FoxP3+ CD39+CD4+ T cells. PMID:21967895

Nicotine drives neutrophil extracellular traps formation and accelerates collagen-induced arthritis.

PubMed

Lee, Jaejoon; Luria, Ayala; Rhodes, Christopher; Raghu, Harini; Lingampalli, Nithya; Sharpe, Orr; Rada, Balazs; Sohn, Dong Hyun; Robinson, William H; Sokolove, Jeremy

2017-04-01

The aim was to investigate the effects of nicotine on neutrophil extracellular traps (NETs) formation in current and non-smokers and on a murine model of RA. We compared spontaneous and phorbol 12-myristate 13-acetate-induced NETosis between current and non-smokers by DNA release binding. Nicotine-induced NETosis from non-smokers was assessed by DNA release binding, NET-specific (myeloperoxidase (MPO)-DNA complex) ELISA and real-time fluorescence microscopy. We also used immunofluorescent staining to detect nicotinic acetylcholine receptors (nAChRs) on neutrophils and performed a functional analysis to assess the role of nAChRs in nicotine-induced NETosis. Finally, we investigated the effects of systemic nicotine exposure on arthritis severity and NETosis in the CIA mouse model. Neutrophils derived from current smokers displayed elevated levels of spontaneous and phorbol 12-myristate 13-acetate-induced NETosis. Nicotine induced dose-dependent NETosis in ex vivo neutrophils from healthy non-smokers, and co-incubation with ACPA-immune complexes or TNF-α facilitated a synergistic effect on NETosis. Real-time fluorescence microscopy revealed robust formation of NET-like structures in nicotine-exposed neutrophils. Immunofluorescent staining demonstrated the presence of the α7 subunit of the nAChR on neutrophils. Stimulation of neutrophils with an α7-specific nAChR agonist induced NETosis, whereas pretreatment with an nAChR antagonist attenuated nicotine-induced NETosis. Nicotine administration to mice with CIA exacerbated inflammatory arthritis, with higher plasma levels of NET-associated MPO-DNA complex. We demonstrate that nicotine is a potent inducer of NETosis, which may play an important role in accelerating arthritis in the CIA model. This study generates awareness of and the mechanisms by which nicotine-containing products, including e-cigarettes, may have deleterious effects on patients with RA. Published by Oxford University Press 2016. This work is written by US Government employees and is in the public domain in the United States.

District Support Systems for the Alignment of Curriculum, Instruction, and Assessment: Can We Predict Student Achievement in Reading and Writing for School Turnaround?

ERIC Educational Resources Information Center

Abbott, Laura Lynn Tanner

2014-01-01

The purpose of this quantitative non-experimental predictive study was to determine if CIA alignment factors and related district support systems are associated with student achievement to enable the turnaround of schools in crisis. This study aimed to utilize the District Snapshot Tool to determine if the district systems that support CIA…

Aryl hydrocarbon receptor suppresses the osteogenesis of mesenchymal stem cells in collagen-induced arthritic mice through the inhibition of β-catenin

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

Tong, Yulong; Niu, Menglin; Department of Blood Transfusion, Peking University Cancer Hospital & Institute, No. 52 Fucheng Rd., Beijing 100142

The contributions of aryl hydrocarbon receptor (Ahr) to the pathogenesis of rheumatoid arthritis (RA), particularly bone loss, have not been clearly explored. The imbalance between osteoblasts and osteoclasts is a major reason for bone loss. The dysfunction of osteoblasts, which are derived from mesenchymal stem cells (MSCs), induced bone erosion occurs earlier and is characterized as more insidious. Here, we showed that the nuclear expression and translocation of Ahr were both significantly increased in MSCs from collagen-induced arthritis (CIA) mice. The enhanced Ahr suppressed the mRNA levels of osteoblastic markers including Alkaline phosphatase (Alp) and Runt-related transcription factor 2 (Runx2)more » in the differentiation of MSCs to osteoblasts in CIA. The 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated activation of Ahr dose-dependently suppressed the expression of osteoblastic markers. In addition, the expression of β-catenin was reduced in CIA MSCs compared with control, and the TCDD-mediated activation of the Ahr significantly inhibited β-catenin expression. The Wnt3a-induced the activation of Wnt/β-catenin pathway partly rescued the osteogenesis decline induced by TCDD. Taken together, these results indicate that activated Ahr plays a negative role in CIA MSCs osteogenesis, possibly by suppressing the expression of β-catenin. - Highlights: • The Ahr pathway displays an activated profile in CIA MSCs. • The activation of Ahr suppresses osteogenesis in CIA MSCs. • TCDD suppresses osteogenesis in a dose-dependent manner. • The activation of Ahr inhibits β-catenin expression to exacerbate bone erosion.« less

Procedures for evaluating corrosion-inhibiting admixtures for structural concrete

DOT National Transportation Integrated Search

2000-06-01

The objectives of this research were to (1) develop procedures for evaluating and qualifying corrosion-inhibiting admixtures (CIAs) and (2) recommend performance criteria for their acceptance. Phase I work included a literature review of CIAs, the re...

40 CFR 80.130 - Agreed upon procedures reports.

Code of Federal Regulations, 2013 CFR

2013-07-01

.... (a) Reports. (1) The CPA or CIA shall issue to the refiner or importer a report summarizing the... EPA within the time specified in § 80.75(m). (b) Record retention. The CPA or CIA shall retain all...

40 CFR 80.130 - Agreed upon procedures reports.

Code of Federal Regulations, 2012 CFR

2012-07-01

.... (a) Reports. (1) The CPA or CIA shall issue to the refiner or importer a report summarizing the... EPA within the time specified in § 80.75(m). (b) Record retention. The CPA or CIA shall retain all...

40 CFR 80.130 - Agreed upon procedures reports.

Code of Federal Regulations, 2014 CFR

2014-07-01

.... (a) Reports. (1) The CPA or CIA shall issue to the refiner or importer a report summarizing the... EPA within the time specified in § 80.75(m). (b) Record retention. The CPA or CIA shall retain all...

40 CFR 80.130 - Agreed upon procedures reports.

Code of Federal Regulations, 2011 CFR

2011-07-01

.... (a) Reports. (1) The CPA or CIA shall issue to the refiner or importer a report summarizing the... EPA within the time specified in § 80.75(m). (b) Record retention. The CPA or CIA shall retain all...

40 CFR 80.130 - Agreed upon procedures reports.

Code of Federal Regulations, 2010 CFR

2010-07-01

.... (a) Reports. (1) The CPA or CIA shall issue to the refiner or importer a report summarizing the... EPA within the time specified in § 80.75(m). (b) Record retention. The CPA or CIA shall retain all...

Insights into chemical weathering of the upper continental crust from the geochemistry of ancient glacial diamictites

NASA Astrophysics Data System (ADS)

Li, Su; Gaschnig, Richard M.; Rudnick, Roberta L.

2016-03-01

Glacial diamictites, with ages ranging from ∼2900 to 0.01 Ma, record the changing composition of the upper continental crust through time (Gaschnig et al., 2014). Li concentrations and isotopic compositions, combined with Pb isotopic compositions, chemical index of alteration (CIA) values and relative Sr concentrations are used here to assess the degree of chemical weathering recorded in these deposits and the origin of this signature. The δ7Li values of most of the diamictites (ranging from -3.9 to +3.5) are lower than those of mantle-derived basalts (+3.7 ± 2, 2σ), and the low δ7Li values are generally accompanied by high CIA and low Sr/Sr∗ values (or Sr depletion factor, Sr/Sr∗ = Sr/(Ce∗Nd)0.5), reflecting a weathering signature that may have derived from pre-depositional, syn-depositional, and/or post-depositional weathering processes. Profiles through three glacial diamictites with relatively high CIA (a fresh road cut of the Neoproterozoic Nantuo Formation (CIA = 62-69), and drill cores through the Paleoproterozoic Timeball Hill (CIA = 66-75) and Duitschland Formations (CIA = 84-91)) do not show evidence of significant post-depositional weathering. High Th/U, reflecting loss of uranium during oxidative weathering, is seen in all Paleozoic and Neoproterozoic diamictites and a few Paleoproterozoic deposits. Pb isotopic systematics suggest that this signature was largely inherited from preexisting crust, although a subset of samples (the Neoproterozoic Konnarock, Paleozoic Dwyka, and several of the Paleoproterozoic Duitschland samples) appears to have experienced post-depositional U loss. Modern glaciomarine sediments record little weathering (CIA = 47, Sr/Sr∗ = 0.7, δ7Li = +1.8), consistent with the cold temperatures accompanying glacial periods, and suggesting that limited syn-depositional weathering has occurred. Thus, the chemical weathering signature observed in ancient glacial diamictites appears to be largely inherited from the upper continental crust (UCC) over which the glaciers traversed. The strength of this weathering signature, based on the CIA, is greatest in the Mesoarchean and some of the Paleoproterozoic diamictites and is weaker in the Neoproterozoic and Phanerozoic glacial diamictites. Combining these data with data for Archean shales and other types of post-Paleoproterozoic sedimentary rocks (i.e., shales, mudstones, etc.), it appears that post-Paleoproterozoic upper continental crust experienced less intense chemical weathering, on average, than Archean and Paleoproterozoic upper continental crust.

The anti-spasticity drug baclofen alleviates collagen-induced arthritis and regulates dendritic cells.

PubMed

Huang, Shichao; Mao, Jianxin; Wei, Bin; Pei, Gang

2015-07-01

Baclofen is used clinically as a drug that treats spasticity, which is a syndrome characterized by excessive contraction of the muscles and hyperflexia in the central nervous system (CNS), by activating GABA(B) receptors (GABA(B)Rs). Baclofen was recently reported to desensitize chemokine receptors and to suppress inflammation through the activation of GABA(B)Rs. GABA(B)Rs are expressed in various immune cells, but the functions of these receptors in autoimmune diseases remain largely unknown. In this study, we investigated the effects of baclofen in murine collagen-induced arthritis (CIA). Oral administration of baclofen alleviated the clinical development of CIA, with a reduced number of IL-17-producing T helper 17 (T(H)17) cells. In addition, baclofen treatment suppressed dendritic cell (DC)-primed T(H)17 cell differentiation by reducing the production of IL-6 by DCs in vitro. Furthermore, the pharmacological and genetic blockade of GABA(B)Rs in DCs weakened the effects of baclofen, indicating that GABA(B)Rs are the molecular targets of baclofen on DCs. Thus, our findings revealed a potential role for baclofen in the treatment of CIA, as well as a previously unknown signaling pathway that regulates DC function. © 2014 Wiley Periodicals, Inc.

Cesarean sections, perfecting the technique and standardizing the practice: an analysis of the book Obstetrícia, by Jorge de Rezende.

PubMed

Nakano, Andreza Rodrigues; Bonan, Claudia; Teixeira, Luiz Antônio

2016-01-01

This article discusses the development of techniques for cesarean sections by doctors in Brazil, during the 20th century, by analyzing the title "Operação Cesárea" (Cesarean Section), of three editions of the textbookObstetrícia, by Jorge de Rezende. His prominence as an author in obstetrics and his particular style of working, created the groundwork for the normalization of the practice of cesarean sections. The networks of meaning practiced within this scientific community included a "provision for feeling and for action" (Fleck) which established the C-section as a "normal" delivery: showing standards that exclude unpredictability, chaos, and dangers associated with the physiology of childbirth, meeting the demand for control, discipline and safety, qualities associated with practices, techniques and technologies of biomedicine.

Performance evaluation of corrosion inhibitors and galvanized steel in concrete exposure specimens.

DOT National Transportation Integrated Search

1999-01-01

Corrosion inhibitor admixtures (CIA) and galvanized reinforcing steel (GS) are used for the corrosion protection for reinforced concrete bridges. The results of a 3.5-year evaluation of exposure specimens containing CIA from three different manufactu...

Myeloid-derived suppressor cells regulate T cell and B cell responses during autoimmune disease.

PubMed

Crook, Kristen R; Jin, Mengyao; Weeks, Michael F; Rampersad, Rishi R; Baldi, Robert M; Glekas, Amy S; Shen, Yajuan; Esserman, Denise A; Little, Paul; Schwartz, Todd A; Liu, Peng

2015-03-01

MDSCs are a heterogeneous group of myeloid cells that suppress T cell activity in cancer and autoimmune disease. The effect of MDSCs on B cell function is not clear. Using the CIA model of autoimmune disease, we found an increase in M-MDSCs in the periphery of WT mice with CIA compared with naïve mice. These MDSCs were absent from the periphery of CCR2(-/-) mice that developed exacerbated disease. M-MDSCs, isolated from immunized mice, inhibited autologous CD4(+) T cell proliferation. The M-MDSC-mediated suppression of T cell proliferation was NO and IFN-γ dependent but IL-17 independent. Furthermore, we demonstrated for the first time that M-MDSCs from CIA mice also inhibited autologous B cell proliferation and antibody production. The suppression of B cells by M-MDSCs was dependent on the production of NO and PGE2 and required cell-cell contact. Administration of M-MDSCs rescued CCR2(-/-) mice from the exacerbated CIA phenotype and ameliorated disease in WT mice. Furthermore, adoptive transfer of M-MDSCs reduced autoantibody production by CCR2(-/-) and WT mice. In summary, M-MDSCs inhibit T cell and B cell function in CIA and may serve as a therapeutic approach in the treatment of autoimmune arthritis. © Society for Leukocyte Biology.

The deca-GX3 proteins Yae1-Lto1 function as adaptors recruiting the ABC protein Rli1 for iron-sulfur cluster insertion

PubMed Central

Paul, Viktoria Désirée; Mühlenhoff, Ulrich; Stümpfig, Martin; Seebacher, Jan; Kugler, Karl G; Renicke, Christian; Taxis, Christof; Gavin, Anne-Claude; Pierik, Antonio J; Lill, Roland

2015-01-01

Cytosolic and nuclear iron-sulfur (Fe-S) proteins are involved in many essential pathways including translation and DNA maintenance. Their maturation requires the cytosolic Fe-S protein assembly (CIA) machinery. To identify new CIA proteins we employed systematic protein interaction approaches and discovered the essential proteins Yae1 and Lto1 as binding partners of the CIA targeting complex. Depletion of Yae1 or Lto1 results in defective Fe-S maturation of the ribosome-associated ABC protein Rli1, but surprisingly no other tested targets. Yae1 and Lto1 facilitate Fe-S cluster assembly on Rli1 in a chain of binding events. Lto1 uses its conserved C-terminal tryptophan for binding the CIA targeting complex, the deca-GX3 motifs in both Yae1 and Lto1 facilitate their complex formation, and Yae1 recruits Rli1. Human YAE1D1 and the cancer-related ORAOV1 can replace their yeast counterparts demonstrating evolutionary conservation. Collectively, the Yae1-Lto1 complex functions as a target-specific adaptor that recruits apo-Rli1 to the generic CIA machinery. DOI: http://dx.doi.org/10.7554/eLife.08231.001 PMID:26182403

Thinking and Writing: Cognitive Science and Intelligence Analysis

DTIC Science & Technology

2010-02-01

well as books and monographs addressing historical, operational, doctrinal, and theoretical aspects of the intelligence profession. It also...Intelligence published an updated version of Heuer’s articles in a book , Psychology of Intelligence Analysis, in 1999. Since reprinted by CIA and available...commercially, the book is now a staple in many analytic training courses. conclusion. This and other examples, he says, il- lustrate how the things

50 Years of Silent Service: Inside the CIA Library.

ERIC Educational Resources Information Center

Wright, Susan L.

1997-01-01

Explains some of the collections and operations of the library at the Central Intelligence Agency (CIA). Highlights include disseminating classified information from the classified collection, subject matter requirements, the unclassified Historical Intelligence Collection which deals with the intelligence profession, client confidentiality, and…

ISS Expedition 18 Multi-User Droplet Combustion Apparatus (MDCA) Chamber Insert Assembly (CIA) in Node 2

NASA Image and Video Library

2008-12-06

ISS018-E-010645 (6 Dec. 2008) --- Astronaut Michael Fincke, Expedition 18 commander, works on the Multi-User Droplet Combustion Apparatus (MDCA) Chamber Insert Assembly (CIA) in the Harmony node of the International Space Station.

32 CFR 1907.02 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... means the United States Central Intelligence Agency acting through the CIA Information and Privacy... Information and Privacy Coordinator acting in the capacity of Executive Secretary of the Agency Release Panel... the documents or information at issue; (i) Originator means the CIA officer who originated the...

Th17 and IL-17 Cause Acceleration of Inflammation and Fat Loss by Inducing α2-Glycoprotein 1 (AZGP1) in Rheumatoid Arthritis with High-Fat Diet.

PubMed

Na, Hyun Sik; Kwon, Jeong-Eun; Lee, Seung Hoon; Jhun, JooYeon; Kim, Sung-Min; Kim, Se-Young; Kim, Eun-Kyung; Jung, KyungAh; Park, Sung-Hwan; Cho, Mi-La

2017-05-01

Rheumatoid arthritis (RA) is a chronic autoimmune disorder that affects the joints. High-fat diet (HFD) is a risk factor for RA and is related to inflammation but responds minimally to medication. Given the association between HFD and inflammation, it is important to understand the function of inflammation-related T cells in RA with HFD. Collagen-induced arthritis (CIA), a model of RA, was induced in HFD mice by injection of collagen II, and metabolic markers and T cells were analyzed. The metabolic index and IgG assay results were higher in HFD-CIA mice than in nonfat diet-CIA mice. Numbers of inflammation-related T cells and macrophages, such as Th1 and Th17 cells and M1 macrophages, were higher in spleens of HFD-CIA mice. HFD-CIA mice had a high level of α 2 -glycoprotein 1 (Azgp1), a soluble protein that stimulates lipolysis. To examine the association between Azgp1 and Th17 cells, the reciprocal effects of Azgp1 and IL-17 on Th17 differentiation and lipid metabolism were measured. Interestingly, Azgp1 increased the Th17 population of splenocytes. Taken together, our data suggest that the acceleration of fat loss caused by Azgp1 in RA with metabolic syndrome is related to the increase of IL-17. Mice injected with the Azgp1-overexpression vector exhibited more severe CIA compared with the mock vector-injected mice. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Single-Center Experience and 1-Year Follow-up Results of 'Sandwich Technique' in the Management of Common Iliac Artery Aneurysms During EVAR

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

Ricci, Carmelo; Ceccherini, Claudio, E-mail: claudiocec@hotmail.it; Cini, Marco

Purpose: Abdominal aortic aneurysm (AAA) accompanied by common iliac artery (CIA) aneurysms requires a more demanding procedure owing to the difficulties in obtaining an adequate distal landing zone for the stent-graft limb(s), a potential site of endoleak. The 'sandwich technique' is a procedure to increase EVAR feasibility in the setting of adverse or challenging CIA anatomy. Its main advantages include no restrictions in terms of CIA diameter or length or internal iliac artery (IIA) diameter, no need to wait for a specific stent-graft. Our purpose is to describe our single-center experience and one year follow-up results of this new procedure.more » Materials and Methods: From April 2009 to June 2010, the sandwich technique was performed in our institution in 7 patients treated for AAA and unilateral CIA aneurysms (n. 5) or bilateral CIA aneurysms (n. 2). Inclusion criteria were the presence of unilateral or bilateral CIA aneurysm (independently from its diameter), IIA artery measuring up to 9 mm in its maximum diameter, not dilatation of IIA and EIA. Results: The mean follow-up length was 15 months (range: 14-20 months). All stent-implanted iliac branches remained patent on 1 year follow-up and IIA flow was preserved. None of the patients had symptoms of pelvic ischemia. CT scan follow-up showed aneurysm shrinkage in five patients, without any sign of endoleaks in all cases. Conclusions: In selected cases, the 'sandwich technique' showed good outcomes confirming to be a safe and easy to perform way to overcome anatomical constraints and expanding the limits of EVAR.« less

An Axiology of Information Security for Futuristic Neuroprostheses: Upholding Human Values in the Context of Technological Posthumanization

PubMed Central

Gladden, Matthew E.

2017-01-01

Previous works exploring the challenges of ensuring information security for neuroprosthetic devices and their users have typically built on the traditional InfoSec concept of the “CIA Triad” of confidentiality, integrity, and availability. However, we argue that the CIA Triad provides an increasingly inadequate foundation for envisioning information security for neuroprostheses, insofar as it presumes that (1) any computational systems to be secured are merely instruments for expressing their human users' agency, and (2) computing devices are conceptually and practically separable from their users. Drawing on contemporary philosophy of technology and philosophical and critical posthumanist analysis, we contend that futuristic neuroprostheses could conceivably violate these basic InfoSec presumptions, insofar as (1) they may alter or supplant their users' biological agency rather than simply supporting it, and (2) they may structurally and functionally fuse with their users to create qualitatively novel “posthumanized” human-machine systems that cannot be secured as though they were conventional computing devices. Simultaneously, it is noted that many of the goals that have been proposed for future neuroprostheses by InfoSec researchers (e.g., relating to aesthetics, human dignity, authenticity, free will, and cultural sensitivity) fall outside the scope of InfoSec as it has historically been understood and touch on a wide range of ethical, aesthetic, physical, metaphysical, psychological, economic, and social values. We suggest that the field of axiology can provide useful frameworks for more effectively identifying, analyzing, and prioritizing such diverse types of values and goods that can (and should) be pursued through InfoSec practices for futuristic neuroprostheses. PMID:29163010

An Axiology of Information Security for Futuristic Neuroprostheses: Upholding Human Values in the Context of Technological Posthumanization.

PubMed

Gladden, Matthew E

2017-01-01

Previous works exploring the challenges of ensuring information security for neuroprosthetic devices and their users have typically built on the traditional InfoSec concept of the "CIA Triad" of confidentiality, integrity, and availability. However, we argue that the CIA Triad provides an increasingly inadequate foundation for envisioning information security for neuroprostheses, insofar as it presumes that (1) any computational systems to be secured are merely instruments for expressing their human users' agency, and (2) computing devices are conceptually and practically separable from their users. Drawing on contemporary philosophy of technology and philosophical and critical posthumanist analysis, we contend that futuristic neuroprostheses could conceivably violate these basic InfoSec presumptions, insofar as (1) they may alter or supplant their users' biological agency rather than simply supporting it, and (2) they may structurally and functionally fuse with their users to create qualitatively novel "posthumanized" human-machine systems that cannot be secured as though they were conventional computing devices. Simultaneously, it is noted that many of the goals that have been proposed for future neuroprostheses by InfoSec researchers (e.g., relating to aesthetics, human dignity, authenticity, free will, and cultural sensitivity) fall outside the scope of InfoSec as it has historically been understood and touch on a wide range of ethical, aesthetic, physical, metaphysical, psychological, economic, and social values. We suggest that the field of axiology can provide useful frameworks for more effectively identifying, analyzing, and prioritizing such diverse types of values and goods that can (and should) be pursued through InfoSec practices for futuristic neuroprostheses.

Biographical Information and Other Government Secrets.

ERIC Educational Resources Information Center

Conger, Lucinda D.

1981-01-01

Covers relevant biographical sources for diplomatic, foreign, and American government personnel, including online services, monographs, back files, the card catalog, State Department and CIA publications, other government documents, and trade publications. Lists of CIA biographical directories and U.S. government agency press offices are appended.…

Quality of life in anorexia nervosa, bulimia nervosa and eating disorder not-otherwise-specified

PubMed Central

2013-01-01

Background This study aimed to assess differences in Quality of Life (QoL) across eating disorder (ED) diagnoses, and to examine the relationship of QoL to specific clinical features. Results 199 patients with a diagnosed ED completed the Clinical Impairment Assessment (CIA) [Cognitive Behavior Therapy and Eating Disorders, 315–318, 2008] and the Eating Disorders Examination (EDE) [Int J Eat Disord 6:1–8]. Differences between diagnostic groups were examined, as were differences between restrictive and binge-purge subtypes. CIA scores and EDE scores were positively correlated and higher in groups with binge-purge behaviours. CIA scores were not correlated with BMI, illness duration or frequency of bingeing/purging behaviours, except in the binge-purge AN group, where CIA scores negatively correlated with BMI. Conclusions Patients with EDs have poor QoL and impairment increases with illness severity. Patients with binge/purge diagnoses are particularly impaired. It remains unclear which clinical features best predict the degree of impairment experienced by patients with EDs. PMID:24999421

33 CFR 164.03 - Incorporation by reference.

Code of Federal Regulations, 2011 CFR

2011-07-01

... inspection at the Navigation Systems Division (CG-553), Coast Guard Headquarters, 2100 2nd St. SW., Stop 7580, Washington, DC 20593-7580 and at the National Archives and Records Administration (NARA). For information on... Testing Fiber Ropes 164.74 Cordage Institute, 350 Lincoln Street, Hingham, MA 02043 CIA-3, Standard Test...

In vivo quantification of mouse autoimmune arthritis by PET/CT

PubMed Central

Kundu-Raychaudhuri, Smriti; Mitra, Anupam; Datta-Mitra, Ananya; Chaudhari, Abhijit J.; Raychaudhuri, Siba P.

2014-01-01

Aim To quantify the progression and severity of mouse collagen-induced arthritis (CIA) using an in vivo imaging tool, 18F-fluorodeoxyglucose (18F-FDG) PET/CT, and validate it against gold standard ‘histopathological’ evaluation. Method The PET radiotracer 18F-FDG, a marker for glucose metabolism, was injected in mice at different stages during the development of CIA and the radiotracer distribution was imaged using a PET scanner. A sequential CT scan provided correlated anatomy. Radiotracer concentration was derived from PET/CT images for individual limb joints and on a per-limb basis at different stages of the disease. The imaging outcomes were subjected to correlation analysis with concurrently-measured clinical and histological score. Results Clinical and histological score, and hence disease severity, showed a strong linear correlation (R2=0.71, p=0.001, and R2=0.87, p<0.001, respectively) with radiotracer concentration measured from PET/CT during the progression of CIA. Conclusions The strong positive correlation of the 18F-FDG PET/CT findings with the histopathological evaluation at different stages of the disease suggest the potential of this imaging tool for the non-invasive assessment of progression and severity in mouse autoimmune arthritis. Thus, 18F-FDG PET/CT can be considered as a non invasive tool in preclinical studies for development of novel therapies of inflammatory arthritis. PMID:24965561

Multi-User Droplet Combustion Apparatus (MDCA) Chamber Insert Assembly (CIA)

NASA Image and Video Library

2013-07-24

ISS036-E-024569 (24 July 2013) --- European Space Agency astronaut Luca Parmitano, Expedition 36 flight engineer, works on the Multi-User Droplet Combustion Apparatus (MDCA) Chamber Insert Assembly (CIA) at a maintenance work station in the Harmony node of the International Space Station.

Multi-User Droplet Combustion Apparatus (MDCA) Chamber Insert Assembly (CIA)

NASA Image and Video Library

2013-07-24

ISS036-E-024605 (24 July 2013) --- European Space Agency astronaut Luca Parmitano, Expedition 36 flight engineer, works on the Multi-User Droplet Combustion Apparatus (MDCA) Chamber Insert Assembly (CIA) at a maintenance work station in the Harmony node of the International Space Station.

Multi-User Droplet Combustion Apparatus (MDCA) Chamber Insert Assembly (CIA)

NASA Image and Video Library

2013-07-24

ISS036-E-024637 (24 July 2013) --- European Space Agency astronaut Luca Parmitano, Expedition 36 flight engineer, works on the Multi-User Droplet Combustion Apparatus (MDCA) Chamber Insert Assembly (CIA) at a maintenance work station in the Harmony node of the International Space Station.

32 CFR 1900.41 - Establishment of appeals structure.

Code of Federal Regulations, 2011 CFR

2011-07-01

... denial. The Executive Secretary of the HRPB is the Director, Information Management. The Chair may... subordinate Agency Release Panel. (1) Membership. The ARP is composed of the Director, Information Management... AGENCY PUBLIC ACCESS TO CIA RECORDS UNDER THE FREEDOM OF INFORMATION ACT (FOIA) Cia Action on Foia...

32 CFR 1900.41 - Establishment of appeals structure.

Code of Federal Regulations, 2012 CFR

2012-07-01

... denial. The Executive Secretary of the HRPB is the Director, Information Management. The Chair may... subordinate Agency Release Panel. (1) Membership. The ARP is composed of the Director, Information Management... AGENCY PUBLIC ACCESS TO CIA RECORDS UNDER THE FREEDOM OF INFORMATION ACT (FOIA) Cia Action on Foia...

32 CFR 1900.41 - Establishment of appeals structure.

Code of Federal Regulations, 2014 CFR

2014-07-01

... denial. The Executive Secretary of the HRPB is the Director, Information Management. The Chair may... subordinate Agency Release Panel. (1) Membership. The ARP is composed of the Director, Information Management... AGENCY PUBLIC ACCESS TO CIA RECORDS UNDER THE FREEDOM OF INFORMATION ACT (FOIA) Cia Action on Foia...

32 CFR 1900.41 - Establishment of appeals structure.

Code of Federal Regulations, 2013 CFR

2013-07-01

... denial. The Executive Secretary of the HRPB is the Director, Information Management. The Chair may... subordinate Agency Release Panel. (1) Membership. The ARP is composed of the Director, Information Management... AGENCY PUBLIC ACCESS TO CIA RECORDS UNDER THE FREEDOM OF INFORMATION ACT (FOIA) Cia Action on Foia...

3. BUNKER HILL LEAD SMELTER. VIEW IS FROM CIA TO ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

3. BUNKER HILL LEAD SMELTER. VIEW IS FROM CIA TO THE SOUTHWEST. BUILDINGS NOTED IN ID-29-2 APPEAR, IN ADDITION TO DRY ORE PLANT AND BONNOT COAL PULVERIZING EQUIPMENT BUILDING ON THE RIGHT. - Bunker Hill Lead Smelter, Bradley Rail Siding, Kellogg, Shoshone County, ID

The CIA-Media Connection.

ERIC Educational Resources Information Center

Zerbinos, Eugenia

The Central Intelligence Agency (CIA) has paid journalists, used information from unpaid journalists, owned foreign media outlets, planted stories, and put the lid on other stories throughout its 30-year history. Journalism makes a good cover for agents because journalists can ask questions without arousing suspicion. It has been estimated that…

77 FR 14594 - Additions to the Identifying Information for an Individual Previously Designated Pursuant to the...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-12

..., Colombia; c/o INVERPUNTO DEL VALLE S.A., Cali, Colombia; c/o INVERSIONES CIFUENTES Y CIA. S. EN C...., Bogota, Colombia; c/o INVERPUNTO DEL VALLE S.A., Cali, Colombia; c/o INVERSIONES CIFUENTES Y CIA. S. EN C...

Matrine Exerts a Strong Anti-Arthritic Effect on Type II Collagen-Induced Arthritis in Rats by Inhibiting Inflammatory Responses

PubMed Central

Pu, Jiang; Fang, Fan-Fu; Li, Xiu-Qing; Shu, Zhi-Heng; Jiang, Yi-Ping; Han, Ting; Peng, Wei; Zheng, Cheng-Jian

2016-01-01

To investigate anti-arthritic effects of matrine isolated from the roots of S. flavescens on type II collagen-induced arthritis (CIA) in rats and to explore its related potential mechanisms, CIA rats were established and administered with matrine (20, 40 or 80 mg/kg/days, for 30 days). Subsequently, blood was collected to determine serum levels of TNF-α, IL-1β, IL-6, IL-8, IL-17A, IL-10, MMP-2, MMP-3 and MMP-9, and hind paws and knee joints were collected for histopathological examination. Furthermore, indices of the thymus and spleen were determined, and synovial tissues were collected to determine the protein expressions of p-IκB, IκB, Cox-2 and iNOS. Our results indicated that matrine significantly suppressed inflammatory reactions and synovial tissue destruction. Matrine inhibited paw swelling, arthritis indices and weight loss in CIA rats. Additionally, matrine decreased the levels of TNF-α, IL-1β, IL-6, IL-8, IL-17A, MMP-2, MMP-3 and MMP-9. Matrine also down-regulated expressions of p-IκB, Cox-2, and iNOS but up-regulated IκB in synovial tissues in CIA rats. The results suggested matrine possesses an anti-arthritic effect in CIA rats via inhibiting the release of pro-inflammatory cytokines and proteins that promote the NF-κB pathway. PMID:27571073

When identities collide: Conflicts in allegiances among LGB people of color.

PubMed

Sarno, Elissa L; Mohr, Jonathan J; Jackson, Skyler D; Fassinger, Ruth E

2015-10-01

Little research has examined the management of multiple minority identities among lesbian, gay, and bisexual (LGB) people of color, despite a growing theoretical literature on such identity intersections. The present study focused on the intersectional construct of conflicts in allegiances (CIA), defined as perceived incompatibility between one's racial/ethnic and sexual orientation identities. CIA was investigated in relation to experiences of parental heterosexism, racism in LGB communities, outness, and racial/ethnic and sexual orientation group identity. Participants were 124 LGB people of color (main sample) and 124 LGB White people (comparison sample) who completed self-report measures of the main variables as part of a larger survey of same-sex couples. CIA was positively correlated with experiences of racism within LGB communities and perceived heterosexism in one's mother (but not one's father), and negatively correlated with outness to family (but not outness to others in one's everyday life). An interaction was found between racial/ethnic and LGB group identity with respect to behavioral engagement: CIA levels were highest among participants with high racial/ethnic behavioral engagement and low sexual orientation behavioral engagement. Results highlight the role of minority and family contexts in CIA among LGB people of color, and, more broadly, the potential value of studying intersectional variables using quantitative methods. Longitudinal and experimental studies are needed to address questions about direction of influence raised by findings. (c) 2015 APA, all rights reserved).

Lactobacillus salivarius Isolated from Patients with Rheumatoid Arthritis Suppresses Collagen-Induced Arthritis and Increases Treg Frequency in Mice.

PubMed

Liu, Xiaofei; Zhang, Juan; Zou, Qinghua; Zhong, Bing; Wang, Heng; Mou, Fangxiang; Wu, Like; Fang, Yongfei

2016-12-01

Previously, we demonstrated that Lactobacillus salivarius was more abundant in patients with rheumatoid arthritis (RA), an inflammatory autoimmune disease wherein the gut microbiota is altered, than in healthy individuals. However, the effect of L. salivarius in RA is unclear. Hence, we investigated the effect of L. salivarius isolated from patients with RA on collagen-induced arthritis (CIA) in mice. L. salivarius UCC118 or L. plantarum WCFS1 isolated from patients with RA was administered orally for 5 weeks, starting from 2 weeks before the induction of arthritis in DBA/1 mice. Clinical score progression, histological changes, serum cytokine concentrations, and the proportion of interleukin (IL)-17-producing T cells [T helper 17 (Th17)] and regulatory T cells (Tregs) in the spleen were evaluated. Bone erosion was evaluated by micro-computed tomography. CIA mice treated with either L. salivarius or L. plantarum showed lower arthritis scores, milder synovial infiltration, and less bone erosion when compared with phosphate-buffered, saline-treated CIA mice. Administration of L. salivarius and L. plantarum reduced the Th17 cell fraction and increased the Treg fraction. L. salivarius-treated CIA mice displayed a significant increase in serum anti-inflammatory IL-10 levels. Thus, pretreatment with L. salivarius could significantly improve CIA in mice and may help alleviate RA in a clinical setting.

Etanercept Promotes Bone Formation via Suppression of Dickkopf-1 Expression in Rats with Collagen-Induced Arthritis

PubMed Central

Tanida, Atsushi; Kishimoto, Yuji; Okano, Toru; Hagino, Hiroshi

2013-01-01

Background Various clinical reports suggest etanercept (ETN) has some efficacy in bone formation in rheumatoid arthritis (RA). To examine this effect, we investigated the gene expression of cytokines relevant to osteoblast/osteoclast differentiation, and evaluated histomorphometric findings in mature rats with collagen-induced arthritis (CIA). Methods Total RNA was extracted from knee joints with CIA after ETN or placebo administration. Subsequently, realtime-PCR was carried out to quantify the mRNAs encoding Wnt-1, Dickkopf-1 (DKK-1), receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegelin (OPG) and TNF (tumor necrosis factor)-alpha. In histomorphometric analysis, the infiltrating pannus volume and pannus surface, and the following items in contact with pannus surface were measured: osteoclast number, osteoid surface, osteoid volume and labeling surface. These were evaluated in the distal femur with CIA with or without ETN administration. Results TNF-alpha, RANKL and OPG mRNA expressions, linked to osteoclastogenesis, were not significantly different with or without ETN administration. ETN administration significantly increased Wnt-1 mRNA expression, the osteoblast promoter, and decreased DKK-1 mRNA expression, the Wnt signal inhibitor. In histomorphometric analysis, pannus volume, pannus surface and osteoclast number, parameters of bone destruction, were not significantly different among groups. Osteoid volume, osteoid surface and labeling surface, parameters of bone formation, increased significantly with ETN administration. Conclusion Our results suggest that ETN suppresses DDK-1 expression, and, as a result, Wnt expression is promoted and osteoblastogenesis becomes more active, independent of the regulation of osteoclast activity. Marked bone formation is attributed to the fact that ETN directly promotes osteoblastogenesis, not as a result of suppressing osteoclastogenesis. PMID:24031147

Community Impact Assessment Handbook.

ERIC Educational Resources Information Center

Northern Alberta Development Council, Peace River.

This handbook is intended for communities that wish to undertake their own community impact assessment (CIA). The goal is to enable communities to plan for changes before they occur, so they can cope with changes when they do occur. CIA involves forecasting and evaluating the full range of unintended consequences for the community of development…

32 CFR 1901.02 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... PRIVACY ACT OF 1974 General § 1901.02 Definitions. For purposes of this part, the following terms have the... the CIA Information and Privacy Coordinator; (b) Days means calendar days when the Agency is operating...) Coordinator means the CIA Information and Privacy Coordinator who serves as the Agency manager of the...

Occupational Aspirations of State FFA Contest and Award Winners.

ERIC Educational Resources Information Center

Bowen, Blannie E.; Doerfert, David L.

1989-01-01

A study explored the occupational aspirations of 300 (of 503) students with high levels of participation in Future Farmers of America's (FFA) Computers in Agriculture (CIA), Proficiency Award (PA), and Prepared and Extemporaneous Speaking (PES) contests. CIA and PES winners aspired to professional occupations more than PA winners. PES winners…

78 FR 47489 - Unblocking of Specially Designated Nationals and Blocked Persons Pursuant to the Foreign...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-05

...; c/o INVERPUNTO DEL VALLE S.A., Cali, Colombia; c/o INVERSIONES CIFUENTES Y CIA. S. EN C., Medellin...: INVERPUNTO DEL VALLE S.A.; Linked To: INVERSIONES CIFUENTES Y CIA. S. EN C.; Linked To: LE CLAUDE, S.A. DE C...

Centralized Cryptographic Key Management and Critical Risk Assessment - CRADA Final Report For CRADA Number NFE-11-03562

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

Abercrombie, R. K.; Peters, Scott

The Department of Energy Office of Electricity Delivery and Energy Reliability (DOE-OE) Cyber Security for Energy Delivery Systems (CSEDS) industry led program (DE-FOA-0000359) entitled "Innovation for Increasing Cyber Security for Energy Delivery Systems (12CSEDS)," awarded a contract to Sypris Electronics LLC to develop a Cryptographic Key Management System for the smart grid (Scalable Key Management Solutions for Critical Infrastructure Protection). Oak Ridge National Laboratory (ORNL) and Sypris Electronics, LLC as a result of that award entered into a CRADA (NFE-11-03562) between ORNL and Sypris Electronics, LLC. ORNL provided its Cyber Security Econometrics System (CSES) as a tool to be modifiedmore » and used as a metric to address risks and vulnerabilities in the management of cryptographic keys within the Advanced Metering Infrastructure (AMI) domain of the electric sector. ORNL concentrated our analysis on the AMI domain of which the National Electric Sector Cyber security Organization Resource (NESCOR) Working Group 1 (WG1) has documented 29 failure scenarios. The computational infrastructure of this metric involves system stakeholders, security requirements, system components and security threats. To compute this metric, we estimated the stakes that each stakeholder associates with each security requirement, as well as stochastic matrices that represent the probability of a threat to cause a component failure and the probability of a component failure to cause a security requirement violation. We applied this model to estimate the security of the AMI, by leveraging the recently established National Institute of Standards and Technology Interagency Report (NISTIR) 7628 guidelines for smart grid security and the International Electrotechnical Commission (IEC) 63351, Part 9 to identify the life cycle for cryptographic key management, resulting in a vector that assigned to each stakeholder an estimate of their average loss in terms of dollars per day of system operation. To further address probabilities of threats, information security analysis can be performed using game theory implemented in dynamic Agent Based Game Theoretic (ABGT) simulations. Such simulations can be verified with the results from game theory analysis and further used to explore larger scale, real world scenarios involving multiple attackers, defenders, and information assets. The strategy for the game was developed by analyzing five electric sector representative failure scenarios contained in the AMI functional domain from NESCOR WG1. From these five selected scenarios, we characterized them into three specific threat categories affecting confidentiality, integrity and availability (CIA). The analysis using our ABGT simulation demonstrated how to model the AMI functional domain using a set of rationalized game theoretic rules decomposed from the failure scenarios in terms of how those scenarios might impact the AMI network with respect to CIA.« less

Cryptographic Key Management and Critical Risk Assessment

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

Abercrombie, Robert K

The Department of Energy Office of Electricity Delivery and Energy Reliability (DOE-OE) CyberSecurity for Energy Delivery Systems (CSEDS) industry led program (DE-FOA-0000359) entitled "Innovation for Increasing CyberSecurity for Energy Delivery Systems (12CSEDS)," awarded a contract to Sypris Electronics LLC to develop a Cryptographic Key Management System for the smart grid (Scalable Key Management Solutions for Critical Infrastructure Protection). Oak Ridge National Laboratory (ORNL) and Sypris Electronics, LLC as a result of that award entered into a CRADA (NFE-11-03562) between ORNL and Sypris Electronics, LLC. ORNL provided its Cyber Security Econometrics System (CSES) as a tool to be modified and usedmore » as a metric to address risks and vulnerabilities in the management of cryptographic keys within the Advanced Metering Infrastructure (AMI) domain of the electric sector. ORNL concentrated our analysis on the AMI domain of which the National Electric Sector Cyber security Organization Resource (NESCOR) Working Group 1 (WG1) has documented 29 failure scenarios. The computational infrastructure of this metric involves system stakeholders, security requirements, system components and security threats. To compute this metric, we estimated the stakes that each stakeholder associates with each security requirement, as well as stochastic matrices that represent the probability of a threat to cause a component failure and the probability of a component failure to cause a security requirement violation. We applied this model to estimate the security of the AMI, by leveraging the recently established National Institute of Standards and Technology Interagency Report (NISTIR) 7628 guidelines for smart grid security and the International Electrotechnical Commission (IEC) 63351, Part 9 to identify the life cycle for cryptographic key management, resulting in a vector that assigned to each stakeholder an estimate of their average loss in terms of dollars per day of system operation. To further address probabilities of threats, information security analysis can be performed using game theory implemented in dynamic Agent Based Game Theoretic (ABGT) simulations. Such simulations can be verified with the results from game theory analysis and further used to explore larger scale, real world scenarios involving multiple attackers, defenders, and information assets. The strategy for the game was developed by analyzing five electric sector representative failure scenarios contained in the AMI functional domain from NESCOR WG1. From these five selected scenarios, we characterized them into three specific threat categories affecting confidentiality, integrity and availability (CIA). The analysis using our ABGT simulation demonstrated how to model the AMI functional domain using a set of rationalized game theoretic rules decomposed from the failure scenarios in terms of how those scenarios might impact the AMI network with respect to CIA.« less

Pharmacological efficacy of anti-IL-1β scFv, Fab and full-length antibodies in treatment of rheumatoid arthritis.

PubMed

Qi, Jianying; Ye, Xianlong; Ren, Guiping; Kan, Fangming; Zhang, Yu; Guo, Mo; Zhang, Zhiyi; Li, Deshan

2014-02-01

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that mainly causes the synovial joint inflammation and cartilage destruction. Interleukin-1β (IL-1β) is an important proinflammatory cytokine involved in the pathogenesis of RA. In this study, we constructed and expressed anti-IL-1β-full-length antibody in CHO-K1-SV, anti-IL-1β-Fab and anti-IL-1β-scFv in Rosetta. We compared the therapeutic efficacy of three anti-IL-1β antibodies for CIA mice. Mice with CIA were subcutaneously injected with humanized anti-IL-1β-scFv, anti-IL-1β-Fab or anti-IL-1β-full-length antibody. The effects of treatment were determined by arthritis severity score, autoreactive humoral, cellular immune responses, histological lesion and cytokines production. Compared with anti-IL-1β-scFv treatments, anti-IL-1β-Fab and anti-IL-1β-full-length antibody therapy resulted in more significant effect in alleviating the severity of arthritis by preventing bone damage and cartilage destruction, reducing humoral and cellular immune responses, and down-regulating the expression of IL-1β, IL-6, IL-2, IFN-γ, TNF-α and MMP-3 in inflammatory tissue. The therapeutic effects of anti-IL-1β-Fab and anti-IL-1β-full-length antibodies on CIA mice had no significant difference. However, production of anti-IL-1β-full-length antibody in eukaryotic system is, in general, time-consuming and more expensive than that of anti-IL-1β-Fab in prokaryotic systems. In conclusion, as a small molecule antibody, anti-IL-1β-Fab is an ideal candidate for RA therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

33 CFR 164.03 - Incorporation by reference.

Code of Federal Regulations, 2010 CFR

2010-07-01

... inspection at the Navigation Systems Division (CG-5413), Coast Guard Headquarters, 2100 2nd St. SW., Stop... information on the availability of this material at NARA, call 202-741-6030, or go to: http://www.archives.gov... Testing Fiber Ropes 164.74 Cordage Institute, 350 Lincoln Street, Hingham, MA 02043 CIA-3, Standard Test...

RIT-CIA Case Study: Classified Research in a University Context.

ERIC Educational Resources Information Center

Carl, W. John, III

A controversy at the Rochester Institute of Technology (RIT) in New York State over that institution's involvement with classified research for the Central Intelligence Agency (CIA) raised issues regarding classified research and institutional leadership. In 1991 M. Richard Rose, then president of RIT, took a 4-month sabbatical to work for the…

OIG News Release: Former EPA official sentenced to 32 months in prison for defrauding government under ‘CIA agent’ guise

EPA Pesticide Factsheets

WASHINGTON – John C. Beale, a former employee of the EPA, today was sentenced to 32 months in prison following a plea agreement in which he admitted perpetrating multiple frauds under the bogus guise of performing undercover work as a CIA agent.

Secrecy: The Communication Dilemma of the CIA.

ERIC Educational Resources Information Center

Gibson, Dirk C.

1987-01-01

Explores the response of the CIA to public criticism when caught in the dilemma of having to put forth information to the public about its activities and yet carry out secret intelligence-gathering and covert operations. Concludes that its response, attempted cover-ups and censorship, failed due to this conflict in its position. (JC)

Protease inhibitors in various flours and breads: Effect of fermentation, baking and in vitro digestion on trypsin and chymotrypsin inhibitory activities.

PubMed

Kostekli, Mine; Karakaya, Sibel

2017-06-01

In this study trypsin (TIA) and chymotrypsin inhibitory (CIA) activities were determined in the extracts of wheat, rye mix, mixed cereals and, whole wheat flours and, breads made with these flours. In addition, effects of fermentation, baking and in vitro digestion on TIA and CIA were studied. Whole wheat flour, dough, and bread did not show any TIA. Other flours displayed TIA. Contrary to, all flours, doughs, and breads exhibited CIA. Although TIA was not detected in the protein extracts obtained from wheat and rye mix breads, protein extract of rye mix flour exhibited TIA. Following in vitro digestion process, TIA of wheat bread was found as 5.91units/mL gastric dialysate and 9.17units/mL intestine dialysate. CIA was determined in dialysates obtained from wheat (2.12CI/mL and 3.78CI/mL for gastric and intestinal dialysate respectively) and rye breads (4.16CI/mL and 2.46CI/mL for gastric and intestinal dialysate respectively). Copyright © 2016 Elsevier Ltd. All rights reserved.

Anti-Inflammatory Effects of Licorice and Roasted Licorice Extracts on TPA-Induced Acute Inflammation and Collagen-Induced Arthritis in Mice

PubMed Central

Kim, Ki Rim; Jeong, Chan-Kwon; Park, Kwang-Kyun; Choi, Jong-Hoon; Park, Jung Han Yoon; Lim, Soon Sung; Chung, Won-Yoon

2010-01-01

The anti-inflammatory activity of licorice (LE) and roated licorice (rLE) extracts determined in the murine phorbol ester-induced acute inflammation model and collagen-induced arthritis (CIA) model of human rheumatoid arthritis. rLE possessed greater activity than LE in inhibiting phorbol ester-induced ear edema. Oral administration of LE or rLE reduced clinical arthritis score, paw swelling, and histopathological changes in a murine CIA. LE and rLE decreased the levels of proinflammatory cytokines in serum and matrix metalloproteinase-3 expression in the joints. Cell proliferation and cytokine secretion in response to type II collagen or lipopolysaccharide stimulation were suppressed in spleen cells from LE or rLE-treated CIA mice. Furthermore, LE and rLE treatment prevented oxidative damages in liver and kidney tissues of CIA mice. Taken together, LE and rLE have benefits in protecting against both acute inflammation and chronic inflammatory conditions including rheumatoid arthritis. rLE may inhibit the acute inflammation more potently than LE. PMID:20300198

The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis

PubMed Central

Malfait, A. M.; Gallily, R.; Sumariwalla, P. F.; Malik, A. S.; Andreakos, E.; Mechoulam, R.; Feldmann, M.

2000-01-01

The therapeutic potential of cannabidiol (CBD), the major nonpsychoactive component of cannabis, was explored in murine collagen-induced arthritis (CIA). CIA was elicited by immunizing DBA/1 mice with type II collagen (CII) in complete Freund's adjuvant. The CII used was either bovine or murine, resulting in classical acute CIA or in chronic relapsing CIA, respectively. CBD was administered after onset of clinical symptoms, and in both models of arthritis the treatment effectively blocked progression of arthritis. CBD was equally effective when administered i.p. or orally. The dose dependency showed a bell-shaped curve, with an optimal effect at 5 mg/kg per day i.p. or 25 mg/kg per day orally. Clinical improvement was associated with protection of the joints against severe damage. Ex vivo, draining lymph node cells from CBD-treated mice showed a diminished CII-specific proliferation and IFN-γ production, as well as a decreased release of tumor necrosis factor by knee synovial cells. In vitro effects of CBD included a dose-dependent suppression of lymphocyte proliferation, both mitogen-stimulated and antigen-specific, and the blockade of the Zymosan-triggered reactive oxygen burst by peritoneal granulocytes. It also was found that CBD administration was capable of blocking the lipopolysaccharide-induced rise in serum tumor necrosis factor in C57/BL mice. Taken together, these data show that CBD, through its combined immunosuppressive and anti-inflammatory actions, has a potent anti-arthritic effect in CIA. PMID:10920191

Associations among psychological distress, high-risk activism, and conflict between ethnic-racial and sexual minority identities in lesbian, gay, bisexual racial/ethnic minority adults.

PubMed

Santos, Carlos E; VanDaalen, Rachel A

2018-03-01

In this brief report, we present results from a study exploring the associations of high-risk activism (HRA) orientation in lesbian, gay, and bisexual (LGB) issues; HRA orientation in racial/ethnic issues; conflicts in allegiances (CIA) between one's ethnic-racial and sexual minority identities; and anxiety among LGB racial/ethnic minority adults. A racially and ethnically diverse sample of 208 LGB racial/ethnic minority adults (age: M = 27.52, SD = 8.76) completed an online survey. Bivariate correlations showed that HRA orientation in LGB and in racial/ethnic issues, as well as CIA, were each positively associated with anxiety. However, regression analyses indicated that CIA moderated the association between anxiety and HRA orientation in LGB issues (but not racial/ethnic minority issues) such that this association was significant and positive at low levels of CIA and nonsignificant at high levels of CIA. These findings can be used to not only inform psychological practice with this population (e.g., by encouraging practitioners to be more attentive to these issues as potential sources of stress), but also more broadly, as knowledge that can inform the burgeoning psychological literature on collective action. We highlight, for example, the importance of distinguishing between types of activism (i.e., high- vs. low-risk types) in relation to mental health outcomes. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Gamma/delta T cells are the predominant source of interleukin-17 in affected joints in collagen-induced arthritis, but not in rheumatoid arthritis.

PubMed

Ito, Yoshinaga; Usui, Takashi; Kobayashi, Shio; Iguchi-Hashimoto, Mikiko; Ito, Hiromu; Yoshitomi, Hiroyuki; Nakamura, Takashi; Shimizu, Masakazu; Kawabata, Daisuke; Yukawa, Naoichiro; Hashimoto, Motomu; Sakaguchi, Noriko; Sakaguchi, Shimon; Yoshifuji, Hajime; Nojima, Takaki; Ohmura, Koichiro; Fujii, Takao; Mimori, Tsuneyo

2009-08-01

Although interleukin-17 (IL-17)-producing gamma/delta T cells were reported to play pathogenic roles in collagen-induced arthritis (CIA), their characteristics remain unknown. The aim of this study was to clarify whether gamma/delta T cells or CD4+ T cells are the predominant IL-17-producing cells, and to determine what stimulates gamma/delta T cells to secret IL-17 in mice with CIA. The involvement of IL-17-producing gamma/delta T cells in SKG mice with autoimmune arthritis and patients with rheumatoid arthritis (RA) was also investigated. IL-17-producing cells in the affected joints of mice with CIA were counted by intracellular cytokine staining during 6 distinct disease phases, and these cells were stimulated with various combinations of cytokines or specific antigens to determine the signaling requirements. Similar studies were performed using SKG mice with arthritis and patients with RA. Gamma/delta T cells were the predominant population in IL-17-producing cells in the swollen joints of mice with CIA, and the absolute numbers of these cells increased in parallel with disease activity. IL-17-producing gamma/delta T cells expressed CC chemokine receptor 6, were maintained by IL-23 but not by type II collagen in vitro, and were induced antigen independently in vivo. Furthermore, IL-17 production by gamma/delta T cells was induced by IL-1beta plus IL-23 independently of T cell receptor. In contrast to what was observed in mice with CIA, IL-17-producing gamma/delta T cells were nearly absent in the affected joints of SKG mice and patients with RA, and Th1 cells were predominant in the joints of patients with RA. Gamma/delta T cells were antigen independently stimulated by inflammation at affected joints and produced enhanced amounts of IL-17 to exacerbate arthritis in mice with CIA but not in SKG mice with arthritis or patients with RA.

The aryl hydrocarbon receptor suppresses osteoblast proliferation and differentiation through the activation of the ERK signaling pathway

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

Yu, Haitao; Du, Yuxuan; Zhang, Xulong

Ahr activation is known to be associated with synovitis and exacerbated rheumatoid arthritis (RA), but its contributions to bone loss have not been completely elucidated. Osteoblast proliferation and differentiation are abnormal at the erosion site in RA. Here, we reported that the expression of Ahr was increased in the hind paws' bone upon collagen-induced arthritis (CIA) in mice, and the levels of Ahr were negatively correlated with bone mineral density (BMD). In addition, immunofluorescent staining showed that the high expression of Ahr was mainly localized in osteoblasts from the CIA mice compared to normal controls. Moreover, the luciferase intensity ofmore » Ahr in the nucleus increased by 12.5% in CIA osteoblasts compared to that in normal controls. In addition, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) activation of the Ahr inhibited pre-osteoblast MC3T3-E1 cellular proliferation and differentiation in a dose-dependent manner. Interestingly, the levels of alkaline phosphatase (ALP) mRNA expression in the osteoblasts of CIA mice were reduced compared to normal controls. In contrast, decreased ALP expression by activated Ahr was completely reversed after pretreatment with an Ahr inhibitor (CH-223191) in MC3T3-E1 cell lines and primary osteoblasts on day 5. Our data further showed that activation of Ahr promoted the phosphorylation of ERK after 5 days. Moreover, Ahr-dependent activation of the ERK signaling pathway decreased the levels of proliferation cells and inhibited ALP activity in MC3T3-E1 cells. These results demonstrated that the high expression of Ahr may suppress osteoblast proliferation and differentiation through activation of the ERK signaling pathway, further enabling bone erosion in CIA mice. - Highlights: • The upregulation of Ahr was localized in osteoblasts of CIA mice. • The overexpression of Ahr suppressed osteoblast development. • The Ahr activated ERK signaling pathway to exacerbate bone erosion.« less

a System Dynamics Model to Study the Importance of Infrastructure Facilities on Quality of Primary Education System in Developing Countries

NASA Astrophysics Data System (ADS)

Pedamallu, Chandra Sekhar; Ozdamar, Linet; Weber, Gerhard-Wilhelm; Kropat, Erik

2010-06-01

The system dynamics approach is a holistic way of solving problems in real-time scenarios. This is a powerful methodology and computer simulation modeling technique for framing, analyzing, and discussing complex issues and problems. System dynamics modeling and simulation is often the background of a systemic thinking approach and has become a management and organizational development paradigm. This paper proposes a system dynamics approach for study the importance of infrastructure facilities on quality of primary education system in developing nations. The model is proposed to be built using the Cross Impact Analysis (CIA) method of relating entities and attributes relevant to the primary education system in any given community. We offer a survey to build the cross-impact correlation matrix and, hence, to better understand the primary education system and importance of infrastructural facilities on quality of primary education. The resulting model enables us to predict the effects of infrastructural facilities on the access of primary education by the community. This may support policy makers to take more effective actions in campaigns.

MDCA Needle 1 Replacement

NASA Image and Video Library

2013-04-22

ISS035-E-025557(22 April 2013) ---Multi-user Droplet Combustion Apparatus (MDCA) Hardware Replacement: Cassidy accessed the Combustion Integration Rack (CIR) Combustion Chamber and removed the MDCA Chamber Insert Assembly (CIA). He then replaced the MDCA Needle 1 due to a fuel line that was damaged during previous activities when the MDCA CIA was being removed from the Combustion Chamber.

77 FR 2606 - Unblocking of Specially Designated Nationals and Blocked Persons Pursuant to Executive Order 12978

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-18

.... RENTERIA CAICEDO, Beatriz Eugenia, c/o INVERSIONES AGROINDUSTRIALES DEL OCCIDENTE LTDA., Bogota, Colombia... ILOVIN S.A., Bogota, Colombia; c/o INVERSIONES DEL PRADO ABDALA SAIEH Y CIA. S.C.A., Barranquilla...., Bogota, Colombia; c/o INVERSIONES DEL PRADO ABDALA SAIEH Y CIA. S.C.A., Barranquilla, Colombia; c/o KAREN...

Prevention of chemotherapy-induced alopecia in rats by CDK inhibitors.

PubMed

Davis, S T; Benson, B G; Bramson, H N; Chapman, D E; Dickerson, S H; Dold, K M; Eberwein, D J; Edelstein, M; Frye, S V; Gampe, R T; Griffin, R J; Harris, P A; Hassell, A M; Holmes, W D; Hunter, R N; Knick, V B; Lackey, K; Lovejoy, B; Luzzio, M J; Murray, D; Parker, P; Rocque, W J; Shewchuk, L; Veal, J M; Walker, D H; Kuyper, L F

2001-01-05

Most traditional cytotoxic anticancer agents ablate the rapidly dividing epithelium of the hair follicle and induce alopecia (hair loss). Inhibition of cyclin-dependent kinase 2 (CDK2), a positive regulator of eukaryotic cell cycle progression, may represent a therapeutic strategy for prevention of chemotherapy-induced alopecia (CIA) by arresting the cell cycle and reducing the sensitivity of the epithelium to many cell cycle-active antitumor agents. Potent small-molecule inhibitors of CDK2 were developed using structure-based methods. Topical application of these compounds in a neonatal rat model of CIA reduced hair loss at the site of application in 33 to 50% of the animals. Thus, inhibition of CDK2 represents a potentially useful approach for the prevention of CIA in cancer patients.

Low-level laser treatment accelerated hair regrowth in a rat model of chemotherapy-induced alopecia (CIA).

PubMed

Wikramanayake, Tongyu Cao; Villasante, Alexandra C; Mauro, Lucia M; Nouri, Keyvan; Schachner, Lawrence A; Perez, Carmen I; Jimenez, Joaquin J

2013-05-01

Chemotherapy-induced alopecia (CIA) is one of the most distressing side effects of antineoplastic chemotherapy for which there is no effective interventional approach. A low-level laser (LLL) device, the HairMax LaserComb®, has been cleared by the FDA to treat androgenetic alopecia. Its effects may be extended to other settings; we have demonstrated that LaserComb treatment induced hair regrowth in a mouse model for alopecia areata. In the current study, we tested whether LLL treatment could promote hair regrowth in a rat model for CIA. Chemotherapy agents cyclophosphamide, etoposide, or a combination of cyclophosphamide and doxorubicin were administered in young rats to induce alopecia, with or without LLL treatment. As expected, 7-10 days later, all the rats developed full body alopecia. However, rats receiving laser treatment regrew hair 5 days earlier than rats receiving chemotherapy alone or sham laser treatment (with the laser turned off). The accelerated hair regrowth in laser-treated rats was confirmed by histology. In addition, LLL treatment did not provide local protection to subcutaneously injected Shay chloroleukemic cells. Taken together, our results demonstrated that LLL treatment significantly accelerated hair regrowth after CIA without compromising the efficacy of chemotherapy in our rat model. Our results suggest that LLL should be explored for the treatment of CIA in clinical trials because LLL devices for home use (such as the HairMax LaserComb®) provide a user-friendly and noninvasive approach that could be translated to increased patient compliance and improved efficacy.

A European patient record study on diagnosis and treatment of chemotherapy-induced anaemia.

PubMed

Ludwig, Heinz; Aapro, M; Bokemeyer, C; Glaspy, J; Hedenus, M; Littlewood, T J; Österborg, A; Rzychon, B; Mitchell, D; Beguin, Y

2014-08-01

Patients with cancer frequently experience chemotherapy-induced anaemia (CIA) and iron deficiency. Erythropoiesis-stimulating agents (ESAs), iron supplementation and blood transfusions are available therapies. This study evaluated routine practice in CIA management. Medical oncologists and/or haematologists from nine European countries (n=375) were surveyed on their last five cancer patients treated for CIA (n=1,730). Information was collected on tests performed at diagnosis of anaemia, levels of haemoglobin (Hb), serum ferritin and transferrin saturation (TSAT), as well as applied anaemia therapies. Diagnostic tests and therapies for CIA varied across Europe. Anaemia and iron status were mainly assessed by Hb (94%) and ferritin (48%) measurements. TSAT was only tested in 14%. At anaemia diagnosis, 74% of patients had Hb ≤ 10 g/dL, including 15% with severe anaemia (Hb <8 g/dL). Low-iron levels (ferritin ≤ 100 ng/mL) were detected in 42% of evaluated patients. ESA was used in 63%of patients, blood transfusions in 52 % and iron supplementation in 31% (74% oral, 26% intravenous iron). Only 30% of ESA-treated patients received a combination of ESA and iron supplementation. Blood transfusions formed part of a regular anaemia treatment regimen in 76% of transfused patients. Management practices were similar in 2009 and 2011. Management of anaemia and iron status in patients treated for CIA varies substantially across Europe. Iron status is only assessed in half of the patients. In contrast to clinical evidence, iron treatment is under utilised and mainly based on oral iron supplementation. Implementation of guidelines needs to be increased to minimize the use of blood transfusions.

Age-Related Differences in Collagen-Induced Arthritis: Clinical and Imaging Correlations

PubMed Central

Wilson-Gerwing, Tracy D; Pratt, Isaac V; Cooper, David M L; Silver, Tawni I; Rosenberg, Alan M

2013-01-01

Arthritis is among the most common chronic diseases in both children and adults. Although intraarticular inflammation is the feature common among all patients with chronic arthritis there are, in addition to age at onset, clinical characteristics that further distinguish the disease in pediatric and adult populations. In this study, we aimed to demonstrate the utility of microCT (µCT) and ultrasonography in characterizing pathologic age-related differences in a collagen-induced arthritis (CIA) rat model. Juvenile (35 d old) and young adult (91 d old) male Wistar rats were immunized with bovine type II collagen and incomplete Freund adjuvant to induce polyarthritis. Naïve male Wistar rats served as controls. All paws were scored on a scale of 0 (normal paw) to 4 (disuse of paw). Rats were euthanized at 14 d after the onset of arthritis and the hindpaws imaged by µCT and ultrasonography. Young adult rats had more severe signs of arthritis than did their juvenile counterparts. Imaging demonstrated that young adult CIA rats exhibited more widespread and severe skeletal lesions of the phalanges, metatarsals, and tarsal bones, whereas juvenile CIA rats had more localized and less proliferative and osteolytic damage that was confined predominantly to the phalanges and metatarsals. This report demonstrates the utility of imaging modalities to compare juvenile and young adult rats with CIA and provides evidence that disease characteristics and progression differ between the 2 age groups. Our observations indicate that the CIA model could help discern age-related pathologic processes in inflammatory joint diseases. PMID:24326225

2. BUNKER HILL LEAD SMELTER. VIEW IS FROM CIA TO ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

2. BUNKER HILL LEAD SMELTER. VIEW IS FROM CIA TO THE SOUTH. IN FOREGROUND, PLANT DRY, SLAG FUMING PLANT, BLAST FURNACE, SMELTER OFFICE, LEAD AND SILVER REFINERIES ARE VISIBLE, L. TO R. HIGH VELOCITY FLUE LEADS FROM LOWER PLANT TO BAG HOUSE AND STACKS AT TOP OF SMELTING FACILITY. - Bunker Hill Lead Smelter, Bradley Rail Siding, Kellogg, Shoshone County, ID

Implications of estimated magmatic additions and recycling losses at the subduction zones of accretionary (non-collisional) and collisional (suturing) orogens

USGS Publications Warehouse

Scholl, D. W.; von Huene, Roland E.

2009-01-01

Arc magmatism at subduction zones (SZs) most voluminously supplies juvenile igneous material to build rafts of continental and intra-oceanic or island arc (CIA) crust. Return or recycling of accumulated CIA material to the mantle is also most vigorous at SZs. Recycling is effected by the processes of sediment subduction, subduction erosion, and detachment and sinking of deeply underthrust sectors of CIA crust. Long-term (>10-20 Ma) rates of additions and losses can be estimated from observational data gathered where oceanic crust underruns modern, long-running (Cenozoic to mid-Mesozoic) ocean-margin subduction zones (OMSZs, e.g. Aleutian and South America SZs). Long-term rates can also be observationally assessed at Mesozoic and older crust-suturing subduction zone (CSSZs) where thick bodies of CIA crust collided in tectonic contact (e.g. Wopmay and Appalachian orogens, India and SE Asia). At modern OMSZs arc magmatic additions at intra-oceanic arcs and at continental margins are globally estimated at c. 1.5 AU and c. 1.0 AU, respectively (1 AU, or Armstrong Unit,= 1 km3 a-1 of solid material). During collisional suturing at fossil CSSZs, global arc magmatic addition is estimated at 0.2 AU. This assessment presumes that in the past the global length of crustal collision zones averaged c. 6000 km, which is one-half that under way since the early Tertiary. The average long-term rate of arc magmatic additions extracted from modern OMSZs and older CSSZs is thus evaluated at 2.7 AU. Crustal recycling at Mesozoic and younger OMSZs is assessed at c. 60 km3 Ma-1 km-1 (c. 60% by subduction erosion). The corresponding global recycling rate is c. 2.5 AU. At CSSZs of Mesozoic, Palaeozoic and Proterozoic age, the combined upper and lower plate losses of CIA crust via subduction erosion, sediment subduction, and lower plate crustal detachment and sinking are assessed far less securely at c. 115 km3 Ma-1 km-1. At a global length of 6000 km, recycling at CSSZs is accordingly c. 0.7 AU. The collective loss of CIA crust estimated for modern OMSZs and for older CSSZs is thus estimated at c. 3.2 AU. SZ additions (2.7 AU) and subtractions (23.2 AU) are similar. Because many uncertainties and assumptions are involved in assessing and applying them to the deep past, the net growth of CIA crust during at least Phanerozoic time is viewed as effectively nil. With increasing uncertainty, the long-term balance can be applied to the Proterozoic, but not before the initiation of the present style of subduction at c. 3 Ga. Allowing that since this time a rounded-down rate of recycling of 3 AU is applicable, a startlingly high volume of CIA crust equal to that existing now has been recycled to the mantle. Although the recycled volume (c. 9 ?? 109 km3) is small (c. 1%) compared with that of the mantle, it is large enough to impart to the mantle the signature of recycled CIA crust. Because subduction zones are not spatially fixed, and their average global lengths have episodically been less or greater than at present, recycling must have contributed significantly to creating recognized heterogeneities in mantle geochemistry. ?? The Geological Society of London 2009.

Integrative Exploratory Analysis of Two or More Genomic Datasets.

PubMed

Meng, Chen; Culhane, Aedin

2016-01-01

Exploratory analysis is an essential step in the analysis of high throughput data. Multivariate approaches such as correspondence analysis (CA), principal component analysis, and multidimensional scaling are widely used in the exploratory analysis of single dataset. Modern biological studies often assay multiple types of biological molecules (e.g., mRNA, protein, phosphoproteins) on a same set of biological samples, thereby creating multiple different types of omics data or multiassay data. Integrative exploratory analysis of these multiple omics data is required to leverage the potential of multiple omics studies. In this chapter, we describe the application of co-inertia analysis (CIA; for analyzing two datasets) and multiple co-inertia analysis (MCIA; for three or more datasets) to address this problem. These methods are powerful yet simple multivariate approaches that represent samples using a lower number of variables, allowing a more easily identification of the correlated structure in and between multiple high dimensional datasets. Graphical representations can be employed to this purpose. In addition, the methods simultaneously project samples and variables (genes, proteins) onto the same lower dimensional space, so the most variant variables from each dataset can be selected and associated with samples, which can be further used to facilitate biological interpretation and pathway analysis. We applied CIA to explore the concordance between mRNA and protein expression in a panel of 60 tumor cell lines from the National Cancer Institute. In the same 60 cell lines, we used MCIA to perform a cross-platform comparison of mRNA gene expression profiles obtained on four different microarray platforms. Last, as an example of integrative analysis of multiassay or multi-omics data we analyzed transcriptomic, proteomic, and phosphoproteomic data from pluripotent (iPS) and embryonic stem (ES) cell lines.

Operational Art of Counterterrorism

DTIC Science & Technology

2001-05-30

perpetrators, respond with all appropriate instruments against the sponsoring organizations and governments, and provide recovery relief to victims as...simultaneity. Effective operational designs employ complementary and reinforcing joint and service capabilities to achieve maximum simultaneity.178...50 The White House, National Security Startegy . 51 CIA, 35. 52 FM 3-0, 1-8. 53 CIA, 56. 54 Ibid, 40. 55 Ibid. 56 Friedman, 322. 57 Bin Laden, 18. 58 US

Double row anchor fixation: a novel technique for a diabetic calanceal insufficiency avulsion fracture.

PubMed

Greenhagen, Robert M; Highlander, Peter D; Burns, Patrick R

2012-01-01

Avulsion fractures of the calcaneal tuberosity represent only 1.3% to 2.7% of calcaneal fractures. These fractures are common pathologically in nature and attributed to decreased bone mineral density. Calcaneal insufficiency avulsion (CIA) fracture in patients with diabetes mellitus is most likely due to Charcot neuroarthropathy (CN) as described by the Brodsky classification (Brodsky 3B). Traditional open reduction and internal fixation is difficult in all calcaneal avulsion fractures because of poor bone quality. The authors report the first known description of the use of fracture fragment excision and double row anchor fixation.A 39-year-old woman with type I diabetes mellitus and a history of CN presented with an avulsion fracture of the calcaneal tuberosity. Excision of the fracture fragment and a gastrocnemius recession and reattachment of the Achilles tendon with double row anchor fixation to the calcaneus were performed. At 1 year, the patient's American Orthopaedic Foot & Ankle Society rearfoot score improved from 27/100 to 88/100. CIA fractures are an infrequently described injury. Because diabetes mellitus is frequently associated with this disease, it most likely represents a CN event. Traditionally, CIA fractures have been operatively treated with open reduction internal fixation. Previous authors have described difficulty with fixation because of poor quality. In the current report, the authors describe a novel operative approach to CIA fractures through the use of double row anchor fixation and excision of the fracture fragments. The authors feel that this previously undescribed treatment is superior to traditional methods and may serve as a new treatment option for all patients who have sustained this unusual pathology regardless of the underlying cause. The current authors provide a novel operative technique that provides inherent advantages to the traditional repair of CIA fractures. We believe CIA fractures represent a CN-type event and care should be taken when evaluating and treating these patients to prevent further sequelae. Copyright © 2012 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Effect of bone marrow-derived CD11b(+)F4/80 (+) immature dendritic cells on the balance between pro-inflammatory and anti-inflammatory cytokines in DBA/1 mice with collagen-induced arthritis.

PubMed

Fu, Jingjing; Zhang, Lingling; Song, Shanshan; Sheng, Kangliang; Li, Ying; Li, Peipei; Song, Shasha; Wang, Qingtong; Chu, Jianhong; Wei, Wei

2014-05-01

To explore the effect of bone marrow-derived CD11b(+)F4/80(+) immature dendritic cells (BM CD11b(+)F4/80(+)iDC) on the balance between pro-inflammatory and anti-inflammatory cytokines in DBA/1 mice with collagen-induced arthritis (CIA). BM CD11b(+)F4/80(+)iDC were induced with rmGM-CSF and rmIL-4, and were identified by the expressions of toll-like receptor 2 (TLR-2), indoleamine 2,3-deoxygenase (IDO), interleukin (IL)-10, transforming growth factor (TGF)-β1 and mixed leukocyte reaction (MLR). CIA was established in DBA/1 mice by immunization with type II collagen. CIA mice were injected intravenously with BM CD11b(+)F4/80(+)iDC three times after immunization. The effect of BM CD11b(+)F4/80(+)iDC on CIA was evaluated by the arthritis index, joint histopathology, body weight, thymus index, thymocytes proliferation, IL-1β, tumor necrosis factor (TNF)-α, IL-17, IL-10 and TGF-β1 levels. BM CD11b(+)F4/80(+)iDC induced with rmGM-CSF and rmIL-4 expressed high levels of TLR-2, IDO, IL-10 and TGF-β1. Infusion of BM CD11b(+)F4/80(+)iDC in CIA mice significantly reduced the arthritis index and pathological scores of joints, recovered the weight, decreased the thymus index and inhibited thymocyte proliferation. Levels of IL-1β, TNF-α and IL-17 were decreased in BM CD11b(+)F4/80(+)iDC-treated mice. BM CD11b(+)F4/80(+)iDC can be induced successfully with rmGM-CSF and rmIL-4. BM CD11b(+)F4/80(+)iDC treatment can ameliorate the development and severity of CIA by regulating the balance between pro-inflammatory cytokines and anti-inflammatory cytokines.

Efficacy and safety of darbepoetin alfa initiated at hemoglobin ≤10 g/dL in patients with stage IV cancer and chemotherapy-induced anemia.

PubMed

Boccia, Ralph V; Henry, David H; Belton, Laura; Bohac, Chet; Ghazal, Hassan H

2016-12-01

Data on efficacy and safety of darbepoetin alfa (DA) administered at hemoglobin (Hb) ≤10 g/dL are limited. In this analysis, we examined DA's efficacy and safety in patients with Stage IV cancers and chemotherapy-induced anemia (CIA) initiated on DA at Hb ≤10 g/dL. Data for patients with Stage IV cancers and CIA and who initiated DA at Hb ≤10 g/dL were extracted from three phase 3 trials identified in a central database of Amgen-sponsored DA studies in CIA. Efficacy outcomes were assessed by achievement of Hb increases of ≥1 g/dL and ≥2 g/dL and red blood cell (RBC) or whole blood transfusion requirements. Data were analyzed for all patients with baseline Hb ≤10 g/dL, and by the subgroups of patients with baseline Hb ≥9 to ≤10 g/dL versus <9 g/dL. Crude and Kaplan-Meier proportions of patients who experienced each outcome and time (days) to each outcome were summarized by treatment. Meta-analysis (fixed-effects inverse-variance model) was performed to compare outcomes for DA versus placebo. Safety was assessed by occurrence of adverse events. Data from 213 patients were analyzed: DA, n = 115; placebo, n = 98. More patients in the DA versus the placebo subgroup achieved Hb increase of ≥1 g/dL (72% vs. 36%; HR: 2.92, 95% CI: 1.95, 4.39) and ≥2 g/dL (44% vs. 18%; HR: 2.98, 95% CI: 1.71, 5.21) during the first 12 treatment weeks. Median times to Hb increase of ≥1 g/dL and ≥2 g/dL were 36 days and 78 days for DA, respectively. RBC or whole blood transfusions were less common in patients in the DA versus the placebo subgroup (24% vs. 45%; HR: 0.44, 95% CI: 0.27, 0.73). No new safety issues were reported. Our results confirm that DA use in patients with Stage IV cancer and CIA is more effective than placebo at increasing Hb levels and at reducing transfusion needs when DA treatment is initiated at Hb ≤10 g/dL. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Next Generation Enterprise Network Business Continuity: Maintaining Operations In A Compromised Environment

DTIC Science & Technology

2016-03-01

analysis CANES Consolidated Afloat Network and Enterprise Services CIA confidentiality, integrity, availability COOP continuity of operations DMZ...exercises, and increased readiness at sea as CANES is deployed to the Fleet. G. METHODS This work reviews published literature on BC, disaster recovery (DR...mitigation efforts [33]. 5. Consolidated Afloat Networks and Enterprise Services Consolidated Afloat Networks and Enterprise Services ( CANES ) is not

[Effect of paeoniflorin on level of glucocorticoid receptor of peripheral blood monocytes in rats of collagen-induced arthritis].

PubMed

Yi, Jian-Feng

2014-03-01

The study is to explore the effect of paeoniflorin on the level of glucocorticoid receptor, including glucocorticoid receptor-alpha (GCRalpha) and glucocorticoid receptor-beta (GCRbeta), of peripheral blood mononuclear cells (PBMCs) in rats of collagen-induced arthritis (CIA). CIA is induced in Wistar rats by an intradermal injection of bovine type II collagen emulsified with complete adjuvant. From the 14th day after primary immunization, the CIA rats were intragastrically administered paeoniflorin 25, 50 and 100 mg x kg(-1) or triptolde 20 microg x kg(-1) or paeoniflorin 50 mg x kg(-1) + RU486 15 mg x kg(-1), once a day, for 28 consecutive days. After administration, apart from PF + RU486 group all experimental rats were took blood by removalling eyeball, then separated PBMCs. The level of GCRalpha, GCRbeta in PBMCs were examined by ELISA, and the mRNA expression of GCRalpha, GCRbeta was detected by RT-PCR. All rats were sacrificed and took the joint with no immunization. The expression of IL-1beta, NF-kappaB p65, TNF-alpha, PGE2 of synovial tissue was detected by immunohistochemistry. Paeoniflorin was able to inhibit the expression of IL-1beta, NF-kappaB p65, TNF-alpha, PGE2 of synovial tissue in CIA rats. While RU486, glucocorticoid receptor's blocker, could weaken the fuction of paeoniflorin. Meanwhile, paeoniflorin obviously induced the expression of GCRalpha and GCRalpha mRNA, while obviously inhibited the expression of GCRbeta and GCRbeta mRNA. These results indicat paeoniflorine suppresses inflammatory mediator production may be relating with it regulating GCR in PBMCs of CIA rats.

A Modified Compound From Paeoniflorin, CP-25, Suppressed Immune Responses and Synovium Inflammation in Collagen-Induced Arthritis Mice.

PubMed

Chen, Jingyu; Wang, Ying; Wu, Huaxun; Yan, Shangxue; Chang, Yan; Wei, Wei

2018-01-01

Paeoniflorin-6'- O -benzene sulfonate (CP-25) is a modified paeoniflorin, which is the main bioactive component of total glucosides of peony. This study evaluated the anti-inflammatory and immunoregulatory effects of CP-25 in mice with collagen-induced arthritis (CIA) and the potential mechanisms underlying these effects. After the onset of CIA, mice were given CP-25 (17.5, 35, or 70 mg/kg) or methotrexate (MTX, 2.0 mg/kg). The arthritis index, swollen joint count, and joint and spleen histopathology were evaluated. T and B cell subsets were assayed using flow cytometry, while the proliferation of these cells and fibroblast-like synoviocytes (FLSs) were evaluated using the Cell Counting Kit-8. β2-adrenoceptor (β2-AR) expression was assayed using flow cytometry, immunohistochemistry, and western blotting. FLS migration and invasion were assayed using Transwells. CP-25 (35 or 70 mg/kg) attenuated the arthritis index and swollen joint count, alleviated joint and spleen histopathology, suppressed excessive T cell activation, and attenuated humoral immunity in CIA mice. CP-25 increased β2-AR expression on T cells, B cells, dendritic cells, and the synovium in CIA mice. CP-25 up-regulated the β2-AR agonist response and attenuated FLS activation; these effects may reflect CP-25-mediated reduction of β2-AR desensitization due to down-regulation of membrane G protein-coupled receptor kinase 2 expression. These results suggest that CP-25 suppressed immune responses and synovium inflammation in mice with CIA, effects that were associated with reduced β2-AR desensitization and the promotion of β2-AR signaling.

Prophylactic Injection of Recombinant Alpha-Enolase Reduces Arthritis Severity in the Collagen-Induced Arthritis Mice Model

PubMed Central

Guillou, Clément; Derambure, Céline; Fréret, Manuel; Verdet, Mathieu; Avenel, Gilles; Golinski, Marie-Laure; Sabourin, Jean-Christophe; Loarer, François Le; Adriouch, Sahil; Boyer, Olivier; Lequerré, Thierry; Vittecoq, Olivier

2015-01-01

Objective To evaluate the ability of the glycolytic enzyme alpha-enolase (ENO1) or its immunodominant peptide (pEP1) to reduce the severity of CIA in DBA/1 mice when injected in a prophylactic way. Methods Mice were treated with mouse ENO1 or pEP1 one day prior to collagen II immunization. Clinical assessment was evaluated using 4 parameters (global and articular scores, ankle thickness and weight). Titers of serum anti-ENO1, anti-cyclic citrullinated peptides (anti-CCP) and anti-CII (total IgG and IgG1/IgG2a isotypes) antibodies were measured by ELISA at different time-points. Disease activity was assessed by histological analysis of both anterior and hind paws at the end of experimentation. Results Prophylactic injection of 100 μg of ENO1 reduced severity of CIA. Serum levels of anti-CII antibodies were reduced in ENO1-treated mice. Concordantly, ENO1-treated mice joints presented less severe histological signs of arthritis. ENO1 did not induce a shift toward a Th2 response since IgG1/IgG2a ratio of anti-CII antibodies remained unchanged and IL-4 serum levels were similar to those measured in the control group. Conclusions Pre-immunization with ENO1 or its immunodominant peptide pEP1 reduces CIA severity at the clinical, immunological and histological levels. Effects of pEP1 were less pronounced. This immunomodulatory effect is associated with a reduction in anti-CII antibodies production but is not due to a Th1/Th2 shift. PMID:26302382

MET18 Connects the Cytosolic Iron-Sulfur Cluster Assembly Pathway to Active DNA Demethylation in Arabidopsis

PubMed Central

Tang, Kai; Zhang, Huiming; Mangrauthia, Satendra K.; Lei, Mingguang; Hsu, Chuan-Chih; Hou, Yueh-Ju; Wang, Chunguo; Li, Yan; Tao, W. Andy; Zhu, Jian-Kang

2015-01-01

DNA demethylation mediated by the DNA glycosylase ROS1 helps determine genomic DNA methylation patterns and protects active genes from being silenced. However, little is known about the mechanism of regulation of ROS1 enzymatic activity. Using a forward genetic screen, we identified an anti-silencing (ASI) factor, ASI3, the dysfunction of which causes transgene promoter hyper-methylation and silencing. Map-based cloning identified ASI3 as MET18, a component of the cytosolic iron-sulfur cluster assembly (CIA) pathway. Mutation in MET18 leads to hyper-methylation at thousands of genomic loci, the majority of which overlap with hypermethylated loci identified in ros1 and ros1dml2dml3 mutants. Affinity purification followed by mass spectrometry indicated that ROS1 physically associates with MET18 and other CIA components. Yeast two-hybrid and split luciferase assays showed that ROS1 can directly interact with MET18 and another CIA component, AE7. Site-directed mutagenesis of ROS1 indicated that the conserved iron-sulfur motif is indispensable for ROS1 enzymatic activity. Our results suggest that ROS1-mediated active DNA demethylation requires MET18-dependent transfer of the iron-sulfur cluster, highlighting an important role of the CIA pathway in epigenetic regulation. PMID:26492035

H2-M polymorphism in mice susceptible to collagen-induced arthritis involves the peptide binding groove

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

Walter, W.; Loos, M.; Maeurer, M.J.

1996-12-31

The ability to develop type II collagen (CII)-induced arthritis (CIA) in mice is associated with the major histocompatibility I-A gene and with as yet poorly defined regulatory molecules of the major histocompatibility complex (MHC) class II antigen processing and presentation pathway. H2-M molecules are thought to be involved in the loading of antigenic peptides into the MHC class II binding cleft. We sequenced H2-Ma, H2-Mb1, and H2-Mb2 genes from CIA-susceptible and -resistant mouse strains and identified four different Ma and Mb2 alleles, and three different Mb1 alleles defined by polymorphic residues within the predicted peptide binding groove. Most CIA-resistant mousemore » strains share common Ma, Mb1, and Mb2 alleles. In contrast, H2-M alleles designated Ma-III, Ma-IV, Mb1-III, and Mb2-IV could be exclusively identified in the CIA-susceptible H2{sup r} and H2{sup q} haplotypes, suggesting that allelic H2-M molecules may modulate the composition of different CII peptides loaded onto MHC class II molecules, presumably presenting {open_quotes}arthritogenic{close_quotes} epitopes to T lymphocytes. 42 refs., 4 figs., 3 tabs.« less

Modeling Combined Immunosuppressive and Anti-inflammatory Effects of Dexamethasone and Naproxen in Rats Predicts the Steroid-Sparing Potential of Naproxen.

PubMed

Li, Xiaonan; DuBois, Debra C; Song, Dawei; Almon, Richard R; Jusko, William J; Chen, Xijing

2017-07-01

Dexamethasone (DEX), a widely prescribed corticosteroid, has long been the cornerstone of the treatment of inflammation and immunologic dysfunctions in rheumatoid arthritis. Corticosteroids are frequently used in combination with other antirheumatic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) and disease-modifying antirheumatic drugs to mitigate disease symptoms and minimize unwanted effects. We explored the steroid dose-sparing potential of the NSAID naproxen (NPX) with in vitro and in vivo studies. The single and joint suppressive effects of DEX and NPX on the in vitro mitogen-induced proliferation of T lymphocytes in blood and their anti-inflammatory actions on paw edema were investigated in female and male Lewis rats with collagen-induced arthritis (CIA). As expected, DEX was far more potent than NPX in these systems. Mathematical models incorporating an interaction term ψ were applied to quantitatively assess the nature and intensity of pharmacodynamic interactions between DEX and NPX. Modest synergistic effects of the two drugs were found in suppressing the mitogenic response of T lymphocytes. A pharmacokinetic/pharmacodynamic/disease progression model integrating dual drug inhibition quantitatively described the pharmacokinetics, time-course of single and joint anti-inflammatory effects (paw edema), and sex differences in CIA rats, and indicated additive effects of DEX and NPX. Further model simulations demonstrated the promising steroid-sparing potential of NPX in CIA rats, with the beneficial effects of the combination therapy more likely in males than females. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Training Cyber Warriors: What Can Be Learned from Defense Language Training?

DTIC Science & Technology

2015-01-01

other agencies. In addition, the National Cryp- tologic School , Foreign Service Institute, and CIA University, among others, each train students for...They provide a variety of services, including group instruction , distance learning , and one-on-one tutoring. Pipeline-Building Programs The Language...commonly monolingual English speakers,1 (2) the U.S. education system provides limited opportunities for students to learn other languages in

Total Saponin from Anemone flaccida Fr. Schmidt Prevents Bone Destruction in Experimental Rheumatoid Arthritis via Inhibiting Osteoclastogenesis.

PubMed

Liu, Chunfang; Yang, Yue; Sun, Danni; Wang, Chao; Wang, Hui; Jia, Shiwei; Liu, Liang; Lin, Na

2015-12-01

Anemone flaccida Fr. Schmidt is used in the clinical compound prescription for the treatment of rheumatoid arthritis (RA) in China and has the traditional use of draining dampness, diminishing swelling, and relieving pain. Total saponins (TS) are the characteristic components and also the main active ingredients of A. flaccida. Previous reports indicated that TS possess anti-inflammatory and immunoregulatory properties; however, the effects of TS on bone destruction of RA have not been evaluated. In this study, our data first showed the therapeutic effects of TS on severity of arthritis and arthritis progression in collagen-induced arthritis (CIA) rats. Then, by microfocal computed tomography (CT) quantification, TS significantly increased bone mineral density, bone volume fraction, and trabecular thickness and decreased trabecular separation of inflamed joints both at peri-articular and extra-articular locations. TS also diminished the level of the bone resorption marker CTX-I and simultaneously increased the bone formation marker osteocalcin in sera of CIA rats. Interestingly, TS prevented bone destruction by reducing the number of osteoclasts in inflamed joints, reducing the expression of receptor activator of nuclear factor-κF (RANK) ligand (RANKL) and RANK, increasing the expression of osteoprotegerin (OPG), at both mRNA and protein levels, and decreasing the ratio of RANKL to OPG in inflamed joints and sera of CIA rats. This was further confirmed in the co-culture system of human fibroblast-like synovial and peripheral blood mononuclear cells. In addition, TS inhibited the levels of pro-inflammatory cytokines implicated in bone resorption, such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNFα), IL-6, IL-17, and IL-23 in sera and joints. These findings offer convincing evidence that TS attenuate RA partially by preventing both focal bone destruction and systemic bone loss. This anti-erosive effect results in part from inhibiting osteoclastogenesis by regulating the RANKL/RANK/OPG signaling pathway. The suppression of systemic and local pro-osteoclastogenic cytokines by TS was also highly effective.

Private Security Contractors in Iraq and Afghanistan: Legal Issues

DTIC Science & Technology

2009-12-22

Afghanistan: Background and Analysis, by Moshe Schwartz. 2 See James Risen and Mark Mazzetti, Blackwater Guards Tied to Secret C.I.A. Raids, NY...contractors, five Blackwater Worldwide employees under contract with the State Department were charged with manslaughter in connection with the 2007...at http://www.usdoj.gov/usao/law/news/wdl20081215.pdf. 125 Press Release, Department of Justice, Five Blackwater Employees Indicted on Manslaughter

Soviet News and Propaganda Analysis Based on RED STAR (The Official Newspaper of the Soviet Defense Establishment), 1 - 31 January 1982. Volume 2, Number 1, 1982.

DTIC Science & Technology

1982-01-01

Letelier, and has tried to murder Castro, Indira Ghandi and Iranian government leaders. From 1961 to 1976 the CIA has con- ducted over 900 clandestine...revolution." "More Afghanistan counterrevolutionary bands are destroyed by the Afghanistan Army." "Indira Ghandi says that the Soviet Union did not inter

Office of Strategic Services Training during World War II

DTIC Science & Technology

2010-06-01

First Central Intelligence Agency (Berkeley: University of California Press, 1972); Thomas F. Troy, Donovan and the CIA: A History of the...William E. Colby Papers, Box 14, Folder 7, Seeley G. Mudd Library, Princeton University, Princeton, New Jer- sey. 50. Gerald K. Haines, “Virginia...subject heading] 29 January 1945, 2–3, CIA Records (RG 263), Thomas Troy Files, Box 6, Folder 46, National Archives, II. In August 2008, the

Army Aviation’s Pacific Rebalance: Evolution Towards Maritime Operations

DTIC Science & Technology

2016-05-26

Training and Doctrine Command Pamphlet (TRADOC PAM) 525-3-1, The US Army Operating Concept: Win in a Complex World 2020-2040 (Washington, DC...influence.81 Figure 3. East Timor in the South Indian Ocean Source: “Indonesia” (map), CIA World Factbook, accessed 2 March 2016, https://www. cia.gov...library/publications/resources/the- world -factbook/geos/id.html. In 1975, Indonesia invaded and annexed the Portuguese colony, Timor Island

A simple algorithm for the identification of clinical COPD phenotypes.

PubMed

Burgel, Pierre-Régis; Paillasseur, Jean-Louis; Janssens, Wim; Piquet, Jacques; Ter Riet, Gerben; Garcia-Aymerich, Judith; Cosio, Borja; Bakke, Per; Puhan, Milo A; Langhammer, Arnulf; Alfageme, Inmaculada; Almagro, Pere; Ancochea, Julio; Celli, Bartolome R; Casanova, Ciro; de-Torres, Juan P; Decramer, Marc; Echazarreta, Andrés; Esteban, Cristobal; Gomez Punter, Rosa Mar; Han, MeiLan K; Johannessen, Ane; Kaiser, Bernhard; Lamprecht, Bernd; Lange, Peter; Leivseth, Linda; Marin, Jose M; Martin, Francis; Martinez-Camblor, Pablo; Miravitlles, Marc; Oga, Toru; Sofia Ramírez, Ana; Sin, Don D; Sobradillo, Patricia; Soler-Cataluña, Juan J; Turner, Alice M; Verdu Rivera, Francisco Javier; Soriano, Joan B; Roche, Nicolas

2017-11-01

This study aimed to identify simple rules for allocating chronic obstructive pulmonary disease (COPD) patients to clinical phenotypes identified by cluster analyses.Data from 2409 COPD patients of French/Belgian COPD cohorts were analysed using cluster analysis resulting in the identification of subgroups, for which clinical relevance was determined by comparing 3-year all-cause mortality. Classification and regression trees (CARTs) were used to develop an algorithm for allocating patients to these subgroups. This algorithm was tested in 3651 patients from the COPD Cohorts Collaborative International Assessment (3CIA) initiative.Cluster analysis identified five subgroups of COPD patients with different clinical characteristics (especially regarding severity of respiratory disease and the presence of cardiovascular comorbidities and diabetes). The CART-based algorithm indicated that the variables relevant for patient grouping differed markedly between patients with isolated respiratory disease (FEV 1 , dyspnoea grade) and those with multi-morbidity (dyspnoea grade, age, FEV 1 and body mass index). Application of this algorithm to the 3CIA cohorts confirmed that it identified subgroups of patients with different clinical characteristics, mortality rates (median, from 4% to 27%) and age at death (median, from 68 to 76 years).A simple algorithm, integrating respiratory characteristics and comorbidities, allowed the identification of clinically relevant COPD phenotypes. Copyright ©ERS 2017.

Doença cística da adventícia na veia basílica: relato de caso

PubMed Central

Vasconcelos, Rafael Sampaio; Cherubim, Cesar Augusto; França, Felipe Mavignier Pereira; D'allacqua, Eduardo de Lucca; Dalio, Marcelo Bellini; Joviliano, Edwaldo Edner

2016-01-01

Resumo A doença cística da adventícia é uma entidade rara que acomete principalmente a artéria poplítea. A ocorrência em veias é muito rara, e sua etiologia é desconhecida. Clinicamente, apresenta-se como isquemia, trombose ou dor a depender do território acometido. Apresentamos o caso de um paciente masculino jovem referindo nódulo no braço esquerdo. A angiorressonância magnética do membro mostrou lesão cística em contato com a veia basílica, com conteúdo homogêneo e sem realce pós-contraste. Foi realizada ressecção da lesão em bloco com o segmento venoso envolvido. O estudo anatomopatológico foi sugestivo de cisto de adventícia de veia basílica.

A Manpower, Budget, Structure, Synergism (MBSS) Model for the Comparison of US-Soviet Military-Space Research Efforts.

DTIC Science & Technology

1983-08-01

particular markets . The US government, on the other hand, has no competition except from foreign governments. Judgments as to the adequacy of...Defense Burden," Naval War College Review, Jul-Aug 81, p 41. 20 TABLE 2-3 SOVIET DEFENSE COST CATEGORY MIX Percentages Rosenfielde CIA () (2...consistent that virtually identical ruble - dollar conversion rates over that period are plausible. The CIA also prepares estimates of cost category mixes

Buprenorphine Alters Inflammatory and Oxidative Stress Molecular Markers in Arthritis

PubMed Central

Hitchon, Carol

2017-01-01

Buprenorphine is recommended for use as an analgesic in animal models including in murine models of collagen-induced arthritis (CIA). However, the effect of buprenorphine on the expression of disease-associated biomarkers is not well defined. We examined the effect of buprenorphine administration on disease progression and the expression of inflammatory and oxidative stress markers, in a murine model of CIA. Buprenorphine administration altered the expression of cytokines, IFN-γ, IL-6, and MMP-3, and oxidative markers, for example, iNOS, superoxide dismutase (SOD1), and catalase (CAT), in the CIA mice. As buprenorphine is an analgesic, we further monitored the association of expression of these biomarkers with pain scores in a human cohort of early rheumatoid arthritis (RA). Serum MMP-3 levels and blood mRNA expression of antioxidants sod1 and cat correlated with pain scores in the RA cohort. We have demonstrated that administration of buprenorphine alters the expression of inflammatory and oxidative stress-related molecular markers in a murine model of CIA. This caveat needs to be considered in animal experiments using buprenorphine as an analgesic, as it can be a confounding factor in murine studies used for prediction of response to therapy. Furthermore, the antioxidant enzymes that showed an association with pain scores in the human cohort may be explored as biomarkers for pain in future studies. PMID:28572711

Acarbose Decreases the Rheumatoid Arthritis Risk of Diabetic Patients and Attenuates the Incidence and Severity of Collagen-induced Arthritis in Mice

PubMed Central

Chen, Hsin-Hua; Chen, Der-Yuan; Chao, Ya-Hsuan; Chen, Yi-Ming; Wu, Chao-Liang; Lai, Kuo-Lung; Lin, Ching-Heng; Lin, Chi-Chen

2015-01-01

Acarbose has been found to decrease some inflammatory parameters in diabetic patients. This study aimed to examine the influence of acarbose on rheumatoid arthritis (RA) risk in diabetes mellitus (DM) patients and on the incidence and severity of collagen-induced arthritis (CIA) in mice. In a nationwide, matched case–control study, we identified 723 incident RA cases and selected 7,230 age-, sex- and RA diagnosis date–matched controls from all newly treated DM patients. We found that use of acarbose at > 16,950 mg per year was associated with a lower RA risk (odds ratio 0.60; 95% CI, 0.41–0.89). In the CIA mouse study, acarbose was orally administered from days -7 to 38 relative to type II collagen (CII) immunization. The results revealed that acarbose at the dose of 500 mg/kg/day attenuated the incidence and severity of arthritis and the expression of proinflammatory cytokines, including TNF-α, IL-6 and IL-17 in the paw tissues. Acarbose further decreased the productions of anti-CII-IgG, IL-17 and IFN-γ by collagen-reactive lymph node cells. This work suggests that the use of acarbose decreased RA risk in DM patients and the incidence of CIA in mice. Acarbose also attenuated the severity of CIA via anti-inflammatory and immunomodulatory effects. PMID:26678745

Acarbose Decreases the Rheumatoid Arthritis Risk of Diabetic Patients and Attenuates the Incidence and Severity of Collagen-induced Arthritis in Mice.

PubMed

Chen, Hsin-Hua; Chen, Der-Yuan; Chao, Ya-Hsuan; Chen, Yi-Ming; Wu, Chao-Liang; Lai, Kuo-Lung; Lin, Ching-Heng; Lin, Chi-Chen

2015-12-18

Acarbose has been found to decrease some inflammatory parameters in diabetic patients. This study aimed to examine the influence of acarbose on rheumatoid arthritis (RA) risk in diabetes mellitus (DM) patients and on the incidence and severity of collagen-induced arthritis (CIA) in mice. In a nationwide, matched case-control study, we identified 723 incident RA cases and selected 7,230 age-, sex- and RA diagnosis date-matched controls from all newly treated DM patients. We found that use of acarbose at > 16,950 mg per year was associated with a lower RA risk (odds ratio 0.60; 95% CI, 0.41-0.89). In the CIA mouse study, acarbose was orally administered from days -7 to 38 relative to type II collagen (CII) immunization. The results revealed that acarbose at the dose of 500 mg/kg/day attenuated the incidence and severity of arthritis and the expression of proinflammatory cytokines, including TNF-α, IL-6 and IL-17 in the paw tissues. Acarbose further decreased the productions of anti-CII-IgG, IL-17 and IFN-γ by collagen-reactive lymph node cells. This work suggests that the use of acarbose decreased RA risk in DM patients and the incidence of CIA in mice. Acarbose also attenuated the severity of CIA via anti-inflammatory and immunomodulatory effects.

Follistatin-like protein 1 is a critical mediator of experimental Lyme arthritis and the humoral response to Borrelia burgdorferi infection.

PubMed

Campfield, Brian T; Nolder, Christi L; Marinov, Anthony; Bushnell, Daniel; Davis, Amy; Spychala, Caressa; Hirsch, Raphael; Nowalk, Andrew J

2014-08-01

Follistatin-like protein 1 (FSTL-1) has recently been described as a critical mediator of CIA and a marker of disease activity. Lyme arthritis, caused by Borrelia burgdorferi, shares similarities with autoimmune arthritis and the experimental murine model collagen-induced arthritis (CIA). Because FSTL-1 is important in CIA and autoimmune arthritides, and Lyme arthritis shares similarities with CIA, we hypothesized that FSTL-1 may be an important mediator of Lyme arthritis. We demonstrate for the first time that FSTL-1 is induced by B. burgdorferi infection and is required for the development of Lyme arthritis in a murine model, utilizing a gene insertion to generate FSTL-1 hypomorphic mice. Using qPCR and qRT-PCR, we found that despite similar early infectious burden, FSTL-1 hypomorphic mice have improved spirochetal clearance in the face of attenuated arthritis and inflammatory cytokine production. Further, FSTL-1 mediates pathogen-specific antibody production and antigen recognition when assessed by ELISA and one- and two-dimensional immunoblotting. This study is the first to describe a role for FSTL-1 in the development of Lyme arthritis and anti-Borrelia response, and the first to demonstrate a role for FSTL-1 in response to infection, highlighting the potential for FSTL-1 as a target in the treatment of B. burgdorferi infection. Copyright © 2014. Published by Elsevier Ltd.

N-(2-Hydroxyphenyl)acetamide: a Novel Suppressor of RANK/RANKL Pathway in Collagen-Induced Arthritis Model in Rats.

PubMed

Gul, Anum; Kunwar, Bimal; Mazhar, Maryam; Perveen, Kahkashan; Simjee, Shabana U

2017-08-01

RANKL and RANK are potential contributors of inflammatory cascade in human and animal model of arthritis. The current study aims to investigate the effect of N-(2-hydroxyphenyl)acetamide (NA-2) on regulation of RANKL pathway in collagen-induced arthritis (CIA) model in rats. CIA was induced using bovine type II collagen in female Wistar rats. The clinical parameters, level of pro-inflammatory and oxidative stress markers were measured to determine the progression of the disease. The mRNA level of RANKL and RANK and downstream mediators of inflammation i.e. c-fos, c-jun, NF-κB and Akt were analysed in spleen tissue using real-time PCR. Immunohistochemical analysis of iNOS, pAkt and c-Fos was also done in spleen tissue. Treatment with NA-2 and indomethacin showed increase in body weight and significant reduction in paw volume and arthritic score (p < 0.0001). Marked reduction in the level of oxidative stress markers, NO, PO and GSH (p < 0.0001), and pro-inflammatory markers, IL-1β (p < 0.0001) and TNF-α (p < 0.01), was also observed. Likewise, NA-2 and indomethacin treatment also significantly suppressed the mRNA expression of RANKL, RANK, c-fos, c-jun, NF-κB (p < 0.0001) and Akt (p < 0.01) and protein expression of iNOS, pAkt and c-Fos (p < 0.0001) compared to the arthritic control group. Our findings suggest that NA-2 is an antiarthritic agent acting in a pleiotropic manner in CIA rats by not only reducing the clinical signs of arthritis, inflammatory cytokines and free radical production but also attenuating the RANK/RANKL signaling pathway.

Long-term outcomes after re-entry device use for recanalization of common iliac artery chronic total occlusions.

PubMed

Kokkinidis, Damianos G; Alvandi, Bejan; Cotter, Ryan; Hossain, Prio; Foley, T Raymond; Singh, Gagan D; Waldo, Stephen W; Laird, John R; Armstrong, Ehrin J

2018-03-09

To examine the impact of re-entry device (RED) use on 1- and 5-year outcomes after endovascular treatment of common iliac artery (CIA) chronic total Occlusions (CTOs). There are not enough data regarding the long-term safety and efficacy of RED. We performed a two-center retrospective study of 115 patients (140 lesions) undergoing CIA CTO endovascular intervention between 2006 and 2016. Baseline characteristics and long-term outcomes were described. A Cox proportional hazard model was developed to determine if REDs were associated with target lesion revascularization (TLR) or major adverse limb events (MALE) after 1 and 5 years. Among 140 lesions, 43 (31%) required use of a RED. The mean age was 63.9 years and the majority (n = 80) of patients were male. An antegrade crossing approach and treatment of restenotic lesions were less common in the RED group (10% vs. 29%, P < .05 and 0% vs. 21%, P < .05, respectively). There were no significant differences in Rutherford class, pre-procedure ABI, or patient presentation. The procedural complication rates were similar between the two groups. The 1- and 5-year TLR rates for lesions treated with re-entry device vs. standard approaches were 11% vs. 9%; P = 0.8 and 29% vs. 29%; P = 0.9 respectively. The 1 and 5-year MALE rates for lesions treated with re-entry device were 5% vs. 6%; P = 0.8 and 11% vs. 11%; P = 0.9 respectively. This retrospective analysis found that recanalization of CIA occlusions using a RED is safe and is associated with long-term clinical outcomes similar to that of standard crossing techniques. © 2018 Wiley Periodicals, Inc.

Accuracy of the Defining Characteristics of the Nursing Diagnosis Hypothermia in Newborns.

PubMed

de Aquino, Wislla Ketlly Menezes; Lopes, Marcos Venícios de Oliveira; da Silva, Viviane Martins; Fróes, Nathaly Bianka Moraes; de Menezes, Angélica Paixão; Almeida, Aline de Aquino Peres; Sobreira, Bianca Alves

2017-09-18

To analyze the accuracy of the defining characteristics of hypothermia in newborns and to verify associations between defining characteristics and clinical variables. A cross-sectional accuracy study with statistical analysis. Slow capillary refill, decrease in ventilation, peripheral vasoconstriction, and insufficient weight gain were the defining characteristics with the highest specificity values, while slow gastric emptying, skin cool to touch, irritability, and bradycardia were the defining characteristics with the highest values for both sensitivity and specificity. Slow gastric emptying, skin cool to touch, irritability, and bradycardia are good clinical indicators to infer initial stages of hypothermia and to confirm its presence. Accuracy measures may contribute to the improvement of the diagnostic inferential process. Analisar acurácia das características definidoras de Hipotermia em recém-nascidos e identificar a associação delas com variáveis clínicas. MÉTODO: Estudo de acurácia transversal com análise estatística. Preenchimento capilar lento, diminuição da ventilação, vasoconstrição periférica e ganho de peso insuficiente apresentaram valores altos de especificidade enquanto esvaziamento gástrico lento, pele fria, irritabilidade e bradicardia apresentaram valores elevados de sensibilidade e especificidade. CONCLUSÃO: Esvaziamento gástrico lento, pele fria, irritabilidade e bradicardia são úteis para inferir estágios iniciais de hipotermia e para confirmação diagnóstica. IMPLICAÇÕES PARA PRÁTICA DE ENFERMAGEM: Medidas de acurácia podem contribuir para o processo de inferência do diagnóstico hipotermia. © 2017 NANDA International, Inc.

Effect of Disease-Related Changes in Plasma Albumin on the Pharmacokinetics of Naproxen in Male and Female Arthritic Rats

PubMed Central

Li, Xiaonan; DuBois, Debra C.; Almon, Richard R.

2017-01-01

Naproxen (NPX) is used in the treatment of rheumatoid arthritis (RA) for alleviation of pain and inflammation. In view of the extensive albumin binding of NPX, this study investigates whether chronic inflammation and sex influence the physiologic albumin concentrations, plasma protein binding, and pharmacokinetics (PK) of NPX. The PK of NPX was evaluated in a rat model of RA [collagen-induced arthritis (CIA) in Lewis rats] and in healthy controls. These PK studies included 1) NPX in female and male CIA rats that received 10, 25, or 50 mg/kg NPX i.p.; and 2) NPX in healthy female and male rats after i.p. dosing of NPX at 50 mg/kg. Plasma albumin concentrations were quantified by enzyme-linked immunosorbent assay, and protein binding was assessed using ultrafiltration. The NPX concentrations in plasma and filtrates were determined by liquid chromatography–tandem mass spectrometry (LC-MS/MS). Plasma concentration-time data of NPX were first assessed by noncompartmental analysis (NCA). Nonlinear PK as indicated by dose-dependent NCA clearances and distribution volumes was observed. A two-compartment model with a first-order absorption process incorporating nonlinear protein binding in plasma and tissues jointly described the PK data of all groups. Saturable albumin binding accounts for the nonlinearity of NPX PK in all rats as well as part of the PK differences in arthritic rats. The CIA rats exhibited reduced albumin concentrations, reduced overall protein binding, and reduced clearances of unbound NPX, consistent with expectations during inflammation. The net effect of chronic inflammation was an elevation of the Cmax and area under the plasma concentration-time curve (AUC) of unbound drug. PMID:28246126

Geochemical evidences for palaeoclimatic fluctuations at the Triassic-Jurassic boundary: southwestern margin of the Neotethys in the Salt Range, Pakistan

NASA Astrophysics Data System (ADS)

Iqbal, Shahid; Wagreich, Michael; Jan, Irfanullah; Kürschner, Wolfram Michael; Gier, Susanne

2017-04-01

The Triassic-Jurassic boundary interval reveals a change from warm-arid to a warm and humid climate in the Tethyan domain. Sea-level reconstruction records across the European basins during this interval reveal an end-Triassic global regression event and is linked to the Central Atlantic Magmatic Province (CAMP) activity and Pangaea breakup. In the Tethyan Salt Range of Pakistan a succession of Upper Triassic dolomites/green-black mudstones (Kingriali Formation), overlying quartzose sandstone, mudstones, laterites and Lower Jurassic conglomerates/pebbly sandstones (Datta Formation) provides information on the palaeoclimatic evolution of the area. Preliminary palynological results from the mudstones indicate a Rhaetian age for the Kingriali Formation and a Hettangian age for the Datta Formation. X-ray diffraction (XRD) analysis of the mudstones (upper part of the Kingriali Formation) indicates the presence of mainly illite while kaolinite is a minor component. The kaolinite content, a reflection of the advanced stage of chemical weathering and hence warm-humid conditions, increases up-section in the overlying sandstone-mudstone succession. The overlying laterite-bauxite horizons lack illite/smectite and are entirely composed of kaolinite, boehmite and haematite. At places these kaolinite rich horizons are mined in the area (Western Salt Range). The bulk rock geochemistry of the succession confirms a similar trend. The Chemical Index of Alteration (CIA) displays an increasing trend from the Upper Triassic shales (CIA 75-80) through the overlying sandstones/mudstones-laterites to the overlying quartz rich sandstones and mudstones (CIA 90-97). The overall results for the succession reveal an increasing chemical maturity trend (increase in the intensity of chemical weathering) from Rhaetian to Hettangian thereby supporting a change from warm-arid to a warm-humid palaeoclimate, probably extreme greenhouse conditions.

Applying a health system perspective to the evolving Farmácia Popular medicines access programme in Brazil

PubMed Central

Chaves, Luisa A; Campos, Monica R; Bertoldi, Andrea D; Silva, Rondineli M; Bigdeli, Maryam; Ross-Degnan, Dennis; Emmerick, Isabel C M

2017-01-01

The Farmácia Popular Program (FPP) launched a subsidy system in Brazil, but in coexistence with the ongoing regular governmental access to medicines (Unified Health System (SUS) dispensings) mechanisms, causing overlaps in terms of financing and target population. This characteristic is quite different from most countries with medicines cost-sharing schemes. This paper aims to analyse the FPP under a health systems perspective considering the different health system levels. We analysed the findings from the study ‘Impact of consecutive subsidies policies on access to and use of medicines in Brazil – ISAUM-Br’, designed with the objective of describing and evaluating the impact of the government medicines subsidy policies implemented between 2004 and 2011. Patient share of copayment increased with the implementation of the intervention, which decreased the reference price and decreased with SNP (Saúde Não Tem Preço; zero copayment for patients). There was an increased number of FPP dispensations over time, but SUS dispensings remained the most important source for medicines, especially for hypertension and diabetes. FPP allowed the establishment of a well-designed pharmaceutical information system in the country. Despite the improvement on control mechanism, fraud remained a problem. There were important effects on the pharmaceutical market and sales of generic medicines. FPP has proven to be a very important policy for promoting access to medicines for hypertension and diabetes in Brazil. Examining this policy with a health system perspective has allowed us to highlight many of its important consequences, including for the first time a broad and consistent information system on access to medicines in the country. PMID:29527335

Conservation of Information: Reverse Engineering Dark Social Systems

DTIC Science & Technology

2010-01-01

Factbook, retrieved 5/20/10 from www.cia.gov). 25 For example, Air- America , a politically liberal talk radio network, said that it would cease operations...attractive targets than mid- America ; see Reding, 2009). Obama Clinton Clinton Obama Lawless et al.: Conservation of Information 13 approached it...indefinitely sustain the control of the Communist Party--i.e., censoring Google--is increasingly at odds with Network China, which is thriving by

Anthocyanin Extracted from Black Soybean Seed Coats Prevents Autoimmune Arthritis by Suppressing the Development of Th17 Cells and Synthesis of Proinflammatory Cytokines by Such Cells, via Inhibition of NF-κB.

PubMed

Min, Hong Ki; Kim, Sung-Min; Baek, Seung-Ye; Woo, Jung-Won; Park, Jin-Sil; Cho, Mi-La; Lee, Jennifer; Kwok, Seung-Ki; Kim, Sae Woong; Park, Sung-Hwan

2015-01-01

Oxidative stress plays a role in the pathogenesis of rheumatoid arthritis (RA). Anthocyanin is a plant antioxidant. We investigated the therapeutic effects of anthocyanin extracted from black soybean seed coats (AEBS) in a murine model of collagen-induced arthritis (CIA) and human peripheral blood mononuclear cells (PBMCs) and explored possible mechanisms by which AEBS might exert anti-arthritic effects. CIA was induced in DBA/1J mice. Cytokine levels were measured via enzyme-linked immunosorbent assays. Joints were assessed in terms of arthritis incidence, clinical arthritis scores, and histological features. The extent of oxidative stress in affected joints was determined by measuring the levels of nitrotyrosine and inducible nitric oxide synthase. NF-κB activity was assayed by measuring the ratio of phosphorylated IκB to total IκB via Western blotting. Th17 cells were stained with antibodies against CD4, IL-17, and STAT3. Osteoclast formation was assessed via TRAP staining and measurement of osteoclast-specific mRNA levels. In the CIA model, AEBS decreased the incidence of arthritis, histological inflammation, cartilage scores, and oxidative stress. AEBS reduced the levels of proinflammatory cytokines in affected joints of CIA mice and suppressed NF-κB signaling. AEBS decreased Th17 cell numbers in spleen of CIA mice. Additionally, AEBS repressed differentiation of Th17 cells and expression of Th17-associated genes in vitro, in both splenocytes of naïve DBA/1J mice and human PBMCs. In vitro, the numbers of both human and mouse tartrate-resistant acid phosphatase+ (TRAP) multinucleated cells fell, in a dose-dependent manner, upon addition of AEBS. The anti-arthritic effects of AEBS were associated with decreases in Th17 cell numbers, and the levels of proinflammatory cytokines synthesized by such cells, mediated via suppression of NF-κB signaling. Additionally, AEBS suppressed osteoclastogenesis and reduced oxidative stress levels.

[Effect of bee venom injection on TrkA and TRPV1 expression in the dorsal root ganglion of rats with collagen-induced arthritis].

PubMed

Xian, Pei-Feng; Chen, Ying; Yang, Lu; Liu, Guo-Tao; Peng, Peng; Wang, Sheng-Xu

2016-06-01

To investigate the therapeutic effect of acupoint injection of bee venom on collagen-induced arthritis (CIA) in rats and explore the mechanism of bee venom therapy in the treatment of rheumatoid arthritis. Fifteen male Wistar rats were randomly divided into bee venom treatment group (BV group), CIA model group, and control group. In the former two groups, CIA was induced by injections of collagen II+IFA (0.2 mL) via the tail vein, and in the control group, normal saline was injected instead. The rats in BV group received daily injection of 0.1 mL (3 mg/mL) bee venom for 7 consecutive days. All the rats were assessed for paw thickness and arthritis index from days 14 to 21, and the pain threshold was determined on day 21. The expressions of TRPV1 and TrkA in the dorsal root ganglion at the level of L4-6 were detected using immunohistochemistry and Western blotting, respectively. The rats in CIA model group started to show paw swelling on day 10, and by day 14, all the rats in this group showed typical signs of CIA. In BV group, the rats receiving been venom therapy for 7 days showed a significantly smaller paw thickness and a low arthritis index than those in the model group. The pain threshold was the highest in the control group and the lowest in the model group. TRPV1-positive cells and TrkA expression in the dorsal root ganglion was significantly reduced in BV group as compared with that in the model group. s Injection of bee venom can decrease expression of TRPV1 and TrkA in the dorsal root ganglion to produce anti-inflammatory and analgesic effects, suggesting the potential value of bee venom in the treatment of rheumatoid arthritis.

Therapeutic effects of total alkaloids of Tripterygium wilfordii Hook f. on collagen-induced arthritis in rats.

PubMed

Zhang, Yuqin; Xu, Wei; Li, Huang; Zhang, Xun; Xia, Yufa; Chu, Kedan; Chen, Lidian

2013-02-13

Tripterygium wilfordii Hook f. is one of Traditional Chinese Medicines which is commonly used to treat rheumatoid arthritis (RA). The total alkaloids were the main constituent part of Tripterygium wilfordii Hook f. It has a great significance to study the effects of the total alkaloids of Tripterygium wilfordii Hook f. (ATW) on RA. This paper aims at investigating the therapeutic effect of ATW on RA and its possible mechanism, and providing a theoretical and experimental basis for the clinical use of ATW. The model of wistar rats of type II collagen-induced arthritis (CIA) was made, and the rats were perfused a stomach with ATW for 4 weeks continuously. Then the levels of interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-, in the serum of CIA rats were detected by enzyme linked immunosorbent assay (ELISA), and the joint pathological section of CIA rats was observed by hematoxylin and eosin (HE) staining method and the expression of IL-6, IL-8, nuclear factor kappa B (NF-κB), TNF-α were measure by immunohistochemistry staining method. Compared with model group, ATW could significantly reduce paw swelling and suppresse articular cartilage degenerated. The results also found that there was significant reduction levels of IL-6, IL-8 and TNF-α in serum of CIA rats treated with ATW and ATW inhibited the expression of IL-6, IL-8, NF-κB, TNF-α in synovial tissue. ATW not only could inhibit the symptom of CIA rats significantly but also could inhibit the production of IL-6, IL-8, TNF-α in serum and the expression of IL-6, IL-8, NF-κB and TNF-α in synovial tissue targeting the inflammatory. ATW would be a drug as a novel botanical drug for the treatment of RA. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Anti-Inflammatory Effects and Joint Protection in Collagen-Induced Arthritis after Treatment with IQ-1S, a Selective c-Jun N-Terminal Kinase Inhibitor

PubMed Central

Schepetkin, Igor A.; Kirpotina, Liliya N.; Hammaker, Deepa; Kochetkova, Irina; Khlebnikov, Andrei I.; Lyakhov, Sergey A.; Firestein, Gary S.

2015-01-01

c-Jun N-terminal kinases (JNKs) participate in many physiologic and pathologic processes, including inflammatory diseases. We recently synthesized the sodium salt of IQ-1S (11H-indeno[1,2-b]quinoxalin-11-one oxime) and demonstrated that it is a high-affinity JNK inhibitor and inhibits murine delayed-type hypersensitivity. Here we show that IQ-1S is highly specific for JNK and that its neutral form is the most abundant species at physiologic pH. Molecular docking of the IQ-1S syn isomer into the JNK1 binding site gave the best pose, which corresponded to the position of cocrystallized JNK inhibitor SP600125 (1,9-pyrazoloanthrone). Evaluation of the therapeutic potential of IQ-1S showed that it inhibited matrix metalloproteinase 1 and 3 gene expression induced by interleukin-1β in human fibroblast-like synoviocytes and significantly attenuated development of murine collagen-induced arthritis (CIA). Treatment with IQ-1S either before or after induction of CIA resulted in decreased clinical scores, and joint sections from IQ-1S–treated CIA mice exhibited only mild signs of inflammation and minimal cartilage loss compared with those from control mice. Collagen II–specific antibody responses were also reduced by IQ-1S treatment. By contrast, the inactive ketone derivative 11H-indeno[1,2-b]quinoxalin-11-one had no effect on CIA clinical scores or collagen II–specific antibody titers. IQ-1S treatment also suppressed proinflammatory cytokine and chemokine levels in joints and lymph node cells. Finally, treatment with IQ-1S increased the number of Foxp3+CD4+CD25+ regulatory T cells in lymph nodes. Thus, IQ-1S can reduce inflammation and cartilage loss associated with CIA and can serve as a small-molecule modulator for mechanistic studies of JNK function in rheumatoid arthritis. PMID:25784649

Anti-Inflammatory Effects and Joint Protection in Collagen-Induced Arthritis after Treatment with IQ-1S, a Selective c-Jun N-Terminal Kinase Inhibitor.

PubMed

Schepetkin, Igor A; Kirpotina, Liliya N; Hammaker, Deepa; Kochetkova, Irina; Khlebnikov, Andrei I; Lyakhov, Sergey A; Firestein, Gary S; Quinn, Mark T

2015-06-01

c-Jun N-terminal kinases (JNKs) participate in many physiologic and pathologic processes, including inflammatory diseases. We recently synthesized the sodium salt of IQ-1S (11H-indeno[1,2-b]quinoxalin-11-one oxime) and demonstrated that it is a high-affinity JNK inhibitor and inhibits murine delayed-type hypersensitivity. Here we show that IQ-1S is highly specific for JNK and that its neutral form is the most abundant species at physiologic pH. Molecular docking of the IQ-1S syn isomer into the JNK1 binding site gave the best pose, which corresponded to the position of cocrystallized JNK inhibitor SP600125 (1,9-pyrazoloanthrone). Evaluation of the therapeutic potential of IQ-1S showed that it inhibited matrix metalloproteinase 1 and 3 gene expression induced by interleukin-1β in human fibroblast-like synoviocytes and significantly attenuated development of murine collagen-induced arthritis (CIA). Treatment with IQ-1S either before or after induction of CIA resulted in decreased clinical scores, and joint sections from IQ-1S-treated CIA mice exhibited only mild signs of inflammation and minimal cartilage loss compared with those from control mice. Collagen II-specific antibody responses were also reduced by IQ-1S treatment. By contrast, the inactive ketone derivative 11H-indeno[1,2-b]quinoxalin-11-one had no effect on CIA clinical scores or collagen II-specific antibody titers. IQ-1S treatment also suppressed proinflammatory cytokine and chemokine levels in joints and lymph node cells. Finally, treatment with IQ-1S increased the number of Foxp3(+)CD4(+)CD25(+) regulatory T cells in lymph nodes. Thus, IQ-1S can reduce inflammation and cartilage loss associated with CIA and can serve as a small-molecule modulator for mechanistic studies of JNK function in rheumatoid arthritis. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Norisoboldine ameliorates collagen-induced arthritis through regulating the balance between Th17 and regulatory T cells in gut-associated lymphoid tissues

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

Tong, Bei; Dou, Yannong; Wang, Ting

Norisoboldine (NOR), the main active ingredient of the dry root of Lindera aggregata, was previously proven to have substantial therapeutic effects on collagen-induced arthritis (CIA) in mice by oral administration. However, it exhibited a very poor bioavailability in normal rats. The pharmacokinetic–pharmacodynamics disconnection attracts us to explore its anti-arthritic mechanism in more detail. In this study, NOR, administered orally, markedly attenuated the pathological changes in CIA rats, which was accompanied by the down-regulation of pro-inflammatory cytokines and the up-regulation of anti-inflammatory cytokine IL-10. Pharmacokinetic studies demonstrated that the plasma concentration of NOR was moderately elevated in CIA rats compared withmore » normal rats, but it was still far lower than the minimal effective concentration required for inhibiting the proliferation and activation of T lymphocytes in vitro. Interestingly, NOR was shown to regulate the balance between Th17 and regulatory T (Treg) cells in the intestinal lymph nodes more strikingly than in other tissues. It could increase the expression of Foxp3 mRNA in both gut and joints, and markedly up-regulate the number of integrin α4β7 (a marker of gut source)-positive Foxp3{sup +} cells in the joints of CIA rats. These results suggest that the gut might be the primary action site of NOR, and NOR exerts anti-arthritis effect through regulating the balance between Th17 and Treg cells in intestinal lymph nodes and yielding a trafficking of lymphocytes (especially Treg cells) from the gut to joint. The findings of the present study also provide a plausible explanation for the anti-arthritic effects of poorly absorbed compounds like NOR. - Highlights: • Norisoboldine, administered orally, markedly attenuates the clinical signs of CIA. • Norisoboldine regulates the balance of Th17/Treg cells in the intestinal lymph node. • Norisoboldine induces the migration of Treg cells from the gut to joint.« less

From Typist to Trailblazer: The Evolving View of Women in the CIA’s Workforce

DTIC Science & Technology

2013-10-30

teenage boy. It helped to have an innocent-looking open face, a sense of humor, stamina, and the fearlessness of the very young. 2 - Elizabeth Swanek...After the war, Page planned to return to Baltimore to restart a career in music , but was recruited back to the new- ly-formed CIA where she quickly...also for managers and supervisors under pressure to equalize gender disparities in the work- force. After the Petticoat Panel presented its findings

Notes from our Attic: A Curator’s Pocket History of the CIA

DTIC Science & Technology

2014-01-01

intercepts are said to have shortened the war by two years. 17 19 COUNTERFEIT NAZI STAMPS Within OSS, Morale Operations was responsible for the...carried this one w hen he parachuted into Nazi -occupied France on his fi rst mission as a member of an OSS Jedburgh team. 27 From OSS to CIA 2 “[After...Missile Crisis. 48 COMMEMORATIVE EMBLEMS Patches and insignia designed for Brigade 2506 in the Bay of Pigs invasion. Bay of Pigs On 17 April 1961

Dextran sulfate nanoparticles as a theranostic nanomedicine for rheumatoid arthritis.

PubMed

Heo, Roun; You, Dong Gil; Um, Wooram; Choi, Ki Young; Jeon, Sangmin; Park, Jong-Sung; Choi, Yuri; Kwon, Seunglee; Kim, Kwangmeyung; Kwon, Ick Chan; Jo, Dong-Gyu; Kang, Young Mo; Park, Jae Hyung

2017-07-01

With the aim of developing nanoparticles for targeted delivery of methotrexate (MTX) to inflamed joints in rheumatoid arthritis (RA), an amphiphilic polysaccharide was synthesized by conjugating 5β-cholanic acid to a dextran sulfate (DS) backbone. Due to its amphiphilic nature, the DS derivative self-assembled into spherical nanoparticles (220 nm in diameter) in aqueous conditions. The MTX was effectively loaded into the DS nanoparticles (loading efficiency: 73.0%) by a simple dialysis method. Interestingly, the DS nanoparticles were selectively taken up by activated macrophages, which are responsible for inflammation and joint destruction, via scavenger receptor class A-mediated endocytosis. When systemically administrated into mice with experimental collagen-induced arthritis (CIA), the DS nanoparticles effectively accumulated in inflamed joints (12-fold more than wild type mice (WT)), implying their high targetability to RA tissues. Moreover, the MTX-loaded DS nanoparticles exhibited significantly improved therapeutic efficacy against CIA in mice compared to free MTX alone. Overall, the data presented here indicate that DS nanoparticles are potentially useful nanomedicines for RA imaging and therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

New findings in pharmacogenetics of schizophrenia.

PubMed

Zai, Clement C; Tiwari, Arun K; Zai, Gwyneth C; Maes, Miriam S; Kennedy, James L

2018-05-01

This review highlights recent advances in the investigation of genetic factors for antipsychotic response and side effects. Antipsychotics prescribed to treat psychotic symptoms are variable in efficacy and propensity for causing side effects. The major side effects include tardive dyskinesia, antipsychotic-induced weight gain (AIWG), and clozapine-induced agranulocytosis (CIA). Several promising associations of polymorphisms in genes including HSPG2, CNR1, and DPP6 with tardive dyskinesia have been reported. In particular, a functional genetic polymorphism in SLC18A2, which is a target of recently approved tardive dyskinesia medication valbenazine, was associated with tardive dyskinesia. Similarly, several consistent findings primarily from genes modulating energy homeostasis have also been reported (e.g. MC4R, HTR2C). CIA has been consistently associated with polymorphisms in the HLA genes (HLA-DQB1 and HLA-B). The association findings between glutamate system genes and antipsychotic response require additional replications. The findings to date are promising and provide us a better understanding of the development of side effects and response to antipsychotics. However, more comprehensive investigations in large, well characterized samples will bring us closer to clinically actionable findings.

Stress-triggered signaling affecting survival or suicide of Streptococcus pneumoniae.

PubMed

Cortes, Paulo R; Piñas, Germán E; Cian, Melina B; Yandar, Nubia; Echenique, Jose

2015-01-01

Streptococcus pneumoniae is a major human pathogen that can survive to stress conditions, such as the acidic environment of inflammatory foci, and tolerates lethal pH through a mechanism known as the acid tolerance response. We previously described that S. pneumoniae activates acidic-stress induced lysis in response to acidified environments, favoring the release of cell wall compounds, DNA and virulence factors. Here, we demonstrate that F(0)F(1)-ATPase is involved in the response to acidic stress. Chemical inhibitors (DCCD, optochin) of this proton pump repressed the ATR induction, but caused an increased ASIL. Confirming these findings, mutants of the subunit c of this enzyme showed the same phenotypes as inhibitors. Importantly, we demonstrated that F(0)F(1)-ATPase and ATR are necessary for the intracellular survival of the pneumococcus in macrophages. Alternatively, a screening of two-component system (TCS) mutants showed that ATR and survival in pneumocytes were controlled in contrasting ways by ComDE and CiaRH, which had been involved in the ASIL mechanism. Briefly, CiaRH was essential for ATR (ComE represses activation) whereas ComE was necessary for ASIL (CiaRH protects against induction). They did not regulate F0F1-ATPase expression, but control LytA expression on the pneumococcal surface. These results suggest that both TCSs and F(0)F(1)-ATPase control a stress response and decide between a survival or a suicide mechanism by independent pathways, either in vitro or in pneumocyte cultures. This biological model contributes to the current knowledge about bacterial response under stress conditions in host tissues, where pathogens need to survive in order to establish infections. Copyright © 2014 Elsevier GmbH. All rights reserved.

Chemistry of sands from the modern Indus River and the Archean Witwatersrand basin: Implications for the composition of the Archean atmosphere

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

Maynard, J.B.; Ritger, S.D.; Sutton, S.J.

1991-03-01

Both the Indus River and the Witwatersrand basin contain sand with grains of detrital uraninite. Because this mineral is easily oxidized, its presence in Archean strata as a detrital particle has been used as evidence for a low-oxygen atmosphere before 2.5 Ga. However, its presence in modern sand from the Indus River system has been used to argue that detrital uraninite does not provide information about the oxygen concentration of Earth's early atmosphere. Petrographic and chemical study of sand from these two sources reveals differences that suggest the modern Indus sand cannot be used as an analog for the Archeanmore » Witwatersrand occurrences. The Witwatersrand quartzites are depleted in Ca, Mg, and Na, indicating that the original sand from which they formed had been subjected to intense weathering. The chemical index of alteration (CIA), a commonly used indicator of degree of weathering, yields an average value of about 0.80 for Witwatersrand quartzites, comparable to modern tropical streams such as the Orinoco that drain deeply weathered terrains under tropical conditions (CIA=0.75). In contrast, the CIA for Indus sand is 0.45, indicating virtually no chemical weathering. The significance of Archean quartz-pebble conglomerates is not just that they contain unstable detrital phases like uraninite and pyrite, but that these particles are associated with rocks whose compositions suggest intense weathering. These conglomerates must have been subjected to intense weathering under tropical conditions, either in their source area or at the site of deposition, and the preservation of minerals like uraninite such conditions is indeed strong evidence for a low-oxygen atmosphere.« less

Decoy receptor 3 attenuates collagen-induced arthritis by modulating T cell activation and B cell expansion.

PubMed

Cheng, Chia-Pi; Sytwu, Huey-Kang; Chang, Deh-Ming

2011-12-01

To investigate the immune-modulated effects of decoy receptor 3 (DCR3) in an experimental model of rheumatoid arthritis (RA). We delivered DCR3 plasmid into collagen-induced arthritis (CIA) mice using the hydrodynamic method and evaluated the serum level of DCR3 protein by ELISA. After immunization, we assessed disease severity of arthritis incidence, arthritis scores, paw thickness, and means of arthritic limbs, and used hematoxylin and eosin staining to observe synovial hyperplasia. We analyzed numbers of murine splenocytes and inguinal lymphocyte cells, cell populations, and serum proinflammatory cytokines by flow cytometry. We investigated B cell proliferation by carboxyfluorescein succinimidyl ester assay. We evaluated serum levels of total IgG2a and type II collagen-specific IgG and IgG2a using ELISA. DCR3 expression in sera significantly attenuated disease severity in CIA mice. We found that DCR3 inhibited the volume of inguinal lymph nodes, numbers of CD19+ B cells, and populations of interferon-γ, interleukin 4 (IL-4), IL-17A, and Foxp3-producing CD4+ T cell in vivo. We found that DCR3 inhibited Pam3CSK4 (Toll-like receptor 1/2 ligand)-induced B220+ B cell proliferation in vitro. DCR3 treatment reduced the serum level of IL-6, total IgG2a, and CII-specific IgG2a antibody. We postulated that the protective effects of DCR3 in CIA resulted from modulation of the immune system by maintaining the B/T cell balance and decreasing lymphocyte expansion. We suggest DCR3 as a prophylactic and potential therapeutic agent in the treatment of RA.

The association of Internet addiction symptoms with impulsiveness, loneliness, novelty seeking and behavioral inhibition system among adults with attention-deficit/hyperactivity disorder (ADHD).

PubMed

Li, Wendi; Zhang, Wei; Xiao, Lin; Nie, Jia

2016-09-30

The aims of this study were to test the associations of the Internet addiction symptoms with impulsiveness, loneliness, novelty seeking and behavioral inhibition systems among adults with attention-deficit/hyperactivity disorder (ADHD) and adults with non-ADHD. A total of 146 adults aged between 19 and 33 years involved in this study. Participants were assessed with the Chinese version of the adult ADHD Self-report scale (ASRS), the Revised Chen Internet Addiction Scale (CIAS-R), the Barratt Impulsiveness Scale 11 (BIS-11), the Tridimensional Personality Questionnaire (TPQ), the UCLA loneliness scale, and the Behavioral Inhibition System and Behavioral Activation System Scale (BIS/BAS Scale). The results of hierarchical regression analysis indicated that impulsiveness, loneliness, and behavioral inhibition system were significant predictors of Internet addition among adults with ADHD. Higher loneliness was significantly associated with more severe Internet addition symptoms among the non-ADHD group. Adults with high impulsiveness, loneliness, and BIS should be treated with caution for preventing Internet addiction. In addition, adults with and without ADHD should be provided with different preventative strategies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Development and 10-year history of a biosimilar: the example of Binocrit®

PubMed Central

Aapro, Matti; Krendyukov, Andriy; Höbel, Nadja; Seidl, Andreas; Gascón, Pere

2018-01-01

Patent expirations for several biological products have prompted the development of alternative versions, termed ‘biosimilars’, which have comparable quality, safety and efficacy to a licensed biological medicine (also referred to as the ‘reference’ medicine). The first biosimilars developed in oncology were the supportive-care agents filgrastim and epoetin. Binocrit® (HX575) is a biosimilar version of epoetin alfa, indicated in the oncology setting for the treatment of chemotherapy-induced anemia (CIA). The process for development and approval of Binocrit® as a biosimilar included extensive analytical characterization and comparison with the reference epoetin alfa. This was followed by a clinical development program comprising phase I pharmacokinetic/pharmacodynamic studies to show bioequivalence to the reference medicine and a confirmatory phase III study to confirm therapeutic effectiveness in CIA. Since its approval, Binocrit® has been extensively used and studied in real-world clinical practice. The accumulated data confirm that Binocrit® is an effective and well-tolerated option for the treatment of CIA in patients with cancer.

Ascorbigen induces dermal papilla cell proliferation in vitro, but fails to modulate chemotherapy-induced alopecia in vivo.

PubMed

Wang, Chih-Hsiu; Huang, Hsu-Shan; Dai, Niann-Tzyy; Sheu, Ming-Jen; Chang, Deh-Ming

2013-12-01

Ascorbigen (ABG) is the predominant indole-derived compound from Brassica vegetables. In this study, we attempted to evaluate the effects of ABG on hair growth. To this end, we examined the proliferation of isolated human dermal papilla (DP) cells and keratinocytes after incubation in various concentrations (0-1.25 mM) of ABG. Furthermore, hair shaft regrowth was monitored in a mouse model of chemotherapy-induced alopecia (CIA), and hematoxylin and eosin staining was performed for histological analyses. We found that 1.25 mM ABG induced a 1.2-fold increase in the growth of DP cells, but not keratinocytes. However, ABG did not exert significant protective effects against CIA in the mouse model. These findings suggest that ABG may not be able to counteract CIA and that further investigation of the therapeutic potential of ABG in disease models is required. Copyright © 2013 John Wiley & Sons, Ltd.

Protective effect of curcumin on experimentally induced arthritic rats: detailed histopathological study of the joints and white blood cell count.

PubMed

Kamarudin, Taty Anna; Othman, Faizah; Mohd Ramli, Elvy Suhana; Md Isa, Nurismah; Das, Srijit

2012-01-01

Curcuma longa (turmeric) rhizomes contains curcumin, an active compound which possesses anti-inflammatory effects. Collagen-induced arthritis (CIA) is an accepted experimental animal model of rheumatoid arthritis. The present study aimed to observe the histological changes in the joints of experimental arthritic rats treated with curcumin. Twenty four male Sprague-Dawley (approximately 7 weeks-old) rats were randomly divided into four groups. Three groups were immunized with 150 µg collagen. All rats with established CIA, with arthritis scores exceeding 1, were orally treated with betamethasone (0.5 mg/ml/kg body weight), curcumin (110 mg/ml/kg body weight) or olive oil (1.0 ml/kg body weight) daily, for two weeks. One remaining group was kept as normal control. Treatment with 110 mg/ml/kg curcumin showed significant mean differences in the average white blood cell (WBC) count (p<0.05), cell infiltration, bone and cartilage erosion scores (p<0.05) compared to the olive oil treated group. Pannus formation scores showed that curcumin supplementation successfully suppressed the pannus formation process that occurred in the articular cartilage of the CIA joints. The mean difference for histological scores for the curcumin group was insignificant compared to the betamethasone treated group. It is concluded that supplementation of curcumin has protective effect on the histopathological and degenerative changes in the joints of CIA rats which was at par with betamethasone.

Gallium nitrate ameliorates type II collagen-induced arthritis in mice.

PubMed

Choi, Jae-Hyeog; Lee, Jong-Hwan; Roh, Kug-Hwan; Seo, Su-Kil; Choi, Il-Whan; Park, Sae-Gwang; Lim, Jun-Goo; Lee, Won-Jin; Kim, Myoung-Hun; Cho, Kwang-rae; Kim, Young-Jae

2014-05-01

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease. Gallium nitrate has been reported to reserve immunosuppressive activities. Therefore, we assessed the therapeutic effects of gallium nitrate in the mouse model of developed type II collagen-induced arthritis (CIA). CIA was induced by bovine type II collagen with Complete Freund's adjuvant. CIA mice were intraperitoneally treated from day 36 to day 49 after immunization with 3.5mg/kg/day, 7mg/kg/day gallium nitrate or vehicle. Gallium nitrate ameliorated the progression of mice with CIA. The clinical symptoms of collagen-induced arthritis did not progress after treatment with gallium nitrate. Gallium nitrate inhibited the increase of CD4(+) T cell populations (p<0.05) and also inhibited the type II collagen-specific IgG2a-isotype autoantibodies (p<0.05). Gallium nitrate reduced the serum levels of TNF-α, IL-6 and IFN-γ (p<0.05) and the mRNA expression levels of these cytokine and MMPs (MMP2 and MMP9) in joint tissues. Western blotting of members of the NF-κB signaling pathway revealed that gallium nitrate inhibits the activation of NF-κB by blocking IκB degradation. These data suggest that gallium nitrate is a potential therapeutic agent for autoimmune inflammatory arthritis through its inhibition of the NF-κB pathway, and these results may help to elucidate gallium nitrate-mediated mechanisms of immunosuppression in patients with RA. Copyright © 2014 Elsevier B.V. All rights reserved.

Protective effect of curcumin on experimentally induced arthritic rats: detailed histopathological study of the joints and white blood cell count

PubMed Central

Kamarudin, Taty Anna; Othman, Faizah; Mohd Ramli, Elvy Suhana; Md Isa, Nurismah; Das, Srijit

2012-01-01

Curcuma longa (turmeric) rhizomes contains curcumin, an active compound which possesses anti-inflammatory effects. Collagen-induced arthritis (CIA) is an accepted experimental animal model of rheumatoid arthritis. The present study aimed to observe the histological changes in the joints of experimental arthritic rats treated with curcumin. Twenty four male Sprague-Dawley (approximately 7 weeks-old) rats were randomly divided into four groups. Three groups were immunized with 150 µg collagen. All rats with established CIA, with arthritis scores exceeding 1, were orally treated with betamethasone (0.5 mg/ml/kg body weight), curcumin (110 mg/ml/kg body weight) or olive oil (1.0 ml/kg body weight) daily, for two weeks. One remaining group was kept as normal control. Treatment with 110 mg/ml/kg curcumin showed significant mean differences in the average white blood cell (WBC) count (p<0.05), cell infiltration, bone and cartilage erosion scores (p<0.05) compared to the olive oil treated group. Pannus formation scores showed that curcumin supplementation successfully suppressed the pannus formation process that occurred in the articular cartilage of the CIA joints. The mean difference for histological scores for the curcumin group was insignificant compared to the betamethasone treated group. It is concluded that supplementation of curcumin has protective effect on the histopathological and degenerative changes in the joints of CIA rats which was at par with betamethasone. PMID:27366139

Patient-reported outcome assessment and objective evaluation of chemotherapy-induced alopecia.

PubMed

Komen, Manon M C; van den Hurk, Corina J G; Nortier, Johan W R; van der Ploeg, T; Smorenburg, Carolien H; van der Hoeven, Jacobus J M

2018-04-01

Alopecia is one of the most distressing side effects of chemotherapy. Evaluating and comparing the efficacy of potential therapies to prevent chemotherapy-induced alopecia (CIA) has been complicated by the lack of a standardized measurement for hair loss. In this study we investigated the correlation between patient-reported outcome assessments and quantitative measurement with the hair check to assess CIA in clinical practice. Scalp cooling efficacy was evaluated by patients by World Health Organisation (WHO) of CIA, Visual Analogue Scale (VAS) and wig use. The Hair Check was used to determine the amount of hair (in mm 2 ) per unit of scalp skin area (in cm 2 ) (Hair Mass Index, HMI). CIA was also evaluated by doctors, nurses and hairdressers. Baseline HMI was not predictive for hair loss. HMI declined throughout all chemotherapy cycles, which was not reflected by patient-reported measures. HMI correlated with patient-reported hair quantity before the start of the therapy, but not with WHO and/or VAS during therapy. Patient's opinion correlated moderately with the opinion of doctors and nurses (ρ = 0.50-0.56 respectively), but strongly with hair dressers (ρ = 0.70). The Hair check is suitable to quantify the amount of hair loss and could complement research on refining outcome of scalp cooling, but the patient's opinion should be considered as the best method to assess hair loss in clinical practice. Trialregister.nl NTR number 3082. Copyright © 2018 Elsevier Ltd. All rights reserved.

Studies in Intelligence. Volume 49, Number 4, 2005

DTIC Science & Technology

2005-01-01

solutions required totally new techniques and technology , contractors, and organizations. Using the rapid developments in satellite systems in the 1960s as...both failed came as a postwar shock, especially to those who thought so highly of Klaus Fuchs as a babysitter .17 Conant provides a new look at how...Estimates wrote one of the articles; Max Millikan, of the Massachusetts Institute of Technology , who had helped create economic intelli- gence at the CIA

Private Security Contractors in Iraq and Afghanistan: Legal Issues

DTIC Science & Technology

2010-01-07

involving Blackwater Worldwide private security guards on contract with the State Department, who reportedly opened fire in the crowded traffic circle in the...Background and Analysis, by Moshe Schwartz. 2 See James Risen and Mark Mazzetti, Blackwater Guards Tied to Secret C.I.A. Raids, NY TIMES, December 10...0360 (RMU), slip op. (D.D.C, .Dec. 31, 2009). 6 See Iraq: U.S. Blackwater Case Dismissal “Unacceptable,” REUTERS, Jan. 1, 2010. 7 See Iraq to

Effectiveness of past and current critical incident analysis on reflective learning and practice change.

PubMed

Vachon, Brigitte; LeBlanc, Jeannette

2011-09-01

Critical incident analysis (CIA) is one of the strategies frequently used to facilitate reflective learning. It involves the thorough description and analysis of an authentic and experienced event within its specific context. However, CIA has also been described as having the potential to expose vulnerabilities, threaten learners' coping mechanisms and increase rather than reduce their anxiety levels. The aim of this study was to compare the analysis of current critical incidents with that of past critical incidents, and to further explore why and how the former is more conducive to reflective learning and practice change than the latter. A collaborative research study was conducted. Eight occupational therapists were recruited to participate in a reflective learning group that convened for 12 meetings held over a 15-month period. The group facilitator planned and adapted the learning strategies to be used to promote reflective learning and guided the group process. Critical incident analysis represented the main activity carried out in the group discussions. The data collected were analysed using the grounded theory method. Three phenomena were found to differentiate between the learning contexts created by the analysis of, respectively, past and current critical incidents: attitudinal disposition; legitimacy of purpose, and the availability of opportunities for experimentation. Analysis of current clinical events was found to improve participants' motivation to self-evaluate, to increase their self-efficacy, and to help them transfer learning into action and to progressively self-regulate. The results of this collaborative research study suggest that the analysis of current clinical events in order to promote reflection offers a safer and more constructive learning environment than does the analysis of incidents that have occurred in the past. This learning strategy is directly grounded in health professional practice. The remaining challenge for continuing education providers is that of creating conditions conducive to its use. © Blackwell Publishing Ltd 2011.

[Analgesic effects of ionotropic glutamate receptor antagonists MK-801 and NBQX on collagen-induced arthritis rats].

PubMed

Zhu, H; Zhu, R; Deng, Z D; Feng, Y C; Shen, H L

2016-12-18

The ionotropic glutamate receptorantagonists include two types: MK-801, antagonist of N-methyl-D-asparticacid (NMDA) receptor, and NBQX, antagonist of non-NMDA receptor.The above-mentioned ionotropic antagonists can block the glutamate and its corresponding receptor binding to produce analgesic effect. The objective of this research was to study two antagonists in analgesic effect on rat behavior,as well as to investigate the down-regulation and up-regulation of cyclooxygenase-2 (COX-2) and Janus-activated kinase (Jak3) in collagen-induced arthritis (CIA) rat serum and tissue fluid after the application of these antagonists, that is, the effect on molecular biology. This study used the ionotropic glutamate receptors as the target and established CIA rat model. Vivo studies were used to observe changes in behavior and molecular biology of the CIA rat.Behavioral assessment includedmechanical allodynia and joint swelling in the CIA rat,where themechanical allodynia was measured using the paw-withdrawal threshold (PWT) with VonFrey filaments according to the "Up-Down" method,and the drainage volume was used to assess joint swelling. Then the blood samples taken from the heart of the rat and the tissue homogenate were collected to detect the down-regulation and up-regulation of COX-2 and Jak3 in the serum and tissue fluid after the antagonists wereused. Using MK-801, NBQX alone or using the combination of these two antagonists,these three methods all could alleviate pain(P<0.01).The analgesic effect lasted more than 24 h.Both antagonists reached the peak of analgesia at the end of 4 hours post-injection. NBQX had stronger analgesic effect than MK-801 (P<0.05).Whether alone or combined use of these two antagonists,could not change the CIA rats' swelling of the joint (P>0.05). MK-801 could decrease the expression of COX-2 (P<0.01).At the same time, NBQX did not have this effect (P>0.05). Using MK-801, NBQX alone or combination of these two antagonists could not affect the increased expression of Jak3 caused by the CIA (P>0.05). MK-801 and NBQX could both alleviate pain, NBQX was much better than MK-801. Neither MK-801 nor NBQX had the effect on the swelling of the joint. NMDA receptor and COX-2 inflammatory pathways had certain interactions. For Jak3, it could not be found to have cross-function with ionotropic glutamate signaling pathways by this experiment.

Computer image analysis traits of cross-sectioned dry-cured hams: a genetic analysis.

PubMed

Bonfatti, V; Cecchinato, A; Sturaro, E; Gallo, L; Carnier, P

2011-08-01

The aims of this study were to estimate genetic parameters of image analysis traits of cross-sectioned dry-cured hams and carcass weight (CW) and to investigate effects of some nongenetic sources of variation on these traits. Computer image analysis (CIA) had been carried out for digital images of the cross-section of 1,319 San Daniele dry-cured hams. The cross-sectional area (SA, cm(2)); the average thickness of subcutaneous fat (FT, cm); and the proportions of lean (LA, %), fat-eye (FEA, %), and subcutaneous fat area (SCF, %) to SA, and of biceps femoris (BFA, %) and semitendinosus muscle area (STA, %) to LA were recorded. Bivariate analyses were carried out for pairs of traits for estimation of genetic parameters using Bayesian methodology and linear models. Linear models included the nongenetic effects of slaughter groups and sex and the additive genetic effects of pigs and their ancestors (1,888 animals). Variation of FEA was nearly 4-fold that of SA and LA. Variation of CIA traits due to sex effect was not large, whereas slaughter group effects were relevant sources of variation for all traits. For all traits, with the exception of FEA, the posterior probability for the true heritability being greater than 0.1, was greater than 0.95. Point estimates of heritabilities for FT and SCF were 0.42 and 0.51, respectively. Heritability estimates for FEA, LA, BFA, and STA were 0.13, 0.44, 0.44, and 0.36, respectively. The genetic correlations between CW and CIA traits were positive and large for SA (0.86), positive and moderate for FT, FEA, and STA (0.47, 0.40, and 0.45, respectively) and negative with LA (-0.28). Although FEA, FT, and SCF were all measures of the extent of fat deposition in the ham, the genetic correlations between FT or SCF and FEA were very low. A very large estimate (0.74) was obtained for the genetic relationship between SA and FEA, suggesting that reduction of ham roundness through selective breeding would be beneficial for decreasing FEA. On the basis of the estimated parameters, genetic selection is expected to be effective in changing size of fatty and lean areas of the cross-section of dry-cured hams. Causes related to the abnormal development of the fat-eye depot remain unknown, but this study provided evidence that influences of polygenic effects on phenotypic variation of FEA are limited. © 2011 American Society of Animal Science. All rights reserved.

Studies in Intelligence. Volume 58, Number 4 (Unclassified Articles from December 2014)

DTIC Science & Technology

2014-12-01

Hastert addressing special joint ses- sion of the Senate and House in New York City’s Federal Hall on 6 September 2012. (Photo © Martin H. Simon/Corbis...RDP80M01133A000800110003-6. 11. Ibid. 12. Memorandum for Dr. Martin , “Displaying Uncertainty to Decisionmakers,” 28 June 1973, CIA-RDP84B00506R000100080023-2...from Truman to Obama, by Peter Kross. The Zhivago Affair: The Kremlin, the CIA, and the Battle Over a Forbidden Book, by Peter Finn and Petra Couvée

Evaluation of the Boson Chemiluminescence Immunoassay as a First-Line Screening Test in the ECDC Algorithm for Syphilis Serodiagnosis in a Population with a High Prevalence of Syphilis

PubMed Central

Qiu, Xin-Hui; Zhang, Ya-Feng; Chen, Yu-Yan; Zhang, Qiao; Chen, Fu-Yi; Liu, Long; Fan, Jin-Yi; Gao, Kun; Zhu, Xiao-Zhen; Zheng, Wei-Hong; Zhang, Hui-Lin; Lin, Li-Rong; Liu, Li-Li; Tong, Man-Li; Zhang, Chang-Gong

2015-01-01

We developed a new Boson chemiluminescence immunoassay (CIA) and evaluated its application with cross-sectional analyses. Our results indicated that the Boson CIA demonstrated strong discriminatory power in diagnosing syphilis and that it can be used as a first-line screening test for syphilis serodiagnosis using the European Centre for Disease Prevention and Control algorithm or as a confirmatory test when combined with a patient's clinical history. PMID:25631792

Brainwashing, LSD, and CIA: historical and ethical perspective.

PubMed

Buckman, J

1977-01-01

The history of various attempts at thought control and chemical warfare is briefly reviewed. Brainwashing, thought control, industrial and national espionage, and covert activities are becoming more sophisticated. These issues have been revived and accentuated by the Vietnam war, the Middle East Crisis, Watergate, the CIA investigations and the Patty Hearst trial. Historical perspective and the ethical implications of these activities are explored. It is suggested that there is a growing level of individual and international mistrust amounting to paranoia and complicating the issues of individual freedom, civil rights and human experimentation.

One Woman’s Contribution to Social Change at CIA

DTIC Science & Technology

2002-01-01

the last minute linkage of racial and sexual discrimination�an ironic twist of legislative and social history. On the Equal Pay Act, see: Cynthia Ellen...Work Force Evolution One Woman�s Contribution to Social Change at CIA Dawn Ellison � I hope to provide Agency women with a better appreciation for...helped rae locate rwo t�hD the ses that were insightful on how the Equal Pay Act and the inclusion of women in the Ci~�il Rights Act came about It was not

Security Analysis of Smart Grid Cyber Physical Infrastructures Using Modeling and Game Theoretic Simulation

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

Abercrombie, Robert K; Sheldon, Frederick T.

Cyber physical computing infrastructures typically consist of a number of sites are interconnected. Its operation critically depends both on cyber components and physical components. Both types of components are subject to attacks of different kinds and frequencies, which must be accounted for the initial provisioning and subsequent operation of the infrastructure via information security analysis. Information security analysis can be performed using game theory implemented in dynamic Agent Based Game Theoretic (ABGT) simulations. Such simulations can be verified with the results from game theory analysis and further used to explore larger scale, real world scenarios involving multiple attackers, defenders, andmore » information assets. We concentrated our analysis on the electric sector failure scenarios and impact analyses by the NESCOR Working Group Study, From the Section 5 electric sector representative failure scenarios; we extracted the four generic failure scenarios and grouped them into three specific threat categories (confidentiality, integrity, and availability) to the system. These specific failure scenarios serve as a demonstration of our simulation. The analysis using our ABGT simulation demonstrates how to model the electric sector functional domain using a set of rationalized game theoretic rules decomposed from the failure scenarios in terms of how those scenarios might impact the cyber physical infrastructure network with respect to CIA.« less

A phylogenetic comparison of urease-positive thermophilic Campylobacter (UPTC) and urease-negative (UN) C. lari.

PubMed

Hirayama, Junichi; Tazumi, Akihiro; Hayashi, Kyohei; Tasaki, Erina; Kuribayashi, Takashi; Moore, John E; Millar, Beverley C; Matsuda, Motoo

2011-06-01

In the present study, the reliability of full-length gene sequence information for several genes including 16S rRNA was examined, for the discrimination of the two representative Campylobacter lari taxa, namely urease-negative (UN) C. lari and urease-positive thermophilic Campylobacter (UPTC). As previously described, 16S rRNA gene sequence are not reliable for the molecular discrimination of UN C. lari from UPTC organisms employing both the unweighted pair group method using arithmetic means analysis (UPGMA) and neighbor joining (NJ) methods. In addition, three composite full-length gene sequences (ciaB, flaC and vacJ) out of seven gene loci examined were reliable for discrimination employing dendrograms constructed by the UPGMA method. In addition, all the dendrograms of the NJ phylogenetic trees constructed based on the nine gene information were not reliable for the discrimination. Three composite full-length gene sequences (ciaB, flaC and vacJ) were reliable for the molecular discrimination between UN C. lari and UPTC organisms employing the UPGMA method, as well as among four thermophilic Campylobacter species. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The United States Army and the Sergeant Problem: The Army’s Systemic Inability to Produce Enough Sergeants and a Proposal to Fix it

DTIC Science & Technology

2014-04-23

Intelligence Agency https://www.cia.gov/ library / publications/the-world-factbook/index.html (accessed November 24, 2013); John Pike, "Royal Thai Army" http...accessed November 24, 2013); Barbara LePoer, Thailand: A Country Study, Area Handbook Series (Washington, DC: Library of Congress, 1989), 246, 259...accessed December 22, 2013); "Professional Leadership Programs: Apprenticeship, Internship, and Multicultural Fellowship", http

Rollout and Installation of Risk Management at the IMINT Directorate, National Reconnaissance Office

DTIC Science & Technology

1999-12-01

strong entry into the 21st century. Programs were forging multiple mission partners and customers into cohesive program delivery systems that could...requires a higher level of cooperation and a meshing of divergent program operations. Customer requirements are more complex and distributed. As a... customers , such as the U.S. Central Intelligence Agency (CIA) and the U.S. Department of Defense (DoD), can warn of potential trouble spots around the

Charlotte Temple: Mapping Social Status through Gender and Value Systems

DTIC Science & Technology

1989-05-01

parental advice to his daughters. Rowson’s warning to "listen not to the voice of love, unless sanctioned by paternal approbation" admits the crucial...RESTRICTIVE MARKINGS UNCLASSIFIED NONE- 3. DISTRIBUTION/AVAILABILITY OF REPORT APPROVED FOR PUBLIC RELEASE; E DISTRIBUTION UNLIMITED. A D-A 217 453 t( S ...5. MONITORING ORGANIZATION REPORT NUMBER( S ) AFIT/CI/CIA- 89-112 6a. NAME OF PERFORMING ORGANIZATION 6b. OFFICE SYMBOL 7a. NAME OF MONITORING

1, 25-dihydroxy-vitamin D3 with tumor necrosis factor-alpha protects against rheumatoid arthritis by promoting p53 acetylation-mediated apoptosis via Sirt1 in synoviocytes

PubMed Central

Gu, Xin; Gu, Bingjie; Lv, Xianhui; Yu, Zhenzhen; Wang, Rong; Zhou, Xiaoli; Qiao, Wanxin; Mao, Zhiyuan; Zuo, Guoping; Li, Qing; Miao, Dengshun; Jin, Jianliang

2016-01-01

Impaired apoptosis of fibroblast-like synoviocytes (FLSs) causes synovial hyperplasia, facilitating destruction of cartilage and bone in rheumatoid arthritis (RA). Tumor necrosis factor (TNF)-α, a dominant inflammatory mediator in RA pathogenesis, promotes progression of RA symptoms. Prevalence of 1, 25-dihydroxy-vitamin D3 (hereafter termed VD) deficiency is 30–63% in patients with RA. Whether VD leads to apoptosis or enhances TNF-α-mediated apoptosis in FLSs to ameliorate RA is unclear. To determine this, 10-week-old CYP27B1-deficient (CYP27B1−/−) mice with collagen-induced arthritis (CIA) were intraperitoneally treated with 1 μg/kg VD every other day for 9 weeks. RA phenotypes were compared between vehicle-treated CYP27B1−/− and wild-type CIA mice. Human rheumatoid FLS-MH7A cells were treated with Dulbecco's modified Eagle's medium (DMEM) without fetal bovine serum (FBS) for 24 h, then with different concentrations of VD and TNF-α, human vitamin D receptor (VDR) siRNA or the p53 pro-apoptotic inhibitor pifithrin-α. Apoptosis and p53 pro-apoptotic signaling were analyzed. The 19-week-old vehicle-treated CYP27B1−/− CIA mice had increased cumulative arthritis scores and levels of serous rheumatoid factors and C-reactive protein. They had exacerbated articular cartilage and bone destruction, joint space narrowing, joint stiffness, deformity and dysfunction, synovitis and TNF-α secretion, FLS hyperplasia with increased proliferation and decreased apoptosis compared to CIA mice. These RA phenotypes that were aggravated in CIA mice by CYP27B1 deficiency were largely rescued by VD treatment. In vitro, VD with TNF-α treatment upregulated p53 acetylation-mediated apoptosis in MH7A cells by promoting Sirt1 translocation from the nucleus to the cytoplasm. These findings indicated that VD with TNF-α protected against RA by promoting apoptosis of FLSs. The results indicated that clinical administration of VD could be a specific therapy to promote FLS apoptosis and prevent RA progression. PMID:27763638

Human epidermal growth factor receptor bispecific ligand trap RB200: abrogation of collagen-induced arthritis in combination with tumour necrosis factor blockade

PubMed Central

2011-01-01

Introduction Rheumatoid arthritis (RA) is a chronic disease associated with inflammation and destruction of bone and cartilage. Although inhibition of TNFα is widely used to treat RA, a significant number of patients do not respond to TNFα blockade, and therefore there is a compelling need to continue to identify alternative therapeutic strategies for treating chronic inflammatory diseases such as RA. The anti-epidermal growth factor (anti-EGF) receptor antibody trastuzumab has revolutionised the treatment of patients with EGF receptor-positive breast cancer. Expression of EGF ligands and receptors (known as HER) has also been documented in RA. The highly unique compound RB200 is a bispecific ligand trap that is composed of full-length extracellular domains of HER1 and HER3 EGF receptors. Because of its pan-HER specificity, RB200 inhibits responses mediated by HER1, HER2 and HER3 in vitro and in vivo. The objective of this study was to assess the effect of RB200 combined with TNF blockade in a murine collagen-induced arthritis (CIA) model of RA. Methods Arthritic mice were treated with RB200 alone or in combination with the TNF receptor fusion protein etanercept. We performed immunohistochemistry to assess CD31 and in vivo fluorescent imaging using anti-E-selectin antibody labelled with fluorescent dye to elucidate the effect of RB200 on the vasculature in CIA. Results RB200 significantly abrogated CIA by reducing paw swelling and clinical scores. Importantly, low-dose RB200 combined with a suboptimal dose of etanercept led to complete abrogation of arthritis. Moreover, the combination of RB200 with etanercept abrogated the intensity of the E-selectin-targeted signal to the level seen in control animals not immunised to CIA. Conclusions The human pan-EGF receptor bispecific ligand trap RB200, when combined with low-dose etanercept, abrogates CIA, suggesting that inhibition of events downstream of EGF receptor activation, in combination with TNFα inhibitors, may hold promise as a future therapy for patients with RA. PMID:21982514

IPB: Predicting an Unpredictable Enemy Why We do it? Why the S2 can’t do it? What the Staff Should

DTIC Science & Technology

2007-03-01

CIA from his work The Psychology of Intelligence Analysis; and Abraham Maslow , the renowned psychologist from his work A Theory of Human Motivation...39 Abraham Maslow . 1943. “A Theory of Human Motivation” Psychological Review, 50, 370-396. 40 Department of the Army...Marsella, Nicholas R. 1994. The Roll of the G2 Planner. MIPB: Military Intelligence Professional Journal, 28. Maslow , Abraham . 1943. “A Theory of

Normative Bilateral Brainstem Evoked Response Data for a Naval Aviation Student Population: Group Statistics

DTIC Science & Technology

1979-08-07

laus levels of the present study all fall within the plus and sinus one -standard deviation boundar; limits of the composite laboratory data plotted by...to be the case in the present study in that the =pz!Aude of the contralateral response prtduced by a given stimulus level follcuzd, in general, that...equivalent Gaussian distribution was applied to Cia study data. Such an analysis, performed by Thornton (36) on the latcncy and amplitude measurements

Analysis of the U.S. Department of Defense’s Contracting and Logistics Support During the First 100 Hours of the 2010 Haitian Disaster Response Operation

DTIC Science & Technology

2011-06-14

earthquakes, and periodic droughts. This makes Haiti one of the most seismically active islands in South America (CIA, 2010). Its long history of deadly...is unlimited. Prepared for: Naval Postgraduate School , Monterey, California 93943 NPS-LM-11-180 ^`nrfpfqflk=obpb^o`e= pmlkploba=obmloq=pbofbp...Aruna Apte, Assistant Professor Graduate School of Business & Public Policy Naval Postgraduate School Report Documentation Page Form ApprovedOMB No

Granma: Cuban News and Propaganda Analysis for the Period, 1-31 December 1984.

DTIC Science & Technology

1984-12-01

homeless people in New York City. Over 7,000 are mentally ill and have been dis- charged from mental institutions. The rest are young people who have no...attacked targets of the University of Puerto Rico and a U.S. Army recruiting office. * The military in Argentina are concerned about the civilian trial of...and troop deploy- ments in the Middle East and Asia. * The Indian government uncovers another CIA spy agency. The Solidarity International Press

Mutagenic potential assessment associated with human exposure to natural radioactivity.

PubMed

Marcon, Alexandre Endres; Navoni, Julio Alejandro; de Oliveira Galvão, Marcos Felipe; Garcia, Anuska Conde Fagundes Soares; do Amaral, Viviane Souza; Petta, Reinaldo Antônio; Campos, Thomas Ferreira da Costa; Panosso, Renata; Quinelato, Antônio Luiz; de Medeiros, Sílvia Regina Batistuzzo

2017-01-01

Lucrécia city, known to harbor a high cancer rate, is located in a semiarid region characterized by the presence of mineral reservoirs, facing a high exposure to metal and natural radioactivity. The present study aimed to assess the environmental scenario at a semiarid region located in Northeastern Brazil. Metal concentration, alpha and beta radiation, and cyanobacteria content in tap water along with indoor radon and gamma emitters (U, K and Th) concentrations were measured. In addition, mutagenic and nuclear instability effects were assessed using buccal micronucleus cytome assay. The study included five samplings corresponding to a period between 2007 and 2009. Drinking water from Lucrécia city presented levels of Mn, Ni and Cr along with cyanobacteria in concentrations one to four times higher than regulatory guidelines considered. Furthermore, high levels of all the tested radionuclides were found. A high percentage of the houses included in this study presented indoor radon concentrations over 100 Bq m -3 . The mean annual effective dose from Lucrécia houses was six times higher than observed in a control region. The levels of exposure in most of the Lucrécia houses were classified as middle to high. A significant mutagenic effect, represented as an increase of micronuclei (MN) frequency and nuclear abnormalities as nuclear buds (NB), binucleated cells (BN), and pyknotic cells (PYC) were found. The results obtained highlight the role of high background radioactivity on the observed mutagenic effect and could help to explain the exacerbated cancer rate reported in this locality. Copyright © 2016. Published by Elsevier Ltd.

Apoptotic cell infusion treats ongoing collagen-induced arthritis, even in the presence of methotrexate, and is synergic with anti-TNF therapy.

PubMed

Bonnefoy, Francis; Daoui, Anna; Valmary-Degano, Séverine; Toussirot, Eric; Saas, Philippe; Perruche, Sylvain

2016-08-11

Apoptotic cell-based therapies have been proposed to treat chronic inflammatory diseases. The aim of this study was to investigate the effect of intravenous (i.v.) apoptotic cell infusion in ongoing collagen-induced arthritis (CIA) and the interaction of this therapy with other treatments used in rheumatoid arthritis (RA), including methotrexate (MTX) or anti-TNF therapy. The effects of i.v. apoptotic cell infusion were evaluated in a CIA mouse model in DBA/1 mice immunized with bovine type II collagen. The number and functions of antigen-presenting cells (APC), regulatory CD4(+) T cells (Treg), and circulating anti-collagen auto-antibodies were analyzed in CIA mice. Treatment of arthritic mice with i.v. apoptotic cell infusion significantly reduced the arthritis clinical score. This therapeutic approach modified T cell responses against the collagen auto-antigen with selective induction of collagen-specific Treg. In addition, we observed that APC from apoptotic-cell-treated animals were resistant to toll-like receptor ligand activation and favored ex vivo Treg induction, indicating APC reprogramming. Apoptotic cell injection-induced arthritis modulation was dependent on transforming growth factor (TGF)-β, as neutralizing anti-TGF-β antibody prevented the effects of apoptotic cells. Methotrexate did not interfere, while anti-TNF therapy was synergic with apoptotic-cell-based therapy. Overall, our data demonstrate that apoptotic-cell-based therapy is efficient in treating ongoing CIA, compatible with current RA treatments, and needs to be evaluated in humans in the treatment of RA.

Effect of a cocoa flavonoid-enriched diet on experimental autoimmune arthritis.

PubMed

Ramos-Romero, Sara; Pérez-Cano, Francisco J; Pérez-Berezo, Teresa; Castellote, Cristina; Franch, Angels; Castell, Margarida

2012-02-01

Previously we established that a cocoa-enriched diet in young rats reduces specific antibody production and the T helper (Th) lymphocyte proportion in lymphoid tissues. The aim of the present study was to ascertain the modulatory ability of a cocoa flavonoid-enriched diet on collagen-induced arthritis (CIA), which is mediated by anti-collagen autoantibody response and Th lymphocyte activation. Female Louvain (LOU) rats were fed with a cocoa-enriched diet, beginning 2 weeks before CIA induction. Hind-paw swelling and serum cytokine and anti-collagen antibody concentrations were determined. Anti-collagen antibody-secreting cell counts and lymphocyte subset proportions were established in inguinal lymph nodes (ILN). Reactive oxygen species (ROS), nitric oxide (NO) and TNFα produced by peritoneal macrophages were determined. Although arthritic cocoa-fed rats showed a similar hind-paw swelling time course as the arthritic animals fed a standard diet, the cocoa intake was able to decrease specific IgG2a, IgG2b and IgG2c titres. Moreover, cocoa intake in CIA rats reduced ROS production, TNFα and NO release from peritoneal macrophages, and decreased the Th:cytotoxic T cell ratio in ILN. In conclusion, a cocoa flavonoid-enriched diet in LOU rats with CIA produced no effect on hind-paw swelling but was able to modulate the specific antibody response and also the Th lymphocyte proportion, as well as the synthesis of pro-inflammatory mediators from peritoneal macrophages. Therefore, a cocoa-enriched diet could be a good adjuvant therapy in disorders with oxidative stress or autoimmune pathogenesis.

Evaluation of the boson chemiluminescence immunoassay as a first-line screening test in the ECDC algorithm for syphilis serodiagnosis in a population with a high prevalence of syphilis.

PubMed

Qiu, Xin-Hui; Zhang, Ya-Feng; Chen, Yu-Yan; Zhang, Qiao; Chen, Fu-Yi; Liu, Long; Fan, Jin-Yi; Gao, Kun; Zhu, Xiao-Zhen; Zheng, Wei-Hong; Zhang, Hui-Lin; Lin, Li-Rong; Liu, Li-Li; Tong, Man-Li; Zhang, Chang-Gong; Niu, Jian-Jun; Yang, Tian-Ci

2015-04-01

We developed a new Boson chemiluminescence immunoassay (CIA) and evaluated its application with cross-sectional analyses. Our results indicated that the Boson CIA demonstrated strong discriminatory power in diagnosing syphilis and that it can be used as a first-line screening test for syphilis serodiagnosis using the European Centre for Disease Prevention and Control algorithm or as a confirmatory test when combined with a patient's clinical history. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Phenotypes of intermediate forms of Fasciola hepatica and F. gigantica in buffaloes from Central Punjab, Pakistan.

PubMed

Afshan, K; Valero, M A; Qayyum, M; Peixoto, R V; Magraner, A; Mas-Coma, S

2014-12-01

Fascioliasis is an important food-borne parasitic disease caused by the two trematode species, Fasciola hepatica and Fasciola gigantica. The phenotypic features of fasciolid adults and eggs infecting buffaloes inhabiting the Central Punjab area, Pakistan, have been studied to characterize fasciolid populations involved. Morphometric analyses were made with a computer image analysis system (CIAS) applied on the basis of standardized measurements. Since it is the first study of this kind undertaken in Pakistan, the results are compared to pure fasciolid populations: (a) F. hepatica from the European Mediterranean area; and (b) F. gigantica from Burkina Faso; i.e. geographical areas where both species do not co-exist. Only parasites obtained from bovines were used. The multivariate analysis showed that the characteristics, including egg morphometrics, of fasciolids from Central Punjab, Pakistan, are between F. hepatica and F. gigantica standard populations. Similarly, the morphometric measurements of fasciolid eggs from Central Punjab are also between F. hepatica and F. gigantica standard populations. These results demonstrate the existence of fasciolid intermediate forms in endemic areas in Pakistan.

Effects and mechanisms of vitamin A and vitamin E on the levels of serum leptin and other related cytokines in rats with rheumatoid arthritis

PubMed Central

XIONG, RI-BO; LI, QING; WAN, WEI-REN; GUO, JIN-QIANG; LUO, BING-DE; GAN, LU

2014-01-01

Leptin has been identified as an important cytokine in the inflammatory networks of rheumatoid arthritis (RA). Higher serum leptin levels may accelerate the development of RA. This study aimed to examine the effects of vitamin A (VitA) and vitamin E (VitE) on the levels of leptin and other related experimental and clinical indices, and to explore the mechanisms of these effects through the Janus kinase/signal transducer and activator of transcription (STAT) signal transduction pathway in rats with collagen-induced arthritis (CIA). CIA model rats were established by the intradermal injection of bovine type II collagen emulsified in incomplete Freund’s adjuvant, followed by a booster intradermal injection. Four weeks later, the CIA model rats were treated with 42.86 μg retinol equivalents/kg body weight (b.w.) VitA or 200 mg/kg b.w. VitE for four weeks. The levels of leptin, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-10, IL-4, C-reactive protein (CRP) and rheumatic factor were measured by ELISA using commercial kits, and the erythrocyte sedimentation rate (ESR) was determined. In addition, the expression levels of phosphorylated (p)-STAT1, p-STAT3 and leptin in the synovium were evaluated by western blot analysis. The results indicated that VitA and VitE significantly reduced the levels of leptin, TNF-α, IL-6 and CRP and the ESR and significantly increased the levels of IL-10 compared with those of the model group. Furthermore, significantly reduced p-STAT3 protein expression levels were observed in the VitA and VitE groups. In conclusion, VitA and VitE reduced the levels of serum leptin protein and other cytokines. Furthermore, VitA and VitE also reduced the p-STAT3 protein levels. The present study may provide a novel approach for the treatment of RA. PMID:25009608

Polypharmacy and Polymorbidity in Older Adults in Brazil: a public health challenge.

PubMed

Ramos, Luiz Roberto; Tavares, Noemia Urruth Leão; Bertoldi, Andréa Dâmaso; Farias, Mareni Rocha; Oliveira, Maria Auxiliadora; Luiza, Vera Lucia; Pizzol, Tatiane da Silva Dal; Arrais, Paulo Sérgio Dourado; Mengue, Sotero Serrate

2016-12-01

To analyze variations in the prevalence of chronic use of medicines by older adults in Brazil according to its possible association with the most prevalent chronic diseases and demographic and health factors, and to identify risk factors for polypharmacy. A study based on data from the National Survey on Access, Use and Promotion of Rational Use of Medicines (PNAUM), a cross-sectional, population-based survey with probability sampling in Brazilian urban areas. The independent variable was the number of chronic-use medicines taken by older adults, linked to eight chronic diseases investigated. The intervening variables were gender, age group, marital status, level of education, socioeconomic status, Brazilian region, body mass index, smoking, self-perceived health, hospitalization in the previous year and having health insurance, besides the investigated chronic diseases. A multivariable analysis identified risk factors for polypharmacy. Prevalence of at least one chronic-use medicines among older adults was 93.0%. Of the total number of older adults, 18.0% used at least five medications (polypharmacy). Polypharmacy was higher among the oldest individuals (20.0%), in the South region (25.0%), in those with poor self-perceived health (35.0%), in obese individuals (26.0%), in those with reported health insurance (23.0%) or hospitalization in the previous year (31.0%), and among those who reported any of the investigated diseases, particularly diabetes (36.0%) and heart diseases (43.0%). The variables remaining in the final risk model for polypharmacy were age, region, perceived health, health insurance, hospitalization in the previous year and all investigated diseases except stroke. Older adults with specific diseases have risk factors for polypharmacy modifiable by actions aimed at the rational use of medicines. With the current population aging and successful drug access policy, the trend is an increase in drug use by older adults, which should feature as a priority in the planning agenda of the Brazilian Unified Health System (SUS). Analisar as variações da prevalência do uso crônico de medicamentos por idosos no Brasil segundo sua possível associação com as doenças crônicas mais prevalentes, fatores sociodemográficos e de saúde, e identificar fatores de risco para polifarmácia. Estudo com dados da Pesquisa Nacional de Acesso, Utilização e Promoção do Uso Racional de Medicamentos, de caráter transversal e amostra probabilística populacional em municípios brasileiros urbanos. A variável independente foi o número de medicamentos de uso crônico por idosos, vinculados às oito doenças crônicas investigadas. As variáveis intervenientes foram sexo, faixa etária, situação conjugal, escolaridade, nível socioeconômico, região do País, índice de massa corporal, hábito de fumar, percepção da própria saúde, internação no último ano e posse de plano de saúde privado, além das doenças crônicas referidas. Uma análise multivariável identificou os fatores de risco para polifarmácia. A prevalência de pelo menos um medicamento de uso crônico entre idosos foi de 93,0%. Do total de idosos, 18,0% utilizavam pelo menos cinco medicamentos (polifarmácia). A polifarmácia foi maior entre os mais idosos (20,0%), na região Sul (25,0%), nos que avaliaram a própria saúde como ruim (35,0%), nos obesos (26,0%), nos que referiram ter plano de saúde (23,0%) ou internação no último ano (31,0%) e entre os que referiram qualquer uma das doenças investigadas, particularmente diabetes (36,0%) e doenças cardíacas (43,0%). No modelo final de risco para polifarmácia permaneceram idade, região, percepção de saúde, posse de plano de saúde, internação no último ano e todas as doenças investigadas exceto acidente vascular cerebral. Idosos com doenças específicas têm fatores de risco para polifarmácia modificáveis por ações que visem o uso racional de medicamentos. Com o envelhecimento populacional em curso e a política exitosa de acesso a medicamentos, a tendência é aumentar a utilização de medicamentos por idosos, que deve ser prioridade na agenda de planejamento do Sistema Único de Saúde.

Clarifying the Rules for Targeted Killing: An Analytical Framework for Policies Involving Long-Range Armed Drones

DTIC Science & Technology

2016-09-08

the ability of the United States to influence how countries will use these systems ex post facto is always limited, as demonstrated by Saudi...Greg Miller, “CIA Didn’t Know Strike Would Hit al-Qaeda Leader,” Washington Post , June 17, 2015 (as of February 29, 2016: https...Targets Two Leaders of Somali Group Allied with al-Qaeda,” Washington Post , June 29, 2011 (as of February 29, 2016: https://www.washingtonpost.com

Cartilage preservation by inhibition of Janus kinase 3 in two rodent models of rheumatoid arthritis

PubMed Central

Milici, Anthony J; Kudlacz, Elizabeth M; Audoly, Laurent; Zwillich, Samuel; Changelian, Paul

2008-01-01

Introduction CP-690550 is a small molecule inhibitor of Janus kinase 3 (JAK3), a critical enzyme in the signaling pathway of multiple cytokines (interleukin (IL)-2, -7, -15 and -21) that are important in various T cell functions including development, activation and homeostasis. The purpose of this study was to evaluate CP-690550 in murine collagen-induced (CIA) and rat adjuvant-induced (AA) models of rheumatoid arthritis (RA). Methods CIA and AA were induced using standard protocols and animals received the JAK3 inhibitor via osmotic mini-pump infusion at doses ranging from 1.5–15 mg/kg/day following disease induction. Arthritis was assessed by clinical scores in the CIA models and paw swelling monitored using a plethysmometer in the AA model until study conclusion, at which time animals were killed and evaluated histologically. Results CP-690550 dose-dependently decreased endpoints of disease in both RA models with greater than 90% reduction observed at the highest administered dose. An approximate ED50 of approximately 1.5 mg/kg/day was determined for the compound based upon disease endpoints in both RA models examined and corresponds to CP-690550 serum levels of 5.8 ng/ml in mice (day 28) and 24 ng/ml in rats (day 24). The compound also reduced inflammatory cell influx and joint damage as measured histologically. Animals receiving a CP-690550 dose of 15 mg/k/d showed no histological evidence of disease. Conclusion The efficacy observed with CP-690550 in CIA and AA suggests JAK3 inhibition may represent a novel therapeutic target for the treatment of RA. PMID:18234077

Does temproray bilateral balloon occlusion of the common iliac arteries reduce the need for intra-operative blood transfusion in cases of placenta accretism?

PubMed

Al-Hadethi, Sinan; Fernando, Shane; Hughes, Simon; Thakorlal, Ajay; Seruga, Adam; Scurry, Bonnie

2017-06-01

Bilateral balloon occlusion has been employed as a prophylactic measure in cases of placenta accretism prior to caesarean section with the aim of reducing blood loss and its associated morbidity/mortality. There is however no clear consensus on its efficacy in the current literature. The objective of this study was to assess the efficacy of bilateral balloon occlusion of the common iliac arteries (CIA) in reducing intra-operative morbidity in cases of placenta accretism. The databases of the pathology department and radiology interventional suite were reviewed over a nine year period. Fifty-two cases of confirmed placental accretism who underwent caesarean section with or without hysterectomy were identified and divided into two groups. Twenty-five cases had temporary occlusion of the common iliac arteries (CIA) during delivery and these were considered the study group. The reminder 27 cases did not have temporary occlusion of the CIA and were considered the control group. The two groups were compared based on gravidity, age group, post-operative haemoglobin, drop in haemoglobin, estimated blood loss (EBL), transfusion requirement and the histopathological sub-types of placenta accretism. There was no statistically difference between the study and the control groups regarding EBL, post-operative haemoglobin drop, transfusion requirement or in the placenta accretism histopathological subtype. Two cases in the study group had acute thromboembolic complications. Both groups had a single patient requiring a massive intra-operative transfusion. Our study was not able to detect a significant difference in blood loss or blood product requirement between patients who underwent CIA balloon in the setting of caesarean section for placenta accreta. This remains a challenging scenario requiring a multidisciplinary approach. © 2016 The Royal Australian and New Zealand College of Radiologists.

Cyanidin-3-glucoside inhibits inflammatory activities in human fibroblast-like synoviocytes and in mice with collagen-induced arthritis.

PubMed

Sun, Yan; Li, Lingling

2018-05-19

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint tissue inflammation. Cyanidin-3-glucoside (C3G) is a major component in the flavonoid family and has shown anti-inflammatory, anti-oxidant and anti-tumor activity. In this study, we investigated the effects of C3G on lipopolysaccharides (LPS)-induced inflammation on human rheumatoid fibroblast-like synoviocytes (FLS) and on collagen-induced arthritis (CIA) mice model. We treated FLS with C3G followed by LPS induction, the expressions of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β) and IL-6 and the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathway were analyzed. CIA was induced in mice and the arthritic mice were treated with C3G for 3 weeks. The disease severity was compared between control and C3G treated mice. The serum levels of TNF-α, IL-1β and IL-6 were analyzed by ELISA. C3G inhibited LPS-induced TNF-α, IL-1β and IL-6 expression in FLS. Moreover, C3G inhibited LPS-induced p65 production and IκBa, p38, ERK and JNK phosphorylation. Administration of C3G significantly attenuated disease in mice with CIA and decreased the serum level of TNF-α, IL-1β and IL-6. C3G inhibited LPS-induced inflammation in human FLS by inhibiting activation of NF-κB and MAPK signaling pathway. C3G exhibited therapeutic effects in mice with CIA. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Patients’ conceptions of their own influence on good treatment response to biological therapy in chronic inflammatory arthritis

PubMed Central

Larsson, Ingrid

2017-01-01

Background Biological therapies are common in the treatment of patients with chronic inflammatory arthritis (CIA). However, despite the fact that many patients respond well to their biological therapies, there are still a number of nonresponders. In order to design the best care for patients, it is important to understand how they conceive their own role in their treatment response. Objective To explore how patients with CIA conceive their own influence on a good treatment response to biological therapy. Methods This study had an exploratory and descriptive design with a phenomenographic approach. Interviews were conducted with 25 patients (11 women and 14 men) aged 17–79 years, with CIA who were undergoing biological therapy and who had low disease activity or were in remission. Results Patients with CIA undergoing biological therapy conceived their own influence on good treatment response in terms of adherence, physical activity, mental attitude, social support, and self-awareness. Adherence was described as the foundation for the patients’ own influence on good treatment response. Physical activity, mental attitude, and social support reflected three essential ways of understanding patients’ influence on good treatment response where the patients spoke about physical strength, mental strength, and social strength. Self-awareness reflected a comprehensive way of influencing good treatment response in which patients balanced their physical, mental, and social resources in partnership with health care professionals. Conclusion Patients conceived that they had a responsibility for adhering to the treatment as well as achieving balance in life in order to ensure good treatment response. Self-awareness was essential for maintaining a good treatment response, and this reflected the patients’ awareness of the complexity of living their lives with a chronic illness. PMID:28706444

Genetics of Rheumatoid Arthritis — A Comprehensive Review

PubMed Central

Kurkó, Júlia; Besenyei, Timea; Laki, Judit; Glant, Tibor T.; Mikecz, Katalin

2013-01-01

The “Bermuda triangle” of genetics, environment and autoimmunity is involved in the pathogenesis of rheumatoid arthritis (RA). Various aspects of genetic contribution to the etiology, pathogenesis and outcome of RA are discussed in this review. The heritability of RA has been estimated to be about 60 %, while the contribution of HLA to heritability has been estimated to be 11–37 %. Apart from known shared epitope (SE) alleles, such as HLA-DRB1*01 and DRB1*04, other HLA alleles, such as HLA-DRB1*13 and DRB1*15 have been linked to RA susceptibility. A novel SE classification divides SE alleles into S1, S2, S3P and S3D groups, where primarily S2 and S3P groups have been associated with predisposition to seropositive RA. The most relevant non-HLA gene single nucleotide polymorphisms (SNPs) associated with RA include PTPN22, IL23R, TRAF1, CTLA4, IRF5, STAT4, CCR6, PADI4. Large genome-wide association studies (GWAS) have identified more than 30 loci involved in RA pathogenesis. HLA and some non-HLA genes may differentiate between anti-citrullinated protein antibody (ACPA) seropositive and seronegative RA. Genetic susceptibility has also been associated with environmental factors, primarily smoking. Some GWAS studies carried out in rodent models of arthritis have confirmed the role of human genes. For example, in the collagen-induced (CIA) and proteoglycan-induced arthritis (PgIA) models, two important loci — Pgia26/Cia5 and Pgia2/Cia2/Cia3, corresponding the human PTPN22/CD2 and TRAF1/C5 loci, respectively — have been identified. Finally, pharmacogenomics identified SNPs or multiple genetic signatures that may be associated with responses to traditional disease-modifying drugs and biologics. PMID:23288628

Genetics of rheumatoid arthritis - a comprehensive review.

PubMed

Kurkó, Júlia; Besenyei, Timea; Laki, Judit; Glant, Tibor T; Mikecz, Katalin; Szekanecz, Zoltán

2013-10-01

The "Bermuda triangle" of genetics, environment and autoimmunity is involved in the pathogenesis of rheumatoid arthritis (RA). Various aspects of genetic contribution to the etiology, pathogenesis and outcome of RA are discussed in this review. The heritability of RA has been estimated to be about 60 %, while the contribution of HLA to heritability has been estimated to be 11-37 %. Apart from known shared epitope (SE) alleles, such as HLA-DRB1*01 and DRB1*04, other HLA alleles, such as HLA-DRB1*13 and DRB1*15 have been linked to RA susceptibility. A novel SE classification divides SE alleles into S1, S2, S3P and S3D groups, where primarily S2 and S3P groups have been associated with predisposition to seropositive RA. The most relevant non-HLA gene single nucleotide polymorphisms (SNPs) associated with RA include PTPN22, IL23R, TRAF1, CTLA4, IRF5, STAT4, CCR6, PADI4. Large genome-wide association studies (GWAS) have identified more than 30 loci involved in RA pathogenesis. HLA and some non-HLA genes may differentiate between anti-citrullinated protein antibody (ACPA) seropositive and seronegative RA. Genetic susceptibility has also been associated with environmental factors, primarily smoking. Some GWAS studies carried out in rodent models of arthritis have confirmed the role of human genes. For example, in the collagen-induced (CIA) and proteoglycan-induced arthritis (PgIA) models, two important loci - Pgia26/Cia5 and Pgia2/Cia2/Cia3, corresponding the human PTPN22/CD2 and TRAF1/C5 loci, respectively - have been identified. Finally, pharmacogenomics identified SNPs or multiple genetic signatures that may be associated with responses to traditional disease-modifying drugs and biologics.

Patients' conceptions of their own influence on good treatment response to biological therapy in chronic inflammatory arthritis.

PubMed

Larsson, Ingrid

2017-01-01

Biological therapies are common in the treatment of patients with chronic inflammatory arthritis (CIA). However, despite the fact that many patients respond well to their biological therapies, there are still a number of nonresponders. In order to design the best care for patients, it is important to understand how they conceive their own role in their treatment response. To explore how patients with CIA conceive their own influence on a good treatment response to biological therapy. This study had an exploratory and descriptive design with a phenomenographic approach. Interviews were conducted with 25 patients (11 women and 14 men) aged 17-79 years, with CIA who were undergoing biological therapy and who had low disease activity or were in remission. Patients with CIA undergoing biological therapy conceived their own influence on good treatment response in terms of adherence, physical activity, mental attitude, social support, and self-awareness. Adherence was described as the foundation for the patients' own influence on good treatment response. Physical activity, mental attitude, and social support reflected three essential ways of understanding patients' influence on good treatment response where the patients spoke about physical strength, mental strength, and social strength. Self-awareness reflected a comprehensive way of influencing good treatment response in which patients balanced their physical, mental, and social resources in partnership with health care professionals. Patients conceived that they had a responsibility for adhering to the treatment as well as achieving balance in life in order to ensure good treatment response. Self-awareness was essential for maintaining a good treatment response, and this reflected the patients' awareness of the complexity of living their lives with a chronic illness.

Open-systems Architecture of a Standardized Command Interface Chip-set for Switching and Control of a Spacecraft Power Bus

NASA Technical Reports Server (NTRS)

Ruiz, B. Ian; Burke, Gary R.; Lung, Gerald; Whitaker, William D.; Nowicki, Robert M.

2004-01-01

This viewgraph presentation reviews the architecture of the The CIA-AlA chip-set is a set of mixed-signal ASICs that provide a flexible high level interface between the spacecraft's command and data handling (C&DH) electronics and lower level functions in other spacecraft subsystems. Due to the open-systems architecture of the chip-set including an embedded micro-controller a variety of applications are possible. The chip-set was developed for the missions to the outer planets. The chips were developed to provide a single solution for both the switching and regulation of a spacecraft power bus. The Open-Systems Architecture allows for other powerful applications.

Results From the VISIBILITY Iliac Study: Primary and Cohort Outcomes at 9 Months.

PubMed

Rundback, John H; Peeters, Patrick; George, Jon C; Jaff, Michael R; Faries, Peter L

2017-06-01

To evaluate the safety and effectiveness of primary stenting of the common (CIA) or external iliac artery (EIA) using the Visi-Pro Balloon-Expandable Peripheral Stent System for treatment of stenotic, restenotic, or occluded lesions. Between 2011 and 2012, 75 patients (mean age 64.2±8.9 years; 46 men) with Rutherford category 2-4 ischemia and atherosclerotic lesions ≤10 cm in length underwent iliac artery stenting at 17 centers in the United States and Europe. The primary outcome of the study was the major adverse event (MAE) rate at 9 months postprocedure [composite of periprocedural death, in-hospital myocardial infarction, clinically driven target lesion revascularization (CD-TLR), and amputation of the treated limb]. Secondary outcomes included 30-day MAE rate, 9-month primary patency, changes in ankle-brachial index (ABI) and the Walking Impairment Questionnaire at 30 days and 9 months postprocedure, device success, and clinically driven target vessel revascularization (CD-TVR) at 30 days and 9 months. Outcomes in specific patient cohorts (ie, gender, stent location, calcification severity, and lesion grade) were analyzed. Eighty-one stents were implanted in 61 CIA and 15 EIA lesions (41 with moderate/severe calcification). The mean lesion treated length was 29.3±13.9 mm. All devices were successfully deployed. MAE occurred in 3 (4.0%) of 75 subjects at 9 months. Primary patency and freedom from CD-TVR at 9 months were both 95.8%. ABI improved from 0.67±0.14 at baseline to 0.94±0.14 and 0.96±0.16 at 30 days and 9-month follow-up, respectively (p<0.001 for both). There were no differences with respect to any of the analyzed patient characteristics, including gender. Nine-month results of the VISIBILITY Iliac stent study ( ClinicalTrials.gov identifier NCT01402700) demonstrated safety and effectiveness for the treatment of atherosclerotic CIA and EIA lesions with the Visi-Pro stent across all treated cohorts.

China Macroeconomic: Documentation Data Banks. Volume 3. Foreign Trade.

DTIC Science & Technology

1984-11-15

1983 data from Chlnese "Cmtan, Statistics," Econmic Infomation and Agency, THoE ong Pr ious years from CIA "International Trade Statistics" Load fram...204,097 145,564 515,062 1984 N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A 6 Sources, see below 19F, 1983 data from Chinese "Customs Statistics," Econmic ...Statistics," EconmIc Information and Agency, F org Previous years fran CIA "Internationl Trade Statistics" Load from rw 12 to row 54 -.96 - A B C D E F G H

A systematic review comparing sex differences in cognitive function in schizophrenia and in rodent models for schizophrenia, implications for improved therapeutic strategies.

PubMed

Leger, Marianne; Neill, Joanna C

2016-09-01

Sex is often overlooked in animal and human research. Cognitive impairment associated with schizophrenia (CIAS) remains an unmet clinical need, as current antipsychotic medication does not provide clinically meaningful improvements. One explanation could be lack of appreciation of gender differences in CIAS. Animal models play a critical role in drug development and improved translation to the clinic is an on-going process. Our systematic review aims to evaluate how well the animal studies translate into clinical findings. Supporting clinical results, our review highlights a male working memory advantage and a female advantage for visual memory and social cognition in rodent models for schizophrenia. Not investigated in animals, a female advantage for attention and speed of processing has been found in schizophrenia patients. Sex differences in reasoning and problem solving are poorly investigated in both human and animal studies. Overall, our review provides evidence of good translation from the animal models into the clinic when sexual dimorphism is assessed. Enhanced understanding of these sex differences will improve the management of CIAS. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mixing of Marine and Terrestrial Sources of Strontium in Coastal Environments

NASA Astrophysics Data System (ADS)

Ryan, Saskia; Crowley, Quentin; Deegan, Eileen; Snoeck, Christophe

2017-04-01

87Sr/86Sr from bulk soils, soil extracts and plant material have been used to investigate and quantify the extent of marine-derived Sr in the terrestrial biosphere. Samples were collected along coastal transects and 87Sr/86Sr biosphere values (plant and soil) converge to marine values with increasing proximity to the coast. R2values indicate highly significant trends in certain regions. The National Soils Database (NSDB), TELLUS and TELLUS Border datasets, all of which are geochemical surveys have been employed to further test the extent of marine elemental contribution. Collectively these data cover all of Ireland and Northern Ireland, with varying degrees of sampling density. A strong spatial correlation exists between the Chemical Index of Alteration (CIA; (Al2O3-(CaO*+Na2O)-K2O)) in topsoil (CIA <60; 27% n = 11651) and areas of blanket peat. The enrichment of Ca and Na in these regions would suggest a significant marine geochemical contribution. Topsoil CIA can therefore be used to identify areas likely to feature significant marine inputs and identify regions where the 87Sr/86Sr budget may deviate from bedrock values.

Illuminating pathways of forest nutrient provision: relative release from soil mineral and organic pools

NASA Astrophysics Data System (ADS)

Hauser, E.; Billings, S. A.

2017-12-01

Depletion of geogenic nutrients during soil weathering can prompt vegetation to rely on other sources, such as organic matter (OM) decay, to meet growth requirements. Weathered soils also tend to permit deep rooting, a phenomenon sometimes attributed to vegetation foraging for geogenic nutrients. This study examines the extent to which OM recycling provides nutrients to vegetation growing in soils with diverse weathering states. We thus address the fundamental problem of how forest vegetation obtains sufficient nutrition to support productivity despite wide variation in soils' nutrient contents. We hypothesized that vegetation growing on highly weathered soils relies on nutrients released from OM decay to a greater extent than vegetation growing on less weathered, more nutrient-rich substrates. For four mineralogically diverse Critical Zone Observatories (CZO) and Critical Zone Exploratory Network sites, we calculated weathering indices and approximated vegetation nutrient demand and nutrient release from OM decay. We also measured nutrient release rates from OM decay at each site. We then assessed the relationship between degree of soil weathering and the estimated fraction of nutrient demand satisfied by OM derived nutrients. Results are consistent with our hypothesis. The chemical index of alteration (CIA), a weathering index that increases in value with mineral depletion, varies predictably from 90 at the highly weathered Calhoun CZO to 60 at the Catalina CZO, where soils are more recently developed. Estimates of rates of K release from OM decay increase with CIA values. The highest release rate is 2.4 gK m-2 y-1 at Calhoun, accounting for 30% of annual vegetation K uptake; at Catalina, less than 0.5 gm-2 y-1 K is released, meeting 14% of vegetation demand. CIA also co-varies with rooting depth across sites: the deepest roots at the Calhoun sites are growing in soils with the highest CIA values, while the deepest roots at Catalina sites are growing in soils with much lower CIA values. Thus, provision of plant-available nutrients from OM decay appears greater at more weathered sites, and dominant nutrient sources accessed by deep roots (OM- vs. rock-derived) may vary predictably with soil weathering stage. On-going incubations will permit us to assess these relationships for multiple geogenic nutrients.

How Drone Strikes and a Fake Vaccination Program Have Inhibited Polio Eradication in Pakistan: An Analysis of National Level Data.

PubMed

Kennedy, Jonathan

2017-10-01

This article investigates whether the United States' counterinsurgency operations have inhibited polio eradication efforts in northwestern Pakistan, the world's last major reservoir of polio. Anecdotal evidence suggests that militants disrupt polio vaccination programs because of suspicions that campaigns are a cover for gathering intelligence on Central Intelligence Agency (CIA) drone targets. This paper analyzes national-level quantitative data to test this argument. Between 2004 and 2012, the number of polio cases in Pakistan closely mirrored the number of drone strikes. But from 2013 onward, polio cases increased while drone strikes fell. This can be explained by the CIA's use of a fake immunization campaign in a failed attempt to obtain the DNA of Osama bin Laden's relatives prior to his assassination in 2011. This seemingly vindicated militants' suspicions that vaccination programs were a cover for espionage. Militants consequently intensified their disruption of immunization campaigns, resulting in an increase in polio cases in Pakistan, as well as in Afghanistan, Syria, and Iraq. For politicians and military planners, drones are attractive because they are said to harm fewer civilians than conventional methods of warfare. However, this paper demonstrates that drone strikes had negative effects on the well-being of civilians in Pakistan and further afield because they undermined global efforts to eradicate polio.

A hidden Late Cretaceous arc and subsequent magmatic events in the Caucasus-Iran-Anatolia (CIA) orogenic belt: Detrital zircon U-Pb and Hf isotopic constraints

NASA Astrophysics Data System (ADS)

Tien, C. Y.; Lin, Y. C.; Chu, M. F.; Chung, S. L.; Bi˙ngöl, A. F.

2017-12-01

The Caucasus-Iran-Anatolia (CIA) orogenic belt formed by "Turkic-type orogeny" consists mainly of subduction-accretion complexes following the collision between Eurasia and Arabia and the closure of Neotethy. This study reports U-Pb and Hf isotopic data of detrital zircon separates from five Eocene to mid-Miocene sandstone samples from Divrigi and Duranlar in the west to the Mus basin in the east, all locating in the northern part of the Bitlis-Zagros suture zone. The U-Pb age data suggest four main magmatic episodes: (1) 100-70 Ma, (2) 60-40 Ma, (3) 30 Ma, and (4) 15 Ma. The Late Cretaceous zircons recovered mainly from the Mus basin are marked by a significant Hf isotopic variation over time, with ɛHf(T) values dropping from +15 to -10. Zircons from the second and third episodes show spatial variations in isotopic compositions, with positive ɛHf(T) values (+10 to +5) in the Mus basin and heterogeneous ɛHf(T) values (+10 to -10) in the west. The fourth and youngest episode of zircons, mainly from Duranlar area, shows uniform ɛHf(T) values around +5. We attribute the Late Cretaceous episode of zircons to the broadly coeval Elazig arc magmatism that, according to our counterpart study, occurred as a short-lived, intra-oceanic arc system by subduction initiation after the formation of Neotethyan ophiolites in the region. Moreover, we argue that this Late Cretaceous arc system may have existed more widely within the southern branch of Neothethys than that suggested by present-day outcrops. The dramatic change in Hf isotopic composition from 100 to 70 Ma, also observed in the rock record by our counterpart study, may be interpreted as a result of subduction to accretion processes. The remaining three episodes of zircons are related to younger stages of magmatism within or around the suture zone that remains poorly studied. Our results indicate that detrital zircon is a useful tool to uncover "hidden" magmatic records in the CIA and other "Turkic-type" orogenic belts where complex interaction of multiple micro-terrains may have taken place during accretionary and collisional orogenesis.

QUALIS EVALUATION OF MEDICINE III: ANALYSIS OF ANESTHESIOLOGY AND GYNECOLOGY AND OBSTETRICS JOURNALS.

PubMed

Calderon, Iracema de Mattos Paranhos

2015-01-01

To know the current publication of Anesthesiology and Obstetrics and Gynecology subareas, to support the updating of Qualis Journals criteria in these specific subareas. Cross-sectional, descriptive study in which was evaluated in quantitatively and qualitatively way the bibliographic production of Anesthesiology and Obstetrics and Gynecology subareas, from January 2010 to December 2012. Were investigated the values ​​of the impact factor; calculated (i) the number (n) and the percentage of journals in each stratum Qualis A1, A2, B1, B2, B3, B4 and B5, and (ii) the median values ​​and their extreme limits (minimum values ​​and maximum) and quartiles (p25; p50; p75; p90) of the impact factors in the different strata. The bibliographic production of the three-year period 2010-2012 was published in 69 journals in Anesthesiology subarea and in 345 in Gynecology and Obstetrics. In Anesthesiology, 44% were within the limits of impact factor of superior A1, A2 and B1; in Obstetrics and Gynecology, 42.4% were in those limits and strata. Despite lagging behind by international standards, publications of Anesthesiology and Obstetrics and Gynecology showed tendency to improve the quality. In these sub-areas, the median of journals impact factor is beyond the limits defined by the area in the last assessment. Therefore, it must be reconsidered new indicators to assess this aspect. Conhecer a publicação atual das subáreas Anestesiologia e Ginecologia e Obstetrícia, para subsidiar a atualização dos critérios Qualis-periódicos, específicos dessas subáreas. Estudo de corte transversal, descritivo, onde avaliou-se, de modo quantitativo e qualitativo, a produção bibliográfica das subáreas Anestesiologia e Ginecologia e Obstetrícia, no período de janeiro de 2010 a dezembro de 2012. Foram definidos os valores do fator de impacto das revistas; foram calculados (i) o número (n) e percentual de periódicos em cada um dos estratos Qualis - A1, A2, B1, B2, B3, B4 e B5 e (ii) os valores de mediana e respectivos limites extremos (valores mínimo e máximo) e quartis (p25; p50; p75; p90) dos fatores de impacto nos diferentes estratos. A produção bibliográfica do triênio 2010-2012 foi divulgada em 69 periódicos na subárea Anestesiologia e em 345 na subárea Ginecologia e Obstetrícia. Na subárea Anestesiologia, 44% dessa produção estava nos limites de fator de impacto dos estratos superiores A1, A2 e B1; na subárea Ginecologia e Obstetrícia, 42,4% estavam nesses limites e estratos. Apesar de aquém do desejado para os padrões internacionais, as publicações das subáreas Anestesiologia e Ginecologia e Obstetrícia mostram tendência para melhorar a qualidade. Nessas subáreas, a mediana do fator de impacto dos periódicos está além dos limites definidos pela área na última avaliação. Impõe-se, portanto, novos indicadores para a avaliação desse quesito.

Depositional environments, provenance and paleoclimatic implications of Ordovician siliciclastic rocks of the Thango Formation, Spiti Valley, Tethys Himalaya, northern India

NASA Astrophysics Data System (ADS)

Rashid, Shaik A.; Ganai, Javid A.

2018-05-01

Recently published findings indicate that the Ordovician period has been much more dynamic than previously anticipated thus making this period significant in geological time. The Ordovician of India can best be studied in the Spiti region because the Spiti basin records the complete uninterrupted history of excellent marine sedimentary rocks starting from Cambrian to Paleogene which were deposited along the northern margin of India. Due to these reasons the geochemical data on the Ordovician rocks from the Spiti region is uncommon. The present geochemical study on the Ordovician Thango Formation (Sanugba Group) is mainly aimed to understand the provenance and the paleoclimatic conditions. The sandstones are the dominant lithology of the Thango Formation with intercalations of minor amount of shales. Detailed petrographic and sedimentological analysis of these rocks suggest that three major depositional environments, viz., fluvial, transitional and marine prevailed in the basin representing transgressive and regressive phases. The major and trace element ratios such as SiO2/Al2O3, K2O/Na2O and La-Th- Sc discrimination diagram suggest that these rocks were deposited in passive margin tectonic settings. Various geochemical discriminants and elemental ratios such as K2O/Na2O, Al2O3/TiO2, La/Sc, Th/Sc, Cr/Th, Zr/Sc, (Gd/Yb)N and pronounced negative Eu anomalies indicate the rocks to be the product of weathering of post-Archean granites. The striking similarities of the multi-elemental spider diagrams of the studied sediments and the Himalayan granitoids indicate that sediments are sourced from the Proterozoic orogenic belts of the Himalayan region. Chemical index of alteration (CIA) values of the studied sediments (55-72) suggest that the source rocks underwent low to moderate degree of chemical weathering. The span of the CIA values (55-72) recorded in the sediments from the Spiti region may have resulted from varying degrees of weathering conditions in the source area. This, in turn, reflects variable climatic conditions prevailing during the Ordovician period, which is consistent with the global studies. The high CIA values observed by numerous studies on siliciclastic sediments may imply warm paleoclimate attributed to an increase in atmospheric carbon dioxide and/or methane levels inducing an acidic weathering environment and enhanced silicate weathering. While the low CIA values indicates prevalence of arid-glacial conditions where negligible chemical alteration is possible. This study documents the noteworthy events like fluctuating (rise and fall) atmospheric CO2 and sea levels during the Ordovician period, a conclusion which is consistent with the other such studies on the Phanerozoic glaciation (or mass extinction) events on Gondwana supercontinent.

Effects of agkistrodon in different dosage forms on collagen-induced arthritis in rats.

PubMed

Bao, Jie; Xie, Zhi-Jun; Chen, Lei-Ming; Sun, Jing; Fan, Yong-Sheng

2016-12-01

To determine the effective dosage and formulation of agkistrodon in collagen-induced arthritis (CIA) rats. CIA was induced by injection of collagen in complete/incomplete Freund's adjuvant. Agkistrodon decoction, agkistrodon powder, and agkistrodon wine were administered daily starting from the onset of arthritis. Paw swelling degree was measured by using a volume-measuring instrument every 7 days after primary immunization. Arthritis index was measured and calculated using the "five scoring method" every 7 days. The levels of serum interleukin-1ß (IL-1ß) and type II collagen IgG antibodies were detected by enzyme-linked immunosorbent assay. Finally, all ankles were removed, and X-ray radiography was performed with In-vivo Imaging System FX. Samples were counterstained with hematoxylin and eosin for analysis. Among the various dosage formulations of agkistrodon, high-dose powder, which was equivalent to an amount of 6 g/day in adults, showed better effects on the inhibition of joint swelling and reduction of arthritis index score. The relatively low levels of serum IL-1 and anti-type II collagen IgG antibodies, as well as the X-ray radiography and pathology results, further proved the superiority of the high-dose powder over the other formulations. The effect of decoction on inhibiting joint swelling was inversely proportional to the dosage. Other effects, such as reduction of arthritis index score and the levels of serum IL-1 and anti-type II collagen IgG antibodies, were directly proportional to the dosage. While the use of large dose agkistrodon wine led to negative effects. These data highlight the potential function of high-dose agkistrodon powder, which was equivalent to an amount of 6 g/day in adults. The powder can quickly relieve the symptoms of rheumatoid arthritis and prevent aggravation of disease, especially during the early period.

Evidence for a chondritic impactor, evaporation-condensation effects and melting of the Precambrian basement beneath the 'target' Deccan basalts at Lonar crater, India

NASA Astrophysics Data System (ADS)

Das Gupta, Rahul; Banerjee, Anupam; Goderis, Steven; Claeys, Philippe; Vanhaecke, Frank; Chakrabarti, Ramananda

2017-10-01

The ∼1.88 km diameter Lonar impact crater formed ∼570 ka ago and is an almost circular depression hosted entirely in the Poladpur suite of the ∼65 Ma old basalts of the Deccan Traps. To understand the effects of impact cratering on basaltic targets, commonly found on the surfaces of inner Solar System planetary bodies, major and trace element concentrations as well as Nd and Sr isotopic compositions were determined on a suite of selected samples composed of: basalts, a red bole sample, which is a product of basalt alteration, impact breccia, and impact glasses, either in the form of spherules (<1 mm in diameter) or non-spherical impact glasses (>1 mm and <1 cm). These data include the first highly siderophile element (HSE) concentrations for the Lonar spherules. The chemical index of alteration (CIA) values for the basalts and impact breccia (36.4-42.7) are low while the red bole sample shows a high CIA value (55.6 in the acid-leached sample), consistent with its origin by aqueous alteration of the basalts. The Lonar spherules are classified into two main groups based on their CIA values. Most spherules show low CIA values (Group 1: 34.7-40.5) overlapping with the basalts and impact breccia, while seven spherules show significantly higher CIA values (Group 2: >43.0). The Group 1 spherules are further subdivided into Groups 1a and 1b, with Group 1a spherules showing higher Ni and mostly higher Cr compared to the Group 1b spherules. Iridium and Cr concentrations of the spherules are consistent with the admixture of 1-8 wt% of a chondritic impactor to the basaltic target rocks. The impactor contribution is most prominent in the Group 1a and Group 2 spherules, which show higher Ni/Co, Ni/Cr and Cr/Co ratios compared to the target basalts. In contrast, the Group 1b spherules show major and trace element compositions that overlap with those of the impact breccia and are characterized by high EFTh (Enrichment Factor for Th defined as the Nb-normalized concentration of Th relative to that of the average basalt) as well as fractionated La/Sm(N), and higher large ion lithophile element (LILE) concentrations compared to the basalts. The relatively more radiogenic Sr and less radiogenic Nd isotopic composition of the impact breccia and non-spherical impact glasses compared to the target basalts are consistent with melting and mixing of the Precambrian basement beneath the Deccan basalt with up to 15 wt% contribution of the basement to these samples. Variations in the moderately siderophile element (MSE) concentration ratios of the impact breccia as well as all the spherules are best explained by contributions from three components - a chondritic impactor, the basaltic target rocks at Lonar and the basement underlying the Deccan basalts. The large variations in concentrations of volatile elements like Zn and Cu and correlated variations of EFCu-EFZn, EFPb-EFZn, EFK-EFZn and EFNa-EFZn, particularly in the Group 1a spherules, are best explained by evaporation-condensation effects during impact. While most spherules, irrespective of their general major and trace element composition, show a loss in volatile elements (e.g., Zn and Cu) relative to the target basalts, some spherules, mainly of Group 1, display enrichments in these elements that are interpreted to reflect the unique preservation of volatile-rich vapour condensates resulting from geochemical fractionation in a vertical direction within the vapour cloud.

Multi-property isotropic intermolecular potentials and predicted spectral lineshapes of collision-induced absorption (CIA), collision-induced light scattering (CILS) and collision-induced hyper-Rayleigh scattering (CIHR) for H2sbnd Ne, -Kr and -Xe

NASA Astrophysics Data System (ADS)

El-Kader, M. S. A.; Godet, J.-L.; Gustafsson, M.; Maroulis, G.

2018-04-01

Quantum mechanical lineshapes of collision-induced absorption (CIA), collision-induced light scattering (CILS) and collision-induced hyper-Rayleigh scattering (CIHR) at room temperature (295 K) are computed for gaseous mixtures of molecular hydrogen with neon, krypton and xenon. The induced spectra are detected using theoretical values for induced dipole moment, pair-polarizability trace and anisotropy, hyper-polarizability and updated intermolecular potentials. Good agreement is observed for all spectra when the literature and the present potentials which are constructed from the transport and thermo-physical properties are used.

Prospective, multicenter study of endovascular repair of aortoiliac and iliac aneurysms using the Gore Iliac Branch Endoprosthesis.

PubMed

Schneider, Darren B; Matsumura, Jon S; Lee, Jason T; Peterson, Brian G; Chaer, Rabih A; Oderich, Gustavo S

2017-09-01

The GORE EXCLUDER Iliac Branch Endoprosthesis (IBE; W. L. Gore and Associates, Flagstaff, Ariz) is an iliac branch stent graft system designed to preserve internal iliac artery perfusion during endovascular repair of aortoiliac aneurysms (AIAs) and common iliac artery (CIA) aneurysms (CIAAs). We report the 6-month primary end point results of the IBE 12-04 United States pivotal trial for endovascular treatment of AIAs and CIAAs using the IBE device. The trial prospectively enrolled 63 patients with AIA or CIAA who underwent implantation of the IBE device at 28 centers in the United States from 2013 to 2015. All patients underwent placement of a single IBE device. Twenty-two patients (34.9%) with bilateral CIAs were enrolled after undergoing staged coil or plug embolization (21 of 22) or surgical revascularization (1 of 22) of the contralateral internal iliac artery. Follow-up at 30 days and 6 months included clinical assessment and computed tomography angiography evaluation as assessed by an independent core laboratory. The primary effectiveness end point was freedom from IBE limb occlusion and reintervention for type I or III endoleak and ≥60% stenosis at 6 months, and the secondary effectiveness end point was freedom from new onset of buttock claudication on the IBE side at 6 months. Mean CIA diameter on the IBE side was 41.0 ± 11.4 mm (range, 25.2-76.3 mm). There were no procedural deaths, and technical success, defined as successful deployment and patency of all IBE components and freedom from type I or III endoleak, was 95.2% (60 of 63). Data for 61 patients were available for primary and secondary effectiveness end point analysis. Internal iliac limb patency was 95.1% (58 of 61), and no new type I or III endoleaks or device migrations were observed at 6 months. The three patients with loss of internal iliac limb patency were asymptomatic, and freedom from new-onset buttock claudication on the IBE side was 100% at 6 months. New-onset buttock claudication occurred on the non-IBE treatment side in six of 21 patients (28.6%) who underwent staged internal iliac artery coil embolization. These results confirm that the IBE device is effective at treating CIAAs and AIAs, maintaining blood flow into the internal iliac artery, and avoiding complications associated with internal iliac artery sacrifice. Follow-up will be continued for 5 years to establish the long-term durability of iliac aneurysm repair with the IBE device. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Virulence gene profiles of Arcobacter species isolated from animals, foods of animal origin, and humans in Andhra Pradesh, India.

PubMed

Sekhar, M Soma; Tumati, S R; Chinnam, B K; Kothapalli, V S; Sharif, N Mohammad

2017-06-01

This study aimed to detect putative virulence genes in Arcobacter species of animal and human origin. A total of 41 Arcobacter isolates (16 Arcobacter butzleri , 13 Arcobacter cryaerophilus , and 12 Arcobacter skirrowii ) isolated from diverse sources such as fecal swabs of livestock (21), raw foods of animal origin (13), and human stool samples (7) were subjected to a set of six uniplex polymerase chain reaction assays targeting Arcobacter putative virulence genes ( ciaB , pldA , tlyA , mviN , cadF , and cj1349 ). All the six virulence genes were detected among all the 16 A. butzleri isolates. Among the 13 A. cryaerophilus isolates, cadF, ciaB , cj1349, mviN , pldA , and tlyA genes were detected in 61.5, 84.6, 76.9, 76.9, 61.5, and 61.5% of isolates, respectively. Among the 12 A. skirrowii isolates, cadF, ciaB , cj1349, mviN , pldA , and tlyA genes were detected in 50.0, 91.6, 83.3, 66.6, 50, and 50% of isolates, respectively. Putative virulence genes were detected in majority of the Arcobacter isolates examined. The results signify the potential of Arcobacter species as an emerging foodborne pathogen.

Anti-inflammatory effects of interleukin-23 receptor cytokine-binding homology region rebalance T cell distribution in rodent collagen-induced arthritis

PubMed Central

Guo, Wei; Yu, Dongmei; Wang, Xin; Luo, Cheng; Chen, Yucong; Lei, Wen; Wang, Chen; Ge, Yaoyao; Xue, Wenyao; Tian, Qiqi; Gao, Xiangdong; Yao, Wenbing

2016-01-01

IL-23 is an important cytokine to regulate Th17 cell differentiation and promote the proliferation of inflammatory cells in Th17-mediated autoimmune diseases. The collagen-induced arthritis (CIA) in rat is a model of rheumatoid arthritis characterized by pronounced inflammatory auto-responses from B and T cells, especially Th17 cells in lesions. In the present study, we used rhIL23R-CHR to block the IL-23 signaling pathway to probe the importance of IL-23 in misbalancing the ratio of Th17/Th9/Treg cells in CIA rats. After treatments with rhIL23R-CHR, the CIA rats showed a significant decrease of secretions of IL-17 and IL-9, whereas FoxP3 was activated in the process, indicating that IL-23 can manipulate the balance of Th17/Th9/Treg cells. Similar to the animal model, IL-23 also possessed remarkable proinflammatory effects on human fibroblast-like synoviocyte cells (HFLS), showing synergetic outcomes with TNF-α. Together, IL-23 could act as a modulator to imbalance the ratio of Th17/Th9/Treg cells, and rhIL23R-CHR could serve as a potential therapeutic agent for RA patients. PMID:27177334

Short post-infusion scalp cooling time in the prevention of docetaxel-induced alopecia.

PubMed

van den Hurk, C J G; Breed, W P M; Nortier, J W R

2012-12-01

The patient impact of chemotherapy-induced alopecia (CIA) is high. Scalp cooling is applied to reduce CIA. The potential optimum post-infusion cooling times (PICTs) are currently unknown. Scalp cooling was applied in 53 patients receiving docetaxel chemotherapy with 90-min PICT (observational part). Also 15 non-scalp-cooled patients were included. If hair preservation was observed in >80 % of the patients, randomisation between 45 and 90-min PICT was planned. Patients reported tolerance of scalp cooling and use of head covering. Observational study: 81 % of scalp-cooled patients did not require head covering versus 27 % of non-scalp-cooled patients. Randomised study: 79 % of 38 patients with 90-min PICT did not need head covering versus 95 % of 38 patients with 45-min PICT (p = 0.04). Scalp cooling was very well tolerated (visual analogue scale = 79). A 45-min PICT can be recommended in 3-weekly docetaxel regimens with a dose of 75 or 100 mg/m(2), administered in 60 min. The shorter PICT is a major advantage in time investment for patients. Patients (women and men) who receive docetaxel, except combined with doxorubicin and cyclophosphamide (taxotere, adriamycin and cyclophosphamide (TAC)) should be informed about the protective effect and high tolerability of scalp cooling in avoiding CIA.

Role of CTA1R7K-COL-DD as a novel therapeutic mucosal tolerance-inducing vector for treatment of collagen-induced arthritis.

PubMed

Hasselberg, Annemarie; Schön, Karin; Tarkowski, Andrej; Lycke, Nils

2009-06-01

To determine whether a cholera toxin-derived, novel immunomodulating fusion protein, CTA1R7K-COL-DD, carrying the class II major histocompatibility complex H-2q-restricted type II collagen peptide aa 259-274, can induce therapeutic tolerance and prevent collagen-induced arthritis (CIA) when administered intranasally in DBA/1 mice, and to assess whether ADP-ribosylation at the mucosal membranes exerts a regulatory function such that the outcome of tolerance or immune enhancement can be controlled. DBA/1 mice with CIA were treated intranasally with CTA1R7K-COL-DD. The therapeutic effect was monitored for 46 days after the onset of disease. Clinical scoring of disease, histologic examination of inflammation, and bone erosion were assessed, and cytokine levels were determined in the serum or supernatants from splenocytes stimulated with recall antigen. The protective effect of CTA1R7K-COL-DD resulted in roughly 60% of the mice having no clinical signs or histologic evidence of disease after treatment, and those with CIA had significantly milder disease with less bone erosion. The protective status was associated with lower serum titers of IgG1, IgG2a, IgG2b, and IgG3 anticollagen and a substantial decrease in the production of interleukin-6 (IL-6), IL-17, and interferon-gamma, while levels of IL-10 were markedly up-regulated both in the serum and at the T cell level. The enzymatically inactive mutant fusion protein CTA1R7K-COL-DD provided substantial therapeutic protection against CIA following intranasal administration. The mechanism behind the effect appears to be mediated by peptide-specific regulatory T cells induced by mucosal exposure to the peptide containing CTA1R7K-COL-DD vector. In addition, ADP-ribosylation at the mucosal membranes acts as a key regulator controlling mucosal tolerance or immunity.

Biosimilar epoetin for the management of chemotherapy-induced anemia in elderly patients

PubMed Central

Kurtz, Jean-Emmanuel; Soubeyran, Pierre; Michallet, Mauricette; Luporsi, Elisabeth; Albrand, Hélène

2016-01-01

Introduction Chemotherapy-induced anemia (CIA) is a frequent complication among cancer patients, with elderly patients more likely to suffer severe effects. Biosimilar erythropoiesis-stimulating agents lower costs of supportive cancer treatment, and thus are particularly relevant in the elderly cancer population, which is growing rapidly worldwide. The goal of this subanalysis was to compare the tolerability and effectiveness of an epoetin biosimilar for treating CIA in patients <70 years old vs patients ≥70 years old. Materials and methods The ORHEO observational trial enrolled patients with CIA (hemoglobin [Hb] <11 g/dL) in association with chemotherapy for solid tumors, lymphoma, or myeloma. Patients received an epoetin biosimilar and were evaluated at 3 and 6 months for response, defined as achieving target Hb without blood transfusions during the 3 weeks preceding measurement, Hb ≥10 g/dL, or Hb increase ≥1 g/dL since study enrollment. Secondary end points included changes in Hb level, treatment interruptions, transfusion rates, and adverse events. Results Among the 2,310 original patients, 1,301 <70 years old were compared to 1,009 ≥70 years old. Almost all patients (99.9%) received the biosimilar epoetin zeta (Retacrit). Patients in both groups responded well to treatment with biosimilar epoetin, with 79.8% and 84% responding at 3 months and 86.3% and 86.8% at 6 months among younger and elderly cohorts, respectively. Biosimilar epoetin therapy was well tolerated, with adverse events reported in only 17.6% and 16.4% of younger and elderly patients, respectively. A greater number of thromboembolic events and a lesser rate of infections were reported in the elderly, but were still lower than reported in clinical registration trials. No treatment fatalities occurred in either group. Conclusion Biosimilar epoetin was an effective and well-tolerated treatment for managing CIA in elderly cancer patients. PMID:27822071

Collagen-induced arthritis in Dark Agouti rats as a model for study of immunological sexual dimorphisms in the human disease.

PubMed

Dimitrijević, Mirjana; Arsenović-Ranin, Nevena; Bufan, Biljana; Nacka-Aleksić, Mirjana; Macanović, Mirjana Lazarević; Milovanović, Petar; Đurić, Marija; Sopta, Jelena; Leposavić, Gordana

2018-05-21

Collagen-induced arthritis (CIA) is a frequently used animal model of rheumatoid arthritis, human autoimmune disease that exhibits clear sex bias in incidence and clinical course. Female Dark Agouti rats immunized for CIA showed also greater incidence and higher arthritic score than their male counterparts. The study investigated sex differences in mechanisms controlling the primary immune responses in draining lymph nodes (dLNs), as a factor contributing to this dimorphism. The higher frequencies of CD4 + CD25 + Foxp3- cells, presumably activated effector T (Teff) cells, and IL-17+, IFN-γ + and IL-17 + IFN-γ + T cells were found in female compared with male rat dLNs. However, the frequency of CD4 + CD25 + Foxp3+ T regulatory cells (Treg) did not differ between sexes. Thus, CD4+ Teff cells/Treg ratio, and IL-17+ T cells/Treg and IFN-γ + T cells/Treg ratios were higher in female than in male rats, and among them was found lower frequency of PD-1+ cells. This suggested less efficient control of (auto)immune Th1/Th17 cell responses in female rat dLNs. On the contrary, the frequency of IL-4+ T cells was lower in female than in male rat dLNs. Consistently, the ratio of serum levels of collagen-specific IgG2a (IFN-γ-dependent, with an important pathogenic role in CIA) and IgG1 (IL-4-dependent) was shifted towards IgG2a in female compared with male rats. As a whole, the study suggests that sexual dimorphism in the control of T cell activation/polarization could contribute to sex bias in the susceptibility to CIA. Moreover, the study advises the use of animals of both sexes in the preclinical testing of new drugs for rheumatoid arthritis. Copyright © 2018 Elsevier Inc. All rights reserved.

Risk Factors of Internet Addiction among Internet Users: An Online Questionnaire Survey

PubMed Central

Wu, Chia-Yi; Lee, Ming-Been; Liao, Shih-Cheng; Chang, Li-Ren

2015-01-01

Backgrounds Internet addiction (IA) has become a major public health issue worldwide and is closely linked to psychiatric disorders and suicide. The present study aimed to investigate the prevalence of IA and its associated psychosocial and psychopathological determinants among internet users across different age groups. Methods The study was a cross-sectional survey initiated by the Taiwan Suicide Prevention Center. The participants were recruited from the general public who responded to the online questionnaire. They completed a series of self-reported measures, including Chen Internet Addiction Scale-revised (CIAS-R), Five-item Brief Symptom Rating Scale (BSRS-5), Maudsley Personality Inventory (MPI), and questions about suicide and internet use habits. Results We enrolled 1100 respondents with a preponderance of female subjects (85.8%). Based on an optimal cutoff for CIAS-R (67/68), the prevalence rate of IA was 10.6%. People with higher scores of CIAS-R were characterized as: male, single, students, high neuroticism, life impairment due to internet use, time for internet use, online gaming, presence of psychiatric morbidity, recent suicide ideation and past suicide attempts. Multiple regression on IA showed that age, gender, neuroticism, life impairment, internet use time, and BSRS-5 score accounted for 31% of variance for CIAS-R score. Further, logistic regression showed that neuroticism, life impairment and internet use time were three main predictors for IA. Compared to those without IA, the internet addicts had higher rates of psychiatric morbidity (65.0%), suicide ideation in a week (47.0%), lifetime suicide attempts (23.1%), and suicide attempt in a year (5.1%). Conclusion Neurotic personality traits, psychopathology, time for internet use and its subsequent life impairment were important predictors for IA. Individuals with IA may have higher rates of psychiatric morbidity and suicide risks. The findings provide important information for further investigation and prevention of IA. PMID:26462196

The good pharmacy practice on Einstein Program at Paraisópolis Community.

PubMed

Oliveira, Lara Tânia de Assumpção Domingues Gonçalves de; Silva, Camila Pontes da; Guedes, Maria das Vitorias; Sousa, Ana Célia de Oliveira; Sarno, Flávio

2016-01-01

To describe indicators and processes developed and implemented for pharmaceutical assistance at the Einstein Program at Paraisópolis Community pharmacy. This was a descriptive study of retrospective data from January 2012 to December 2015. Data were obtained from spreadsheets developed for monitoring the productivity and care quality provided at the pharmacy. The evaluated variables were pharmaceutical assistance to prescription, pharmaceutical intervention, orientation (standard and pharmaceutical) and pharmaceutical orientation rate. The pharmacy assisted, on average, 2,308 prescriptions monthly, dispensing 4,871 items, including medications, materials and food supplements. Since March 2015, virtually, the pharmacist analyzed all prescriptions, prior to dispensing. In the analyzed period, there was an increase in monthly pharmaceutical interventions from 7 to 32 on average, and, although there was a decrease in the number of standard orientation, the pharmaceutical orientation had an increase, causing a rise of pharmaceutical orientation rate from 4 to 11%. The processes developed and implemented at the program pharmacy sought to follow the good pharmacy practice, and help patients to make the best use of their medications. Descrever os indicadores e os processos desenvolvidos e implantados para assistência farmacêutica na farmácia do Programa Einstein na Comunidade de Paraisópolis. Tratase de um estudo descritivo de dados retrospectivos de janeiro de 2012 a dezembro de 2015. Os dados foram obtidos de planilhas desenvolvidas para acompanhamento da produtividade e da qualidade de assistência prestada na farmácia. As variáveis avaliadas foram: atenção farmacêutica à prescrição, intervenção farmacêutica, orientação (padrão e farmacêutica) e taxa de orientação farmacêutica. A farmácia atendeu, em média, 2.308 prescrições ao mês, dispensando 4.871 itens, incluindo medicamentos, materiais e suplementos alimentares. Desde março de 2015, praticamente todas as prescrições foram analisadas pelo farmacêutico antes da dispensação. Houve incremento nas intervenções farmacêuticas mensais, de 7 para 32 em média e, apesar de ter havido diminuição no número de orientações padrão, a orientação farmacêutica aumentou, fazendo com que a taxa de orientação subisse de 4 para 11%. Os indicadores e os processos desenvolvidos e implantados na farmácia do programa procuraram seguir as boas práticas de farmácia e ajudar os pacientes a fazerem melhor uso de seus medicamentos.

Serum levels of interleukin-1 beta, interleukin-6 and melatonin over summer and winter in kidney deficiency syndrome in Bizheng rats.

PubMed

Zhang, Miao; Wang, Tong; Chen, Huai-Min; Chen, Yan-Qin; Deng, Yang-Chun; Li, Ya-Tian

2014-06-01

To observe the seasonal changes in serum levels of interleukin-1 beta (IL-1β), interleukin-6 (IL-6) and melatonin (MT) in Bizheng rat model, and explore the relationship between MT and the pathogenesis of rheumatoid arthritis. One hundred and sixty Sprague-Dawley rats were randomly divided into four groups in summer (n=80) and winter (n=80) respectively: normal group, collagen-induced arthritis (CIA) model group, operation group, and sham-operation group (n=20 in each group). The CIA model group was injected with collagen emulsion at the base of the tail to induce arthritis. The rats in the operation group received pineal gland resection, and 7 days after the first operation, underwent testectomy or oophorectomy. The rats in the sham-operation group were operated to ligature the sagittal sinus, without extracting the pineal gland. After the operations, the operation group and the sham-operation group both were immunized as the CIA group was. The serum levels of IL-1β, IL-6 and MT in different groups were measured by radioimmunoassay. Compared with the normal group, the serum levels of IL-1β and IL-6 increased in the CIA model, operation, and sham-operation groups both in summer and in winter (IL-1β in summer, P=0.008, P<0.01, P=0.012; IL-1β in winter, P=0.019, P<0.01, P=0.027; IL-6 in summer, P=0.028, P<0.01, P=0.024; IL-6 in winter, P=0.006, P<0.01, P=0.008). In the operation group, the serum levels of IL-1β and IL-6 in winter were higher than in summer, but with no statistically significant differences (P=0.844, 0.679). Compared with the normal group, the serum level of MT significantly increased in summer and winter in both the CIA model group (P=0.002, 0.008) and the sham-operation group (P=0.003, 0.007), while significantly decreased in the operation group (P=0.023, 0.003). There was no significant difference in MT level in the operation group between summer and winter (P=0.947). The increase of serum levels of IL-1β and IL-6 may exacerbate the inflammatory reaction and cause a more severe condition in the rheumatoid arthritis. The concentrations of IL-1β, IL-6, and MT correspond with the change of seasons, confirming that there are connections between nature and human body.

Occurrence of virulence-associated genes in Arcobacter butzleri and Arcobacter cryaerophilus isolates from foodstuff, water, and clinical samples within the Czech Republic.

PubMed

Šilha, David; Vacková, Barbora; Šilhová, Lucie

2018-06-24

Bacteria of the Arcobacter (A.) genus, originating mainly from food and water, are dreaded germs for humans as well as animals. However, the virulence of these bacteria has not been fully elucidated yet. This study looked at the occurrence of eight virulence-associated factors (ciaB, cj1349, pldA, irgA, hecA, tlyA, mviN, hecB) in a total of 80 isolates of Arcobacter butzleri and 22 isolates of A. cryaerophilus. The isolates were derived from food, water, and clinical samples. A polymerase chain reaction using specific primers was used to detect these virulence-associated genes. The presence of all genes in the isolates of A. butzleri (98.8% ciaB, 95.0% cj1349, 98.8% pldA, 22.5% irgA, 31.3% hecA, 95.0% tlyA, 97.5% mviN, 38.8% hecB) and A. cryaerophilus (95.5% ciaB, 0.0% cj1349, 9.1% pldA, 0.0% irgA, 0.0% hecA, 31.8% tlyA, 90.9% mviN, 0.0% hecB) was monitored. Among the tested isolates, there were 13 isolates (12.7%) of A. butzleri, in which the presence of all eight virulence-associated genes was recorded in the genome. In contrast, in one A. cryaerophilus strain, none of the observed genes were detected. The presence of ciaB and mviN genes was significantly more frequent in A. cryaerophilus isolates than other genes (P < 0.05). In general, more virulence-associated genes have been detected in A. butzleri isolates compared to A. cryaerophilus. The most common gene combination (ciaB, cj1349, pldA, tlyA, mviN) was detected in case of 39 isolates. In 50.0% of A. butzleri isolates derived from clinical samples, all eight virulence-associated genes were significantly more frequently detected (P < 0.05). The tlyA gene occurred significantly more frequent in A. butzleri isolates from meat and water samples and irgA and hecB genes in clinical samples. Therefore, our study provides information about occurrence of virulence-associated genes in genome of Arcobacter isolates. These findings could be hazardous to human health, because the presence of virulence-associated genes is the assumption for potential dangerousness of these bacteria. Our results indicate high incidence of virulence-associated genes in Arcobacter genomes and hence potentially pathogenic properties of the studied strains.

Soviet News and Propaganda Analysis Based on RED STAR (The Official Newspaper of the Soviet Defense Establishment) for the Period 1-30 April 1985. Volume 5, Number 4.

DTIC Science & Technology

1985-04-30

May. " The CIA is responsible for aiding Nazi war criminals to escape to South America. There are 40,000 Nazis that live in Paraguay, Argentina and...University professor). -20- fI -7 777 " Poverty in the United States and Western Europe. - West Germany has over 200,000 homeless people and 2.6 million...delegations from Warsaw Pact countries. The occasion for the event was the 40th anniversary of the Great Victory and the solidarity of socialist block

Tibet and Beyond: Magmatic Records from CIA (Caucasus-Iran-Anatolia) and Southern Tibet with Implications for Asian Orogeny and Continental Growth

NASA Astrophysics Data System (ADS)

Chung, Sun-Lin

2016-04-01

This study, based on an ongoing joint research project "Tibet and Beyond", presents a synthesis of principal magmatic records from the CIA (Caucasus-Iran-Anatolia) and Tibet-Himalaya orogens resulting from the continental collisions of Arabia and India, respectively, with Eurasia. In both orogens, through this and other recent studies, the temporal and spatial variations in magmatism pre-, syn- and post-dating the collisions can now be much better defined, thus improving our understanding of collision zone magmatism that appears to have evolved with changes in the lithospheric structures over time and space by collisional processes. The two "collisional" Tethyan orogens were preceded by accretionary orogenic processes, which not only had produced a substantial amount of juvenile continental crust but also fulfill the "orogenic cycle" that evolved from an accretionary into a collisional system. Geochemical data reveal that in contrast to generating vast portions of juvenile crust in the early, accretionary stages of orogenic development, crustal recycling plays a more important role in the later, collisional stages. The latter, as exemplified in SE Turkey and southern Tibet, involves addition of older continental crust material back into the mantle, which subsequently melted and caused compositional transformation of the juvenile crust produced in the accretionary stages. Similar features are observed in young volcanic rocks from eastern Taiwan, the northern Luzon arc complex and part of the active subduction/accretion/collision system in Southeast Asia that may evolve one day to resemble the eastern Tethyan and central Asian orogenic belts by collision with the advancing Australian continent.

T-614, a novel immunomodulator, attenuates joint inflammation and articular damage in collagen-induced arthritis

PubMed Central

Du, Fang; Lü, Liang-jing; Fu, Qiong; Dai, Min; Teng, Jia-lin; Fan, Wei; Chen, Shun-le; Ye, Ping; Shen, Nan; Huang, Xin-fang; Qian, Jie; Bao, Chun-de

2008-01-01

Introduction T-614 is a novel oral antirheumatic agent for the treatment of rheumatoid arthritis. Whether it has immunomodulatory or disease-modifying properties and its mechanism of action are largely undetermined. Methods Rats with collagen-induced arthritis (CIA) were treated with T-614 (5 and 20 mg/kg) daily. Animals receiving methotrexate (1 mg/kg every 3 days) and the nonsteroidal anti-inflammatory agent nimesulide (10 mg/kg per day) were used as controls. A combination therapy group was treated with both T-614(10 mg/kg per day) and methotrexate (1 mg/kg every 3 days). Hind paw swelling was evaluated and radiographic scores calculated. Serum cytokine levels were assessed by Bio-plex analysis. Quantitative PCR was used to evaluate expression of mRNA for interferon-γ, IL-4 and IL-17. Serum IL-17 and anti-type II collagen antibodies (total IgG, IgG1, IgG2a, IgG2b and IgM) were measured using ELISA. Results Oral T-614 inhibited paw swelling and offered significant protection against arthritis-induced cartilage and bone erosion, comparable to the effects of methotrexate. CIA rats treated with T-614 exhibited decreases in both mRNA expression of IL-17 in peripheral blood mononuclear cells and lymph node cells, and circulating IL-17 in a dose-dependent manner. T-614 also reduced serum levels of tumor necrosis factor-α, IL-1β and IL-6. A synergistic effect was observed for the combination of methotrexate and T-614. In addition, T-614 (20 mg/kg per day) depressed production of anti-type II collagen antibodies and differentially affected levels of IgG2a subclasses in vivo, whereas IgM level was decreased without any change in the IgG1 level. Together, the findings presented here indicate that the novel agent T-614 has disease-modifying effects against experimental arthritis, as opposed to nimesulide. Conclusions Our data suggested that T-614 is an effective disease-modifying agent that can prevent bone/cartilage destruction and inflammation in in CIA rats. Combination with methotrexate markedly enhances the therapeutic effect of T-614. PMID:19019215

Holocene vegetation and climatic variations in Central India: A study based on multiproxy evidences

NASA Astrophysics Data System (ADS)

Chauhan, M. S.; Sharma, Anupam; Phartiyal, Binita; Kumar, Kamlesh

2013-11-01

Palynology, texture, mineralogy, geochemistry, and magnetic susceptibility analysis of a 2 m deep sediment core from Padauna Swamp, southeastern Madhya Pradesh infers that between 8600 and 7500 cal yr BP a warm and relatively less-humid climate prevailed with open tree-savannahs dominated by grasses followed by sedges, Artemisia and members of Chenopodiaceae/Amaranthaceae with scanty trees viz., Schrebera, Aegle marmelos and Sterculia urens. This is well supported by lower organic to carbonate carbon ratio, coarser texture having relatively low CIA and magnetic susceptibility values and presence of some primary minerals. Between 7500 and 6250 cal yr BP the tree-savannahs were succeeded by open mixed deciduous forests with the invasion of a few more trees viz., Madhuca indica, Holoptelea, Emblica officinalis, Mitragyna parvifolia and members of Anacardiaceae in response to onset of a warm and humid climate. A considerable rise in organic carbon generated from the degradation of plentiful biomass along with increase in clay content with signs of kaolinite and increase in immobile over mobile elements with slightly higher CIA and magnetic susceptibility values also suggest climatic amelioration. The presence of ruderal plants such as Artemisia, Cannabis sativa and Cheno/Am further infers initiation of human activities in the region. Between 6250 and 2800 cal yr BP, the mixed deciduous forests became more diverse and dense, subduing grasses and other herbaceous elements. Sporadic incursion of Shorea robusta (Sal) in forest floristic was recorded around 5000 cal yr BP. The overall change in the vegetation mosaic reflects that a warm and more-humid climate prevailed in the region, probably on account of invigoration of southwest monsoon. This observation is further corroborated by other proxy data showing a spurt in organic/inorganic carbon ratio, increase in clay content with matured mineralogy, significantly higher CIA and magnetic susceptibility values. Since 2800 cal yr BP onwards, the modern Sal dominated deciduous forests were established indicating continuation of warm and more-humid climate including timely arrival of SW monsoon coinciding with the shedding of Sal seeds as they are viable for a very short period.

Ginsenoside Rc from Korean Red Ginseng (Panax ginseng C.A. Meyer) Attenuates Inflammatory Symptoms of Gastritis, Hepatitis and Arthritis.

PubMed

Yu, Tao; Rhee, Man Hee; Lee, Jongsung; Kim, Seung Hyung; Yang, Yanyan; Kim, Han Gyung; Kim, Yong; Kim, Chaekyun; Kwak, Yi-Seong; Kim, Jong-Hoon; Cho, Jae Youl

2016-01-01

Korean Red Ginseng (KRG) is an herbal medicine prescribed worldwide that is prepared from Panax ginseng C.A. Meyer (Araliaceae). Out of ginseng's various components, ginsenosides are regarded as the major ingredients, exhibiting anticancer and anti-inflammatory activities. Although recent studies have focused on understanding the anti-inflammatory activities of KRG, compounds that are major anti-inflammatory components, precisely how these can suppress various inflammatory processes has not been fully elucidated yet. In this study, we aimed to identify inhibitory saponins, to evaluate the in vivo efficacy of the saponins, and to understand the inhibitory mechanisms. To do this, we employed in vitro lipopolysaccharide-treated macrophages and in vivo inflammatory mouse conditions, such as collagen (type II)-induced arthritis (CIA), EtOH/HCl-induced gastritis, and lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-triggered hepatitis. Molecular mechanisms were also verified by real-time PCR, immunoblotting analysis, and reporter gene assays. Out of all the ginsenosides, ginsenoside Rc (G-Rc) showed the highest inhibitory activity against the expression of tumor necrosis factor (TNF)-[Formula: see text], interleukin (IL)-1[Formula: see text], and interferons (IFNs). Similarly, this compound attenuated inflammatory symptoms in CIA, EtOH/HCl-mediated gastritis, and LPS/D-galactosamine (D-GalN)-triggered hepatitis without altering toxicological parameters, and without inducing gastric irritation. These anti-inflammatory effects were accompanied by the suppression of TNF-[Formula: see text] and IL-6 production and the induction of anti-inflammatory cytokine IL-10 in mice with CIA. G-Rc also attenuated the increased levels of luciferase activity by IRF-3 and AP-1 but not NF-[Formula: see text]B. In support of this phenomenon, G-Rc reduced TBK1, IRF-3, and ATF2 phosphorylation in the joint and liver tissues of mice with hepatitis. Therefore, our results strongly suggest that G-Rc may be a major component of KRG with useful anti-inflammatory properties due to its suppression of IRF-3 and AP-1 pathways.

Cumulative therapeutic effects of phytochemicals in Arnica montana flower extract alleviated collagen-induced arthritis: inhibition of both pro-inflammatory mediators and oxidative stress.

PubMed

Sharma, Shikha; Arif, Mohammad; Nirala, Ranjeet Kumar; Gupta, Ritu; Thakur, Sonu Chand

2016-03-30

The plant Arnica montana is used in folk medicine to alleviate pain, inflammation and swelling of muscles and joints associated with rheumatoid arthritis and other inflammatory conditions. The present study aimed to investigate the therapeutic effects and mechanism of action of A. montana flower methanol extract (AMME) against both inflammation and oxidative stress in a collagen-induced arthritis (CIA) rat model. Oral administration of AMME was found to reduce clinical signs and improve the histological and radiological status of the hind limb joints. AMME-treated rats had lower expression levels of nitric oxide, tumor necrosis factor-α, interleukins (IL-1β, IL-6 and IL-12) and titer of anti-type II collagen antibody compared with untreated CIA rats. Furthermore, by inhibiting these mediators, AMME also contributed towards the reversal of disturbed antioxidant levels and peroxidative damage. The alleviation of arthritis in rats was very likely due to the combined action of phenolic and flavonoid compounds, the major constituents identified by gas chromatography/mass spectrometry (GC/MS) analysis. The study also shed some light on mechanisms involved in diminution of inflammatory mediators and free radical-generating toxicants and enhancement of the antioxidant armory, thereby preventing further tissue damage, injury and synovial hyperproliferation in arthritis. © 2015 Society of Chemical Industry.

A novel mutation in the CIAS1/NLRP3 gene associated with an unexpected phenotype of cryopyrin-associated periodic syndromes.

PubMed

Insalaco, Antonella; Prencipe, Giusi; Buonuomo, Paola Sabrina; Ceccherini, Isabella; Bracaglia, Claudia; Pardeo, Manuela; Nicolai, Rebecca; De Benedetti, Fabrizio

2014-01-01

Cryopyrin-associated periodic syndromes (CAPS) comprise a spectrum of distinct, rare, autosomal dominant autoinflammatory disorders of increasing severity caused by NLRP3 gene mutations. We describe a 13-year-old female who presented, in the initial phase of the disease, recurrent episodes of high fever, pericarditis, arthralgia, arthritis of the knees, abdominal pain and marked increase in inflammatory markers. In the subsequent months she developed recurrent episodes of chest pain, skin rash and swelling of the subcutaneous tissue, without fever, and with spontaneous resolution. Molecular analysis of the CIAS1 gene revealed the presence of the Q703K variant and also a c.1105C>A mutation in the heterozygous state, that predicts a L369M amino acid substitution. The latter variant has never been reported. The L369M mutation was predicted to significantly affect protein structure (scoring as 'dangerous' and 'deleterious') by the Variant Effect Predictor tool. Therapy with anakinra was started with rapid disappearance of clinical symptoms and normalization of CRP levels in 24 hours. The rapid response to IL-1 inhibition suggests that the disease of this patient is driven by IL-1 and supports the conclusion that this novel mutation is pathogenic and may be associated with a new CAPS phenotype. The role played by the concomitant presence of the mutation Q703K remains to be clarified.

Prophylactic and therapeutic treatment with a synthetic analogue of a parasitic worm product prevents experimental arthritis and inhibits IL-1β production via NRF2-mediated counter-regulation of the inflammasome.

PubMed

Rzepecka, Justyna; Pineda, Miguel A; Al-Riyami, Lamyaa; Rodgers, David T; Huggan, Judith K; Lumb, Felicity E; Khalaf, Abedawn I; Meakin, Paul J; Corbet, Marlene; Ashford, Michael L; Suckling, Colin J; Harnett, Margaret M; Harnett, William

2015-06-01

Rheumatoid arthritis (RA) remains a debilitating autoimmune condition as many patients are refractory to existing conventional and biologic therapies, and hence successful development of novel treatments remains a critical requirement. Towards this, we now describe a synthetic drug-like small molecule analogue, SMA-12b, of an immunomodulatory parasitic worm product, ES-62, which acts both prophylactically and therapeutically against collagen-induced arthritis (CIA) in mice. Mechanistic analysis revealed that SMA-12b modifies the expression of a number of inflammatory response genes, particularly those associated with the inflammasome in mouse bone marrow-derived macrophages and indeed IL-1β was the most down-regulated gene. Consistent with this, IL-1β was significantly reduced in the joints of mice with CIA treated with SMA-12b. SMA-12b also increased the expression of a number of genes associated with anti-oxidant responses that are controlled by the transcription factor NRF2 and critically, was unable to inhibit expression of IL-1β by macrophages derived from the bone marrow of NRF2(-/-) mice. Collectively, these data suggest that SMA-12b could provide the basis of an entirely novel approach to fulfilling the urgent need for new treatments for RA. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Mineralogy and geochemistry of the Mahi River sediments in tectonically active western India: Implications for Deccan large igneous province source, weathering and mobility of elements in a semi-arid climate

NASA Astrophysics Data System (ADS)

Sharma, Anupam; Sensarma, Sarajit; Kumar, Kamlesh; Khanna, P. P.; Saini, N. K.

2013-03-01

Large igneous provinces (LIPs) hosting mafic rocks over million km2 are likely to influence global sediment production and distribution and help in resolving discrepancies in upper continental crust (UCC) compositions. This work focuses on the texture, mineralogy, and compositions including REE of fine sand/silt deposited by a small to medium-sized river, the Mahi River (about 600 km) in a tectonically active, semi-arid region draining the Deccan Traps in western India, one of the largest LIPs in the world. The results are also applied to a sedimentary rock of fluvial origin (Siwalik mudstone/siltstone) to ascertain the source characteristics of this alluvium and evaluate comparative element (K, Ba, Sr, Na, Ca and Mg) mobility. The Mahi sediments are lithiarenite, mostly composed of quartz and basalt fragments with lesser pyroxene, biotite, feldspar, calcite and clay minerals (smectite ± illite). The Mahi sediments have higher FeOt (⩽10.9 wt.%), TiO2 (⩽2.41 wt.%), Al2O3 (⩽15.2 wt.%), Cr (⩽737 ppm), Co (⩽36 ppm), Cu (⩽107 ppm) than the UCC and PAAS; Ni (⩽54 ppm) higher than the UCC (33.5 ppm), but similar to PAAS (60 ppm). The low CIA (37-59) values and presence of basalt fragments and smectite in the samples suggest incipient weathering in the semi-arid Mahi catchment. In agreement with the mineralogy, the UCC-normalized LREE depleted patterns (LREE/HREE < 1) in the Mahi sediments confirm Deccan basalt contributions from the provenance with about 70-75% basalts and 25-30% Archean biotite-rich granitoids. The mafic contribution, in addition to the UCC, is important for the Siwalik rocks too. Similarly limited depletion of Ba, K and Ca (Ba ⩾ K > Ca) in weathering-limited Mahi (aver CIA 47.5) and transport-limited Siwalik (aver CIA 69) systems indicate their climate insensitivity. At the same time, more Ba depletion than Ca is new for the Deccan Traps River. Decoupling of Ca and Sr, however, could be mineralogy controlled.

Results From the VISIBILITY Iliac Study: Primary and Cohort Outcomes at 9 Months

PubMed Central

Rundback, John H.; Peeters, Patrick; George, Jon C.; Jaff, Michael R.; Faries, Peter L.

2017-01-01

Purpose: To evaluate the safety and effectiveness of primary stenting of the common (CIA) or external iliac artery (EIA) using the Visi-Pro Balloon-Expandable Peripheral Stent System for treatment of stenotic, restenotic, or occluded lesions. Methods: Between 2011 and 2012, 75 patients (mean age 64.2±8.9 years; 46 men) with Rutherford category 2–4 ischemia and atherosclerotic lesions ≤10 cm in length underwent iliac artery stenting at 17 centers in the United States and Europe. The primary outcome of the study was the major adverse event (MAE) rate at 9 months postprocedure [composite of periprocedural death, in-hospital myocardial infarction, clinically driven target lesion revascularization (CD-TLR), and amputation of the treated limb]. Secondary outcomes included 30-day MAE rate, 9-month primary patency, changes in ankle-brachial index (ABI) and the Walking Impairment Questionnaire at 30 days and 9 months postprocedure, device success, and clinically driven target vessel revascularization (CD-TVR) at 30 days and 9 months. Outcomes in specific patient cohorts (ie, gender, stent location, calcification severity, and lesion grade) were analyzed. Results: Eighty-one stents were implanted in 61 CIA and 15 EIA lesions (41 with moderate/severe calcification). The mean lesion treated length was 29.3±13.9 mm. All devices were successfully deployed. MAE occurred in 3 (4.0%) of 75 subjects at 9 months. Primary patency and freedom from CD-TVR at 9 months were both 95.8%. ABI improved from 0.67±0.14 at baseline to 0.94±0.14 and 0.96±0.16 at 30 days and 9-month follow-up, respectively (p<0.001 for both). There were no differences with respect to any of the analyzed patient characteristics, including gender. Conclusion: Nine-month results of the VISIBILITY Iliac stent study (ClinicalTrials.gov identifier NCT01402700) demonstrated safety and effectiveness for the treatment of atherosclerotic CIA and EIA lesions with the Visi-Pro stent across all treated cohorts. PMID:28351204

NWA 7034 Martian Breccia: Disturbed Rb-Sr Systematics, Preliminary Is Approximately 4.4 Ga Sm-Nd Age

NASA Technical Reports Server (NTRS)

Nyquist, L. E.; Shih, C.-Y.; Peng, Zhan Xiong; Agee, C

2013-01-01

Agee et al. [1] reported a Rb-Sr age of 2.089 [plus or minus] 0.081 Ga for the unique Martian meteoritic breccia NWA 7034 making it the oldest Martian basalt, dating to the early Am-azonian epoch [2] of Martian geologic history. We have attempt-ed to confirm this exciting result. Our new Rb-Sr analyses show the Rb-Sr isotopic system to be disturbed, but preliminary Sm-Nd data suggest an even older age of approximately 4.4 Ga for at least some brec-cia components.

32 CFR 1907.14 - Transmission.

Code of Federal Regulations, 2014 CFR

2014-07-01

... from the CIA as well as corporate or other federal agency security departments. Action on Challenges ... the holder transmit same in full accordance with established security procedures. In general...

32 CFR 1907.14 - Transmission.

Code of Federal Regulations, 2013 CFR

2013-07-01

... from the CIA as well as corporate or other federal agency security departments. Action on Challenges ... the holder transmit same in full accordance with established security procedures. In general...

32 CFR 1907.14 - Transmission.

Code of Federal Regulations, 2012 CFR

2012-07-01

... from the CIA as well as corporate or other federal agency security departments. Action on Challenges ... the holder transmit same in full accordance with established security procedures. In general...

32 CFR 1907.14 - Transmission.

Code of Federal Regulations, 2011 CFR

2011-07-01

... from the CIA as well as corporate or other federal agency security departments. Action on Challenges ... the holder transmit same in full accordance with established security procedures. In general...

32 CFR 1907.14 - Transmission.

Code of Federal Regulations, 2010 CFR

2010-07-01

... from the CIA as well as corporate or other federal agency security departments. Action on Challenges ... the holder transmit same in full accordance with established security procedures. In general...

A Zebrafish Larval Model to Assess Virulence of Porcine Streptococcus suis Strains.

PubMed

Zaccaria, Edoardo; Cao, Rui; Wells, Jerry M; van Baarlen, Peter

2016-01-01

Streptococcus suis is an encapsulated Gram-positive bacterium, and the leading cause of sepsis and meningitis in young pigs resulting in considerable economic losses in the porcine industry. It is also considered an emerging zoonotic agent. In the environment, both avirulent and virulent strains occur in pigs, and virulent strains appear to cause disease in both humans and pigs. There is a need for a convenient, reliable and standardized animal model to assess S. suis virulence. A zebrafish (Danio rerio) larvae infection model has several advantages, including transparency of larvae, low cost, ease of use and exemption from ethical legislation up to 6 days post fertilization, but has not been previously established as a model for S. suis. Microinjection of different porcine strains of S. suis in zebrafish larvae resulted in highly reproducible dose- and strain-dependent larval death, strongly correlating with presence of the S. suis capsule and to the original virulence of the strain in pigs. Additionally we compared the virulence of the two-component system mutant of ciaRH, which is attenuated for virulence in both mice and pigs in vivo. Infection of larvae with the ΔciaRH strain resulted in significantly higher survival rate compared to infection with the S10 wild-type strain. Our data demonstrate that zebrafish larvae are a rapid and reliable model to assess the virulence of clinical porcine S. suis isolates.

Characterisation of antimicrobial usage in cats and dogs attending UK primary care companion animal veterinary practices.

PubMed

Buckland, E L; O'Neill, D; Summers, J; Mateus, A; Church, D; Redmond, L; Brodbelt, D

2016-11-12

There is scant evidence describing antimicrobial (AM) usage in companion animal primary care veterinary practices in the UK. The use of AMs in dogs and cats was quantified using data extracted from 374 veterinary practices participating in VetCompass. The frequency and quantity of systemic antibiotic usage was described.Overall, 25 per cent of 963,463 dogs and 21 per cent of 594,812 cats seen at veterinary practices received at least one AM over a two-year period (2012-2014) and 42 per cent of these animals were given repeated AMs. The main agents used were aminopenicillin types and cephalosporins. Of the AM events, 60 per cent in dogs and 81 per cent in cats were AMs classified as critically important (CIAs) to human health by the World Health Organisation. CIAs of highest importance (fluoroquinolones, macrolides, third-generation cephalosporins) accounted for just over 6 per cent and 34 per cent of AMs in dogs and cats, respectively. The total quantity of AMs used within the study population was estimated to be 1473 kg for dogs and 58 kg for cats.This study has identified a high frequency of AM usage in companion animal practice and for certain agents classified as of critical importance in human medicine. The study highlights the usefulness of veterinary practice electronic health records for studying AM usage. British Veterinary Association.

A Zebrafish Larval Model to Assess Virulence of Porcine Streptococcus suis Strains

PubMed Central

Zaccaria, Edoardo; Cao, Rui; Wells, Jerry M.; van Baarlen, Peter

2016-01-01

Streptococcus suis is an encapsulated Gram-positive bacterium, and the leading cause of sepsis and meningitis in young pigs resulting in considerable economic losses in the porcine industry. It is also considered an emerging zoonotic agent. In the environment, both avirulent and virulent strains occur in pigs, and virulent strains appear to cause disease in both humans and pigs. There is a need for a convenient, reliable and standardized animal model to assess S. suis virulence. A zebrafish (Danio rerio) larvae infection model has several advantages, including transparency of larvae, low cost, ease of use and exemption from ethical legislation up to 6 days post fertilization, but has not been previously established as a model for S. suis. Microinjection of different porcine strains of S. suis in zebrafish larvae resulted in highly reproducible dose- and strain-dependent larval death, strongly correlating with presence of the S. suis capsule and to the original virulence of the strain in pigs. Additionally we compared the virulence of the two-component system mutant of ciaRH, which is attenuated for virulence in both mice and pigs in vivo. Infection of larvae with the ΔciaRH strain resulted in significantly higher survival rate compared to infection with the S10 wild-type strain. Our data demonstrate that zebrafish larvae are a rapid and reliable model to assess the virulence of clinical porcine S. suis isolates. PMID:26999052

New architectural paradigms for multi-petabyte distributed storage systems

NASA Technical Reports Server (NTRS)

Lee, Richard R.

1994-01-01

In the not too distant future, programs such as NASA's Earth Observing System, NSF/ARPA/NASA's Digital Libraries Initiative and Intelligence Community's (NSA, CIA, NRO, etc.) mass storage system upgrades will all require multi-petabyte (petabyte: 1015 bytes of bitfile data) (or larger) distributed storage solutions. None of these requirements, as currently defined, will meet their objectives utilizing either today's architectural paradigms or storage solutions. Radically new approaches will be required to not only store and manage veritable 'mountain ranges of data', but to make the cost of ownership affordable, much less practical in today's (and certainly the future's) austere budget environment! Within this paper we will explore new architectural paradigms and project systems performance benefits and dollars per petabyte of information stored. We will discuss essential 'top down' approaches to achieving an overall systems level performance capability sufficient to meet the challenges of these major programs.

Anatomical Features and Early Outcomes of Endovascular Repair of Abdominal Aortic Aneurysm from a Korean Multicenter Registry.

PubMed

Kwon, Hyunwook; Lee, Do Yun; Choi, Soo Jin Na; Park, Ki Hyuk; Min, Seung-Kee; Chang, Jeong-Hwan; Huh, Seung; Jeon, Yong Sun; Won, Jehwan; Byun, Seung Jae; Park, Sang Jun; Jang, Lee Chan; Kwon, Tae-Won

2015-09-01

To introduce a nation-based endovascular aneurysm repair (EVAR) registry in South Korea and to analyze the anatomical features and early clinical outcomes of abdominal aortic aneurysms (AAA) in patients who underwent EVAR. The Korean EVAR registry (KER) was a template-based online registry developed and established in 2009. The KER recruited 389 patients who underwent EVAR from 13 medical centers in South Korea from January 2010 to June 2010. We retrospectively reviewed the anatomic features and 30-day clinical outcomes. Initial deployment without open conversion was achieved in all cases and procedure-related 30-day mortality rate was 1.9%. Anatomic features showed the following variables: proximal aortic neck angle 48.8±25.7° (mean±standard deviation), vertical neck length 35.0±17.2 mm, aneurysmal sac diameter 57.2±14.2 mm, common iliac artery (CIA) involvement in 218 (56.3%) patients, and median right CIA length 34.9 mm. Two hundred and nineteen (56.3%) patients showed neck calcification, 98 patients (25.2%) had neck thrombus, and the inferior mesenteric arteries of 91 patients (23.4%) were occluded. Anatomical features of AAA in patients from the KER were characterized as having angulated proximal neck, tortuous iliac artery, and a higher rate of CIA involvement. Long-term follow-up and ongoing studies are required.

Therapeutic improvements expected in the near future for schizophrenia and schizoaffective disorder: an appraisal of phase III clinical trials of schizophrenia-targeted therapies as found in US and EU clinical trial registries.

PubMed

Garay, Ricardo P; Citrome, Leslie; Samalin, Ludovic; Liu, Chen-Chung; Thomsen, Morten S; Correll, Christoph U; Hameg, Ahcène; Llorca, Pierre-Michel

2016-01-01

In this review, the authors describe medications in phase III of clinical development for schizophrenia and schizoaffective disorder, and provide an opinion on how current treatment can be improved in the near future. Recent (post 2013) phase III clinical trials of schizophrenia-targeted therapies were found in US and EU clinical trial registries. Two hundred fifty-three trials were identified, that included 16 investigational compounds. The antipsychotics brexpiprazole and cariprazine have been approved in the US, and although both are dopamine D2 receptor partial agonists, they differ markedly in their pharmacodynamic profiles. Encenicline and valbenazine are first-in-class candidates for treatment of cognitive impairment associated with schizophrenia (CIAS) and tardive dyskinesia, respectively. Eleven add-on compounds were previously approved for other therapeutic indications and are for the most part being studied at academic medical centers and smaller pharmaceutical companies for negative symptoms and CIAS or for specific populations (comorbidities, antipsychotic-induced obesity). Promising new agents are emerging for schizophrenia and schizoaffective disorder. In addition to better-tolerated antipsychotics that treat positive symptoms, we could see the arrival of the first effective drug for negative symptoms and CIAS, which would strongly facilitate the ultimate goal of recovery in persons with schizophrenia.

Prognostic impact of the integration of volumetric quantification of the solid part of the tumor on 3DCT and FDG-PET imaging in clinical stage IA adenocarcinoma of the lung.

PubMed

Furumoto, Hideyuki; Shimada, Yoshihisa; Imai, Kentaro; Maehara, Sachio; Maeda, Junichi; Hagiwara, Masaru; Okano, Tetsuya; Masuno, Ryuhei; Kakihana, Masatoshi; Kajiwara, Naohiro; Ohira, Tatsuo; Ikeda, Norihiko

2018-07-01

The aim of this study was to conduct comparative analyses of the biological malignant potential of clinical stage IA adenocarcinoma using positron emission tomography/computed tomography (PET/CT), high-resolution CT (HRCT), and three-dimensional CT (3DCT). The predictive performance of these parameters was evaluated in terms of clinical outcomes and pathological invasiveness (positive lymphatic permeation, blood-vessel invasion, pleural invasion, and lymph-node metastasis). We enrolled 170 patients with c-IA adenocarcinoma who underwent PET/CT, HRCT, and 3D reconstruction of lung structures using the Synapse Vincent system (Fujifilm Corporation, Tokyo, Japan) followed by complete resection. Maximum standardized uptake values (SUV max ) of F 18 -fluorodeoxyglucose and the size and volume of the solid part of the tumor were quantified and analyzed in relation to surgical outcomes. Univariate analysis demonstrated that all the three parameters and whole-tumor volume were associated with unfavorable disease-free survival (DFS), while the volume of the solid part was the independent predictor on multivariate analysis (p < .001). The receiver operating characteristic curves for pathological invasiveness, determined using the variables dichotomized at each cut-off level (SUV max 2.4; solid-part size 1.23 cm; solid-part volume 779 mm 3 ), showed that all were significantly correlated with pathological invasiveness and prognosis, whereas the combination of SUV max and the solid-part volume was the most powerful predictor of survival and pathological invasiveness compared to any other parameters: the 4-year DFS and proportion of pathological invasiveness in patients with SUV max  > 2.4 and solid-part volume > 779 mm 3 versus those with SUV max  ≤ 2.4 or solid-part volume ≤779 mm 3 were 81.2% versus 98.3% (p < .001) and 84.3% versus 15.1% (p < .001), respectively. In c-IA adenocarcinoma, the volume of the solid part of the tumor was the independent predictor for unfavorable DFS, and the integration of the volume of the solid part and SUV max was highly beneficial for the prediction of survival and pathological invasiveness. Copyright © 2018 Elsevier B.V. All rights reserved.

More Declassified Evidence Implicates CIA Physicians in Unethical Research.

PubMed

Llanusa-Cestero, Renée

2017-01-01

In 2010, in an article in this journal, I argued that declassified documents implicated Central Intelligence Agency (CIA) physicians in the conduct of unethical research on enhanced interrogation using detainee subjects. The focus, then as now, is upon physicians at the Office of Medical Services (OMS). The 2010 article highlighted the heavily redacted "Draft OMS Guidelines on Medical and Psychological Support to Detainee Interrogations" (the Draft). This commentary focuses upon the recently declassified final version of that document revealing further culpable evidence of unethical human subject research. The commentary locates that unethical research in historical context and the development of the Nuremberg Code. The commentary also locates enhanced interrogation in contemporary political context and considers how to hold OMS physicians accountable for the conduct of unethical human research using detainee subjects.

Power Pattern Sensitivity to Calibration Errors and Mutual Coupling in Linear Arrays through Circular Interval Arithmetics

PubMed Central

Anselmi, Nicola; Salucci, Marco; Rocca, Paolo; Massa, Andrea

2016-01-01

The sensitivity to both calibration errors and mutual coupling effects of the power pattern radiated by a linear array is addressed. Starting from the knowledge of the nominal excitations of the array elements and the maximum uncertainty on their amplitudes, the bounds of the pattern deviations from the ideal one are analytically derived by exploiting the Circular Interval Analysis (CIA). A set of representative numerical results is reported and discussed to assess the effectiveness and the reliability of the proposed approach also in comparison with state-of-the-art methods and full-wave simulations. PMID:27258274

Temporary prophylactic intravascular balloon occlusion of the common iliac arteries before cesarean hysterectomy for controlling operative blood loss in abnormal placentation.

PubMed

Chou, Min Min; Kung, Hsiao Fan; Hwang, Jen I; Chen, Wei Chi; Tseng, Jenn Jhy

2015-10-01

The purpose of this study was to investigate the efficacy and safety of temporary prophylactic intravascular balloon occlusion of the common iliac arteries (CIA) before planned cesarean hysterectomy for controlling operative blood loss in abnormal placentation. A retrospective study of 13 pregnant women at risk for placenta accreta identified using sequential obstetric ultrasonography and magnetic resonance imaging from January 2007 to December 2009 was performed. Temporary prophylactic intravascular balloon catheterization of the bilateral CIA before cesarean hysterectomy was performed by interventional radiologists. The maximum duration of occlusion time of CIA must not exceed 60 minutes. The primary outcome for this study included estimated blood loss and secondary outcomes included the development of thromboembolism, disseminated intravascular coagulation and surgical complications. Among these 13 patients, the mean age of the patients was 32.8 ± 0.7 years (range 29-37 years). The mean gestational age at cesarean hysterectomy was 32.2 ± 0.9 weeks (range 28-36 weeks), and the mean intraoperative blood loss was 1902.3 ± 578.8 mL (range 500-8000 mL). Operative bleeding was controlled by conservative treatment without additional surgery in two cases. Importantly, two patients (15.8%) had severe complications possibly related to the interventional procedure. One patient was noted to have a popliteal artery thrombosis. A second patient had an external iliac artery thrombosis with 80-90% occlusion. Both patients required antithrombotic treatment without sequelae. With limited experience in this small series, we observed a statistically significant reduction in operative blood loss after the use of temporary prophylactic balloon occlusion of the CIA technique compared with historical controls of similar demographic characteristics previously published (1902.3 ± 578.8 mL, range 500-8000 mL vs. 4445.7 ± 996.48 mL, range 1040-15,000 mL, p = 0.0402). Additionally, two patients had arterial thrombosis. These preliminary findings are based on a small number of patients, and therefore further investigation is needed to determine the effectiveness and safety of this new technique. Copyright © 2015. Published by Elsevier B.V.

Provenance, Source Rock Characteristics And Paleoweathering Conditions Of The Nearshore Continental Sediments Off Pondicherry, South East Coast Of India

NASA Astrophysics Data System (ADS)

Natarajan, T.; Seshachalam, S.; Ponniah, J.; Varadhan, R.; M, S.

2008-05-01

Geochemical studies, comprising major elements and trace elements, including the Rare Earth Elements (REE), have been carried out on the modern sediments of inner continental shelf representing nearshore marine environments. Concentrations were normalized with Chondrite and PAAS show LREE enriched and flat HREE patterns with slight positive Eu anomaly which is due to the influence of feldspar rich source materials. The LREE enriched and flat HREE patterns with positive Eu anomaly have been considered as the typical character of post- Archaean Sediments. The La/Th ratio ranges from 1.66 to 8.84 with an average value of 4.09, which indicates a heterogenitic source for the sediments of the study area. The La-Th-Sc ternary plot suggests all the samples fall close to the field dominated by tonalite to granite and away from the basalt and komatiite compositions and appear to be derived from sources enriched in felsic components. The transition metal ratios such as Cr/V, Ni/CO and V/Ni indicate both Archaean and Post-Archaean nature to the sediments indicating that the sediments have been derived from heterogenitic sources. The ternary diagram plot of Th-Hf-Co and La-Th-Sc falls in the field of upper continental crust of post Archaean age. This clearly indicates the terrestrial source for the sediments from the nearby landmass. The data are slightly offset from the upper crustal composition away from the Hf apex. This is probably a result of Zircon concentration. Geochemical data have also helped in ascertaining the weathering trends. The Chemical Index of Alteration (CIA) has been used to quantify the degree of weathering. The calculated CIA values for sediments demonstrate both low CIA values of less than 50 percent (low silicate weathering) and intermediate CIA values (60-70 percent) indicating that the sediments are possibly the product of sedimentary and metasedimentary rocks that have undergone intermediate chemical weathering. On an A—CN—K diagram, the data fall closer to the trend parallel to Al2O3 (CaO*+Na2O) join, suggesting that the sediments represent weathered products from granite and charnockite.

32 CFR 1900.31 - Procedures for business information.

Code of Federal Regulations, 2014 CFR

2014-07-01

... AGENCY PUBLIC ACCESS TO CIA RECORDS UNDER THE FREEDOM OF INFORMATION ACT (FOIA) Additional Administrative... contended to be a trade secret or confidential commercial information; (C) Explain how the information is...

32 CFR 1900.31 - Procedures for business information.

Code of Federal Regulations, 2012 CFR

2012-07-01

... AGENCY PUBLIC ACCESS TO CIA RECORDS UNDER THE FREEDOM OF INFORMATION ACT (FOIA) Additional Administrative... contended to be a trade secret or confidential commercial information; (C) Explain how the information is...

Myostatin Promotes Interleukin-1β Expression in Rheumatoid Arthritis Synovial Fibroblasts through Inhibition of miR-21-5p.

PubMed

Hu, Sung-Lin; Chang, An-Chen; Huang, Chien-Chung; Tsai, Chun-Hao; Lin, Cheng-Chieh; Tang, Chih-Hsin

2017-01-01

Rheumatoid arthritis (RA) is characterized by the infiltration of a number of pro-inflammatory cytokines into synovial fluid and patients with RA often develop joint destruction and deficits in muscle mass. The growth factor myostatin is a key regulator linking muscle mass and bone structure. We sought to determine whether myostatin regulates rheumatoid synovial fibroblast activity and inflammation in RA. We found that levels of myostatin and interleukin (IL)-1β (a key pro-inflammatory cytokine in RA) in synovial fluid from RA patients were overexpressed and positively correlated. In in vitro investigations, we found that myostatin dose-dependently regulated IL-1β expression through the ERK, JNK, and AP-1 signal-transduction pathways. Computational analysis confirmed that miR-21-5p directly targets the expression of the 3' untranslated region (3' UTR) of IL-1β. Treatment of cells with myostatin inhibited miR-21-5p expression and miR-21-5p mimic prevented myostatin-induced enhancement of IL-1β expression, showing an inverse correlation between miR-21-5p and IL-1β expression during myostatin treatment. We also found significantly increased paw swelling in an animal model of collagen-induced arthritis (CIA), compared with controls; immunohistochemistry staining revealed substantially higher levels of myostatin and IL-1β expression in CIA tissue. Our evidence indicates that myostatin regulates IL-1β production. Thus, targeting myostatin may represent a potential therapeutic target for RA.

Access to medicines for chronic diseases in Brazil: a multidimensional approach.

PubMed

Oliveira, Maria Auxiliadora; Luiza, Vera Lucia; Tavares, Noemia Urruth Leão; Mengue, Sotero Serrate; Arrais, Paulo Sergio Dourado; Farias, Mareni Rocha; Pizzol, Tatiane da Silva Dal; Ramos, Luiz Roberto; Bertoldi, Andréa Dâmaso

2016-12-01

To analyze the access to medicines to treat non-communicable diseases in Brazil according to socioeconomic, demographic, and health-related factors, from a multidimensional perspective. Analysis of data from the National Survey on Access, Use and Promotion of Rational Use of Medicines (PNAUM), household survey, sampling plan by conglomerates with representativeness of the Brazilian population and large areas of the country, according to sex and age domains. Data collected in 2013-2014 with sample of adults (≥ 20 years) who reported having non-communicable diseases and medical indication for use of medicines (n = 12,725). We assessed the prevalence of access to medicines for self-reported non-communicable diseases, considering four dimensions: availability, geographic accessibility, acceptability, and affordability. We applied Pearson's Chi-square test to assess the statistical significance of the differences between strata, considering the level of significance of 5%. We found prevalence of 94.3%, 5.2%, and 0.5% for full, partial, and null access, respectively. Higher prevalence was observed among seniors in the South compared to the Northeast; for those who reported having one non-communicable disease compared to those who reported having two or more; for those who needed one medicine compared to those who needed three or more; and for those who self-assessed their health as good or very good. Geographic accessibility was similar in the Unified Health System and in the private pharmacies (72.0%). Total availability of medicines was 45.2% in the Unified Health System, 67.4% in the Popular Pharmacy Program, and 88.5% in private pharmacies. Acceptability was 92.5% in the Unified Health System, 97.8% in the Popular Pharmacy Program, and 98.7% in private pharmacies. As to affordability, 2.6% of the individuals failed to take the medicines they should in the 30-day period prior to the interview due to financial difficulty. Prevalence of full access to medicines for non-communicable diseases in Brazil is high and presents significant differences for age group, region of the country, number of non-communicable diseases, and for medicines prescribed and self-assessment of health. The major barriers to access to medicines were identified in the dimensions analyzed. Analisar o acesso a medicamentos para tratar doenças crônicas não transmissíveis no Brasil segundo fatores socioeconômicos, demográficos e de saúde, sob perspectiva multidimensional. Análise de dados da Pesquisa Nacional sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos (PNAUM), inquérito domiciliar, plano amostral por conglomerados com representatividade da população brasileira e grandes regiões do País, segundo domínios de sexo e idade. Dados coletados em 2013-2014 com amostra constituída por adultos (≥ 20 anos) que referiram ter doenças crônicas não transmissíveis e indicação médica para usar medicamentos (n = 12.725). Avaliou-se a prevalência de acesso aos medicamentos para doenças crônicas não transmissíveis autorreferidas, considerando quatro dimensões: disponibilidade, acessibilidade geográfica, aceitabilidade e capacidade aquisitiva. Aplicou-se teste Qui-quadrado de Pearson para avaliar a significância estatística das diferenças entre os estratos, considerando o nível de significância de 5%. Foram encontradas prevalências de 94,3%, 5,2% e 0,5% para acesso total, parcial e nulo, respectivamente. Maiores prevalências ocorreram entre os idosos, na região Sul comparada à região Nordeste; naqueles que referiram ter uma doença crônica não transmissível comparados aos que referiram ter duas ou mais; naqueles que precisavam de um medicamento comparados aos que precisavam de três ou mais; e naqueles que autoavaliaram sua saúde como boa ou muito boa. A acessibilidade geográfica foi semelhante no Sistema Único de Saúde e nas farmácias privadas (72,0%). A disponibilidade total de medicamentos foi de 45,2% no Sistema Único de Saúde, 67,4% no Programa Farmácia Popular e 88,5% nas farmácias privadas. A aceitabilidade foi de 92,5% no Sistema Único de Saúde, 97,8% no Programa Farmácia Popular e 98,7% nas farmácias privadas. Quanto à capacidade aquisitiva, 2,6% dos indivíduos não tomou os medicamentos que deveria nos 30 dias anteriores à entrevista devido à dificuldade financeira. A prevalência do acesso total aos medicamentos para doenças crônicas não transmissíveis no Brasil é alta e apresenta diferenças significativas por faixa etária, região do País, número de doenças crônicas não transmissíveis e de medicamentos prescritos e autoavaliação da saúde. Foram identificadas as principais barreiras ao acesso a medicamentos nas dimensões analisadas.

Cooking Up World-Class Training.

ERIC Educational Resources Information Center

Zemke, Ron

1997-01-01

The Culinary Institute of America (CIA), a training ground for aspiring chefs, is a sophisticated training organization that practices many philosophies and techniques, including team learning, training the whole cook, and training the trainer. (JOW)

Intelligence and arms control - a marriage of convenience

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

Hirschfeld, T.J.

1987-01-01

This book offers the first comprehensive look at how the vast US intelligence network enables negotiators to forge viable arms control agreements. The intelligence role in all three phases of the arms control process is discussed - from the design phase when reliable information is needed, to the execution phase when proposals are modified, to the maintenance phase when agreed-upon obligations begin to constrain adversary behavior and compliance becomes the key political issue. Contributors include: former CIA Director William E. Colby; Douglas George, Chief of the CIA's Control Intelligence Staff, Admiral Bobby R. Inman, former NSA Director; Hans Mark, formermore » Air Force Secretary and NSA administrator; Walt W. Rostow, National Security Adviser to President Johnson; and Paul Warnke, former Director of the Arms Control and Disarmament Agency and Chief Negotiator for SALT II.« less

Fracture and Collapse of Balloon-Expandable Stents in the Bilateral Common Iliac Arteries Due to Shiatsu Massage

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

Ichihashi, Shigeo, E-mail: shigeoichihashi@yahoo.co.jp; Higashiura, Wataru; Itoh, Hirofumi

2012-12-15

We report a case of stent fracture and collapse of balloon-expandable stents caused by shiatsu massage. A 76-year-old man presented with complaints of intermittent claudication of the right lower extremity. Stenoses of the bilateral common iliac arteries (CIAs) were detected. Balloon-expandable stents were deployed in both CIAs, resulting in resolution of symptoms. Five months later, pelvis x-ray showed collapse of both stents. Despite the stent collapse, the patient was asymptomatic, and his ankle brachial index values were within the normal range. Further history showed that the patient underwent daily shiatsu therapy in the umbilical region, which may have triggered collapsemore » of the stent. Physicians should advise patients to avoid compression of the abdominal wall after implantation of a stent in the iliac artery.« less

Hydroxyl Radical Modification of Collagen Type II Increases Its Arthritogenicity and Immunogenicity

PubMed Central

Shahab, Uzma; Ahmad, Saheem; Moinuddin; Dixit, Kiran; Habib, Safia; Alam, Khursheed; Ali, Asif

2012-01-01

Background The oxidation of proteins by endogenously generated free radicals causes structural modifications in the molecules that lead to generation of neo-antigenic epitopes that have implications in various autoimmune disorders, including rheumatoid arthritis (RA). Collagen induced arthritis (CIA) in rodents (rats and mice) is an accepted experimental model for RA. Methodology/Principal Findings Hydroxyl radicals were generated by the Fenton reaction. Collagen type II (CII) was modified by •OH radical (CII-OH) and analysed by ultraviolet-visible (UV-VIS), fluorescence and circular dichroism (CD) spectroscopy. The immunogenicity of native and modified CII was checked in female Lewis rats and specificity of the induced antibodies was ascertained by enzyme linked immunosorbent assay (ELISA). The extent of CIA was evaluated by visual inspection. We also estimated the oxidative and inflammatory markers in the sera of immunized rats. A slight change in the triple helical structure of CII as well as fragmentation was observed after hydroxyl radical modification. The modified CII was found to be highly arthritogenic and immunogenic as compared to the native form. The CII-OH immunized rats exhibited increased oxidative stress and inflammation as compared to the CII immunized rats in the control group. Conclusions/Significance Neo-antigenic epitopes were generated on •OH modified CII which rendered it highly immunogenic and arthritogenic as compared to the unmodified form. Since the rodent CIA model shares many features with human RA, these results illuminate the role of free radicals in human RA. PMID:22319617

Microsurgical Bypass Training Rat Model, Part 1: Technical Nuances of Exposure of the Aorta and Iliac Arteries.

PubMed

Tayebi Meybodi, Ali; Lawton, Michael T; Mokhtari, Pooneh; Yousef, Sonia; Gandhi, Sirin; Benet, Arnau

2017-11-01

Animal models using rodents are frequently used for practicing microvascular anastomosis-an essential technique in cerebrovascular surgery. However, safely and efficiently exposing rat's target vessels is technically difficult. Such difficulty may lead to excessive hemorrhage and shorten animal survival. This limits the ability to perform multiple anastomoses on a single animal and may increase the overall training time and costs. We report our model for microsurgical bypass training in rodents in 2 consecutive articles. In part 1, we describe the technical nuances for a safe and efficient exposure of the rat abdominal aorta and common iliac arteries (CIAs) for bypass. Over a 2-year period, 50 Sprague-Dawley rats underwent inhalant anesthesia for practicing microvascular anastomosis on the abdominal aorta and CIAs. Lessons learned regarding the technical nuances of vessel exposure were recorded. Several technical nuances were important for avoiding intraoperative bleeding and preventing animal demise while preparing an adequate length of vessels for bypass. The most relevant technical nuances include (1) generous subcutaneous dissection; (2) use of cotton swabs for the blunt dissection of the retroperitoneal fat; (3) combination of sharp and blunt dissection to isolate the aorta and iliac arteries from the accompanying veins; (4) proper control of the posterior branches of the aorta; and (5) efficient division and mobilization of the left renal pedicle. Applying the aforementioned technical nuances enables safe and efficient preparation of the rat abdominal aorta and CIAs for microvascular anastomosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Curcumin protects against collagen-induced arthritis via suppression of BAFF production.

PubMed

Huang, Gang; Xu, Zhizhen; Huang, Yan; Duan, Xiaojun; Gong, Wei; Zhang, Yan; Fan, Jishan; He, Fengtian

2013-04-01

The aim of the present study was to evaluate whether the anti-Rheumatoid arthritis (RA) effect of curcumin is associated with the regulation of B cell-activating factor belonging to the TNF family (BAFF) production. Collagen-induced arthritis (CIA) was induced in DBA/1 J mice by immunization with bovine type II collagen. To investigate the anti-arthritic effect of curcumin in the CIA model, mice were injected intraperitoneally with curcumin (50 mg/kg) on every other day either from day 1 or from day 28 after the first immunization. The clinical severity of arthritis was monitored. BAFF, interleukin-6 (IL-6) and interferon-γ (IFNγ) production in serum were measured. Furthermore, the effect of curcumin on IFNγ-induced BAFF expression and transcriptional activation in B lymphocytes was determined by qPCR, Western Blot, and luciferase assay. Finally, IFNγ related signal transducers and activators of transcription 1 (STAT1) signaling in B lymphocytes were studied using Western Blot. Curcumin dramatically attenuated the progression and severity of CIA in DBA/1 J mice, accompanied with decrease of BAFF production in serum and spleen cells as well as decrease of serum IFNγ and IL-6. Treatment of B lymphocytes with curcumin suppressed IFNγ-induced BAFF expression, STAT1 phosphorylation and nuclear translocation, suggesting that curcumin may repress IFNγ-induced BAFF expression via negatively interfering with STAT1 signaling. The results of the present study suggest that suppression of BAFF production may be a novel mechanism by which curcumin improves RA.

The DUF59 Family Gene AE7 Acts in the Cytosolic Iron-Sulfur Cluster Assembly Pathway to Maintain Nuclear Genome Integrity in Arabidopsis[C][W][OA

PubMed Central

Luo, Dexian; Bernard, Delphine G.; Balk, Janneke; Hai, Huang; Cui, Xiaofeng

2012-01-01

Eukaryotic organisms have evolved a set of strategies to safeguard genome integrity, but the underlying mechanisms remain poorly understood. Here, we report that ASYMMETRIC LEAVES1/2 ENHANCER7 (AE7), an Arabidopsis thaliana gene encoding a protein in the evolutionarily conserved Domain of Unknown Function 59 family, participates in the cytosolic iron-sulfur (Fe-S) cluster assembly (CIA) pathway to maintain genome integrity. The severe ae7-2 allele is embryo lethal, whereas plants with the weak ae7 (ae7-1) allele are viable but exhibit highly accumulated DNA damage that activates the DNA damage response to arrest the cell cycle. AE7 is part of a protein complex with CIA1, NAR1, and MET18, which are highly conserved in eukaryotes and are involved in the biogenesis of cytosolic and nuclear Fe-S proteins. ae7-1 plants have lower activities of the cytosolic [4Fe-4S] enzyme aconitase and the nuclear [4Fe-4S] enzyme DNA glycosylase ROS1. Additionally, mutations in the gene encoding the mitochondrial ATP binding cassette transporter ATM3/ABCB25, which is required for the activity of cytosolic Fe-S enzymes in Arabidopsis, also result in defective genome integrity similar to that of ae7-1. These results indicate that AE7 is a central member of the CIA pathway, linking plant mitochondria to nuclear genome integrity through assembly of Fe-S proteins. PMID:23104832

Vancomycin tolerance in clinical and laboratory Streptococcus pneumoniae isolates depends on reduced enzyme activity of the major LytA autolysin or cooperation between CiaH histidine kinase and capsular polysaccharide.

PubMed

Moscoso, Miriam; Domenech, Mirian; García, Ernesto

2010-08-01

Vancomycin is frequently added to standard therapy for pneumococcal meningitis. Although vancomycin-resistant Streptococcus pneumoniae strains have not been isolated, reports on the emergence of vancomycin-tolerant pneumococci are a cause of concern. To date, the molecular basis of vancomycin tolerance in S. pneumoniae is essentially unknown. We examined two vancomycin-tolerant clinical isolates, i.e. a purported autolysin negative (LytA(-)), serotype 23F isolate (strain S3) and the serotype 14 strain 'Tupelo', which is considered a paradigm of vancomycin tolerance. S3 was characterized here as carrying a frameshift mutation in the lytA gene encoding the main pneumococcal autolysin. The vancomycin tolerance of strain S3 was abolished by transformation to the autolysin-proficient phenotype. The original Tupelo strain was discovered to be a mixture: a strain showing a vancomycin-tolerant phenotype (Tupelo_VT) and a vancomycin-nontolerant strain (Tupelo_VNT). The two strains differed only in terms of a single mutation in the ciaH gene present in the VT strain. Most interestingly, although the vancomycin tolerance of Tupelo_VT could be overcome by increasing the LytA dosage upon transformation by a multicopy plasmid or by externally adding the autolysin, we show that vancomycin tolerance in S. pneumoniae requires the simultaneous presence of a mutated CiaH histidine kinase and capsular polysaccharide. © 2010 Blackwell Publishing Ltd.

Geochemistry of Selected Kaolins from Cameroon and Nigeria

NASA Astrophysics Data System (ADS)

Bukalo, Nenita N.; Ekosse, Georges-Ivo E.; Odiyo, John O.; Ogola, Jason S.

2017-12-01

The geochemical characteristics of selected kaolins from Cameroon and Nigeria are presented, with an attempt to elucidate on their possible industrial applications by comparing them to world-known kaolin deposits. Major oxides concentrations were subjected to factor analyses in interpreting their relationships. Geochemical indices, including chemical index of alteration (CIA), chemical index of weathering (CIW) and the index of compositional variability (ICV) were computed and plotted on binary and ternary diagrams to determine the intensity of weathering of the kaolins and discriminate their different source rock types. Kaolinite was the major phase, followed by quartz, illite and goethite as minor phases. Minerals in trace phases included smectite, anatase, muscovite, gibbsite, microcline, palygorskite and calcite. Mean abundances of major oxides in wt% were: SiO2 (56.96)>Al2O3 (24.09)>Fe2O3 (3.78)>TiO2 (1.53)> K2O (1.26)> MgO (0.27)>CaO (0.20)>Na2O (0.17)>P2O5 (0.05)>MnO (0.04). The CIW versus CIA and ICV versus CIA plots showed that most of the kaolins clearly depicted extreme silicate weathering. The current applications of kaolins from Cameroon and Nigeria include ceramics and manufacturing of bricks and tiles. Low MgO, CaO, Na2O, K2O and TiO2 further position the kaolins for pharmaceutics, cosmetics, rubber and plastic applications. Thus, the studied kaolins have the potential to contribute to improved economic development of these countries.

Disease modifying anti-rheumatic activity of the alkaloid montanine on experimental arthritis and fibroblast-like synoviocytes.

PubMed

Farinon, Mirian; Clarimundo, Vanessa S; Pedrazza, Graziele P R; Gulko, Pércio S; Zuanazzi, José A S; Xavier, Ricardo M; de Oliveira, Patricia G

2017-03-15

Montanine is an alkaloid isolated from Rhodophiala bifida bulb with potential anti-arthritic activity. In this context, we evaluated whether montanine has a disease modifying anti-rheumatic activity in two arthritis models and its effect in vitro on lymphocyte proliferation and on invasiveness of fibroblast-like synoviocytes (FLS). Antigen-induced arthritis (AIA) was performed in Balb/C mice with methylated bovine serum albumin, and nociception and leukocytes migration into the knee joint were evaluated. Collagen-induced arthritis (CIA) was performed in DBA/1J mice, and arthritis development and severity were assessed by clinical and histological scoring and articular nociception. Montanine was administered intraperitoneally twice a day. Lymphocyte proliferation stimulated by concanavalin A in 48h was performed with MTT assay, while FLS invasion in 24h was assayed in a Matrigel-coated transwell system. Administration of montanine decreased nociception (P<0.001) and leukocyte articular migration (P<0.001) in mice with AIA. In mice with CIA, treatment with montanine reduced severity of arthritis and joint damage assessed by clinical (P<0.001) and histological (P<0.05) scores and ameliorated articular nociception (P<0.05). In vitro, montanine inhibited lymphocyte proliferation stimulated with ConA (P<0.001) and decreased FLS invasion (P<0.05) by 54%, with an action independent of cytotoxicity. Our findings suggest that montanine can be further explored as an innovative pharmacological approach for autoimmune diseases such as arthritis. Copyright © 2017 Elsevier B.V. All rights reserved.

32 CFR 1806.3 - Procedures governing acceptance of service of process.

Code of Federal Regulations, 2011 CFR

2011-07-01

... physically located, process servers generally will not be allowed to enter CIA Headquarters for the purpose... sole discretion of the Director, NACIC, process servers will generally not be permitted to enter NACIC...

32 CFR 1900.33 - Allocation of resources; agreed extensions of time.

Code of Federal Regulations, 2011 CFR

2011-07-01

... INTELLIGENCE AGENCY PUBLIC ACCESS TO CIA RECORDS UNDER THE FREEDOM OF INFORMATION ACT (FOIA) Additional... Intelligence or otherwise by law, (3) The information review and release demands imposed by the Congress or...

32 CFR 1900.03 - Contact for general information and requests.

Code of Federal Regulations, 2011 CFR

2011-07-01

... INTELLIGENCE AGENCY PUBLIC ACCESS TO CIA RECORDS UNDER THE FREEDOM OF INFORMATION ACT (FOIA) General § 1900.03... communication in writing to the Information and Privacy Coordinator, Central Intelligence Agency, Washington, DC...

32 CFR 1900.03 - Contact for general information and requests.

Code of Federal Regulations, 2013 CFR

2013-07-01

... INTELLIGENCE AGENCY PUBLIC ACCESS TO CIA RECORDS UNDER THE FREEDOM OF INFORMATION ACT (FOIA) General § 1900.03... communication in writing to the Information and Privacy Coordinator, Central Intelligence Agency, Washington, DC...

32 CFR 1900.33 - Allocation of resources; agreed extensions of time.

Code of Federal Regulations, 2013 CFR

2013-07-01

... INTELLIGENCE AGENCY PUBLIC ACCESS TO CIA RECORDS UNDER THE FREEDOM OF INFORMATION ACT (FOIA) Additional... Intelligence or otherwise by law, (3) The information review and release demands imposed by the Congress or...

32 CFR 1900.22 - Action and determination(s) by originator(s) or any interested party.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Defense CENTRAL INTELLIGENCE AGENCY PUBLIC ACCESS TO CIA RECORDS UNDER THE FREEDOM OF INFORMATION ACT... confidential commercial information and personal information (about persons other than the requester). (b...

76 FR 59031 - Classification Challenge Regulations

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-23

... CENTRAL INTELLIGENCE AGENCY 32 CFR Part 1907 Classification Challenge Regulations AGENCY: Central Intelligence Agency. ACTION: Final rule. SUMMARY: Consistent with Executive Order 13526, the Central Intelligence Agency (CIA) has undertaken and completed a review of its public Classification Challenge...

32 CFR 1907.02 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY CHALLENGES TO... means the United States Central Intelligence Agency acting through the CIA Information and Privacy... Agency Release Panel; (g) Information means any knowledge that can be communicated or documentary...

32 CFR 1907.02 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY CHALLENGES TO... means the United States Central Intelligence Agency acting through the CIA Information and Privacy... Agency Release Panel; (g) Information means any knowledge that can be communicated or documentary...

32 CFR 1907.02 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY CHALLENGES TO... means the United States Central Intelligence Agency acting through the CIA Information and Privacy... Agency Release Panel; (g) Information means any knowledge that can be communicated or documentary...

CCSD(T) potential energy and induced dipole surfaces for N2–H2(D2): retrieval of the collision-induced absorption integrated intensities in the regions of the fundamental and first overtone vibrational transitions.

PubMed

Buryak, Ilya; Lokshtanov, Sergei; Vigasin, Andrey

2012-09-21

The present work aims at ab initio characterization of the integrated intensity temperature variation of collision-induced absorption (CIA) in N(2)-H(2)(D(2)). Global fits of potential energy surface (PES) and induced dipole moment surface (IDS) were made on the basis of CCSD(T) (coupled cluster with single and double and perturbative triple excitations) calculations with aug-cc-pV(T,Q)Z basis sets. Basis set superposition error correction and extrapolation to complete basis set (CBS) limit techniques were applied to both energy and dipole moment. Classical second cross virial coefficient calculations accounting for the first quantum correction were employed to prove the quality of the obtained PES. The CIA temperature dependence was found in satisfactory agreement with available experimental data.

In-Q-Tel, the strategic investment firm for the U.S. Intelligence Community

NASA Astrophysics Data System (ADS)

Ulvick, S. J.; Tighe, D. W.

2008-04-01

In-Q-Tel is a strategic investment firm that works to identify, adapt, and deliver innovative technology solutions to support the missions of the Central Intelligence Agency and the broader U.S. Intelligence Community (IC). Launched by the CIA in 1999 as a private, independent, not-for-profit organization, IQT's mission is to identify and partner with companies developing cutting-edge technologies that serve the national security interests of the United States. Working from an evolving strategic blueprint defining the Intelligence Community's critical technology needs, IQT engages with entrepreneurs, growth companies, researchers, and venture capitalists to deliver technologies that provide superior capabilities for the CIA and the broader IC. To date, IQT has reviewed more than 6,300 business proposals, invested in more than 100 companies, and delivered more than 140 technology solutions to the U.S. Intelligence Community.

Solid oxide fuel cell with multi-unit construction and prismatic design

DOEpatents

McPheeters, Charles C.; Dees, Dennis W.; Myles, Kevin M.

1999-01-01

A single cell unit of a solid oxide fuel cell that is individually fabricated and sintered prior to being connected to adjacent cells to form a solid oxide fuel cell. The single cell unit is comprised of a shaped anode sheet positioned between a flat anode sheet and an anode-electrolyte-cathode (A/E/C) sheet, and a shaped cathode sheet positioned between the A/E/C sheet and a cathode-interconnect-anode (C/I/A) sheet. An alternate embodiment comprises a shaped cathode sheet positioned between an A/E/C sheet and a C/I/A sheet. The shaped sheets form channels for conducting reactant gases. Each single cell unit is individually sintered to form a finished sub-assembly. The finished sub-assemblies are connected in electrical series by interposing connective material between the end surfaces of adjacent cells, whereby individual cells may be inspected for defects and interchanged with non-defective single cell units.

Adoptive Cell Therapy of Induced Regulatory T Cells Expanded by Tolerogenic Dendritic Cells on Murine Autoimmune Arthritis.

PubMed

Yang, Jie; Liu, Lidong; Yang, Yiming; Kong, Ning; Jiang, Xueyu; Sun, Juan; Xie, Rufeng

2017-01-01

Tolerogenic dendritic cells (tDCs) can expand TGF- β -induced regulatory T cells (iTregs); however, the therapeutic utility of these expanded iTregs in autoimmune diseases remains unknown. We sought to determine the properties of iTregs expanded by mature tolerogenic dendritic cells (iTreg mtDC ) in vitro and explore their potential to ameliorate collagen-induced arthritis (CIA) in a mouse model. After induction by TGF- β and expansion by mature tDCs (mtDCs), the phenotype and proliferation of iTreg mtDC were assessed by flow cytometry. The ability of iTregs and iTreg mtDC to inhibit CD4 + T cell proliferation and suppress Th17 cell differentiation was compared. Following adoptive transfer of iTregs and iTreg mtDC to mice with CIA, the clinical and histopathologic scores, serum levels of IFN- γ , TNF- α , IL-17, IL-6, IL-10, TGF- β and anti-CII antibodies, and the distribution of the CD4 + Th subset were assessed. Compared with iTregs, iTreg mtDC expressed higher levels of Foxp3 and suppressed CD4 + T cell proliferation and Th17 cell differentiation to a greater extent. In vivo, iTreg mtDC reduced the severity and progression of CIA more significantly than iTregs, which was associated with a modulated inflammatory cytokine profile, reduced anti-CII IgG levels, and polarized Treg/Th17 balance. This study highlights the potential therapeutic utility of iTreg mtDC in autoimmune arthritis and should facilitate the future design of iTreg immunotherapeutic strategies.

Adoptive Cell Therapy of Induced Regulatory T Cells Expanded by Tolerogenic Dendritic Cells on Murine Autoimmune Arthritis

PubMed Central

Liu, Lidong; Kong, Ning; Jiang, Xueyu; Sun, Juan; Xie, Rufeng

2017-01-01

Objective Tolerogenic dendritic cells (tDCs) can expand TGF-β-induced regulatory T cells (iTregs); however, the therapeutic utility of these expanded iTregs in autoimmune diseases remains unknown. We sought to determine the properties of iTregs expanded by mature tolerogenic dendritic cells (iTregmtDC) in vitro and explore their potential to ameliorate collagen-induced arthritis (CIA) in a mouse model. Methods After induction by TGF-β and expansion by mature tDCs (mtDCs), the phenotype and proliferation of iTregmtDC were assessed by flow cytometry. The ability of iTregs and iTregmtDC to inhibit CD4+ T cell proliferation and suppress Th17 cell differentiation was compared. Following adoptive transfer of iTregs and iTregmtDC to mice with CIA, the clinical and histopathologic scores, serum levels of IFN-γ, TNF-α, IL-17, IL-6, IL-10, TGF-β and anti-CII antibodies, and the distribution of the CD4+ Th subset were assessed. Results Compared with iTregs, iTregmtDC expressed higher levels of Foxp3 and suppressed CD4+ T cell proliferation and Th17 cell differentiation to a greater extent. In vivo, iTregmtDC reduced the severity and progression of CIA more significantly than iTregs, which was associated with a modulated inflammatory cytokine profile, reduced anti-CII IgG levels, and polarized Treg/Th17 balance. Conclusion This study highlights the potential therapeutic utility of iTregmtDC in autoimmune arthritis and should facilitate the future design of iTreg immunotherapeutic strategies. PMID:28702462

Epigenetic role for the conserved Fe-S cluster biogenesis protein AtDRE2 in Arabidopsis thaliana.

PubMed

Buzas, Diana Mihaela; Nakamura, Miyuki; Kinoshita, Tetsu

2014-09-16

On fertilization in Arabidopsis thaliana, one maternal gamete, the central cell, forms a placenta-like tissue, the endosperm. The DNA glycosylase DEMETER (DME) excises 5-methylcytosine via the base excision repair pathway in the central cell before fertilization, creating patterns of asymmetric DNA methylation and maternal gene expression across DNA replications in the endosperm lineage (EDL). Active DNA demethylation in the central cell is essential for transcriptional activity in the EDL of a set of genes, including FLOWERING WAGENINGEN (FWA). A DME-binding motif for iron-sulfur (Fe-S) cluster cofactors is indispensable for its catalytic activity. We used an FWA-GFP reporter to find mutants defective in maternal activation of FWA-GFP in the EDL, and isolated an allele of the yeast Dre2/human antiapoptotic factor CIAPIN1 homolog, encoding an enzyme previously implicated in the cytosolic Fe-S biogenesis pathway (CIA), which we named atdre2-2. We found that AtDRE2 acts in the central cell to regulate genes maternally activated in the EDL by DME. Furthermore, the FWA-GFP expression defect in atdre2-2 was partially suppressed genetically by a mutation in the maintenance DNA methyltransferase MET1; the DNA methylation levels at four DME targets increased in atdre2-2 seeds relative to WT. Although atdre2-2 shares zygotic seed defects with CIA mutants, it also uniquely manifests dme phenotypic hallmarks. These results demonstrate a previously unidentified epigenetic function of AtDRE2 that may be separate from the CIA pathway.

32 CFR 1907.02 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY CHALLENGES TO... means the United States Central Intelligence Agency acting through the CIA Information and Privacy... specifically authorized by the Central Intelligence Agency to possess and use on official business classified...

Flexibility in Management of Modernization in Construction - Electrical Works/ Elastyczność W Zarządzaniu Modernizacją Obiektów Budowlanych Na Przykładzie Robót Elektrycznych

NASA Astrophysics Data System (ADS)

Nowotarski, Piotr; Pasławski, Jerzy

2015-06-01

The article presents the general principles of flexible approach, illustrated with case study regarding flexibility in modernization. Flexibility is understood in the present case as a skilful adaptation to changes in the dynamically changing environment. The essence of flexibility approach is being staged to make decisions based on environmental and process monitoring in progress. Presented case study of upgrading the electrical system in the multi-family housing in the common area is based on step by step procedure responding to damage state of this system. Simple analysis is based on cost comparison but there are other criteria (environmental, social etc.) and conflict solving situations taken into account in presented paper. Artykuł prezentuje możliwość zastosowania elastyczności w modernizacjach istniejących obiektów budowlanych na przykładzie instalacji oświetleniowej. Elastyczność jest rozumiana w tym przypadku jako umiejętne dostosowanie się do zmian w dynamicznie zmieniającym się środowisku. Istotą podejścia elastycznego jest podejmowanie odpowiednich decyzji w odpowiednim czasie opartych na monitoringu środowiska i procesu w toku. Prezentowane studium przypadku modernizacji instalacji elektrycznej w budownictwie wielorodzinnym w częściach wspólnych obiektu (korytarze, klatki schodowe, hala garażowa) opiera się na wymianie i modernizacji tylko tych punktów, które w danym momencie ulegają awarii. Prosta analiza oby typów modernizacji opiera się na porównaniu kosztów, natomiast trzeba zaznaczyć, że możliwe są także inne kryteria (środowiskowe, konfliktu społecznego, itp.), które będą przedmiotem kolejnych publikacji. Zastąpienie tradycyjnych żarówek rozwiązaniami opartymi na technologii LED z zastosowaniem czujników ruchu może prowadzić do znacznych oszczędności, ale może też oznaczać obniżenie komfortu dla użytkowników (np. dla osób starszych, którym jeden cykl działania oświetlenia nie jest wystarczający do pokonania całej drogi na korytarzu). Osiągnięcie kompromisu w tego typu konfliktach interesów może być rozwiązane za pomocą podejścia elastycznego i zwinnego.

76 FR 59032 - Mandatory Declassification Review

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-23

... CENTRAL INTELLIGENCE AGENCY 32 CFR Part 1908 Mandatory Declassification Review AGENCY: Central... Central Intelligence Agency (CIA) has undertaken and completed a review of its public Mandatory Declassification Review (MDR) regulations that govern certain aspects of its processing of MDR requests. As a...

76 FR 59071 - Freedom of Information Act Regulations

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-23

... CENTRAL INTELLIGENCE AGENCY 32 CFR Part 1900 Freedom of Information Act Regulations AGENCY: Central Intelligence Agency. ACTION: Proposed rule. SUMMARY: Consistent with the Freedom of Information...,'' and Executive Orders 13526 and 13392, the Central Intelligence Agency (CIA) has undertaken and...

Forward Deployment of U.S. Naval Forces to Australia

DTIC Science & Technology

2007-12-14

and commentary, not only mass media products but also periodic reports governmental and other organizations focused on international relations, are......professor and former CIA psychologist Jerrold Post, “has the core characteristics of the most dangerous personality disorder, malignant narcissism

32 CFR 1910.1 - General.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY DEBARMENT AND SUSPENSION PROCEDURES § 1910.1 General. The Central Intelligence Agency (CIA), in accordance with its authorities under the Central Intelligence Agency Act of 1949, as amended, and the National Security Act of 1947, as...

32 CFR 1904.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY PROCEDURES GOVERNING ACCEPTANCE OF SERVICE OF PROCESS § 1904.2 Definitions. (a) Agency or CIA means the Central Intelligence Agency and include all staff elements of the Director of Central Intelligence. (b) Process means a...

32 CFR 1904.2 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY PROCEDURES GOVERNING ACCEPTANCE OF SERVICE OF PROCESS § 1904.2 Definitions. (a) Agency or CIA means the Central Intelligence Agency and include all staff elements of the Director of Central Intelligence. (b) Process means a...

32 CFR 1904.2 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY PROCEDURES GOVERNING ACCEPTANCE OF SERVICE OF PROCESS § 1904.2 Definitions. (a) Agency or CIA means the Central Intelligence Agency and include all staff elements of the Director of Central Intelligence. (b) Process means a...

32 CFR 1904.2 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY PROCEDURES GOVERNING ACCEPTANCE OF SERVICE OF PROCESS § 1904.2 Definitions. (a) Agency or CIA means the Central Intelligence Agency and include all staff elements of the Director of Central Intelligence. (b) Process means a...

32 CFR 1904.2 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY PROCEDURES GOVERNING ACCEPTANCE OF SERVICE OF PROCESS § 1904.2 Definitions. (a) Agency or CIA means the Central Intelligence Agency and include all staff elements of the Director of Central Intelligence. (b) Process means a...

32 CFR 1910.1 - General.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY DEBARMENT AND SUSPENSION PROCEDURES § 1910.1 General. The Central Intelligence Agency (CIA), in accordance with its authorities under the Central Intelligence Agency Act of 1949, as amended, and the National Security Act of 1947, as...

32 CFR 1910.1 - General.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY DEBARMENT AND SUSPENSION PROCEDURES § 1910.1 General. The Central Intelligence Agency (CIA), in accordance with its authorities under the Central Intelligence Agency Act of 1949, as amended, and the National Security Act of 1947, as...

32 CFR 1910.1 - General.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY DEBARMENT AND SUSPENSION PROCEDURES § 1910.1 General. The Central Intelligence Agency (CIA), in accordance with its authorities under the Central Intelligence Agency Act of 1949, as amended, and the National Security Act of 1947, as...

32 CFR 1910.1 - General.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY DEBARMENT AND SUSPENSION PROCEDURES § 1910.1 General. The Central Intelligence Agency (CIA), in accordance with its authorities under the Central Intelligence Agency Act of 1949, as amended, and the National Security Act of 1947, as...

Joint Transformation and the Decision to Use Force

DTIC Science & Technology

2007-03-09

and visitors necessary for detecting terrorists. Business interests would oppose the cost increases associated with restricting the international...Channels: The Inteligence Community; Drug Plant Attack on Target, Says CIA Chief,” The Washington Post, 21 October 1999 [database on-line]; available from

Of Bushwahckers, Termites and Moles.

ERIC Educational Resources Information Center

Smelter, Richard W.

2003-01-01

Retired school administrator describes five types of school personnel that make an administrator's job difficult: Bushwackers, termites, CIA moles, rumor-mill addicts, and sartorial slobs. For example, termites are staff members who purposely volunteer for committees so they can sabotage the group's efforts from within. (PKP)

32 CFR 1909.02 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

...” means the Agency official responsible for the management of the CIA's various historical programs including the management of access granted under this section; (g) Director of Personnel Security means the... any knowledge that can be communicated or documentary material, regardless of its physical form that...

Economic Motives Behind the 2011 Egyptian Revolution

DTIC Science & Technology

2014-09-01

23 Figure 3. Poverty Headcount Ratio at $2 a day (PPP) (% of population) (from The World Bank, 2013...2013). .................................................................................................28 Figure 5. Similarity of World Food Price...Rate Annually, 2000‒2012.......................................................30 Figure 7. Egypt’s Population Growth since 2000 (from CIA World

Differentiated all-trans retinoic acid response of naive CD4+CD25– cells isolated from rats with collagen-induced arthritis and healthy ones under in vitro conditions

PubMed Central

Żyromska, Edyta; Piasecki, Tomasz; Rossowska, Joanna; Kędzierska, Anna; Nowak, Marcin; Żyromski, Marcin; Chełmońska-Soyta, Anna

2017-01-01

Aim o the study To compare the potential of CD4+CD25– cells, isolated from both healthy rats and rats with CIA (Collagen-Induced Arthritis), for differentiation into regulatory T cells in the presence of all-trans retinoic acid in order to learn more about the activation mechanisms and therapeutic potential of regulatory T cells. Material and methods Sorted CD4+CD25– cells were cultured in vitro with/without ATRA, and then the frequency of regulatory T cells and their ability to secrete IL-10 by CD4+ FOXP3+ cells was examined. Gene expression of the foxp3, rarα, rarβ, rxrβ, and ppar β/δ and protein expression of the Rarα, Rarβ, and Rxrβ in cells after stimulation with ATRA were also investigated. Results CD4+CD25– cells isolated from healthy animals or from animals with CIA are characterised by different potential of the differentiation into CD4+CD25+ FOXP3+ cells. Retinoic acid receptor Rxrβ is present in the CD4+CD25– cells isolated from rats with CIA. Conclusions We showed that although ATRA did not increase the frequency of Treg in culture, it significantly increased expression of rarβ and rxrβ only in lymphocytes taken from diseased animals and foxp3 expression only in healthy animals. Moreover, after ATRA stimulation, the frequency of Treg-produced IL-10 tended to be lower in diseased animals than in the healthy group. The results imply that the potential of naïve cell CD4 lymphocytes to differentiate into Tregs and their putative suppressive function is dependent on the donor’s health status. PMID:28680330

Establishing a sample-to cut-off ratio for lab-diagnosis of hepatitis C virus in Indian context.

PubMed

Tiwari, Aseem K; Pandey, Prashant K; Negi, Avinash; Bagga, Ruchika; Shanker, Ajay; Baveja, Usha; Vimarsh, Raina; Bhargava, Richa; Dara, Ravi C; Rawat, Ganesh

2015-01-01

Lab-diagnosis of hepatitis C virus (HCV) is based on detecting specific antibodies by enzyme immuno-assay (EIA) or chemiluminescence immuno-assay (CIA). Center for Disease Control reported that signal-to-cut-off (s/co) ratios in anti-HCV antibody tests like EIA/CIA can be used to predict the probable result of supplemental test; above a certain s/co value it is most likely to be true-HCV positive result and below that certain s/co it is most likely to be false-positive result. A prospective study was undertaken in patients in tertiary care setting for establishing this "certain" s/co value. The study was carried out in consecutive patients requiring HCV testing for screening/diagnosis and medical management. These samples were tested for anti-HCV on CIA (VITROS(®) Anti-HCV assay, Ortho-Clinical Diagnostics, New Jersey) for calculating s/co value. The supplemental nucleic acid test used was polymerase chain reaction (PCR) (Abbott). PCR test results were used to define true negatives, false negatives, true positives, and false positives. Performance of different putative s/co ratios versus PCR was measured using sensitivity, specificity, positive predictive value and negative predictive value and most appropriate s/co was considered on basis of highest specificity at sensitivity of at least 95%. An s/co ratio of ≥6 worked out to be over 95% sensitive and almost 92% specific in 438 consecutive patient samples tested. The s/co ratio of six can be used for lab-diagnosis of HCV infection; those with s/co higher than six can be diagnosed to have HCV infection without any need for supplemental assays.

Sotatercept (ACE-011) for the treatment of chemotherapy-induced anemia in patients with metastatic breast cancer or advanced or metastatic solid tumors treated with platinum-based chemotherapeutic regimens: results from two phase 2 studies.

PubMed

Raftopoulos, Haralambos; Laadem, Abderrahmane; Hesketh, Paul J; Goldschmidt, Jerome; Gabrail, Nashat; Osborne, Cynthia; Ali, Muhammad; Sherman, Matthew L; Wang, Ding; Glaspy, John A; Puccio-Pick, Marie; Zou, Jun; Crawford, Jeffrey

2016-04-01

Sotatercept may represent a novel approach to the treatment of chemotherapy-induced anemia (CIA). We report the results from two phase 2 randomized studies examining the use of sotatercept for the treatment of CIA in patients with metastatic cancer. In study A011-08, patients with metastatic breast cancer were randomized to 2:2:2:1 to receive sotatercept 0.1, 0.3, or 0.5 mg/kg, or placebo, respectively, every 28 days. In study ACE-011-NSCL-001, patients with solid tumors treated with platinum-based chemotherapy received sotatercept 15 or 30 mg every 42 days. The primary endpoint for both studies was hematopoietic response, defined as a hemoglobin (Hb) increase of ≥1 g/dL from baseline. Both studies were terminated early due to slow patient accrual. Among patients treated with sotatercept in the A011-08 and ACE-011-NSCL-001 studies, more patients achieved a mean Hb increase of ≥1 g/dL in the combined sotatercept 0.3 mg/kg and 15 mg (66.7 %) group and sotatercept 0.5 mg/kg and 30 mg (38.9 %) group versus the sotatercept 0.1 mg/kg (0 %) group. No patients achieved a mean Hb increase of ≥1 g/dL in the placebo group. The incidence of treatment-related adverse events (AEs) was low in both studies, and treatment discontinuations due to AEs were uncommon. Although both studies were terminated early, these results indicate that sotatercept is active and has an acceptable safety profile in the treatment of CIA.

Results of scalp cooling during anthracycline containing chemotherapy depend on scalp skin temperature.

PubMed

Komen, M M C; Smorenburg, C H; Nortier, J W R; van der Ploeg, T; van den Hurk, C J G; van der Hoeven, J J M

2016-12-01

The success of scalp cooling in preventing or reducing chemotherapy induced alopecia (CIA) is highly variable between patients undergoing similar chemotherapy regimens. A decrease of the scalp skin temperature seems to be an important factor, but data on the optimum temperature reached by scalp cooling to prevent CIA are lacking. This study investigated the relation between scalp skin temperature and its efficacy to prevent CIA. In this explorative study, scalp skin temperature was measured during scalp cooling in 62 breast cancer patients undergoing up to six cycles of anthracycline containing chemotherapy. Scalp skin temperature was measured by using two thermocouples at both temporal sides of the head. The primary end-point was the need for a wig or other head covering. Maximal cooling was reached after 45 min and was continued for 90 min after chemotherapy infusion. The scalp skin temperature after 45 min cooling varied from 10 °C to 31 °C, resulting in a mean scalp skin temperature of 19 °C (SEM: 0,4). Intrapersonal scalp skin temperatures during cooling were consistent for each chemotherapy cycle (ANOVA: P = 0,855). Thirteen out of 62 patients (21%) did not require a wig or other head covering. They appeared to have a significantly lower mean scalp skin temperature (18 °C; SEM: 0,7) compared to patients with alopecia (20 °C; SEM: 0,5) (P = 0,01). The efficacy of scalp cooling during chemotherapy is temperature dependent. A precise cut-off point could not be detected, but the best results seem to be obtained when the scalp temperature decreases below 18 °C. TRIALREGISTER. 3082. Copyright © 2016 Elsevier Ltd. All rights reserved.

Incidence and predictive factors of Internet addiction among Chinese secondary school students in Hong Kong: a longitudinal study.

PubMed

Lau, Joseph T F; Gross, Danielle L; Wu, Anise M S; Cheng, Kit-Man; Lau, Mason M C

2017-06-01

Internet use has global influences on all aspects of life and has become a growing concern. Cross-sectional studies on Internet addiction (IA) have been reported but causality is often unclear. More longitudinal studies are warranted. We investigated incidence and predictors of IA conversion among secondary school students. A 12-month longitudinal study was conducted among Hong Kong Chinese Secondary 1-4 students (N = 8286). Using the 26-item Chen Internet Addiction Scale (CIAS; cut-off >63), non-IA cases were identified at baseline. Conversion to IA during the follow-up period was detected, with incidence and predictors derived using multi-level models. Prevalence of IA was 16.0% at baseline and incidence of IA was 11.81 per 100 person-years (13.74 for males and 9.78 for females). Risk background factors were male sex, higher school forms, and living with only one parent, while protective background factors were having a mother/father with university education. Adjusted for all background factors, higher baseline CIAS score (ORa = 1.07), longer hours spent online for entertainment and social communication (ORa = 1.92 and 1.63 respectively), and Health Belief Model (HBM) constructs (except perceived severity of IA and perceived self-efficacy to reduce use) were significant predictors of conversion to IA (ORa = 1.07-1.45). Prevalence and incidence of IA conversion were high and need attention. Interventions should take into account risk predictors identified, such as those of the HBM, and time management skills should be enhanced. Screening is warranted to identify those at high risk (e.g. high CIAS score) and provide them with primary and secondary interventions.

Influence of carrier concentration on the performance of CIAS solar cell

NASA Astrophysics Data System (ADS)

Patel, Kinjal; Ray, Jaymin

2018-05-01

Photovoltaic research has moved beyond the use of single crystalline materials such as Group IV elemental Si and Group III-V compounds like GaAs to much more complex compounds of the Group I-III-VI2 with chalcopyrite structure. The ternary ABC2 chalcopyrites (A=Cu; B=In, Ga or Al; C= S, Se or Te) form a large group of semiconducting materials with diverse structural and electrical properties. These materials are attractive for thin film photovoltaic application for a number of reasons. The bandgap of CuInSe2 is relatively low, 1.04 eV, but it can be adjusted to better match the solar spectrum either by substituting part of In by Ga or part of Se by S. Most reported and popular Cu(In,Ga)Se2 (CIGS) is one of its derivative. Efficiency of the CIGS devices with Eg >1.3 eV is reduced by the degradation of the electronic properties of the absorber leading to losses in the fill-factor and the open-circuit voltage. Alternatively, the performance can be improved by the addition of Al to form CuInAlSe2 (CIAS) absorber layers with an increase in the bandgap energy, which matches closely with the solar spectrum. In the present work an effort was made in the direction of improving the conversion efficiency by studying the influence of carrier concentration. SCAPS simulation program is used to simulate the CIAS structure numerically. The obtained results intended the significant variation in the values of conversion efficiency. Variation in the efficiency can be considered because of the relation optical absorption and carrier concentration. Observed highest efficiency is 10 %, which can be further improved by considering actual parameters of the device as well as the operating condition.

Impact Delivery of Reduced Greenhouse Gases on Early MARS

NASA Technical Reports Server (NTRS)

Haberle, R. M.; Zahnle, K.

2017-01-01

While there is abundant evidence for flowing liquid water on the ancient Martian surface, a widely accepted greenhouse mechanism for explaining this in the presence of a faint young sun has yet to emerge. Gases such as NH3, CO2 alone, SO2, clouds, and CH4, have sustainability issues or limited greenhouse power. Recently, Ramirez et al. proposed that CO2-H2 atmospheres, through collision induced absorptions (CIA), could solve the problem if large amounts are present (1.3-4 bars of CO2, 50-20% H2). However, they had to estimate the strength of the H2- CO2 interaction from the measured strength of the H2- N2 interaction. Recent ab initio calculations show that the strength of CO2-H2 CIA is greater than Ramirez et al. assumed. Wordsworth et al. also calculated the absorption coefficients for CO2-CH4 CIA and show that on early Mars a 0.5 bar CO2 atmosphere with percent levels of H2 or CH4 can raise mean annual temperatures by tens of degrees Kelvin. Freezing temperatures can be reached in atmospheres containing 1-2 bars of CO2 and 2-10% H2 and CH4. The new work demonstrates that less CO2 and reduced gases are needed than Ramirez et al. originally proposed, which improves prospects for their hypothesis. If thick weakly reducing atmospheres are the solution to the faint young sun paradox, then plausible mechanisms must be found to generate and sustain the required concentrations of H2 and CH4. Possible sources of reducing gases include volcanic outgassing, serpentinization, and impact delivery; sinks include photolysis, oxidation, and hydrogen escape. The viability of the reduced greenhouse hypothesis depends, therefore, on the strength of these sources and sinks.

Clinical Trials of Potential Cognitive-Enhancing Drugs in Schizophrenia: What Have We Learned So Far?

PubMed Central

Keefe, Richard S. E.; Buchanan, Robert W.; Marder, Stephen R.; Schooler, Nina R.; Dugar, Ashish; Zivkov, Milana; Stewart, Michelle

2013-01-01

In light of the number of studies conducted to examine the treatment of cognitive impairment associated with schizophrenia (CIAS), we critically reviewed recent CIAS trials. Trials were identified through searches of the website “www.clinicaltrials.gov” using the terms “schizophrenia AND cognition,” “schizophrenia AND neurocognition,” “schizophrenia AND neurocognitive tests,” “schizophrenia AND MATRICS,” “schizophrenia AND MCCB,” “schizophrenia AND BACS,” “schizophrenia AND COGSTATE,” and “schizophrenia AND CANTAB” and “first-episode schizophrenia AND cognition.” The cutoff date was 20 April 2011. Included trials were conducted in people with schizophrenia, the effects on cognition were either a primary or secondary outcome, and the effect of a pharmacologically active substance was examined. Drug challenge, pharmacokinetic, pharmacodynamic, or prodrome of psychosis studies were excluded. We identified 118 trials, with 62% using an add-on parallel group design. The large majority of completed trials were underpowered to detect moderate effect sizes, had ≤8 weeks duration, and were performed in samples of participants with chronic stable schizophrenia. The ongoing add-on trials are longer, have larger sample sizes (with a number of them being adequately powered to detect moderate effect sizes), and are more likely to use a widely accepted standardized cognitive battery (eg, the MATRICS Consensus Cognitive Battery) and MATRICS guidelines. Ongoing studies performed in subjects with recent onset schizophrenia may help elucidate which subjects are most likely to show an effect in cognition. New insights into the demands of CIAS trial design and methodology may help increase the probability of identifying treatments with beneficial effect on cognitive impairment in schizophrenia. PMID:22114098

Identification of early HIV infections using the fourth generation Abbott ARCHITECT HIV Ag/Ab Combo chemiluminescent microparticle immunoassay (CIA) in San Diego County.

PubMed

Manlutac, Anna Liza M; Giesick, Jill S; McVay, Patricia A

2013-12-01

HIV screening assays have gone through several generations of development in an effort to narrow the "window period" of detection. Utilizing a fourth generation HIV screening assay has the potential to detect earlier HIV infection, thus reducing HIV-1 transmission. To identify acute infections to decrease HIV transmission in San Diego County. Serum specimens were collected from clients seen by multiple submitters in San Diego County. All acceptable specimens were screened using the 4th Gen Combo Assay. Initially reactive specimens were repeated in duplicate and if repeatedly reactive, were confirmed by HIV-1 Immunofluorescent Antibody Assay (IFA). IFA negative/inconclusive specimens were sent for HIV-1 NAT and HIV-2 antibody testing to referral laboratories. BioRad Multispot HIV-1/HIV-2 Rapid Test was also performed on a subset of specimens. Of 14,559 specimens received in 20 months, 14,517 specimens were tested. Of the 14,517 specimens that were tested, a total of 279 (1.9%) specimens were CIA repeatedly reactive and 240 of the 279 confirmed by HIV-1 IFA. Thirty-nine gave IFA negative/inconclusive result and 30 were further tested for HIV-1 NAT and 36 for HIV-2 antibody. Thirteen specimens were considered false positives by CIA and 17 specimens were classified as acute infections. Eleven of 39 IFA negative/inconclusive specimens were further tested by Multispot. Five of the 11 were positive by Multispot. The fourth generation Abbott ARCHITECT HIV Ag/Ab Combo Assay identified 17 patients who may have been missed by the prior HIV-1 screening assay used at San Diego County Public Health Laboratory. Copyright © 2013 Elsevier B.V. All rights reserved.

Hydroxyl radical mediates cisplatin-induced apoptosis in human hair follicle dermal papilla cells and keratinocytes through Bcl-2-dependent mechanism.

PubMed

Luanpitpong, Sudjit; Nimmannit, Ubonthip; Chanvorachote, Pithi; Leonard, Stephen S; Pongrakhananon, Varisa; Wang, Liying; Rojanasakul, Yon

2011-08-01

Induction of massive apoptosis of hair follicle cells by chemotherapy has been implicated in the pathogenesis of chemotherapy-induced alopecia (CIA), but the underlying mechanisms of regulation are not well understood. The present study investigated the apoptotic effect of cisplatin in human hair follicle dermal papilla cells and HaCaT keratinocytes, and determined the identity and role of specific reactive oxygen species (ROS) involved in the process. Treatment of the cells with cisplatin induced ROS generation and a parallel increase in caspase activation and apoptotic cell death. Inhibition of ROS generation by antioxidants inhibited the apoptotic effect of cisplatin, indicating the role of ROS in the process. Studies using specific ROS scavengers further showed that hydroxyl radical, but not hydrogen peroxide or superoxide anion, is the primary oxidative species responsible for the apoptotic effect of cisplatin. Electron spin resonance studies confirmed the formation of hydroxyl radicals induced by cisplatin. The mechanism by which hydroxyl radical mediates the apoptotic effect of cisplatin was shown to involve down-regulation of the anti-apoptotic protein Bcl-2 through ubiquitin-proteasomal degradation. Bcl-2 was also shown to have a negative regulatory role on hydroxyl radical. Together, our results indicate an essential role of hydroxyl radical in cisplatin-induced cell death of hair follicle cells through Bcl-2 regulation. Since CIA is a major side effect of cisplatin and many other chemotherapeutic agents with no known effective treatments, the knowledge gained from this study could be useful in the design of preventive treatment strategies for CIA through localized therapy without compromising the chemotherapy efficacy.

Oleanolic acid acetate inhibits rheumatoid arthritis by modulating T cell immune responses and matrix-degrading enzymes

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

Choi, Jin Kyeong; Molecular Immunology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892; Kim, Sung-Wan

ABSTRACT: Rheumatoid arthritis (RA) is a chronic autoimmune disease associated with a combination of synovium joint inflammation, synovium hyperplasia, and destruction of cartilage and bone. Oleanolic acid acetate (OAA), a compound isolated from Vigna angularis, has been known to possess pharmacological activities, including anti-inflammation and anti-bone destruction. In this study, we investigated the effects of OAA on RA and the underlying mechanisms of action by using a type-II collagen-induced arthritis (CIA) mouse model and tumor necrosis factor (TNF)-α-stimulated RA synovial fibroblasts. Oral administration of OAA decreased the clinical arthritis symptoms, paw thickness, histologic and radiologic changes, and serum total andmore » anti-type II collagen IgG, IgG1, and IgG2a levels. OAA administration reduced Th1/Th17 phenotype CD4{sup +} T lymphocyte expansions and inflammatory cytokine productions in T cell activated draining lymph nodes and spleen. OAA reduced the expression and production of inflammatory mediators, such as cytokines and matrix metalloproteinase (MMP)-1/3, in the ankle joint tissue and RA synovial fibroblasts by down-regulating Akt, mitogen-activated protein kinases, and nuclear factor-κB. Our results clearly support that OAA plays a therapeutic role in RA pathogenesis by modulating helper T cell immune responses and matrix-degrading enzymes. The immunosuppressive effects of OAA were comparable to dexamethasone and ketoprofen. We provide evidences that OAA could be a potential therapeutic candidate for RA. - Highlights: • OAA attenuated chronic CIA symptoms. • OAA had a regulating effect on the T helper cell immune reaction for CIA. • The effect of OAA on the RA was comparable to the dexamethasone or ketoprofen. • OAA might be a candidate for the treatment of arthritic diseases.« less

In Vivo Expansion of Activated Foxp3+ Regulatory T Cells and Establishment of a Type 2 Immune Response upon IL-33 Treatment Protect against Experimental Arthritis.

PubMed

Biton, Jérôme; Khaleghparast Athari, Sara; Thiolat, Allan; Santinon, François; Lemeiter, Delphine; Hervé, Roxane; Delavallée, Laure; Levescot, Anais; Roga, Stéphane; Decker, Patrice; Girard, Jean-Philippe; Herbelin, André; Boissier, Marie-Christophe; Bessis, Natacha

2016-09-01

IL-33 is strongly involved in several inflammatory and autoimmune disorders with both pro- and anti-inflammatory properties. However, its contribution to chronic autoimmune inflammation, such as rheumatoid arthritis, is ill defined and probably requires tight regulation. In this study, we aimed at deciphering the complex role of IL-33 in a model of rheumatoid arthritis, namely, collagen-induced arthritis (CIA). We report that repeated injections of IL-33 during induction (early) and during development (late) of CIA strongly suppressed clinical and histological signs of arthritis. In contrast, a late IL-33 injection had no effect. The cellular mechanism involved in protection was related to an enhanced type 2 immune response, including the expansion of eosinophils, Th2 cells, and type 2 innate lymphoid cells, associated with an increase in type 2 cytokine levels in the serum of IL-33-treated mice. Moreover, our work strongly highlights the interplay between IL-33 and regulatory T cells (Tregs), demonstrated by the dramatic in vivo increase in Treg frequencies after IL-33 treatment of CIA. More importantly, Tregs from IL-33-treated mice displayed enhanced capacities to suppress IFN-γ production by effector T cells, suggesting that IL-33 not only favors Treg proliferation but also enhances their immunosuppressive properties. In concordance with these observations, we found that IL-33 induced the emergence of a CD39(high) Treg population in a ST2L-dependent manner. Our findings reveal a powerful anti-inflammatory mechanism by which IL-33 administration inhibits arthritis development. Copyright © 2016 by The American Association of Immunologists, Inc.

Is Internet addiction transitory or persistent? Incidence and prospective predictors of remission of Internet addiction among Chinese secondary school students.

PubMed

Lau, Joseph T F; Wu, Anise M S; Gross, Danielle L; Cheng, Kit-Man; Lau, Mason M C

2017-11-01

Internet addiction (IA) is prevalent among adolescents but it is potentially revertible. Only three Taiwan adolescent studies reported IA remission and a few related factors. We investigated incidence and predictors of remission among Hong Kong Chinese secondary school students with a 12-month longitudinal study. IA was defined as Chen Internet Addiction Scale (CIAS) score>63. Validated measures were used to assess students' psychosocial wellbeing at baseline and follow-up. Of 1545 students with IA at baseline, 1296 (83.9%) provided matched baseline/12-month follow-up data; their data were analyzed. Incidence of remission (CIAS≤63 at follow-up) was 59.29/100 person-years. Significant predictors included: 1) baseline CIAS score (ORa=.95), 2) baseline health belief model (HBM) constructs [perception of having severe IA (ORa=.34), perceived susceptibility to IA (ORa=0.82), perceived barrier (ORa=0.95), cue to action from parents (ORa=0.82), and self-efficacy for reducing Internet use (ORa=1.13)], and 3) baseline psychosocial health measures [self-esteem (ORa=1.03), severe depression (ORa=0.72) and social anxiety (ORa=0.96)] and their changes over time [depression (ORa=.95), anxiety (ORa=.94), loneliness (ORa=.93), self-esteem (ORa=1.07), positive affect (ORa=1.10) and family support (ORa=1.03)]. Two-thirds (64.3%) of the remission group presented reduced CIAS score>1.5 SD, and recorded larger improvements in psychosocial status over time than the non-remission group. Without noticeable interventions, incidence of remission was high and related to improvements in psychosocial health. Most of the HBM constructs, and baseline/changes in psychosocial measures predicted remission. Interventions to increase remission should modify these factors. Copyright © 2017 Elsevier Ltd. All rights reserved.

USSR Report, International Affairs

DTIC Science & Technology

1987-03-11

among states. In turn, General Edgardo Mercado Jarrin sharply condemned the interventionist actions of the CIA against Libya and Nicaragua, and...activities in the municipalities . We have no practical experience in these kinds of matters, and this shows that we are poorly prepared; we have not able to

32 CFR 1900.34 - Requests for expedited processing.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 6 2011-07-01 2011-07-01 false Requests for expedited processing. 1900.34 Section 1900.34 National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY PUBLIC ACCESS TO CIA RECORDS UNDER THE FREEDOM OF INFORMATION ACT (FOIA) Additional Administrative...

32 CFR 1900.34 - Requests for expedited processing.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 6 2013-07-01 2013-07-01 false Requests for expedited processing. 1900.34 Section 1900.34 National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY PUBLIC ACCESS TO CIA RECORDS UNDER THE FREEDOM OF INFORMATION ACT (FOIA) Additional Administrative...

32 CFR 1908.02 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Information and Privacy Coordinator; (b) Days means calendar days when the Agency is operating and... means the CIA Information and Privacy Coordinator who serves as the Agency manager of the information... physical interest in the documents or information at issue; (h) NARA means the National Archives and...

Hearing improvement in a patient with variant Muckle‐Wells syndrome in response to interleukin 1 receptor antagonism

PubMed Central

Rynne, M; Maclean, C; Bybee, A; McDermott, M F; Emery, P

2006-01-01

Background Muckle‐Wells syndrome (MWS), familial cold autoinflammatory syndrome, and neonatal onset multisystem inflammatory disease, also called chronic, infantile, neurological, cutaneous, and articular syndrome, are three hereditary autoinflammatory syndromes caused by mutations affecting the CIAS1/NALP3 gene on chromosome 1q44. The proinflammatory cytokine, interleukin 1β, is believed to have a fundamental role in their pathogenesis. Case report The case is described of a 59 year old white woman who presented with increasingly severe MWS‐type features over a 15 year period. The response to interleukin 1β inhibition with anakinra was dramatic, including a reduction in intracranial pressure with associated auditory improvement, as demonstrated by serial audiometry. Conclusions The confirmed improvement in hearing after initiation of interleukin 1 receptor antagonism corroborates previous reports that specific blockade of this single cytokine reverses most of the symptoms of this group of CIAS1/NALP3 related autoinflammatory conditions, including the sensorineural deafness, which has not been previously reported. PMID:16531551

A layered trust information security architecture.

PubMed

de Oliveira Albuquerque, Robson; Villalba, Luis Javier García; Orozco, Ana Lucila Sandoval; Buiati, Fábio; Kim, Tai-Hoon

2014-12-01

Information can be considered the most important asset of any modern organization. Securing this information involves preserving confidentially, integrity and availability, the well-known CIA triad. In addition, information security is a risk management job; the task is to manage the inherent risks of information disclosure. Current information security platforms do not deal with the different facets of information technology. This paper presents a layered trust information security architecture (TISA) and its creation was motivated by the need to consider information and security from different points of view in order to protect it. This paper also extends and discusses security information extensions as a way of helping the CIA triad. Furthermore, this paper suggests information representation and treatment elements, operations and support components that can be integrated to show the various risk sources when dealing with both information and security. An overview of how information is represented and treated nowadays in the technological environment is shown, and the reason why it is so difficult to guarantee security in all aspects of the information pathway is discussed.

Unique variation in genetic selection among Black North American women and its potential influence on pregnancy outcome.

PubMed

Jaffe, Shirlee; Normand, Neil; Jayaram, Aswathi; Orfanelli, Theofano; Doulaveris, Georgios; Passos, Mariana; Kanninen, Tomi T; Bongiovanni, Ann Marie; Linhares, Iara M; Witkin, Steven S

2013-11-01

We hypothesize that variations in the frequency of genetic polymorphisms, reflecting ancestral differences in living conditions and exposure to microorganisms, increase susceptibility to adverse pregnancy outcome among present day Black North American women. Striking differences were observed in the frequency of genetic variants between Black and White or Hispanic women in 5 genes (IL1RN, MBL2, PPARA, ATG16L1, CIAS1) associated with inflammation and anti-microbial immunity. The CIAS1 and IL1RN polymorphisms were associated with altered interleukin-1β serum levels; the MBL2 polymorphism resulted in a decreased serum mannose-binding lectin concentration. Gene polymorphisms associated with an alteration in innate immunity were most frequent in Black women. This may reflect an evolutionary selection in response to an ancient environment containing a high multitude of microorganisms, and may increase susceptibility of Black women to infection-associated preterm birth in the current North American environment. Copyright © 2013 Elsevier Ltd. All rights reserved.

Solid oxide fuel cell with multi-unit construction and prismatic design

DOEpatents

McPheeters, C.C.; Dees, D.W.; Myles, K.M.

1999-03-16

A single cell unit of a solid oxide fuel cell is described that is individually fabricated and sintered prior to being connected to adjacent cells to form a solid oxide fuel cell. The single cell unit is comprised of a shaped anode sheet positioned between a flat anode sheet and an anode-electrolyte-cathode (A/E/C) sheet, and a shaped cathode sheet positioned between the A/E/C sheet and a cathode-interconnect-anode (C/I/A) sheet. An alternate embodiment comprises a shaped cathode sheet positioned between an A/E/C sheet and a C/I/A sheet. The shaped sheets form channels for conducting reactant gases. Each single cell unit is individually sintered to form a finished sub-assembly. The finished sub-assemblies are connected in electrical series by interposing connective material between the end surfaces of adjacent cells, whereby individual cells may be inspected for defects and interchanged with non-defective single cell units. 7 figs.

The Binary Collision-Induced Second Overtone Band of Gaseous Hydrogen: Modelling and Laboratory Measurements

NASA Technical Reports Server (NTRS)

Brodbeck, C.; Bouanich, J.-P.; Nguyen, Van Thanh; Borysow, Aleksandra

1999-01-01

Collision-induced absorption (CIA) is the major source of the infrared opacity of dense planetary atmospheres which are composed of nonpolar molecules. Knowledge of CIA absorption spectra of H2-H2 pairs is important for modelling the atmospheres of planets and cold stars that are mainly composed of hydrogen. The spectra of hydrogen in the region of the second overtone at 0.8 microns have been recorded at temperatures of 298 and 77.5 K for gas densities ranging from 100 to 800 amagats. By extrapolation to zero density of the absorption coefficient measured every 10 cm(exp -1) in the spectral range from 11100 to 13800 cm(exp -1), we have determined the binary absorption coefficient. These extrapolated measurements are compared with calculations based on a model that was obtained by using simple computer codes and lineshape profiles. In view of the very weak absorption of the second overtone band, we find the agreement between results of the model and experiment to be reasonable.

Determining the Optimum Cut-Off Grades in Sulfide Copper Deposits / Określanie Optymalnej Wartości Odcięcia Zawartości Procentowej Pierwiastka Użytecznego W Złożach Siarczku Miedzi

NASA Astrophysics Data System (ADS)

Rahimi, Esmaeil; Oraee, Kazem; Shafahi, Zia Aldin; Ghasemzadeh, Hasan

2015-03-01

Optimum cut-off grades determination in mining life affects production planning and ultimate pit limit and it is also important from social, economical and environmental aspects. Calculation of optimum cut-off grades has been less considered for mines containing various mineral processing methods. In this paper, an optimization technique is applied to obtain optimum cut-off grades for both concentration and heap leaching processes. In this technique, production costs and different recoveries of heap leaching method directed into modeling different annual cash flows in copper mines. Considering the governing constraints, the Lagrange multiplier method is practiced to optimize the cut-off grades in which the objective function is supposed to maximize Net Present Value. The results indicate the effect of heap leaching process on the optimum cut-off grades of primary and secondary sulfide deposits. Określanie optymalnego poziomu odcięcia dla zawartości procentowej pierwiastka użytecznego ma poważny wpływ na planowanie produkcji, określanie ostatecznych limitów zasobów złoża; jest to także ważna kwestia z punktu widzenia kwestii społecznych, ekonomicznych i środowiskowych. Obliczanie optymalnego poziomu odcięcia dla zawartości procentowej pierwiastka użytecznego nie było zwykle szeroko rozważane w przypadku kopalni prowadzących ciągły system przeróbki. W pracy tej przedstawiono technikę optymalizacji określania poziomu zawartości procentowej pierwiastka użytecznego z uwzględnieniem zarówno procesów koncentracji jak i ługowania. W metodzie uwzględniono koszty produkcji i różne wskaźniki odzysku rudy, wielkości te wykorzystane zostały do modelowania rocznych przepływów gotówki w kopalniach miedzi. Uwzględniając narzucone ograniczenia, zastosowano metodę mnożników Lagrange'a w celu optymalizacji określania poziomu zawartości procentowej pierwiastka użytecznego, gdzie przyjętą funkcją celu jest maksymalizacja wartości bieżącej netto. Wyniki wskazują wpływ procesów ługowania na zawartość procentową pierwiastka użytecznego w rudzie pochodzącej z pierwotnych lub wtórnych złóż siarczku miedzi.

Open-systems architecture of a standardized command interface chip-set for switching and control of a spacecraft power bus

NASA Technical Reports Server (NTRS)

Ruiz, Ian B.; Burke, Gary R.; Lung, Gerald; Whitaker, William D.; Nowicki, Robert M.

2004-01-01

The Jet Propulsion Laboratory (JPL) has developed a command interface chip-set that primarily consists of two mixed-signal ASICs'; the Command Interface ASIC (CIA) and Analog Interface ASIC (AIA). The Open-systems architecture employed during the design of this chip-set enables its use as both an intelligent gateway between the system's flight computer and the control, actuation, and activation of the spacecraft's loads, valves, and pyrotechnics respectfully as well as the regulator of the spacecraft power bus. Furthermore, the architecture is highly adaptable and employed fault-tolerant design methods enabling a host of other mission uses including reliable remote data collection. The objective of this design is to both provide a needed flight component that meets the stringent environmental requirements of current deep space missions and to add a new element to a growing library that can be used as a standard building block for future missions to the outer planets.

Assessment of Caregiver Inventory for Rett Syndrome

ERIC Educational Resources Information Center

Lane, Jane B.; Salter, Amber R.; Jones, Nancy E.; Cutter, Gary; Horrigan, Joseph; Skinner, Steve A.; Kaufmann, Walter E.; Glaze, Daniel G.; Neul, Jeffrey L.; Percy, Alan K.

2017-01-01

Rett syndrome (RTT) requires total caregiver attention and leads to potential difficulties throughout life. The Caregiver Burden Inventory, designed for Alzheimer disease, was modified to a RTT Caregiver Inventory Assessment (RTT CIA). Reliability and face, construct, and concurrent validity were assessed in caregivers of individuals with RTT. Chi…

32 CFR 1900.04 - Suggestions and complaints.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 6 2013-07-01 2013-07-01 false Suggestions and complaints. 1900.04 Section 1900.04 National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY PUBLIC ACCESS TO CIA RECORDS UNDER THE FREEDOM OF INFORMATION ACT (FOIA) General § 1900.04 Suggestions and...

32 CFR 1900.04 - Suggestions and complaints.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 6 2011-07-01 2011-07-01 false Suggestions and complaints. 1900.04 Section 1900.04 National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY PUBLIC ACCESS TO CIA RECORDS UNDER THE FREEDOM OF INFORMATION ACT (FOIA) General § 1900.04 Suggestions and...

Unlawful Combatants at the Controls: The CIA, Armed RPAS and LOAC

DTIC Science & Technology

2011-02-16

career judge advocate, beginning military service with the Judge Advocate General’s Corps, United States Navy . After a brief stint in private...of Xe Services, formerly known as Blackwater , the private security firm that has been at the forefront of other allegations concerning civilians

32 CFR 99.9 - Terms of indemnification.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 1 2014-07-01 2014-07-01 false Terms of indemnification. 99.9 Section 99.9 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE PERSONNEL, MILITARY AND CIVILIAN... prohibiting the disclosure of criminal history record information to the DoD, OPM, or CIA for the purposes...

32 CFR 99.9 - Terms of indemnification.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 1 2013-07-01 2013-07-01 false Terms of indemnification. 99.9 Section 99.9 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE PERSONNEL, MILITARY AND CIVILIAN... prohibiting the disclosure of criminal history record information to the DoD, OPM, or CIA for the purposes...

32 CFR 99.9 - Terms of indemnification.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 1 2012-07-01 2012-07-01 false Terms of indemnification. 99.9 Section 99.9 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE PERSONNEL, MILITARY AND CIVILIAN... prohibiting the disclosure of criminal history record information to the DoD, OPM, or CIA for the purposes...

32 CFR 99.9 - Terms of indemnification.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 1 2011-07-01 2011-07-01 false Terms of indemnification. 99.9 Section 99.9 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE PERSONNEL, MILITARY AND CIVILIAN... prohibiting the disclosure of criminal history record information to the DoD, OPM, or CIA for the purposes...

32 CFR 99.9 - Terms of indemnification.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 1 2010-07-01 2010-07-01 false Terms of indemnification. 99.9 Section 99.9 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE PERSONNEL, MILITARY AND CIVILIAN... prohibiting the disclosure of criminal history record information to the DoD, OPM, or CIA for the purposes...

ESP and LSD on the CIA's dime

NASA Astrophysics Data System (ADS)

Whitaker, Andrew

2012-08-01

Any reader who expects David Kaiser's new book about quantum-information theory to be an orthodox treatise will be disabused by the book's front cover, which depicts a naked man standing on his head, his modesty retained by a bright yellow, strategically superimposed image of a nucleus in a Bohr-type atom.

32 CFR 1900.34 - Requests for expedited processing.

Code of Federal Regulations, 2010 CFR

2010-07-01

... processing and will notify the requester of its decision. The certification shall set forth with specificity... 32 National Defense 6 2010-07-01 2010-07-01 false Requests for expedited processing. 1900.34... AGENCY PUBLIC ACCESS TO CIA RECORDS UNDER THE FREEDOM OF INFORMATION ACT (FOIA) Additional Administrative...

Technology as a Craft of Deceit.

ERIC Educational Resources Information Center

Thompson, Mark E.

This essay briefly presents the evolution of technology and the resulting warnings that many prominent writers have offered in defense of an analytic inquiry into man's interaction with technology. Various ways in which technology has been used to manipulate people are described, e.g., Vietnam, Watergate, the CIA, the Tuskegee Study, Subliminal…

US Intelligence Community Reform Studies Since 1947

DTIC Science & Technology

2005-04-01

their gratitude for the assistance of Douglas Garthoff, Richard Giza , Woodrow Kuhns, Mark Lowenthal, and Kevin Scheid, as well as the staff of CSI...of the intelligence enterprise. CIA was “the apex of a pyramidal intelligence structure,” but it had not met the expectation that it would be the

32 CFR 1901.44 - Action by appeals authority.

Code of Federal Regulations, 2010 CFR

2010-07-01

... request, the document(s) (sanitized and full text) at issue, and the findings of the concerned Deputy... appearances shall be permitted without the express permission of the Panel. (c) Decision by the Historical... refer the request to the CIA Historical Records Policy Board which acts as the senior corporate board...

32 CFR 1900.32 - Procedures for information concerning other persons.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 6 2011-07-01 2011-07-01 false Procedures for information concerning other persons. 1900.32 Section 1900.32 National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY PUBLIC ACCESS TO CIA RECORDS UNDER THE FREEDOM OF INFORMATION ACT (FOIA) Additional...

32 CFR 1900.32 - Procedures for information concerning other persons.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 6 2013-07-01 2013-07-01 false Procedures for information concerning other persons. 1900.32 Section 1900.32 National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY PUBLIC ACCESS TO CIA RECORDS UNDER THE FREEDOM OF INFORMATION ACT (FOIA) Additional...

Knowing What We Knew: Intelligence Failures and Knowledge Management

DTIC Science & Technology

2011-02-28

2000, the CIA was watching Khalid al-Mihdhar in a Malaysia terrorism planning meeting, and on September 11, 2001, he helped crash an American Airlines...The intelligence franchise [organization] is based upon the business of information, not secrets, and its product is people, experts…not paper.”27

Beyond the Enthymeme: Sorites, Critical Thinking, and the Composing Process.

ERIC Educational Resources Information Center

Hill, Carolyn

A teacher presents a writing exercise designed to facilitate audience-directed, critical thinking during the process of composing, that starts students thinking in terms of sorites and enthymemes. Students first read a CIA manual, "Psychological Operations in Guerrilla Warfare," that instructs the Contra guerrillas in illegal acts and…

32 CFR 1908.02 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... means the CIA Information and Privacy Coordinator who serves as the Agency manager of the information... authorities as may be established in the future; (k) Referral means coordination with or transfer of action to... General § 1908.02 Definitions. For purposes of this part, the following terms have the meanings as...

32 CFR 1908.02 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... means the CIA Information and Privacy Coordinator who serves as the Agency manager of the information... authorities as may be established in the future; (k) Referral means coordination with or transfer of action to... General § 1908.02 Definitions. For purposes of this part, the following terms have the meanings as...

Brent Olson - Director, Office of Internal Audit | NREL

Science.gov Websites

improve the effectiveness and efficiency of governance, risk management, and control processes. Using this the Treadway Commission's 2013 Internal Control Framework, Standards for Internal Control in the additional certifications from IIA including Certified Internal Auditor (CIA); Certification in Control Self

32 CFR 1900.33 - Allocation of resources; agreed extensions of time.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Information and Privacy Coordinator is responsible for management of the Agency-wide program defined by this..., Information Management through the Agency Release Panel shall provide policy and resource direction as... INTELLIGENCE AGENCY PUBLIC ACCESS TO CIA RECORDS UNDER THE FREEDOM OF INFORMATION ACT (FOIA) Additional...

32 CFR 1900.33 - Allocation of resources; agreed extensions of time.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Information and Privacy Coordinator is responsible for management of the Agency-wide program defined by this..., Information Management through the Agency Release Panel shall provide policy and resource direction as... INTELLIGENCE AGENCY PUBLIC ACCESS TO CIA RECORDS UNDER THE FREEDOM OF INFORMATION ACT (FOIA) Additional...

32 CFR 1900.33 - Allocation of resources; agreed extensions of time.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Information and Privacy Coordinator is responsible for management of the Agency-wide program defined by this..., Information Management through the Agency Release Panel shall provide policy and resource direction as... INTELLIGENCE AGENCY PUBLIC ACCESS TO CIA RECORDS UNDER THE FREEDOM OF INFORMATION ACT (FOIA) Additional...

76 FR 4695 - Notice of Agreements Filed

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-26

..., S.A.; COSCO Container Lines Company, Limited; Dole Ocean Cargo Express; Hamburg-S[uuml]d; Hoegh Autoliners A/S; Hyundai Merchant Marine Co. Ltd.; Independent Container Line Ltd.; Kawasaki Kisen Kaisha, Ltd.... Parties: Alianca Navegacao e Logistica Ltda. & Cia.; China Shipping Container Lines Co., Ltd.; CMA CGM S.A...

Partners or Competitors?: The Evolution of the DoD/CIA Relationship Since Desert Storm and its Prospects for the Future

DTIC Science & Technology

2013-05-23

Afghanistan.” 39 the shoulders of these two organizations, but on Congressional choices as well. It...Christopher J. Lamb . United States Special Operations Forces. New York, NY: Columbia University Press, 2007. Walker, Stephen G, Akan Malici, and Mark

United States Air Force Summary, Fifth Edition

DTIC Science & Technology

1979-03-01

t911 COPPER BAUXITE UNITED STATES ZINC CBROIJJI. C!’ NICKEL SOURCE. CIA -HANDBOOK OF ECONOMIC STATISTICS, 19711 IINC it IANSINESE COBALT IRON().pueUI...Wilson, Charles (TX) Boggs, Lindy (Mrs. Hole)(LA) Benjomin, Adam Jr. (IN) Dicks, Norman D. (WAI McHugh "Mafhew F. (NY) Ginn, So (GA) lehman, Williom

Critical Homeland Infrastructure Protection

DTIC Science & Technology

2007-01-01

talent. Examples include: * Detection of surveillance activities; * Stand-off detection of chemical, biological, nuclear, radiation and explosive ...Manager Guardian DARPA Overview Mr. Roger Gibbs DARPA LLNL Technologies in Support of Infrastructure Mr. Don Prosnitz LLNL Protection Sandia National...FP Antiterrorism/Force Protection CBRNE Chemical Biological Radiological Nuclear Explosive CERT Commuter Emergency Response Team CIA Central

Open to Attack?

ERIC Educational Resources Information Center

Poremba, Sue Marquette

2012-01-01

Who hasn't received mail from a company notifying them that their personal information may have been compromised? No organization--not Amazon, not the CIA--is immune to cyberattacks, and higher education is no exception. Indeed, colleges and universities may be even more susceptible to security breaches than their corporate brethren, and the…

Aging and health: Self-efficacy for Self-direction in Health Scale.

PubMed

Oliveira, Albertina L; Silva, José T; Lima, Margarida P

2016-07-04

To validate the Escala de Autoeficácia para a Autodireção na Saúde (EAAS - Self-efficacy for Self-direction in Health Scale). Non-experimental quantitative study of EAAS validation, by confirmatory factorial analyses, evaluating a sample of 508 older adults from the north and the center of Portugal with mean age of 71.67 (from 51 to 96 years), to whom the Self-efficacy for Self-direction in Health Scale, the Rosenberg Self-esteem Scale, the Positive and Negative Affect Schedule, the Satisfaction with Life Scale, and the Instrumental Activities of Daily Living Scale were applied. The EAAS was developed from the theoretical constructs of self-efficacy and from self-directed learning within the PALADIN European project framework, aiming to develop an instrument able to assess the extent to which older adults take good care of their health. The internal consistency was 0.87 (Cronbach's alpha) and confirmatory factorial analyses enabled to find a model near the one theoretically proposed, indicating a structure consisting of four dimensions: physical exercise, healthy diet, engaging in health-related learning, and visits to health professionals. From the psychometric point of view, the model in four factors showed quite satisfactory fit indicators. The Self-efficacy for Self-direction in Health Scale, with 16 items, is adequate to evaluate to what extent older adults have confidence in their ability to take care of their own health, with high degree of autonomy. Validar a Escala de Autoeficácia para a Autodireção no domínio da Saúde (EAAS). Estudo quantitativo não experimental de validação da EAAS, por meio de análises fatoriais confirmatórias, avaliando amostra de 508 seniores e idosos provenientes das regiões Norte e Centro de Portugal com média etária de 71.67 (51 a 96 anos), a quem foram aplicadas a Escala de Autoeficácia para a Autodireção na Saúde, a Escala de Autoestima de Rosenberg, a Escala de Afeto Positivo e Afeto Negativo, a Escala de Satisfação Com a Vida e a escala de Atividades Instrumentais da Vida Diária. A EAAS foi desenvolvida a partir dos construtos teóricos da autoeficácia e da aprendizagem autodirigida no âmbito do projeto europeu PALADIN, visando constituir um instrumento apto a avaliar até que ponto os seniores cuidam bem da sua saúde. A consistência interna encontrada foi de 0.87 (alfa de Cronbach) e as análises fatoriais confirmatórias permitiram encontrar um modelo próximo ao proposto teoricamente, indicando uma estrutura constituída por quatro dimensões: exercício físico, alimentação saudável, envolvimento em aprendizagens relativas à saúde e visitas a profissionais de saúde. Do ponto de vista psicométrico, o modelo em quatro fatores mostrou indicadores de ajustamento bastante satisfatórios. A Escala de Autoeficácia para a Autodireção na Saúde, com 16 itens, é adequada para avaliar em que medida os seniores têm confiança na sua capacidade para tomar conta da própria saúde, com elevado grau de autonomia.

Cryopyrin-associated periodic syndromes: otolaryngologic and audiologic manifestations.

PubMed

Ahmadi, Neda; Brewer, Carmen C; Zalewski, Christopher; King, Kelly A; Butman, John A; Plass, Nicole; Henderson, Cailin; Goldbach-Mansky, Raphaela; Kim, H Jeffrey

2011-08-01

Cryopyrin-associated periodic syndromes (CAPS) represent a spectrum of CIAS1 gene-mediated autoinflammatory diseases characterized by recurrent systemic inflammation. The clinical spectrum of CAPS varies from mild to severe and includes the syndromes historically described as familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease (NOMID). This article presents the largest cohort of patients with CAPS. The objective is to describe the pathogenesis, otolaryngologic, and audiologic manifestations of CAPS. Prospective (2003-2009). National Institutes of Health. Fifty-seven patients with a diagnosis of CAPS were identified (31 NOMID, 11 NOMID/MWS, 9 MWS, and 6 FCAS). Comprehensive data regarding clinical manifestations, audiologic phenotype, and fluid attenuation inversion recovery MRI (FLAIR-MRI) of the brain and inner ear were obtained. Complete audiologic data obtained on 70% of ears revealed conductive hearing loss in 4 (11%) NOMID ears and mixed hearing loss in 5 (13%) NOMID and 2 (14%) NOMID/MWS ears. Sensorineural hearing loss (SNHL), worse in higher frequencies, was the most common type of hearing loss and was present in 23 (61%) NOMID, 10 (71%) NOMID/MWS, and 4 (33%) MWS ears. All of the patients with FCAS had normal hearing except 2, who had SNHL from 4 to 8 kHz. On FLAIR-MRI sequence, cochlear enhancement was noted in 26 of 29 (90%) NOMID, 6 of 11 (55%) NOMID/MWS, 3 of 9 (33%) MWS, and 1 of 6 (17%) FCAS patients and was significantly associated with the presence of hearing loss. Maxillary sinus hypoplasia and mucosal thickening were found in 39% and 86% of the cohort, respectively. CIAS1 pathway–mediated CAPS is associated with unregulated autoinflammation mediated by interleukin-1 in the cochlea and hearing loss. Timely diagnosis is crucial to initiate early treatment with interleukin-1 receptor antagonists.

PGK1, a glucose metabolism enzyme, may play an important role in rheumatoid arthritis.

PubMed

Zhao, Yan; Yan, Xinfeng; Li, Xia; Zheng, Yabing; Li, Shufeng; Chang, Xiaotian

2016-10-01

Some studies have indicated that glucose metabolism plays an important role in the pathogenesis of rheumatoid arthritis (RA). This study aimed to find the novel genes affecting glucose metabolism in RA. Synovial tissues of collagen-induced arthritis (CIA) were analyzed with Rat Glucose Metabolism RT(2) Profiler™ PCR Array to screen those genes with special expressions in glucose metabolism. Real-time PCR, western blotting, and ELISA were used to confirm the result in synovial tissues and blood of human RA. Culture synovial fibroblast cells (RASF) was treated with siRNA to suppress expressions of the target genes. CCK-8 cell proliferation assay and two-compartment transwell system were performed to examine cell proliferation and cell migration of the treated RASF. Both PCR array and real-time PCR detected the up-regulation of ENO1, HK2, and PGK1 and the down-regulation of PCK1 and PDK4 in synovial tissues of CIA rats. Real-time PCR and western blotting detected the increased expression of ENO1 and PGK1 in RA synovial tissues. ELISA detected a high level of PGK1 in the blood of RA patients. Decreased cell proliferation and cell migration capabilities were significantly detected in RASF following treatment of anti-PGK1 siRNA. IL-1β and IFN-γ rather than TNF-α and IL-1α levels were significantly declined in supernatants of the treated RASF. PGK1, a glycolytic enzyme catalyzing the conversion of 3-phosphoglycerate into 2-phosphoglycerate, has increased expression in synovial tissues and blood of RA, which may be involved in pro-inflammation and synovial hyperplasia of the disease.

Geochemistry of Archean metasedimentary rocks of the Aravalli craton, NW India: Implications for provenance, paleoweathering and supercontinent reconstruction

NASA Astrophysics Data System (ADS)

Ahmad, Iftikhar; Mondal, M. E. A.; Satyanarayanan, M.

2016-08-01

Basement complex of the Aravalli craton (NW India) known as the Banded Gneissic Complex (BGC) is classified into two domains viz. Archean BGC-I and Proterozoic BGC-II. We present first comprehensive geochemical study of the Archean metasedimentary rocks occurring within the BGC-I. These rocks occur associated with intrusive amphibolites in a linear belt within the basement gneisses. The association is only concentrated on the western margin of the BGC-I. The samples are highly mature (MSm) to very immature (MSi), along with highly variable geochemistry. Their major (SiO2/Al2O3, Na2O/K2O and Al2O3/TiO2) and trace (Th/Sc, Cr/Th, Th/Co, La/Sc, Zr/Sc) element ratios, and rare earth element (REE) patterns are consistent with derivation of detritus from the basement gneisses and its mafic enclaves, with major contribution from the former. Variable mixing between the two end members and closed system recycling (cannibalism) resulted in the compositional heterogeneity. Chemical index of alteration (CIA) of the samples indicate low to moderate weathering of the source terrain in a sub-tropical environment. In A-CN-K ternary diagram, some samples deceptively appear to have undergone post-depositional K-metasomatism. Nevertheless, their petrography and geochemistry (low K2O and Rb) preclude the post-depositional alteration. We propose non-preferential leaching of elements during cannibalism as the cause of the deceptive K-metasomatism as well as enigmatic low CIA values of some highly mature samples. The Archean metasedimentary rocks were deposited on stable basement gneisses, making the BGC-I a plausible participant in the Archean Ur supercontinent.

A comparative study of matrix metalloproteinase and aggrecanase mediated release of latent cytokines at arthritic joints.

PubMed

Mullen, Lisa; Adams, Gill; Foster, Julie; Vessillier, Sandrine; Köster, Mario; Hauser, Hansjörg; Layward, Lorna; Gould, David; Chernajovsky, Yuti

2014-09-01

Latent cytokines are engineered by fusing the latency associated peptide (LAP) derived from transforming growth factor-β (TGF-β) with the therapeutic cytokine, in this case interferon-β (IFN-β), via an inflammation-specific matrix metalloproteinase (MMP) cleavage site. To demonstrate latency and specific delivery in vivo and to compare therapeutic efficacy of aggrecanase-mediated release of latent IFN-β in arthritic joints to the original MMP-specific release. Recombinant fusion proteins with MMP, aggrecanase or devoid of cleavage site were expressed in CHO cells, purified and characterised in vitro by Western blotting and anti-viral protection assays. Therapeutic efficacy and half-life were assessed in vivo using the mouse collagen-induced arthritis model (CIA) of rheumatoid arthritis and a model of acute paw inflammation, respectively. Transgenic mice with an IFN-regulated luciferase gene were used to assess latency in vivo and targeted delivery to sites of disease. Efficient localised delivery of IFN-β to inflamed paws, with low levels of systemic delivery, was demonstrated in transgenic mice using latent IFN-β. Engineering of latent IFN-β with an aggrecanase-sensitive cleavage site resulted in efficient cleavage by ADAMTS-4, ADAMTS-5 and synovial fluid from arthritic patients, with an extended half-life similar to the MMP-specific molecule and greater therapeutic efficacy in the CIA model. Latent cytokines require cleavage in vivo for therapeutic efficacy, and they are delivered in a dose dependent fashion only to arthritic joints. The aggrecanase-specific cleavage site is a viable alternative to the MMP cleavage site for the targeting of latent cytokines to arthritic joints. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

32 CFR 99.7 - Procedures for requesting an indemnification agreement.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 1 2011-07-01 2011-07-01 false Procedures for requesting an indemnification agreement. 99.7 Section 99.7 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE... prohibiting the disclosure of criminal history record information to the DoD, OPM, or CIA; and (b) Append to...

32 CFR 99.7 - Procedures for requesting an indemnification agreement.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 1 2014-07-01 2014-07-01 false Procedures for requesting an indemnification agreement. 99.7 Section 99.7 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE... prohibiting the disclosure of criminal history record information to the DoD, OPM, or CIA; and (b) Append to...

32 CFR 99.5 - Eligibility for indemnification.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 1 2012-07-01 2012-07-01 false Eligibility for indemnification. 99.5 Section 99.5 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE PERSONNEL, MILITARY AND... history record information to the DoD, OPM, or CIA. (b) A State or locality is also eligible for an...

32 CFR 99.5 - Eligibility for indemnification.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 1 2013-07-01 2013-07-01 false Eligibility for indemnification. 99.5 Section 99.5 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE PERSONNEL, MILITARY AND... history record information to the DoD, OPM, or CIA. (b) A State or locality is also eligible for an...

32 CFR 99.7 - Procedures for requesting an indemnification agreement.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 1 2013-07-01 2013-07-01 false Procedures for requesting an indemnification agreement. 99.7 Section 99.7 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE... prohibiting the disclosure of criminal history record information to the DoD, OPM, or CIA; and (b) Append to...

32 CFR 99.7 - Procedures for requesting an indemnification agreement.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 1 2012-07-01 2012-07-01 false Procedures for requesting an indemnification agreement. 99.7 Section 99.7 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE... prohibiting the disclosure of criminal history record information to the DoD, OPM, or CIA; and (b) Append to...

32 CFR 99.7 - Procedures for requesting an indemnification agreement.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 1 2010-07-01 2010-07-01 false Procedures for requesting an indemnification agreement. 99.7 Section 99.7 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE... prohibiting the disclosure of criminal history record information to the DoD, OPM, or CIA; and (b) Append to...

32 CFR 99.5 - Eligibility for indemnification.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 1 2010-07-01 2010-07-01 false Eligibility for indemnification. 99.5 Section 99.5 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE PERSONNEL, MILITARY AND... history record information to the DoD, OPM, or CIA. (b) A State or locality is also eligible for an...

32 CFR 99.5 - Eligibility for indemnification.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 1 2014-07-01 2014-07-01 false Eligibility for indemnification. 99.5 Section 99.5 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE PERSONNEL, MILITARY AND... history record information to the DoD, OPM, or CIA. (b) A State or locality is also eligible for an...

32 CFR 99.5 - Eligibility for indemnification.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 1 2011-07-01 2011-07-01 false Eligibility for indemnification. 99.5 Section 99.5 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE PERSONNEL, MILITARY AND... history record information to the DoD, OPM, or CIA. (b) A State or locality is also eligible for an...

32 CFR 1909.16 - Action by Agency Release Panel (ARP).

Code of Federal Regulations, 2012 CFR

2012-07-01

...) for decision. In the event of a disagreement with any decision by D/IMS, Directorate heads may appeal to the Associate Deputy Director, CIA (ADD) for resolution. The final Agency decision shall reflect the vote of the ARP, unless changed by the D/IMS or the ADD. [76 FR 59035, Sept. 23, 2011] ...

32 CFR 1909.16 - Action by Agency Release Panel (ARP).

Code of Federal Regulations, 2013 CFR

2013-07-01

...) for decision. In the event of a disagreement with any decision by D/IMS, Directorate heads may appeal to the Associate Deputy Director, CIA (ADD) for resolution. The final Agency decision shall reflect the vote of the ARP, unless changed by the D/IMS or the ADD. [76 FR 59035, Sept. 23, 2011] ...

32 CFR 1909.16 - Action by Agency Release Panel (ARP).

Code of Federal Regulations, 2014 CFR

2014-07-01

...) for decision. In the event of a disagreement with any decision by D/IMS, Directorate heads may appeal to the Associate Deputy Director, CIA (ADD) for resolution. The final Agency decision shall reflect the vote of the ARP, unless changed by the D/IMS or the ADD. [76 FR 59035, Sept. 23, 2011] ...

The National School Orchestra Contests: 1929-1937

ERIC Educational Resources Information Center

Hash, Phillip M.

2016-01-01

The purpose of this study was to examine the National School Orchestra Contests sponsored by the National Bureau for the Advancement of Music and the Committee on Instrumental Affairs (CIA) of Music Supervisors National Conference from 1929 to 1937. Research questions examined contest (a) organization and operation, (b) rules and procedures, (c)…

32 CFR 1900.44 - Action by appeals authority.

Code of Federal Regulations, 2010 CFR

2010-07-01

... complete record of the request consisting of the request, the document(s) (sanitized and full text) at... Panel. (c) Decision by the Historical Records Policy Board. In any cases of divided vote by the ARP, any member of that body is authorized to refer the request to the CIA Historical Records Policy Board which...

32 CFR 1908.35 - Action by appeals authority.

Code of Federal Regulations, 2010 CFR

2010-07-01

... consisting of the request, the document(s) (sanitized and full text) at issue, and the findings of the... of the Panel. (b) Action by Historical Records Policy Board. In any cases of divided vote by the ARP, any member of that body is authorized to refer the request to the CIA Historical Records Policy Board...

A Standardized and Portable Field Bioassay to Evaluate Interior Residual Sprays for Control of Malaria

DTIC Science & Technology

2008-10-01

by exports of marine products, citrus, sugar cane, and bananas (CIA Factbook 2008). The occurrence of malaria in Belize is generally lower in...chemical compounds (similar to the natural chemical pyrethrins which come from Chrysanthemum spp. flowers ) that are recommended by the WHO for use

An Interagency Smart Power Approach from the Sea

DTIC Science & Technology

2009-01-01

S~Yict CeiIDs Dptklan 2 (~/l] ~~ ; t1’, T;:rlO, j.ttitrnbl~k.g:st."’r:mDJmo1Dg1st 18 Nloil’’’e p~:",ct5t:()rll:~r 6 ( SiSl ’ ~:: \\ N~~e 17 C~.~I~A" :4

DESIGN AND DEVELOPMENT OF A LOW COST, MULTIFUNCTION, REGIONALLY APPROPRIATE SOLAR OVEN FOR DEVELOPING COUNTRIES IN LATIN AMERICA

EPA Science Inventory

In the average Latin American country, 45% of the population is below the poverty line and 36% live in rural settings (CIA World Factbook). For these sectors, solar ovens might represent their only affordable means of cooking and sterilization. Significant research efforts i...

75 FR 3523 - Additional Designation of Entities and Individuals Pursuant to Executive Order 12978

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-21

... AE048871 (Colombia); (INDIVIDUAL) [SDNT]. Individuals 1. CIFUENTES VARGAS, Carmen Viviana, c/o INVERSIONES... (Colombia); (INDIVIDUAL) [SDNT]. 11. LOPEZ RODRIGUEZ, Walter, c/o CARMILE INVERSIONES LOPEZ Y CIA. S.C.A., Cali, Colombia; c/o CONSTRUCTORA SANTA TERESITA S.A., Cali, Colombia; c/o INVERSIONES MEDICAS Y...

North Korea’s Nuclear Weapons: Technical Issues

DTIC Science & Technology

2009-07-01

news.bbc.co.uk/2/hi/asia-pacific/6216385.stm. 20 Warren Strobel , “North Korean nuclear documents challenge CIA assertions,” McClatchyNewspapers, May 28, 2008...78 “N. Korea ‘Slowing Disablement of Nuclear Facilities,” Chosun Ilbo, January 29, 2008. 79 Lee Chi-dong, “N Korea Complains

North Korea’s Nuclear Weapons: Technical Issues

DTIC Science & Technology

2009-12-16

News, http://news.bbc.co.uk/2/hi/asia-pacific/6216385.stm. 20 Warren Strobel , “North Korean nuclear documents challenge CIA assertions...Facilities,” Chosun Ilbo, January 29, 2008. 81 Lee Chi-dong, “N Korea Complains About Slow Provision of Energy Aid,” Yonhap News, June 5, 2008. 82 “N

North Korea’s Nuclear Weapons: Technical Issues

DTIC Science & Technology

2009-05-26

Warren Strobel , “North Korean nuclear documents challenge CIA assertions,” McClatchyNewspapers, May 28, 2008. 23 “N.K. says plutonium ‘weaponized’ and...Chosun Ilbo, January 29, 2008. 78 Lee Chi-dong, “N Korea Complains About Slow Provision of Energy Aid,” Yonhap News, June 5, 2008. 79 “N. Korea

North Korea’s Nuclear Weapons

DTIC Science & Technology

2009-05-05

South,” BBC News, http://news.bbc.co.uk/2/hi/asia-pacific/6216385.stm. 22 Warren Strobel , “North Korean nuclear documents challenge CIA assertions...Chosun Ilbo, January 29, 2008. 74 Lee Chi-dong, “N Korea Complains About Slow Provision of Energy Aid,” Yonhap News, June 5, 2008. 75 “N. Korea can

U.S. Government Security Response to Attacks on its Diplomatic Missions, 1979-2012: How Effective?

DTIC Science & Technology

2013-06-14

Wars: The Secret History of the CIA, Afghanistan, and Bin Laden, from the Soviet 14 Invasion to September 10, 2001 contained relevant information...with the totals from the other fiscal year budgets, to show the department’s budget authority from 1979 through 2012. History of the Bureau of

Interactions between Snow Chemistry, Mercury Inputs and Microbial Population Dynamics in an Arctic Snowpack

PubMed Central

Larose, Catherine; Prestat, Emmanuel; Cecillon, Sébastien; Berger, Sibel; Malandain, Cédric; Lyon, Delina; Ferrari, Christophe; Schneider, Dominique; Dommergue, Aurélien; Vogel, Timothy M.

2013-01-01

We investigated the interactions between snowpack chemistry, mercury (Hg) contamination and microbial community structure and function in Arctic snow. Snowpack chemistry (inorganic and organic ions) including mercury (Hg) speciation was studied in samples collected during a two-month field study in a high Arctic site, Svalbard, Norway (79°N). Shifts in microbial community structure were determined by using a 16S rRNA gene phylogenetic microarray. We linked snowpack and meltwater chemistry to changes in microbial community structure by using co-inertia analyses (CIA) and explored changes in community function due to Hg contamination by q-PCR quantification of Hg-resistance genes in metagenomic samples. Based on the CIA, chemical and microbial data were linked (p = 0.006) with bioavailable Hg (BioHg) and methylmercury (MeHg) contributing significantly to the ordination of samples. Mercury was shown to influence community function with increases in merA gene copy numbers at low BioHg levels. Our results show that snowpacks can be considered as dynamic habitats with microbial and chemical components responding rapidly to environmental changes. PMID:24282515

Factors influencing the effectiveness of scalp cooling in the prevention of chemotherapy-induced alopecia.

PubMed

Komen, Manon M C; Smorenburg, Carolien H; van den Hurk, Corina J G; Nortier, Johan W R

2013-01-01

The success of scalp cooling in preventing or reducing chemotherapy-induced alopecia (CIA) is highly variable between patients and chemotherapy regimens. The outcome of hair preservation is often unpredictable and depends on various factors. Methods. We performed a structured search of literature published from 1970 to February 2012 for articles that reported on factors influencing the effectiveness of scalp cooling to prevent CIA in patients with cancer. Results. The literature search identified 192 reports, of which 32 studies were considered relevant. Randomized studies on scalp cooling are scarce and there is little information on the determinants of the result. The effectiveness of scalp cooling for hair preservation depends on dose and type of chemotherapy, with less favorable results at higher doses. Temperature seems to be an important determinant. Various studies suggest that a subcutaneous scalp temperature less than 22 °C is required for hair preservation. Conclusions. The effectiveness of scalp cooling for hair preservation varies by chemotherapy type and dose, and probably by the degree and duration of cooling.

A Layered Trust Information Security Architecture

PubMed Central

de Oliveira Albuquerque, Robson; García Villalba, Luis Javier; Sandoval Orozco, Ana Lucila; Buiati, Fábio; Kim, Tai-Hoon

2014-01-01

Information can be considered the most important asset of any modern organization. Securing this information involves preserving confidentially, integrity and availability, the well-known CIA triad. In addition, information security is a risk management job; the task is to manage the inherent risks of information disclosure. Current information security platforms do not deal with the different facets of information technology. This paper presents a layered trust information security architecture (TISA) and its creation was motivated by the need to consider information and security from different points of view in order to protect it. This paper also extends and discusses security information extensions as a way of helping the CIA triad. Furthermore, this paper suggests information representation and treatment elements, operations and support components that can be integrated to show the various risk sources when dealing with both information and security. An overview of how information is represented and treated nowadays in the technological environment is shown, and the reason why it is so difficult to guarantee security in all aspects of the information pathway is discussed. PMID:25470490

Resistance to collagen-induced arthritis in SHPS-1 mutant mice

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

Okuzawa, Chie; Kaneko, Yoriaki; Murata, Yoji

SHPS-1 is a transmembrane protein that binds the protein tyrosine phosphatases SHP-1 and SHP-2 through its cytoplasmic region and is abundantly expressed on dendritic cells and macrophages. Here we show that mice expressing a mutant form of SHPS-1 fail to develop type-II collagen (CII)-induced arthritis (CIA), a model for rheumatoid arthritis in humans. Histological examinations of the arthritic paws from immunized wild-type mice revealed that cartilage was destroyed in association with marked mononuclear cell infiltration, while only mild cell infiltration was observed in immunized SHPS-1 mutant mice. Consistently, the serum levels of both IgG and IgG2a specific to CII andmore » of IL-1{beta} in immunized SHPS-1 mutant mice were markedly reduced compared with those apparent for wild-type mice. The CII-induced proliferation of, and production of cytokines by, T cells from immunized SHPS-1 mutant mice were reduced compared to wild-type cells. These results suggest that SHPS-1 is essential for development of CIA.« less

Rebamipide suppresses collagen-induced arthritis through reciprocal regulation of th17/treg cell differentiation and heme oxygenase 1 induction.

PubMed

Moon, Su-Jin; Park, Jin-Sil; Woo, Yun-Ju; Lim, Mi-Ae; Kim, Sung-Min; Lee, Seon-Yeong; Kim, Eun-Kyung; Lee, Hee Jin; Lee, Weon Sun; Park, Sang-Hi; Jeong, Jeong-Hee; Park, Sung-Hwan; Kim, Ho-Youn; Cho, Mi-La; Min, Jun-Ki

2014-04-01

Rebamipide, a gastroprotective agent, has the ability to scavenge reactive oxygen radicals. Increased oxidative stress is implicated in the pathogenesis of rheumatoid arthritis (RA). We undertook this study to investigate the impact of rebamipide on the development of arthritis and the pathophysiologic mechanisms by which rebamipide attenuates arthritis severity in a murine model of RA. Collagen-induced arthritis (CIA) was induced in DBA/1J mice. Anti-type II collagen antibody titers and interleukin-17 (IL-17) levels were determined using enzyme-linked immunosorbent assay. The expression of transcription factors was analyzed by immunostaining and Western blotting. Frequencies of IL-17-producing CD4+ T cells (Th17 cells) and CD4+CD25+FoxP3+ Treg cells were analyzed by flow cytometry. Rebamipide reduced the clinical arthritis score and severity of histologic inflammation and cartilage destruction in a dose-dependent manner. The joints isolated from rebamipide-treated mice with CIA showed decreased expression of nitrotyrosine, an oxidative stress marker. Rebamipide-treated mice showed lower circulating levels of type II collagen-specific IgG, IgG1, and IgG2a. Whereas the number of Th17 cells in spleens was decreased in rebamipide-treated mice with CIA, a significant increase in the number of Treg cells in spleens was observed. In vitro, rebamipide inhibited Th17 cell differentiation through STAT-3/retinoic acid receptor-related orphan nuclear receptor γt and reciprocally induced Treg cell differentiation through FoxP3. Rebamipide increased Nrf2 nuclear activities in murine CD4+ T cells and LBRM-33 murine T lymphoma cells. Heme oxygenase 1 (HO-1) expression in the spleens was markedly increased in rebamipide-treated mice. The inhibitory effects of rebamipide on joint inflammation are associated with recovery from an imbalance between Th17 cells and Treg cells and with activation of an Nrf2/HO-1 antioxidant pathway. Copyright © 2014 by the American College of Rheumatology.

Inhibition of cytokine response to TLR stimulation and alleviation of collagen-induced arthritis in mice by Schistosoma japonicum peptide SJMHE1.

PubMed

Wang, Xuefeng; Li, Li; Wang, Jun; Dong, Liyang; Shu, Yang; Liang, Yong; Shi, Liang; Xu, Chengcheng; Zhou, Yuepeng; Wang, Yi; Chen, Deyu; Mao, Chaoming

2017-03-01

Helminth-derived products have recently been shown to prevent the development of inflammatory diseases in mouse models. However, most identified immunomodulators from helminthes are mixtures or macromolecules with potentially immunogenic side effects. We previously identified an immunomodulatory peptide called SJMHE1 from the HSP60 protein of Schistosoma japonicum. In this study, we assessed the ability of SJMHE1 to affect murine splenocytes and human peripheral blood mononuclear cells (PBMCs) stimulated by toll-like receptor (TLR) ligands in vitro and its treatment effect on mice with collagen-induced arthritis (CIA). We show that SJMHE1 not only modulates the cytokine production of murine macrophage (MΦ) and dendritic cell but also affects cytokine production upon coculturing with allogeneic CD4 + T cell. SJMHE1 potently inhibits the cytokine response to TLR ligands lipopolysaccharide (LPS), CpG oligodeoxynucleotides (CpG) or resiquimod (R848) from mouse splenocytes, and human PBMCs stimulated by LPS. Furthermore, SJMHE1 suppressed clinical signs of CIA in mice and blocked joint erosion progression. This effect was mediated by downregulation of key cytokines involved in the pathogenesis of CIA, such as interferon-γ (IFN-γ), tumour necrosis factor-α (TNF-α), interleukin (IL)-6, IL-17, and IL-22 and up-regulation of the inhibitory cytokine IL-10, Tgf-β1 mRNA, and CD4 + CD25 + Foxp3 + Tregs. This study provides new evidence that the peptide from S. japonicum, which is the 'safe' selective generation of small molecule peptide that has evolved during host-parasite interactions, is of great value in the search for novel anti-inflammatory agents and therapeutic targets for autoimmune diseases. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Impact of chemotherapy-induced alopecia distress on body image, psychosocial well-being, and depression in breast cancer patients.

PubMed

Choi, Eun Kyung; Kim, Im-Ryung; Chang, Oliver; Kang, Danbee; Nam, Seok-Jin; Lee, Jeong Eon; Lee, Se Kyung; Im, Young-Hyuck; Park, Yeon Hee; Yang, Jung-Hyun; Cho, Juhee

2014-10-01

This study aims to evaluate the impact of chemotherapy-induced alopecia (CIA) distress on body image, psychosocial well-being, and depression among breast cancer patients. A cross-sectional survey was conducted at the breast cancer advocacy events held at 16 hospitals in Korea. Alopecia distress was assessed using the 'Chemotherapy-Induced Alopecia Distress Scale', body image and psychosocial well-being were measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and breast specific module (BR23), and depression was measured using the Center for Epidemiological Studies Depression scale. Means of outcomes were compared between low and high CIA distress groups. Univariable and multivariable linear regression models were used to analyze the relationship between the CIA distress and body image, psychosocial well-being, and depression. One hundred sixty-eight breast cancer patients participated in the study; the mean age was 48.4 (SD = 8.4) years, and 55.3% of the patients experienced higher distress from alopecia. In fully adjusted models, the high distress group was more likely to have a poorer body image than the low distress group (35.2 vs. 62.0; p < 0.001). Distressed patients were also more likely to report lower emotional (55.3 vs. 76.9; p < 0.001), role (58.6 vs. 72.0; p < 0.001), and social functioning (51.3 vs. 70.9; p < 0.001). The high distress group was also more likely to have depression compared with the low distress group (19.6 vs. 14.8; p < 0.001). Chemotherapy-induced alopecia distress was negatively associated with body image, psychosocial well-being, and depression in women with breast cancer. It is necessary to develop specific interventions to minimize distress due to alopecia for women with breast cancer. Copyright © 2014 John Wiley & Sons, Ltd.

Altered default network resting-state functional connectivity in adolescents with Internet gaming addiction.

PubMed

Ding, Wei-na; Sun, Jin-hua; Sun, Ya-wen; Zhou, Yan; Li, Lei; Xu, Jian-rong; Du, Ya-song

2013-01-01

Excessive use of the Internet has been linked to a variety of negative psychosocial consequences. This study used resting-state functional magnetic resonance imaging (fMRI) to investigate whether functional connectivity is altered in adolescents with Internet gaming addiction (IGA). Seventeen adolescents with IGA and 24 normal control adolescents underwent a 7.3 minute resting-state fMRI scan. Posterior cingulate cortex (PCC) connectivity was determined in all subjects by investigating synchronized low-frequency fMRI signal fluctuations using a temporal correlation method. To assess the relationship between IGA symptom severity and PCC connectivity, contrast images representing areas correlated with PCC connectivity were correlated with the scores of the 17 subjects with IGA on the Chen Internet Addiction Scale (CIAS) and Barratt Impulsiveness Scale-11 (BIS-11) and their hours of Internet use per week. There were no significant differences in the distributions of the age, gender, and years of education between the two groups. The subjects with IGA showed longer Internet use per week (hours) (p<0.0001) and higher CIAS (p<0.0001) and BIS-11 (p = 0.01) scores than the controls. Compared with the control group, subjects with IGA exhibited increased functional connectivity in the bilateral cerebellum posterior lobe and middle temporal gyrus. The bilateral inferior parietal lobule and right inferior temporal gyrus exhibited decreased connectivity. Connectivity with the PCC was positively correlated with CIAS scores in the right precuneus, posterior cingulate gyrus, thalamus, caudate, nucleus accumbens, supplementary motor area, and lingual gyrus. It was negatively correlated with the right cerebellum anterior lobe and left superior parietal lobule. Our results suggest that adolescents with IGA exhibit different resting-state patterns of brain activity. As these alterations are partially consistent with those in patients with substance addiction, they support the hypothesis that IGA as a behavioral addiction that may share similar neurobiological abnormalities with other addictive disorders.

Altered Default Network Resting-State Functional Connectivity in Adolescents with Internet Gaming Addiction

PubMed Central

Li, Lei; Xu, Jian-rong

2013-01-01

Purpose Excessive use of the Internet has been linked to a variety of negative psychosocial consequences. This study used resting-state functional magnetic resonance imaging (fMRI) to investigate whether functional connectivity is altered in adolescents with Internet gaming addiction (IGA). Methods Seventeen adolescents with IGA and 24 normal control adolescents underwent a 7.3 minute resting-state fMRI scan. Posterior cingulate cortex (PCC) connectivity was determined in all subjects by investigating synchronized low-frequency fMRI signal fluctuations using a temporal correlation method. To assess the relationship between IGA symptom severity and PCC connectivity, contrast images representing areas correlated with PCC connectivity were correlated with the scores of the 17 subjects with IGA on the Chen Internet Addiction Scale (CIAS) and Barratt Impulsiveness Scale-11 (BIS-11) and their hours of Internet use per week. Results There were no significant differences in the distributions of the age, gender, and years of education between the two groups. The subjects with IGA showed longer Internet use per week (hours) (p<0.0001) and higher CIAS (p<0.0001) and BIS-11 (p = 0.01) scores than the controls. Compared with the control group, subjects with IGA exhibited increased functional connectivity in the bilateral cerebellum posterior lobe and middle temporal gyrus. The bilateral inferior parietal lobule and right inferior temporal gyrus exhibited decreased connectivity. Connectivity with the PCC was positively correlated with CIAS scores in the right precuneus, posterior cingulate gyrus, thalamus, caudate, nucleus accumbens, supplementary motor area, and lingual gyrus. It was negatively correlated with the right cerebellum anterior lobe and left superior parietal lobule. Conclusion Our results suggest that adolescents with IGA exhibit different resting-state patterns of brain activity. As these alterations are partially consistent with those in patients with substance addiction, they support the hypothesis that IGA as a behavioral addiction that may share similar neurobiological abnormalities with other addictive disorders. PMID:23555827

Oral Escherichia coli Colonization Factor Antigen I (CFA/I) Fimbriae Ameliorate Arthritis via IL-35, not IL-27

PubMed Central

Kochetkova, Irina; Thornburg, Theresa; Callis, Gayle; Holderness, Kathryn; Maddaloni, Massimo; Pascual, David W.

2014-01-01

A Salmonella therapeutic expressing enterotoxigenic E. coli colonization factor antigen I (CFA/I) fimbriae protects against collagen-induced arthritis (CIA) by eliciting two regulatory T cell (Treg) subsets: TGF-β-producing Foxp3−CD39+CD4+ and IL-10-producing Foxp3+CD39+CD4+ T cells. However, it is unclear if CFA/I fimbriae alone are protective, and if other regulatory cytokines are involved especially in the context for the EBI3-sharing cytokines, Treg-derived IL-35 and APC-derived IL-27, both capable of suppressing Th17 cells and regulating autoimmune diseases. Subsequent evaluation revealed that a single oral dose of purified, soluble CFA/I fimbriae protected against CIA as effectively as Salmonella-CFA/I, and found Foxp3+CD39+CD4+ T cells as the source of secreted IL-35, whereas IL-27 production by CD11c+ cells was inhibited. Inquiring into their relevance, CFA/I fimbriae-treated IL-27 receptor-deficient (WSX-1−/−) mice were equally protected against CIA as wild-type mice suggesting a limited role for IL-27. In contrast, CFA/I fimbriae-mediated protection was abated in EBI3−/− mice accompanied by the loss of TGF-β- and IL-10-producing Tregs. Adoptive transfer of B6 CD39+CD4+ T cells to EBI3−/− mice with concurrent CFA/I plus IL-35 treatment effectively stimulated Tregs suppressing proinflammatory CII-specific Th cells. Opposingly, recipients co-transferred with B6 and EBI3−/− CD39+CD4+ T cells and treated with CFA/I plus IL-35 failed in protecting mice implicating the importance for endogenous IL-35 to confer CFA/I-mediated protection. Thus, CFA/I fimbriae stimulate IL-35 required for the co-induction of TGF-β and IL-10. PMID:24337375

Escherichia coli heat-labile enterotoxin B subunit prevents autoimmune arthritis through induction of regulatory CD4+ T cells.

PubMed

Luross, Jeffrey A; Heaton, Tricia; Hirst, Timothy R; Day, Michael J; Williams, Neil A

2002-06-01

The receptor-binding B subunit of Escherichia coli heat-labile enterotoxin (EtxB) is a highly stable, nontoxic protein that is capable of modulating immune responses. This study was conducted to determine whether mucosal administration of EtxB can block collagen-induced arthritis (CIA) and to investigate the mechanisms involved. Clinical arthritis in DBA/1 mice was monitored following mucosal administration of EtxB on 4 occasions. The dependence of disease prevention on receptor binding by EtxB and the associated alterations to the immune response to type II collagen (CII) were assessed. Adoptive transfer experiments and lymph node cell cocultures were used to investigate the underlying mechanisms. Both intranasal and intragastric delivery of EtxB were effective in preventing CIA; a 1-microg dose of EtxB was protective after intranasal administration. A non-receptor-binding mutant of EtxB failed to prevent disease. Intranasal EtxB lowered both the incidence and severity of arthritis when given either at the time of disease induction or 25 days later. EtxB markedly reduced levels of anti-CII IgG2a antibodies and interferon-gamma (IFNgamma) production while not affecting levels of IgG1, interleukin-4 (IL-4), or IL-10. Disease protection could be transferred by CD4+ T cells from treated mice, an effect that was abrogated upon depletion of the CD25+ population. In addition, CD4+CD25+ T cells from treated mice were able to suppress anti-CII IFNgamma production by CII-primed lymph node cells. Mucosal administration of EtxB can be used to prevent or treat CIA. Modulation of the anti-CII immune response by EtxB is associated with a reduction in Th1 cell reactivity without a concomitant shift toward Th2. Instead, EtxB mediates its effects through enhancing the activity of a population of CD4+ regulatory T cells.

Hair mass index obtained by cross-section trichometry: an objective and clinically useful parameter to quantify hair in chemotherapy-induced alopecia.

PubMed

Vleut, Rowena E; van Poppel, Joyce E A M; Dercksen, Marcus W; Peerbooms, Mijke; Houterman, Saskia; Breed, Wim P M

2013-07-01

In order to evaluate the efficacy of scalp cooling for the prevention of chemotherapy-induced alopecia (CIA), it is essential to precisely quantify the amount of hair mass that is present. We wanted to determine if the hair mass index (HMI), obtained by cross-section trichometry (CST), was a suitable parameter for hair mass measurement, and whether or not marking the measurement site on the scalp was necessary. Ten patients receiving chemotherapy were sequentially measured using CST during their treatment. At the same time, they were asked to report severity of hair loss via three subjective parameters: World Health Organization (WHO) grade, visual analog scale (VAS) score, and patients' need to wear wig or head cover. To investigate the need of marking of the measurement area, differences in HMI between a random 2 × 2-cm site (HMI-C) and four surrounding areas (HMI-S4) on the scalp of eight volunteers and eight chemotherapy patients were calculated and compared. Using CTS, hair loss due to CIA was quite measurable and ranged from 13 to 82 %. Reported VAS scores and WHO grades showed an increase in patients in time; 50 % of patients reported the need to wear a wig or head cover. The difference between HMI-S4 and the HMI-C values in all subjects of the marking group was homogeneously distributed between -11 and +10 and was not statistically different between the volunteer and the patient groups (p = 0.465). CST for HMI measurement is a useful mechanical modality for assessing hair loss in CIA patients. It is quantitatively more precise than existing non-mechanical measuring methods. It is recommended when detection of minor changes in hair quantity is required. Marking a fixed sampling area to ensure return to the exact same site is only required when a minor change in pre- and posttreatment HMI values is anticipated and the mid-line locating device is not/cannot be used.

The Bruton tyrosine kinase inhibitor PCI-32765 ameliorates autoimmune arthritis by inhibition of multiple effector cells

PubMed Central

2011-01-01

Introduction The aim was to determine the effect of the Bruton tyrosine kinase (Btk)-selective inhibitor PCI-32765, currently in Phase I/II studies in lymphoma trials, in arthritis and immune-complex (IC) based animal models and describe the underlying cellular mechanisms. Methods PCI-32765 was administered in a series of murine IC disease models including collagen-induced arthritis (CIA), collagen antibody-induced arthritis (CAIA), reversed passive anaphylactic reaction (RPA), and passive cutaneous anaphylaxis (PCA). Clinical and pathologic features characteristic of each model were examined following treatment. PCI-32765 was then examined in assays using immune cells relevant to the pathogenesis of arthritis, and where Btk is thought to play a functional role. These included proliferation and calcium mobilization in B cells, cytokine and chemokine production in monocytes/macrophages, degranulation of mast cells and its subsequent cytokine/chemokine production. Results PCI-32765 dose-dependently and potently reversed arthritic inflammation in a therapeutic CIA model with an ED50 of 2.6 mg/kg/day. PCI-32765 also prevented clinical arthritis in CAIA models. In both models, infiltration of monocytes and macrophages into the synovium was completely inhibited and importantly, the bone and cartilage integrity of the joints were preserved. PCI-32765 reduced inflammation in the Arthus and PCA assays. In vitro, PCI-32765 inhibited BCR-activated primary B cell proliferation (IC50 = 8 nM). Following FcγR stimulation, PCI-32765 inhibited TNFα, IL-1β and IL-6 production in primary monocytes (IC50 = 2.6, 0.5, 3.9 nM, respectively). Following FcεRI stimulation of cultured human mast cells, PCI-32765 inhibited release of histamine, PGD2, TNF-α, IL-8 and MCP-1. Conclusions PCI-32765 is efficacious in CIA, and in IC models that do not depend upon autoantibody production from B cells. Thus PCI-32765 targets not only B lymphocytes but also monocytes, macrophages and mast cells, which are important Btk-expressing effector cells in arthritis. PMID:21752263

Strategic Intelligence and National Security. A Selected Bibliography

DTIC Science & Technology

1992-09-01

Rendel , Alexander M. APPOINTMENT IN CRETE: THE STORY OF A BRITISH \\GENT. London: Wingate, 1953. (MHI D810 $8R4) THE ROTE KAPELLE: THE CIA’s HISTORY OF...MEMOIRS OF AN AUSTRALIAN INTELLIGENCE ANALYST. Boston: Allen & Unwin. 1982. (UB251 A8M37) Phelps, Ruth H.; Englert, Judith A.; and Mutter, Sharon A