Accelerated measles control--Cambodia, 1999-2002.

PubMed

2003-01-10

Cambodia is recovering from approximately 30 years of civil war that resulted in the breakdown of the country's public health infrastructure. In 1999, the Ministry of Health initiated a measles-control program with the goal of reducing the annual incidence of measles to <10,000 cases in 2005 by strengthening measles surveillance, improving routine vaccination coverage, implementing supplementary measles immunization activities (SIAs), and providing vitamin A during outbreak investigations and SIAs. This report summarizes measles-vaccination activities and their impact in reducing reported measles cases from 13,827 in 1999 to 1,234 in 2002 and suggests options for future measles-control efforts in postconflict situations.

Intradermal Administration of Fractional Doses of Inactivated Poliovirus Vaccine: A Dose-Sparing Option for Polio Immunization.

PubMed

Okayasu, Hiromasa; Sein, Carolyn; Chang Blanc, Diana; Gonzalez, Alejandro Ramirez; Zehrung, Darin; Jarrahian, Courtney; Macklin, Grace; Sutter, Roland W

2017-07-01

A fractional dose of inactivated poliovirus vaccine (fIPV) administered by the intradermal route delivers one fifth of the full vaccine dose administered by the intramuscular route and offers a potential dose-sparing strategy to stretch the limited global IPV supply while further improving population immunity. Multiple studies have assessed immunogenicity of intradermal fIPV compared with the full intramuscular dose and demonstrated encouraging results. Novel intradermal devices, including intradermal adapters and disposable-syringe jet injectors, have also been developed and evaluated as alternatives to traditional Bacillus Calmette-Guérin needles and syringes for the administration of fIPV. Initial experience in India, Pakistan, and Sri Lanka suggests that it is operationally feasible to implement fIPV vaccination on a large scale. Given the available scientific data and operational feasibility shown in early-adopter countries, countries are encouraged to consider introducing a fIPV strategy into their routine immunization and supplementary immunization activities. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Outbreak of Type 2 Vaccine-Derived Poliovirus in Nigeria: Emergence and Widespread Circulation in an Underimmunized Population

PubMed Central

Pate, Muhammad Ali; Wannemuehler, Kathleen; Jenks, Julie; Burns, Cara; Chenoweth, Paul; Abanida, Emmanuel Ade; Adu, Festus; Baba, Marycelin; Gasasira, Alex; Iber, Jane; Mkanda, Pascal; Williams, A. J.; Shaw, Jing; Pallansch, Mark; Kew, Olen

2011-01-01

Wild poliovirus has remained endemic in northern Nigeria because of low coverage achieved in the routine immunization program and in supplementary immunization activities (SIAs). An outbreak of infection involving 315 cases of type 2 circulating vaccine-derived poliovirus (cVDPV2; >1% divergent from Sabin 2) occurred during July 2005–June 2010, a period when 23 of 34 SIAs used monovalent or bivalent oral poliovirus vaccine (OPV) lacking Sabin 2. In addition, 21 “pre-VDPV2” (0.5%–1.0% divergent) cases occurred during this period. Both cVDPV and pre-VDPV cases were clinically indistinguishable from cases due to wild poliovirus. The monthly incidence of cases increased sharply in early 2009, as more children aged without trivalent OPV SIAs. Cumulative state incidence of pre-VDPV2/cVDPV2 was correlated with low childhood immunization against poliovirus type 2 assessed by various means. Strengthened routine immunization programs in countries with suboptimal coverage and balanced use of OPV formulations in SIAs are necessary to minimize risks of VDPV emergence and circulation. PMID:21402542

Assessment of cold-chain maintenance in vaccine carriers during Pulse Polio National Immunization Day in a rural block of India.

PubMed

Pakhare, Abhijit P; Bali, Surya; Pawar, Radhakishan B; Lokhande, Ganesh S

2014-01-01

India was certified polio free on 27 March 2014. Supplementary immunization activities, in the form of national immunization days, is one of the core strategies for eradication, where oral polio vaccine is administered to children aged under 5 years throughout the country. Oral polio vaccine is heat sensitive and requires maintenance of a stringent cold chain. Therefore, vaccine carriers with ice packs are used in the Pulse Polio Immunization (PPI) programme. This study assessed whether the cold chain is maintained during National Immunization Day in Beed district. A cross-sectional study was conducted at six randomly selected booths, one each from six primary health centres in Georai block of Beed district in Maharashtra. Electronic data loggers, configured to measure half-hourly temperatures, were kept in vaccine carriers throughout the day of PPI. The vaccine carrier temperature was below 8 °C at all six booths; minimum temperature recorded was -9.5 °C, while the maximum was 4.5 °C. The vaccine vial monitor did not reach discard point in any booth. A vaccine carrier with four ice packs very effectively maintains the cold chain required for oral polio vaccine.

Trend in proportions of missed children during polio supplementary immunization activities in the African Region: evidence from independent monitoring data 2010-2012.

PubMed

Okeibunor, Joseph; Gasasira, Alex; Mihigo, Richard; Salla, Mbaye; Poy, Alain; Orkeh, Godwin; Shaba, Keith; Nshimirimana, Deo

2014-02-19

This is a comparative analysis of independent monitoring data collected between 2010 and 2012, following the implementation of supplementary immunization activities (SIAs) in countries in the three sub regional blocs of World Health Organization in the African Region. The sub regional blocs are Central Africa, West Africa, East and Southern Africa. In addition to the support for SIAs, the Central and West African blocs, threatened with importation and re-establishment of polio transmission received intensive coordination through weekly teleconferences. The later, East and Southern African bloc with low polio threats was not engaged in the intensive coordination through teleconferences. The key indicator of the success of SIAs is the proportion of children missed during SIAs. The results showed that generally there was a decrease in the proportion of children missed during SIAs in the region, from 7.94% in 2010 to 5.95% in 2012. However, the decrease was mainly in the Central and West African blocs. The East and Southern African bloc had countries with as much as 25% missed children. In West Africa and Central Africa, where more coordinated SIAs were conducted, there were progressive and consistent drops, from close to 20-10% at the maximum. At the country and local levels, steps were undertaken to ameliorate situation of low immunization uptake. Wherever an area is observed to have low coverage, local investigations were conducted to understand reasons for low coverage, plans to improve coverage are made and implemented in a coordinated manner. Lessons learned from close monitoring of polio eradication SIAs are will be applied to other campaigns being conducted in the African Region to accelerate control of other vaccine preventable diseases including cerebrospinal meningitis A, measles and yellow fever. Copyright © 2013 Elsevier Ltd. All rights reserved.

Lot quality assurance sampling to monitor supplemental immunization activity quality: an essential tool for improving performance in polio endemic countries.

PubMed

Brown, Alexandra E; Okayasu, Hiromasa; Nzioki, Michael M; Wadood, Mufti Z; Chabot-Couture, Guillaume; Quddus, Arshad; Walker, George; Sutter, Roland W

2014-11-01

Monitoring the quality of supplementary immunization activities (SIAs) is a key tool for polio eradication. Regular monitoring data, however, are often unreliable, showing high coverage levels in virtually all areas, including those with ongoing virus circulation. To address this challenge, lot quality assurance sampling (LQAS) was introduced in 2009 as an additional tool to monitor SIA quality. Now used in 8 countries, LQAS provides a number of programmatic benefits: identifying areas of weak coverage quality with statistical reliability, differentiating areas of varying coverage with greater precision, and allowing for trend analysis of campaign quality. LQAS also accommodates changes to survey format, interpretation thresholds, evaluations of sample size, and data collection through mobile phones to improve timeliness of reporting and allow for visualization of campaign quality. LQAS becomes increasingly important to address remaining gaps in SIA quality and help focus resources on high-risk areas to prevent the continued transmission of wild poliovirus. © Crown copyright 2014.

Progress toward poliomyelitis eradication--India, January 2004-May 2005.

PubMed

2005-07-08

Since 1988, the global incidence of polio has decreased by more than 99%, and three World Health Organization (WHO) regions (Americas, Western Pacific, and European) have been certified as polio-free . India, the largest of the six countries where polio remains endemic, experienced a large polio outbreak (1,600 cases) in 2002. Since then, the Government of India (GOI) has accelerated its polio eradication activities by increasing the number and quality of supplementary immunization activities (SIAs), which reduced the number of reported cases to 225 in 2003, 134 in 2004, and 18 in 2005 (as of June 18). During 2004 and early 2005, taking advantage of the geographic restriction of wild poliovirus (WPV) circulation, GOI and its partners launched several immunization and surveillance strategies to maximize the probability of eliminating poliovirus transmission in India. With continued high-quality interventions, interruption of WPV transmission in India by the end of 2005 appears feasible. This report summarizes progress toward polio elimination during January 2004-May 2005 toward that end.

Progress toward measles elimination--European Region, 2005--2008.

PubMed

2009-02-20

In 2002, the World Health Organization (WHO) Regional Committee for the European Region (EUR) revised earlier targets to eliminate indigenous measles and achieve rubella control by resolving to 1) eliminate both diseases in EUR member states by 2010, using a combination of routine and supplementary immunization strategies, and 2) monitor progress toward this goal through improved surveillance. This report summarizes progress toward measles elimination during 2005--2008 and updates a previous report from 2005. In 2005 and 2006, large-scale outbreaks occurred in the eastern EUR member states. However, in 2007 and 2008, overall measles incidence in EUR declined to a historic low of <10 cases per 1 million population, with the majority of cases reported from Western Europe. During 2005-2007, routine vaccination coverage with 1 dose of measles-containing vaccine (MCV) among children aged 12--23 months in EUR reached a high of 93%-94%, up from 90%-91% during 2000-2004. Nevertheless, two major challenges to measles elimination remain: 1) suboptimal vaccination coverage in many countries, which has led to continued outbreaks and the resurgence of indigenous measles in some Western European countries, and 2) setbacks with implementation of supplementary immunization activities (SIAs) in Eastern Europe in 2008. Achieving the measles elimination goal by 2010 will require 1) development of approaches to sustain and increase vaccination coverage, 2) promotion of effective outbreak prevention and control measures, and 3) further strengthening of surveillance.

Measles outbreak prevention and control among adults: Lessons from an importation outbreak in Yunnan province, China, 2015.

PubMed

Zhao, Zhixian; Zhou, Rongrong; Yu, Wen; Li, Liqun; Li, Qiongfen; Hu, Pei

2018-04-03

The incidence of measles in Yunnan Province among vaccine target-age children has decreased markedly after attaining and sustaining high 2-dose coverage of measles containing vaccine (MCV) through routine immunization services and supplementary immunization activities (SIAs). Most cases of measles now occur among adults. In 2015, we investigated a measles outbreak among adults to determine transmission patterns and the potential role of nosocomial transmission. We enhanced measles surveillance using retrospective active case search. We conducted case investigations to determine sources of infection and routes of transmission; laboratory testing included serologic and molecular diagnostic methods. Twenty-two outbreak-associated cases of measles were identified; most (86.36%) were among individuals 20 to 39 years of age (range, 7 months to 43 years). We interviewed 19 individuals who had acquired measles. The first 3 cases were infected in Tibet; 12 (63%) were hospital-acquired infections; 2 (11%) were community-acquired; and 2 (11%) were family-contact cases. We conducted outbreak response immunization (ORI) that provided MCV without regard to vaccination status; 10,596 residents between 20 and 40 years of age were vaccinated. A serological survey conducted during the ORI showed that 84% of the 20-40 year-olds were immune to measles prior to vaccination. Post-vaccination serological testing showed 100% were immune. Despite high population immunity among children and adolescents, imported measles virus transmission occurred among adults in a provincial cross-border area. Nosocomial transmission and measles immunity gaps among adults poses a threat to measles elimination and highlights the strategy of targeting adults during ORI to outbreaks with adult-to-adult transmission.

Evaluation of Immune Responses Mediated by Listeria-Stimulated Human Dendritic Cells: Implications for Cancer Vaccine Therapy

DTIC Science & Technology

2012-07-01

Mediated by Listeria -Stimulated Human Dendritic Cells: Implications for Cancer Vaccine Therapy PRINCIPAL INVESTIGATOR: David J. Chung, M D , Ph D...CONTRACT NUMBER Evaluation of Immune Responses Mediated by Listeria -Stimulated Human Dendritic Cells: Implications for Cancer Vaccine Therapy 5b...Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The purpose of this project is to study the immunomodulatory effect of Listeria on

Identifying Immune Drivers of Gulf War Illness Using a Novel Daily Sampling Approach

DTIC Science & Technology

2016-10-01

for Public Release ; Distribution Unlimited The views, opinions and/or findings contained in this report are those of the author(s) and should not be...MONITOR’S REPORT NUMBER(S) 12. DISTRIBUTION / AVAILABILITY STATEMENT Approved for Public Release ; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14...Gulf War Illness, cytokines , microglia, daily, immune, phlebotomy, fibromyalgia 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER

Enhancement of Immune Memory Responses to Respiratory Infection

DTIC Science & Technology

2017-08-01

Unlimited Distribution 13. SUPPLEMENTARY NOTES 14. ABSTRACT Maintenance of long - term immunological memory against pathogens is crucial for the rapid...highly expressed in memory B cells in mice, and Atg7 is required for maintenance of long - term memory B cells needed to protect against influenza...AWARD NUMBER: W81XWH-16-1-0360 TITLE: Enhancement of Immune Memory Responses to Respiratory Infection PRINCIPAL INVESTIGATORs: Dr Min Chen PhD

Publisher Correction: Unravelling the immune signature of Plasmodium falciparum transmission-reducing immunity.

PubMed

Stone, Will J R; Campo, Joseph J; Ouédraogo, André Lin; Meerstein-Kessel, Lisette; Morlais, Isabelle; Da, Dari; Cohuet, Anna; Nsango, Sandrine; Sutherland, Colin J; van de Vegte-Bolmer, Marga; Siebelink-Stoter, Rianne; van Gemert, Geert-Jan; Graumans, Wouter; Lanke, Kjerstin; Shandling, Adam D; Pablo, Jozelyn V; Teng, Andy A; Jones, Sophie; de Jong, Roos M; Fabra-García, Amanda; Bradley, John; Roeffen, Will; Lasonder, Edwin; Gremo, Giuliana; Schwarzer, Evelin; Janse, Chris J; Singh, Susheel K; Theisen, Michael; Felgner, Phil; Marti, Matthias; Drakeley, Chris; Sauerwein, Robert; Bousema, Teun; Jore, Matthijs M

2018-04-11

The original version of this Article contained errors in Fig. 3. In panel a, bars from a chart depicting the percentage of antibody-positive individuals in non-infectious and infectious groups were inadvertently included in place of bars depicting the percentage of infectious individuals, as described in the Article and figure legend. However, the p values reported in the Figure and the resulting conclusions were based on the correct dataset. The corrected Fig. 3a now shows the percentage of infectious individuals in antibody-negative and -positive groups, in both the PDF and HTML versions of the Article. The incorrect and correct versions of Figure 3a are also presented for comparison in the accompanying Publisher Correction as Figure 1.The HTML version of the Article also omitted a link to Supplementary Data 6. The error has now been fixed and Supplementary Data 6 is available to download.

Assessment of attitudes towards adverse events following immunization with oral poliovirus vaccine: a pilot study among high school students of Kinshasa, the Democratic Republic of Congo.

PubMed

Kinuani, Léon; Nzolo, Didier Bomene; Aloni, Michel Ntetani; Makolo, Pavel; Ntamabyaliro, Nsengi; Ntamba, Yves Lula; Kazadi, Crispin; Nyembwe, Michel; Ekila, Mathilde Bothale; Mesia, Gauthier Kahunu

2014-09-01

The aim of this study is to evaluate the reaction of students to adverse events following immunization in order to offer a baseline for developing a communication and risk management plan. This is a cross-sectional study conducted in Kinshasa. A survey was conducted between the third and the fourth rounds of Supplementary Immunization Activity. Nine hundred and fifty questionnaires were used and addressed students who attended this university from 1 to 10 June 2011. Completed questionnaires were received from 848 students, with 485 females (57·2%), 343 males (40·4%), and 20 unknown (2·4%); 46·9% of students were from the faculty of medicine and 24·7% was from the third graduate degree. From those who completed the questionnaire, 136 (16·4%) reported experiencing an adverse events following immunization. Concerning the attitude of students towards adverse events following immunization, 79 students (58·5%) did nothing; 54 (40·0%) opted for self-medication; 2 (1·5%) went to the hospital. The main finding of our study is the low rate of people referring to health-care providers for vaccine-related problems, more specially for adverse events following immunization. A risk management plan should be focused in strategies to increase communication between population and health-care providers.

Progress toward measles elimination in the People's Republic of China, 2000-2009.

PubMed

Ma, Chao; An, Zhijie; Hao, Lixin; Cairns, K Lisa; Zhang, Yan; Ma, Jing; Cao, Lei; Wen, Ning; Xu, Wenbo; Liang, Xiaofeng; Yang, Weizhong; Luo, Huiming

2011-07-01

In 2006, China set a goal of measles elimination by 2012. To describe progress toward this goal, we reviewed relevant policies and strategies and analyzed national data for 2000-2009. In response to implementation of these strategies, including increased routine measles vaccination coverage and province-specific supplementary immunization activities (SIAs), reported measles incidence decreased to a historically low level of 39.5 cases per million in 2009. A synchronized nationwide SIA was scheduled in 2010 to further decrease susceptibility to measles. However, reaching and maintaining measles elimination will require strong political commitment and efforts for strengthening surveillance, increasing 2-dose vaccine coverage to >95%, stricter enforcement of the requirement to check immunization status at school entry, and careful attention to measles susceptibility in those aged ≥15 years. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.

Evaluation of Immune Responses Mediated by Listeria-Stimulated Human Dendritic Cells: Implications for Cancer Vaccine Therapy

DTIC Science & Technology

2013-07-01

by Listeria -Stimulated Human Dendritic Cells: Implications for Cancer Vaccine Therapy PRINCIPAL INVESTIGATOR: David J. Chung, MD, PhD...2013 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-11-1-0384 Evaluation of Immune Responses Mediated by Listeria -Stimulated Human Dendritic...Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The purpose of this project is to study the immunomodulatory effect of Listeria on human

Parental perceptions surrounding polio and self-reported non-participation in polio supplementary immunization activities in Karachi, Pakistan: a mixed methods study.

PubMed

Khowaja, Asif Raza; Khan, Sher Ali; Nizam, Naveeda; Omer, Saad Bin; Zaidi, Anita

2012-11-01

To assess parent's knowledge and perceptions surrounding polio and polio vaccination, self-reported participation in polio supplementary immunization activities (SIAs) targeting children aged < 5 years, and reasons for non-participation. The mixed methods study began with a cross-sectional survey in Karachi, Pakistan. A structured questionnaire was administered to assess parental knowledge of polio and participation in polio SIAs conducted in September and October 2011. Additionally, 30 parents of Pashtun ethnicity (a high-risk group) who refused to vaccinate their children were interviewed in depth to determine why. Descriptive and bivariate analyses by ethnic and socioeconomic group were performed for quantitative data; thematic analysis was conducted for qualitative interviews with Pashtun parents. Of 1017 parents surveyed, 412 (41%) had never heard of polio; 132 (13%) did not participate in one SIA and 157 (15.4%) did not participate in either SIA. Among non-participants, 34 (21.6%) reported not having been contacted by a vaccinator; 116 (73.9%) reported having refused to participate, and 7 (4.5%) reported that the child was absent from home when the vaccinator visited. Refusals clustered in low-income Pashtun (43/441; 9.8%) and high-income families of any ethnic background (71/153; 46.4%). Low-income Pashtuns were more likely to not have participated in polio SIAs than low-income non-Pashtuns (odds ratio, OR: 7.1; 95% confidence interval, CI: 3.47-14.5). Reasons commonly cited among Pashtuns for refusing vaccination included fear of sterility; lack of faith in the polio vaccine; scepticism about the vaccination programme, and fear that the vaccine might contain religiously forbidden ingredients. In Karachi, interruption of polio transmission requires integrated and participatory community interventions targeting high-risk populations.

Transitioning Lessons Learned and Assets of the Global Polio Eradication Initiative to Global and Regional Measles and Rubella Elimination.

PubMed

Kretsinger, Katrina; Strebel, Peter; Kezaala, Robert; Goodson, James L

2017-07-01

The Global Polio Eradication Initiative has built an extensive infrastructure with capabilities and resources that should be transitioned to measles and rubella elimination efforts. Measles continues to be a major cause of child mortality globally, and rubella continues to be the leading infectious cause of birth defects. Measles and rubella eradication is feasible and cost saving. The obvious similarities in strategies between polio elimination and measles and rubella elimination include the use of an extensive surveillance and laboratory network, outbreak preparedness and response, extensive communications and social mobilization networks, and the need for periodic supplementary immunization activities. Polio staff and resources are already connected with those of measles and rubella, and transitioning existing capabilities to measles and rubella elimination efforts allows for optimized use of resources and the best opportunity to incorporate important lessons learned from polio eradication, and polio resources are concentrated in the countries with the highest burden of measles and rubella. Measles and rubella elimination strategies rely heavily on achieving and maintaining high vaccination coverage through the routine immunization activity infrastructure, thus creating synergies with immunization systems approaches, in what is termed a "diagonal approach." © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

A combined omics study on activated macrophages--enhanced role of STATs in apoptosis, immunity and lipid metabolism.

PubMed

Dinasarapu, Ashok Reddy; Gupta, Shakti; Ram Maurya, Mano; Fahy, Eoin; Min, Jun; Sud, Manish; Gersten, Merril J; Glass, Christopher K; Subramaniam, Shankar

2013-11-01

Macrophage activation by lipopolysaccharide and adenosine triphosphate (ATP) has been studied extensively because this model system mimics the physiological context of bacterial infection and subsequent inflammatory responses. Previous studies on macrophages elucidated the biological roles of caspase-1 in post-translational activation of interleukin-1β and interleukin-18 in inflammation and apoptosis. However, the results from these studies focused only on a small number of factors. To better understand the host response, we have performed a high-throughput study of Kdo2-lipid A (KLA)-primed macrophages stimulated with ATP. The study suggests that treating mouse bone marrow-derived macrophages with KLA and ATP produces 'synergistic' effects that are not seen with treatment of KLA or ATP alone. The synergistic regulation of genes related to immunity, apoptosis and lipid metabolism is observed in a time-dependent manner. The synergistic effects are produced by nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and activator protein (AP)-1 through regulation of their target cytokines. The synergistically regulated cytokines then activate signal transducer and activator of transcription (STAT) factors that result in enhanced immunity, apoptosis and lipid metabolism; STAT1 enhances immunity by promoting anti-microbial factors; and STAT3 contributes to downregulation of cell cycle and upregulation of apoptosis. STAT1 and STAT3 also regulate glycerolipid and eicosanoid metabolism, respectively. Further, western blot analysis for STAT1 and STAT3 showed that the changes in transcriptomic levels were consistent with their proteomic levels. In summary, this study shows the synergistic interaction between the toll-like receptor and purinergic receptor signaling during macrophage activation on bacterial infection. Time-course data of transcriptomics and lipidomics can be queried or downloaded from http://www.lipidmaps.org. shankar@ucsd.edu. Supplementary data are available at Bioinformatics online.

mEBT: multiple-matching Evidence-based Translator of Murine Genomic Responses for Human Immunity Studies.

PubMed

Tae, Donghyun; Seok, Junhee

2018-05-29

In this paper, we introduce multiple-matching Evidence-based Translator (mEBT) to discover genomic responses from murine expression data for human immune studies, which are significant in the given condition of mice and likely have similar responses in the corresponding condition of human. mEBT is evaluated over multiple data sets and shows improved inter-species agreement. mEBT is expected to be useful for research groups who use murine models to study human immunity. http://cdal.korea.ac.kr/mebt/. jseok14@korea.ac.kr. Supplementary data are available at Bioinformatics online.

Poliomyelitis eradication in China: 1953-2012.

PubMed

Yu, Wen-Zhou; Wen, Ning; Zhang, Yong; Wang, Hai-Bo; Fan, Chun-Xiang; Zhu, Shuang-Li; Xu, Wen-Bo; Liang, Xiao-Feng; Luo, Hui-Ming; Li, Li

2014-11-01

Poliomyelitis has historically been endemic in China and has been considered an important cause of disability and death. We reviewed strategies and measures of poliomyelitis control and eradication from 1953 to 2012. Data from notifiable disease and routine immunization reporting systems and acute flaccid paralysis (AFP) surveillance were analyzed. About 20 000 poliomyelitis cases were reported annually in the prevaccine era. During 1965-1977, live, attenuated oral poliomyelitis vaccine (OPV) was administered to children through annual mass campaigns in the winter, and the number of poliomyelitis cases started to decline. A cold chain system was established during 1982, and OPV coverage increased during the early stage of the Expanded Programme on Immunization, from 1978 to 1988. Between 1989 and 1999, routine immunization was strengthened, supplementary immunization activities (SIAs) were conducted, and the AFP surveillance system was established. China reported a last indigenous poliomyelitis case in 1994 and was certified as free of polio in 2000. To maintain its polio-free status, China kept >90% coverage of 3 doses of OPV, conducted SIAs in high-risk areas, and maintained high-quality of AFP surveillance. China succeeded in stopping the outbreak in Xinjiang in 2011. China's polio-free status was achieved and maintained through strengthening routine immunization and implementing SIAs and AFP surveillance. © The Author 2014. 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.

Assessment of source of information for polio supplementary immunization activities in 2014 and 2015, Somali, Ethiopia.

PubMed

Bedada, Selamawit Yilma; Gallagher, Kathleen; Aregay, Aron Kassahun; Mohammed, Bashir; Maalin, Mohammed Adem; Hassen, Hassen Abdisemed; Ali, Yusuf Mohammed; Braka, Fiona; Kilebou, Pierre M'pele

2017-01-01

Communication is key for the successful implementation of polio vaccination campaigns. The purpose of this study is to review and analyse the sources of information utilized by caregivers during polio supplementary immunization activities (SIAs) in Somali, Ethiopia in 2014 and 2015. Data on sources of information about the polio campaign were collected post campaign from caregivers by trained data collectors as part of house to house independent monitoring. The sources of information analysed in this paper include town criers (via megaphones), health workers, religious leaders, kebele leaders (Kebele is the lowest administrative structure in Ethiopia), radio, television, text message and others. The repetition of these sources of information was analysed across years and zones for trends. Polio vaccination campaign coverage was also reviewed by year and zones within the Somali region in parallel with the major sources of information used in the respective year and zones. 57,745 responses were used for this analysis but the responses were received from < or = 57,745 individuals since some of them may provide more than one response. Moreover, because sampling of households is conducted independently during each round of independent monitoring, the same household may have been included more than once in our analysis. The methodology used for independent monitoring does not allow for the calculation of response rates. Monitors go from house to house until information from 20 households is received. From the total 57,745 responses reviewed, over 37% of respondents reported that town criers were their source for information about the 2014 and 2015 polio SIAs. Zonal trends in using town criers as a major source of information in both study years remained consistent except in two zones. 87.5% of zones that reported at least 90% coverage during both study years had utilized town criers as a major source of information while the rest (12.5%) used health workers. We found that town criers were consistently the major source of information about the polio campaigns for Somali region parents and caregivers during polio immunization days held in 2014 and 2015. Health workers and kebele leaders were also important sources of information about the polio campaign for parents.

Laboratory surveillance for wild and vaccine-derived polioviruses, January 2004-June 2005.

PubMed

2005-09-30

A global network of 145 virology laboratories has been established by the World Health Organization (WHO) to support surveillance activities of the Polio Eradication Initiative (PEI). The Global Polio Laboratory Network analyzes stool specimens from patients with acute flaccid paralysis (AFP) and environmental samples for the presence of polioviruses. Surveillance systems detect at least one AFP case per 100,000 persons aged <15 years, collect adequate stool samples from patients, and send the samples to network laboratories for analysis. Laboratory data are used to identify locations where wild polioviruses (WPVs) or vaccine-derived polioviruses (VDPVs) are circulating, target supplementary immunization activities (SIAs) to interrupt transmission chains, and investigate genetic relationships among viral isolates. This report updates previous publications and describes the laboratory network's performance during the period January 2004-June 2005.

Immune response to functionalized mesoporous silica nanoparticles for targeted drug delivery

NASA Astrophysics Data System (ADS)

Heidegger, Simon; Gößl, Dorothée; Schmidt, Alexandra; Niedermayer, Stefan; Argyo, Christian; Endres, Stefan; Bein, Thomas; Bourquin, Carole

2015-12-01

Multifunctional mesoporous silica nanoparticles (MSN) have attracted substantial attention with regard to their high potential for targeted drug delivery. For future clinical applications it is crucial to address safety concerns and understand the potential immunotoxicity of these nanoparticles. In this study, we assess the biocompatibility and functionality of multifunctional MSN in freshly isolated, primary murine immune cells. We show that the functionalized silica nanoparticles are rapidly and efficiently taken up into the endosomal compartment by specialized antigen-presenting cells such as dendritic cells. The silica nanoparticles showed a favorable toxicity profile and did not affect the viability of primary immune cells from the spleen in relevant concentrations. Cargo-free MSN induced only very low immune responses in primary cells as determined by surface expression of activation markers and release of pro-inflammatory cytokines such as Interleukin-6, -12 and -1β. In contrast, when surface-functionalized MSN with a pH-responsive polymer capping were loaded with an immune-activating drug, the synthetic Toll-like receptor 7 agonist R848, a strong immune response was provoked. We thus demonstrate that MSN represent an efficient drug delivery vehicle to primary immune cells that is both non-toxic and non-inflammagenic, which is a prerequisite for the use of these particles in biomedical applications.Multifunctional mesoporous silica nanoparticles (MSN) have attracted substantial attention with regard to their high potential for targeted drug delivery. For future clinical applications it is crucial to address safety concerns and understand the potential immunotoxicity of these nanoparticles. In this study, we assess the biocompatibility and functionality of multifunctional MSN in freshly isolated, primary murine immune cells. We show that the functionalized silica nanoparticles are rapidly and efficiently taken up into the endosomal compartment by specialized antigen-presenting cells such as dendritic cells. The silica nanoparticles showed a favorable toxicity profile and did not affect the viability of primary immune cells from the spleen in relevant concentrations. Cargo-free MSN induced only very low immune responses in primary cells as determined by surface expression of activation markers and release of pro-inflammatory cytokines such as Interleukin-6, -12 and -1β. In contrast, when surface-functionalized MSN with a pH-responsive polymer capping were loaded with an immune-activating drug, the synthetic Toll-like receptor 7 agonist R848, a strong immune response was provoked. We thus demonstrate that MSN represent an efficient drug delivery vehicle to primary immune cells that is both non-toxic and non-inflammagenic, which is a prerequisite for the use of these particles in biomedical applications. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06122a

Imported Genotype 2B Rubella Virus Caused the 2012 Outbreak in Anqing City, China.

PubMed

Zhu, Zhen; Pan, Guixia; Zhou, Shujie; Dai, Jingjing; Chen, Xia; Tang, Jihai; Chen, Shuping; Zheng, Yilun; Song, Jie; Xu, Wenbo

2015-01-01

A rubella outbreak occurred in Anqing city of Anhui province, China, from February to July of 2012, and a total of 241 clinically diagnosed or lab-confirmed patients were reported. The highest number of rubella cases during this outbreak was recorded in teenagers between 10 and 19 years of age who had not previously received the rubella vaccine. Genotyping results indicated that the genotype 2B rubella virus (RV) was responsible for the outbreak. However, a phylogenetic analysis showed that the genotype 2B RVs isolated in Anqing City were not related to 2B RVs found in other cities of Anhui province and in other provinces of China, thus providing evidence for importation. After importation, the transmission of Anqing RVs was interrupted owing to an effective immunization campaign against rubella, suggesting the timeliness and effectiveness of contingency vaccination. Strengthening rubella surveillance, including the integration of epidemiologic information and laboratory data, is a vital strategy for rubella control and elimination. In addition, except for routine immunization, targeted supplementary immunization activities aimed at susceptible groups according to sero-epidemiological surveillance data also play a key role in stopping the continuous transmission of rubella viruses and in preventing further congenital rubella syndrome cases.

Progress in global measles control and mortality reduction, 2000-2007.

PubMed

2008-12-05

Despite the availability of a safe and effective vaccine since 1963, measles has been a major killer of children in developing countries (causing an estimated 750,000 deaths as recently as 2000), primarily because of underutilization of the vaccine. At the World Health Assembly in 2008, all World Health Organization (WHO) member states reaffirmed their commitment to achieving a 90% reduction in measles mortality by 2010 compared with 2000, a goal that was established in 2005 as part of the Global Immunization Vision and Strategy (2). This WHO-UNICEF comprehensive strategy for measles mortality reduction (1) focuses on 47 priority countries. The strategy's components include 1) achieving and maintaining high coverage (>90%) with the routinely scheduled first dose of measles-containing vaccine (MCV1) among children aged 1 year; 2) ensuring that all children receive a second opportunity for measles immunization (either through a second routine dose or through periodic supplementary immunization activities [SIAs]); 3) implementing effective laboratory-supported disease surveillance; and 4) providing appropriate clinical management for measles cases. This report updates previously published reports and describes immunization and surveillance activities implemented during 2007. Increased routine measles vaccine coverage and SIAs implemented during 2000--2007 resulted in a 74% decrease in the estimated number of measles deaths globally. An estimated 197,000 deaths from measles occurred in 2007; of these, 136,000 (69%) occurred in the WHO South-East Asian Region. Achievement of the 2010 goal will require full implementation of measles mortality reduction strategies, especially in the WHO South-East Asian Region.

Measles outbreak in Northern Central African Republic 3 years after the last national immunization campaign.

PubMed

Tricou, Vianney; Pagonendji, Marilou; Manengu, Casimir; Mutombo, Jeff; Mabo, Rock Ouambita; Gouandjika-Vasilache, Ionela

2013-02-26

Despite huge efforts to promote widespread vaccination, measles remains an important cause of morbidity and mortality worldwide, especially in African children. In March 2011, an abnormally high number of cases were reported from the Ouham Prefecture, Central African Republic to the national measles case-based surveillance system. In response, reactive vaccination activities were implemented. The aims of this study were to investigate this outbreak and describe the response. Measles cases were defined according to WHO recommendations. In the first weeks of the outbreak, blood samples were collected and sent to the Institut Pasteur in Bangui for laboratory confirmation by detection of IgM antibodies against measles virus. In addition, a portion of viral RNA was amplified from 5 IgM positive patient samples and the amplicons were sequenced for phylogenetic analysis. Between March and September 2011, 723 clinical cases originated from the Ouham Prefecture, including 2 deaths, were reported. Amongst 59 blood samples collected, 49 were positive for the detection of IgM. A high number of self-declared vaccinated subjects (31%) were found amongst the cases. Most of the cases were under 5 years. The causative virus was found to belong to genotype B3.1. In response, 2 sub-national supplementary immunization activities were quickly conducted and limited this outbreak to mainly 2 sub-prefectures. This outbreak was the largest epidemic of measles in CAR since 2002. Its occurrence, 3 years after the last national immunization campaign, highlights the necessity to pursue efforts and improve and extend immunization programs in order to reach measles elimination goal in Africa.

Updating the evidence base on the operational costs of supplementary immunization activities for current and future accelerated disease control, elimination and eradication efforts

PubMed Central

2014-01-01

Background To achieve globally or regionally defined accelerated disease control, elimination and eradication (ADC/E/E) goals against vaccine-preventable diseases requires complementing national routine immunization programs with intensive, time-limited, and targeted Supplementary Immunization Activities (SIAs). Many global and country-level SIA costing efforts have historically relied on what are now outdated benchmark figures. Mobilizing adequate resources for successful implementation of SIAs requires updated estimates of non-vaccine costs per target population. Methods This assessment updates the evidence base on the SIA operational costs through a review of literature between 1992 and 2012, and an analysis of actual expenditures from 142 SIAs conducted between 2004 and 2011 and documented in country immunization plans. These are complemented with an analysis of budgets from 31 SIAs conducted between 2006 and 2011 in order to assess the proportion of total SIA costs per person associated with various cost components. All results are presented in 2010 US dollars. Results Existing evidence indicate that average SIA operational costs were usually less than US$0.50 per person in 2010 dollars. However, the evidence is sparse, non-standardized, and largely out of date. Average operational costs per person generated from our analysis of country immunization plans are consistently higher than published estimates, approaching US$1.00 for injectable vaccines. The results illustrate that the benchmarks often used to project needs underestimate the true costs of SIAs and the analysis suggests that SIA operational costs have been increasing over time in real terms. Our assessment also illustrates that operational costs vary across several dimensions. Variations in the actual costs of SIAs likely to reflect the extents to which economies of scale associated with campaign-based delivery can be attained, the underlying strength of the immunization program, sensitivities to the relative ease of vaccine administration (i.e. orally, or by injection), and differences in disease-specific programmatic approaches. The assessment of SIA budgets by cost component illustrates that four cost drivers make up the largest proportion of costs across all vaccines: human resources, program management, social mobilization, and vehicles and transportation. These findings suggest that SIAs leverage existing health system infrastructure, reinforcing the fact that strong routine immunization programs are an important pre-requisite for achieving ADC/E/E goals. Conclusions The results presented here will be useful for national and global-level actors involved in planning, budgeting, resource mobilization, and financing of SIAs in order to create more realistic assessments of resource requirements for both existing ADC/E/E efforts as well as for new vaccines that may deploy a catch-up campaign-based delivery component. However, limitations of our analysis suggest a need to conduct further research into operational costs of SIAs. Understanding the changing face of delivery costs and cost structures for SIAs will continue to be critical to avoid funding gaps and in order to improve vaccination coverage, reduce health inequities, and achieve the ADC/E/E goals many of which have been endorsed by the World Health Assembly and are included in the Decade of Vaccines Global Vaccine Action Plan. PMID:24450832

Updating the evidence base on the operational costs of supplementary immunization activities for current and future accelerated disease control, elimination and eradication efforts.

PubMed

Gandhi, Gian; Lydon, Patrick

2014-01-22

To achieve globally or regionally defined accelerated disease control, elimination and eradication (ADC/E/E) goals against vaccine-preventable diseases requires complementing national routine immunization programs with intensive, time-limited, and targeted Supplementary Immunization Activities (SIAs). Many global and country-level SIA costing efforts have historically relied on what are now outdated benchmark figures. Mobilizing adequate resources for successful implementation of SIAs requires updated estimates of non-vaccine costs per target population. This assessment updates the evidence base on the SIA operational costs through a review of literature between 1992 and 2012, and an analysis of actual expenditures from 142 SIAs conducted between 2004 and 2011 and documented in country immunization plans. These are complemented with an analysis of budgets from 31 SIAs conducted between 2006 and 2011 in order to assess the proportion of total SIA costs per person associated with various cost components. All results are presented in 2010 US dollars. Existing evidence indicate that average SIA operational costs were usually less than US$0.50 per person in 2010 dollars. However, the evidence is sparse, non-standardized, and largely out of date. Average operational costs per person generated from our analysis of country immunization plans are consistently higher than published estimates, approaching US$1.00 for injectable vaccines. The results illustrate that the benchmarks often used to project needs underestimate the true costs of SIAs and the analysis suggests that SIA operational costs have been increasing over time in real terms. Our assessment also illustrates that operational costs vary across several dimensions. Variations in the actual costs of SIAs likely to reflect the extents to which economies of scale associated with campaign-based delivery can be attained, the underlying strength of the immunization program, sensitivities to the relative ease of vaccine administration (i.e. orally, or by injection), and differences in disease-specific programmatic approaches. The assessment of SIA budgets by cost component illustrates that four cost drivers make up the largest proportion of costs across all vaccines: human resources, program management, social mobilization, and vehicles and transportation. These findings suggest that SIAs leverage existing health system infrastructure, reinforcing the fact that strong routine immunization programs are an important pre-requisite for achieving ADC/E/E goals. The results presented here will be useful for national and global-level actors involved in planning, budgeting, resource mobilization, and financing of SIAs in order to create more realistic assessments of resource requirements for both existing ADC/E/E efforts as well as for new vaccines that may deploy a catch-up campaign-based delivery component. However, limitations of our analysis suggest a need to conduct further research into operational costs of SIAs. Understanding the changing face of delivery costs and cost structures for SIAs will continue to be critical to avoid funding gaps and in order to improve vaccination coverage, reduce health inequities, and achieve the ADC/E/E goals many of which have been endorsed by the World Health Assembly and are included in the Decade of Vaccines Global Vaccine Action Plan.

Challenges of maintaining polio-free status of the European Region.

PubMed

Khetsuriani, Nino; Pfeifer, Dina; Deshevoi, Sergei; Gavrilin, Eugene; Shefer, Abigail; Butler, Robb; Jankovic, Dragan; Spataru, Roman; Emiroglu, Nedret; Martin, Rebecca

2014-11-01

The European region, certified as polio free in 2002, had recent wild poliovirus (WPV) introductions, resulting in a major outbreak in Central Asian countries and Russia in 2010 and in current widespread WPV type 1 circulation in Israel, which endangered the polio-free status of the region. We assessed the data on the major determinants of poliovirus transmission risk (population immunity, surveillance, and outbreak preparedness) and reviewed current threats and measures implemented in response to recent WPV introductions. Despite high regional vaccination coverage and functioning surveillance, several countries in the region are at high or intermediate risk of poliovirus transmission. Coverage remains suboptimal in some countries, subnational geographic areas, and population groups, and surveillance (acute flaccid paralysis, enterovirus, and environmental) needs further strengthening. Supplementary immunization activities, which were instrumental in the rapid interruption of WPV1 circulation in 2010, should be implemented in high-risk countries to close population immunity gaps. National polio outbreak preparedness plans need strengthening. Immunization efforts to interrupt WPV transmission in Israel should continue. The European region has successfully maintained its polio-free status since 2002, but numerous challenges remain. Staying polio free will require continued coordinated efforts, political commitment and financial support from all countries. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Progress toward measles elimination--Western Pacific Region, 2009-2012.

PubMed

2013-06-07

In 2005, the World Health Organization (WHO) Regional Committee for the Western Pacific Region (WPR) resolved that WPR should aim to eliminate measles by 2012. The recommended measles elimination strategies in WPR include 1) achieving and maintaining high (≥95%) coverage with 2 doses of measles-containing vaccine (MCV) through routine immunization services and by implementing supplementary immunization activities (SIAs), when required; 2) conducting high-quality, case-based measles surveillance; 3) ensuring high-quality laboratory surveillance, with timely and accurate testing of specimens to confirm or discard suspected cases and detect measles virus for genotyping and molecular analysis; and 4) establishing and maintaining measles outbreak preparedness for rapid response and ensuring appropriate case management. This report updates the previous report and describes progress toward eliminating measles in WPR during 2009-2012. During this period, measles incidence reached a historic low, decreasing by 83%, from 34.0 to 5.9 cases per million population. However, to achieve measles elimination in WPR, additional efforts are needed to strengthen routine immunization services in countries and areas with <95% coverage with the routine first (MCV1) or second dose of MCV (MCV2), to introduce a MCV2 dose in the four remaining countries and areas that do not yet have a routine 2-dose MCV schedule, and to use SIAs to close immunity gaps among measles-susceptible populations in countries and areas that have ongoing measles virus transmission.

Interpreting the transmissibility of measles in two different post periods of supplementary immunization activities in Hubei, China.

PubMed

Chong, Ka Chun; Zhang, Chi; Zee, Benny Chung Ying; Luo, Tongyong; Wang, Lei; Tam, Greta Chun Huen; Jia, Katherine Min; Sun, Riyang; Wang, Maggie Haitian; Guan, Xuhua

2017-02-15

Although evidence has shown that supplementary immunization activity (SIA) campaigns greatly reduce the incidence of measles, their effects on disease transmissibility have seldom been monitored. A great decrease in the number of cases may be a false signal of early success towards measles elimination to policy makers. By interpreting the transmissibility in two different post-SIA periods in Hubei, China, the current study showed sustained measles transmissions despite a reduced number of cases. Two population-based cross-sectional serological surveys of measles antibodies were conducted in Hubei province in mid-2010 and mid-2011 after the implementation of SIAs. Immunoglobulin G (IgG) antibodies against measles were measured by enzyme-linked immunosorbent assay (ELISA). Based on the estimated age-specific susceptibility levels, the effective reproduction number (R), a key indicator of disease transmissibility, was determined by the next generation matrix in transmission model. The results revealed an overall IgG seroprevalence of 88.0% (95% confidence interval [CI]: 85.6-90.4%) and 89.6% (95%CI: 88.0-91.2%), respectively, in the two different periods. Comparatively lower seroprevalence rates were observed among children less than 24months of age and young adults 15 to 19years of age in 2011. The Rs were 0.76 and 1.53 for the two study periods. In conclusion, even though the incidence was reduced to below 1/100,000 in both 2010 and 2011, the reproduction number in 2011 indicates a high risk for sustained measles transmission. This finding was potentially due to a lower seropositivity rate among young adults that had not been covered in the first SIA. Thus, implementation of SIA targeted to appropriate age groups is recommended. Regular monitoring of seroprevalence is also suggested to track disease transmissibility and to align SIA with the appropriate age groups. Copyright © 2017 Elsevier Ltd. All rights reserved.

Impact of measles supplementary immunization activities on reaching children missed by routine programs.

PubMed

Portnoy, Allison; Jit, Mark; Helleringer, Stéphane; Verguet, Stéphane

2018-01-02

Measles supplementary immunization activities (SIAs) are vaccination campaigns that supplement routine vaccination programs with a recommended second dose opportunity to children of different ages regardless of their previous history of measles vaccination. They are conducted every 2-4 years and over a few weeks in many low- and middle-income countries. While SIAs have high vaccination coverage, it is unclear whether they reach the children who miss their routine measles vaccine dose. Determining who is reached by SIAs is vital to understanding their effectiveness, as well as measure progress towards measles control. We examined SIAs in low- and middle-income countries from 2000 to 2014 using data from the Demographic and Health Surveys. Conditional on a child's routine measles vaccination status, we examined whether children participated in the most recent measles SIA. The average proportion of zero-dose children (no previous routine measles vaccination defined as no vaccination date before the SIA) reached by SIAs across 14 countries was 66%, ranging from 28% in São Tomé and Príncipe to 91% in Nigeria. However, when also including all children with routine measles vaccination data, this proportion decreased to 12% and to 58% when imputing data for children with vaccination reported by the mother and vaccination marks on the vaccination card across countries. Overall, the proportions of zero-dose children reached by SIAs declined with increasing household wealth. Some countries appeared to reach a higher proportion of zero-dose children using SIAs than others, with proportions reached varying according to the definition of measles vaccination (e.g., vaccination dates on the vaccination card, vaccination marks on the vaccination card, and/or self-reported data). This suggests that some countries could improve their targeting of SIAs to children who miss other measles vaccine opportunities. Across all countries, SIAs played an important role in reaching children from poor households. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Parental perceptions surrounding polio and self-reported non-participation in polio supplementary immunization activities in Karachi, Pakistan: a mixed methods study

PubMed Central

Khowaja, Asif Raza; Khan, Sher Ali; Nizam, Naveeda; Omer, Saad Bin

2012-01-01

Abstract Objective To assess parent’s knowledge and perceptions surrounding polio and polio vaccination, self-reported participation in polio supplementary immunization activities (SIAs) targeting children aged < 5 years, and reasons for non-participation. Methods The mixed methods study began with a cross-sectional survey in Karachi, Pakistan. A structured questionnaire was administered to assess parental knowledge of polio and participation in polio SIAs conducted in September and October 2011. Additionally, 30 parents of Pashtun ethnicity (a high-risk group) who refused to vaccinate their children were interviewed in depth to determine why. Descriptive and bivariate analyses by ethnic and socioeconomic group were performed for quantitative data; thematic analysis was conducted for qualitative interviews with Pashtun parents. Findings Of 1017 parents surveyed, 412 (41%) had never heard of polio; 132 (13%) did not participate in one SIA and 157 (15.4%) did not participate in either SIA. Among non-participants, 34 (21.6%) reported not having been contacted by a vaccinator; 116 (73.9%) reported having refused to participate, and 7 (4.5%) reported that the child was absent from home when the vaccinator visited. Refusals clustered in low-income Pashtun (43/441; 9.8%) and high-income families of any ethnic background (71/153; 46.4%). Low-income Pashtuns were more likely to not have participated in polio SIAs than low-income non-Pashtuns (odds ratio, OR: 7.1; 95% confidence interval, CI: 3.47–14.5). Reasons commonly cited among Pashtuns for refusing vaccination included fear of sterility; lack of faith in the polio vaccine; scepticism about the vaccination programme, and fear that the vaccine might contain religiously forbidden ingredients. Conclusion In Karachi, interruption of polio transmission requires integrated and participatory community interventions targeting high-risk populations. PMID:23226894

Assessment of some innate immune responses in dab (Limanda limanda L.) from the North Sea as part of an integrated biological effects monitoring

NASA Astrophysics Data System (ADS)

Skouras, Andreas; Lang, Thomas; Vobach, Michael; Danischewski, Dirk; Wosniok, Werner; Scharsack, Jörn Peter; Steinhagen, Dieter

2003-10-01

The marine flatfish dab (Limanda limanda), which lives in direct contact with contaminated sediments, is frequently used as a sentinel species in international monitoring programmes on the biological effects of contaminants. In this study, immune responses were recorded as indicators of sublethal chronic effects of contaminants, in addition to measurement of the induction of mono-oxygenase ethoxyresorufin O-deethylase (EROD) in liver cells, the inhibition of acetylcholin esterase (AChE) in muscle and a quantification of grossly visible diseases and parasites. In total, 336 dab were analysed from five sampling areas in the North Sea, including the German Bight, the Dogger Bank, the Firth of Forth, and two locations close to oil and gas platforms (Ekofisk and Danfield). When considering plasma lysozyme levels, pinocytosis and respiratory burst activity of head kidney leucocytes, a clear gradient could be observed with decreased levels in individuals collected from the Firth of Forth and locations near the oil or gas platforms compared with dab from the Dogger Bank or the German Bight. Individuals with induced EROD activity displayed reduced lysozyme and respiratory burst activities. Lysozyme levels were also reduced in dab with lymphocystis or with nematodes. The data obtained indicate that the assessment of innate immune parameters in a monitoring programme provides supplementary information about immunomodulatory effects associated with the exposure of fish to contaminants. In particular, concentrations of plasma lysozyme, which can be analysed in an easy and inexpensive assay, are considered to be an appropriate parameter for use in a battery of other bioindicators.

Progress toward poliomyelitis eradication - Nigeria, January 2009-June 2010.

PubMed

2010-07-09

Nigeria has maintained a high incidence of wild poliovirus (WPV) cases attributed to persistently high proportions of under- and unimmunized children, and, for many years, the country has served as a reservoir for substantial international spread. In 2008, Nigeria reported 798 polio cases, the highest number of any country in the world. This report provides an update on poliovirus epidemiology in Nigeria during the past 18 months, January 2009-June 2010, and describes activities planned to interrupt transmission. Reported WPV cases in Nigeria decreased to 388 during 2009 (24% of global cases), and WPV incidence in Nigeria reached an all-time low during January--June 2010, with only three reported cases. Cases of circulating type 2 vaccine-derived poliovirus (cVDPV2), which first occurred in Nigeria in 2005, also declined, from 148 during the 12 months of 2009, to eight during the 6-month period, January-June 2010. One indicator of the effectiveness of immunization activities is the proportion of children with nonpolio acute flaccid paralysis (AFP) who never have received oral poliovirus vaccine (OPV). In seven high-incidence northern states of Nigeria, this proportion declined from 17.6% in 2008 to 10.7% in 2009. During 2009-2010, increased engagement of traditional, religious, and political leaders has improved community acceptance of vaccination and implementation of high-quality supplementary immunization activities (SIAs). Enhanced surveillance for polioviruses, further strengthened implementation of SIAs, and immediate immunization responses to newly identified WPV and cVDPV2 cases will be pivotal in interrupting WPV and cVDPV2 transmission in Nigeria.

Carboxyl-functionalized polyurethane nanoparticles with immunosuppressive properties as a new type of anti-inflammatory platform

NASA Astrophysics Data System (ADS)

Huang, Yen-Jang; Hung, Kun-Che; Hsieh, Fu-Yu; Hsu, Shan-Hui

2015-12-01

The interaction of nanoparticles (NPs) with the body immune system is critically important for their biomedical applications. Most NPs stimulate the immune response of macrophages. Here we show that synthetic polyurethane nanoparticles (PU NPs, diameter 34-64 nm) with rich surface COO- functional groups (zeta potential -70 to -50 mV) can suppress the immune response of macrophages. The specially-designed PU NPs reduce the gene expression levels of proinflammatory cytokines (IL-1β, IL-6, and TNF-α) for endotoxin-treated macrophages. The PU NPs increase the intracellular calcium of macrophages (4.5-6.5 fold) and activate autophagy. This is in contrast to the autophagy dysfunction generally observed upon NP exposure. These PU NPs may further decrease the nuclear factor-κB-related inflammation via autophagy pathways. The immunosuppressive activities of PU NPs can prevent animal death by inhibiting the macrophage recruitment and proinflammatory responses, confirmed by an in vivo zebrafish model. Therefore, the novel biodegradable PU NPs demonstrate COO- dependent immunosuppressive properties without carrying any anti-inflammatory agents. This study suggests that NP surface chemistry may regulate the immune response, which provides a new paradigm for potential applications of NPs in anti-inflammation and immunomodulation.The interaction of nanoparticles (NPs) with the body immune system is critically important for their biomedical applications. Most NPs stimulate the immune response of macrophages. Here we show that synthetic polyurethane nanoparticles (PU NPs, diameter 34-64 nm) with rich surface COO- functional groups (zeta potential -70 to -50 mV) can suppress the immune response of macrophages. The specially-designed PU NPs reduce the gene expression levels of proinflammatory cytokines (IL-1β, IL-6, and TNF-α) for endotoxin-treated macrophages. The PU NPs increase the intracellular calcium of macrophages (4.5-6.5 fold) and activate autophagy. This is in contrast to the autophagy dysfunction generally observed upon NP exposure. These PU NPs may further decrease the nuclear factor-κB-related inflammation via autophagy pathways. The immunosuppressive activities of PU NPs can prevent animal death by inhibiting the macrophage recruitment and proinflammatory responses, confirmed by an in vivo zebrafish model. Therefore, the novel biodegradable PU NPs demonstrate COO- dependent immunosuppressive properties without carrying any anti-inflammatory agents. This study suggests that NP surface chemistry may regulate the immune response, which provides a new paradigm for potential applications of NPs in anti-inflammation and immunomodulation. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06379e

Maximizing protection from use of oral cholera vaccines in developing country settings

PubMed Central

Desai, Sachin N; Cravioto, Alejandro; Sur, Dipika; Kanungo, Suman

2014-01-01

When oral vaccines are administered to children in lower- and middle-income countries, they do not induce the same immune responses as they do in developed countries. Although not completely understood, reasons for this finding include maternal antibody interference, mucosal pathology secondary to infection, malnutrition, enteropathy, and previous exposure to the organism (or related organisms). Young children experience a high burden of cholera infection, which can lead to severe acute dehydrating diarrhea and substantial mortality and morbidity. Oral cholera vaccines show variations in their duration of protection and efficacy between children and adults. Evaluating innate and memory immune response is necessary to understand V. cholerae immunity and to improve current cholera vaccine candidates, especially in young children. Further research on the benefits of supplementary interventions and delivery schedules may also improve immunization strategies. PMID:24861554

Assessment of source of information for polio supplementary immunization activities in 2014 and 2015, Somali, Ethiopia

PubMed Central

Bedada, Selamawit Yilma; Gallagher, Kathleen; Aregay, Aron Kassahun; Mohammed, Bashir; Maalin, Mohammed Adem; Hassen, Hassen Abdisemed; Ali, Yusuf Mohammed; Braka, Fiona; Kilebou, Pierre M’pele

2017-01-01

Introduction Communication is key for the successful implementation of polio vaccination campaigns. The purpose of this study is to review and analyse the sources of information utilized by caregivers during polio supplementary immunization activities (SIAs) in Somali, Ethiopia in 2014 and 2015. Methods Data on sources of information about the polio campaign were collected post campaign from caregivers by trained data collectors as part of house to house independent monitoring. The sources of information analysed in this paper include town criers (via megaphones), health workers, religious leaders, kebele leaders (Kebele is the lowest administrative structure in Ethiopia), radio, television, text message and others. The repetition of these sources of information was analysed across years and zones for trends. Polio vaccination campaign coverage was also reviewed by year and zones within the Somali region in parallel with the major sources of information used in the respective year and zones. 57,745 responses were used for this analysis but the responses were received from < or = 57,745 individuals since some of them may provide more than one response. Moreover, because sampling of households is conducted independently during each round of independent monitoring, the same household may have been included more than once in our analysis. The methodology used for independent monitoring does not allow for the calculation of response rates. Monitors go from house to house until information from 20 households is received. Results From the total 57,745 responses reviewed, over 37% of respondents reported that town criers were their source for information about the 2014 and 2015 polio SIAs. Zonal trends in using town criers as a major source of information in both study years remained consistent except in two zones. 87.5% of zones that reported at least 90% coverage during both study years had utilized town criers as a major source of information while the rest (12.5%) used health workers. Conclusion We found that town criers were consistently the major source of information about the polio campaigns for Somali region parents and caregivers during polio immunization days held in 2014 and 2015. Health workers and kebele leaders were also important sources of information about the polio campaign for parents. PMID:28983395

Adding interventions to mass measles vaccinations in India

PubMed Central

Verguet, Stéphane; Morris, Shaun K; Sharma, Jitendar K; Ram, Usha; Gauvreau, Cindy; Jones, Edward; Jha, Prabhat; Jit, Mark

2016-01-01

Abstract Objective To quantify the impact on mortality of offering a hypothetical set of technically feasible, high-impact interventions for maternal and child survival during India’s 2010–2013 measles supplementary immunization activity. Methods We developed Lives Saved Tool models for 12 Indian states participating in the supplementary immunization, based on state- and sex-specific data on mortality from India’s Million Deaths Study and on health services coverage from Indian household surveys. Potential add-on interventions were identified through a literature review and expert consultations. We quantified the number of lives saved for a campaign offering measles vaccine alone versus a campaign offering measles vaccine with six add-on interventions (nutritional screening and complementary feeding for children, vitamin A and zinc supplementation for children, multiple micronutrient and calcium supplementation in pregnancy, and free distribution of insecticide-treated bednets). Findings The measles vaccination campaign saved an estimated 19 016 lives of children younger than 5 years. A hypothetical campaign including measles vaccine with add-on interventions was projected to save around 73 900 lives (range: 70 200–79 300), preventing 73 700 child deaths (range: 70 000–79 000) and 300 maternal deaths (range: 200–400). The most effective interventions in the whole package were insecticide-treated bednets, measles vaccine and preventive zinc supplementation. Girls accounted for 66% of expected lives saved (12 712/19 346) for the measles vaccine campaign, and 62% of lives saved (45 721/74 367) for the hypothetical campaign including add-on interventions. Conclusion In India, a measles vaccination campaign including feasible, high-impact interventions could substantially increase the number of lives saved and mitigate gender-related inequities in child mortality. PMID:27843161

Polio Eradication Initiative contribution in strengthening immunization and integrated disease surveillance data management in WHO African region, 2014.

PubMed

Poy, Alain; Minkoulou, Etienne; Shaba, Keith; Yahaya, Ali; Gaturuku, Peter; Dadja, Landoh; Okeibunor, Joseph; Mihigo, Richard; Mkanda, Pascal

2016-10-10

The PEI Programme in the WHO African region invested in recruitment of qualified staff in data management, developing data management system and standards operating systems since the revamp of the Polio Eradication Initiative in 1997 to cater for data management support needs in the Region. This support went beyond polio and was expanded to routine immunization and integrated surveillance of priority diseases. But the impact of the polio data management support to other programmes such as routine immunization and disease surveillance has not yet been fully documented. This is what this article seeks to demonstrate. We reviewed how Polio data management area of work evolved progressively along with the expansion of the data management team capacity and the evolution of the data management systems from initiation of the AFP case-based to routine immunization, other case based disease surveillance and Supplementary immunization activities. IDSR has improved the data availability with support from IST Polio funded data managers who were collecting them from countries. The data management system developed by the polio team was used by countries to record information related to not only polio SIAs but also for other interventions. From the time when routine immunization data started to be part of polio data management team responsibility, the number of reports received went from around 4000 the first year (2005) to >30,000 the second year and to >47,000 in 2014. Polio data management has helped to improve the overall VPD, IDSR and routine data management as well as emergency response in the Region. As we approach the polio end game, the African Region would benefit in using the already set infrastructure for other public health initiative in the Region. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

The Role of Brain Inflammation in Epileptogenesis in TSC

DTIC Science & Technology

2013-07-01

and adaptive immunity during epileptogenesis and spontaneous seizures: evidence from experimental models and human temporal lobe epilepsy . Neurobiol...tissue obtained from epilepsy patients, such as with mesial temporal sclerosis. Different types of inflammatory mediators and pathways have been...13. SUPPLEMENTARY NOTES 14. ABSTRACT Epilepsy is a common, disabling problem in patients with tuberous sclerosis complex (TSC) and

Poliomyelitis Outbreak,Pointe-Noire, Republic of the Congo, September 2010–February 2011

PubMed Central

Llosa, Augusto E.; Mouniaman-Nara, Isabelle; Kouassi, Felix; Ngala, Joseph; Boxall, Naomi; Porten, Klaudia; Grais, Rebecca F.

2011-01-01

On November 4, 2010, the Republic of the Congo declared a poliomyelitis outbreak. A cross-sectional survey in Pointe-Noire showed poor sanitary conditions and low vaccination coverage (55.5%), particularly among young adults. Supplementary vaccination should focus on older age groups in countries with evidence of immunity gaps. PMID:21801636

Imported Genotype 2B Rubella Virus Caused the 2012 Outbreak in Anqing City, China

PubMed Central

Dai, Jingjing; Chen, Xia; Tang, Jihai; Chen, Shuping; Zheng, Yilun; Song, Jie; Xu, Wenbo

2015-01-01

A rubella outbreak occurred in Anqing city of Anhui province, China, from February to July of 2012, and a total of 241 clinically diagnosed or lab-confirmed patients were reported. The highest number of rubella cases during this outbreak was recorded in teenagers between 10 and 19 years of age who had not previously received the rubella vaccine. Genotyping results indicated that the genotype 2B rubella virus (RV) was responsible for the outbreak. However, a phylogenetic analysis showed that the genotype 2B RVs isolated in Anqing City were not related to 2B RVs found in other cities of Anhui province and in other provinces of China, thus providing evidence for importation. After importation, the transmission of Anqing RVs was interrupted owing to an effective immunization campaign against rubella, suggesting the timeliness and effectiveness of contingency vaccination. Strengthening rubella surveillance, including the integration of epidemiologic information and laboratory data, is a vital strategy for rubella control and elimination. In addition, except for routine immunization, targeted supplementary immunization activities aimed at susceptible groups according to sero-epidemiological surveillance data also play a key role in stopping the continuous transmission of rubella viruses and in preventing further congenital rubella syndrome cases. PMID:26402467

Evaluation of nationwide supplementary immunization in Lao People's Democratic Republic: Population-based seroprevalence survey of anti-measles and anti-rubella IgG in children and adults, mathematical modelling and a stability testing of the vaccine

PubMed Central

Miyano, Shinsuke; Mori, Yoshio; Vynnycky, Emilia; Keungsaneth, Phath; Vongphrachanh, Phengta; Xeuatvongsa, Anonh; Sisouk, Thongchanh; Som-Oulay, Vilasak; Khamphaphongphane, Bouaphan; Sengkeopaseuth, Bounthanom; Pathammavong, Chansay; Phounphenghak, Kongxay; Kitamura, Tomomi; Takeda, Makoto; Komase, Katsuhiro

2018-01-01

Background Measles outbreaks have occurred in some countries despite supplementary immunization activities (SIA) using measles-containing vaccine with high vaccination coverage. We conducted a cross-sectional seroprevalence survey to estimate population immunity in Lao People's Democratic Republic where repeated mass immunization has failed to eliminate measles. Methods and findings In this nationwide multistage cluster sampling survey conducted in 2014 based on probability proportionate to size sampling, blood samples were collected from 2,135 children and adults living in 52 randomly selected villages. Anti-measles and anti-rubella IgG were measured, and IgG prevalence was calculated. We applied mathematical modelling to estimate the number of cases of congenital rubella syndrome (CRS) in 2013 that were averted by the 2011 SIA. A stability testing was applied to the MR vaccine at 4°C, 25°C, and 35°C to examine stability differences between measles and rubella vaccine components. Measles IgG prevalence was significantly lower in the target age groups (5–21 years) of the 2011 SIA using a combination vaccine for measles and rubella vaccine (MR vaccine) than in young adults (22–39 years) (86.8% [95% CI: 83.0–90.6] vs. 99.0% [98.3–99.8]; p<0.001), whereas rubella IgG prevalence was significantly higher (88.2% [84.5–91.8] vs. 74.6% [70.7–78.5]; p<0.001). In the SIA target age groups, prevalence of measles IgG, but not rubella IgG, increased with age. CRS cases prevented in 2013 ranged from 16 [0–50] to 92 [32–180] if the force of infection had remained unchanged or had been reduced by 75%, respectively. In freeze-dried conditions, the measles vaccine component was more heat sensitive than the rubella component. Conclusions Inconsistent IgG prevalence between measles and rubella in Lao PDR can be partly explained by different stability of the measles and rubella vaccine components under heat exposure. Suboptimal vaccine handling may cause insufficient immunogenicity for measles, which subsequently leads to an outbreak despite high SIA coverage, while direct evidence is lacking. Temperature monitoring of the vaccine should be conducted. PMID:29596472

Evaluation of nationwide supplementary immunization in Lao People's Democratic Republic: Population-based seroprevalence survey of anti-measles and anti-rubella IgG in children and adults, mathematical modelling and a stability testing of the vaccine.

PubMed

Hachiya, Masahiko; Miyano, Shinsuke; Mori, Yoshio; Vynnycky, Emilia; Keungsaneth, Phath; Vongphrachanh, Phengta; Xeuatvongsa, Anonh; Sisouk, Thongchanh; Som-Oulay, Vilasak; Khamphaphongphane, Bouaphan; Sengkeopaseuth, Bounthanom; Pathammavong, Chansay; Phounphenghak, Kongxay; Kitamura, Tomomi; Takeda, Makoto; Komase, Katsuhiro

2018-01-01

Measles outbreaks have occurred in some countries despite supplementary immunization activities (SIA) using measles-containing vaccine with high vaccination coverage. We conducted a cross-sectional seroprevalence survey to estimate population immunity in Lao People's Democratic Republic where repeated mass immunization has failed to eliminate measles. In this nationwide multistage cluster sampling survey conducted in 2014 based on probability proportionate to size sampling, blood samples were collected from 2,135 children and adults living in 52 randomly selected villages. Anti-measles and anti-rubella IgG were measured, and IgG prevalence was calculated. We applied mathematical modelling to estimate the number of cases of congenital rubella syndrome (CRS) in 2013 that were averted by the 2011 SIA. A stability testing was applied to the MR vaccine at 4°C, 25°C, and 35°C to examine stability differences between measles and rubella vaccine components. Measles IgG prevalence was significantly lower in the target age groups (5-21 years) of the 2011 SIA using a combination vaccine for measles and rubella vaccine (MR vaccine) than in young adults (22-39 years) (86.8% [95% CI: 83.0-90.6] vs. 99.0% [98.3-99.8]; p<0.001), whereas rubella IgG prevalence was significantly higher (88.2% [84.5-91.8] vs. 74.6% [70.7-78.5]; p<0.001). In the SIA target age groups, prevalence of measles IgG, but not rubella IgG, increased with age. CRS cases prevented in 2013 ranged from 16 [0-50] to 92 [32-180] if the force of infection had remained unchanged or had been reduced by 75%, respectively. In freeze-dried conditions, the measles vaccine component was more heat sensitive than the rubella component. Inconsistent IgG prevalence between measles and rubella in Lao PDR can be partly explained by different stability of the measles and rubella vaccine components under heat exposure. Suboptimal vaccine handling may cause insufficient immunogenicity for measles, which subsequently leads to an outbreak despite high SIA coverage, while direct evidence is lacking. Temperature monitoring of the vaccine should be conducted.

Polio immunity and the impact of mass immunization campaigns in the Democratic Republic of the Congo.

PubMed

Voorman, Arend; Hoff, Nicole A; Doshi, Reena H; Alfonso, Vivian; Mukadi, Patrick; Muyembe-Tamfum, Jean-Jacques; Wemakoy, Emile Okitolonda; Bwaka, Ado; Weldon, William; Gerber, Sue; Rimoin, Anne W

2017-10-09

In order to prevent outbreaks from wild and vaccine-derived poliovirus, maintenance of population immunity in non-endemic countries is critical. We estimated population seroprevalence using dried blood spots collected from 4893 children 6-59months olds in the 2013-2014 Demographic and Health Survey in the Democratic Republic of the Congo (DRC). Population immunity was 81%, 90%, and 70% for poliovirus types 1, 2, and 3, respectively. Among 6-59-month-old children, 78% reported at least one dose of polio in routine immunization, while only 15% had three doses documented on vaccination cards. All children in the study had been eligible for at least two trivalent oral polio vaccine campaigns at the time of enrollment; additional immunization campaigns seroconverted 5.0%, 14%, and 5.5% of non-immune children per-campaign for types 1, 2, and 3, respectively, averaged over relevant campaigns for each serotype. Overall polio immunity was high at the time of the study, though pockets of low immunity cannot be ruled out. The DRC still relies on supplementary immunization campaigns, and this report stresses the importance of the quality and coverage of those campaigns over their quantity, as well as the importance of routine immunization. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Defense Against Cannibalism: The SdpI Family of Bacterial Immunity/Signal Transduction Proteins

PubMed Central

Povolotsky, Tatyana Leonidovna; Orlova, Ekaterina; Tamang, Dorjee G.

2010-01-01

The SdpI family consists of putative bacterial toxin immunity and signal transduction proteins. One member of the family in Bacillus subtilis, SdpI, provides immunity to cells from cannibalism in times of nutrient limitation. SdpI family members are transmembrane proteins with 3, 4, 5, 6, 7, 8, or 12 putative transmembrane α-helical segments (TMSs). These varied topologies appear to be genuine rather than artifacts due to sequencing or annotation errors. The basic and most frequently occurring element of the SdpI family has 6 TMSs. Homologues of all topological types were aligned to determine the homologous TMSs and loop regions, and the positive-inside rule was used to determine sidedness. The two most conserved motifs were identified between TMSs 1 and 2 and TMSs 4 and 5 of the 6 TMS proteins. These showed significant sequence similarity, leading us to suggest that the primordial precursor of these proteins was a 3 TMS–encoding genetic element that underwent intragenic duplication. Various deletional and fusional events, as well as intragenic duplications and inversions, may have yielded SdpI homologues with topologies of varying numbers and positions of TMSs. We propose a specific evolutionary pathway that could have given rise to these distantly related bacterial immunity proteins. We further show that genes encoding SdpI homologues often appear in operons with genes for homologues of SdpR, SdpI’s autorepressor. Our analyses allow us to propose structure–function relationships that may be applicable to most family members. Electronic supplementary material The online version of this article (doi:10.1007/s00232-010-9260-7) contains supplementary material, which is available to authorized users. PMID:20563570

Response to a Large Polio Outbreak in a Setting of Conflict - Middle East, 2013-2015.

PubMed

Mbaeyi, Chukwuma; Ryan, Michael J; Smith, Philip; Mahamud, Abdirahman; Farag, Noha; Haithami, Salah; Sharaf, Magdi; Jorba, Jaume C; Ehrhardt, Derek

2017-03-03

As the world advances toward the eradication of polio, outbreaks of wild poliovirus (WPV) in polio-free regions pose a substantial risk to the timeline for global eradication. Countries and regions experiencing active conflict, chronic insecurity, and large-scale displacement of persons are particularly vulnerable to outbreaks because of the disruption of health care and immunization services (1). A polio outbreak occurred in the Middle East, beginning in Syria in 2013 with subsequent spread to Iraq (2). The outbreak occurred 2 years after the onset of the Syrian civil war, resulted in 38 cases, and was the first time WPV was detected in Syria in approximately a decade (3,4). The national governments of eight countries designated the outbreak a public health emergency and collaborated with partners in the Global Polio Eradication Initiative (GPEI) to develop a multiphase outbreak response plan focused on improving the quality of acute flaccid paralysis (AFP) surveillance* and administering polio vaccines to >27 million children during multiple rounds of supplementary immunization activities (SIAs). † Successful implementation of the response plan led to containment and interruption of the outbreak within 6 months of its identification. The concerted approach adopted in response to this outbreak could serve as a model for responding to polio outbreaks in settings of conflict and political instability.

[Analysis on epidemiological characteristics of measles before and after measles vaccine supplement immunization activities in Changzhou municipal in 2007].

PubMed

Zhang, Qian; Zhang, Jian-Tao; Bian, Chen

2010-02-01

To analyze the epidemiological characteristics of measles before and after measles attenuated live vaccine (MV) supplementary immunization activities (SIAs) in Changzhou municipal in 2007-2008 and approach measures of measles elimination. Analyze measles epidemiology and control measures with descriptive epidemiology. After SIAs in Nov.2007, the reported measles incidence was 24.13/100000, and increased by 91.60% in 2008 than in 2007, except Jintan and Liyang town, the others were higher in 2008 than in 2007. The reported measles incidence of 5-9 years old was lower in 2008 than in 2007. However, the reported measles incidence of other age groups was higher. One incidence peak reached 216.92/100000 was found in < 1 year old group and another peak appeared at aged 20-30 years old group. The proportions of measles cases of 8 months-14 years old in 2007 and 2008 were 53.47% and 54.38%. 7.37% and 4.18% of them received MV respectively. The reported cases in 2008 increased and 68.05% of them were floating population. Low coverage of MVwas the main cause of high measles incidence. It indicated that a timely and strengthened routine vaccination, a high quality SIA, and well organized floating population management and surveillance are essential strategies to eliminate measles.

The Journalists Initiatives on Immunisation Against Polio and Improved Acceptance of the Polio Vaccine in Northern Nigeria 2007-2015.

PubMed

Warigon, Charity; Mkanda, Pascal; Banda, Richard; Zakari, Furera; Damisa, Eunice; Idowu, Audu; Bawa, Samuel; Gali, Emmanuel; Tegegne, Sisay G; Hammanyero, Kulchumi; Nsubuga, Peter; Korir, Charles; Vaz, Rui G

2016-05-01

The polio eradication initiative had major setbacks in 2003 and 2007 due to media campaigns in which renowned scholars and Islamic clerics criticized polio vaccines. The World Health Organization (WHO) partnered with journalists in 2007 to form the Journalists Initiatives on Immunisation Against Polio (JAP), to develop communication initiatives aimed at highlighting polio eradication activities and the importance of immunization in northern Nigeria. We evaluated the impact of JAP activities in Kaduna State by determining the total number of media materials produced and the number of newspaper clips and bulletins published in support of polio eradication. We also determined the number of households in noncompliant communities that became compliant with vaccination during 2015 supplementary immunization activities (SIAs) after JAP interventions and compared caregivers' sources of information about SIAs in 2007 before and after the JAP was formed. Since creation of the JAP, >500 reports have been published and aired, with most portraying polio vaccine positively. During June 2015 SIAs in high-risk wards of Kaduna STATE, JAP interventions resulted in vaccination of 5122 of 5991 children (85.5%) from noncompliant households. During early 2007, the number of caregivers who had heard about SIA rounds from the media increased from 26% in January, before the JAP was formed, to 33% in March, after the initiation of JAP activities. The formation of the JAP resulted in measurable improvement in the acceptance of polio vaccine in northern Nigeria. © 2016 World Health Organization; licensee Oxford Journals.

Poor supplementary motor area activation differentiates auditory verbal hallucination from imagining the hallucination☆

PubMed Central

Raij, Tuukka T.; Riekki, Tapani J.J.

2012-01-01

Neuronal underpinnings of auditory verbal hallucination remain poorly understood. One suggested mechanism is brain activation that is similar to verbal imagery but occurs without the proper activation of the neuronal systems that are required to tag the origins of verbal imagery in one's mind. Such neuronal systems involve the supplementary motor area. The supplementary motor area has been associated with awareness of intention to make a hand movement, but whether this region is related to the sense of ownership of one's verbal thought remains poorly known. We hypothesized that the supplementary motor area is related to the distinction between one's own mental processing (auditory verbal imagery) and similar processing that is attributed to non-self author (auditory verbal hallucination). To test this hypothesis, we asked patients to signal the onset and offset of their auditory verbal hallucinations during functional magnetic resonance imaging. During non-hallucination periods, we asked the same patients to imagine the hallucination they had previously experienced. In addition, healthy control subjects signaled the onset and offset of self-paced imagery of similar voices. Both hallucinations and the imagery of hallucinations were associated with similar activation strengths of the fronto-temporal language-related circuitries, but the supplementary motor area was activated more strongly during the imagery than during hallucination. These findings suggest that auditory verbal hallucination resembles verbal imagery in language processing, but without the involvement of the supplementary motor area, which may subserve the sense of ownership of one's own verbal imagery. PMID:24179739

Tracking global changes induced in the CD4 T-cell receptor repertoire by immunization with a complex antigen using short stretches of CDR3 protein sequence.

PubMed

Thomas, Niclas; Best, Katharine; Cinelli, Mattia; Reich-Zeliger, Shlomit; Gal, Hilah; Shifrut, Eric; Madi, Asaf; Friedman, Nir; Shawe-Taylor, John; Chain, Benny

2014-11-15

The clonal theory of adaptive immunity proposes that immunological responses are encoded by increases in the frequency of lymphocytes carrying antigen-specific receptors. In this study, we measure the frequency of different T-cell receptors (TcR) in CD4 + T cell populations of mice immunized with a complex antigen, killed Mycobacterium tuberculosis, using high throughput parallel sequencing of the TcRβ chain. Our initial hypothesis that immunization would induce repertoire convergence proved to be incorrect, and therefore an alternative approach was developed that allows accurate stratification of TcR repertoires and provides novel insights into the nature of CD4 + T-cell receptor recognition. To track the changes induced by immunization within this heterogeneous repertoire, the sequence data were classified by counting the frequency of different clusters of short (3 or 4) continuous stretches of amino acids within the antigen binding complementarity determining region 3 (CDR3) repertoire of different mice. Both unsupervised (hierarchical clustering) and supervised (support vector machine) analyses of these different distributions of sequence clusters differentiated between immunized and unimmunized mice with 100% efficiency. The CD4 + TcR repertoires of mice 5 and 14 days postimmunization were clearly different from that of unimmunized mice but were not distinguishable from each other. However, the repertoires of mice 60 days postimmunization were distinct both from naive mice and the day 5/14 animals. Our results reinforce the remarkable diversity of the TcR repertoire, resulting in many diverse private TcRs contributing to the T-cell response even in genetically identical mice responding to the same antigen. However, specific motifs defined by short stretches of amino acids within the CDR3 region may determine TcR specificity and define a new approach to TcR sequence classification. The analysis was implemented in R and Python, and source code can be found in Supplementary Data. b.chain@ucl.ac.uk Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press.

Supplementary Teaching Materials for Business Courses.

ERIC Educational Resources Information Center

Boulden, Alfred W., Ed.

This teaching guide for business education contains supplementary instructional materials for the subjects of accounting, business English, business mathematics, career education, consumer education, data processing, and office procedures. The units differ in format and in types of learning activities presented. The learning activity package for…

Timely measles vaccination in Tianjin, China: a cross-sectional study of immunization records and mothers.

PubMed

Wagner, Abram L; Zhang, Ying; Montgomery, JoLynn P; Ding, Yaxing; Carlson, Bradley F; Boulton, Matthew L

2014-08-29

Measles is a highly infectious disease, and timely administration of two doses of vaccine can ensure adequate protection against measles for all ages in a population. This study aims to estimate the proportion of children aged 8 months to 6 years vaccinated on time with measles-containing vaccines (MCV) and vaccinated during the 2008 and 2010 measles supplementary immunization activities. This study also characterizes differences in mean age at vaccination and vaccination timeliness by demographic characteristics, and describes maternal knowledge of measles vaccination. Immunization records were selected from a convenience sample of immunization clinics in Tianjin, China. From the records, overall vaccination coverage and timely vaccination coverage were calculated for different demographic groups. Mothers were also interviewed at these clinics to ascertain their knowledge of measles vaccination. Within the 329 immunization clinic records, child's birth year and district of residence were found to be significant predictors of different measures of vaccine timeliness. Children born in 2009 had a lower age at MCV dose 2 administration (17.96 months) than children born in 2005 (22.00 months). Children living in Hebei, a district in the urban center of Tianjin were less likely to be vaccinated late than children living in districts further from the urban core of Tianjin. From the 31 interviews with mothers, most women believed that timely vaccination was very important and more than one dose was very necessary; most did not know whether their child needed another dose. When reviewing MCV coverage in China, most studies do not consider timeliness. However, this study shows that overall vaccination coverage can greatly overestimate vaccination coverage within certain segments of the population, such as young infants.

An Outbreak of Type Π Vaccine-Derived Poliovirus in Sichuan Province, China: Emergence and Circulation in an Under-Immunized Population

PubMed Central

Fan, Chun-Xiang; Liu, Qing-Lian; Hao, Li-Xin; Liu, Yu; Zheng, Jing-Shan; Qin, Zhi-Ying; Xia, Wei; Zhang, Shi-Yue; Yin, Zun-Dong; Jing, Qiong; Zhang, Yan-Xia; Huang, Rong-Na; Yang, Ru-Pei; Tong, Wen-Bin; Qi, Qi; Guan, Xu-Jing; Jing, Yu-Lin; Ma, Qian-Li; Wang, Jin; Ma, Xiao-Zhen; Chen, Na; Zheng, Hong-Ru; Li, Yin-Qiao; Ma, Chao; Su, Qi-Ru; Reilly, Kathleen H.; Luo, Hui-Ming; Wu, Xian-Ping; Wen, Ning; Yang, Wei-Zhong

2014-01-01

Background During August 2011–February 2012, an outbreak of type Π circulating vaccine-derived poliovirus (cVDPVs) occurred in Sichuan Province, China. Methods A field investigation of the outbreak was conducted to characterize outbreak isolates and to guide emergency response. Sequence analysis of poliovirus capsid protein VP1 was performed to determine the viral propagation, and a coverage survey was carried out for risk assessment. Results One clinical compatible polio case and three VDPV cases were determined in Ngawa County, Ngawa Tibetan and Qiang Autonomous Prefecture, Sichuan Province. Case patients were unimmunized children, 0.8–1 years old. Genetic sequencing showed that the isolates diverged from the VP1 region of the type Π Sabin strain by 5–12 nucleotides (nt) and shared the same 5 nt VP1 substitutions, which indicate single lineage of cVDPVs. Of the 7 acute flaccid paralysis cases (all>6 months) reported in Ngawa Prefecture in 2011, 4 (57.1%) cases (including 2 polio cases) did not receive oral attenuated poliovirus vaccine. Supplementary immunization activities (SIAs) were conducted in February–May, 2012, and the strain has not been isolated since. Conclusion High coverage of routine immunization should be maintained among children until WPV transmission is globally eradicated. Risk assessments should be conducted regularly to pinpoint high risk areas or subpopulations, with SIAs developed if necessary. PMID:25503964

Feasibility of using global system for mobile communication (GSM)-based tracking for vaccinators to improve oral poliomyelitis vaccine campaign coverage in rural Pakistan.

PubMed

Chandir, Subhash; Dharma, Vijay Kumar; Siddiqi, Danya Arif; Khan, Aamir Javed

2017-09-05

Despite multiple rounds of immunization campaigns, it has not been possible to achieve optimum immunization coverage for poliovirus in Pakistan. Supplementary activities to improve coverage of immunization, such as door-to-door campaigns are constrained by several factors including inaccurate hand-drawn maps and a lack of means to objectively monitor field teams in real time, resulting in suboptimal vaccine coverage during campaigns. Global System for Mobile Communications (GSM) - based tracking of mobile subscriber identity modules (SIMs) of vaccinators provides a low-cost solution to identify missed areas and ensure effective immunization coverage. We conducted a pilot study to investigate the feasibility of using GSM technology to track vaccinators through observing indicators including acceptability, ease of implementation, costs and scalability as well as the likelihood of ownership by District Health Officials. The real-time location of the field teams was displayed on a GSM tracking web dashboard accessible by supervisors and managers for effective monitoring of workforce attendance including 'time in-time out', and discerning if all target areas - specifically remote and high-risk locations - had been reached. Direct access to this information by supervisors eliminated the possibility of data fudging and inaccurate reporting by workers regarding their mobility. The tracking cost per vaccinator was USD 0.26/month. Our study shows that GSM-based tracking is potentially a cost-efficient approach, results in better monitoring and accountability, is scalable and provides the potential for improved geographic coverage of health services. Copyright © 2017 Elsevier Ltd. All rights reserved.

[The historical development of immunization in Germany. From compulsory smallpox vaccination to a National Action Plan on Immunization].

PubMed

Klein, S; Schöneberg, I; Krause, G

2012-11-01

In the German Reich, smallpox vaccinations were organized by the state. A mandatory vaccination throughout the empire was introduced in 1874, which was continued in the Federal Republic of Germany (FRG) and the German Democratic Republic (GDR) until 1982/1983. From 1935, health departments were responsible for vaccinations. In the GDR, immunization was tightly organized: The state made great efforts to achieve high vaccination rates. Responsibilities were clearly defined at all levels and for all ages. While vaccination was initially mandatory only at the regional level, the legally mandated immunization schedule later contained compulsory vaccinations, e.g., against measles. In the beginning there were mandatory vaccinations in the FRG at the Länder level. Since 1961, the Federal Epidemics Act has impeded obligatory vaccinations. Instead, voluntary vaccinations based on recommendations were stressed. Since the 1980s, vaccinations have been shifted from the public health service sector to office-based physicians. Today, public health authorities offer mainly supplementary vaccinations. In 2007, protective immunizations were introduced as compulsory benefits of the statutory health insurance (SHI). Recently, the German federal states developed a National Vaccination Plan to support immunization strategies.

The Journalists Initiatives on Immunisation Against Polio and Improved Acceptance of the Polio Vaccine in Northern Nigeria 2007–2015

PubMed Central

Warigon, Charity; Mkanda, Pascal; Banda, Richard; Zakari, Furera; Damisa, Eunice; Idowu, Audu; Bawa, Samuel; Gali, Emmanuel; Tegegne, Sisay G.; Hammanyero, Kulchumi; Nsubuga, Peter; Korir, Charles; Vaz, Rui G.

2016-01-01

Background. The polio eradication initiative had major setbacks in 2003 and 2007 due to media campaigns in which renowned scholars and Islamic clerics criticized polio vaccines. The World Health Organization (WHO) partnered with journalists in 2007 to form the Journalists Initiatives on Immunisation Against Polio (JAP), to develop communication initiatives aimed at highlighting polio eradication activities and the importance of immunization in northern Nigeria. Methods. We evaluated the impact of JAP activities in Kaduna State by determining the total number of media materials produced and the number of newspaper clips and bulletins published in support of polio eradication. We also determined the number of households in noncompliant communities that became compliant with vaccination during 2015 supplementary immunization activities (SIAs) after JAP interventions and compared caregivers’ sources of information about SIAs in 2007 before and after the JAP was formed. Results. Since creation of the JAP, >500 reports have been published and aired, with most portraying polio vaccine positively. During June 2015 SIAs in high-risk wards of Kaduna STATE, JAP interventions resulted in vaccination of 5122 of 5991 children (85.5%) from noncompliant households. During early 2007, the number of caregivers who had heard about SIA rounds from the media increased from 26% in January, before the JAP was formed, to 33% in March, after the initiation of JAP activities. Conclusions. The formation of the JAP resulted in measurable improvement in the acceptance of polio vaccine in northern Nigeria. PMID:26721745

Cross-species Virus-host Protein-Protein Interactions Inhibiting Innate Immunity

DTIC Science & Technology

2016-07-01

Distribution A: Approved for public release; distribution is unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The single- stranded negative sense RNA...focused upon members of three negative-sense single- stranded RNA (ssRNA(-)) virus families with know or suspected histories of changes in host-species...however, the N and C-termini are disordered extended strands . In contrast, our covariance analysis mapped hotspots for protein interaction to the

The impact of Supplementary Immunization Activities on the epidemiology of measles in Tianjin, China

PubMed Central

Wagner, Abram L.; Zhang, Ying; Mukherjee, Bhramar; Ding, Yaxing; Wells, Eden V.; Boulton, Matthew L.

2016-01-01

Summary Objectives China has repeatedly used supplemental immunization activities (SIAs) to work towards measles elimination, but it is unknown if the SIAs are reaching non-locals, migrants from rural to urban areas. This study characterizes temporal trends in measles incidence by local and non-local residency and evaluates the impact of SIAs on measles incidence in Tianjin, China. Methods Daily measles case counts were tabulated separately by residency. These two datasets were combined so that each day had two observations. We conducted Poisson regression using generalized estimating equations with an exchangeable working correlation structure to estimate rate ratios (RRs). Results There were 12,465 measles cases in Tianjin over the 10-year period. The rate of measles was higher in non-locals than locals before the 2008 SIA (RR: 3.60, 95% CI: 3.27, 3.96), but this attenuates to a RR of 1.22 between the 2008 and 2010 SIAs (95% CI: 1.02, 1.45). Following the 2010 SIA, non-locals had a lower rate of measles (RR: 0.78, 95% CI: 0.69, 0.87). Conclusions The disparity in measles incidence between locals and non-locals was reduced following two SIAs. Sustained public health interventions will be needed to maintain low measles incidence among non-locals given ongoing migration of people throughout China. PMID:26972042

Geo-spatial reporting for monitoring of household immunization coverage through mobile phones: Findings from a feasibility study.

PubMed

Kazi, A M; Ali, M; K, Ayub; Kalimuddin, H; Zubair, K; Kazi, A N; A, Artani; Ali, S A

2017-11-01

The addition of Global Positioning System (GPS) to a mobile phone makes it a very powerful tool for surveillance and monitoring coverage of health programs. This technology enables transfer of data directly into computer applications and cross-references to Geographic Information Systems (GIS) maps, which enhances assessment of coverage and trends. Utilization of these systems in low and middle income countries is currently limited, particularly for immunization coverage assessments and polio vaccination campaigns. We piloted the use of this system and discussed its potential to improve the efficiency of field-based health providers and health managers for monitoring of the immunization program. Using "30×7" WHO sampling technique, a survey of children less than five years of age was conducted in random clusters of Karachi, Pakistan in three high risk towns where a polio case was detected in 2011. Center point of the cluster was calculated by the application on the mobile. Data and location coordinates were collected through a mobile phone. This data was linked with an automated mHealth based monitoring system for monitoring of Supplementary Immunization Activities (SIAs) in Karachi. After each SIA, a visual report was generated according to the coordinates collected from the survey. A total of 3535 participants consented to answer to a baseline survey. We found that the mobile phones incorporated with GIS maps can improve efficiency of health providers through real-time reporting and replacing paper based questionnaire for collection of data at household level. Visual maps generated from the data and geospatial analysis can also give a better assessment of the immunization coverage and polio vaccination campaigns. The study supports a model system in resource constrained settings that allows routine capture of individual level data through GPS enabled mobile phone providing actionable information and geospatial maps to local public health managers, policy makers and study staff monitoring immunization coverage. Copyright © 2017 Elsevier B.V. All rights reserved.

Measles and Rubella Global Strategic Plan 2012-2020 midterm review.

PubMed

Orenstein, W A; Hinman, A; Nkowane, B; Olive, J M; Reingold, A

2018-01-11

1. Measles eradication is the ultimate goal but it is premature to set a date for its accomplishment. Existing regional elimination goals should be vigorously pursued to enable setting a global target by 2020. 2. The basic strategic approaches articulated in the Global Measles and Rubella Strategic Plan 2012-2020 are valid to achieve the goals but have not been fully implemented (or not appropriately adapted to local situations). 3. The report recommends a shift from primary reliance on supplementary immunization activities (SIAs) to assure two doses of measles-containing vaccine (MCV) are delivered to the target population to primary reliance on ongoing services to assure administration of two doses of MCV. Regular high quality SIAs will still be necessary while ongoing services are being strengthened. 4. The report recommends a shift from primary reliance on coverage to measure progress to incorporating disease incidence as a major indicator. 5. The report recommends that the measles/rubella vaccination program be considered an indicator for the quality of the overall immunization program and that measles/rubella incidence and measles and rubella vaccination coverage be considered as primary indicators of immunization program performance. 6. Polio transition presents both risks and opportunities: risks should be minimized and opportunities maximized. 7. A school entry immunization check could contribute significantly to strengthening overall immunization services with assurance that recommended doses of measles and rubella vaccines as well as other vaccines have been delivered and providing those vaccines at that time if the child is un- or under-vaccinated. 8. Program decisions should increasingly be based on good quality data and appropriate analysis. 9. The incorporation of rubella vaccination into the immunization program needs to be accelerated - it should be accorded equivalent emphasis as measles. 10. Outbreak investigation and response are critical but the most important thing is to prevent outbreaks. Copyright © 2017 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

Projections of costs, financing, and additional resource requirements for low- and lower middle-income country immunization programs over the decade, 2011-2020.

PubMed

Gandhi, Gian; Lydon, Patrick; Cornejo, Santiago; Brenzel, Logan; Wrobel, Sandra; Chang, Hugh

2013-04-18

The Decade of Vaccines Global Vaccine Action Plan has outlined a set of ambitious goals to broaden the impact and reach of immunization across the globe. A projections exercise has been undertaken to assess the costs, financing availability, and additional resource requirements to achieve these goals through the delivery of vaccines against 19 diseases across 94 low- and middle-income countries for the period 2011-2020. The exercise draws upon data from existing published and unpublished global forecasts, country immunization plans, and costing studies. A combination of an ingredients-based approach and use of approximations based on past spending has been used to generate vaccine and non-vaccine delivery costs for routine programs, as well as supplementary immunization activities (SIAs). Financing projections focused primarily on support from governments and the GAVI Alliance. Cost and financing projections are presented in constant 2010 US dollars (US$). Cumulative total costs for the decade are projected to be US$57.5 billion, with 85% for routine programs and the remaining 15% for SIAs. Delivery costs account for 54% of total cumulative costs, and vaccine costs make up the remainder. A conservative estimate of total financing for immunization programs is projected to be $34.3 billion over the decade, with country governments financing 65%. These projections imply a cumulative funding gap of $23.2 billion. About 57% of the total resources required to close the funding gap are needed just to maintain existing programs and scale up other currently available vaccines (i.e., before adding in the additional costs of vaccines still in development). Efforts to mobilize additional resources, manage program costs, and establish mutual accountability between countries and development partners will all be necessary to ensure the goals of the Decade of Vaccines are achieved. Establishing or building on existing mechanisms to more comprehensively track resources and commitments for immunization will help facilitate these efforts. Copyright © 2013 Elsevier Ltd. All rights reserved.

Responding to a cVDPV1 outbreak in Ukraine: Implications, challenges and opportunities.

PubMed

Khetsuriani, Nino; Perehinets, Ihor; Nitzan, Dorit; Popovic, Dragoslav; Moran, Thomas; Allahverdiyeva, Vusala; Huseynov, Shahin; Gavrilin, Eugene; Slobodianyk, Liudmyla; Izhyk, Olha; Sukhodolska, Anna; Hegazi, Sahar; Bulavinova, Katerina; Platov, Sergei; O'Connor, Patrick

2017-08-24

The European Region, certified polio-free in 2002, remains at risk of wild poliovirus reintroduction and emergence of circulating vaccine-derived polioviruses (cVDPV) until global polio eradication is achieved, as demonstrated by the cVDPV1 outbreak in Ukraine in 2015. We reviewed epidemiologic, clinical and virology data on cVDPV cases, surveillance and immunization coverage data, and reports of outbreak-related surveys, country missions, and expert group meetings. In Ukraine, 3-dose polio vaccine coverage declined from 91% in 2008 to 15% by mid-2015. In summer, 2015, two unrelated children from Zakarpattya province were paralyzed by a highly divergent cVDPV1. The isolates were 20 and 26 nucleotide divergent from prototype Sabin strain (with 18 identical mutations) consistent with their common origin and ∼2-year evolution. Outbreak response recommendations developed with international partner support included conducting three nationwide supplementary immunization activities (SIAs) with tOPV, strengthening surveillance and implementing communication interventions. SIAs were conducted during October 2015-February 2016 (officially reported coverage, round 1-64.4%, round 2-71.7%, and round 3-80.7%). Substantial challenges to outbreak response included lack of high-level support, resistance to OPV use, low perceived risk of polio, widespread vaccine hesitancy, anti-vaccine media environment, economic crisis and military conflict. Communication activities improved caregiver awareness of polio and confidence in vaccination. Surveillance was enhanced but did not consistently meet applicable performance standards. Post-outbreak assessments concluded that cVDPV1 transmission in Ukraine has likely stopped following the response, but significant gaps in population immunity and surveillance remained. Chronic under-vaccination in Ukraine resulted in the accumulation of children susceptible to polioviruses and created favorable conditions for VDPV1 emergence and circulation, leading to the outbreak. Until programmatic gaps in immunization and surveillance are addressed, Ukraine will remain at high-risk for VDPV emergence and circulation, as well as at risk for other vaccine-preventable diseases. Published by Elsevier Ltd.

Long-term changes in explosive and effusive behaviour at andesitic arc volcanoes: Chronostratigraphy of the Centre Hills Volcano, Montserrat

NASA Astrophysics Data System (ADS)

Coussens, Maya; Cassidy, Michael; Watt, Sebastian F. L.; Jutzeler, Martin; Talling, Peter J.; Barfod, Dan; Gernon, Thomas M.; Taylor, Rex; Hatter, Stuart J.; Palmer, Martin R.; Montserrat Volcano Observatory

2017-03-01

Volcanism on Montserrat (Lesser Antilles arc) has migrated southwards since the formation of the Silver Hills 2.5 Ma, and has formed three successively active volcanic centres. The Centre Hills volcano was the focus of volcanism from 1-0.4 Ma, before activity commenced at the currently active Soufrière Hills volcano. The history of activity at these two volcanoes provides an opportunity to investigate the pattern of volcano behaviour on an andesitic arc island over the lifetime of individual volcanoes. Here, we describe the pyroclastic stratigraphy of subaerial exposures around central Montserrat; identifying 11 thick (> 1 m) pumiceous units derived from sustained explosive eruptions of Centre Hills from 0.8-0.4 Ma. Over 10 other, less well- exposed pumiceous units have also been identified. The pumice-rich units are interbedded with andesite lava breccias derived from effusive, dome-forming eruptions of Centre Hills. The stratigraphy indicates that large (up to magnitude 5) explosive eruptions occurred throughout the history of Centre Hills, alongside effusive activity. This behaviour at Centre Hills contrasts with Soufrière Hills, where deposits from sustained explosive eruptions are much less common and restricted to early stages of activity at the volcano, from 175-130 ka. Subsequent eruptions at Soufriere Hills have been dominated by andesitic effusive eruptions. The bulk composition, petrography and mineral chemistry of volcanic rocks from Centre Hills and Soufrière Hills are similar throughout the history of both volcanoes, except for occasional, transient departures to different magma compositions, which mark shifts in vent location or dominant eruption style. For example, the final recorded eruption of Centre Hills, before the initiation of activity at Soufrière Hills, was more silicic than any other identified eruption on Montserrat; and the basaltic South Soufrière Hills episode marked the transition to the current stage of predominantly effusive Soufrière Hills activity. The compositional stability observed throughout the history of Centre Hills and Soufrière Hills suggests that a predominance towards effusive or explosive eruption styles is not driven by major compositional shifts of magma, but may reflect local changes in long-term magma storage conditions that characterise individual episodes (on 105 year timescales) of volcanism on Montserrat. Supplementary Table 2: Complete XRF analyses for all analysed samples Supplementary Table 3: Complete ICP-MS analyses for all analysed samples. Supplementary Table 4: Plagioclase composition and precision data from SEM analysis Supplementary Table 5: Clinopyroxene composition and precision data from SEM analysis Supplementary Table 6: Orthopyroxene composition and precision data from SEM analysis Supplementary Table 7: Amphibole composition and precision data from SEM analysis Supplementary Table 8: Glass compositions from EMP analysis Supplementary Table 9: Standard Deviation of glass compositions from EMP analysis. Supplementary Table 10: Isotopic composition of argon from plagioclase crystals from select units. Data obtained using an ARGUS V multi-collector mass spectrometer.

National Advisory Committee on Immunization (NACI). Supplementary statement MMR vaccine and anaphylactic hypersensitivity to egg or egg-related antigens.

PubMed

1996-07-15

The fourth edition of the Canadian Immunization Guide (1993) recommends that "persons who have a history of anaphylactic hypersensitivity to hens' eggs (urticaria, swelling of the mouth and throat, difficulty in breathing or hypotension) should not be given measles vaccine except under special precautions." The precautions outlined include skin testing with diluted vaccine and graded challenge vaccination if the skin test is positive. Results of several recent studies have questioned such a cautious approach. NACI has reviewed all available data and revised its guidelines accordingly. The following revised guidelines are a major departure from the previously published recommendations. They will appear in the next edition of the Canadian Immunization Guide. A measles-rubella combination vaccine (Mo-Ru Viraten Berna TM) recently licensed in Canada contains no avian proteins and therefore can be used without regard to egg allergy.

Integrating Neglected Tropical Disease and Immunization Programs: The Experiences of the Tanzanian Ministry of Health

PubMed Central

Mwingira, Upendo John; Means, Arianna Rubin; Chikawe, Maria; Kilembe, Bernard; Lyimo, Dafrossa; Crowley, Kathryn; Rusibamayila, Neema; Nshala, Andreas; Mphuru, Alex

2016-01-01

Global health practitioners are increasingly advocating for the integration of community-based health-care platforms as a strategy for increasing the coverage of programs, encouraging program efficiency, and promoting universal health-care goals. To leverage the strengths of compatible programs and avoid geographic and temporal duplications in efforts, the Tanzanian Ministry of Health and Social Welfare coordinated immunization and neglected tropical disease programs for the first time in 2014. Specifically, a measles and rubella supplementary vaccine campaign, mass drug administration (MDA) of ivermectin and albendazole, and Vitamin A were provisionally integrated into a shared community-based delivery platform. Over 21 million people were targeted by the integrated campaign, with the immunization program and MDA program reaching 97% and 93% of targeted individuals, respectively. The purpose of this short report is to share the Tanzanian experience of launching and managing this integrated campaign with key stakeholders. PMID:27246449

Progress toward measles elimination—Philippines, 1998-2014.

PubMed

Takashima, Yoshihiro; Schluter, W William; Mariano, Kayla Mae L; Diorditsa, Sergey; de Quiroz Castro, Maricel; Ou, Alan C; Ducusin, Maria Joyce U; Garcia, Luzviminda C; Elfa, Dulce C; Dabbagh, Alya; Rota, Paul; Goodson, James L

2015-04-10

In 2005, the Regional Committee for the World Health Organization (WHO) Western Pacific Region (WPR) established a goal to eliminate measles by 2012.The recommended elimination strategies in WPR include 1) ≥95% 2-dose coverage with measles-containing vaccine (MCV) through routine immunization services and supplementary immunization activities (SIAs); 2) high-quality case-based measles surveillance; 3) laboratory surveillance with timely and accurate testing of specimens to confirm or discard suspected cases and detect measles virus genotypes; and 4) measles outbreak preparedness, rapid response, and appropriate case management. In the WPR, the Philippines set a national goal in 1998 to eliminate measles by 2008. This report describes progress toward measles elimination in the Philippines during 1998-2014 and challenges remaining to achieve the goal. WHO-United Nations Children's Fund (UNICEF)-estimated coverage with the routine first dose of MCV (MCV1) increased from 80% in 1998 to 90% in 2013, and coverage with the routine second dose of MCV (MCV2) increased from 10% after nationwide introduction in 2010 to 53% in 2013. After nationwide SIAs in 1998 and 2004, historic lows in the numbers and incidence of reported measles cases occurred in 2006. Despite nationwide SIAs in 2007 and 2011, the number of reported cases and incidence generally increased during 2007-2012, and large measles outbreaks occurred during 2013-2014 that affected infants, young children, older children, and young adults and that were prolonged by delayed and geographically limited outbreak response immunization activities during 2013-2014. For the goal of measles elimination in WPR to be achieved, sustained investments are required in the Philippines to strengthen health systems, implement the recommended elimination strategies, and develop additional strategies to identify and reduce measles susceptibility in specific geographic areas and older age groups.

Computational approaches for discovery of common immunomodulators in fungal infections: towards broad-spectrum immunotherapeutic interventions.

PubMed

Kidane, Yared H; Lawrence, Christopher; Murali, T M

2013-10-07

Fungi are the second most abundant type of human pathogens. Invasive fungal pathogens are leading causes of life-threatening infections in clinical settings. Toxicity to the host and drug-resistance are two major deleterious issues associated with existing antifungal agents. Increasing a host's tolerance and/or immunity to fungal pathogens has potential to alleviate these problems. A host's tolerance may be improved by modulating the immune system such that it responds more rapidly and robustly in all facets, ranging from the recognition of pathogens to their clearance from the host. An understanding of biological processes and genes that are perturbed during attempted fungal exposure, colonization, and/or invasion will help guide the identification of endogenous immunomodulators and/or small molecules that activate host-immune responses such as specialized adjuvants. In this study, we present computational techniques and approaches using publicly available transcriptional data sets, to predict immunomodulators that may act against multiple fungal pathogens. Our study analyzed data sets derived from host cells exposed to five fungal pathogens, namely, Alternaria alternata, Aspergillus fumigatus, Candida albicans, Pneumocystis jirovecii, and Stachybotrys chartarum. We observed statistically significant associations between host responses to A. fumigatus and C. albicans. Our analysis identified biological processes that were consistently perturbed by these two pathogens. These processes contained both immune response-inducing genes such as MALT1, SERPINE1, ICAM1, and IL8, and immune response-repressing genes such as DUSP8, DUSP6, and SPRED2. We hypothesize that these genes belong to a pool of common immunomodulators that can potentially be activated or suppressed (agonized or antagonized) in order to render the host more tolerant to infections caused by A. fumigatus and C. albicans. Our computational approaches and methodologies described here can now be applied to newly generated or expanded data sets for further elucidation of additional drug targets. Moreover, identified immunomodulators may be used to generate experimentally testable hypotheses that could help in the discovery of broad-spectrum immunotherapeutic interventions. All of our results are available at the following supplementary website: http://bioinformatics.cs.vt.edu/~murali/supplements/2013-kidane-bmc.

Computational approaches for discovery of common immunomodulators in fungal infections: towards broad-spectrum immunotherapeutic interventions

PubMed Central

2013-01-01

Background Fungi are the second most abundant type of human pathogens. Invasive fungal pathogens are leading causes of life-threatening infections in clinical settings. Toxicity to the host and drug-resistance are two major deleterious issues associated with existing antifungal agents. Increasing a host’s tolerance and/or immunity to fungal pathogens has potential to alleviate these problems. A host’s tolerance may be improved by modulating the immune system such that it responds more rapidly and robustly in all facets, ranging from the recognition of pathogens to their clearance from the host. An understanding of biological processes and genes that are perturbed during attempted fungal exposure, colonization, and/or invasion will help guide the identification of endogenous immunomodulators and/or small molecules that activate host-immune responses such as specialized adjuvants. Results In this study, we present computational techniques and approaches using publicly available transcriptional data sets, to predict immunomodulators that may act against multiple fungal pathogens. Our study analyzed data sets derived from host cells exposed to five fungal pathogens, namely, Alternaria alternata, Aspergillus fumigatus, Candida albicans, Pneumocystis jirovecii, and Stachybotrys chartarum. We observed statistically significant associations between host responses to A. fumigatus and C. albicans. Our analysis identified biological processes that were consistently perturbed by these two pathogens. These processes contained both immune response-inducing genes such as MALT1, SERPINE1, ICAM1, and IL8, and immune response-repressing genes such as DUSP8, DUSP6, and SPRED2. We hypothesize that these genes belong to a pool of common immunomodulators that can potentially be activated or suppressed (agonized or antagonized) in order to render the host more tolerant to infections caused by A. fumigatus and C. albicans. Conclusions Our computational approaches and methodologies described here can now be applied to newly generated or expanded data sets for further elucidation of additional drug targets. Moreover, identified immunomodulators may be used to generate experimentally testable hypotheses that could help in the discovery of broad-spectrum immunotherapeutic interventions. All of our results are available at the following supplementary website: http://bioinformatics.cs.vt.edu/~murali/supplements/2013-kidane-bmc PMID:24099000

Impact of an Intervention to Use a Measles, Rubella, and Polio Mass Vaccination Campaign to Strengthen Routine Immunization Services in Nepal.

PubMed

Wallace, Aaron S; Bohara, Rajendra; Stewart, Steven; Subedi, Giri; Anand, Abhijeet; Burnett, Eleanor; Giri, Jagat; Shrestha, Jagat; Gurau, Suraj; Dixit, Sameer; Rajbhandari, Rajesh; Schluter, W William

2017-07-01

The potential to strengthen routine immunization (RI) services through supplementary immunization activities (SIAs) is an important benefit of global measles and rubella elimination and polio eradication strategies. However, little evidence exists on how best to use SIAs to strengthen RI. As part the 2012 Nepal measles-rubella and polio SIA, we developed an intervention package designed to improve RI processes and evaluated its effect on specific RI process measures. The intervention package was incorporated into existing SIA activities and materials to improve healthcare providers' RI knowledge and practices throughout Nepal. In 1 region (Central Region) we surveyed the same 100 randomly selected health facilities before and after the SIA and evaluated the following RI process measures: vaccine safety, RI planning, RI service delivery, vaccine supply chain, and RI data recording practices. Data collection included observations of vaccination sessions, interviews with the primary healthcare provider who administered vaccines at each facility, and administrative record reviews. Pair-matched analytical methods were used to determine whether statistically significant changes in the selected RI process measures occurred over time. After the SIA, significant positive changes were measured in healthcare provider knowledge of adverse events following immunization (11% increase), availability of RI microplans (+17%) and maps (+12%), and awareness of how long a reconstituted measles vial can be used before it must be discarded (+14%). For the SIA, 42% of providers created an SIA high-risk villages list, and >50% incorporated this information into RI outreach session site planning. Significant negative changes occurred in correct knowledge of measles vaccination contraindications (-11%), correct definition for a measles outbreak (-21%), and how to treat a child with a severe adverse event following immunization (-10%). Twenty percent of providers reported cancelling ≥1 RI sessions during the SIA. Many RI process measures were at high proportions (>90%) before the SIA and remained high afterward, including proper vaccine administration techniques, proper vaccine waste management, and availability of vaccine carriers and vaccine registers. Focusing on activities that are easily linked between SIAs and RI services, such as using SIA high-risk village list to strengthen RI microplanning and examining ways to minimize the impact of an SIA on RI session scheduling, should be prioritized when implementing SIAs. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

76 FR 20042 - Agency Information Collection Activities: Proposed Collection, Comments Requested

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-11

... Collection Under Review: Revision of a currently approved collection; Supplementary Homicide Report. [[Page...: Supplementary Homicide Report. (3) The agency form number, if any, and the applicable component of the...

32 CFR 56.9 - Ensuring compliance with this part in Federal financial assistance programs and activities.

Code of Federal Regulations, 2012 CFR

2012-07-01

... approval of these supplementary guidelines from the ASD(MRA&L), or designee, before issuing them. Prior to their issuance, the ASD(MRA&L), or designee, shall submit supplementary guidelines prepared pursuant to... Components deal with the employment of civilians in programs and activities subject to this part the ASD(MRA...

32 CFR 56.9 - Ensuring compliance with this part in Federal financial assistance programs and activities.

Code of Federal Regulations, 2013 CFR

2013-07-01

... approval of these supplementary guidelines from the ASD(MRA&L), or designee, before issuing them. Prior to their issuance, the ASD(MRA&L), or designee, shall submit supplementary guidelines prepared pursuant to... Components deal with the employment of civilians in programs and activities subject to this part the ASD(MRA...

32 CFR 56.9 - Ensuring compliance with this part in Federal financial assistance programs and activities.

Code of Federal Regulations, 2014 CFR

2014-07-01

... approval of these supplementary guidelines from the ASD(MRA&L), or designee, before issuing them. Prior to their issuance, the ASD(MRA&L), or designee, shall submit supplementary guidelines prepared pursuant to... Components deal with the employment of civilians in programs and activities subject to this part the ASD(MRA...

How Do I Manage? An Introduction to Management. Supplementary Material and Workbook.

ERIC Educational Resources Information Center

North West Regional Management Centre, Chorley (England).

This book contains supplementary material for a British self-study course in management designed as an introduction to the course for the Certificate in Management Studies. The materials in this book are learning activities referenced to various topics in the course materials. The nine activities include a case study of a production supervision…

Seroprevalence of antibodies to measles and rubella eight months after a vaccination campaign in the southeast of Iran.

PubMed

Izadi, Shahrokh; Zahraei, Seyed Mohsen; Mokhtari-Azad, Talat

2018-02-08

Eight months after the mass immunization campaign of November 2015 against measles and rubella in the southeast of Iran, in order to evaluate the sero-immunity level of the people living in the mentioned region, a serosurvey study was performed. Using a multi-stage probability proportional to size cluster sampling, the sera of 1,056 participants, ranging from 15 months to 20 years old, were tested for measles and rubella IgG antibodies in the National Reference Laboratory at Tehran University of Medical Sciences, Tehran, Iran. The seroprevalence rates of antibodies against measles and rubella in the age groups below 16 years were respectively 98.4 and 93.2%. In the age group of 16 to 20 years, who was not the target of the mass immunization campaign, the said rates were respectively 91.7% and 87.4%. The herd immunity of the age groups below 16 years, who were the target of the campaign, is favourably high and reassuring both for measles and for rubella. Campaigns of supplementary vaccination play a substantial role for filling the gaps in the herd immunity.

Progress Toward Measles Elimination - Western Pacific Region, 2013-2017.

PubMed

Hagan, José E; Kriss, Jennifer L; Takashima, Yoshihiro; Mariano, Kayla Mae L; Pastore, Roberta; Grabovac, Varja; Dabbagh, Alya J; Goodson, James L

2018-05-04

In 2005, the Regional Committee for the World Health Organization (WHO) Western Pacific Region (WPR)* established a goal for measles elimination † by 2012 (1). To achieve this goal, the 37 WPR countries and areas implemented the recommended strategies in the WPR Plan of Action for Measles Elimination (2) and the Field Guidelines for Measles Elimination (3). The strategies include 1) achieving and maintaining ≥95% coverage with 2 doses of measles-containing vaccine (MCV) through routine immunization services and supplementary immunization activities (SIAs), when required; 2) conducting high-quality case-based measles surveillance, including timely and accurate testing of specimens to confirm or discard suspected cases and detect measles virus for genotyping and molecular analysis; and 3) establishing and maintaining measles outbreak preparedness to ensure rapid response and appropriate case management. This report updates the previous report (4) and describes progress toward measles elimination in WPR during 2013-2017. During 2013-2016, estimated regional coverage with the first MCV dose (MCV1) decreased from 97% to 96%, and coverage with the routine second MCV dose (MCV2) increased from 91% to 93%. Eighteen (50%) countries achieved ≥95% MCV1 coverage in 2016. Seven (39%) of 18 nationwide SIAs during 2013-2017 reported achieving ≥95% administrative coverage. After a record low of 5.9 cases per million population in 2012, measles incidence increased during 2013-2016 to a high of 68.9 in 2014, because of outbreaks in the Philippines and Vietnam, as well as increased incidence in China, and then declined to 5.2 in 2017. To achieve measles elimination in WPR, additional measures are needed to strengthen immunization programs to achieve high population immunity, maintain high-quality surveillance for rapid case detection and confirmation, and ensure outbreak preparedness and prompt response to contain outbreaks.

Eradication of poliomyelitis in countries affected by conflict.

PubMed Central

Tangermann, R. H.; Hull, H. F.; Jafari, H.; Nkowane, B.; Everts, H.; Aylward, R. B.

2000-01-01

The global initiative to eradicate poliomyelitis is focusing on a small number of countries in Africa (Angola, Democratic Republic of the Congo, Liberia, Sierra Leone, Somalia, Sudan) and Asia (Afghanistan, Tajikistan), where progress has been hindered by armed conflict. In these countries the disintegration of health systems and difficulties of access are major obstacles to the immunization and surveillance strategies necessary for polio eradication. In such circumstances, eradication requires special endeavours, such as the negotiation of ceasefires and truces and the winning of increased direct involvement by communities. Transmission of poliovirus was interrupted during conflicts in Cambodia, Colombia, El Salvador, Peru, the Philippines, and Sri Lanka. Efforts to achieve eradication in areas of conflict have led to extra health benefits: equity in access to immunization, brought about because every child has to be reached; the revitalization and strengthening of routine immunization services through additional externally provided resources; and the establishment of disease surveillance systems. The goal of polio eradication by the end of 2000 remains attainable if supplementary immunization and surveillance can be accelerated in countries affected by conflict. PMID:10812729

Eradication of poliomyelitis in countries affected by conflict.

PubMed

Tangermann, R H; Hull, H F; Jafari, H; Nkowane, B; Everts, H; Aylward, R B

2000-01-01

The global initiative to eradicate poliomyelitis is focusing on a small number of countries in Africa (Angola, Democratic Republic of the Congo, Liberia, Sierra Leone, Somalia, Sudan) and Asia (Afghanistan, Tajikistan), where progress has been hindered by armed conflict. In these countries the disintegration of health systems and difficulties of access are major obstacles to the immunization and surveillance strategies necessary for polio eradication. In such circumstances, eradication requires special endeavours, such as the negotiation of ceasefires and truces and the winning of increased direct involvement by communities. Transmission of poliovirus was interrupted during conflicts in Cambodia, Colombia, El Salvador, Peru, the Philippines, and Sri Lanka. Efforts to achieve eradication in areas of conflict have led to extra health benefits: equity in access to immunization, brought about because every child has to be reached; the revitalization and strengthening of routine immunization services through additional externally provided resources; and the establishment of disease surveillance systems. The goal of polio eradication by the end of 2000 remains attainable if supplementary immunization and surveillance can be accelerated in countries affected by conflict.

Deep Learning Improves Antimicrobial Peptide Recognition.

PubMed

Veltri, Daniel; Kamath, Uday; Shehu, Amarda

2018-03-24

Bacterial resistance to antibiotics is a growing concern. Antimicrobial peptides (AMPs), natural components of innate immunity, are popular targets for developing new drugs. Machine learning methods are now commonly adopted by wet-laboratory researchers to screen for promising candidates. In this work we utilize deep learning to recognize antimicrobial activity. We propose a neural network model with convolutional and recurrent layers that leverage primary sequence composition. Results show that the proposed model outperforms state-of-the-art classification models on a comprehensive data set. By utilizing the embedding weights, we also present a reduced-alphabet representation and show that reasonable AMP recognition can be maintained using nine amino-acid types. Models and data sets are made freely available through the Antimicrobial Peptide Scanner vr.2 web server at: www.ampscanner.com. amarda@gmu.edu for general inquiries and dan.veltri@gmail.com for web server information. Supplementary data are available at Bioinformatics online.

Stimulation of immune systems by conjugated polymers and their potential as an alternative vaccine adjuvant

NASA Astrophysics Data System (ADS)

Gong, Hua; Xiang, Jian; Xu, Ligeng; Song, Xuejiao; Dong, Ziliang; Peng, Rui; Liu, Zhuang

2015-11-01

Recently, conjugated polymers have been widely explored in the field of nanomedicine. Careful evaluations of their biological effects are thus urgently needed. Hereby, we systematically evaluated the biological effects of different types of conjugated polymers on macrophages and dendritic cells (DCs), which play critical roles in the innate and adaptive immune systems, respectively. While naked poly-(3,4-ethylenedioxythiophene):poly(4-styrenesulfonate) (PEDOT:PSS) exhibits a high level of cytotoxicity, polyethylene glycol (PEG) modified PEDOT:PSS (PEDOT:PSS-PEG) shows greatly reduced toxicity to various types of cells. To our surprise, PEGylation of PEDOT:PSS could obviously enhance the cellular uptake of these nanoparticles, leading to subsequent immune stimulations of both macrophages and DCs. In contrast, another type of conjugated polymer, polypyrrole (PPy), is found to be an inert material with neither significant cytotoxicity nor noticeable immune-stimulation activity. Interestingly, utilizing ovalbumin (OVA) as a model antigen, it is further uncovered in our ex vivo experiment that PEDOT:PSS-PEG may serve as an adjuvant to greatly enhance the immunogenicity of OVA upon simple mixing. Our study on the one hand suggests the promise of developing novel nano-adjuvants based on conjugated polymers, and on the other hand highlights the importance of careful evaluations of the impacts of any new nanomaterials developed for nanomedicine on the immune systems.Recently, conjugated polymers have been widely explored in the field of nanomedicine. Careful evaluations of their biological effects are thus urgently needed. Hereby, we systematically evaluated the biological effects of different types of conjugated polymers on macrophages and dendritic cells (DCs), which play critical roles in the innate and adaptive immune systems, respectively. While naked poly-(3,4-ethylenedioxythiophene):poly(4-styrenesulfonate) (PEDOT:PSS) exhibits a high level of cytotoxicity, polyethylene glycol (PEG) modified PEDOT:PSS (PEDOT:PSS-PEG) shows greatly reduced toxicity to various types of cells. To our surprise, PEGylation of PEDOT:PSS could obviously enhance the cellular uptake of these nanoparticles, leading to subsequent immune stimulations of both macrophages and DCs. In contrast, another type of conjugated polymer, polypyrrole (PPy), is found to be an inert material with neither significant cytotoxicity nor noticeable immune-stimulation activity. Interestingly, utilizing ovalbumin (OVA) as a model antigen, it is further uncovered in our ex vivo experiment that PEDOT:PSS-PEG may serve as an adjuvant to greatly enhance the immunogenicity of OVA upon simple mixing. Our study on the one hand suggests the promise of developing novel nano-adjuvants based on conjugated polymers, and on the other hand highlights the importance of careful evaluations of the impacts of any new nanomaterials developed for nanomedicine on the immune systems. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06081h

Assessing the cost-effectiveness of different measles vaccination strategies for children in the Democratic Republic of Congo.

PubMed

Doshi, Reena H; Eckhoff, Philip; Cheng, Alvan; Hoff, Nicole A; Mukadi, Patrick; Shidi, Calixte; Gerber, Sue; Wemakoy, Emile Okitolonda; Muyembe-Tafum, Jean-Jacques; Kominski, Gerald F; Rimoin, Anne W

2017-10-27

One of the goals of the Global Measles and Rubella Strategic Plan is the reduction in global measles mortality, with high measles vaccination coverage as one of its core components. While measles mortality has been reduced more than 79%, the disease remains a major cause of childhood vaccine preventable disease burden globally. Measles immunization requires a two-dose schedule and only countries with strong, stable immunization programs can rely on routine services to deliver the second dose. In the Democratic Republic of Congo (DRC), weak health infrastructure and lack of provision of the second dose of measles vaccine necessitates the use of supplementary immunization activities (SIAs) to administer the second dose. We modeled three vaccination strategies using an age-structured SIR (Susceptible-Infectious-Recovered) model to simulate natural measles dynamics along with the effect of immunization. We compared the cost-effectiveness of two different strategies for the second dose of Measles Containing Vaccine (MCV) to one dose of MCV through routine immunization services over a 15-year time period for a hypothetical birth cohort of 3 million children. Compared to strategy 1 (MCV1 only), strategy 2 (MCV2 by SIA) would prevent a total of 5,808,750 measles cases, 156,836 measles-related deaths and save U.S. $199 million. Compared to strategy 1, strategy 3 (MCV2 by RI) would prevent a total of 13,232,250 measles cases, 166,475 measles-related deaths and save U.S. $408 million. Vaccination recommendations should be tailored to each country, offering a framework where countries can adapt to local epidemiological and economical circumstances in the context of other health priorities. Our results reflect the synergistic effect of two doses of MCV and demonstrate that the most cost-effective approach to measles vaccination in DRC is to incorporate the second dose of MCV in the RI schedule provided that high enough coverage can be achieved. Published by Elsevier Ltd.

The end of measles and congenital rubella: an achievable dream?

PubMed

Adamo, G; Sturabotti, G; D'Andrea, E; Baccolini, V; Romano, F; Iannazzo, S; Marzuillo, C; Villari, P

2017-01-01

Despite substantial progress towards measles and rubella control, outbreaks continue to threaten elimination goals worldwide. This paper aims to document progress towards the global eradication of measles and rubella. In particular, it investigates the major challenges faced by Italy in reaching the elimination goals. A review of the most important literature was carried out. Furthermore, a systematic review of the scientific literature on measles and rubella in the Italian setting was performed for the period 2000-2016. In the National Plan 2010-2015, Italy renewed its commitment to eliminate measles and rubella by 2015. However, Italy recently experienced a high measles burden (2,205 cases in 2013, 1,694 in 2014). Between June 2015 and May 2016, 515 cases were reported, accounting for 28% all cases in Europe. Immunization coverage decreased in recent years, with no Region reaching the 95% target. The systematic review included a total of 175 papers, with an upward trend in the number of published articles, which demonstrates an increasing interest in the field of measles and rubella. The review highlights the need to improve the commitment of the Italian Regions to the elimination goals; to promote Supplementary Immunization Activities (SIAs); to improve the communication skills of health care workers; to improve the health literacy of citizens; and to enhance integrated measles and rubella surveillance. Elimination of measles and rubella in Italy will require a substantial improvement in both commitment of the 21 Regions and activity of the whole country towards the WHO goals.

Resurgence of measles in Serbia 2010-2011 highlights the need for supplementary immunization activities.

PubMed

Nedeljković, J; Rakić Adrović, S; Tasić, G; Kovačević-Jovanović, V; Lončarević, G; Hübschen, J M; Muller, C P

2016-04-01

Between December 2010 and August 2011 an outbreak of measles occurred in Serbia with 363 reported cases. Sera and/or nose/throat swabs were collected from 193 patients and tested for measles-specific IgM antibodies by ELISA and viral RNA by RT-PCR, respectively. Epidemiological data were obtained from the surveillance database of the Institute of Public Health of Serbia. Of the 363 cases involved in the outbreak, 113 were laboratory confirmed. More than one third of the patients were hospitalized (n = 130, 35·8%) and for 15 (4·1% of the reported outbreak cases) the infection was complicated by pneumonia. Mostly pre-school children aged ⩽4 years (37·8%) and adults aged ⩾30 years (27·3%) were affected. The majority of patients belonged to the Roma population with a preponderance of female cases (57·0%). Nearly 94% of the patients were either unvaccinated or of unknown vaccination status. The main outbreak virus was the D4-Hamburg strain. The outbreak in Serbia occurred after several years of very low measles incidence despite a high routine immunization coverage in the general population, suggesting that special efforts to identify and vaccinate susceptible population groups are required even in countries with apparently good disease control.

Progress toward polio eradication - worldwide, 2014-2015.

PubMed

Hagan, José E; Wassilak, Steven G F; Craig, Allen S; Tangermann, Rudolf H; Diop, Ousmane M; Burns, Cara C; Quddus, Arshad

2015-05-22

In 1988, the World Health Assembly of the World Health Organization (WHO) resolved to eradicate polio worldwide. Wild poliovirus (WPV) transmission has been interrupted in all but three countries (Afghanistan, Nigeria, and Pakistan). No WPV type 2 cases have been detected worldwide since 1999, and the last WPV type 3 case was detected in Nigeria in November 2012; since 2012, only WPV type 1 has been detected. Circulating vaccine-derived poliovirus (cVDPV), usually type 2, continues to cause cases of paralytic polio in communities with low population immunity. In 2012, the World Health Assembly declared global polio eradication "a programmatic emergency for global public health", and in 2014, WHO declared the international spread of WPV to previously polio-free countries to be "a public health emergency of international concern". This report summarizes global progress toward polio eradication during 2014-2015 and updates previous reports. In 2014, a total of 359 WPV cases were reported in nine countries worldwide. Although reported WPV cases increased in Pakistan and Afghanistan, cases in Nigeria decreased substantially in 2014, and encouraging progress toward global WPV transmission interruption has occurred. Overcoming ongoing challenges to interruption of WPV transmission globally will require sustained programmatic enhancements, including improving the quality of supplementary immunization activities (SIAs) to interrupt transmission in Afghanistan and Pakistan and to prevent WPV exportation to polio-free countries.

Functionalized iron oxide nanoparticles for controlling the movement of immune cells

NASA Astrophysics Data System (ADS)

White, Ethan E.; Pai, Alex; Weng, Yiming; Suresh, Anil K.; van Haute, Desiree; Pailevanian, Torkom; Alizadeh, Darya; Hajimiri, Ali; Badie, Behnam; Berlin, Jacob M.

2015-04-01

Immunotherapy is currently being investigated for the treatment of many diseases, including cancer. The ability to control the location of immune cells during or following activation would represent a powerful new technique for this field. Targeted magnetic delivery is emerging as a technique for controlling cell movement and localization. Here we show that this technique can be extended to microglia, the primary phagocytic immune cells in the central nervous system. The magnetized microglia were generated by loading the cells with iron oxide nanoparticles functionalized with CpG oligonucleotides, serving as a proof of principle that nanoparticles can be used to both deliver an immunostimulatory cargo to cells and to control the movement of the cells. The nanoparticle-oligonucleotide conjugates are efficiently internalized, non-toxic, and immunostimulatory. We demonstrate that the in vitro migration of the adherent, loaded microglia can be controlled by an external magnetic field and that magnetically-induced migration is non-cytotoxic. In order to capture video of this magnetically-induced migration of loaded cells, a novel 3D-printed ``cell box'' was designed to facilitate our imaging application. Analysis of cell movement velocities clearly demonstrate increased cell velocities toward the magnet. These studies represent the initial step towards our final goal of using nanoparticles to both activate immune cells and to control their trafficking within the diseased brain.Immunotherapy is currently being investigated for the treatment of many diseases, including cancer. The ability to control the location of immune cells during or following activation would represent a powerful new technique for this field. Targeted magnetic delivery is emerging as a technique for controlling cell movement and localization. Here we show that this technique can be extended to microglia, the primary phagocytic immune cells in the central nervous system. The magnetized microglia were generated by loading the cells with iron oxide nanoparticles functionalized with CpG oligonucleotides, serving as a proof of principle that nanoparticles can be used to both deliver an immunostimulatory cargo to cells and to control the movement of the cells. The nanoparticle-oligonucleotide conjugates are efficiently internalized, non-toxic, and immunostimulatory. We demonstrate that the in vitro migration of the adherent, loaded microglia can be controlled by an external magnetic field and that magnetically-induced migration is non-cytotoxic. In order to capture video of this magnetically-induced migration of loaded cells, a novel 3D-printed ``cell box'' was designed to facilitate our imaging application. Analysis of cell movement velocities clearly demonstrate increased cell velocities toward the magnet. These studies represent the initial step towards our final goal of using nanoparticles to both activate immune cells and to control their trafficking within the diseased brain. Electronic supplementary information (ESI) available: Transmission electron microscopy images of the particles, additional independent experiments for the NFκB activity and exocytosis assays, TEM images for the SPION untreated cells, bright field microscopy images of the cells alone in the presence and absence of magnet, images of the magnetic movement experiments at higher doses of SPION, full uncropped images of the post-migration LIVE/DEAD assay, and a video file of cell movement. See DOI: 10.1039/c3nr04421a

Determination of Novel Strategies for Hastening Corneal Wound Healing and Reducing Tissue Inflammation

DTIC Science & Technology

2011-10-01

blocking buffer, 5% fat -free milk in 0.1% Tris-buffered solution/Tween-20, for 1 hour at room temperature and then probed overnight at 5°C with...and blotting onto Immun-Blot PVDF membrane (Bio-Rad, Hercules, CA). Membranes were blocked with blocking buffer, 5% fat -free milk in 1x PBS buffer...distribution unlimited 13. SUPPLEMENTARY NOTES The aim of this study is to uncover novel transient receptor potential protein vanilloid-1 (TRPV1

Quantifying the impact of expanded age group campaigns for polio eradication.

PubMed

Wagner, Bradley G; Behrend, Matthew R; Klein, Daniel J; Upfill-Brown, Alexander M; Eckhoff, Philip A; Hu, Hao

2014-01-01

A priority of the Global Polio Eradication Initiative (GPEI) 2013-2018 strategic plan is to evaluate the potential impact on polio eradication resulting from expanding one or more Supplementary Immunization Activities (SIAs) to children beyond age five-years in polio endemic countries. It has been hypothesized that such expanded age group (EAG) campaigns could accelerate polio eradication by eliminating immunity gaps in older children that may have resulted from past periods of low vaccination coverage. Using an individual-based mathematical model, we quantified the impact of EAG campaigns in terms of probability of elimination, reduction in polio transmission and age stratified immunity levels. The model was specifically calibrated to seroprevalence data from a polio-endemic region: Zaria, Nigeria. We compared the impact of EAG campaigns, which depend only on age, to more targeted interventions which focus on reaching missed populations. We found that EAG campaigns would not significantly improve prospects for polio eradication; the probability of elimination increased by 8% (from 24% at baseline to 32%) when expanding three annual SIAs to 5-14 year old children and by 18% when expanding all six annual SIAs. In contrast, expanding only two of the annual SIAs to target hard-to-reach populations at modest vaccination coverage-representing less than one tenth of additional vaccinations required for the six SIA EAG scenario-increased the probability of elimination by 55%. Implementation of EAG campaigns in polio endemic regions would not improve prospects for eradication. In endemic areas, vaccination campaigns which do not target missed populations will not benefit polio eradication efforts.

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Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-17

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Progress Toward Poliomyelitis Eradication--Afghanistan, January 2014‒August 2015.

PubMed

Mbaeyi, Chukwuma; Saatcioglu, Akif; Tangermann, Rudolf H; Hadler, Stephen; Ehrhardt, Derek

2015-10-23

Despite recent progress toward global polio eradication, endemic transmission of wild poliovirus (WPV) continues to be reported in Afghanistan and Pakistan. The Afghanistan program must overcome many challenges to remain on track toward achieving the objectives set in the 2013–2018 strategic plan of the Global Polio Eradication Initiative (GPEI). Cross-border transmission of WPV type 1 (WPV1) continues to occur among children traveling to and from Pakistan. The country's routine immunization system remains weak and unable to reach recommended benchmarks in most regions; hence, the national Polio Eradication Initiative (PEI) relies mainly on providing children aged <5 years with oral poliovirus vaccine (OPV), administered during supplementary immunization activities (SIAs). Because of ongoing conflict and insecurity, some children continue to be missed during SIAs in areas not under government control; however, the majority of missed children live in accessible areas and are often unreached because of a failure to plan, implement, and supervise SIAs efficiently. This report describes polio eradication activities and progress in Afghanistan during January 2014‒August 2015 and updates previous reports. During 2014, a total of 28 WPV1 cases were reported in Afghanistan, compared with 14 cases in 2013; nine cases were reported during January‒August 2015, the same number as during the same period in 2014. To eliminate poliovirus transmission in Afghanistan, emergency operations centers (EOCs) need to be established at the national level and in critical regions without delay to improve overall coordination and oversight of polio eradication activities. The recently revised National Emergency Action Plan for polio eradication needs to be fully implemented, including detailed microplanning and enhanced monitoring and supervision of SIAs, as well as improved cross-border coordination with Pakistan.

SARC Supplementary Tutor Handbook: Supporting Literacy for People with Intellectual/Developmental Challenges.

ERIC Educational Resources Information Center

Lockert, Richard

This handbook, which is intended for tutors, disability practitioners, and others working with adults with intellectual/developmental disabilities, contains supplementary materials for and about supporting literacy for people with intellectual/developmental challenges. The handbook is a product of the following activities: extensive research of…

Cost-benefit analyses of supplementary measles immunisation in the highly immunized population of New Zealand.

PubMed

Hayman, D T S; Marshall, J C; French, N P; Carpenter, T E; Roberts, M G; Kiedrzynski, T

2017-09-05

As endemic measles is eliminated from countries through increased immunisation, the economic benefits of enhanced immunisation programs may come into question. New Zealand has suffered from outbreaks after measles introductions from abroad and we use it as a model system to understand the benefits of catch up immunisation in highly immunised populations. We provide cost-benefit analyses for measles supplementary immunisation in New Zealand. We model outbreaks based on estimates of the basic reproduction number in the vaccinated population (R v , the number of secondary infections in a partially immunised population), based on the number of immunologically-naïve people at district and national levels, considering both pre- and post-catch up vaccination scenarios. Our analyses suggest that measles R v often includes or exceeds one (0.18-3.92) despite high levels of population immunity. We calculate the cost of the first 187 confirmed and probable measles cases in 2014 to be over NZ$1 million (∼US$864,200) due to earnings lost, case management and hospitalization costs. The benefit-cost ratio analyses suggest additional vaccination beyond routine childhood immunisation is economically efficient. Supplemental vaccination-related costs are required to exceed approximately US$66 to US$1877 per person, depending on different scenarios, before supplemental vaccination is economically inefficient. Thus, our analysis suggests additional immunisation beyond childhood programs to target naïve individuals is economically beneficial even when childhood immunisation rates are high. Copyright © 2017 Elsevier Ltd. All rights reserved.

Project Learning Tree. A Program of the American Forest Foundation.

ERIC Educational Resources Information Center

American Forest Foundation, Washington, DC.

Project Learning Tree (PLT) is a supplementary environmental education program intended for use in and out of the classroom with young people, their leaders, and teachers in kindergarten through grade 12. The PLT curriculum provides supplementary activities in various subject areas, such as social studies, language arts, mathematics, science, and…

Agricultural Science I. Supplementary Units. Instructor Information.

ERIC Educational Resources Information Center

Martin, Donna; And Others

These supplementary units are designed to help students with special needs learn and apply agricultural skills in the areas of animal breeding, animal nutrition, leadership, and power tools. Specific competencies are listed as study questions at the beginning of each of the 10 self-paced and self-contained units. Skill sheets, activity sheets, and…

Integrating Supplementary Application-Based Tutorials in the Multivariable Calculus Course

ERIC Educational Resources Information Center

Verner, I. M.; Aroshas, S.; Berman, A.

2008-01-01

This article presents a study in which applications were integrated in the Multivariable Calculus course at the Technion in the framework of supplementary tutorials. The purpose of the study was to test the opportunity of extending the conventional curriculum by optional applied problem-solving activities and get initial evidence on the possible…

78 FR 44122 - Agency Information Collection Activities; Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-23

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Feature selection using a one dimensional naïve Bayes’ classifier increases the accuracy of support vector machine classification of CDR3 repertoires

PubMed Central

Cinelli, Mattia; Sun, , Yuxin; Best, Katharine; Heather, James M.; Reich-Zeliger, Shlomit; Shifrut, Eric; Friedman, Nir; Shawe-Taylor, John; Chain, Benny

2017-01-01

Abstract Motivation: Somatic DNA recombination, the hallmark of vertebrate adaptive immunity, has the potential to generate a vast diversity of antigen receptor sequences. How this diversity captures antigen specificity remains incompletely understood. In this study we use high throughput sequencing to compare the global changes in T cell receptor β chain complementarity determining region 3 (CDR3β) sequences following immunization with ovalbumin administered with complete Freund’s adjuvant (CFA) or CFA alone. Results: The CDR3β sequences were deconstructed into short stretches of overlapping contiguous amino acids. The motifs were ranked according to a one-dimensional Bayesian classifier score comparing their frequency in the repertoires of the two immunization classes. The top ranking motifs were selected and used to create feature vectors which were used to train a support vector machine. The support vector machine achieved high classification scores in a leave-one-out validation test reaching >90% in some cases. Summary: The study describes a novel two-stage classification strategy combining a one-dimensional Bayesian classifier with a support vector machine. Using this approach we demonstrate that the frequency of a small number of linear motifs three amino acids in length can accurately identify a CD4 T cell response to ovalbumin against a background response to the complex mixture of antigens which characterize Complete Freund’s Adjuvant. Availability and implementation: The sequence data is available at www.ncbi.nlm.nih.gov/sra/?term¼SRP075893. The Decombinator package is available at github.com/innate2adaptive/Decombinator. The R package e1071 is available at the CRAN repository https://cran.r-project.org/web/packages/e1071/index.html. Contact: b.chain@ucl.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online. PMID:28073756

Progress Toward Poliomyelitis Eradication - Afghanistan, January 2015‒August 2016.

PubMed

Mbaeyi, Chukwuma; Shukla, Hemant; Smith, Philip; Tangermann, Rudolf H; Martinez, Maureen; Jorba, Jaume C; Hadler, Stephen; Ehrhardt, Derek

2016-11-04

Only 74 cases of wild poliovirus (WPV) were reported globally in 2015, the lowest number of cases ever reported worldwide (1,2). All of the reported cases were WPV type 1 (WPV1), the only known WPV type still circulating; WPV type 2 has been eradicated, and WPV type 3 has not been detected since November 2012 (1). In 2015 in Afghanistan, WPV detection also declined from 2014, and trends observed in 2016 suggest that circulation of the virus is limited to a few localized areas. Despite the progress, there are concerns about the ability of the country's Polio Eradication Initiative (PEI) to meet the goal of interrupting endemic WPV transmission by the end of 2016 (3). The deteriorating security situation in the Eastern and Northeastern regions of the country considerably limits the ability to reach and vaccinate children in these regions. Furthermore, because of frequent population movements to and from Pakistan, cross-border transmission of WPV1 continues (4). Although the national PEI has taken steps to improve the quality of supplementary immunization activities (SIAs),* significant numbers of children living in accessible areas are still being missed during SIAs, and routine immunization services remain suboptimal in many parts of the country. This report describes polio eradication activities and progress in Afghanistan during January 2015‒August 2016 and updates previous reports (5,6). During 2015, a total of 20 WPV1 cases were reported in Afghanistan, compared with 28 cases in 2014; eight cases were reported during January‒August 2016, compared with nine cases reported during the same period in 2015. To achieve interruption of poliovirus transmission in Afghanistan, it is important that the 2016-2017 National Emergency Action Plan † for polio eradication be systematically implemented, including 1) improving the quality of SIAs and routine immunization services, 2) ensuring ongoing dialogue between PEI leaders and local authorities, 3) adopting innovative strategies for reaching children in security-compromised and inaccessible areas, and 4) strengthening cross-border coordination of polio vaccination and surveillance activities with Pakistan.

Induction and Characterization of Immune Responses in Small Animals Using a Venezuelan Equine Encephalitis Virus (VEE) Replicon System, Expressing Human Immunodeficiency Virus Type 1 (HIV-1) Envelope Genes

DTIC Science & Technology

2003-01-01

Immunodeficiency Virus Type-1 (HIV-1) Envelope Genes beyond brief excerpts is with permission of the copyright owner, and will save and hold harmless the...VEE) REPLICON SYSTEM, EXPRESSING HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 (HIV-1) ENVELOPE GENES 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM...release, distribution unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Human immunodeficiency virus type 1 (HIV-1) is the lentivirus responsible for the

Repurposing Drugs in Oncology (ReDO)—diclofenac as an anti-cancer agent

PubMed Central

Pantziarka, Pan; Sukhatme, Vidula; Bouche, Gauthier; Meheus, Lydie; Sukhatme, Vikas P

2016-01-01

Diclofenac (DCF) is a well-known and widely used non-steroidal anti-inflammatory drug (NSAID), with a range of actions which are of interest in an oncological context. While there has long been an interest in the use of NSAIDs in chemoprevention, there is now emerging evidence that such drugs may have activity in a treatment setting. DCF, which is a potent inhibitor of COX-2 and prostaglandin E2 synthesis, displays a range of effects on the immune system, the angiogenic cascade, chemo- and radio-sensitivity and tumour metabolism. Both pre-clinical and clinical evidence of these effects, in multiple cancer types, is assessed and summarised and relevant mechanisms of action outlined. Based on this evidence the case is made for further clinical investigation of the anticancer effects of DCF, particularly in combination with other agents - with a range of possible multi-drug and multi-modality combinations outlined in the supplementary materials accompanying the main paper. PMID:26823679

Progress Toward Measles Elimination - South-East Asia Region, 2003-2013.

PubMed

Thapa, Arun; Khanal, Sudhir; Sharapov, Umid; Swezy, Virginia; Sedai, Tika; Dabbagh, Alya; Rota, Paul; Goodson, James L; McFarland, Jeffrey

2015-06-12

In 2013, the 66th session of the Regional Committee of the World Health Organization (WHO) South-East Asia Region adopted the goal of measles elimination and rubella and congenital rubella syndrome control by 2020 after rigorous prior consultations. The recommended strategies include 1) achieving and maintaining ≥95% coverage with 2 doses of measles- and rubella-containing vaccine in every district through routine or supplementary immunization activities (SIAs); 2) developing and sustaining a sensitive and timely case-based measles surveillance system that meets recommended performance indicators; 3) developing and maintaining an accredited measles laboratory network; and 4) achieving timely identification, investigation, and response to measles outbreaks. This report updates previous reports and summarizes progress toward measles elimination in the South-East Asia Region during 2003-2013. Within the region, coverage with the first dose of a measles-containing vaccine (MCV1) increased from 67% to 78%; an estimated 286 million children (95% of the target population) were vaccinated in SIAs; measles incidence decreased 73%, from 59 to 16 cases per million population; and estimated measles deaths decreased 63%. To achieve measles elimination in the region, additional efforts are needed in countries with <95% 2-dose routine MCV coverage, particularly in India and Indonesia, to strengthen routine immunization services, conduct periodic high-quality SIAs, and strengthen measles case-based surveillance and laboratory diagnosis of measles.

Progress toward poliomyelitis eradication --- India, January 2009-October 2010.

PubMed

2010-12-10

India is one of only four countries (including Afghanistan, Nigeria, and Pakistan) where wild poliovirus (WPV) transmission has never been interrupted. Historically, WPV transmission in India has centered largely in Uttar Pradesh and Bihar, two states with low routine vaccination coverage, large migrant and remote populations, and lower relative vaccine effectiveness than other areas of the country. However, during a 9-month period from November 2009 to August 2010, no WPV type 1 (WPV1) cases were reported in Uttar Pradesh or Bihar. This report summarizes the substantial progress made in India toward polio eradication during January 2009-October 2010, according to data reported as of December 4, and updates previous reports. During January-October 2010, only 40 WPV cases were confirmed in India, a 94% decrease from the 626 WPV cases confirmed during the same period in 2009; the decrease likely resulted, in large part, from the introduction of bivalent oral poliovirus vaccine types 1 and 3 (bOPV). Increasingly important contributors to WPV transmission are large migrant subpopulations; surveys have indicated that up to 11% of children aged <5 years in these subpopulations were missed during supplementary immunization activities (SIAs). Interruption of all WPV transmission in India will require maintaining high levels of immunity in Uttar Pradesh and Bihar and additional efforts directed toward children in migrant subpopulations that are not vaccinated as readily during SIAs.

Predictors of measles vaccination coverage among children 6-59 months of age in the Democratic Republic of the Congo.

PubMed

Ashbaugh, Hayley R; Hoff, Nicole A; Doshi, Reena H; Alfonso, Vivian H; Gadoth, Adva; Mukadi, Patrick; Okitolonda-Wemakoy, Emile; Muyembe-Tamfum, Jean Jacques; Gerber, Sue K; Cherry, James D; Rimoin, Anne W

2018-01-25

Measles is a significant contributor to child mortality in the Democratic Republic of the Congo (DRC), despite routine immunization programs and supplementary immunization activities (SIA). Further, national immunization coverage levels may hide disparities among certain groups of children, making effective measles control even more challenging. This study describes measles vaccination coverage and reporting methods and identifies predictors of vaccination among children participating in the 2013-2014 DRC Demographic and Health Survey (DHS). We examined vaccination coverage of 6947 children aged 6-59 months. A multivariate logistic regression model was used to identify predictors of vaccination among children reporting vaccination via dated card in order to identify least reached children. We also assessed spatial distribution of vaccination report type by rural versus urban residence. Urban children with educated mothers were more likely to be vaccinated (OR = 4.1, 95% CI: 1.6, 10.7) versus children of mothers with no education, as were children in wealthier rural families (OR = 2.9, 95% CI: 1.9, 4.4). At the provincial level, urban areas more frequently reported vaccination via dated card than rural areas. Results indicate that, while the overall coverage level of 70% is too low, socioeconomic and geographic disparities also exist which could make some children even less likely to be vaccinated. Dated records of measles vaccination must be increased, and groups of children with the greatest need should be targeted. As access to routine vaccination services is limited in DRC, identifying and targeting under-reached children should be a strategic means of increasing country-wide effective measles control. Published by Elsevier Ltd.

Measles immunity gaps and the progress towards elimination: a multi-country modelling analysis.

PubMed

Trentini, Filippo; Poletti, Piero; Merler, Stefano; Melegaro, Alessia

2017-10-01

The persistent circulation of measles in both low-income and high-income countries requires a better characterisation of present epidemiological trends and existing immunity gaps across different sociodemographic settings. Serological surveys, which provide direct measures of population protection against the infection, are underexploited and often supply fragmentary estimates of population immunity. This study aims to investigate how measles immunity has changed over time across different socioeconomic settings, as a result of demographic changes and past immunisation policies. For this multi-country modelling analysis, we developed a transmission model to simulate measles circulation during the past 65 years in nine countries with distinct demographic and vaccination histories. The model was calibrated on historical serological data and used to estimate the reduction of disease burden as a result of vaccination and present age-specific residual susceptibility. Our model shows that estimated residual susceptibility to measles ranges from 3% in the UK to more than 10% in Kenya and Ethiopia. In high-income countries, such as Italy, Singapore, and South Korea, where routine first-dose administration produced more than 90% of immunised individuals, only about 20% of susceptible individuals are younger than 5 years. We also observed that the reduction in fertility that has occurred during the past decades in high-income countries has contributed to almost half of the reduction in measles incidence. In low-income countries, where fertility is high, the population is younger and routine vaccination has been suboptimum. Susceptible individuals are concentrated in early childhood, with about 60% of susceptible individuals in Ethiopia younger than 10 years. In these countries, Supplementary Immunization Activities (SIAs) were responsible for more than 25% of immunised individuals (up to 45% in Ethiopia), mitigating the consequences of suboptimum routine vaccination coverage. Future vaccination strategies in high-fertility countries should focus on increasing childhood immunisation rates, either by raising first-dose coverage or by making erratic SIAs more frequent and regular. Immunisation campaigns targeting adolescents and adults are required in low-fertility countries, where the susceptibility in these age groups will otherwise sustain measles circulation. European Research Council. Copyright © 2017 Elsevier Ltd. All rights reserved.

Three cases of neonatal tetanus in Papua New Guinea lead to development of national action plan for maternal and neonatal tetanus elimination

PubMed Central

Barnabas, Roland; Sitther, Adeline; Guarenti, Laura; Toikilik, Steven; Kariwiga, Grace; Sui, Gerard Pai

2013-01-01

Maternal or neonatal tetanus causes deaths primarily in Asia and Africa and is usually the result of poor hygiene during delivery. In 2011, three neonatal tetanus cases were investigated in Papua New Guinea, and all three cases were delivered at home by untrained assistants. The babies were normal at birth but subsequently developed spasms. A neonatal tetanus case must be viewed as a sentinel event indicating a failure of public health services including immunization, antenatal care and delivery care. The confirmation of these cases led to the drafting of the Papua New Guinea National Action Plan for Maternal and Neonatal Tetanus Elimination. This included three rounds of a tetanus toxoid supplementary immunization campaign targeting women of childbearing age (WBCA) and strengthening of other clean delivery practices. The first immunization round was conducted in April and May 2012, targeting 1.6 million WBCA and achieved coverage of 77%. The government of Papua New Guinea should ensure detailed investigation of all neonatal tetanus cases reported in the health information system and perform subprovincial analysis of tetanus toxoid coverage following completion of all three immunization rounds. Efforts also should be made to strengthen clean delivery practices to help eliminate maternal and neonatal tetanus in Papua New Guinea. PMID:24015370

Exploration of graphene oxide as an intelligent platform for cancer vaccines

NASA Astrophysics Data System (ADS)

Yue, Hua; Wei, Wei; Gu, Zonglin; Ni, Dezhi; Luo, Nana; Yang, Zaixing; Zhao, Lin; Garate, Jose Antonio; Zhou, Ruhong; Su, Zhiguo; Ma, Guanghui

2015-11-01

We explored an intelligent vaccine system via facile approaches using both experimental and theoretical techniques based on the two-dimensional graphene oxide (GO). Without extra addition of bio/chemical stimulators, the microsized GO imparted various immune activation tactics to improve the antigen immunogenicity. A high antigen adsorption was acquired, and the mechanism was revealed to be a combination of electrostatic, hydrophobic, and π-π stacking interactions. The ``folding GO'' acted as a cytokine self-producer and antigen reservoir and showed a particular autophagy, which efficiently promoted the activation of antigen presenting cells (APCs) and subsequent antigen cross-presentation. Such a ``One but All'' modality thus induced a high level of anti-tumor responses in a programmable way and resulted in efficient tumor regression in vivo. This work may shed light on the potential use of a new dimensional nano-platform in the development of high-performance cancer vaccines.We explored an intelligent vaccine system via facile approaches using both experimental and theoretical techniques based on the two-dimensional graphene oxide (GO). Without extra addition of bio/chemical stimulators, the microsized GO imparted various immune activation tactics to improve the antigen immunogenicity. A high antigen adsorption was acquired, and the mechanism was revealed to be a combination of electrostatic, hydrophobic, and π-π stacking interactions. The ``folding GO'' acted as a cytokine self-producer and antigen reservoir and showed a particular autophagy, which efficiently promoted the activation of antigen presenting cells (APCs) and subsequent antigen cross-presentation. Such a ``One but All'' modality thus induced a high level of anti-tumor responses in a programmable way and resulted in efficient tumor regression in vivo. This work may shed light on the potential use of a new dimensional nano-platform in the development of high-performance cancer vaccines. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr04986e

Gene expression profiling reveals two separate mechanisms regulating apoptosis in rectal carcinomas in vivo

PubMed Central

de Bruin, Elza C.; van de Pas, Simone; van de Velde, Cornelis J. H.; van Krieken, J. Han J. M.; Peltenburg, Lucy T. C.; Marijnen, Corrie A. M.

2007-01-01

The level of apoptosis in rectal carcinomas of patients treated by surgery only predicts local failure; patients with intrinsically high-apoptotic tumors develop less local recurrences than patients with low levels of apoptosis. To identify genes involved in this intrinsic apoptotic process in vivo, 47 rectal tumors with known apoptotic phenotype (24 low- and 23 high-apoptotic) were analyzed by oligonucleotide microarray technology. We identified several genes differentially expressed between low- and high-apoptotic tumors. Unsupervised clustering of the tumors based on expression levels of these genes separated the low-apoptotic from the high-apoptotic tumors, indicating a gene expression-dependent regulation. In addition, this clustering revealed two subgroups of high-apoptotic tumors. One high-apoptotic subgroup showed subtle differences in mRNA and protein expression of the known apoptotic regulators BAX, cIAP2 and ARC compared to the low-apoptotic tumors. The other subgroup of high-apoptotic tumors showed high expression of immune-related genes; predominantly HLA class II and chemokines, but also HLA class I and interferon-inducible genes were highly expressed. Immunohistochemistry revealed HLA-DR expression in epithelial tumor cells in 70% of these high-apoptotic tumors. The expression data suggest that high levels of apoptosis in rectal carcinoma patients can be the result of either slightly altered expression of known pro- and anti-apoptotic genes or high expression of immune-related genes. Electronic supplementary material The online version of this article (doi: 10.1007/s10495-007-0088-2) contains supplementary material, which is available to authorized users. PMID:17610066

Infectious Disease Risk and Vaccination in Northern Syria after 5 Years of Civil War: The MSF Experience.

PubMed

de Lima Pereira, Alan; Southgate, Rosamund; Ahmed, Hikmet; O'Connor, Penelope; Cramond, Vanessa; Lenglet, Annick

2018-02-02

In 2015, following an influx of population into Kobanê in northern Syria, Médecins Sans Frontières (MSF) in collaboration with the Kobanê Health Administration (KHA) initiated primary healthcare activities. A vaccination coverage survey and vaccine-preventable disease (VPD) risk analysis were undertaken to clarify the VPD risk and vaccination needs. This was followed by a measles Supplementary Immunization Activity (SIA). We describe the methods and results used for this prioritisation activity around vaccination in Kobanê in 2015. We implemented a pre-SIA survey in 135 randomly-selected households in Kobanê using a vaccination history questionnaire for all children <5 years. We conducted a VPD Risk Analysis using MSF 'Preventive Vaccination in Humanitarian Emergencies' guidance to prioritize antigens with the highest public health threat for mass vaccination activities. A Measles SIA was then implemented and followed by vaccine coverage survey in 282 randomly-selected households targeting children <5 years. The pre-SIA survey showed that 168/212 children (79.3%; 95%CI=72.7-84.6%) had received one vaccine or more in their lifetime. Forty-three children (20.3%; 95%CI: 15.1-26.6%) had received all vaccines due by their age; only one was <12 months old and this child had received all vaccinations outside of Syria. The VPD Risk Analysis prioritised measles, Haemophilus Influenza type B (Hib) and Pneumococcus vaccinations. In the measles SIA, 3410 children aged 6-59 months were vaccinated. The use of multiple small vaccination sites to reduce risks associated with crowds in this active conflict setting was noted as a lesson learnt. The post-SIA survey estimated 82% (95%CI: 76.9-85.9%; n=229/280) measles vaccination coverage in children 6-59 months. As a result of the conflict in Syria, the progressive collapse of the health care system in Kobanê has resulted in low vaccine coverage rates, particularly in younger age groups. The repeated displacements of the population, attacks on health institutions and exodus of healthcare workers, challenge the resumption of routine immunization in this conflict setting and limit the use of SIAs to ensure sustainable immunity to VPDs. We have shown that the risk for several VPDs in Kobanê remains high. We call on all health actors and the international community to work towards re-establishment of routine immunisation activities as a priority to ensure that children who have had no access to vaccination in the last five years are adequately protected for VPDs as soon as possible.

Nanowire array chips for molecular typing of rare trafficking leukocytes with application to neurodegenerative pathology

NASA Astrophysics Data System (ADS)

Kwak, Minsuk; Kim, Dong-Joo; Lee, Mi-Ri; Wu, Yu; Han, Lin; Lee, Sang-Kwon; Fan, Rong

2014-05-01

Despite the presence of the blood-brain barrier (BBB) that restricts the entry of immune cells and mediators into the central nervous system (CNS), a small number of peripheral leukocytes can traverse the BBB and infiltrate into the CNS. The cerebrospinal fluid (CSF) is one of the major routes through which trafficking leukocytes migrate into the CNS. Therefore, the number of leukocytes and their phenotypic compositions in the CSF may represent important sources to investigate immune-to-brain interactions or diagnose and monitor neurodegenerative diseases. Due to the paucity of trafficking leucocytes in the CSF, a technology capable of efficient isolation, enumeration, and molecular typing of these cells in the clinical settings has not been achieved. In this study, we report on a biofunctionalized silicon nanowire array chip for highly efficient capture and multiplexed phenotyping of rare trafficking leukocytes in small quantities (50 microliters) of clinical CSF specimens collected from neurodegenerative disease patients. The antibody coated 3D nanostructured materials exhibited vastly improved rare cell capture efficiency due to high-affinity binding and enhanced cell-substrate interactions. Moreover, our platform creates multiple cell capture interfaces, each of which can selectively isolate specific leukocyte phenotypes. A comparison with the traditional immunophenotyping using flow cytometry demonstrated that our novel silicon nanowire-based rare cell analysis platform can perform rapid detection and simultaneous molecular characterization of heterogeneous immune cells. Multiplexed molecular typing of rare leukocytes in CSF samples collected from Alzheimer's disease patients revealed the elevation of white blood cell counts and significant alterations in the distribution of major leukocyte phenotypes. Our technology represents a practical tool for potentially diagnosing and monitoring the pathogenesis of neurodegenerative diseases by allowing an effective hematological analysis of the CSF from patients.Despite the presence of the blood-brain barrier (BBB) that restricts the entry of immune cells and mediators into the central nervous system (CNS), a small number of peripheral leukocytes can traverse the BBB and infiltrate into the CNS. The cerebrospinal fluid (CSF) is one of the major routes through which trafficking leukocytes migrate into the CNS. Therefore, the number of leukocytes and their phenotypic compositions in the CSF may represent important sources to investigate immune-to-brain interactions or diagnose and monitor neurodegenerative diseases. Due to the paucity of trafficking leucocytes in the CSF, a technology capable of efficient isolation, enumeration, and molecular typing of these cells in the clinical settings has not been achieved. In this study, we report on a biofunctionalized silicon nanowire array chip for highly efficient capture and multiplexed phenotyping of rare trafficking leukocytes in small quantities (50 microliters) of clinical CSF specimens collected from neurodegenerative disease patients. The antibody coated 3D nanostructured materials exhibited vastly improved rare cell capture efficiency due to high-affinity binding and enhanced cell-substrate interactions. Moreover, our platform creates multiple cell capture interfaces, each of which can selectively isolate specific leukocyte phenotypes. A comparison with the traditional immunophenotyping using flow cytometry demonstrated that our novel silicon nanowire-based rare cell analysis platform can perform rapid detection and simultaneous molecular characterization of heterogeneous immune cells. Multiplexed molecular typing of rare leukocytes in CSF samples collected from Alzheimer's disease patients revealed the elevation of white blood cell counts and significant alterations in the distribution of major leukocyte phenotypes. Our technology represents a practical tool for potentially diagnosing and monitoring the pathogenesis of neurodegenerative diseases by allowing an effective hematological analysis of the CSF from patients. Electronic supplementary information (ESI) available: Additional data are available in the supplementary tables and supplementary figures. See DOI: 10.1039/c3nr06465d

Measles prevention in adolescents: lessons learnt from implementing a high school catch-up vaccination programme in New South Wales, Australia, 2014–2015

PubMed Central

Seale, Holly; Sheppeard, Vicky; Campbell-Lloyd, Sue

2016-01-01

Introduction In response to a significant increase of measles cases and a high percentage of unvaccinated adolescents in New South Wales, Australia, a measles high school catch-up vaccination programme was implemented between August and December 2014. This study aimed to explore the factors affecting school-based supplementary immunization activities (SIAs) and to inform future SIA and routine school-based vaccination programme implementation and service provision. Methods Focus group analysis was conducted among public health unit (PHU) staff responsible for implementing the SIA catch-up programme. Key areas discussed were pre-programme planning, implementation, resources, consent materials, media activity and future directions for school vaccination programme delivery. Sessions were audio recorded, transcribed verbatim and reviewed. Thematic analysis was conducted to identify the major themes. Results Two independent focus groups with 32 participants were conducted in January 2015. Barriers to the SIA implementation included lead time, consent processes, interagency collaboration, access to the targeted cohort and the impact of introducing a SIA to an already demanding curriculum and school programme immunization schedule. A positive PHU school coordinator rapport and experience of PHU staff facilitated the implementation. Consideration of different approaches for pre-clinic vaccination status checks, student involvement in the vaccination decision, online consent, workforce sharing between health districts and effective programme planning time were identified for improving future SIA implementation. Conclusion Although many barriers to school programme implementation have been identified in this study, with adequate resourcing and lead time, SIAs implemented via a routine school vaccination programme are an appropriate model to target adolescents. PMID:27757258

Extracellular entrapment and degradation of single-walled carbon nanotubes

NASA Astrophysics Data System (ADS)

Farrera, Consol; Bhattacharya, Kunal; Lazzaretto, Beatrice; Andón, Fernando T.; Hultenby, Kjell; Kotchey, Gregg P.; Star, Alexander; Fadeel, Bengt

2014-05-01

Neutrophils extrude neutrophil extracellular traps (NETs) consisting of a network of chromatin decorated with antimicrobial proteins to enable non-phagocytic killing of microorganisms. Here, utilizing a model of ex vivo activated human neutrophils, we present evidence of entrapment and degradation of carboxylated single-walled carbon nanotubes (SWCNTs) in NETs. The degradation of SWCNTs was catalyzed by myeloperoxidase (MPO) present in purified NETs and the reaction was facilitated by the addition of H2O2 and NaBr. These results show that SWCNTs can undergo acellular, MPO-mediated biodegradation and imply that the immune system may deploy similar strategies to rid the body of offending microorganisms and engineered nanomaterials.Neutrophils extrude neutrophil extracellular traps (NETs) consisting of a network of chromatin decorated with antimicrobial proteins to enable non-phagocytic killing of microorganisms. Here, utilizing a model of ex vivo activated human neutrophils, we present evidence of entrapment and degradation of carboxylated single-walled carbon nanotubes (SWCNTs) in NETs. The degradation of SWCNTs was catalyzed by myeloperoxidase (MPO) present in purified NETs and the reaction was facilitated by the addition of H2O2 and NaBr. These results show that SWCNTs can undergo acellular, MPO-mediated biodegradation and imply that the immune system may deploy similar strategies to rid the body of offending microorganisms and engineered nanomaterials. Electronic supplementary information (ESI) available: Suppl. Fig. 1 - length distribution of SWCNTs; suppl. Fig. 2 - characterization of pristine vs. oxidized SWCNTs; suppl. Fig. 3 - endotoxin evaluation; suppl. Fig. 4 - NET characterization; suppl. Fig. 5 - UV-Vis/NIR analysis of biodegradation of oxidized SWCNTs; suppl. Fig. 6 - cytotoxicity of partially degraded SWCNTs. See DOI: 10.1039/c3nr06047k

Progress toward measles preelimination--African Region, 2011-2012.

PubMed

Masresha, Balcha G; Kaiser, Reinhard; Eshetu, Messeret; Katsande, Reggis; Luce, Richard; Fall, Amadou; Dosseh, Annick R G A; Naouri, Boubker; Byabamazima, Charles R; Perry, Robert; Dabbagh, Alya J; Strebel, Peter; Kretsinger, Katrina; Goodson, James L; Nshimirimana, Deo

2014-04-04

In 2008, the 46 member states of the World Health Organization (WHO) African Region (AFR) adopted a measles preelimination goal to reach by the end of 2012 with the following targets: 1) >98% reduction in estimated regional measles mortality compared with 2000, 2) annual measles incidence of fewer than five reported cases per million population nationally, 3) >90% national first dose of measles-containing vaccine (MCV1) coverage and >80% MCV1 coverage in all districts, and 4) >95% MCV coverage in all districts by supplementary immunization activities (SIAs). Surveillance performance objectives were to report two or more cases of nonmeasles febrile rash illness per 100,000 population, one or more suspected measles cases investigated with blood specimens in ≥80% of districts, and 100% completeness of surveillance reporting from all districts. This report updates previous reports and describes progress toward the measles preelimination goal during 2011-2012. In 2012, 13 (28%) member states had >90% MCV1 coverage, and three (7%) reported >90% MCV1 coverage nationally and >80% coverage in all districts. During 2011-2012, four (15%) of 27 SIAs with available information met the target of >95% coverage in all districts. In 2012, 16 of 43 (37%) member states met the incidence target of fewer than five cases per million, and 19 of 43 (44%) met both surveillance performance targets. In 2011, the WHO Regional Committee for AFR established a goal to achieve measles elimination by 2020. To achieve this goal, intensified efforts to identify and close population immunity gaps and improve surveillance quality are needed, as well as committed leadership and ownership of the measles elimination activities and mobilization of adequate resources to complement funding from global partners.

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

Not Available

This report contains the following information from the Instrumentation and Controls Division of Oak Ridge National Laboratory: supplementary activities; seminars; publications and presentations; scientific and professional activities, achievements, and awards; and division organization charts.

Achieving high seroprevalence against polioviruses in Sri Lanka--results from a serological survey, 2014.

PubMed

Gamage, Deepa; Palihawadana, Paba; Mach, Ondrej; Weldon, William C; Oberste, Steven M; Sutter, Roland W

2015-12-01

The immunization program in Sri Lanka consistently reaches >90% coverage with oral poliovirus vaccines (OPV), and no polio supplementary vaccination campaigns have been conducted since 2003. We evaluated serological protection against polioviruses in children. A cross-sectional community-based survey was performed in three districts of Sri Lanka (Colombo, Badulla, and Killinochi). Randomly selected children in four age groups (9-11 months, 3-4 years, 7-9 years, and 15 years) were tested for poliovirus neutralizing antibodies. All 400 enrolled children completed the study. The proportion of seropositive children for poliovirus Type 1 and Type 2 was >95% for all age groups; for poliovirus Type 3 it was 95%, 90%, 77%, and 75% in the respective age groups. The vaccination coverage in our sample based on vaccination cards or parental recall was >90% in all age groups. Most Sri Lankan children are serologically protected against polioviruses through routine immunization only. This seroprevalence survey provided baseline data prior to the anticipated addition of inactivated poliovirus vaccine (IPV) into the Sri Lankan immunization program and the switch from trivalent OPV (tOPV) to bivalent OPV (bOPV). Copyright © 2015 Ministry of Health, Saudi Arabia. Published by Elsevier Ltd. All rights reserved.

Assessment of the nutritional status of Nigerian rural children and mothers' perceptions of quality of life.

PubMed

Ojofeitimi, E O

1984-01-01

One hundred and fourteen preschool school children and their 30 mothers from three selected villages in Ile-Ife, Nigeria were assessed for nutritional status using selected and sensitive anthropometric techniques. The mothers' dietary patterns, their perceptions as to components of a good quality of life, infants' immunization status and major cause of infant death were also examined. Approximately 56% of the children and 80% of the women were identified to be suffering from mild to moderate malnutrition. The major cause of infant death as reported by the mothers was high fever and convulsion. Practically all the children under 3 years had not received any form of immunization. Ability to have plenty of children, good health and money, were highly perceived as measures of essential components of quality of life by all the mothers, while 20% listed good feeding, housing, clothing, and only 7% listed potable water. The need for effective health services, regular home visits, supplementary feeding programmes for school children and an effective health education campaign on the importance of immunization and nutrition for rural people are discussed. The training of agricultural extension workers in the use of simple anthropometric techniques to identify covert malnutrition is also highlighted.

Measles cases among adolescents in southern Pakistan 2012-2015: The case for revisiting vaccination strategies.

PubMed

Shakoor, Sadia; Khan, Erum; Rajput, Muhammad Imran; Rahimoon, Wali Muhammad

2017-07-03

Surveillance of adult measles in Pakistan is a challenge as it does not enjoy the status of a reportable disease unlike childhood cases and therefore cases remain undetected and unreported or misdiagnosed. Consequently no data or estimates of young adult cases, seroprevalence, or estimates of susceptible preadolescent or young adult population exist. We have presented both laboratory conformed and clinically suspected cases of measles occurring in adolescents and adults in the southern province of Sindh in Pakistan. Through an examination of 2 independent databases, i.e. a laboratory database of measles IgM positive cases and clinically detected cases on surveillance performed by the Disease Early Warning System, we have analyzed and reported age-specific positivity rates from 2012 to 2015 in Sindh, Pakistan. High rates of laboratory confirmed measles were observed in those aged 9 y and younger. Among adolescents and adults, significantly higher positivity rates were observed among those aged 10-19 y. Clinically detected cases from Sindh showed similar distribution of cases. High burden of cases among children <9 y of age confirm that supplementary immunization activities (SIAs) among this age group are inadequate and need to be strengthened. Cases among those 10-19 y further demonstrate the need for consolidating SIAs with an additional strategy to vaccinate those who remain non-immune at college entry and in institutions where outbreaks can be prevented. Such measures are essential to achieving the goal of measles elimination in the country and region.

Alloimmune responses and atherosclerotic disease after kidney transplantation.

PubMed

Ducloux, Didier; Courivaud, Cécile; Bamoulid, Jamal; Bisaccia, Vincent; Roubiou, Caroline; Crepin, Thomas; Gaugler, Béatrice; Laheurte, Caroline; Rebibou, Jean-Michel; Chalopin, Jean-Marc; Saas, Philippe

2015-01-01

Chronic exposure to exogenous antigens causes accumulation of proinflammatory CD57(+)CD28(-) hyperactivated CD8(+) T cells that may promote atherosclerosis. We hypothesized that persistent alloimmune responses may induce immune activation and contribute to posttransplant atherosclerosis. This hypothesis was tested in a single-center cohort of 577 kidney transplant patients. Propensity score analysis was performed to address potential confounding variables by indication. Immune exhaustion was studied in subcohort of 103 patients. Five hundred seventy-seven consecutive renal transplant recipients were included. Seventy-seven atherosclerotic events (AE) (12.3%) occurred during a mean follow-up of 7 years. The cumulative incidence of AE increased with the number of human leukocyte antigen (HLA) mismatches (18%, 10%, and 5% in patients with 5-6, 3-4, and 0-2 mismatches, respectively; P=0.012). Human leukocyte antigen mismatch number (hazards ratio, 1.35; 95% confidence interval, 1.10-1.66, for each supplementary mismatch; P=0.005) was an independent risk factor for AE. In the propensity score match analysis, having received a well-matched kidney conferred a reduced risk of AE (hazards ratio, 0.22; 95% confidence interval, 0.05-0.95; P=0.044). We observed a significant correlation between HLA mismatch numbers and circulating CD57(+)CD28(-) CD8(+) T cells (R=0.31; P=0.017). These CD8(+) T cells were more frequent in patients with more HLA mismatches (P<0.0001). Overall, our results suggest that chronic allogeneic stimulation participates to accelerated atherosclerosis observed after transplantation.

Effects of vibratory stimulation-induced kinesthetic illusions on the neural activities of patients with stroke.

PubMed

Kodama, Takayuki; Nakano, Hideki; Ohsugi, Hironori; Murata, Shin

2016-01-01

[Purpose] This study evaluated the influence of vibratory stimulation-induced kinesthetic illusion on brain function after stroke. [Subjects] Twelve healthy individuals and 13 stroke patients without motor or sensory loss participated. [Methods] Electroencephalograms were taken at rest and during vibratory stimulation. As a neurophysiological index of brain function, we measured the μ-rhythm, which is present mainly in the kinesthetic cortex and is attenuated by movement or motor imagery and compared the data using source localization analyses in the Standardized Low Resolution Brain Electromagnetic Tomography (sLORETA) program. [Results] At rest, μ-rhythms appeared in the sensorimotor and supplementary motor cortices in both healthy controls and stroke patients. Under vibratory stimulation, no μ-rhythm appeared in the sensorimotor cortex of either group. Moreover, in the supplementary motor area, which stores the motor imagery required for kinesthetic illusions, the μ-rhythms of patients were significantly stronger than those of the controls, although the μ-rhythms of both groups were reduced. Thus, differences in neural activity in the supplementary motor area were apparent between the subject groups. [Conclusion] Kinesthetic illusions do occur in patients with motor deficits due to stroke. The neural basis of the supplementary motor area in stroke patients may be functionally different from that found in healthy controls.

Effects of vibratory stimulation-induced kinesthetic illusions on the neural activities of patients with stroke

PubMed Central

Kodama, Takayuki; Nakano, Hideki; Ohsugi, Hironori; Murata, Shin

2016-01-01

[Purpose] This study evaluated the influence of vibratory stimulation-induced kinesthetic illusion on brain function after stroke. [Subjects] Twelve healthy individuals and 13 stroke patients without motor or sensory loss participated. [Methods] Electroencephalograms were taken at rest and during vibratory stimulation. As a neurophysiological index of brain function, we measured the μ-rhythm, which is present mainly in the kinesthetic cortex and is attenuated by movement or motor imagery and compared the data using source localization analyses in the Standardized Low Resolution Brain Electromagnetic Tomography (sLORETA) program. [Results] At rest, μ-rhythms appeared in the sensorimotor and supplementary motor cortices in both healthy controls and stroke patients. Under vibratory stimulation, no μ-rhythm appeared in the sensorimotor cortex of either group. Moreover, in the supplementary motor area, which stores the motor imagery required for kinesthetic illusions, the μ-rhythms of patients were significantly stronger than those of the controls, although the μ-rhythms of both groups were reduced. Thus, differences in neural activity in the supplementary motor area were apparent between the subject groups. [Conclusion] Kinesthetic illusions do occur in patients with motor deficits due to stroke. The neural basis of the supplementary motor area in stroke patients may be functionally different from that found in healthy controls. PMID:27065525

The effects of UV radiation during the vegetative period on antioxidant compounds and postharvest quality of broccoli (Brassica oleracea L.).

PubMed

Topcu, Yasin; Dogan, Adem; Kasimoglu, Zehra; Sahin-Nadeem, Hilal; Polat, Ersin; Erkan, Mustafa

2015-08-01

In this study, the effects of supplementary UV radiation during the vegetative period on antioxidant compounds, antioxidant activity and postharvest quality of broccoli heads during long term storage was studied. The broccolis were grown under three different doses of supplementary UV radiation (2.2, 8.8 and 16.4 kJ/m(2)/day) in a soilless system in a glasshouse. Harvested broccoli heads were stored at 0 °C in modified atmosphere packaging for 60 days. The supplementary UV radiation (280-315 nm) during the vegetative period significantly decreased total carotenoid, the chlorophyll a and chlorophyll b content but increased the ascorbic acid, total phenolic and flavonoid contents of broccolis. All supplementary UV treatments slightly reduced the antioxidant activity of the broccolis, however, no remarkable change was observed between 2.2 and 8.8 kJ/m(2) radiation levels. The sinigrin and glucotropaeolin contents of the broccolis were substantially increased by UV treatments. The prolonged storage period resulted in decreased ascorbic acid, total phenolic and flavonoid contents, as well as antioxidant activity. Discoloration of the heads, due to decreased chlorophyll and carotenoid contents, was also observed with prolonged storage duration. Glucosinolates levels showed an increasing tendency till the 45th day of storage, and then their levels started to decline. The weight loss of broccoli heads during storage progressively increased with storage time in all treatments. Total soluble solids, solids content and titratable acidity decreased continuously during storage. Titratable acidity was not affected by UV radiation doses during the storage time whereas soluble solids and solids content (dry matter) were significantly affected by UV doses. Supplementary UV radiation increased the lightness (L*) and chroma (C*) values of the broccoli heads. Pre-harvest UV radiation during vegetative period seems to be a promising tool for increasing the beneficial health components of broccolis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Neuropsychiatric SLE: from animal model to human.

PubMed

Pikman, R; Kivity, S; Levy, Y; Arango, M-T; Chapman, J; Yonath, H; Shoenfeld, Y; Gofrit, S G

2017-04-01

Animal models are a key element in disease research and treatment. In the field of neuropsychiatric lupus research, inbred, transgenic and disease-induced mice provide an opportunity to study the pathogenic routes of this multifactorial illness. In addition to achieving a better understanding of the immune mechanisms underlying the disease onset, supplementary metabolic and endocrine influences have been discovered and investigated. The ever-expanding knowledge about the pathologic events that occur at disease inception enables us to explore new drugs and therapeutic approaches further and to test them using the same animal models. Discovery of the molecular targets that constitute the pathogenic basis of the disease along with scientific advancements allow us to target these molecules with monoclonal antibodies and other specific approaches directly. This novel therapy, termed "targeted biological medication" is a promising endeavor towards producing drugs that are more effective and less toxic. Further work to discover additional molecular targets in lupus' pathogenic mechanism and to produce drugs that neutralize their activity is needed to provide patients with safe and efficient methods of controlling and treating the disease.

Anticancer and immunoregulatory activity of Gynostemma pentaphyllum polysaccharides in H22 tumor-bearing mice.

PubMed

Liu, Jun; Zhang, Lihua; Ren, Yingang; Gao, Yanli; Kang, Li; Qiao, Qing

2014-08-01

A neutral polysaccharide fraction (CGPP) was extracted from Gynostemma pentaphyllum by water extraction and ethanol precipitation. Gas chromatography (GC) analysis showed that the CGPP was mainly composed of mannose, glucose, arabinose, rhamnose, galactose and glucuronic acid in molar ratios of 2.0:2.2:1.3:2.2:1.2:2.5. The present study aimed at evaluating the antitumor potentials of CGPP on the growth of H22 tumor transplanted in mice and the underlying mechanism. The results showed that CGPP (50 and 200mg/kg) could effectively inhibit the solid tumor growth of H22 hepatocarcinoma transplanted in ICR mice. Besides, the body weight, spleen/thymus indexes and splenocytes proliferation of H22 tumor bearing mice were also improved in CGPP-treated groups. Furthermore, the level of the cytokines, such as IL-2, TNF-α and IFN-γ, as well as the activity of natural killer (NK) cells and cytotoxic T lymphocytes (CTL) in tumor-bearing mice were markedly promoted by CGPP oral administration. In addition, CGPP treatment greatly prolonged the survival period in H22 ascites tumor-bearing mice. Taken together, these findings indicate that CGPP has antitumor activity in vivo at least partly via improving immune responses of host organism, and seems to be a safe and effective supplementary agent for the treatment of hepatocellular carcinoma (HCC). Copyright © 2014 Elsevier B.V. All rights reserved.

Demand Creation for Polio Vaccine in Persistently Poor-Performing Communities of Northern Nigeria: 2013-2014.

PubMed

Warigon, Charity; Mkanda, Pascal; Muhammed, Ado; Etsano, Andrew; Korir, Charles; Bawa, Samuel; Gali, Emmanuel; Nsubuga, Peter; Erbeto, Tesfaya B; Gerlong, George; Banda, Richard; Yehualashet, Yared G; Vaz, Rui G

2016-05-01

Poliomyelitis remains a global threat despite availability of oral polio vaccine (OPV), proven to reduce the burden of the paralyzing disease. In Nigeria, children continue to miss the opportunity to be fully vaccinated, owing to factors such as unmet health needs and low uptake in security-compromised and underserved communities. We describe the implementation and evaluation of several activities to create demand for polio vaccination in persistently poor-performing local government areas (LGAs). We assessed the impact of various polio-related interventions, to measure the contribution of demand creation activities in 77 LGAs at very high risk for polio, located across 10 states in northern Nigeria. Interventions included provision of commodities along with the polio vaccine. There was an increasing trend in the number of children reached by different demand creation interventions. A total of 4 819 847 children were vaccinated at health camps alone. There was a reduction in the number of wards in which >10% of children were missed by supplementary immunization activities due to noncompliance with vaccination recommendations, a rise in the proportion of children who received ≥4 OPV doses, and a decrease in the proportion of children who were underimmunized or unimmunized. Demand creation interventions increased the uptake of polio vaccines in persistently poor-performing high-risk communities in northern Nigeria during September 2013-November 2014. © 2016 World Health Organization; licensee Oxford Journals.

Beyond anorexia -cachexia. Nutrition and modulation of cancer patients' metabolism: supplementary, complementary or alternative anti-neoplastic therapy?

PubMed

Laviano, Alessandro; Seelaender, Marilia; Sanchez-Lara, Karla; Gioulbasanis, Ioannis; Molfino, Alessio; Rossi Fanelli, Filippo

2011-09-01

Anorexia and muscle wasting are frequently observed in cancer patients and influence their clinical outcome. The better understanding of the mechanisms underlying behavioral changes and altered metabolism yielded to the development of specialized nutritional support, which enhances utilization of provided calories and proteins by counteracting some of the metabolic derangements occurring during tumor growth. Inflammation appears to be a key factor determining the cancer-associated biochemical abnormalities eventually leading to anorexia and cachexia. Interestingly, inflammation is also involved in carcinogenesis, cancer progression and metastasis by impairing immune surveillance, among other mechanisms. Therefore, nutritional interventions aiming at modulating inflammation to restore nutritional status may also result in improved response to pharmacological anti-cancer therapies. Recent clinical data show that supplementation with nutrients targeting inflammation and immune system increases response rate and survival in cancer patients. This suggests that nutrition therapy should be considered as an important adjuvant strategy in the multidimensional approach to cancer patients. Copyright © 2011 Elsevier B.V. All rights reserved.

SUPPLEMENTARY COMPARISON: COOMET.RI(II)-S1.Rn-222 (169/UA/98): Rn-222 volume activity comparison

NASA Astrophysics Data System (ADS)

Skliarov, V.; Röttger, A.; Honig, A.; Korostin, S.; Kuznetsov, S.; Lapenas, A.; Milevsky, V.; Ivaniukovich, A.; Kharitonov, I.; Sepman, S.

2009-01-01

According to a first program, a supplementary comparison of Rn-222 volume activity was drawn up as a bilateral supplementary comparison between NSC 'Institute of Metrology', Ukraine, and VNIIFTRI, Russia. It took place in March 2005. In April 2005, at the 5th meeting of COOMET held in Braunschweig (Germany), representatives of these institutes exchanged data which showed the comparability of the national standards of Ukraine and Russia for the check points. During the discussion of the procedure some other institutes decided to join the comparison program, which was extended to BelGIM (Belarus), PTB (Germany), VNIIM (Russia) and RMTC (Latvia). The national standards of volume activity of radon-222 were thus calibrated using one standard radon radiometer as the transfer standard. Results are shown in the Final Report of the comparison. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by COOMET, according to the provisions of the CIPM Mutual Recognition Arrangement (MRA).

Effects of the Health Activities Project on Student Attitudes toward Health.

ERIC Educational Resources Information Center

Sheldon, Daniel S.

1980-01-01

The impact of the Health Activities Project (HAP), an activity-centered, supplementary health education program for fifth- to eighth-grade students, on their attitudes toward health education was studied. Results indicated a positive change. (JD)

Health: the basic right of every child.

PubMed

Tandon, B N

1989-01-01

Through the efforts of organizations such as the National Children's Board, the health of children in India has shown considerable improvement in the post-independence period. The Integrated Child Development Services Program, launched in 1975, has brought together government and voluntary organizations in multisectoral, comprehensive activities aimed at enhancing children's physical, mental, and psychosocial well-being. Nonetheless, on essential child health indicators, India falls behind many other developing countries with even fewer technical resources. India's perinatal, neonatal, infant, and under-5 mortality rates stand at 84, 65, 95 and 152/1000, respectively. 30% of infants are low birthweight. 35% of children under 5 suffer from malnutrition and only 17% receive measles vaccination. 62% of Indian children do not complete primary school. These inadequacies persist despite programs directed at prenatal care, breastfeeding promotion, immunization, supplementary nutrition to preschoolers, iron and folic acid tablet distribution, oral rehydration for diarrhea, management of acute respiratory infection, safe drinking water, and preschool education. For these programs to have the intended impact, coordination and management must be improved at the village level. The mass media and village-level health workers must be enlisted in outreach activities to reach mothers with messages on child health and nutrition. Finally, any efforts to improve child health must be accompanied by family planning programs.

Progress toward poliomyelitis eradication--poliomyelitis outbreak in Sudan, 2004.

PubMed

2005-02-04

After the World Health Assembly of the World Health Organization (WHO) resolved in 1988 to eradicate poliomyelitis globally, the number of countries in which polio is endemic declined from 125 to six by 2003. However, in 2004, polio cases caused by wild poliovirus (WPV) originating from northern Nigeria were reported in 11 countries--Benin, Botswana, Cameroon, Guinea, Mali, Saudi Arabia, Burkina Faso, Central African Republic, Chad, Cote d'Ivoire, and Sudan--reestablishing transmission in the latter five countries. Sudan, a member state of the WHO Eastern Mediterranean Region, initiated poliomyelitis eradication activities in the northern area of the country in 1994 and in the south in 1998. Since 1998, Sudan has made substantial progress in implementing polio eradication strategies, with no WPV reported from May 2001 through April 2004. However, in May 2004, a WPV case was detected in West Darfur, and a polio outbreak is currently affecting 17 of the country's 26 states. This report describes the outbreak and response and provides an update on acute flaccid paralysis (AFP) surveillance and supplementary immunization activities (SIAs) in Sudan. The outbreak underscores the importance of continued SIAs in polio-free countries with low routine vaccination coverage, even in areas with moderate to low population density, as well as the need to ensure uniformly high-quality AFP surveillance.

Polio elimination in Nigeria: A review.

PubMed

Nasir, Usman Nakakana; Bandyopadhyay, Ananda Sankar; Montagnani, Francesca; Akite, Jacqueline Elaine; Mungu, Etaluka Blanche; Uche, Ifeanyi Valentine; Ismaila, Ahmed Mohammed

2016-03-03

Nigeria has made tremendous strides towards eliminating polio and has been free of wild polio virus (WPV) for more than a year as of August 2015. However, sustained focus towards getting rid of all types of poliovirus by improving population immunity and enhancing disease surveillance will be needed to ensure it sustains the polio-free status. We reviewed the pertinent literature including published and unpublished, official reports and working documents of the Global Polio Eradication Initiative (GPEI) partners as well as other concerned organizations. The literature were selected based on the following criteria: published in English Language, published after year 2000, relevant content and conformance to the theme of the review and these were sorted accordingly. The challenges facing the Polio Eradication Initiative (PEI) in Nigeria were found to fall into 3 broad categories viz failure to vaccinate, failure of the Oral Polio Vaccine (OPV) and epidemiology of the virus. Failure to vaccinate resulted from insecurity, heterogeneous political support, programmatic limitation in implementation of vaccination campaigns, poor performance of vaccination teams in persistently poor performing Local Government areas and sporadic vaccine refusals in Northern Nigeria. Sub optimal effectiveness of OPV in some settings as well as the rare occurrence of VDPVs associated with OPV type 2 in areas of low immunization coverage were also found to be key issues. Some of the innovations which helped to manage the threats to the PEI include a strong government accountability frame work, change from type 2 containing OPV to bi valent OPVs for supplementary immunization activities (SIA), enhancing environmental surveillance in key states (Sokoto, Kano and Borno) along with an overall improvement in SIA quality. There has been an improvement in coverage of routine immunization and vaccination campaigns, which has resulted in Nigeria being removed from the list of endemic countries following an absence of new cases for an entire year as of September 2015. However, the last mile remains to be crossed and there is need to further improve and sustain the momentum to complete the journey toward polio elimination.

Polio elimination in Nigeria: A review

PubMed Central

Nasir, Usman Nakakana; Bandyopadhyay, Ananda Sankar; Montagnani, Francesca; Akite, Jacqueline Elaine; Mungu, Etaluka Blanche; Uche, Ifeanyi Valentine; Ismaila, Ahmed Mohammed

2016-01-01

abstract Nigeria has made tremendous strides towards eliminating polio and has been free of wild polio virus (WPV) for more than a year as of August 2015. However, sustained focus towards getting rid of all types of poliovirus by improving population immunity and enhancing disease surveillance will be needed to ensure it sustains the polio-free status. We reviewed the pertinent literature including published and unpublished, official reports and working documents of the Global Polio Eradication Initiative (GPEI) partners as well as other concerned organizations. The literature were selected based on the following criteria: published in English Language, published after year 2000, relevant content and conformance to the theme of the review and these were sorted accordingly. The challenges facing the Polio Eradication Initiative (PEI) in Nigeria were found to fall into 3 broad categories viz failure to vaccinate, failure of the Oral Polio Vaccine (OPV) and epidemiology of the virus. Failure to vaccinate resulted from insecurity, heterogeneous political support, programmatic limitation in implementation of vaccination campaigns, poor performance of vaccination teams in persistently poor performing Local Government areas and sporadic vaccine refusals in Northern Nigeria. Sub optimal effectiveness of OPV in some settings as well as the rare occurrence of VDPVs associated with OPV type 2 in areas of low immunization coverage were also found to be key issues. Some of the innovations which helped to manage the threats to the PEI include a strong government accountability frame work, change from type 2 containing OPV to bi valent OPVs for supplementary immunization activities (SIA), enhancing environmental surveillance in key states (Sokoto, Kano and Borno) along with an overall improvement in SIA quality. There has been an improvement in coverage of routine immunization and vaccination campaigns, which has resulted in Nigeria being removed from the list of endemic countries following an absence of new cases for an entire year as of September 2015. However, the last mile remains to be crossed and there is need to further improve and sustain the momentum to complete the journey toward polio elimination. PMID:26383769

Supplementary motor area and primary auditory cortex activation in an expert break-dancer during the kinesthetic motor imagery of dance to music.

PubMed

Olshansky, Michael P; Bar, Rachel J; Fogarty, Mary; DeSouza, Joseph F X

2015-01-01

The current study used functional magnetic resonance imaging to examine the neural activity of an expert dancer with 35 years of break-dancing experience during the kinesthetic motor imagery (KMI) of dance accompanied by highly familiar and unfamiliar music. The goal of this study was to examine the effect of musical familiarity on neural activity underlying KMI within a highly experienced dancer. In order to investigate this in both primary sensory and motor planning cortical areas, we examined the effects of music familiarity on the primary auditory cortex [Heschl's gyrus (HG)] and the supplementary motor area (SMA). Our findings reveal reduced HG activity and greater SMA activity during imagined dance to familiar music compared to unfamiliar music. We propose that one's internal representations of dance moves are influenced by auditory stimuli and may be specific to a dance style and the music accompanying it.

Evidence for parallel activation of the pre-supplementary motor area and inferior frontal cortex during response inhibition: a combined MEG and TMS study

PubMed Central

Singh, Krish D.; Verbruggen, Frederick

2018-01-01

This pre-registered experiment sought to uncover the temporal relationship between the inferior frontal cortex (IFC) and the pre-supplementary motor area (pre-SMA) during stopping of an ongoing action. Both regions have previously been highlighted as being central to cognitive control of actions, particularly response inhibition. Here we tested which area is activated first during the stopping process using magnetoencephalography, before assessing the relative chronometry of each region using functionally localized transcranial magnetic stimulation. Both lines of evidence pointed towards simultaneous activity across both regions, suggesting that parallel, mutually interdependent processing may form the cortical basis of stopping. Additional exploratory analysis, however, provided weak evidence in support of previous suggestions that the pre-SMA may provide an ongoing drive of activity to the IFC. PMID:29515852

Teachers' Guide for Aviation Education for Use in Grades Two through Six.

ERIC Educational Resources Information Center

Aviation/Space, 1979

1979-01-01

This teacher's guide provides supplementary activities in aviation designed for students in grades 2-6. The activities stress communication arts, science, and social studies. The guide contains performance objectives, instructional procedures, student activities, and outcomes. (MA)

HIV-associated chronic immune activation

PubMed Central

Paiardini, Mirko; Müller-Trutwin, Michaela

2013-01-01

Summary Systemic chronic immune activation is considered today as the driving force of CD4+ T-cell depletion and acquired immunodeficiency syndrome (AIDS). A residual chronic immune activation persists even in HIV-infected patients in which viral replication is successfully inhibited by antiretroviral therapy, with the extent of this residual immune activation being associated with CD4+ T-cell loss. Unfortunately, the causal link between chronic immune activation and CD4+ T-cell loss has not been formally established. This article provides first a brief historical overview on how the perception of the causative role of immune activation has changed over the years and lists the different kinds of immune activation that have been observed to be characteristic for human immunodeficiency virus (HIV) infection. The mechanisms proposed to explain the chronic immune activation are multiple and are enumerated here, as well as the mechanisms proposed on how chronic immune activation could lead to AIDS. In addition, we summarize the lessons learned from natural hosts that know how to ‘show AIDS the door’, and discuss how these studies informed the design of novel immune modulatory interventions that are currently being tested. Finally, we review the current approaches aimed at targeting chronic immune activation and evoke future perspectives. PMID:23772616

Selective imaging of cathepsin L in breast cancer by fluorescent activity-based probes† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7sc04303a

PubMed Central

Rut, Wioletta; Vizovisek, Matej; Groborz, Katarzyna; Kasperkiewicz, Paulina; Finlay, Darren; Vuori, Kristiina; Turk, Dusan; Turk, Boris; Salvesen, Guy S.

2018-01-01

Cysteine cathepsins normally function in the lysosomal degradation system where they are critical for the maintenance of cellular homeostasis and the MHC II immune response, and have been found to have major roles in several diseases and in tumor progression. Selective visualization of individual protease activity within a complex proteome is of major importance to establish their roles in both normal and tumor cells, thereby facilitating our understanding of the regulation of proteolytic networks. A generally accepted means to monitor protease activity is the use of small molecule substrates and activity-based probes. However, there are eleven human cysteine cathepsins, with a few of them displaying overlapping substrate specificity, making the development of small molecules that selectively target a single cathepsin very challenging. Here, we utilized HyCoSuL, a positional scanning substrate approach, to develop a highly-selective fluorogenic substrate and activity-based probe for monitoring cathepsin L activity in the breast cancer cell line MDA-MB-231. Use of this probe enabled us to distinguish the activity of cathepsin L from that of other cathepsins, particularly cathepsin B, which is abundant and ubiquitously expressed in normal and transformed cell types. We found that cathepsin L localization in MDA-MB-231 cells greatly overlaps with that of cathepsin B, however, several cathepsin L-rich lysosomes lacked cathepsin B activity. Overall, these studies demonstrate that HyCoSuL-derived small molecule probes are valuable tools to image cathepsin L activity in living cells. This approach thus enables evaluation of cathepsin L function in tumorigenesis and is applicable to other cysteine cathepsins. PMID:29719685

78 FR 16914 - Proposed Collection; Comment Request for Revenue Procedure 2010-13

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-19

... soliciting comments concerning Revenue Procedure 2010-13, Section 469 Grouping activities. DATES: Written... . SUPPLEMENTARY INFORMATION: Title: Section 469 Grouping activities. OMB Number: 1545-2156. Notice Number: Revenue... Service their groupings and regroupings of activities and the addition of specific activities within their...

75 FR 51525 - Railroad Safety Advisory Committee (RSAC); Working Group Activity Update

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-20

.... 63] Railroad Safety Advisory Committee (RSAC); Working Group Activity Update AGENCY: Federal Railroad... Committee (RSAC) Working Group Activities. SUMMARY: The FRA is updating its announcement of RSAC's Working.... SUPPLEMENTARY INFORMATION: This notice serves to update FRA's last announcement of working group activities and...

Infectious Disease Risk and Vaccination in Northern Syria after 5 Years of Civil War: The MSF Experience

PubMed Central

de Lima Pereira, Alan; Southgate, Rosamund; Ahmed, Hikmet; O’Connor, Penelope; Cramond, Vanessa; Lenglet, Annick

2018-01-01

Introduction: In 2015, following an influx of population into Kobanê in northern Syria, Médecins Sans Frontières (MSF) in collaboration with the Kobanê Health Administration (KHA) initiated primary healthcare activities. A vaccination coverage survey and vaccine-preventable disease (VPD) risk analysis were undertaken to clarify the VPD risk and vaccination needs. This was followed by a measles Supplementary Immunization Activity (SIA). We describe the methods and results used for this prioritisation activity around vaccination in Kobanê in 2015. Methods: We implemented a pre-SIA survey in 135 randomly-selected households in Kobanê using a vaccination history questionnaire for all children <5 years. We conducted a VPD Risk Analysis using MSF ‘Preventive Vaccination in Humanitarian Emergencies’ guidance to prioritize antigens with the highest public health threat for mass vaccination activities. A Measles SIA was then implemented and followed by vaccine coverage survey in 282 randomly-selected households targeting children <5 years. Results: The pre-SIA survey showed that 168/212 children (79.3%; 95%CI=72.7-84.6%) had received one vaccine or more in their lifetime. Forty-three children (20.3%; 95%CI: 15.1-26.6%) had received all vaccines due by their age; only one was <12 months old and this child had received all vaccinations outside of Syria. The VPD Risk Analysis prioritised measles, Haemophilus Influenza type B (Hib) and Pneumococcus vaccinations. In the measles SIA, 3410 children aged 6-59 months were vaccinated. The use of multiple small vaccination sites to reduce risks associated with crowds in this active conflict setting was noted as a lesson learnt. The post-SIA survey estimated 82% (95%CI: 76.9-85.9%; n=229/280) measles vaccination coverage in children 6-59 months. Discussion: As a result of the conflict in Syria, the progressive collapse of the health care system in Kobanê has resulted in low vaccine coverage rates, particularly in younger age groups. The repeated displacements of the population, attacks on health institutions and exodus of healthcare workers, challenge the resumption of routine immunization in this conflict setting and limit the use of SIAs to ensure sustainable immunity to VPDs. We have shown that the risk for several VPDs in Kobanê remains high. Conclusion: We call on all health actors and the international community to work towards re-establishment of routine immunisation activities as a priority to ensure that children who have had no access to vaccination in the last five years are adequately protected for VPDs as soon as possible. PMID:29511602

(Neuro)transmitter systems in circulating immune cells: a target of immunopharmacological interventions?

PubMed

Tayebati, Seyed Khosrow; Amenta, Francesco

2008-01-01

Increasing evidence indicates the existence of an association between nervous and immune systems. The two systems communicate with each-other to maintain immune homeostasis. Activated immune cells secrete cytokines that influence central nervous system activity. Nervous system, through its peripheral and/or autonomic divisions activates output regulating levels of immune cell activity and the subsequent magnitude of an immune response. On the other hand, neurotransmitters, which represent the main substances involved in nerve cell communications, can influence immune function. Immune organs and circulating immune cells express several (neuro)transmitter systems that can be involved in regulating their activity. The expression of neurotransmitter systems by different subsets of circulating immune cells was reviewed. The regulatory role of different families of (neuro)transmitters (catecholamines, 5-hydroxytryptamine, acetylcholine, histamine and neuropeptides) in modulating levels of immune mediators or specific immune responses is discussed.

Effect of nanovaccine chemistry on humoral immune response kinetics and maturation

NASA Astrophysics Data System (ADS)

Haughney, Shannon L.; Ross, Kathleen A.; Boggiatto, Paola M.; Wannemuehler, Michael J.; Narasimhan, Balaji

2014-10-01

Acute respiratory infections represent a significant portion of global morbidity and mortality annually. There is a critical need for efficacious vaccines against respiratory pathogens. To vaccinate against respiratory disease, pulmonary delivery is an attractive route because it mimics the route of natural infection and can confer both mucosal and systemic immunity. We have previously demonstrated that a single dose, intranasal vaccine based on polyanhydride nanoparticles elicited a protective immune response against Yersinia pestis for at least 40 weeks after immunization with F1-V. Herein, we investigate the effect of nanoparticle chemistry and its attributes on the kinetics and maturation of the antigen-specific serum antibody response. We demonstrate that manipulation of polyanhydride nanoparticle chemistry facilitated differential kinetics of development of antibody titers, avidity, and epitope specificity. The results provide new insights into the underlying role(s) of nanoparticle chemistry in providing long-lived humoral immunity and aid in the rational design of nanovaccine formulations to induce long-lasting and mature antibody responses.Acute respiratory infections represent a significant portion of global morbidity and mortality annually. There is a critical need for efficacious vaccines against respiratory pathogens. To vaccinate against respiratory disease, pulmonary delivery is an attractive route because it mimics the route of natural infection and can confer both mucosal and systemic immunity. We have previously demonstrated that a single dose, intranasal vaccine based on polyanhydride nanoparticles elicited a protective immune response against Yersinia pestis for at least 40 weeks after immunization with F1-V. Herein, we investigate the effect of nanoparticle chemistry and its attributes on the kinetics and maturation of the antigen-specific serum antibody response. We demonstrate that manipulation of polyanhydride nanoparticle chemistry facilitated differential kinetics of development of antibody titers, avidity, and epitope specificity. The results provide new insights into the underlying role(s) of nanoparticle chemistry in providing long-lived humoral immunity and aid in the rational design of nanovaccine formulations to induce long-lasting and mature antibody responses. Electronic supplementary information (ESI) available: Fig. S1. See DOI: 10.1039/c4nr03724c

Vaccine-Derived Poliovirus Outbreaks and Events - Three Provinces, Democratic Republic of the Congo, 2017.

PubMed

Alleman, Mary M; Chitale, Rohit; Burns, Cara C; Iber, Jane; Dybdahl-Sissoko, Naomi; Chen, Qi; Van Koko, Djo-Roy; Ewetola, Raimi; Riziki, Yogolelo; Kavunga-Membo, Hugo; Dah, Cheikh; Andriamihantanirina, Rija

2018-03-16

The last confirmed wild poliovirus (WPV) case in Democratic Republic of the Congo (DRC) had paralysis onset in December 2011 (1). DRC has had cases of vaccine-derived polioviruses (VDPVs) documented since 2004 (Table 1) (1-6). After an outbreak of 30 circulating VDPV type 2 (cVDPV2) cases during 2011-2012, only five VDPV2 cases were reported during 2013-2016 (Table 1) (1-6). VDPVs can emerge from oral poliovirus vaccine (OPV types 1, 2, or 3; Sabin) polioviruses that have genetically mutated resulting in reversion to neurovirulence. This process occurs during extensive person-to-person transmission in populations with low immunity or after extended replication in the intestines of immune-deficient persons following vaccination (1-6). During 2017 (as of March 8, 2018), 25 VDPV cases were reported in three provinces in DRC: in Tanganyika province, an emergence with one VDPV2 case (pending final classification) in Kabalo health zone and an emergence with one ambiguous VDPV type 1 (aVDPV1) case in Ankoro health zone; in Maniema province, an emergence with two cVDPV2 cases; and in Haut Lomami province, an emergence with 20 cVDPV2 cases that originated in Haut Lomami province and later spread to Tanganyika province (hereafter referred to as the Haut Lomami outbreak area) and an emergence with one aVDPV type 2 (aVDPV2) case in Lwamba health zone (Table 1) (Figure) (6). Outbreak response supplementary immunization activities (SIAs) were conducted during June-December 2017 (Table 2) (6). Because of limitations in surveillance and suboptimal SIA quality and geographic scope, cVDPV2 circulation is likely continuing in 2018, requiring additional SIAs. DRC health officials and Global Polio Eradication Initiative (GPEI) partners are increasing human and financial resources to improve all aspects of outbreak response.

Comparison of the effectiveness of two protocols of antirabies bait distribution for foxes (Vulpes vulpes).

PubMed

Vuillaume, P; Bruyere, V; Aubert, M

1998-01-01

In a plateau and hill region of France (the Doubs), two protocols of rabies vaccine bait distribution targeted at foxes were compared: helicopter distribution of vaccine baits alone (control zone) and a combined aerial distribution by helicopter with an additional deposit of vaccine baits at fox den entrances by foot (test zone). In the test zone covering an area of 436 km2, baits were distributed by helicopter at a rate of 13.4 baits/km2. Additionally, an average of 11.4 vaccine baits at the entrances of 871 fox dens were terrestrially distributed by 110 persons (9,964 baits). In this test zone, 90% of the young foxes were marked with tetracycline which permitted estimation of the bait consumption; however, only 38% had significant titre of rabies antibodies and less than one fox cub per 2.4 of those having consumed at least one bait were immunized. In the control zone, these percentages were significantly lower: respectively, 35 and 17% and one fox cub per 4.2. The relative lack of benefit between bait uptake and rate of immunological response may be due to maternal immunity which could have interfered with fox cub active immunization. A booster effect following a second distribution of baits by foot may be suggested in both adult foxes and their offspring. That these baits needed to be terrestrially distributed in order to obtain a booster effect is uncertain. Terrestrial distribution at fox den entrances is difficult to do and entails additional expenses not incurred in aerial distribution. The cost of terrestrial vaccination is 3.5 times higher than classical aerial vaccination and takes 63.5 times longer. A cost effective analysis of this type of supplementary terrestrial intervention determined that bait deposit at den entrances can be recommended for restricted areas, where residual focii exist, as a complement to the aerial distribution of baits.

Progress Toward Measles Elimination - Nepal, 2007-2014.

PubMed

Khanal, Sudhir; Sedai, Tika Ram; Choudary, Ganga Ram; Giri, Jagat Narain; Bohara, Rajendra; Pant, Rajendra; Gautam, Mukunda; Sharapov, Umid M; Goodson, James L; Alexander, James; Dabbagh, Alya; Strebel, Peter; Perry, Robert T; Bah, Sunil; Abeysinghe, Nihal; Thapa, Arun

2016-03-04

In 2013, the 66th session of the Regional Committee of the World Health Organization (WHO) South-East Asia Region (SEAR) established a goal to eliminate measles and to control rubella and congenital rubella syndrome (CRS) in SEAR by 2020. Current recommended measles elimination strategies in the region include 1) achieving and maintaining ≥95% coverage with 2 doses of measles-containing vaccine (MCV) in every district, delivered through the routine immunization program or through supplementary immunization activities (SIAs); 2) developing and sustaining a sensitive and timely measles case-based surveillance system that meets minimum recommended performance indicators; 3) developing and maintaining an accredited measles laboratory network; and 4) achieving timely identification, investigation, and response to measles outbreaks. In 2013, Nepal, one of the 11 SEAR member states, adopted a goal for national measles elimination by 2019. This report updates a previous report and summarizes progress toward measles elimination in Nepal during 2007-2014. During 2007-2014, estimated coverage with the first MCV dose (MCV1) increased from 81% to 88%. Approximately 3.9 and 9.7 million children were vaccinated in SIAs conducted in 2008 and 2014, respectively. Reported suspected measles incidence declined by 13% during 2007-2014, from 54 to 47 cases per 1 million population. However, in 2014, 81% of districts did not meet the measles case-based surveillance performance indicator target of ≥2 discarded non-measles cases per 100,000 population per year. To achieve and maintain measles elimination, additional measures are needed to strengthen routine immunization services to increase coverage with MCV1 and a recently introduced second dose of MCV (MCV2) to ≥95% in all districts, and to enhance sensitivity of measles case-based surveillance by adopting a more sensitive case definition, expanding case-based surveillance sites nationwide, and ensuring timely transport of specimens to the accredited national laboratory.

77 FR 24257 - Railroad Safety Advisory Committee (RSAC); Working Group Activity Update

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-23

.... 69] Railroad Safety Advisory Committee (RSAC); Working Group Activity Update AGENCY: Federal Railroad... Committee (RSAC) Working Group Activities. SUMMARY: The FRA is updating its announcement of the RSAC Working.... SUPPLEMENTARY INFORMATION: This notice serves to update FRA's last announcement of working group activities and...

[The effect of active immunization with Acanthamoeba culbertsoni in mice born to immune mother].

PubMed

Kong, H H; Seo, S A; Shin, C O; Im, K I

1993-06-01

Acanthamoeba culbertsoni is a pathogenic free-living amoeba causing primary amoebic meningoencephalitis (PAME) in human and mouse. Several reports on the immune responses in mice with this amoebic infection have been published, but the effects of transferred passive immunity on the active immunization in offspring mice have not been demonstrated. This experiment was done to observe the effect of active immunization with Acanthamoeba culbertsoni in mice born to immune mothers. Acanthamoeba culbertsoni was cultured in the CGV medium axenically. Female BALB/c mice weighing about 20g were immunized through the intraperitoneal injection of Acanthamoeba culbertsoni trophozoites 1 x 10(6) each three times at the interval of one week. Offspring mice were immunized two times. The mice were inoculated intranasally with 1 x 10(4) trophozoites under secobarbital anesthesia. There was a statistical difference in mortality between the transferred immunity group and the active immunization group. Statistical differences were not demonstrated in antibody titer between both groups. But L3T4+ T cell/Ly2+ T cell ratio was increased in the transferred immunity group more than active immunization group of the offspring mice at the age of 5 weeks. There was no differences statistically in mortality between both groups. It was recognized that active immunization in offspring mice born to immune mother could modulate the immune status according to the time of immunization.

Conservation Seeds Activities Book. An Early Childhood Conservation Education Program.

ERIC Educational Resources Information Center

Griffin, Sherri

This activities book is used with an early childhood conservation education program. The activities are presented in four color-coded sections, each section representing one of the four seasons. Each activity includes a statement of purpose, list of materials needed, instructional strategies, and a list of supplementary activities. In addition to…

Estimation of immunization providers' activities cost, medication cost, and immunization dose errors cost in Iraq.

PubMed

Al-lela, Omer Qutaiba B; Bahari, Mohd Baidi; Al-abbassi, Mustafa G; Salih, Muhannad R M; Basher, Amena Y

2012-06-06

The immunization status of children is improved by interventions that increase community demand for compulsory and non-compulsory vaccines, one of the most important interventions related to immunization providers. The aim of this study is to evaluate the activities of immunization providers in terms of activities time and cost, to calculate the immunization doses cost, and to determine the immunization dose errors cost. Time-motion and cost analysis study design was used. Five public health clinics in Mosul-Iraq participated in the study. Fifty (50) vaccine doses were required to estimate activities time and cost. Micro-costing method was used; time and cost data were collected for each immunization-related activity performed by the clinic staff. A stopwatch was used to measure the duration of activity interactions between the parents and clinic staff. The immunization service cost was calculated by multiplying the average salary/min by activity time per minute. 528 immunization cards of Iraqi children were scanned to determine the number and the cost of immunization doses errors (extraimmunization doses and invalid doses). The average time for child registration was 6.7 min per each immunization dose, and the physician spent more than 10 min per dose. Nurses needed more than 5 min to complete child vaccination. The total cost of immunization activities was 1.67 US$ per each immunization dose. Measles vaccine (fifth dose) has a lower price (0.42 US$) than all other immunization doses. The cost of a total of 288 invalid doses was 744.55 US$ and the cost of a total of 195 extra immunization doses was 503.85 US$. The time spent on physicians' activities was longer than that spent on registrars' and nurses' activities. Physician total cost was higher than registrar cost and nurse cost. The total immunization cost will increase by about 13.3% owing to dose errors. Copyright © 2012 Elsevier Ltd. All rights reserved.

Monitoring progress toward measles elimination by genetic diversity analysis of measles viruses in China 2009-2010.

PubMed

Zhang, Y; Wang, H; Xu, S; Mao, N; Zhu, Z; Shi, J; Huang, G; Liu, C; Bo, F; Feng, D; Lu, P; Liu, Y; Wang, Y; Lei, Y; Chen, M; Chen, H; Wang, C; Fu, H; Li, C; He, J; Gao, H; Gu, S; Wang, S; Ling, H; Liu, Y; Ding, Z; Ba, Z; Feng, Y; Zheng, H; Tang, X; Lei, Y; Xiong, Y; Bellini, W J; Rota, P A; Jee, Y; Xu, W

2014-09-01

With the achievement of high coverage for routine immunization and supplementary immunization activities (SIAs), measles incidence in mainland China reached its lowest level in 2010. The proportion of measles cases in the vaccination-targeted population decreased during 2007-2010 after the SIAs. More than 60% of measles cases were in adults or infants, especially in the coastal and eastern provinces during 2009 and 2010. A total 567 isolates of measles virus were obtained from clinical specimens from 27 of 31 provinces in mainland China during 2009 and 2010. Except for two vaccine-associated cases, one genotype D4 strain, two genotype D9 strains, and four genotype D11 strains, the other 558 strains were genotype H1 cluster H1a. Genotype H1 has been the only endemic genotype detected in China since surveillance began in 1993. Only genotype H1 was found in mainland China during 1993-2008, except for one detection of genotype H2. More recently, multiple genotypes of imported measles were detected even with the background of endemic genetotype H1 viruses. Analysis of the 450-nucleotide sequencing window of the measles virus N gene showed that the overall genetic diversity of the recent geneotype H1 strains decreased between 2008 and 2010. The lower genetic diversity of H1 strains suggested that enhanced vaccination may have reduced the co-circulating lineages of endemic genotype H1 strains in mainland China. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

Progress Toward Polio Eradication — Somalia, 1998–2013

PubMed Central

Mbaeyi, Chukwuma; Kamadjeu, Raoul; Mahamud, Abdirahman; Webeck, Jenna; Ehrhardt, Derek; Mulugeta, Abraham

2015-01-01

Since the 1988 resolution of the World Health Assembly to eradicate polio, significant progress has been made toward achieving this goal, with the result that only Afghanistan, Nigeria, and Pakistan have never successfully interrupted endemic transmission of wild poliovirus. However, one of the greatest challenges of the Global Polio Eradication Initiative has been that of maintaining the polio-free status of countries in unstable regions with weak healthcare infrastructure, a challenge exemplified by Somalia, a country in the Horn of Africa region. Somalia interrupted indigenous transmission of wild poliovirus in 2002, four years after establishing its national polio eradication programme. But political instability and protracted armed conflict, with significant disruption of the healthcare system, left the country vulnerable to two subsequent imported outbreaks of wild poliovirus. The first occurred during 2005–2007, resulting in over 200 cases of paralytic polio, while the second importation in 2013 is currently ongoing. Despite immense challenges, the country has a sensitive surveillance system that has facilitated prompt detection of outbreaks, but its weak routine immunization system means that supplementary immunization activities constitute the primary strategy for reaching children with polio vaccines. Conducting vaccination campaigns in a setting of conflict has been at times hazardous but the country’s polio programme has demonstrated resilience in overcoming many obstacles to ensure that children receive life-saving polio vaccines. Regaining and maintaining Somalia’s polio-free status will, however, depend on finding innovative and lasting solutions to the challenge of administering vaccines in a setting of ongoing conflict and instability. PMID:25316833

Progress toward measles elimination--Eastern Mediterranean Region, 2008-2012.

PubMed

Teleb, Nadia; Lebo, Emmaculate; Ahmed, Hinda; Hossam, Abdel Rahman; El Sayed, El Tayeb; Dabbagh, Alya; Strebel, Peter; Rota, Paul; Alexander, James

2014-06-13

In 1997, the 22 countries in the World Health Organization (WHO) Eastern Mediterranean Region (EMR) adopted a goal of measles elimination by 2010. To achieve this goal, the WHO Regional Office for the Eastern Mediterranean Region (EMRO) developed a four-pronged strategy: 1) achieve ≥ 95% vaccination coverage of children with the first dose of measles-containing vaccine (MCV1) in every district of each country through routine immunization services, 2) achieve ≥ 95% vaccination coverage with the second dose of measles-containing vaccine (MCV2) in every district of each country either through a routine 2-dose vaccination schedule or through supplementary immunization activities (SIAs), 3) conduct high-quality, case-based surveillance in all countries, and 4) provide optimal clinical case management, including supplementing diets with vitamin A. Although significant progress was made toward measles elimination in the EMR during 1997-2007, the measles elimination goal was not reached by the target date of 2010, and the date was revised to 2015. This report updates previous reports and summarizes the progress made toward measles elimination in EMR during 2008-2012. From 2008 to 2012, large outbreaks occurred in countries with a high incidence of measles, and reported annual measles cases in EMR increased from 12,186 to 36,456. To achieve measles elimination in EMR, efforts are needed to increase 2-dose vaccination coverage, especially in countries with high incidence of measles and in conflict-affected countries, and to implement innovative strategies to reach populations at high risk in areas with poor access to vaccination services or with civil strife.

Continued Endemic Wild Poliovirus Transmission in Security-Compromised Areas - Nigeria, 2016.

PubMed

Nnadi, Chimeremma; Damisa, Eunice; Esapa, Lisa; Braka, Fiona; Waziri, Ndadilnasiya; Siddique, Anisur; Jorba, Jaume; Nganda, Gatei Wa; Ohuabunwo, Chima; Bolu, Omotayo; Wiesen, Eric; Adamu, Usman

2017-02-24

On August 10, 2016, 2 years after the most recent wild poliovirus (WPV) case was reported in Nigeria (in July 2014) (1), two WPV cases were reported in the northeastern state of Borno, which has been severely affected by insurgency-related insecurity since 2013. On September 9 and 26, 2016, two additional WPV cases were reported in Borno in children whose families migrated from security-compromised, inaccessible areas of the state. All four cases were WPV serotype 1 (WPV1), with genetic differences indicating prolonged undetected transmission. A large-scale emergency response plan was developed and implemented. The plan initially called for vaccination of 815,791 children during August 15-18 in five local government areas (LGAs) in the immediate vicinity of the first two WPV cases. Subsequently, the plan was expanded to regionally synchronized supplementary immunization activities (SIAs), conducted during August 27-December 6 in five Lake Chad basin countries at increased risk for national and regional WPV1 transmission (Cameroon, Central African Republic, Chad, Niger, and Nigeria). In addition, retrospective searches for missed cases of acute flaccid paralysis (AFP), enhanced environmental surveillance for polioviruses, and polio surveillance system reviews were conducted. Prolonged undetected WPV1 transmission in Borno State is a consequence of low population immunity and severe surveillance limitations associated with insurgency-related insecurity and highlights the risk for local and international WPV spread (2). Increasing polio vaccination coverage and implementing high-quality polio surveillance, especially among populations in newly secured and difficult-to-access areas in Borno and other Lake Chad basin areas are urgently needed.

Fractional-Dose Inactivated Poliovirus Vaccine Campaign - Sindh Province, Pakistan, 2016.

PubMed

Pervaiz, Aslam; Mbaeyi, Chukwuma; Baig, Mirza Amir; Burman, Ashley; Ahmed, Jamal A; Akter, Sharifa; Jatoi, Fayaz A; Mahamud, Abdirahman; Asghar, Rana Jawad; Azam, Naila; Shah, Muhammad Nadeem; Laghari, Mumtaz Ali; Soomro, Kamaluddin; Wadood, Mufti Zubair; Ehrhardt, Derek; Safdar, Rana M; Farag, Noha

2017-12-01

Following the declaration of eradication of wild poliovirus (WPV) type 2 in September 2015, trivalent oral poliovirus vaccine (tOPV) was withdrawn globally to reduce the risk for type 2 vaccine-derived poliovirus (VDPV2) transmission; all countries implemented a synchronized switch to bivalent OPV (type 1 and 3) in April 2016 (1,2). Any isolation of VDPV2 after the switch is to be treated as a potential public health emergency and might indicate the need for supplementary immunization activities (3,4). On August 9, 2016, VDPV2 was isolated from a sewage sample taken from an environmental surveillance site in Hyderabad, Sindh province, Pakistan. Possible vaccination activities in response to VDPV2 isolation include the use of injectable inactivated polio vaccine (IPV), which poses no risk for vaccine-derived poliovirus transmission. Fractional-dose, intradermal IPV (fIPV), one fifth of the standard intramuscular dose, has been developed to more efficiently manage limited IPV supplies. fIPV has been shown in some studies to be noninferior to full-dose IPV (5,6) and was used successfully in response to a similar detection of a single VDPV2 isolate from sewage in India (7). Injectable fIPV was used for response activities in Hyderabad and three neighboring districts. This report describes the findings of an assessment of preparatory activities and subsequent implementation of the fIPV campaign. Despite achieving high coverage (>80%), several operational challenges were noted. The lessons learned from this campaign could help to guide the planning and implementation of future fIPV vaccination activities.

The Universe Adventure - Teachers

Science.gov Websites

Go Teachers The Universe Adventure provides a variety of supplementary resources to bring cosmology Bangs Activity .doc .rtf List of Relevant California Science Standards .doc .rtf Class Discussion Calendar" Activity .doc .rtf Practice with Orders of Magnitude Activity .doc .rtf Ordering the Events

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Career Activities in Science: Grades 7, 8, 9.

ERIC Educational Resources Information Center

Boise City Independent School District, ID.

The career activities guide in science, part of an Idaho State Department of Vocational Education career exploration series for grades 7, 8, and 9, is designed as supplementary material to enrich the regular curriculum. Any one activity in the guide might be used without involving any other activities. The cross-referenced index indicates grades,…

Career Activities in Social Science: Grades 7, 8, 9.

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Boise City Independent School District, ID.

The career activities guide in social science, part of an Idaho State Department of Vocational Education career exploration series for grades 7, 8, and 9, is designed as supplementary material to enrich the regular curriculum. Any one activity in the guide might be used without involving any other activities. The cross-referenced index indicates…

Career Activities in Mathematics: Grades 7, 8, 9.

ERIC Educational Resources Information Center

Boise City Independent School District, ID.

The career activities guide in mathematics, part of an Idaho State Department of Vocational Education career exploration series for grades 7, 8, and 9, is designed as supplementary material to enrich the regular curriculum. Any one activity in the guide might be used without involving any other activities. The cross-referenced index indicates…

Teaching about U.S. History: A Comparative Approach, 33 Activities. History Series, Volume 2.

ERIC Educational Resources Information Center

Smith, Gary R.

This book contains 33 supplementary activities on U.S. history. Although the activities were written for junior and senior high school students, most activities are adaptable for use with elementary school students also. The activities attempt to develop skills in three areas: (1) discovery skills (collecting, analyzing, and evaluating data;…

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Demand Creation for Polio Vaccine in Persistently Poor-Performing Communities of Northern Nigeria: 2013–2014

PubMed Central

Warigon, Charity; Mkanda, Pascal; Muhammed, Ado; Etsano, Andrew; Korir, Charles; Bawa, Samuel; Gali, Emmanuel; Nsubuga, Peter; Erbeto, Tesfaya B.; Gerlong, George; Banda, Richard; Yehualashet, Yared G.; Vaz, Rui G.

2016-01-01

Introduction. Poliomyelitis remains a global threat despite availability of oral polio vaccine (OPV), proven to reduce the burden of the paralyzing disease. In Nigeria, children continue to miss the opportunity to be fully vaccinated, owing to factors such as unmet health needs and low uptake in security-compromised and underserved communities. We describe the implementation and evaluation of several activities to create demand for polio vaccination in persistently poor-performing local government areas (LGAs). Methods. We assessed the impact of various polio-related interventions, to measure the contribution of demand creation activities in 77 LGAs at very high risk for polio, located across 10 states in northern Nigeria. Interventions included provision of commodities along with the polio vaccine. Results. There was an increasing trend in the number of children reached by different demand creation interventions. A total of 4 819 847 children were vaccinated at health camps alone. There was a reduction in the number of wards in which >10% of children were missed by supplementary immunization activities due to noncompliance with vaccination recommendations, a rise in the proportion of children who received ≥4 OPV doses, and a decrease in the proportion of children who were underimmunized or unimmunized. Conclusions. Demand creation interventions increased the uptake of polio vaccines in persistently poor-performing high-risk communities in northern Nigeria during September 2013–November 2014. PMID:26908717

Real-Time Monitoring of Vaccination Campaign Performance Using Mobile Phones - Nepal, 2016.

PubMed

Oh, David H; Dabbagh, Alya; Goodson, James L; Strebel, Peter M; Thapa, Sanjita; Giri, Jagat Narain; Shakya, Sagar Ratna; Khanal, Sudhir

2016-10-07

In 2012, the Global Vaccine Action Plan* established a goal to achieve measles and rubella elimination in five of the six World Health Organization (WHO) regions (194 countries) by 2020 (1). Measles elimination strategies aim to achieve ≥95% coverage with 2 routine doses of measles-containing vaccine (2), and implement supplementary immunization activities (SIAs) † in settings where routine coverage is low or where there are subpopulations at high risk. To ensure SIA quality and to achieve ≥95% SIA coverage nationally, rapid convenience monitoring (RCM) is used during or immediately after SIAs (3,4). The objective of RCM is to find unvaccinated children and to identify reasons for nonvaccination in areas with persons at high risk, to enable immediate implementation of corrective actions (e.g., reassigning teams to poorly vaccinated areas, modifying the timing of vaccination, or conducting mop-up vaccination activities). This report describes pilot testing of RCM using mobile phones (RCM-MP) during the second phase of an SIA in Nepal in 2016. Use of RCM-MP resulted in 87% timeliness and 94% completeness of data reporting and found that, although 95% of children were vaccinated, 42% of areas required corrective vaccination activities. RCM-MP challenges included connecting to mobile networks, small phone screen size, and capturing Global Positioning System (GPS) coordinates. Nonetheless, use of RCM-MP led to faster data transmission, analysis, and decision-making and to increased accountability among levels of the health system.

78 FR 66105 - Agency Information Collection Activities Under OMB Review

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Instrumentation and Controls Division progress report, July 1, 1990--June 30, 1992. Volume 2

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

Not Available

1993-01-01

This report contains the following information from the Instrumentation and Controls Division of Oak Ridge National Laboratory: supplementary activities; seminars; publications and presentations; scientific and professional activities, achievements, and awards; and division organization charts.

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Gut health immunomodulatory and anti-inflammatory functions of gut enzyme digested high protein micro-nutrient dietary supplement-Enprocal.

PubMed

Kanwar, Jagat R; Kanwar, Rupinder K

2009-01-31

Enprocal is a high-protein micro-nutrient rich formulated supplementary food designed to meet the nutritional needs of the frail elderly and be delivered to them in every day foods. We studied the potential of Enprocal to improve gut and immune health using simple and robust bioassays for gut cell proliferation, intestinal integrity/permeability, immunomodulatory, anti-inflammatory and anti-oxidative activities. Effects of Enprocal were compared with whey protein concentrate 80 (WPC), heat treated skim milk powder, and other commercially available milk derived products. Enprocal (undigested) and digested (Enprocal D) selectively enhanced cell proliferation in normal human intestinal epithelial cells (FHs74-Int) and showed no cytotoxicity. In a dose dependent manner Enprocal induced cell death in Caco-2 cells (human colon adencarcinoma epithelial cells). Digested Enprocal (Enprocal D: gut enzyme cocktail treated) maintained the intestinal integrity in transepithelial resistance (TEER) assay, increased the permeability of horseradish peroxidase (HRP) and did not induce oxidative stress to the gut epithelial cells. Enprocal D upregulated the surface expression of co-stimulatory (CD40, CD86, CD80), MHC I and MHC II molecules on PMA differentiated THP-1 macrophages in coculture transwell model, and inhibited the monocyte/lymphocyte (THP-1/Jurkat E6-1 cells)-epithelial cell adhesion. In cytokine secretion analyses, Enprocal D down-regulated the secretion of proinflammatory cytokines (IL-1beta and TNF-alpha) and up-regulated IFN-gamma, IL-2 and IL-10. Our results indicate that Enprocal creates neither oxidative injury nor cytotoxicity, stimulates normal gut cell proliferation, up regulates immune cell activation markers and may aid in the production of antibodies. Furthermore, through downregulation of proinflammatory cytokines, Enprocal appears to be beneficial in reducing the effects of chronic gut inflammatory diseases such as inflammatory bowel disease (IBD). Stimulation of normal human fetal intestinal cell proliferation without cell cytotoxicity indicates it may also be given as infant food particularly for premature babies.

Gold nanocluster-based vaccines for dual-delivery of antigens and immunostimulatory oligonucleotides

NASA Astrophysics Data System (ADS)

Tao, Yu; Zhang, Yan; Ju, Enguo; Ren, Hui; Ren, Jinsong

2015-07-01

We here report a facile one-pot synthesis of fluorescent gold nanoclusters (AuNCs) via the peptide biomineralization method, which can elicit specific immunological responses. The as-prepared peptide-protected AuNCs (peptide-AuNCs) display strong red fluorescence, and more importantly, as compared to the peptide alone, the immune stimulatory ability of the resulting peptide-AuNCs can not only be retained, but can also be efficaciously enhanced. Moreover, through a dual-delivery of antigen peptides and cytosine-phosphate-guanine (CpG) oligodeoxynucleotides (ODNs), the as-prepared peptide-AuNC-CpG conjugates can also act as smart self-vaccines to assist in the generation of high immunostimulatory activity, and be applied as a probe for intracellular imaging. Both in vitro and in vivo studies provide strong evidence that the AuNC-based vaccines may be utilized as safe and efficient immunostimulatory agents that are able to prevent and/or treat a variety of ailments.We here report a facile one-pot synthesis of fluorescent gold nanoclusters (AuNCs) via the peptide biomineralization method, which can elicit specific immunological responses. The as-prepared peptide-protected AuNCs (peptide-AuNCs) display strong red fluorescence, and more importantly, as compared to the peptide alone, the immune stimulatory ability of the resulting peptide-AuNCs can not only be retained, but can also be efficaciously enhanced. Moreover, through a dual-delivery of antigen peptides and cytosine-phosphate-guanine (CpG) oligodeoxynucleotides (ODNs), the as-prepared peptide-AuNC-CpG conjugates can also act as smart self-vaccines to assist in the generation of high immunostimulatory activity, and be applied as a probe for intracellular imaging. Both in vitro and in vivo studies provide strong evidence that the AuNC-based vaccines may be utilized as safe and efficient immunostimulatory agents that are able to prevent and/or treat a variety of ailments. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr02240a

Vitamin D accelerates clinical recovery from tuberculosis: results of the SUCCINCT Study [Supplementary Cholecalciferol in recovery from tuberculosis]. A randomized, placebo-controlled, clinical trial of vitamin D supplementation in patients with pulmonary tuberculosis'.

PubMed

Salahuddin, Nawal; Ali, Farheen; Hasan, Zahra; Rao, Nisar; Aqeel, Masooma; Mahmood, Faisal

2013-01-19

Vitamin D enhances host protective immune responses to Mycobacterium tuberculosis by suppressing Interferon-gamma (IFN-g) and reducing disease associated inflammation in the host. The objectives of this study were to determine whether vitamin D supplementation to patients with tuberculosis (TB) could influence recovery. Two hundred and fifty nine patients with pulmonary TB were randomized to receive either 600,000 IU of Intramuscular vitamin D3 or placebo for 2 doses. Assessments were performed at 4, 8 and 12 weeks. Early secreted and T cell activated 6 kDa (ESAT6) and Mycobacterium tuberculosis sonicate (MTBs) antigen induced whole blood stimulated IFN-g responses were measured at 0 and 12 weeks. Statistical comparisons between outcome variables at 0 and 12 weeks were performed using Student's t-test and Chi2 tests. After 12 weeks, the vitamin D supplemented arm demonstrated significantly greater mean weight gain (kg)+3.75, (3.16-4.34) versus+2.61 (95% CI 1.99-3.23) p 0.009 and lesser residual disease by chest radiograph; number of zones involved 1.35 v/s 1.82 p 0.004 (95% CI 0.15, 0.79) and 50% or greater reduction in cavity size 106 (89.8%) v/s 111 (94.8%), p 0.035. Vitamin D supplementation led to significant increase in MTBs-induced IFN-g secretion in patients with baseline 'Deficient' 25-hydroxyvitamin D serum levels (p 0.021). Supplementation with high doses of vitamin D accelerated clinical, radiographic improvement in all TB patients and increased host immune activation in patients with baseline 'Deficient' serum vitamin D levels. These results suggest a therapeutic role for vitamin D in the treatment of TB. ClinicalTrials.gov; No. NCT01130311; URL: clinicaltrials.gov.

Breast-feeding and the development of cows' milk protein allergy.

PubMed

Saarinen, K M; Juntunen-Backman, K; Järvenpää, A L; Klemetti, P; Kuitunen, P; Lope, L; Renlund, M; Siivola, M; Vaarala, O; Savilahti, E

2000-01-01

Early feeding with cows' milk (CM) may cause cows' milk allergy (CMA). Breast milk contains many immune factors which compensate for the undeveloped defence mechanisms of the gut of the newborn infant. We studied the effect of supplementary CM feeding at the maternity hospital on the subsequent incidence of CMA, the effects of formula and breast feeding on the subsequent immunologic types of CMA, and the importance of immune factors present in colostrum in the immune responses of infants with CMA. In a cohort of 6209 infants, 824 were exclusively breast-fed and 87% required supplementary milk while in the maternity hospital: 1789 received CM formula, 1859 pasteurized human milk, and 1737 whey hydrolysate formula. The cumulative incidence of CMA, verified by a CM elimination-challenge test, was 2.4% in the CM, 1.7% in the pasteurized human milk and 1.5% in the whey hydrolysate group. Among these infants, exposure to CM at hospital and a positive atopic heredity increased the risk of CMA. Of the exclusively breast-fed infants, 2.1% had CMA. Risk factors for the development of IgE-mediated CMA were: exposure to CM at hospital, breast-feeding during the first 8 weeks at home either exclusively or combined with infrequent exposure to small amounts of CM and long breast-feeding. The content of transforming growth factor-beta1 (TGF-beta1) in colostrum from mothers of infants with IgE-mediated CMA was lower than from mothers of infants with non-IgE-mediated CMA. In infants with CMA, TGF-beta1 in colostrum negatively correlated with the result of skin prick test and the stimulation of peripheral blood mononuclear cells to CM, but positively with infants' IgA and IgG antibodies to CM proteins. Feeding of CM formula at maternity hospital increases the risk of CMA, but exclusive breast-feeding does not eliminate the risk. Prolonged breast-feeding exclusively or combined with infrequent exposure to small amounts of CM during the first 8 weeks induces the development of IgE-mediated CMA. Colostral TGF-beta1 may inhibit IgE- and cell mediated reactions and promote IgG-IgA antibody production to CM in infants prone to developing CMA.

'It's showed me the skills that he has': pharmacists' and mentors' views on pharmacist supplementary prescribing.

PubMed

Lloyd, Fran; Parsons, Carole; Hughes, Carmel M

2010-02-01

Supplementary prescribing has seen pharmacists assume greater responsibility for prescribing in collaboration with doctors. This study explored the context and experiences, in relation to the practice of supplementary prescribing, of pharmacists and physicians (who acted as their training mentors) at least 12 months after pharmacists had qualified as supplementary prescribers. The setting was primary and secondary healthcare sectors in Northern Ireland. Pharmacists and mentors who had participated in a pre-training study were invited to take part. All pharmacists (n = 47) were invited to participate in focus groups, while mentors (n = 35) were asked to participate in face-to-face semi-structured interviews. The research took place between May 2005 and September 2007. All discussions and interviews were audiotaped, transcribed and analysed using constant comparison. Nine pharmacist focus groups were convened (number per group ranging from three to six; total n = 40) and 31 semi-structured interviews with mentors were conducted. The six main themes that emerged were optimal practice setting, professional progression for prescribing pharmacists, outcomes for prescribing pharmacists, mentors and patients, relationships, barriers to implementation and the future of pharmacist prescribing. Where practised, pharmacist prescribing had been accepted, worked best for chronic disease management, was perceived to have reduced doctors' workload and improved continuity of care for patients. However, three-quarters of pharmacists qualified to practise as supplementary prescribers were not actively prescribing, largely due to logistical and organisational barriers rather than inter-professional tensions. Independent prescribing was seen as contentious by mentors, particularly because of the diagnostic element. Supplementary prescribing has been successful where it has been implemented but a number of barriers remain which are preventing the wider acceptance of this practice innovation.

Supplementary physicians' fees: a sustainable system?

PubMed

Calcoen, Piet; van de Ven, Wynand P M M

2018-01-25

In Belgium and France, physicians can charge a supplementary fee on top of the tariff set by the mandatory basic health insurance scheme. In both countries, the supplementary fee system is under pressure because of financial sustainability concerns and a lack of added value for the patient. Expenditure on supplementary fees is increasing much faster than total health expenditure. So far, measures taken to curb this trend have not been successful. For certain categories of physicians, supplementary fees represent one-third of total income. For patients, however, the added value of supplementary fees is not that clear. Supplementary fees can buy comfort and access to physicians who refuse to treat patients who are not willing to pay supplementary fees. Perceived quality of care plays an important role in patients' willingness to pay supplementary fees. Today, there is no evidence that physicians who charge supplementary fees provide better quality of care than physicians who do not. However, linking supplementary fees to objectively proven quality of care and limiting access to top quality care to patients able and willing to pay supplementary fees might not be socially acceptable in many countries. Our conclusion is that supplementary physicians' fees are not sustainable.

Polio eradication: mobilizing and managing the human resources.

PubMed Central

Aylward, R. Bruce; Linkins, Jennifer

2005-01-01

Between 1988 and 2004, the Global Polio Eradication Initiative grew to become the largest international health effort in history, operating in every country of the world. An estimated 10 million health workers and volunteers have been engaged in implementing the necessary polio supplementary immunization activities (SIAs) on a recurring basis, and at least 35,000 well-trained workers have been conducting polio surveillance. A combination of task simplification, technological innovations and adaptation of strategies to fit local circumstances has allowed the Initiative to use a wide range of workers and volunteers, from both inside and outside the health sector, to deliver the polio vaccine during SIAs and to monitor progress in virtually every area of every country, regardless of the health infrastructure, conflict, geography and/or culture. This approach has required sustained political advocacy and mass community mobilization, together with strong management and supervisory processes. Non-monetary incentives, reimbursement of costs and substantial technical assistance have been essential. Given the unique features of eradication programmes in general, and polio eradication in particular, the implications of this approach for the broader health system must continue to be studied if it is to be replicated for the delivery and monitoring of other interventions. PMID:15868017

Polio eradication: mobilizing and managing the human resources.

PubMed

Aylward, R Bruce; Linkins, Jennifer

2005-04-01

Between 1988 and 2004, the Global Polio Eradication Initiative grew to become the largest international health effort in history, operating in every country of the world. An estimated 10 million health workers and volunteers have been engaged in implementing the necessary polio supplementary immunization activities (SIAs) on a recurring basis, and at least 35,000 well-trained workers have been conducting polio surveillance. A combination of task simplification, technological innovations and adaptation of strategies to fit local circumstances has allowed the Initiative to use a wide range of workers and volunteers, from both inside and outside the health sector, to deliver the polio vaccine during SIAs and to monitor progress in virtually every area of every country, regardless of the health infrastructure, conflict, geography and/or culture. This approach has required sustained political advocacy and mass community mobilization, together with strong management and supervisory processes. Non-monetary incentives, reimbursement of costs and substantial technical assistance have been essential. Given the unique features of eradication programmes in general, and polio eradication in particular, the implications of this approach for the broader health system must continue to be studied if it is to be replicated for the delivery and monitoring of other interventions.

Association between latent proviral characteristics and immune activation in antiretrovirus-treated human immunodeficiency virus type 1-infected adults.

PubMed

Liang, Emily C; Sceats, Lindsay; Bayless, Nicholas L; Strauss-Albee, Dara M; Kubo, Jessica; Grant, Philip M; Furman, David; Desai, Manisha; Katzenstein, David A; Davis, Mark M; Zolopa, Andrew R; Blish, Catherine A

2014-08-01

Generalized immune activation during HIV infection is associated with an increased risk of cardiovascular disease, neurocognitive disease, osteoporosis, metabolic disorders, and physical frailty. The mechanisms driving this immune activation are poorly understood, particularly for individuals effectively treated with antiretroviral medications. We hypothesized that viral characteristics such as sequence diversity may play a role in driving HIV-associated immune activation. We therefore sequenced proviral DNA isolated from peripheral blood mononuclear cells from HIV-infected individuals on fully suppressive antiretroviral therapy. We performed phylogenetic analyses, calculated viral diversity and divergence in the env and pol genes, and determined coreceptor tropism and the frequency of drug resistance mutations. Comprehensive immune profiling included quantification of immune cell subsets, plasma cytokine levels, and intracellular signaling responses in T cells, B cells, and monocytes. These antiretroviral therapy-treated HIV-infected individuals exhibited a wide range of diversity and divergence in both env and pol genes. However, proviral diversity and divergence in env and pol, coreceptor tropism, and the level of drug resistance did not significantly correlate with markers of immune activation. A clinical history of virologic failure was also not significantly associated with levels of immune activation, indicating that a history of virologic failure does not inexorably lead to increased immune activation as long as suppressive antiretroviral medications are provided. Overall, this study demonstrates that latent viral diversity is unlikely to be a major driver of persistent HIV-associated immune activation. Chronic immune activation, which is associated with cardiovascular disease, neurologic disease, and early aging, is likely to be a major driver of morbidity and mortality in HIV-infected individuals. Although treatment of HIV with antiretroviral medications decreases the level of immune activation, levels do not return to normal. The factors driving this persistent immune activation, particularly during effective treatment, are poorly understood. In this study, we investigated whether characteristics of the latent, integrated HIV provirus that persists during treatment are associated with immune activation. We found no relationship between latent viral characteristics and immune activation in treated individuals, indicating that qualities of the provirus are unlikely to be a major driver of persistent inflammation. We also found that individuals who had previously failed treatment but were currently effectively treated did not have significantly increased levels of immune activation, providing hope that past treatment failures do not have a lifelong "legacy" impact. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment.

PubMed

Yu, Hua; Kortylewski, Marcin; Pardoll, Drew

2007-01-01

Immune cells in the tumour microenvironment not only fail to mount an effective anti-tumour immune response, but also interact intimately with the transformed cells to promote oncogenesis actively. Signal transducer and activator of transcription 3 (STAT3), which is a point of convergence for numerous oncogenic signalling pathways, is constitutively activated both in tumour cells and in immune cells in the tumour microenvironment. Constitutively activated STAT3 inhibits the expression of mediators necessary for immune activation against tumour cells. Furthermore, STAT3 activity promotes the production of immunosuppressive factors that activate STAT3 in diverse immune-cell subsets, altering gene-expression programmes and, thereby, restraining anti-tumour immune responses. As such, STAT3 propagates several levels of crosstalk between tumour cells and their immunological microenvironment, leading to tumour-induced immunosuppression. Consequently, STAT3 has emerged as a promising target for cancer immunotherapy.

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Identification of an immune-responsive mesolimbocortical serotonergic system: Potential role in regulation of emotional behavior

PubMed Central

Lowry, C.A.; Hollis, J.H.; de Vries, A.; Pan, B.; Brunet, L.R.; Hunt, J.R.F.; Paton, J.F.R.; van Kampen, E.; Knight, D.M.; Evans, A.K.; Rook, G.A.W.; Lightman, S.L.

2007-01-01

Peripheral immune activation can have profound physiological and behavioral effects including induction of fever and sickness behavior. One mechanism through which immune activation or immunomodulation may affect physiology and behavior is via actions on brainstem neuromodulatory systems, such as serotonergic systems. We have found that peripheral immune activation with antigens derived from the nonpathogenic, saprophytic bacterium, Mycobacterium vaccae, activated a specific subset of serotonergic neurons in the interfascicular part of the dorsal raphe nucleus (DRI) of mice, as measured by quantification of c-Fos expression following intratracheal (12 h) or s.c. (6 h) administration of heat-killed, ultrasonically disrupted M. vaccae, or heat-killed, intact M. vaccae, respectively. These effects were apparent after immune activation by M. vaccae or its components but not by ovalbumin, which induces a qualitatively different immune response. The effects of immune activation were associated with increases in serotonin metabolism within the ventromedial prefrontal cortex, consistent with an effect of immune activation on mesolimbocortical serotonergic systems. The effects of M. vaccae administration on serotonergic systems were temporally associated with reductions in immobility in the forced swim test, consistent with the hypothesis that the stimulation of mesolimbocortical serotonergic systems by peripheral immune activation alters stress-related emotional behavior. These findings suggest that the immune-responsive subpopulation of serotonergic neurons in the DRI is likely to play an important role in the neural mechanisms underlying regulation of the physiological and pathophysiological responses to both acute and chronic immune activation, including regulation of mood during health and disease states. Together with previous studies, these findings also raise the possibility that immune stimulation activates a functionally and anatomically distinct subset of serotonergic neurons, different from the subset of serotonergic neurons activated by anxiogenic stimuli or uncontrollable stressors. Consequently, selective activation of specific subsets of serotonergic neurons may have distinct behavioral outcomes. PMID:17367941

Modeling the Impact of Alternative Immunization Strategies: Using Matrices as Memory Lanes

PubMed Central

Alonso, Wladimir J.; Rabaa, Maia A.; Giglio, Ricardo; Miller, Mark A.; Schuck-Paim, Cynthia

2015-01-01

Existing modeling approaches are divided between a focus on the constitutive (micro) elements of systems or on higher (macro) organization levels. Micro-level models enable consideration of individual histories and interactions, but can be unstable and subject to cumulative errors. Macro-level models focus on average population properties, but may hide relevant heterogeneity at the micro-scale. We present a framework that integrates both approaches through the use of temporally structured matrices that can take large numbers of variables into account. Matrices are composed of several bidimensional (time×age) grids, each representing a state (e.g. physiological, immunological, socio-demographic). Time and age are primary indices linking grids. These matrices preserve the entire history of all population strata and enable the use of historical events, parameters and states dynamically in the modeling process. This framework is applicable across fields, but particularly suitable to simulate the impact of alternative immunization policies. We demonstrate the framework by examining alternative strategies to accelerate measles elimination in 15 developing countries. The model recaptured long-endorsed policies in measles control, showing that where a single routine measles-containing vaccine is employed with low coverage, any improvement in coverage is more effective than a second dose. It also identified an opportunity to save thousands of lives in India at attractively low costs through the implementation of supplementary immunization campaigns. The flexibility of the approach presented enables estimating the effectiveness of different immunization policies in highly complex contexts involving multiple and historical influences from different hierarchical levels. PMID:26509976

The Immune Response to Acute Focal Cerebral Ischemia and Associated Post-stroke Immunodepression: A Focused Review

PubMed Central

Famakin, Bolanle M.

2014-01-01

It is currently well established that the immune system is activated in response to transient or focal cerebral ischemia. This acute immune activation occurs in response to damage, and injury, to components of the neurovascular unit and is mediated by the innate and adaptive arms of the immune response. The initial immune activation is rapid, occurs via the innate immune response and leads to inflammation. The inflammatory mediators produced during the innate immune response in turn lead to recruitment of inflammatory cells and the production of more inflammatory mediators that result in activation of the adaptive immune response. Under ideal conditions, this inflammation gives way to tissue repair and attempts at regeneration. However, for reasons that are just being understood, immunosuppression occurs following acute stroke leading to post-stroke immunodepression. This review focuses on the current state of knowledge regarding innate and adaptive immune activation in response to focal cerebral ischemia as well as the immunodepression that can occur following stroke. A better understanding of the intricate and complex events that take place following immune response activation, to acute cerebral ischemia, is imperative for the development of effective novel immunomodulatory therapies for the treatment of acute stroke. PMID:25276490

Experimental verification and molecular basis of active immunization against fungal pathogens in termites.

PubMed

Liu, Long; Li, Ganghua; Sun, Pengdong; Lei, Chaoliang; Huang, Qiuying

2015-10-13

Termites are constantly exposed to many pathogens when they nest and forage in the field, so they employ various immune strategies to defend against pathogenic infections. Here, we demonstrate that the subterranean termite Reticulitermes chinensis employs active immunization to defend against the entomopathogen Metarhizium anisopliae. Our results showed that allogrooming frequency increased significantly between fungus-treated termites and their nestmates. Through active social contact, previously healthy nestmates only received small numbers of conidia from fungus-treated individuals. These nestmates experienced low-level fungal infections, resulting in low mortality and apparently improved antifungal defences. Moreover, infected nestmates promoted the activity of two antioxidant enzymes (SOD and CAT) and upregulated the expression of three immune genes (phenoloxidase, transferrin, and termicin). We found 20 differentially expressed proteins associated with active immunization in R. chinensis through iTRAQ proteomics, including 12 stress response proteins, six immune signalling proteins, and two immune effector molecules. Subsequently, two significantly upregulated (60S ribosomal protein L23 and isocitrate dehydrogenase) and three significantly downregulated (glutathione S-transferase D1, cuticle protein 19, and ubiquitin conjugating enzyme) candidate immune proteins were validated by MRM assays. These findings suggest that active immunization in termites may be regulated by different immune proteins.

Protect Minnesota's Agricultural Land: Components and Activities for Elementary Students.

ERIC Educational Resources Information Center

Noy, Laura

An endeavor to alert elementary teachers and students to the need to protect and conserve one of Minnesota's basic resources, soil, these supplementary instructional activities are designed for easy integration into science, social studies, language arts, mathematics, and art subject and skill areas. Each activity includes a brief description of…

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Immune Checkpoint Blockade for Breast Cancer.

PubMed

Swoboda, April; Nanda, Rita

An effective antitumor immune response requires interaction between cells of the adaptive and innate immune system. Three key elements are required: generation of activated tumor-directed T cells, infiltration of activated T cells into the tumor microenvironment, and killing of tumor cells by activated T cells. Tumor immune evasion can occur as a result of the disruption of each of these three key T cell activities, resulting in three distinct cancer-immune phenotypes. The immune inflamed phenotype, characterized by the presence of a robust tumor immune infiltrate, suggests impaired activated T cell killing of tumor cells related to the presence of inhibitory factors. Programmed death receptor-1 (PD-1) is an inhibitory transmembrane protein expressed on T cells, B cells, and NK cells. The interaction between PD-1 and its ligands (PD-L1/L2) functions as an immune checkpoint against unrestrained cytotoxic T effector cell activity-it promotes peripheral T effector cell exhaustion and conversion of T effector cells to immunosuppressive T regulatory (Treg) cells. Immune checkpoint inhibitors, which block the PD-1/PD-L1 axis and reactivate cytotoxic T effector cell function, are actively being investigated for the treatment of breast cancer.

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Facts About Drug Abuse: Trainer's Manual.

ERIC Educational Resources Information Center

Link, William E.; And Others

Following an introductory survey of the course, this modular drug abuse trainer's manual contains all course-specified materials. These materials are: the course goals and objectives; time/activity sheets; trainer guidelines, process notes, and exercise instructions; detailed lectures and supplementary information. The time/activity sheets contain…

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The caBIG® Life Science Business Architecture Model

PubMed Central

Boyd, Lauren Becnel; Hunicke-Smith, Scott P.; Stafford, Grace A.; Freund, Elaine T.; Ehlman, Michele; Chandran, Uma; Dennis, Robert; Fernandez, Anna T.; Goldstein, Stephen; Steffen, David; Tycko, Benjamin; Klemm, Juli D.

2011-01-01

Motivation: Business Architecture Models (BAMs) describe what a business does, who performs the activities, where and when activities are performed, how activities are accomplished and which data are present. The purpose of a BAM is to provide a common resource for understanding business functions and requirements and to guide software development. The cancer Biomedical Informatics Grid (caBIG®) Life Science BAM (LS BAM) provides a shared understanding of the vocabulary, goals and processes that are common in the business of LS research. Results: LS BAM 1.1 includes 90 goals and 61 people and groups within Use Case and Activity Unified Modeling Language (UML) Diagrams. Here we report on the model's current release, LS BAM 1.1, its utility and usage, and plans for future use and continuing development for future releases. Availability and Implementation: The LS BAM is freely available as UML, PDF and HTML (https://wiki.nci.nih.gov/x/OFNyAQ). Contact: lbboyd@bcm.edu; laurenbboyd@gmail.com Supplementary information: Supplementary data) are avaliable at Bioinformatics online. PMID:21450709

The potential impact of immunization campaign budget re-allocation on global eradication of paediatric infectious diseases

PubMed Central

2011-01-01

Background The potential benefits of coordinating infectious disease eradication programs that use campaigns such as supplementary immunization activities (SIAs) should not be over-looked. One example of a coordinated approach is an adaptive "sequential strategy": first, all annual SIA budget is dedicated to the eradication of a single infectious disease; once that disease is eradicated, the annual SIA budget is re-focussed on eradicating a second disease, etc. Herd immunity suggests that a sequential strategy may eradicate several infectious diseases faster than a non-adaptive "simultaneous strategy" of dividing annual budget equally among eradication programs for those diseases. However, mathematical modeling is required to understand the potential extent of this effect. Methods Our objective was to illustrate how budget allocation strategies can interact with the nonlinear nature of disease transmission to determine time to eradication of several infectious diseases under different budget allocation strategies. Using a mathematical transmission model, we analyzed three hypothetical vaccine-preventable infectious diseases in three different countries. A central decision-maker can distribute funding among SIA programs for these three diseases according to either a sequential strategy or a simultaneous strategy. We explored the time to eradication under these two strategies under a range of scenarios. Results For a certain range of annual budgets, all three diseases can be eradicated relatively quickly under the sequential strategy, whereas eradication never occurs under the simultaneous strategy. However, moderate changes to total SIA budget, SIA frequency, order of eradication, or funding disruptions can create disproportionately large differences in the time and budget required for eradication under the sequential strategy. We find that the predicted time to eradication can be very sensitive to small differences in the rate of case importation between the countries. We also find that the time to eradication of all three diseases is not necessarily lowest when the least transmissible disease is targeted first. Conclusions Relatively modest differences in budget allocation strategies in the near-term can result in surprisingly large long-term differences in time required to eradicate, as a result of the amplifying effects of herd immunity and the nonlinearities of disease transmission. More sophisticated versions of such models may be useful to large international donors or other organizations as a planning or portfolio optimization tool, where choices must be made regarding how much funding to dedicate to different infectious disease eradication efforts. PMID:21955853

The potential impact of immunization campaign budget re-allocation on global eradication of paediatric infectious diseases.

PubMed

Fitzpatrick, Tiffany; Bauch, Chris T

2011-09-28

The potential benefits of coordinating infectious disease eradication programs that use campaigns such as supplementary immunization activities (SIAs) should not be over-looked. One example of a coordinated approach is an adaptive "sequential strategy": first, all annual SIA budget is dedicated to the eradication of a single infectious disease; once that disease is eradicated, the annual SIA budget is re-focussed on eradicating a second disease, etc. Herd immunity suggests that a sequential strategy may eradicate several infectious diseases faster than a non-adaptive "simultaneous strategy" of dividing annual budget equally among eradication programs for those diseases. However, mathematical modeling is required to understand the potential extent of this effect. Our objective was to illustrate how budget allocation strategies can interact with the nonlinear nature of disease transmission to determine time to eradication of several infectious diseases under different budget allocation strategies. Using a mathematical transmission model, we analyzed three hypothetical vaccine-preventable infectious diseases in three different countries. A central decision-maker can distribute funding among SIA programs for these three diseases according to either a sequential strategy or a simultaneous strategy. We explored the time to eradication under these two strategies under a range of scenarios. For a certain range of annual budgets, all three diseases can be eradicated relatively quickly under the sequential strategy, whereas eradication never occurs under the simultaneous strategy. However, moderate changes to total SIA budget, SIA frequency, order of eradication, or funding disruptions can create disproportionately large differences in the time and budget required for eradication under the sequential strategy. We find that the predicted time to eradication can be very sensitive to small differences in the rate of case importation between the countries. We also find that the time to eradication of all three diseases is not necessarily lowest when the least transmissible disease is targeted first. Relatively modest differences in budget allocation strategies in the near-term can result in surprisingly large long-term differences in time required to eradicate, as a result of the amplifying effects of herd immunity and the nonlinearities of disease transmission. More sophisticated versions of such models may be useful to large international donors or other organizations as a planning or portfolio optimization tool, where choices must be made regarding how much funding to dedicate to different infectious disease eradication efforts.

Effects of oxidised dietary fish oil and high-dose vitamin E supplementation on growth performance, feed utilisation and antioxidant defence enzyme activities of juvenile large yellow croaker (Larmichthys crocea).

PubMed

Wang, Jun; Xu, Houguo; Zuo, Rantao; Mai, Kangsen; Xu, Wei; Ai, Qinghui

2016-05-01

This study was conducted to elucidate the effects of oxidised dietary lipids and high-dose vitamin E (VE) on growth performance and immune responses of large yellow croaker. Juvenile fish (initial average body weight of 7·82 (sem 0·68) g) were fed diets containing either fresh fish oil (fresh diet, peroxide value (POV)=1·72 mEq/kg) or fish oil oxidised to varying degrees (oxidised diets, POV=28·29-104·21 mEq/kg), with or without supplementary 600 mg VE/kg diet, for 10 weeks in floating cages. Growth was significantly lower and feed intake (g/100 g body weight per d) was higher in fish fed the oxidised diet. Supplementation with VE increased the growth of fish fed the oxidised diets, but significantly decreased the growth of fish fed the fresh diet. Hepatosomatic index increased with increasing dietary POV and decreased with VE supplementation. Hepatic catalase activity, superoxide dismutase (SOD) activity and malondialdehyde content were significantly higher in fish fed the oxidised diets, and these values decreased significantly following VE supplementation. However, hepatic SOD activity was enhanced by VE supplementation in fish fed the fresh diet. Air-exposure mortality was significantly increased by dietary POV, and this effect was inhibited by VE supplementation. These results suggest that dietary oxidised fish oil could stimulate the activities of antioxidant defence enzymes in stressed large yellow croaker. High-dose VE supplementation can alleviate oxidative stress of large yellow croaker fed oxidised fish oil, but can exert deleterious effects on fish in the absence of oxidative stress.

The Split Virus Influenza Vaccine rapidly activates immune cells through Fcγ receptors.

PubMed

O'Gorman, William E; Huang, Huang; Wei, Yu-Ling; Davis, Kara L; Leipold, Michael D; Bendall, Sean C; Kidd, Brian A; Dekker, Cornelia L; Maecker, Holden T; Chien, Yueh-Hsiu; Davis, Mark M

2014-10-14

Seasonal influenza vaccination is one of the most common medical procedures and yet the extent to which it activates the immune system beyond inducing antibody production is not well understood. In the United States, the most prevalent formulations of the vaccine consist of degraded or "split" viral particles distributed without any adjuvants. Based on previous reports we sought to determine whether the split influenza vaccine activates innate immune receptors-specifically Toll-like receptors. High-dimensional proteomic profiling of human whole-blood using Cytometry by Time-of-Flight (CyTOF) was used to compare signaling pathway activation and cytokine production between the split influenza vaccine and a prototypical TLR response ex vivo. This analysis revealed that the split vaccine rapidly and potently activates multiple immune cell types but yields a proteomic signature quite distinct from TLR activation. Importantly, vaccine induced activity was dependent upon the presence of human sera indicating that a serum factor was necessary for vaccine-dependent immune activation. We found this serum factor to be human antibodies specific for influenza proteins and therefore immediate immune activation by the split vaccine is immune-complex dependent. These studies demonstrate that influenza virus "splitting" inactivates any potential adjuvants endogenous to influenza, such as RNA, but in previously exposed individuals can elicit a potent immune response by facilitating the rapid formation of immune complexes. Copyright © 2014 Elsevier Ltd. All rights reserved.

A 60-year review on the changing epidemiology of measles in capital Beijing, China, 1951-2011

PubMed Central

2013-01-01

Background China pledged to join the global effort to eliminate measles by 2012. To improve measles control strategy, the epidemic trend and population immunity of measles were investigated in 1951–2011 in Beijing. Methods The changing trend of measles since 1951 was described based on measles surveillance data from Beijing Centre of Disease Control and Prevention (CDC). The measles vaccination coverage and antibody level were assessed by routinely reported measles vaccination data and twenty-one sero-epidemiological surveys. Results The incidence of measles has decreased significantly from 593.5/100,000 in 1951 (peaked at 2721.0/100,000 in 1955), to 0.5/100,000 in 2011 due to increasing vaccination coverage of 95%-99%. Incidence rebounded from 6.6/100,000 to 24.5/100,000 since 2005 and decreased after measles vaccine (MV) supplementary immunization activities (SIAs) in 2010. Measles antibody positive rate was 85%-95% in most of years since 1981. High-risk districts were spotted in Chaoyang, Fengtai and Changping districts in recent 15 years. Age-specific incidence and proportion of measles varied over time. The most affected population were younger children of 1–4 years before 1978, older children of 5–14 years in 1978–1996, infant of <1 years and adults of ≥15 years in period of aim to measles elimination. Conclusion Strategies at different stages had a prevailing effect on the epidemic dynamics of measles in recent 60 years in Beijing. It will be essential to validate reported vaccination coverage, improve vaccination coverage in adults and strengthen measles surveillance in the anticipated elimination campaign for measles. PMID:24143899

Description of a large measles epidemic in Democratic Republic of Congo, 2010-2013.

PubMed

Mancini, Silvia; Coldiron, Matthew E; Ronsse, Axelle; Ilunga, Benoît Kebela; Porten, Klaudia; Grais, Rebecca F

2014-01-01

Although measles mortality has declined dramatically in Sub-Saharan Africa, measles remains a major public health problem in countries like the Democratic Republic of Congo (DRC). Here, we describe the large measles epidemic that occurred in the Democratic Republic of Congo between 2010 and 2013 using data from the national surveillance system as well as vaccine coverage surveys to provide a snapshot of the epidemiology of measles in DRC. Standardized national surveillance data were used to describe measles cases from 2010 to 2013. Attack rates and case fatality ratios were calculated and the temporal and spatial evolution of the epidemic described. Data on laboratory confirmation and vaccination coverage surveys as a part of routine program monitoring are also presented. Between week 1 of 2010 and week 45 of 2013, a total of 294,455 cases and 5,045 deaths were reported. The cumulative attack rate (AR) was 0.4%. The Case Fatality Ratio (CFR) was 1.7% among cases reported in health structures through national surveillance. A total of 186,178 cases (63%) were under 5 years old, representing an estimated AR of 1.4% in this age group. Following the first mass vaccination campaigns, weekly reported cases decreased by 21.5%. Results of post-vaccination campaign coverage surveys indicated sub-optimal (under 95%) vaccination coverage among children surveyed. The data reported here highlight the need to seek additional means to reinforce routine immunization as well as ensure the timely implementation of Supplementary Immunization Activities to prevent large and repeated measles epidemics in DRC. Although reactive campaigns were conducted in response to the epidemic, strategies to ensure that children are vaccinated in the routine system remains the foundation of measles control.

Antecedent causes of a measles resurgence in the Democratic Republic of the Congo

PubMed Central

Scobie, Heather Melissa; Ilunga, Benoît Kebela; Mulumba, Audry; Shidi, Calixte; Coulibaly, Tiekoura; Obama, Ricardo; Tamfum, Jean-Jacques Muyembe; Simbu, Elisabeth Pukuta; Smit, Sheilagh Brigitte; Masresha, Balcha; Perry, Robert Tyrrell; Alleman, Mary Margaret; Kretsinger, Katrina; Goodson, James

2015-01-01

Introduction Despite accelerated measles control efforts, a massive measles resurgence occurred in the Democratic Republic of the Congo (DRC) starting in mid-2010, prompting an investigation into likely causes. Methods We conducted a descriptive epidemiological analysis using measles immunization and surveillance data to understand the causes of the measles resurgence and to develop recommendations for elimination efforts in DRC. Results During 2004-2012, performance indicator targets for case-based surveillance and routine measles vaccination were not met. Estimated coverage with the routine first dose of measles-containing vaccine (MCV1) increased from 57% to 73%. Phased supplementary immunization activities (SIAs) were conducted starting in 2002, in some cases with sub-optimal coverage (≤95%). In 2010, SIAs in five of 11 provinces were not implemented as planned, resulting in a prolonged interval between SIAs, and a missed birth cohort in one province. During July 1, 2010-December 30, 2012, high measles attack rates (>100 cases per 100,000 population) occurred in provinces that had estimated MCV1 coverage lower than the national estimate and did not implement planned 2010 SIAs. The majority of confirmed case-patients were aged <10 years (87%) and unvaccinated or with unknown vaccination status (75%). Surveillance detected two genotype B3 and one genotype B2 measles virus strains that were previously identified in the region. Conclusion The resurgence was likely caused by an accumulation of unvaccinated, measles-susceptible children due to low MCV1 coverage and suboptimal SIA implementation. To achieve the regional goal of measles elimination by 2020, efforts are needed in DRC to improve case-based surveillance and increase two-dose measles vaccination coverage through routine services and SIAs. PMID:26401224

World Witnesses a Tumultuous Year while India Reports an Eventful Decade in the Long Story of Polio Eradication.

PubMed

Chaturvedi, Sanjay

2014-04-01

With recent outbreaks in Syria and Horn of Africa, silent circulation of wild poliovirus type 1 (WPV1) in Israel, West Bank, and Gaza, and fresh spate of violence against vaccinators and their security personnel in Pakistan, the world is facing a turbulent final ascent to the summit of polio eradication. On the positive side, we may also be witnessing the end of wild poliovirus type 3 (WPV3) and defused programmatic crisis caused by funding gaps, while India registers third consecutive polio-free year. Having a cogent endgame plan 2013-2018, informed by some cardinal lessons learned from an eventful decade in India, is also a very significant development. Now, there is a parallel pursuit against WPV and vaccine-derived poliovirus (VDPV). Endgame would also involve integration of at least one dose of affordable inactivated polio vaccine (IPV) to up-scaled routine immunization (RI), switch from trivalent oral polio vaccine (tOPV) to bivalent oral polio vaccine (bOPV) in 144 countries before 2018, stockpiling of mOPV, and simultaneous global cessation of bOPV before 2020. Role of antivirals in post-eradication era is still unclear. Some specific threats emerging at this stage are as follows: Global buildup of new birth cohorts in non-endemic countries with weak RI and downscaled supplementary immunization activities (SIAs), tremendous pressure on peripheral health workers, and fatigued systems. Cultural resistance to transnational programs is taking a violent shape in some areas. Differential interpretations of 'right to say no', on both sides of the divide, are damaging a global cause. Amidst all these concerns, let us not forget to underline the sacrifice made by frontline vaccinators working in some of the most challenging circumstances.

Progress toward polio eradication--Somalia, 1998-2013.

PubMed

Mbaeyi, Chukwuma; Kamadjeu, Raoul; Mahamud, Abdirahman; Webeck, Jenna; Ehrhardt, Derek; Mulugeta, Abraham

2014-11-01

Since the 1988 resolution of the World Health Assembly to eradicate polio, significant progress has been made toward achieving this goal, with the result that only Afghanistan, Nigeria, and Pakistan have never successfully interrupted endemic transmission of wild poliovirus. However, one of the greatest challenges of the Global Polio Eradication Initiative has been that of maintaining the polio-free status of countries in unstable regions with weak healthcare infrastructure, a challenge exemplified by Somalia, a country in the Horn of Africa region. Somalia interrupted indigenous transmission of wild poliovirus in 2002, 4 years after the country established its national polio eradication program. But political instability and protracted armed conflict, with significant disruption of the healthcare system, have left Somalia vulnerable to 2 imported outbreaks of wild poliovirus. The first occurred during 2005-2007, resulting in >200 cases of paralytic polio, whereas the second, which began in 2013, is currently ongoing. Despite immense challenges, the country has a sensitive surveillance system that has facilitated prompt detection of outbreaks, but its weak routine immunization system means that supplementary immunization activities constitute the primary strategy for reaching children with polio vaccines. Conducting vaccination campaigns in a setting of conflict has been at times hazardous, but the country's polio program has demonstrated resilience in overcoming many obstacles to ensure that children receive lifesaving polio vaccines. Regaining and maintaining Somalia's polio-free status will depend on finding innovative and lasting solutions to the challenge of administering vaccines in a setting of ongoing conflict and instability. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Antimicrobial potency of cationic antimicrobial peptides can be predicted from their amino acid composition: Application to the detection of "cryptic" antimicrobial peptides.

PubMed

Pane, Katia; Durante, Lorenzo; Crescenzi, Orlando; Cafaro, Valeria; Pizzo, Elio; Varcamonti, Mario; Zanfardino, Anna; Izzo, Viviana; Di Donato, Alberto; Notomista, Eugenio

2017-04-21

Cationic antimicrobial peptides (CAMPs) are essential components of innate immunity. Here we show that antimicrobial potency of CAMPs is linearly correlated to the product C m H n L where C is the net charge of the peptide, H is a measure of its hydrophobicity and L its length. Exponents m and n define the relative contribution of charge and hydrophobicity to the antimicrobial potency. Very interestingly the values of m and n are strain specific. The ratio n/(m+n) can vary between ca. 0.5 and 1, thus indicating that some strains are sensitive to highly charged peptides, whereas others are particularly susceptible to more hydrophobic peptides. The slope of the regression line describing the correlation "antimicrobial potency"/"C m H n L product" changes from strain to strain indicating that some strains acquired a higher resistance to CAMPs than others. Our analysis provides also an effective computational strategy to identify CAMPs included inside the structure of larger proteins or precursors, which can be defined as "cryptic" CAMPs. We demonstrate that it is not only possible to identify and locate with very good precision the position of cryptic peptides, but also to analyze the internal structure of long CAMPs, thus allowing to draw an accurate map of the molecular determinants of their antimicrobial activity. A spreadsheet, provided in the Supplementary material, allows performing the analysis of protein sequences. Our strategy is also well suited to analyze large pools of sequences, thus significantly improving the identification of new CAMPs and the study of innate immunity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Progress Toward Measles Elimination - Bangladesh, 2000-2016.

PubMed

Khanal, Sudhir; Bohara, Rajendra; Chacko, Stephen; Sharifuzzaman, Mohammad; Shamsuzzaman, Mohammad; Goodson, James L; Dabbagh, Alya; Kretsinger, Katrina; Dhongde, Deepak; Liyanage, Jayantha; Bahl, Sunil; Thapa, Arun

2017-07-21

In 2013, at the 66th session of the Regional Committee of the World Health Organization (WHO) South-East Asia Region (SEAR), a regional goal was established to eliminate measles and control rubella and congenital rubella syndrome* by 2020 (1). WHO-recommended measles elimination strategies in SEAR countries include 1) achieving and maintaining ≥95% coverage with 2 doses of measles-containing vaccine (MCV) in every district, delivered through the routine immunization program or through supplementary immunization activities (SIAs) † ; 2) developing and sustaining a sensitive and timely measles case-based surveillance system that meets targets for recommended performance indicators; and 3) developing and maintaining an accredited measles laboratory network (2). In 2014, Bangladesh, one of 11 countries in SEAR, adopted a national goal for measles elimination by 2018 (2,3). This report describes progress and challenges toward measles elimination in Bangladesh during 2000-2016. Estimated coverage with the first MCV dose (MCV1) increased from 74% in 2000 to 94% in 2016. The second MCV dose (MCV2) was introduced in 2012, and MCV2 coverage increased from 35% in 2013 to 93% in 2016. During 2000-2016, approximately 108.9 million children received MCV during three nationwide SIAs conducted in phases. During 2000-2016, reported confirmed measles incidence decreased 82%, from 34.2 to 6.1 per million population. However, in 2016, 56% of districts did not meet the surveillance performance target of ≥2 discarded nonmeasles, nonrubella cases § per 100,000 population. Additional measures that include increasing MCV1 and MCV2 coverage to ≥95% in all districts with additional strategies for hard-to-reach populations, increasing sensitivity of measles case-based surveillance, and ensuring timely transport of specimens to the national laboratory will help achieve measles elimination.

Antecedent causes of a measles resurgence in the Democratic Republic of the Congo.

PubMed

Scobie, Heather Melissa; Ilunga, Benoît Kebela; Mulumba, Audry; Shidi, Calixte; Coulibaly, Tiekoura; Obama, Ricardo; Tamfum, Jean-Jacques Muyembe; Simbu, Elisabeth Pukuta; Smit, Sheilagh Brigitte; Masresha, Balcha; Perry, Robert Tyrrell; Alleman, Mary Margaret; Kretsinger, Katrina; Goodson, James

2015-01-01

Despite accelerated measles control efforts, a massive measles resurgence occurred in the Democratic Republic of the Congo (DRC) starting in mid-2010, prompting an investigation into likely causes. We conducted a descriptive epidemiological analysis using measles immunization and surveillance data to understand the causes of the measles resurgence and to develop recommendations for elimination efforts in DRC. During 2004-2012, performance indicator targets for case-based surveillance and routine measles vaccination were not met. Estimated coverage with the routine first dose of measles-containing vaccine (MCV1) increased from 57% to 73%. Phased supplementary immunization activities (SIAs) were conducted starting in 2002, in some cases with sub-optimal coverage (≤95%). In 2010, SIAs in five of 11 provinces were not implemented as planned, resulting in a prolonged interval between SIAs, and a missed birth cohort in one province. During July 1, 2010-December 30, 2012, high measles attack rates (>100 cases per 100,000 population) occurred in provinces that had estimated MCV1 coverage lower than the national estimate and did not implement planned 2010 SIAs. The majority of confirmed case-patients were aged <10 years (87%) and unvaccinated or with unknown vaccination status (75%). Surveillance detected two genotype B3 and one genotype B2 measles virus strains that were previously identified in the region. The resurgence was likely caused by an accumulation of unvaccinated, measles-susceptible children due to low MCV1 coverage and suboptimal SIA implementation. To achieve the regional goal of measles elimination by 2020, efforts are needed in DRC to improve case-based surveillance and increase two-dose measles vaccination coverage through routine services and SIAs.

Convergent and Divergent Signaling in PAMP-Triggered Immunity and Effector-Triggered Immunity.

PubMed

Peng, Yujun; van Wersch, Rowan; Zhang, Yuelin

2018-04-01

Plants use diverse immune receptors to sense pathogen attacks. Recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors localized on the plasma membrane leads to PAMP-triggered immunity (PTI). Detection of pathogen effectors by intracellular or plasma membrane-localized immune receptors results in effector-triggered immunity (ETI). Despite the large variations in the magnitude and duration of immune responses triggered by different PAMPs or pathogen effectors during PTI and ETI, plasma membrane-localized immune receptors activate similar downstream molecular events such as mitogen-activated protein kinase activation, oxidative burst, ion influx, and increased biosynthesis of plant defense hormones, indicating that defense signals initiated at the plasma membrane converge at later points. On the other hand, activation of ETI by immune receptors localized to the nucleus appears to be more directly associated with transcriptional regulation of defense gene expression. Here, we review recent progress in signal transductions downstream of different groups of plant immune receptors, highlighting the converging and diverging molecular events.

U.S. Immunization program adult immunization activities and resources.

PubMed

Woods, LaDora O; Bridges, Carolyn B; Graitcer, Samuel B; Lamont, Brock

2016-04-02

Adults are recommended to receive vaccines based on their age, medical conditions, prior vaccinations, occupation and lifestyle. However, adult immunization coverage is low in the United States and lags substantially below Healthy People 2020 goals. To assess activities and resources designated for adult immunization programs by state and local health department immunization programs in the United States, we analyzed 2012 and 2013 data from the Centers for Disease Control and Prevention's (CDC) Program Annual Reports and Progress Assessments (PAPA) survey of CDC-funded immunization programs. Fifty-six of 64 funded US immunization programs' responses were included in the analysis. Eighty-two percent of (n = 46) programs reported having a designated adult immunization coordinator in 2012 and 73% (n = 41) in 2013. Of the 46 coordinators reported in 2012, 30% (n = 14) spent more than 50% of their time on adult immunization activities, and only 24% (n = 10) of the 41 adult coordinators in 2013 spent more than 50% of their time on adult immunization activities. In 2012, 23% (n = 13) of the 56 programs had a separate immunization coalition for adults and 68% (n = 38) included adult issues in their overall immunization program coalition. In 2013, 25% (n = 14) had a separate adult immunization coalition while 57% (n = 32) incorporated adult immunizations into their overall immunization program coalition. The results indicate substantial variation across the US in public health infrastructure to support adult immunizations. Continued assessment of adult immunization resources and activities will be important in improving adult immunization coverage levels though program support. With many programs having limited resources dedicated to improving adult immunization rates in the in US, efforts by the health departments to collaborate with providers and other partners in their jurisdictions to increase awareness, increase the use of proven strategies to improve vaccination of adults, and implement the Standards for Adult Immunization Practice may lead to improved adult immunization coverage and fewer illnesses, hospitalizations and deaths from vaccine preventable diseases.

U.S. Immunization program adult immunization activities and resources

PubMed Central

Woods, LaDora O.; Bridges, Carolyn B.; Graitcer, Samuel B.; Lamont, Brock

2016-01-01

ABSTRACT Adults are recommended to receive vaccines based on their age, medical conditions, prior vaccinations, occupation and lifestyle. However, adult immunization coverage is low in the United States and lags substantially below Healthy People 2020 goals. To assess activities and resources designated for adult immunization programs by state and local health department immunization programs in the United States, we analyzed 2012 and 2013 data from the Centers for Disease Control and Prevention's (CDC) Program Annual Reports and Progress Assessments (PAPA) survey of CDC-funded immunization programs. Fifty-six of 64 funded US immunization programs' responses were included in the analysis. Eighty-two percent of (n = 46) programs reported having a designated adult immunization coordinator in 2012 and 73% (n = 41) in 2013. Of the 46 coordinators reported in 2012, 30% (n = 14) spent more than 50% of their time on adult immunization activities, and only 24% (n = 10) of the 41 adult coordinators in 2013 spent more than 50% of their time on adult immunization activities. In 2012, 23% (n = 13) of the 56 programs had a separate immunization coalition for adults and 68% (n = 38) included adult issues in their overall immunization program coalition. In 2013, 25% (n = 14) had a separate adult immunization coalition while 57% (n = 32) incorporated adult immunizations into their overall immunization program coalition. The results indicate substantial variation across the US in public health infrastructure to support adult immunizations. Continued assessment of adult immunization resources and activities will be important in improving adult immunization coverage levels though program support. With many programs having limited resources dedicated to improving adult immunization rates in the in US, efforts by the health departments to collaborate with providers and other partners in their jurisdictions to increase awareness, increase the use of proven strategies to improve vaccination of adults, and implement the Standards for Adult Immunization Practice may lead to improved adult immunization coverage and fewer illnesses, hospitalizations and deaths from vaccine preventable diseases. PMID:26577532

77 FR 12871 - Agency Information Collection Activities: Comment Request

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Modelling the Immune Response to Cancer: An Individual-Based Approach Accounting for the Difference in Movement Between Inactive and Activated T Cells.

PubMed

Macfarlane, Fiona R; Lorenzi, Tommaso; Chaplain, Mark A J

2018-06-01

A growing body of experimental evidence indicates that immune cells move in an unrestricted search pattern if they are in the pre-activated state, whilst they tend to stay within a more restricted area upon activation induced by the presence of tumour antigens. This change in movement is not often considered in the existing mathematical models of the interactions between immune cells and cancer cells. With the aim to fill such a gap in the existing literature, in this work we present a spatially structured individual-based model of tumour-immune competition that takes explicitly into account the difference in movement between inactive and activated immune cells. In our model, a Lévy walk is used to capture the movement of inactive immune cells, whereas Brownian motion is used to describe the movement of antigen-activated immune cells. The effects of activation of immune cells, the proliferation of cancer cells and the immune destruction of cancer cells are also modelled. We illustrate the ability of our model to reproduce qualitatively the spatial trajectories of immune cells observed in experimental data of single-cell tracking. Computational simulations of our model further clarify the conditions for the onset of a successful immune action against cancer cells and may suggest possible targets to improve the efficacy of cancer immunotherapy. Overall, our theoretical work highlights the importance of taking into account spatial interactions when modelling the immune response to cancer cells.

Immune activation and paediatric HIV-1 disease outcome.

PubMed

Roider, Julia M; Muenchhoff, Maximilian; Goulder, Philip J R

2016-03-01

The paediatric HIV epidemic is changing. Over the past decade, new infections have substantially reduced, whereas access to antiretroviral therapy (ART) has increased. Overall this success means that numbers of children living with HIV are climbing. In addition, the problems observed in adult infection resulting from chronic inflammation triggered by persistent immune activation even following ART mediated suppression of viral replication are magnified in children infected from birth. Features of immune ontogeny favour low immune activation in early life, whereas specific aspects of paediatric HIV infection tend to increase it. A subset of ART-naïve nonprogressing children exists in whom normal CD4 cell counts are maintained in the setting of persistent high viremia and yet in the context of low immune activation. This sooty mangabey-like phenotype contrasts with nonprogressing adult infection which is characterized by the expression of protective HLA class I molecules and low viral load. The particular factors contributing to raised or lowered immune activation in paediatric infection, which ultimately influence disease outcome, are discussed. Novel strategies to circumvent the unwanted long-term consequences of HIV infection may be possible in children in whom natural immune ontogeny in early life militates against immune activation. Defining the mechanisms underlying low immune activation in natural HIV infection would have applications beyond paediatric HIV.

A River Runs through It: Austin Youth River Watch Final Report 1993-94.

ERIC Educational Resources Information Center

Turner, Jeannine

The City of Austin (Texas) provided funds for a supplementary educational activity to involve at-risk minority high school students in water quality issues. The program attempts to provide an interesting and authentic activity that also develops academic skills. Principal activities were testing river water for pollutants and the tutoring of…

Problem-Centered Supplemental Instruction in Biology: Influence on Content Recall, Content Understanding, and Problem Solving Ability

ERIC Educational Resources Information Center

Gardner, Joel; Belland, Brian R.

2017-01-01

To address the need for effective, efficient ways to apply active learning in undergraduate biology courses, in this paper, we propose a problem-centered approach that utilizes supplemental web-based instructional materials based on principles of active learning. We compared two supplementary web-based modules using active learning strategies: the…

Supplementary Activities for Enriching the Teaching of Earth Science: Astronomy, Geology, Meteorology, Oceanography.

ERIC Educational Resources Information Center

Exline, Joseph D., Ed.

This publication is intended to be an aid for secondary school science teachers in providing some additional student-oriented activities to enrich the earth science program. These activities have been classroom tested by teachers and have been considered by these teachers to be educationally successful. This publication is a product of the Earth…

76 FR 67249 - Reports, Forms and Recordkeeping Requirements; Agency Information Collection Activity Under OMB...

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2011-10-31

.... SUPPLEMENTARY INFORMATION: Maritime Administration (MARAD). Title: Shipbuilding Orderbook and Shipyard.... Abstract: MARAD collects this information from the shipbuilding and ship repair industry primarily to...

Altered cortico-basal ganglia motor pathways reflect reduced volitional motor activity in schizophrenia.

PubMed

Bracht, Tobias; Schnell, Susanne; Federspiel, Andrea; Razavi, Nadja; Horn, Helge; Strik, Werner; Wiest, Roland; Dierks, Thomas; Müller, Thomas J; Walther, Sebastian

2013-02-01

Little is known about the neurobiology of hypokinesia in schizophrenia. Therefore, the aim of this study was to investigate alterations of white matter motor pathways in schizophrenia and to relate our findings to objectively measured motor activity. We examined 21 schizophrenia patients and 21 healthy controls using diffusion tensor imaging and actigraphy. We applied a probabilistic fibre tracking approach to investigate pathways connecting the dorsolateral prefrontal cortex (dlPFC), the rostral anterior cingulate cortex (rACC), the pre-supplementary motor area (pre-SMA), the supplementary motor area proper (SMA-proper), the primary motor cortex (M1), the caudate nucleus, the striatum, the pallidum and the thalamus. Schizophrenia patients had lower activity levels than controls. In schizophrenia we found higher probability indices forming part of a bundle of interest (PIBI) in pathways connecting rACC, pre-SMA and SMA-proper as well as in pathways connecting M1 and pre-SMA with caudate nucleus, putamen, pallidum and thalamus and a reduced spatial extension of motor pathways in schizophrenia. There was a positive correlation between PIBI and activity level in the right pre-SMA-pallidum and the left M1-thalamus connection in healthy controls, and in the left pre-SMA-SMA-proper pathway in schizophrenia. Our results point to reduced volitional motor activity and altered motor pathway organisation in schizophrenia. The identified associations between the amount of movement and structural connectivity of motor pathways suggest dysfunction of cortico-basal ganglia pathways in the pathophysiology of hypokinesia in schizophrenia. Schizophrenia patients may use cortical pathways involving the supplementary motor area to compensate for basal ganglia dysfunction. Copyright © 2012 Elsevier B.V. All rights reserved.

Immunizations: Active vs. Passive

MedlinePlus

... Listen Español Text Size Email Print Share Immunizations: Active vs. Passive Page Content Article Body Pediatricians can protect your child by administering not only active immunizations , but sometimes they can use what physicians ...

Prebiotics as immunostimulants in aquaculture: a review.

PubMed

Song, Seong Kyu; Beck, Bo Ram; Kim, Daniel; Park, John; Kim, Jungjoon; Kim, Hyun Duk; Ringø, Einar

2014-09-01

Prebiotics are indigestible fibers that increase beneficial gut commensal bacteria resulting in improvements of the host's health. The beneficial effects of prebiotics are due to the byproducts generated from their fermentation by gut commensal bacteria. In this review, the direct effects of prebiotics on the innate immune system of fish are discussed. Prebiotics, such as fructooligosaccharide, mannanoligosaccharide, inulin, or β-glucan, are called immunosaccharides. They directly enhance innate immune responses including: phagocytic activation, neutrophil activation, activation of the alternative complement system, increased lysozyme activity, and more. Immunosaccharides directly activate the innate immune system by interacting with pattern recognition receptors (PRR) expressed on innate immune cells. They can also associate with microbe associated molecular patterns (MAMPs) to activate innate immune cells. However, the underlying mechanisms involved in innate immune cell activation need to be further explored. Many studies have indicated that immunosaccharides are beneficial to both finfish and shellfish. Copyright © 2014 Elsevier Ltd. All rights reserved.

Immune activity elevates energy expenditure of house sparrows: a link between direct and indirect costs?

PubMed Central

Martin, Lynn B; Scheuerlein, Alex; Wikelski, Martin

2003-01-01

The activation of an immune response is beneficial for organisms but may also have costs that affect fitness. Documented immune costs include those associated with acquisition of special nutrients, as well as immunopathology or autoimmunity. Here, we test whether an experimental induction of the immune system with a non-pathological stimulant can elevate energy turnover in passerine birds. We injected phytohaemagglutinin (PHA), a commonly used mitogen that activates the cell-mediated immune response, into the wing web of house sparrows, Passer domesticus. We then examined energetic costs resulting from this immune activity and related those costs to other physiological activities. We found that PHA injection significantly elevated resting metabolic rate (RMR) of challenged sparrows relative to saline controls. We calculated the total cost of this immune activity to be ca. 4.20 kJ per day (29% RMR), which is equivalent to the cost of production of half of an egg (8.23 kJ egg(-1)) in this species. We suggest that immune activity in wild passerines increases energy expenditure, which in turn may influence important life-history characteristics such as clutch size, timing of breeding or the scheduling of moult. PMID:12590753

Covert representation of second-next movement in the pre-supplementary motor area of monkeys.

PubMed

Nakajima, Toshi; Hosaka, Ryosuke; Mushiake, Hajime; Tanji, Jun

2009-04-01

We attempted to analyze the nature of premovement activity of neurons in medial motor areas [supplementary motor area (SMA) and pre-SMA] from a perspective of coding multiple movements. Monkeys were trained to perform a series of two movements with an intervening delay: supination or pronation with either forearm. Movements were initially instructed with visual signals but had to be remembered thereafter. Although a well-known type of premovement activity representing the forthcoming movements was found in the two areas, we found an unexpected type of activity that represented a second-next movement before initiating the first of the two movements. Typically in the pre-SMA, such activity selective for the second-next movement peaked before the initiation of the first movement, decayed thereafter, and remained low in magnitude while initiating the second movement. This type of activity may tentatively hold information for the second movement while initiating the first. That information may be fed into another group of neurons that themselves build a preparatory activity required to plan the second movements. Alternatively, the activity could serve as a signal to inhibit a premature exertion of the motor command for the second movement.

75 FR 68038 - Agency Information Collection (Veterans Mortgage Life Insurance Statement) Activity Under OMB Review

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... Mortgage Life Insurance Statement) Activity Under OMB Review AGENCY: Veterans Benefits Administration... . Please refer to ``OMB Control No. 2900- 0212.'' SUPPLEMENTARY INFORMATION: Title: Veterans Mortgage Life... currently approved collection. Abstract: Veterans complete VA Form 29-8636 to decline Veterans Mortgage Life...

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2010-01-28

... Information Collection Activities: Request for Comments for New Information Collection AGENCY: Federal Highway... information collection, which is summarized below under SUPPLEMENTARY INFORMATION. We published a Federal Register Notice with a 60-day public comment period on this information collection on November 5, 2009. We...

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SWAHILI, ADDITIONAL DIALOGUES TO FOLLOW "SWAHILI, AN ACTIVE INTRODUCTION, GENERAL CONVERSATION."

ERIC Educational Resources Information Center

INDAKWA, JOHN; AND OTHERS

THESE SUPPLEMENTARY DIALOGUES WERE DESIGNED TO FOLLOW THE FOREIGN SERVICE INSTITUTE TEXT "AN ACTIVE INTRODUCTION TO SWAHILI, GENERAL CONVERSATION". BASED ON THE TOPICS PRESENTED IN THE TEXT, THE DIALOGUES APPEAR IN PHONEMIC TRANSCRIPTION OF SWAHILI IN THE LEFT-HAND COLUMN, WITH ENGLISH TRANSLATION ON THE RIGHT. (AM)

Approach for Estimating Exposures and Incremental Health Effects from Lead During Renovation, Repair, and Painting Activities in Public and Commercial Buildings

EPA Science Inventory

Approach for Estimating Exposures and Incremental Health Effects from Lead During Renovation, Repair, and Painting Activities in Public and Commercial Buildings” (Technical Approach Document). Also available for public review and comment are two supplementary documents: the detai...

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Getting Oil out of Kazakhstan

ERIC Educational Resources Information Center

Gersmehl, Phil

2018-01-01

This activity is part of a larger set of activities and presentations developed by the Michigan Geographic Alliance to help teachers meet the proposed Social Studies standards in 6th and 7th grade. The Michigan Geographic Alliance website also has explanatory presentations, supplementary maps, and readings. In this 20-40 minute intermediate…

78 FR 35353 - Agency Information Collection Activities: Request for Comments for a New Information Collection

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78 FR 52235 - Proposed Collection; Comment Request for Form 8825

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... Form 8825, Rental Real Estate Income and Expenses of a Partnership or an S Corporation. DATES: [email protected] . SUPPLEMENTARY INFORMATION: Title: Rental Real Estate Income and Expenses of a... rental real estate activities, including net income or loss from rental real estate activities that flow...

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ACTIVE IMMUNIZATION AGAINST POLIOMYELITIS IN MONKEYS.

PubMed

Brodie, M; Goldbloom, A

1931-05-31

1. A combination of poliomyelitis virus and specific human serum is effective for the production of active immunity. 2. For each gram of active virus given intradermally as an emulsion, 6 cc. of human immune serum, injected subcutaneously, was required in our experiments to protect a monkey from paralysis. Some degree of active immunity was induced. 3. Immunity, without symptom of the disease, was secured when the serum was given at the time of inoculation, or within 3 days preceding or following inoculation of the virus. 4. For the production of immunity, virus, preceded by serum administration, is probably less effective than when it is given simultaneously with, or before, the injection of serum. 5. The virus neutralization test is more sensitive than the direct intracerebral test for determining the production of immunity.

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The magmatic evolution and genesis of the Quaternary basanite-trachyphonolite suite of Itasy (Madagascar) as inferred by geochemistry, Sr-Nd-Pb isotopes and trace element distribution in coexisting phases

NASA Astrophysics Data System (ADS)

Melluso, L.; Tucker, R. D.; Cucciniello, C.; le Roex, A. P.; Morra, V.; Zanetti, A.; Rakotoson, R. L.

2018-06-01

The Itasy is a Pleistocene-Holocene volcanic field in central Madagascar, located to the west of the Ankaratra volcanic complex. It comprises scoria cones and lava domes (>120), with associated pyroclastic fall and mafic lava flows, covering an area of ab. 400 km2. The last volcanic episodes probably dated ca. 6000-7100 y BP; warm springs and geysers are active. The juvenile samples comprise a peculiar, almost bimodal, rock suite ranging from potassic leucite-kaersutite-bearing basanites, tephrites and phonotephrites, to benmoreites and titanite-haüyne-bearing trachyphonolites (MgO from 9-10 wt% to 0.1 wt%). These rocks show continuous and overlapping variations in the bulk-rock and phase composition (olivine, clinopyroxene, amphibole, feldspar, leucite, haüyne, nepheline, oxides, apatite, titanite, glass and other accessories). The basanites have homogeneous isotopic composition (87Sr/86Sr = 0.70366-0.70378, 143Nd/144Nd = 0.51274-0.51277, 206Pb/204Pb = 18.7-18.9, 207Pb/204Pb = 15.53-15.56; 208Pb/204Pb = 38.89-39.01), and a marked enrichment in the most incompatible elements (LILE and HFSE reach 100-215 times primitive mantle). These features are consistent with low degrees of partial melting of a volatile-, LILE- and HFSE-rich, amphibole-bearing peridotitic mantle induced by uplift during an E-W-directed extensional regime, as is found in central Madagascar. The marked changes in the geochemical composition, and small variations of the Sr-Nd-Pb isotopes in the trachyphonolites (87Sr/86Sr = 0.70425-0.70446, 143Nd/144Nd = 0.51266-0.51269, 206Pb/204Pb = 18.18-18.39, 207Pb/204Pb = 15.49-15.51; 208Pb/204Pb = 38.38-39.57) with respect to basanites and tephrites point to a limited amount of crustal contamination by the relatively low-206Pb/204Pb, low-143Nd/144Nd, high-87Sr/86Sr Precambrian basement rocks (of Middle Archean to Late Proterozoic age), and highlight the geochemical effects of titanite and anorthoclase removal on the trace element fractionation trends, a feature also shown in the trace element composition of the phenocrysts in trachyphonolites. Supplementary Table S2: synopsis of the mineral assemblages of the main lithotypes of the Itasy complex. Supplementary Table S3: composition of olivine of the Itasy rocks. Supplementary Table S4: composition of oxides of the Itasy rocks. Supplementary Table S5: composition of pyroxene of the Itasy rocks. Supplementary Table S6: composition of amphibole, biotite and rhönite of the Itasy rocks. Supplementary Table S7: composition of feldspar and glass of the Itasy rocks. Supplementary Table S8: composition of feldspathoids of the Itasy rocks. Supplementary Table S9: composition of titanite, apatite, other accessories of the Itasy rocks. Supplementary Table S10: Recapitulation of mass balance calculations between rocks of different degree of magmatic evolution, and detailed results. The composition of the phases is reported in the supplementary tables. Supplementary Table S11: average REE mineral/bulk rock ratios for titanite, amphibole and clinopyroxene. The partition coefficients of titanite, clinopyroxene, apatite and amphibole are taken from Olin and Wolff (2012), Fedele et al. (2009, 2015) and Tiepolo et al. (2007). Note that amphibole of RT-06I-355 could not be considered in equilibrium with the host rock (cf. Supplementary Figs. S1a, S1b, S1c).

Associations between transcriptional changes and protein phenotypes provide insights into immune regulation in corals.

PubMed

Fuess, Lauren E; Pinzόn C, Jorge H; Weil, Ernesto; Mydlarz, Laura D

2016-09-01

Disease outbreaks in marine ecosystems have driven worldwide declines of numerous taxa, including corals. Some corals, such as Orbicella faveolata, are particularly susceptible to disease. To explore the mechanisms contributing to susceptibility, colonies of O. faveolata were exposed to immune challenge with lipopolysaccharides. RNA sequencing and protein activity assays were used to characterize the response of corals to immune challenge. Differential expression analyses identified 17 immune-related transcripts that varied in expression post-immune challenge. Network analyses revealed several groups of transcripts correlated to immune protein activity. Several transcripts, which were annotated as positive regulators of immunity were included in these groups, and some were downregulated following immune challenge. Correlations between expression of these transcripts and protein activity results further supported the role of these transcripts in positive regulation of immunity. The observed pattern of gene expression and protein activity may elucidate the processes contributing to the disease susceptibility of species like O. faveolata. Copyright © 2016 Elsevier Ltd. All rights reserved.

Modulation of Immune Function by Polyphenols: Possible Contribution of Epigenetic Factors

PubMed Central

Cuevas, Alejandro; Saavedra, Nicolás; Salazar, Luis A.; Abdalla, Dulcineia S. P.

2013-01-01

Several biological activities have been described for polyphenolic compounds, including a modulator effect on the immune system. The effects of these biologically active compounds on the immune system are associated to processes as differentiation and activation of immune cells. Among the mechanisms associated to immune regulation are epigenetic modifications as DNA methylation of regulatory sequences, histone modifications and posttranscriptional repression by microRNAs that influences the gene expression of key players involved in the immune response. Considering that polyphenols are able to regulate the immune function and has been also demonstrated an effect on epigenetic mechanisms, it is possible to hypothesize that there exists a mediator role of epigenetic mechanisms in the modulation of the immune response by polyphenols. PMID:23812304

Toll immune signal activates cellular immune response via eicosanoids.

PubMed

Shafeeq, Tahir; Ahmed, Shabbir; Kim, Yonggyun

2018-07-01

Upon immune challenge, insects recognize nonself. The recognition signal will propagate to nearby immune effectors. It is well-known that Toll signal pathway induces antimicrobial peptide (AMP) gene expression. Eicosanoids play crucial roles in mediating the recognition signal to immune effectors by enhancing humoral immune response through activation of AMP synthesis as well as cellular immune responses, suggesting a functional cross-talk between Toll and eicosanoid signals. This study tested a cross-talk between these two signals. Two signal transducing factors (MyD88 and Pelle) of Toll immune pathway were identified in Spodoptera exigua. RNA interference (RNAi) of either SeMyD88 or SePelle expression interfered with the expression of AMP genes under Toll signal pathway. Bacterial challenge induced PLA 2 enzyme activity. However, RNAi of these two immune factors significantly suppressed the induction of PLA 2 enzyme activity. Furthermore, RNAi treatment prevented gene expression of cellular PLA 2 . Inhibition of PLA 2 activity reduced phenoloxidase activity and subsequent suppression in cellular immune response measured by hemocyte nodule formation. However, immunosuppression induced by RNAi of Toll signal molecules was significantly reversed by addition of arachidonic acid (AA), a catalytic product of PLA 2 . The addition also significantly reduced the enhanced fungal susceptibility of S. exigua treated by RNAi against two Toll signal molecules. These results indicate that there is a cross-talk between Toll and eicosanoid signals in insect immunity. Copyright © 2018 Elsevier Ltd. All rights reserved.

Public School District Immunity Status in the United States.

ERIC Educational Resources Information Center

Kemper Insurance Group, Chicago, IL.

This paper compiles results of a State-by-State survey of public school district immunity. The survey sought to discover if (1) school districts in each State have governmental immunity for liability, (2) this immunity applies only to governmental activities or to proprietary activities also, (3) board members and employees have immunity, (4) the…

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Motor system hyperconnectivity in juvenile myoclonic epilepsy: a cognitive functional magnetic resonance imaging study.

PubMed

Vollmar, Christian; O'Muircheartaigh, Jonathan; Barker, Gareth J; Symms, Mark R; Thompson, Pamela; Kumari, Veena; Duncan, John S; Janz, Dieter; Richardson, Mark P; Koepp, Matthias J

2011-06-01

Juvenile myoclonic epilepsy is the most frequent idiopathic generalized epilepsy syndrome. It is characterized by predominant myoclonic jerks of upper limbs, often provoked by cognitive activities, and typically responsive to treatment with sodium valproate. Neurophysiological, neuropsychological and imaging studies in juvenile myoclonic epilepsy have consistently pointed towards subtle abnormalities in the medial frontal lobes. Using functional magnetic resonance imaging with an executive frontal lobe paradigm, we investigated cortical activation patterns and interaction between cortical regions in 30 patients with juvenile myoclonic epilepsy and 26 healthy controls. With increasing cognitive demand, patients showed increasing coactivation of the primary motor cortex and supplementary motor area. This effect was stronger in patients still suffering from seizures, and was not seen in healthy controls. Patients with juvenile myoclonic epilepsy showed increased functional connectivity between the motor system and frontoparietal cognitive networks. Furthermore, we found impaired deactivation of the default mode network during cognitive tasks with persistent activation in medial frontal and central regions in patients. Coactivation in the motor cortex and supplementary motor area with increasing cognitive load and increased functional coupling between the motor system and cognitive networks provide an explanation how cognitive effort can cause myoclonic jerks in juvenile myoclonic epilepsy. The supplementary motor area represents the anatomical link between these two functional systems, and our findings may be the functional correlate of previously described structural abnormalities in the medial frontal lobe in juvenile myoclonic epilepsy.

Publisher Correction: Resistance to nonribosomal peptide antibiotics mediated by D-stereospecific peptidases.

PubMed

Li, Yong-Xin; Zhong, Zheng; Hou, Peng; Zhang, Wei-Peng; Qian, Pei-Yuan

2018-03-07

In the version of this article originally published, the links and files for the Supplementary Information, including Supplementary Tables 1-5, Supplementary Figures 1-25, Supplementary Note, Supplementary Datasets 1-4 and the Life Sciences Reporting Summary, were missing in the HTML. The error has been corrected in the HTML version of this article.

Author Correction: Uplift of the central transantarctic mountains.

PubMed

Wannamaker, Phil; Hill, Graham; Stodt, John; Maris, Virginie; Ogawa, Yasuo; Selway, Kate; Boren, Goran; Bertrand, Edward; Uhlmann, Daniel; Ayling, Bridget; Green, A Marie; Feucht, Daniel

2018-02-16

The original version of this Article incorrectly referenced the Figures in the Supplementary Information. References in the main Article to Supplementary Figure 7 through to Supplementary Figure 20 were previously incorrectly cited as Supplementary Figure 5 through to Supplementary Figure 18, respectively. This has now been corrected in both the PDF and HTML versions of the Article.

Neonatal tetanus elimination in Pakistan: progress and challenges.

PubMed

Lambo, Jonathan A; Nagulesapillai, Tharsiya

2012-12-01

Pakistan is one of the 34 countries that have not achieved the neonatal tetanus (NT) global elimination target set by the World Health Organization (WHO). NT, caused by Clostridium tetani, is a highly fatal infection of the neonatal period. It is one of the most underreported diseases and remains a major but preventable cause of neonatal and infant mortality in many developing countries. In 1989, the World Health Assembly called for the elimination of NT by 1995, and since then considerable progress has been made using the following strategies: clean delivery practices, routine tetanus toxoid (TT) immunization of pregnant women, and immunization of all women of childbearing age with three doses of TT vaccine in high-risk areas during supplementary immunization campaigns. This review presents the activities, progress, and challenges in achieving NT elimination in Pakistan. A review of the literature found TT vaccination coverage in Pakistan ranged from 60% to 74% over the last decade. Low vaccination coverage, the main driver for NT in Pakistan, is due to many factors, including demand failure for TT vaccine resulting from inadequate knowledge of TT vaccine among reproductive age females and inadequate information about the benefits of TT provided by health care workers and the media. Other factors linked to low vaccination coverage include residing in rural areas, lack of formal education, poor knowledge about place and time to get vaccinated, and lack of awareness about the importance of vaccination. A disparity exists in TT vaccination coverage and antenatal care between urban and rural areas due to access and utilization of health care services. NT reporting is incomplete, as cases from the private sector and rural areas are underreported. To successfully eliminate NT, women of reproductive age must be made aware of the benefits of TT vaccine, not only to themselves, but also to their families. Effective communication strategies for TT vaccine delivery and health education focusing on increasing awareness of NT are strongly suggested. It is imperative that the private and government sectors work cooperatively to report NT cases and improve routine TT vaccination coverage. Copyright © 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Strategic Engagement of Technical Surge Capacity for Intensified Polio Eradication Initiative in Nigeria, 2012-2015.

PubMed

Yehualashet, Yared G; Mkanda, Pascal; Gasasira, Alex; Erbeto, Tesfaye; Onimisi, Anthony; Horton, Janet; Banda, Richard; Tegegn, Sisay G; Ahmed, Haruna; Afolabi, Oluwole; Wadda, Alieu; Vaz, Rui G; Nsubuga, Peter

2016-05-01

Following the 65th World Health Assembly (WHA) resolution on intensification of the Global Poliomyelitis Eradication Initiative (GPEI), the Nigerian government, with support from the World Health Organization (WHO) and other partners, implemented a number of innovative strategies to curb the transmission of wild poliovirus (WPV) in the country. One of the innovations successfully implemented since mid 2012 is the WHO's engagement of surge capacity personnel. The WHO reorganized its functional structure, adopted a transparent recruitment and deployment process, provided focused technical and management training, and applied systematic accountability framework to successfully manage the surge capacity project in close collaboration with the national counterparts and partners. The deployment of the surge capacity personnel was guided by operational and technical requirement analysis. Over 2200 personnel were engaged, of whom 92% were strategically deployed in 11 states classified as high risk on the basis of epidemiological risk analysis and compromised security. These additional personnel were directly engaged in efforts aimed at improving the performance of polio surveillance, vaccination campaigns, increased routine immunization outreach sessions, and strengthening partnership with key stakeholders at the operational level, including community-based organizations. Programmatic interventions were sustained in states in which security was compromised and the risk of polio was high, partly owing to the presence of the surge capacity personnel, who are engaged from the local community. Since mid-2012, significant programmatic progress was registered in the areas of polio supplementary immunization activities, acute flaccid paralysis surveillance, and routine immunization with the support of the surge capacity personnel. As of 19 June 2015, the last case of WPV was reported on 24 July 2014. The surge infrastructure has also been instrumental in building local capacity; supporting other public health emergencies, such as the Ebola outbreak response and measles and meningitis outbreaks; and strengthening the integrated disease surveillance and response. Due to weak health systems in the country, it is vital to maintain a reasonable level of the surge capacity for successful implementation of the 2013-2018 global polio endgame strategy and beyond. © 2016 World Health Organization; licensee Oxford Journals.

Strategic Engagement of Technical Surge Capacity for Intensified Polio Eradication Initiative in Nigeria, 2012–2015

PubMed Central

Yehualashet, Yared G.; Mkanda, Pascal; Gasasira, Alex; Erbeto, Tesfaye; Onimisi, Anthony; Horton, Janet; Banda, Richard; Tegegn, Sisay G.; Ahmed, Haruna; Afolabi, Oluwole; Wadda, Alieu; Vaz, Rui G.; Nsubuga, Peter

2016-01-01

Background. Following the 65th World Health Assembly (WHA) resolution on intensification of the Global Poliomyelitis Eradication Initiative (GPEI), the Nigerian government, with support from the World Health Organization (WHO) and other partners, implemented a number of innovative strategies to curb the transmission of wild poliovirus (WPV) in the country. One of the innovations successfully implemented since mid 2012 is the WHO's engagement of surge capacity personnel. Methods. The WHO reorganized its functional structure, adopted a transparent recruitment and deployment process, provided focused technical and management training, and applied systematic accountability framework to successfully manage the surge capacity project in close collaboration with the national counterparts and partners. The deployment of the surge capacity personnel was guided by operational and technical requirement analysis. Results. Over 2200 personnel were engaged, of whom 92% were strategically deployed in 11 states classified as high risk on the basis of epidemiological risk analysis and compromised security. These additional personnel were directly engaged in efforts aimed at improving the performance of polio surveillance, vaccination campaigns, increased routine immunization outreach sessions, and strengthening partnership with key stakeholders at the operational level, including community-based organizations. Discussion. Programmatic interventions were sustained in states in which security was compromised and the risk of polio was high, partly owing to the presence of the surge capacity personnel, who are engaged from the local community. Since mid-2012, significant programmatic progress was registered in the areas of polio supplementary immunization activities, acute flaccid paralysis surveillance, and routine immunization with the support of the surge capacity personnel. As of 19 June 2015, the last case of WPV was reported on 24 July 2014. The surge infrastructure has also been instrumental in building local capacity; supporting other public health emergencies, such as the Ebola outbreak response and measles and meningitis outbreaks; and strengthening the integrated disease surveillance and response. Due to weak health systems in the country, it is vital to maintain a reasonable level of the surge capacity for successful implementation of the 2013–2018 global polio endgame strategy and beyond. PMID:26912379

Immune cell-poor melanomas benefit from PD-1 blockade after targeted type I IFN activation.

PubMed

Bald, Tobias; Landsberg, Jennifer; Lopez-Ramos, Dorys; Renn, Marcel; Glodde, Nicole; Jansen, Philipp; Gaffal, Evelyn; Steitz, Julia; Tolba, Rene; Kalinke, Ulrich; Limmer, Andreas; Jönsson, Göran; Hölzel, Michael; Tüting, Thomas

2014-06-01

Infiltration of human melanomas with cytotoxic immune cells correlates with spontaneous type I IFN activation and a favorable prognosis. Therapeutic blockade of immune-inhibitory receptors in patients with preexisting lymphocytic infiltrates prolongs survival, but new complementary strategies are needed to activate cellular antitumor immunity in immune cell-poor melanomas. Here, we show that primary melanomas in Hgf-Cdk4(R24C) mice, which imitate human immune cell-poor melanomas with a poor outcome, escape IFN-induced immune surveillance and editing. Peritumoral injections of immunostimulatory RNA initiated a cytotoxic inflammatory response in the tumor microenvironment and significantly impaired tumor growth. This critically required the coordinated induction of type I IFN responses by dendritic, myeloid, natural killer, and T cells. Importantly, antibody-mediated blockade of the IFN-induced immune-inhibitory interaction between PD-L1 and PD-1 receptors further prolonged the survival. These results highlight important interconnections between type I IFNs and immune-inhibitory receptors in melanoma pathogenesis, which serve as targets for combination immunotherapies. Using a genetically engineered mouse melanoma model, we demonstrate that targeted activation of the type I IFN system with immunostimulatory RNA in combination with blockade of immune-inhibitory receptors is a rational strategy to expose immune cell-poor tumors to cellular immune surveillance. ©2014 American Association for Cancer Research.

Mast cell activators as novel immune regulators.

PubMed

Johnson-Weaver, Brandi; Choi, Hae Woong; Abraham, Soman N; Staats, Herman F

2018-05-26

Mast cells are an important cell type of the innate immune system that when activated, play a crucial role in generating protective innate host responses after bacterial and viral infection. Additionally, activated mast cells influence lymph node composition to regulate the induction of adaptive immune responses. The recognition that mast cells play a beneficial role in host responses to microbial infection and induction of adaptive immunity has provided the rationale to evaluate mast cell activators for use as antimicrobials or vaccine adjuvants. This review summarizes the role of mast cell activators in antimicrobial responses while also discussing the use of different classes of mast cell activators as potent vaccine adjuvants that enhance the induction of protective immune responses. Copyright © 2018 Elsevier Ltd. All rights reserved.

Mice are actively immunized after passive monoclonal antibody prophylaxis and ricin toxin challenge. (Reannouncement with new availability information)

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

Lemley, P.V.; Wright, D.C.

1992-12-31

Mice passively immunized by a protective, anti-ricin A-chain monoclonal antibody, then challenged intravenously with ricin, were protected from a subsequent ricin challenge, and were actively immunized. Two significant advantages accrued from this experiment: the monoclonal antibody neutralized the toxicity of the ricin immunogen, and active immunization was achieved with very low antigen load (approx. 0.5 micrograms/mouse). We ruled out the possibility that residual monoclonal antibody provided the protection by using three independent criteria. There was significant (four orders of magnitude) enhancement of the immune response in the presence of the monoclonal antibody; control immunizations of mice with ricin A-chain, ricinmore » B-chain or either chain with the monoclonal antibody did not induce active immunity; and the active immunization could not be replicated when protective goat polyclonal antibody was substituted for the monoclonal antibody. Because high titers were achieved rapidly without any adjuvant, we are currently investigating haptenized ricin to determine if anti-hapten monoclonal antibodies can be produced by this refined procedure.« less

Downregulation of CD4+CD25+ regulatory T cells may underlie enhanced Th1 immunity caused by immunization with activated autologous T cells.

PubMed

Cao, Qi; Wang, Li; Du, Fang; Sheng, Huiming; Zhang, Yan; Wu, Juanjuan; Shen, Baihua; Shen, Tianwei; Zhang, Jingwu; Li, Dangsheng; Li, Ningli

2007-07-01

Regulatory T cells (Treg) play important roles in immune system homeostasis, and may also be involved in tumor immunotolerance by suppressing Th1 immune response which is involved in anti-tumor immunity. We have previously reported that immunization with attenuated activated autologous T cells leads to enhanced anti-tumor immunity and upregulated Th1 responses in vivo. However, the underlying molecular mechanisms are not well understood. Here we show that Treg function was significantly downregulated in mice that received immunization of attenuated activated autologous T cells. We found that Foxp3 expression decreased in CD4+CD25+ T cells from the immunized mice. Moreover, CD4+CD25+Foxp3+ Treg obtained from immunized mice exhibited diminished immunosuppression ability compared to those from naïve mice. Further analysis showed that the serum of immunized mice contains a high level of anti-CD25 antibody (about 30 ng/ml, p<0.01 vs controls). Consistent with a role of anti-CD25 response in the downregulation of Treg, adoptive transfer of serum from immunized mice to naïve mice led to a significant decrease in Treg population and function in recipient mice. The triggering of anti-CD25 response in immunized mice can be explained by the fact that CD25 was induced to a high level in the ConA activated autologous T cells used for immunization. Our results demonstrate for the first time that immunization with attenuated activated autologous T cells evokes anti-CD25 antibody production, which leads to impeded CD4+CD25+Foxp3+ Treg expansion and function in vivo. We suggest that dampened Treg function likely contributes to enhanced Th1 response in immunized mice and is at least part of the mechanism underlying the boosted anti-tumor immunity.

"Life Is Like a River": The Austin Youth River Watch Final Report, 1994-95. Publication Number 94.15.

ERIC Educational Resources Information Center

Turner, Jeannine

The City of Austin (Texas) provided funds for a supplementary educational activity to involve at-risk minority high school students in water quality issues. The program encourages at-risk students to remain in school by providing an interesting and authentic activity to use in the development of academic skills. Program activities included testing…

Effects of supplementary lighting by natural light for growth of Brassica chinensis

NASA Astrophysics Data System (ADS)

Yeh, Shih-Chuan; Lee, Hui-Ping; Kao, Shih-Tse; Lu, Ju-Lin

2016-04-01

This paper present a model of cultivated chamber with supplementary natural colour light. We investigate the effects of supplementary natural red light and natural blue light on growth of Brassica chinensis under natural white light illumination. After 4 weeks of supplementary colour light treatment, the experiment results shown that the weight of fresh leaf were not affected by supplementary natural blue light. However, those Brassica chinensis were cultivated in the chambers with supplementary natural red light obtained a significant increasing of fresh weight of leaf under both white light illuminate models. The combination of natural white light with supplementary natural red light illumination will be benefits in growth for cultivation and energy saving.

Suppression of proliferation and oxidative stress by extracts of Ganoderma lucidum in the ovarian cancer cell line OVCAR-3.

PubMed

Hsieh, Tze-Chen; Wu, Joseph M

2011-12-01

Lingzhi (LZ) is a medical mushroom also known as Ganoderma lucidum, which has been used in traditional Chinese medicine for more than 4,000 years and moreover, due to its presumed health benefits and apparent absence of side-effects it has also been widely consumed as a dietary supplement by cancer patients and by individuals diagnosed with various chronic diseases. The reported benefits of Ganoderma lucidum may be largely ascribed to its biologically active constituent polysaccharides and triterpenes known as ganoderic acids having structural similarity to steroid hormones. Laboratory studies have shown that Ganoderma lucidum enhances immune functions and also inhibits growth of various cancer cells both in vitro and in vivo. However, the mechanism by which Ganoderma lucidum exerts its chemopreventive activities remains unknown. In this study, we investigated whether Ganoderma lucidum elicits its anti-tumor effects by suppressing cell growth and inducing antioxidative/detoxification activity in human ovarian OVCAR-3 cells. The results showed that Ganoderma lucidum inhibits cell growth and disruption of cell cycle progression via down regulation of cyclin D1. Chemopreventive activities elicited by Ganoderma lucidum were demonstrated by the induction of antioxidant SOD and catalase as well as the phase II detoxification enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1) and glutathione S-transferase P1 (GSTP1) via the Nrf2 mediated signaling pathway known to provide chemoprotection against carcinogenicity. These findings indicate that Ganoderma lucidum possesses chemopreventive potential contributing to its overall health effects and further suggest that Ganoderma lucidum may have clinical applications as an adjunct supplementary agent in chemotherapy.

Independent and interactive effects of immune activation and larval diet on adult immune function, growth and development in the greater wax moth (Galleria mellonella).

PubMed

Kangassalo, Katariina; Valtonen, Terhi M; Sorvari, Jouni; Kecko, Sanita; Pölkki, Mari; Krams, Indrikis; Krama, Tatjana; Rantala, Markus J

2018-06-29

Organisms in the wild are likely to face multiple immune challenges as well as additional ecological stressors, yet their interactive effects on immune function are poorly understood. Insects are found to respond to cues of increased infection risk by enhancing their immune capacity. However, such adaptive plasticity in immune function may be limited by physiological and environmental constraints. Here, we investigated the effects of two environmental stressors - poor larval diet and an artificial parasite-like immune challenge at the pupal stage - on adult immune function, growth and development in the greater wax moth (Galleria mellonella). Males whose immune system was activated with an artificial parasite-like immune challenge had weaker immune response - measured as strength of encapsulation response - as adults compared to the control groups, but only when raised in high-nutrition larval diet. Immune activation did not negatively affect adult immune response in males reared in low-nutrition larval diet, indicating that poor larval diet improved the capacity of the insects to respond to repeated immune challenges. Low-nutrition larval diet also had a positive independent effect on immune capacity in females, yet it negatively affected development time and adult body mass in both sexes. As in the nature immune challenges are rarely isolated, and adverse nutritional environment may indicate an elevated risk of infection, resilience to repeated immune challenges as a response to poor nutritional environment could provide a significant fitness advantage. The present study highlights the importance of considering environmental context when investigating effects of immune activation in insects. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Assessing age-dependent susceptibility to measles in Japan.

PubMed

Kinoshita, Ryo; Nishiura, Hiroshi

2017-06-05

Routine vaccination against measles in Japan started in 1978. Whereas measles elimination was verified in 2015, multiple chains of measles transmission were observed in 2016. We aimed to reconstruct the age-dependent susceptibility to measles in Japan so that future vaccination strategies can be elucidated. An epidemiological model was used to quantify the age-dependent immune fraction using datasets of vaccination coverage and seroepidemiological survey. The second dose was interpreted in two different scenarios, i.e., booster and random shots. The effective reproduction number, the average number of secondary cases generated by a single infected individual, and the age at infection were explored using the age-dependent transmission model and the next generation matrix. While the herd immunity threshold of measles likely ranges from 90% to 95%, assuming that the basic reproductive number ranges from 10 to 20, the estimated immune fraction in Japan was below those thresholds in 2016, despite the fact that the estimates were above 80% for all ages. If the second dose completely acted as the booster shot, a proportion immune above 90% was achieved only among those aged 5years or below in 2016. Alternatively, if the second dose was randomly distributed regardless of primary vaccination status, a proportion immune over 90% was achieved among those aged below 25years. The effective reproduction number was estimated to range from 1.50 to 3.01 and from 1.50 to 3.00, respectively, for scenarios 1 and 2 in 2016; if the current vaccination schedule were continued, the reproduction number is projected to range from 1.50 to 3.01 and 1.39 to 2.78, respectively, in 2025. Japan continues to be prone to imported cases of measles. Supplementary vaccination among adults aged 20-49years would be effective if the chains of transmission continue to be observed in that age group. Copyright © 2017 Elsevier Ltd. All rights reserved.

A review of the human vs. porcine female genital tract and associated immune system in the perspective of using minipigs as a model of human genital Chlamydia infection.

PubMed

Lorenzen, Emma; Follmann, Frank; Jungersen, Gregers; Agerholm, Jørgen S

2015-09-28

Sexually transmitted diseases constitute major health issues and their prevention and treatment continue to challenge the health care systems worldwide. Animal models are essential for a deeper understanding of the diseases and the development of safe and protective vaccines. Currently a good predictive non-rodent model is needed for the study of genital chlamydia in women. The pig has become an increasingly popular model for human diseases due to its close similarities to humans. The aim of this review is to compare the porcine and human female genital tract and associated immune system in the perspective of genital Chlamydia infection. The comparison of women and sows has shown that despite some gross anatomical differences, the structures and proportion of layers undergoing cyclic alterations are very similar. Reproductive hormonal cycles are closely related, only showing a slight difference in cycle length and source of luteolysing hormone. The epithelium and functional layers of the endometrium show similar cyclic changes. The immune system in pigs is very similar to that of humans, even though pigs have a higher percentage of CD4(+)/CD8(+) double positive T cells. The genital immune system is also very similar in terms of the cyclic fluctuations in the mucosal antibody levels, but differs slightly regarding immune cell infiltration in the genital mucosa - predominantly due to the influx of neutrophils in the porcine endometrium during estrus. The vaginal flora in Göttingen Minipigs is not dominated by lactobacilli as in humans. The vaginal pH is around 7 in Göttingen Minipigs, compared to the more acidic vaginal pH around 3.5-5 in women. This review reveals important similarities between the human and porcine female reproductive tracts and proposes the pig as an advantageous supplementary model of human genital Chlamydia infection.

Extending the Cortical Grasping Network: Pre-supplementary Motor Neuron Activity During Vision and Grasping of Objects

PubMed Central

Lanzilotto, Marco; Livi, Alessandro; Maranesi, Monica; Gerbella, Marzio; Barz, Falk; Ruther, Patrick; Fogassi, Leonardo; Rizzolatti, Giacomo; Bonini, Luca

2016-01-01

Grasping relies on a network of parieto-frontal areas lying on the dorsolateral and dorsomedial parts of the hemispheres. However, the initiation and sequencing of voluntary actions also requires the contribution of mesial premotor regions, particularly the pre-supplementary motor area F6. We recorded 233 F6 neurons from 2 monkeys with chronic linear multishank neural probes during reaching–grasping visuomotor tasks. We showed that F6 neurons play a role in the control of forelimb movements and some of them (26%) exhibit visual and/or motor specificity for the target object. Interestingly, area F6 neurons form 2 functionally distinct populations, showing either visually-triggered or movement-related bursts of activity, in contrast to the sustained visual-to-motor activity displayed by ventral premotor area F5 neurons recorded in the same animals and with the same task during previous studies. These findings suggest that F6 plays a role in object grasping and extend existing models of the cortical grasping network. PMID:27733538

[Indicators of the persistent pro-inflammatory activation of the immune system in depression].

PubMed

Cubała, Wiesław Jerzy; Godlewska, Beata; Trzonkowski, Piotr; Landowski, Jerzy

2006-01-01

The aetiology of depression remains tentative. Current hypotheses on the aetiology of the depressive disorder tend to integrate monoaminoergic, neuroendocrine and immunological concepts of depression. A number of research papers emphasise the altered hormonal and immune status of patients with depression with pronounced cytokine level variations. Those studies tend to link the variable course of depression in relation to the altered proinflammatory activity of the immune system. The results of the studies on the activity of the selected elements of the immune system are ambiguous indicating both increased and decreased activities of its selected elements. However, a number of basic and psychopharmacological studies support the hypothesis of the increased proinflammatory activity of the immune system in the course of depression which is the foundation for the immunological hypothesis of depression. The aim of this paper is to review the functional abnormalities that are observed in depression focusing on the monoaminoergic deficiency and increased immune activation as well as endocrine dysregulation. This paper puts together and discusses current studies related to this subject with a detailed insight into interactions involving nervous, endocrine and immune systems.

Suppression of antigen-specific lymphocyte activation in modeled microgravity

NASA Technical Reports Server (NTRS)

Cooper, D.; Pride, M. W.; Brown, E. L.; Risin, D.; Pellis, N. R.; McIntire, L. V. (Principal Investigator)

2001-01-01

Various parameters of immune suppression are observed in lymphocytes from astronauts during and after a space flight. It is difficult to ascribe this suppression to microgravity effects on immune cells in crew specimens, due to the complex physiological response to space flight and the resultant effect on in vitro immune performance. Use of isolated immune cells in true and modeled microgravity in immune performance tests, suggests a direct effect of microgravity on in vitro cellular function. Specifically, polyclonal activation of T-cells is severely suppressed in true and modeled microgravity. These recent findings suggest a potential suppression of oligoclonal antigen-specific lymphocyte activation in microgravity. We utilized rotating wall vessel (RWV) bioreactors as an analog of microgravity for cell cultures to analyze three models of antigen-specific activation. A mixed-lymphocyte reaction, as a model for a primary immune response, a tetanus toxoid response and a Borrelia burgdorferi response, as models of a secondary immune response, were all suppressed in the RWV bioreactor. Our findings confirm that the suppression of activation observed with polyclonal models also encompasses oligoclonal antigen-specific activation.

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Acute and Subacute Oral Toxicity of Periodate in Rats

DTIC Science & Technology

2014-11-17

presence of decreased TSH, a pattern associated with uremia. Sodium periodate exposed rats exhibited both activation of the innate immune system and...associated with kidney disease are characterized by activation of the innate immune system coupled with immune deficiency. Sodium periodate exposed rats...exhibited both activation of the innate immune system and lymphocyte depletion; however, the pattern of effects was more indicative of a stress leukogram

Identifying risk factors of immune reconstitution inflammatory syndrome in AIDS patients receiving highly active anti-retroviral therapy.

PubMed

He, Bo; Zheng, Yuhuang; Liu, Meng; Zhou, Guoqiang; Chen, Xia; Mamadou, Diallo; He, Yan; Zhou, Huaying; Chen, Zi

2013-01-01

Immune reconstitution inflammation syndrome typically occurs within days after patients undergo highly active anti-retroviral therapy and is a big hurdle for effective treatment of AIDS patients. In this study, we monitored immune reconstitution inflammation syndrome occurrence in 238 AIDS patients treated with highly active anti-retroviral therapy. Among them, immune reconstitution inflammation syndrome occurred in 47 cases (19.7%). Immune reconstitution inflammation syndrome patients had significantly higher rate of opportunistic infection (p<0.001) and persistently lower CD4(+) cell count (p<0.001) compared to the non-immune reconstitution inflammation syndrome patients. In contrast, no significant differences in HIV RNA loads were observed between the immune reconstitution inflammation syndrome group and non-immune reconstitution inflammation syndrome group. These data suggest that a history of opportunistic infection and CD4(+) cell counts at baseline may function as risk factors for immune reconstitution inflammation syndrome occurrence in AIDS patients as well as potential prognostic markers. These findings will improve the management of AIDS with highly active anti-retroviral therapy. Copyright © 2013 Elsevier Editora Ltda. All rights reserved.

The innate immune system in chronic cardiomyopathy: a European Society of Cardiology (ESC) scientific statement from the Working Group on Myocardial Function of the ESC

PubMed Central

Falcao‐Pires, Ines; Balligand, Jean‐Luc; Bauersachs, Johann; Brutsaert, Dirk; Ciccarelli, Michele; Dawson, Dana; de Windt, Leon J.; Giacca, Mauro; Hamdani, Nazha; Hilfiker‐Kleiner, Denise; Hirsch, Emilio; Leite‐Moreira, Adelino; Mayr, Manuel; Thum, Thomas; Tocchetti, Carlo G.; van der Velden, Jolanda; Varricchi, Gilda; Heymans, Stephane

2018-01-01

Activation of the immune system in heart failure (HF) has been recognized for over 20 years. Initially, experimental studies demonstrated a maladaptive role of the immune system. However, several phase III trials failed to show beneficial effects in HF with therapies directed against an immune activation. Preclinical studies today describe positive and negative effects of immune activation in HF. These different effects depend on timing and aetiology of HF. Therefore, herein we give a detailed review on immune mechanisms and their importance for the development of HF with a special focus on commonalities and differences between different forms of cardiomyopathies. The role of the immune system in ischaemic, hypertensive, diabetic, toxic, viral, genetic, peripartum, and autoimmune cardiomyopathy is discussed in depth. Overall, initial damage to the heart leads to disease specific activation of the immune system whereas in the chronic phase of HF overlapping mechanisms occur in different aetiologies. PMID:29333691

Fostering Innovation Through Robotics Exploration

DTIC Science & Technology

2015-06-01

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Multinational Activities of Major U.S. Automotive Producers : Volume 4. A Preliminary Evaluation of Technology Innovation and Transfer

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1978-09-01

While the major focus of the present study, as reflected in Volume II, III, and V, has been upon the overseas activities of the four U.S. automobile manufacturers, a supplementary concern has been to develop insights into the flows or transfers of te...

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Water: A Vital Resource. Environmental Education Supplementary Instructional Guide. Sixth Grade Level.

ERIC Educational Resources Information Center

Young, Donald B.; And Others

Water related activities for sixth-grade students are presented as one possible way to incorporate environmental education into the existing curriculum of Hawaii schools. Designed as an interdisciplinary approach, the activities integrate numerous thematic and subject areas to teach that fresh water is a limited but vital natural resource. Topics…

The American Indian Social Studies Curriculum Activity Guide, Grades 9-12.

ERIC Educational Resources Information Center

Stutzman, Esther

Designed to provide supplementary information on American Indians for the teaching of American history, the activity guide for grades 9-12 offers background knowledge and suggested discussion topics for students. Contents of the guide include: a historical timeline outlining major events from 15,000 B.C. to the present; Hollywood's influence on…

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Trade in the Ancient World--Evidence from a Shipwreck

ERIC Educational Resources Information Center

Gersmehl, Phil

2018-01-01

This activity is part of a larger set of activities and presentations developed by the Michigan Geographic Alliance to help teachers meet the proposed Social Studies standards in 6th and 7th grade. The Michigan Geographic Alliance website also has explanatory presentations, supplementary maps, and readings. In this 10-20 minute intermediate…

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Oral immunization with Escherichia coli K-12 of the fifth instar larvae of the silkworm, Bombyx mori, reared on an artificial diet under completely aseptic conditions.

PubMed

Ichimori, H; Yuhki, T; Mori, H; Matsubara, F; Sumida, M

1992-01-01

1. Effect of oral administration of live or formalin-treated Escherichia coli (E. coli) K-12 to the fifth instar, days 1 and 3 larvae of the silkworm, Bombyx mori, on induction of antibacterial activity in the haemolymph was investigated using the silkworms reared on an artificial diet under completely aseptic conditions. 2. When live E. coli was administered to the male day 1 larvae, low but significant antibacterial activity of 3.8 mm was detectable in the haemolymph of one individual at 48 hr after immunization. The proportion of the larvae to express antibacterial activity increased thereafter and at 120 hr after immunization, all three individuals showed antibacterial activity. In day 3 male larvae, activity was detectable at 48 and 72 hr after immunization. 3. When formalin-treated E. coli was orally administered to days 1 and 3 male larvae, no activity was detectable at any time post-immunization. 4. In the second experiment, when day 1 larvae, females and males were orally immunized with live E. coli, only females showed antibacterial activity in the haemolymph, beginning from 24 hr after immunization and up to 96 hr. 5. Removal of an antibiotic, chloramphenicol, from ingredients of an artificial diet was required for induction of antibacterial activity with oral administration of live E. coli. 6. When live E. coli that grows at pH 9.0 was selected and used for oral immunization, antibacterial activity was induced both in females and males at 72 hr after immunization and the activity was observed at 96 hr. 7. These results suggest that establishment of oral immunization with live E. coli in the silkworm larvae requires multiplication of E. coli in the midgut lumen and possibly its colonization on the luminal surface.

Persistent inflammation in HIV infection: established concepts, new perspectives.

PubMed

Nasi, Milena; Pinti, Marcello; Mussini, Cristina; Cossarizza, Andrea

2014-10-01

Immune activation is now considered a main driving force for the progressive immune failure in HIV infection. During the early phases of infection, a rapid depletion of gastrointestinal CD4+ T cells occurs that is followed by a deterioration of the gut epithelium and by the subsequent translocation of microbial products into the blood. Activation of innate immunity results in massive production of proinflammatory cytokines, which can trigger activation induced cell death phenomena among T lymphocytes. Moreover, persistent antigenic stimulation and inflammatory status causes immune exhaustion. The chronic immune activation also damages lymphoid tissue architecture, so contributing to the impairment of immune reconstitution. Recently, new mechanisms were identified, so opening new perspective on the innate immune sensing in HIV-1 infection. Cell death is followed by the release of molecules containing "damage-associated molecular patterns", that trigger a potent innate immune response through the engagement of Toll-like receptors. Then, also different types of HIV-related nucleic acids can act as potent stimulators of innate immunity. All these events contribute to the loss of T cell homeostatic regulation and to the failure of adaptive immunity. Copyright © 2014 Elsevier B.V. All rights reserved.

Insect immunology and hematopoiesis.

PubMed

Hillyer, Julián F

2016-05-01

Insects combat infection by mounting powerful immune responses that are mediated by hemocytes, the fat body, the midgut, the salivary glands and other tissues. Foreign organisms that have entered the body of an insect are recognized by the immune system when pathogen-associated molecular patterns bind host-derived pattern recognition receptors. This, in turn, activates immune signaling pathways that amplify the immune response, induce the production of factors with antimicrobial activity, and activate effector pathways. Among the immune signaling pathways are the Toll, Imd, Jak/Stat, JNK, and insulin pathways. Activation of these and other pathways leads to pathogen killing via phagocytosis, melanization, cellular encapsulation, nodulation, lysis, RNAi-mediated virus destruction, autophagy and apoptosis. This review details these and other aspects of immunity in insects, and discusses how the immune and circulatory systems have co-adapted to combat infection, how hemocyte replication and differentiation takes place (hematopoiesis), how an infection prepares an insect for a subsequent infection (immune priming), how environmental factors such as temperature and the age of the insect impact the immune response, and how social immunity protects entire groups. Finally, this review highlights some underexplored areas in the field of insect immunobiology. Copyright © 2015 Elsevier Ltd. All rights reserved.

Inhibitory effects of chloroquine on the activation of plasmacytoid dendritic cells in SIVmac239-infected Chinese rhesus macaques

PubMed Central

Ma, Jian-Ping; Xia, Hou-Jun; Zhang, Gao-Hong; Han, Jian-Bao; Zhang, Li-Guo; Zheng, Yong-Tang

2012-01-01

It is currently widely accepted that immune activation in HIV-infected individuals leads to a severe loss of CD4+ T cells and the progression to AIDS. However, the underlying mechanism of this immune activation remains unclear. Experimental data suggest that the activation of plasmacytoid dendritic cells (pDCs) by plasma viremia may play a critical role in HIV-induced immune activation. In this study, we found that the level of immune activation was higher in the late phase of SIVmac239 infection compared with chronic infection, which suggests that immune activation might be related to disease progression in SIVmac239-infected non-human primate models. Our work also showed that chloroquine could effectively inhibit the activation of pDCs in vitro and in vivo. However, chloroquine treatment of SIVmac239-infected macaques had no significant influence on the Cellular composition of peripheral blood in these animals. PMID:22885523

Local and systemic tumor immune dynamics

NASA Astrophysics Data System (ADS)

Enderling, Heiko

Tumor-associated antigens, stress proteins, and danger-associated molecular patterns are endogenous immune adjuvants that can both initiate and continually stimulate an immune response against a tumor. In retaliation, tumors can hijack intrinsic immune regulatory programs that are intended to prevent autoimmune disease, thereby facilitating continued growth despite the activated antitumor immune response. In metastatic disease, this ongoing tumor-immune battle occurs at each site. Adding an additional layer of complexity, T cells activated at one tumor site can cycle through the blood circulation system and extravasate in a different anatomic location to surveil a distant metastasis. We propose a mathematical modeling framework that incorporates the trafficking of activated T cells between metastatic sites. We extend an ordinary differential equation model of tumor-immune system interactions to multiple metastatic sites. Immune cells are activated in response to tumor burden and tumor cell death, and are recruited from tumor sites elsewhere in the body. A model of T cell trafficking throughout the circulatory system can inform the tumor-immune interaction model about the systemic distribution and arrival of T cells at specific tumor sites. Model simulations suggest that metastases not only contribute to immune surveillance, but also that this contribution varies between metastatic sites. Such information may ultimately help harness the synergy of focal therapy with the immune system to control metastatic disease.

Modulation of occluding junctions alters the hematopoietic niche to trigger immune activation

PubMed Central

Khadilkar, Rohan J; Vogl, Wayne; Goodwin, Katharine

2017-01-01

Stem cells are regulated by signals from their microenvironment, or niche. During Drosophila hematopoiesis, a niche regulates prohemocytes to control hemocyte production. Immune challenges activate cell-signalling to initiate the cellular and innate immune response. Specifically, certain immune challenges stimulate the niche to produce signals that induce prohemocyte differentiation. However, the mechanisms that promote prohemocyte differentiation subsequent to immune challenges are poorly understood. Here we show that bacterial infection induces the cellular immune response by modulating occluding-junctions at the hematopoietic niche. Occluding-junctions form a permeability barrier that regulates the accessibility of prohemocytes to niche derived signals. The immune response triggered by infection causes barrier breakdown, altering the prohemocyte microenvironment to induce immune cell production. Moreover, genetically induced barrier ablation provides protection against infection by activating the immune response. Our results reveal a novel role for occluding-junctions in regulating niche-hematopoietic progenitor signalling and link this mechanism to immune cell production following infection. PMID:28841136

An acute flaccid paralysis surveillance-based serosurvey of poliovirus antibodies in Western Uttar Pradesh, India.

PubMed

Bahl, Sunil; Gary, Howard E; Jafari, Hamid; Sarkar, Bidyut K; Pathyarch, Surendra K; Sethi, Raman; Deshpande, Jagadish

2014-11-01

Despite intensified use of monovalent oral poliovirus type 1 vaccine and improved coverage of immunization campaigns, wild poliovirus type 1 persisted in Indian states of Uttar Pradesh and Bihar during 2006 to 2009. A serosurvey was conducted among cases of acute flaccid paralysis in the 25 high-polio-incidence districts of western Uttar Pradesh. Children were recruited by age group (6-11 months, 12-24 months, and 25-69 months) from among cases reported through the acute flaccid paralysis surveillance system between November 2008 and August 2009. Seroprevalence for type 1 wild poliovirus was >96.4% for each age group. The seroprevalence of wild poliovirus types 2 and 3 increased with age, from 36.7% to 73.4% for type 2 and from 39.0% to 74.1% for type 3. In addition to the number of type-specific vaccine doses, father's level of education, being from a Muslim family, height for age, and female sex were the socioeconomic risk factors associated with seronegativity to poliovirus. The seroprevalence and risk factors identified in this study were consistent with the epidemiology of polio, and the findings were instrumental in optimizing vaccination strategy in western Uttar Pradesh with respect to the choice of OPV types, the frequency of supplementary immunization campaigns, and the urgency to improve routine immunization services. © The Author 2014. 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.

Evaluation of the innate immune-stimulating activity of amazake using a silkworm muscle contraction assay.

PubMed

Maruki-Uchida, Hiroko; Sai, Masahiko; Sekimizu, Kazuhisa

2017-11-22

We evaluated the innate immune-stimulating activity of amazake using a silkworm muscle contraction assay. Sake cake, a raw material used to make amazake, had high innate immunity-stimulating activity, whereas rice malt, another raw material used to make amazake, did not, even after fermentation. These results suggest that the silkworm muscle contraction assay is a useful tool to screen foods with high innate immune-stimulating activity and that amazake made from sake cake has immunomodulatory potential.

Local activation of p53 in the tumor microenvironment overcomes immune suppression and enhances antitumor immunity

PubMed Central

Guo, Gang; Yu, Miao; Xiao, Wei; Celis, Esteban; Cui, Yan

2017-01-01

Mutations in tumor suppressor p53 remain a vital mechanism of tumor escape from apoptosis and senescence. Emerging evidence suggests that p53 dysfunction also fuels inflammation and supports tumor immune evasion, thereby serving as an immunological driver of tumorigenesis. Therefore, targeting p53 in the tumor microenvironment (TME) also represents an immunologically desirable strategy for reversing immunosuppression and enhancing antitumor immunity. Using a pharmacological p53 activator nutlin-3a, we show that local p53 activation in TME comprising overt tumor infiltrating leukocytes (TILeus) induces systemic antitumor immunity and tumor regression, but not in TME with scarce TILeus, such as B16 melanoma. Maneuvers that recruit leukocytes to TME, such as TLR3 ligand in B16 tumors, greatly enhanced nutlin-induced antitumor immunity and tumor control. Mechanistically, nutlin-3a-induced antitumor immunity was contingent on two non-redundant but immunologically synergistic p53-dependent processes: reversal of immunosuppression in TME and induction of tumor immunogenic cell death (ICD), leading to activation and expansion of polyfunctional CD8 CTLs and tumor regression. Our study demonstrates that unlike conventional tumoricidal therapies, which rely on effective p53 targeting in each tumor cell and often associate with systemic toxicity, this immune-based strategy requires only limited local p53 activation to alter the immune landscape of TME and subsequently amplify immune response to systemic antitumor immunity. Hence, targeting the p53 pathway in TME can be exploited to reverse immunosuppression and augment therapeutic benefits beyond tumoricidal effects to harness tumor-specific, durable, and systemic antitumor immunity with minimal toxicity. PMID:28280037

Immunomodulatory effects of Hericium erinaceus derived polysaccharides are mediated by intestinal immunology.

PubMed

Sheng, Xiaotong; Yan, Jingmin; Meng, Yue; Kang, Yuying; Han, Zhen; Tai, Guihua; Zhou, Yifa; Cheng, Hairong

2017-03-22

This study was aimed at investigating the immunomodulating activity of Hericium erinaceus polysaccharide (HEP) in mice, by assessing splenic lymphocyte proliferation (cell-mediated immunity), serum hemolysin levels (humoral immunity), phagocytic capacity of peritoneal cavity phagocytes (macrophage phagocytosis), and NK cell activity. ELISA of immunoglobulin A (SIgA) in the lamina propria, and western blotting of small intestinal proteins were also performed to gain insight into the mechanism by which HEP affects the intestinal immune system. Here, we report that HEP improves immune function by functionally enhancing cell-mediated and humoral immunity, macrophage phagocytosis, and NK cell activity. In addition, HEP was found to upregulate the secretion of SIgA and activate the MAPK and AKT cellular signaling pathways in the intestine. In conclusion, all these results allow us to postulate that the immunomodulatory effects of HEP are most likely attributed to the effective regulation of intestinal mucosal immune activity.

Assessing herd immunity against rubella in Japan: a retrospective seroepidemiological analysis of age-dependent transmission dynamics

PubMed Central

Kinoshita, Ryo; Nishiura, Hiroshi

2016-01-01

Objective We aimed to epidemiologically assess rubella herd immunity as a function of time, age and gender in Japan, with reference to the recent 2012–2014 rubella epidemic. Design This study is a retrospective seroepidemiological analysis. Main outcome measures The susceptible fraction of the population was examined as a function of age and time. The age at infection was assessed using reported case data. Results Whereas 30 years ago rubella cases were seen only among children, the median (25–75th centiles) age of cases in 2014 was elevated to 32.0 (17.0–42.0) years among males and 27.0 (7.0–37.0) years among females. Susceptible pockets among male birth cohorts 1989–1993 and 1974–1978 were identified, with seropositive proportions of 70.0% and 68.0%, respectively. The majority of female age groups had greater seropositive proportions than the herd immunity threshold, with a minor susceptible pocket for those born from 1989 to 1993 (78.3% seropositive). The age-standardised seronegative proportion decreased to 18.3% (95% CI 16.8% to 19.8%) among males and 15.6% (95% CI 10.0% to 21.2%) among females in 2013, and the immune fraction was not sufficiently below the herd immunity threshold. While the number of live births born to susceptible mothers in 1983 was estimated at 171 876 across Japan, in 2013 it was reduced to 23 698. Conclusions An elevated age at rubella virus infection and the presence of susceptible pockets among adults were observed in Japan. Although, overall, the absolute number of rubella cases has steadily declined in Japan, the elevated age of rubella cases, along with increased numbers of susceptible adults, contributed to the observation of as many as 45 congenital rubella syndrome (CRS) cases, which calls for supplementary vaccination among susceptible adults. Assessing herd immunity is considered essential for routinely monitoring the risk of future rubella epidemics and CRS cases. PMID:26817640

Assessing herd immunity against rubella in Japan: a retrospective seroepidemiological analysis of age-dependent transmission dynamics.

PubMed

Kinoshita, Ryo; Nishiura, Hiroshi

2016-01-27

We aimed to epidemiologically assess rubella herd immunity as a function of time, age and gender in Japan, with reference to the recent 2012-2014 rubella epidemic. This study is a retrospective seroepidemiological analysis. The susceptible fraction of the population was examined as a function of age and time. The age at infection was assessed using reported case data. Whereas 30 years ago rubella cases were seen only among children, the median (25-75th centiles) age of cases in 2014 was elevated to 32.0 (17.0-42.0) years among males and 27.0 (7.0-37.0) years among females. Susceptible pockets among male birth cohorts 1989-1993 and 1974-1978 were identified, with seropositive proportions of 70.0% and 68.0%, respectively. The majority of female age groups had greater seropositive proportions than the herd immunity threshold, with a minor susceptible pocket for those born from 1989 to 1993 (78.3% seropositive). The age-standardised seronegative proportion decreased to 18.3% (95% CI 16.8% to 19.8%) among males and 15.6% (95% CI 10.0% to 21.2%) among females in 2013, and the immune fraction was not sufficiently below the herd immunity threshold. While the number of live births born to susceptible mothers in 1983 was estimated at 171,876 across Japan, in 2013 it was reduced to 23,698. An elevated age at rubella virus infection and the presence of susceptible pockets among adults were observed in Japan. Although, overall, the absolute number of rubella cases has steadily declined in Japan, the elevated age of rubella cases, along with increased numbers of susceptible adults, contributed to the observation of as many as 45 congenital rubella syndrome (CRS) cases, which calls for supplementary vaccination among susceptible adults. Assessing herd immunity is considered essential for routinely monitoring the risk of future rubella epidemics and CRS cases. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Parental Legacy in Insects: Variation of Transgenerational Immune Priming during Offspring Development

PubMed Central

Trauer, Ute; Hilker, Monika

2013-01-01

In insects, a parental immune challenge can prepare and enhance offspring immune activity. Previous studies of such transgenerational immune priming (TGIP) mainly focused on a single offspring life stage. However, different developmental stages may be exposed to different risks and show different susceptibility to parental immune priming. Here we addressed the question (i) whether TGIP effects on the immunity of Manduca sexta offspring vary among the different developmental offspring stages. We differentiated between unchallenged and immunochallenged offspring; for the latter type of offspring, we further investigated (ii) whether TGIP has an impact on the time that enhanced immune levels persist after offspring immune challenge. Finally, we determined (iii) whether TGIP effects on offspring performance depend on the offspring stage. Our results show that TGIP effects on phenoloxidase (PO) activity, but not on antibacterial activity, vary among unchallenged offspring stages. In contrast, TGIP effects on PO and antibacterial activity did not vary among immunochallenged offspring stages. The persistence of enhanced immune levels in immunochallenged offspring was dependent on the parental immune state. Antibacterial (but not PO) activity in offspring of immunochallenged parents decreased over five days after pupal immune challenge, whereas no significant change over time was detectable in offspring of control parents. Finally, TGIP effects on the developmental time of unchallenged offspring varied among stages; young larvae of immunochallenged parents developed faster and gained more weight than larvae of control parents. However, offspring females of immunochallenged parents laid fewer eggs than females derived from control parents. These findings suggest that the benefits which the offspring gains from TGIP during juvenile development are paid by the adults with reduced reproductive power. Our study shows that TGIP effects vary among offspring stages and depend on the type of immunity (PO or antibacterial activity) as well as the time past offspring immune challenge. PMID:23700423

Role of immune activation in CD4+ T-cell depletion in HIV-1 infected Indian patients.

PubMed

Vajpayee, M; Kaushik, S; Sreenivas, V; Mojumdar, K; Mendiratta, S; Chauhan, N K

2009-01-01

The correlation of immune activation with CD4(+) depletion and HIV-1 disease progression has been evidenced by several studies involving mainly clade B virus. However, this needs to be investigated in developing countries such as India predominately infected with clade C virus. In a cross-sectional study of 68 antiretroviral treatment naïve, HIV-1 infected Indian patients, we studied the association between CD4(+) T cells, plasma HIV-1 RNA levels, and immune activation markers using unadjusted and adjusted correlative analyses. Significant negative correlations of higher magnitude were observed between the CD4(+) T cell percentages and plasma HIV-1 RNA levels in the study population when adjusted for the effects of immune activation markers. However, the negative association of CD4(+) T cells with immune activation markers remained unaffected when controlled for the effects of plasma HIV-1 RNA levels. Our results support the important role of immune activation in CD4(+) T cell depletion and disease progression during untreated HIV-1 infection.

Trends of vaccine-preventable diseases in Afghanistan from the Disease Early Warning System, 2009–2015

PubMed Central

Mubarak, Mohammad Y.; Johnson, Laura E.; Porth, Julia M.; Yousif, Jenna E.; Boulton, Matthew L.

2017-01-01

Background Afghanistan’s public health system was neglected during decades of military and civil conflict, and trends in infectious disease occurrence remain poorly characterized. This study examines cyclical and long-term trends of six vaccine-preventable diseases: pneumonia, diarrhea, meningitis, typhoid, measles, and acute viral hepatitis. Methods Using weekly data collected between 2009 and 2015 through Afghanistan’s Disease Early Warning System, we calculated monthly case counts, and fit a Poisson regression with a Fourier transformation for seasonal cycles and dummy variables for year. Results We found the greatest incidence of diarrhea and typhoid in the summer, pneumonia in the winter, and measles in the late spring. Meningitis and acute viral hepatitis did not demonstrate substantial seasonality. Rates of pneumonia and diarrhea were constant across years whereas rates of meningitis, typhoid, and acute viral hepatitis decreased. Measles incidence increased in 2015. Conclusions Communicable disease reporting systems can guide public health operations–such as the implementation of new vaccines, and permit evaluation of health interventions. For example, measles supplementary immunization activities in Afghanistan have not slowed long-term transmission of the disease, but decreases in typhoid fever and acute viral hepatitis are probably tied to improvements in sanitation in the country. PMID:28570694

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48 CFR 836.576 - Supplementary labor standards provisions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Supplementary labor... 836.576 Supplementary labor standards provisions. The contracting officer shall insert the clause at 852.236-85, Supplementary labor standards provisions, in solicitations and contracts for construction...

Enhancing mHealth Technology in the PCMH Environment to Activate Chronic Care Patients

DTIC Science & Technology

2017-09-01

AVAILABILITY STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES - 14. ABSTRACT - The potential of mobile health (mHealth...biometric data, electronic coaching, electronic-based health education, secure e-mail communication between visits, and electronic collection of lifestyle...influence patient activation and self-care activities. 15. SUBJECT TERMS MHCE, Mobile Health Care Environment mHealth, mobile health MHS, Military Health

Context-Aware Active Authentication using Touch Gestures, Typing Patterns and Body Movement

DTIC Science & Technology

2016-03-01

Division Information Directorate This report is published in the interest of scientific and technical information exchange, and its publication does...CA policy clarification memorandum dated 16 Jan 09. 13. SUPPLEMENTARY NOTES 14. ABSTRACT Design, develop and evaluate a desktop based active...of this project was to design, develop and evaluate a desktop active authentication system that uses the following keystroke timing based biometric

An active-learning laboratory on immunizations.

PubMed

Donohoe, Krista L; Mawyer, Tonya M; Stevens, J Tyler; Morgan, Laura A; Harpe, Spencer E

2012-12-12

To implement and evaluate an active-learning laboratory activity to teach pharmacy students about influenza, pneumococcal, and shingles vaccines. The laboratory session was divided into 6 immunization stations: 3 stations on influenza including a pediatrics station, and 1 station each for pneumococcal, shingles, and anaphylaxis. Although 118 of 123 (95.9%) students had completed an immunization training certificate prior to attending the laboratory, the average score on a pre-assessment to measure immunization knowledge and confidence was 56%. The post-assessment score was 87.4%. Students' confidence improved by 18.7% to 51.2% in each of the 5 areas assessed. Most respondents rated the activity overall as good or excellent on a post-activity evaluation. An active-learning approach to teaching immunizations allowed students to gain knowledge in simulated real-world experiences and reinforced key concepts on influenza, pneumococcal, and shingles vaccines.

An evolving new paradigm: endothelial cells – conditional innate immune cells

PubMed Central

2013-01-01

Endothelial cells (ECs) are a heterogeneous population that fulfills many physiological processes. ECs also actively participate in both innate and adaptive immune responses. ECs are one of the first cell types to detect foreign pathogens and endogenous metabolite-related danger signals in the bloodstream, in which ECs function as danger signal sensors. Treatment with lipopolysaccharide activates ECs, causing the production of pro-inflammatory cytokines and chemokines, which amplify the immune response by recruiting immune cells. Thus, ECs function as immune/inflammation effectors and immune cell mobilizers. ECs also induce cytokine production by immune cells, in which ECs function as immune regulators either by activating or suppressing immune cell function. In addition, under certain conditions, ECs can serve as antigen presenting cells (antigen presenters) by expressing both MHC I and II molecules and presenting endothelial antigens to T cells. These facts along with the new concept of endothelial plasticity suggest that ECs are dynamic cells that respond to extracellular environmental changes and play a meaningful role in immune system function. Based on these novel EC functions, we propose a new paradigm that ECs are conditional innate immune cells. This paradigm provides a novel insight into the functions of ECs in inflammatory/immune pathologies. PMID:23965413

An evolving new paradigm: endothelial cells--conditional innate immune cells.

PubMed

Mai, Jietang; Virtue, Anthony; Shen, Jerry; Wang, Hong; Yang, Xiao-Feng

2013-08-22

Endothelial cells (ECs) are a heterogeneous population that fulfills many physiological processes. ECs also actively participate in both innate and adaptive immune responses. ECs are one of the first cell types to detect foreign pathogens and endogenous metabolite-related danger signals in the bloodstream, in which ECs function as danger signal sensors. Treatment with lipopolysaccharide activates ECs, causing the production of pro-inflammatory cytokines and chemokines, which amplify the immune response by recruiting immune cells. Thus, ECs function as immune/inflammation effectors and immune cell mobilizers. ECs also induce cytokine production by immune cells, in which ECs function as immune regulators either by activating or suppressing immune cell function. In addition, under certain conditions, ECs can serve as antigen presenting cells (antigen presenters) by expressing both MHC I and II molecules and presenting endothelial antigens to T cells. These facts along with the new concept of endothelial plasticity suggest that ECs are dynamic cells that respond to extracellular environmental changes and play a meaningful role in immune system function. Based on these novel EC functions, we propose a new paradigm that ECs are conditional innate immune cells. This paradigm provides a novel insight into the functions of ECs in inflammatory/immune pathologies.

A comparison of results of empirical studies of supplementary search techniques and recommendations in review methodology handbooks: a methodological review.

PubMed

Cooper, Chris; Booth, Andrew; Britten, Nicky; Garside, Ruth

2017-11-28

The purpose and contribution of supplementary search methods in systematic reviews is increasingly acknowledged. Numerous studies have demonstrated their potential in identifying studies or study data that would have been missed by bibliographic database searching alone. What is less certain is how supplementary search methods actually work, how they are applied, and the consequent advantages, disadvantages and resource implications of each search method. The aim of this study is to compare current practice in using supplementary search methods with methodological guidance. Four methodological handbooks in informing systematic review practice in the UK were read and audited to establish current methodological guidance. Studies evaluating the use of supplementary search methods were identified by searching five bibliographic databases. Studies were included if they (1) reported practical application of a supplementary search method (descriptive) or (2) examined the utility of a supplementary search method (analytical) or (3) identified/explored factors that impact on the utility of a supplementary method, when applied in practice. Thirty-five studies were included in this review in addition to the four methodological handbooks. Studies were published between 1989 and 2016, and dates of publication of the handbooks ranged from 1994 to 2014. Five supplementary search methods were reviewed: contacting study authors, citation chasing, handsearching, searching trial registers and web searching. There is reasonable consistency between recommended best practice (handbooks) and current practice (methodological studies) as it relates to the application of supplementary search methods. The methodological studies provide useful information on the effectiveness of the supplementary search methods, often seeking to evaluate aspects of the method to improve effectiveness or efficiency. In this way, the studies advance the understanding of the supplementary search methods. Further research is required, however, so that a rational choice can be made about which supplementary search strategies should be used, and when.

Development of Novel PD1/PD-L1 Antagonists Using Circular Cys-Knotted Micro Proteins

DTIC Science & Technology

2017-06-01

positive bacte- ria.[67] Similar antibacterial activities have been found in cyclo- tides isolated from Hedyota biflora (Rubiaceae family)[68] and C...immune control. Hence, reversing the inhibition of the adaptive immunity can lead to the activation of a patient’s immunity. For example, inhibition of...receptor and PD-L1, to block immune checkpoints, and facilitate antitumor activity . These checkpoint-blocking antibodies have demonstrated clinical

Diet Modifies the Neuroimmune System by Influencing Macrophage Activation

ERIC Educational Resources Information Center

Sherry, Christina Lynn

2009-01-01

It has long been appreciated that adequate nutrition is required for proper immune function and it is now recognized that dietary components contribute to modulation of immune cells, subsequently impacting the whole body's response during an immune challenge. Macrophage activation plays a critical role in the immune system and directs the…

The innate immune system in chronic cardiomyopathy: a European Society of Cardiology (ESC) scientific statement from the Working Group on Myocardial Function of the ESC.

PubMed

Frantz, Stefan; Falcao-Pires, Ines; Balligand, Jean-Luc; Bauersachs, Johann; Brutsaert, Dirk; Ciccarelli, Michele; Dawson, Dana; de Windt, Leon J; Giacca, Mauro; Hamdani, Nazha; Hilfiker-Kleiner, Denise; Hirsch, Emilio; Leite-Moreira, Adelino; Mayr, Manuel; Thum, Thomas; Tocchetti, Carlo G; van der Velden, Jolanda; Varricchi, Gilda; Heymans, Stephane

2018-03-01

Activation of the immune system in heart failure (HF) has been recognized for over 20 years. Initially, experimental studies demonstrated a maladaptive role of the immune system. However, several phase III trials failed to show beneficial effects in HF with therapies directed against an immune activation. Preclinical studies today describe positive and negative effects of immune activation in HF. These different effects depend on timing and aetiology of HF. Therefore, herein we give a detailed review on immune mechanisms and their importance for the development of HF with a special focus on commonalities and differences between different forms of cardiomyopathies. The role of the immune system in ischaemic, hypertensive, diabetic, toxic, viral, genetic, peripartum, and autoimmune cardiomyopathy is discussed in depth. Overall, initial damage to the heart leads to disease specific activation of the immune system whereas in the chronic phase of HF overlapping mechanisms occur in different aetiologies. © 2018 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Potential for Cell-Mediated Immune Responses in Mouse Models of Pelizaeus-Merzbacher Disease

PubMed Central

Southwood, Cherie M.; Fykkolodziej, Bozena; Dachet, Fabien; Gow, Alexander

2013-01-01

Although activation of the innate and adaptive arms of the immune system are undoubtedly involved in the pathophysiology of neurodegenerative diseases, it is unclear whether immune system activation is a primary or secondary event. Increasingly, published studies link primary metabolic stress to secondary inflammatory responses inside and outside of the nervous system. In this study, we show that the metabolic stress pathway known as the unfolded protein response (UPR) leads to secondary activation of the immune system. First, we observe innate immune system activation in autopsy specimens from Pelizaeus-Merzbacher disease (PMD) patients and mouse models stemming from PLP1 gene mutations. Second, missense mutations in mildly- and severely-affected Plp1-mutant mice exhibit immune-associated expression profiles with greater disease severity causing an increasingly proinflammatory environment. Third, and unexpectedly, we find little evidence for dysregulated expression of major antioxidant pathways, suggesting that the unfolded protein and oxidative stress responses are separable. Together, these data show that UPR activation can precede innate and/or adaptive immune system activation and that neuroinflammation can be titrated by metabolic stress in oligodendrocytes. Whether or not such activation leads to autoimmune disease in humans is unclear, but the case report of steroid-mitigated symptoms in a PMD patient initially diagnosed with multiple sclerosis lends support. PMID:24575297

Multiple co morbid conditions in patient with Mast Cell Activation Syndrome

DTIC Science & Technology

2017-10-26

conditions in patient \\\\·ith Mast Cell Activation Syndron1e Sb. GRANT NUMBER Sc. PROGRAM.ELEMENT NUMBER 6. AUTHOR(S) Sd. PROJECT NUMBER Maj Sofia...13. SUPPLEMENTARY NOTES 14. ABSTRACT Multiple co-n1orhid conditions in patient \\Vith Mast Cell Activation Syndrotne Sofia M. Szari.MD. and James...Defense. !NTR()D{JCT!ON: Mast cell activation disorders {MCAD) have been associated \\Vilh Connective Tissue Disorders (CTD) and orthostatic

40 CFR 152.406 - Submission of supplementary data.

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2010-07-01

... of supplementary data do not constitute a change in the type of registration action requested. [53 FR... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Submission of supplementary data. 152... supplementary data. Applicants may submit data to supplement pending applications without incurring additional...

40 CFR 152.406 - Submission of supplementary data.

Code of Federal Regulations, 2014 CFR

2014-07-01

... of supplementary data do not constitute a change in the type of registration action requested. [53 FR... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Submission of supplementary data. 152... supplementary data. Applicants may submit data to supplement pending applications without incurring additional...

40 CFR 152.406 - Submission of supplementary data.

Code of Federal Regulations, 2012 CFR

2012-07-01

... of supplementary data do not constitute a change in the type of registration action requested. [53 FR... 40 Protection of Environment 25 2012-07-01 2012-07-01 false Submission of supplementary data. 152... supplementary data. Applicants may submit data to supplement pending applications without incurring additional...

40 CFR 152.406 - Submission of supplementary data.

Code of Federal Regulations, 2013 CFR

2013-07-01

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20 CFR 416.2097 - Combined supplementary/SSI payment levels.

Code of Federal Regulations, 2010 CFR

2010-04-01

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40 CFR 152.406 - Submission of supplementary data.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Submission of supplementary data. 152... supplementary data. Applicants may submit data to supplement pending applications without incurring additional... of supplementary data do not constitute a change in the type of registration action requested. [53 FR...

Seasonal benefits of a natural propolis envelope to honey bee immunity and colony health.

PubMed

Borba, Renata S; Klyczek, Karen K; Mogen, Kim L; Spivak, Marla

2015-11-01

Honey bees, as social insects, rely on collective behavioral defenses that produce a colony-level immune phenotype, or social immunity, which in turn impacts the immune response of individuals. One behavioral defense is the collection and deposition of antimicrobial plant resins, or propolis, in the nest. We tested the effect of a naturally constructed propolis envelope within standard beekeeping equipment on the pathogen and parasite load of large field colonies, and on immune system activity, virus and storage protein levels of individual bees over the course of a year. The main effect of the propolis envelope was a decreased and more uniform baseline expression of immune genes in bees during summer and autumn months each year, compared with the immune activity in bees with no propolis envelope in the colony. The most important function of the propolis envelope may be to modulate costly immune system activity. As no differences were found in levels of bacteria, pathogens and parasites between the treatment groups, the propolis envelope may act directly on the immune system, reducing the bees' need to activate the physiologically costly production of humoral immune responses. Colonies with a natural propolis envelope had increased colony strength and vitellogenin levels after surviving the winter in one of the two years of the study, despite the fact that the biological activity of the propolis diminished over the winter. A natural propolis envelope acts as an important antimicrobial layer enshrouding the colony, benefiting individual immunity and ultimately colony health. © 2015. Published by The Company of Biologists Ltd.

Aberrant supplementary motor complex and limbic activity during motor preparation in motor conversion disorder

PubMed Central

Voon, V; Brezing, C; Gallea, C; Hallett, M

2014-01-01

Background Conversion disorder is characterized by unexplained neurological symptoms presumed related to psychological issues. The main hypotheses to explain conversion paralysis, characterized by a lack of movement, include impairments in either motor intention or disruption of motor execution, and further, that hyperactive self-monitoring, limbic processing or top-down regulation from higher order frontal regions may interfere with motor execution. We have recently shown that conversion disorder with positive abnormal or excessive motor symptoms was associated with greater amygdala activity to arousing stimuli along with greater functional connectivity between the amgydala and supplementary motor area. Here we studied patients with such symptoms focusing on motor initiation. Methods Subjects performed either an internally or externally generated two-button action selection task in a functional MRI study. Results Eleven conversion disorder patients without major depression and 11 age- and gender-matched normal volunteers were assessed. During both internally and externally generated movement, conversion disorder patients relative to normal volunteers had lower left supplementary motor area (SMA) (implicated in motor initiation) and higher right amygdala, left anterior insula and bilateral posterior cingulate activity (implicated in assigning emotional salience). These findings were confirmed in a subgroup analysis of patients with tremor symptoms. During internally versus externally generated action in CD patients, the left SMA had lower functional connectivity with bilateral dorsolateral prefrontal cortices. Conclusion We propose a theory in which previously mapped conversion motor representations may in an arousing context hijack the voluntary action selection system which is both hypoactive and functionally disconnected from prefrontal top-down regulation. PMID:21935985

Aberrant supplementary motor complex and limbic activity during motor preparation in motor conversion disorder.

PubMed

Voon, Valerie; Brezing, Christina; Gallea, Cecile; Hallett, Mark

2011-11-01

Conversion disorder (CD) is characterized by unexplained neurological symptoms presumed related to psychological issues. The main hypotheses to explain conversion paralysis, characterized by a lack of movement, include impairments in either motor intention or disruption of motor execution, and further, that hyperactive self-monitoring, limbic processing or top-down regulation from higher order frontal regions may interfere with motor execution. We have recently shown that CD with positive abnormal or excessive motor symptoms was associated with greater amygdala activity to arousing stimuli along with greater functional connectivity between the amygdala and supplementary motor area. Here we studied patients with such symptoms focusing on motor initiation. Subjects performed either an internally or externally generated 2-button action selection task in a functional MRI study. Eleven CD patients without major depression and 11 age- and gender-matched normal volunteers were assessed. During both internally and externally generated movement, conversion disorder patients relative to normal volunteers had lower left supplementary motor area (SMA) (implicated in motor initiation) and higher right amygdala, left anterior insula, and bilateral posterior cingulate activity (implicated in assigning emotional salience). These findings were confirmed in a subgroup analysis of patients with tremor symptoms. During internally versus externally generated action in CD patients, the left SMA had lower functional connectivity with bilateral dorsolateral prefrontal cortices. We propose a theory in which previously mapped conversion motor representations may in an arousing context hijack the voluntary action selection system, which is both hypoactive and functionally disconnected from prefrontal top-down regulation. Copyright © 2011 Movement Disorder Society.

Energy Use and the Environment. Concepts & Activities for the Classroom: Mathematics Module. Environmental Education Supplementary Instructional Guide.

ERIC Educational Resources Information Center

Hawaii State Dept. of Education, Honolulu. Office of Instructional Services.

As part of a comprehensive, interdisciplinary environmental education program for elementary and secondary education in Hawaii, this teaching guide provides a variety of energy education activities for secondary school mathematics. An extensive introduction outlines the total program and how it fits into the general education program and explains…

Time Management: A Lesson Plan, Transparencies, Handouts and Media Evaluations on the Topic.

ERIC Educational Resources Information Center

Campbell, Clifton P.

Intended for use in a 3-hour instructional program at the graduate level, the packet contains an outline of the instructional content, 9 transparencies, 12 handouts, and 7 supplementary materials. The outline is organized in terms of content, instructor activity (such as showing a transparency), and student activity. Instruction covers the…

Ewe (for Togo): Communication and Culture Handbook. Peace Corps Language Handbook Series.

ERIC Educational Resources Information Center

Kozelka, Paul R.

This handbook, concerning the Ewe language and culture of Togo, presents classroom activities that require the learner to exchange messages in a way that is appropriate to the cultural context. These activities are presented in 30 lessons containing both basic and supplementary material that deal with situations and topics which will be useful to…

77 FR 26824 - Agency Information Collection; Activity Under OMB Review; Submission of Audit Reports-Part 248

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-07

... RITA 2008-0002] Agency Information Collection; Activity Under OMB Review; Submission of Audit Reports.... SUPPLEMENTARY INFORMATION: OMB Approval No. 2138-0004. Title: Submission of Audit Reports--Part 248. Form No... having an annual audit must file a statement that no such audit has been performed. In lieu of the audit...

Active targeted delivery of immune therapeutics to lymph nodes.

PubMed

Bahmani, Baharak; Vohra, Ishaan; Kamaly, Nazila; Abdi, Reza

2018-02-01

Organ transplantation is a life-saving procedure and the only option for patients with end-organ failure. Immune therapeutics have been key to the success of organ transplantation. However, immune therapeutics are still unable to eliminate graft rejection and their toxicity has been implicated in poorer long-term transplant outcomes. Targeted nanodelivery has the potential to enhance not only the therapeutic index but also the bioavailability of the immune therapeutics. One of the key sites of immune therapeutics delivery is lymph node where the priming of immune cells occur. The focus of this review is on nanomedicine research to develop the targeted delivery of immune therapeutics to lymph nodes for controlling immune activation. As nanomedicine creates its niche in clinical care, it provides novel immunotherapy platforms for transplant recipients. Draining lymph nodes are the primary loci of immune activation and represent a formidable site for delivery of wide variety of immune therapeutics. There have been relentless efforts to improve the properties of nanomedicines, to have in-depth knowledge of antigen and drug loading, and, finally, to explore various routes of passive and active targeted delivery to lymph nodes. The application of nanotechnology principles in the delivery of immune therapeutics to the lymph node has created enormous excitement as a paradigm shifting approach that enables targeted delivery of a gamut of molecules to achieve a desired immune response. Therefore, innovative strategies that improve their efficacy while reducing their toxicity are among the highest unmet needs in transplantation.

Active Immunization with Pneumolysin versus 23-Valent Polysaccharide Vaccine for Streptococcus pneumoniae Keratitis

PubMed Central

Norcross, Erin W.; Sanders, Melissa E.; Moore, Quincy C.; Taylor, Sidney D.; Tullos, Nathan A.; Caston, Rhonda R.; Dixon, Sherrina N.; Nahm, Moon H.; Burton, Robert L.; Thompson, Hilary; McDaniel, Larry S.

2011-01-01

Purpose. The purpose of this study was to determine whether active immunization against pneumolysin (PLY), or polysaccharide capsule, protects against the corneal damage associated with Streptococcus pneumoniae keratitis. Methods. New Zealand White rabbits were actively immunized with Freund's adjuvant mixed with pneumolysin toxoid (ψPLY), Pneumovax 23 (PPSV23; Merck, Whitehouse Station, NJ), or phosphate-buffered saline (PBS), before corneal infection with 105 colony-forming units (CFU) of S. pneumoniae. Serotype-specific rabbit polyclonal antisera or mock antisera were passively administered to rabbits before either intravenous infection with 1011 CFU S. pneumoniae or corneal infection with 105 CFU of S. pneumoniae. Results. After active immunization, clinical scores of corneas of the rabbits immunized with ψPLY and Freund's adjuvant were significantly lower than scores of the rabbits that were mock immunized with PBS and Freund's adjuvant or with PPSV23 and Freund's adjuvant at 48 hours after infection (P ≤ 0.0010), whereas rabbits immunized with PPSV23 and Freund's adjuvant failed to show differences in clinical scores compared with those in mock-immunized rabbits (P = 1.00) at 24 and 48 hours after infection. Antisera from rabbits actively immunized with PPSV23 and Freund's adjuvant were nonopsonizing. Bacterial loads recovered from infected corneas were higher for the ψPLY- and PPSV23-immunized rabbits after infection with WU2, when compared with the mock-immunized rabbits (P ≤ 0.007). Conversely, after infection with K1443, the ψPLY-immunized rabbits had lower bacterial loads than the control rabbits (P = 0.0008). Quantitation of IgG, IgA, and IgM in the sera of ψPLY-immunized rabbits showed high concentrations of PLY-specific IgG. Furthermore, anti-PLY IgG purified from ψPLY-immunized rabbits neutralized the cytolytic effects of PLY on human corneal epithelial cells. Passive administration of serotype-specific antisera capable of opsonizing and killing S. pneumoniae protected against pneumococcal bacteremia (P ≤ 0.05), but not against keratitis (P ≥ 0.476). Conclusions. Active immunization with pneumococcal capsular polysaccharide and Freund's adjuvant fails to produce opsonizing antibodies, and passive administration of serotype specific opsonizing antibodies offers no protection against pneumococcal keratitis in the rabbit, whereas active immunization with the conserved protein virulence factor PLY and Freund's adjuvant is able to reduce corneal inflammation associated with pneumococcal keratitis, but has variable effects on bacterial loads in the cornea. PMID:22039231

Immune-Modulating Perspectives for Low Frequency Electromagnetic Fields in Innate Immunity

PubMed Central

Rosado, Maria Manuela; Simkó, Myrtill; Mattsson, Mats-Olof; Pioli, Claudio

2018-01-01

In recent years, the effects of electromagnetic fields (EMFs) on the immune system have received a considerable interest, not only to investigate possible negative health impact but also to explore the possibility to favorably modulate immune responses. To generate beneficial responses, the immune system should eradicate pathogens while “respecting” the organism and tolerating irrelevant antigens. According to the current view, damage-associated molecules released by infected or injured cells, or secreted by innate immune cells generate danger signals activating an immune response. These signals are also relevant to the subsequent activation of homeostatic mechanisms that control the immune response in pro- or anti-inflammatory reactions, a feature that allows modulation by therapeutic treatments. In the present review, we describe and discuss the effects of extremely low frequency (ELF)-EMF and pulsed EMF on cell signals and factors relevant to the activation of danger signals and innate immunity cells. By discussing the EMF modulating effects on cell functions, we envisage the use of EMF as a therapeutic agent to regulate immune responses associated with wound healing. PMID:29632855

Immune-Modulating Perspectives for Low Frequency Electromagnetic Fields in Innate Immunity.

PubMed

Rosado, Maria Manuela; Simkó, Myrtill; Mattsson, Mats-Olof; Pioli, Claudio

2018-01-01

In recent years, the effects of electromagnetic fields (EMFs) on the immune system have received a considerable interest, not only to investigate possible negative health impact but also to explore the possibility to favorably modulate immune responses. To generate beneficial responses, the immune system should eradicate pathogens while "respecting" the organism and tolerating irrelevant antigens. According to the current view, damage-associated molecules released by infected or injured cells, or secreted by innate immune cells generate danger signals activating an immune response. These signals are also relevant to the subsequent activation of homeostatic mechanisms that control the immune response in pro- or anti-inflammatory reactions, a feature that allows modulation by therapeutic treatments. In the present review, we describe and discuss the effects of extremely low frequency (ELF)-EMF and pulsed EMF on cell signals and factors relevant to the activation of danger signals and innate immunity cells. By discussing the EMF modulating effects on cell functions, we envisage the use of EMF as a therapeutic agent to regulate immune responses associated with wound healing.

Cancer immunoediting by the innate immune system in the absence of adaptive immunity

PubMed Central

O’Sullivan, Timothy; Saddawi-Konefka, Robert; Vermi, William; Koebel, Catherine M.; Arthur, Cora; White, J. Michael; Uppaluri, Ravi; Andrews, Daniel M.; Ngiow, Shin Foong; Teng, Michele W.L.; Smyth, Mark J.; Schreiber, Robert D.

2012-01-01

Cancer immunoediting is the process whereby immune cells protect against cancer formation by sculpting the immunogenicity of developing tumors. Although the full process depends on innate and adaptive immunity, it remains unclear whether innate immunity alone is capable of immunoediting. To determine whether the innate immune system can edit tumor cells in the absence of adaptive immunity, we compared the incidence and immunogenicity of 3′methylcholanthrene-induced sarcomas in syngeneic wild-type, RAG2−/−, and RAG2−/−x γc−/− mice. We found that innate immune cells could manifest cancer immunoediting activity in the absence of adaptive immunity. This activity required natural killer (NK) cells and interferon γ (IFN-γ), which mediated the induction of M1 macrophages. M1 macrophages could be elicited by administration of CD40 agonists, thereby restoring editing activity in RAG2−/−x γc−/− mice. Our results suggest that in the absence of adaptive immunity, NK cell production of IFN-γ induces M1 macrophages, which act as important effectors during cancer immunoediting. PMID:22927549

Network Enabled Capabilities - Grassroots Perspectives

DTIC Science & Technology

2006-10-01

public release, distribution unlimited 13. SUPPLEMENTARY NOTES See also ADM202422., The original document contains color images. 14. ABSTRACT 15...RTO-MP-IST-062 UNCLASSIFIED/UNLIMITED UNCLASSIFIED/UNLIMITED ActiveX component. The other parts of the page depend on the application requirements

78 FR 76391 - Agency Information Collection Activities: Notice of Request for Extension of Currently Approved...

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The Great Boundary Crossing: Perceptions on Training Pharmacists as Supplementary Prescribers in the UK

ERIC Educational Resources Information Center

Tann, Jennifer; Blenkinsopp, Alison; Grime, Janet; Evans, Amanda

2010-01-01

Objective: To explore the perceptions of General Medical Practitioners and pharmacist supplementary prescribers of the training provided for qualification as a pharmacist supplementary prescriber, and the experience of pharmacist supplementary prescribers of subsequent continuing professional development in practice. Design: A qualitative study of…

Author Correction: Biochemical phosphates observed using hyperpolarized 31P in physiological aqueous solutions.

PubMed

Nardi-Schreiber, Atara; Gamliel, Ayelet; Harris, Talia; Sapir, Gal; Sosna, Jacob; Gomori, J Moshe; Katz-Brull, Rachel

2018-05-22

The original version of the Supplementary Information associated with this Article contained an error in Supplementary Figure 2 and Supplementary Figure 5 in which the 31 P NMR spectral lines were missing. The HTML has been updated to include a corrected version of the Supplementary Information.

15 CFR 2.7 - Supplementary regulations.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 15 Commerce and Foreign Trade 1 2011-01-01 2011-01-01 false Supplementary regulations. 2.7 Section... SETTLEMENT OF CLAIMS UNDER THE FEDERAL TORT CLAIMS ACT § 2.7 Supplementary regulations. (a) The Assistant General Counsel for Finance and Litigation may from time to time issue such supplementary regulations or...

34 CFR 300.42 - Supplementary aids and services.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 34 Education 2 2013-07-01 2013-07-01 false Supplementary aids and services. 300.42 Section 300.42... CHILDREN WITH DISABILITIES General Definitions Used in This Part § 300.42 Supplementary aids and services. Supplementary aids and services means aids, services, and other supports that are provided in regular education...

34 CFR 300.42 - Supplementary aids and services.

Code of Federal Regulations, 2012 CFR

2012-07-01

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34 CFR 300.42 - Supplementary aids and services.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 34 Education 2 2014-07-01 2013-07-01 true Supplementary aids and services. 300.42 Section 300.42... CHILDREN WITH DISABILITIES General Definitions Used in This Part § 300.42 Supplementary aids and services. Supplementary aids and services means aids, services, and other supports that are provided in regular education...

20 CFR 416.2098 - Supplementary payment levels.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Supplementary payment levels. 416.2098... Supplementary payment levels. (a) General. For the purpose of determining the combined supplementary/SSI payment levels described in § 416.2097(a) (i.e., the levels that must be provided in any month after March 1983...

Immune activation by medium-chain triglyceride-containing lipid emulsions is not modulated by n-3 lipids or toll-like receptor 4.

PubMed

Olthof, Evelyn D; Gülich, Alexandra F; Renne, Mike F; Landman, Sija; Joosten, Leo A B; Roelofs, Hennie M J; Wanten, Geert J A

2015-10-01

Saturated medium-chain triglycerides (MCT) as part of the parenteral lipid regimen (50% MCT and 50% long chain triglycerides (LCT)) activate the immune system in vitro. Fish oil (FO)-derived n-3 fatty acids (FA) inhibit saturated FA-induced immune activation via a toll-like receptor (TLR)-4 mediated mechanism. We hypothesized that effects of parenteral MCTs on immune cells involve TLR-4 signaling and that these effects are modulated by n-3 FA that are present in FO. To test this hypothesis we assessed effects of addition of various commercially available mixed parenteral lipid emulsions, n-3 FA and of TLR-4 inhibition on MCT-induced human immune cell activation by evaluation of the expression of leukocyte membrane activation markers and reactive oxygen species (ROS) production. All MCT-containing lipid emulsions activated leukocytes by inducing changes in expression of membrane markers and stimulus induced ROS production, whereas MCT-free lipid emulsions lacked this effect. Moreover, addition of n-3 FA to LCT/MCT did not prevent MCT-induced immune activation. TLR-4 inhibitors did not distinctly modulate MCT-induced changes in immune function. Taken together, these findings suggest that leukocyte activation by parenteral MCTs does not involve TLR-4 signaling and is not modulated by n-3 FA in FO-, but is exerted via different signaling pathways. Copyright © 2015 Elsevier Ltd. All rights reserved.

Recommendations of 2nd National Consultative Meeting of Indian Academy of Pediatrics (IAP) on polio eradication and improvement of routine immunization.

PubMed

Vashishtha, Vipin M; Kalra, Ajay; John, T Jacob; Thacker, Naveen; Agarwal, R K

2008-05-01

Persistence of intense wild poliovirus (WPV) transmission, particularly type 3 in northern India necessitated the Indian Academy of Pediatrics (IAP) to convene a National Consultative Meeting to review its earlier recommendations on polio eradication and improvement of routine immunization. More than thirty experts were invited and intense deliberations were held over two days to draw consensus statements on various issues related with polio eradication. To review the ongoing strategy, identify the existing challenges, and suggest modifications to the current strategy for eradication of poliomyelitis in India. IAP reiterates its support to ongoing efforts on polio eradication but demand some flexibility in the strategy. The immediate challenges identified include persistent WPV type 1 transmission in Uttar Pradesh (UP) and Bihar, intense type 3 transmission also in UP and Bihar, and maintaining polio-free status of all other states. Circulating vaccine derived poliovirus (cVDPV), particularly type 2, was identified as a great future threat. Neglect of routine immunization (RI), poor efficacy of oral polio vaccine (OPV), operational issues, and inadequate uptake of OPV in the 2 endemic states are the main reasons of failure to interrupt transmission of WPV 1 and 3. However, for the first time in history the intensity of WPV 1 circulation is very low in western UP. IAP suggests that high-quality, uniform and consistent performance of supplementary immunization activities (SIAs) in all districts of western UP, particularly using mOPV1(monovalent OPV1) should be maintained to avoid reestablishment of circulation of type 1 poliovirus. A judicious mix of mOPV1 and mOPV3, given sequentially or even simultaneously (after validating the efficacies) will be necessary to address the upsurge of WPV3. Re-establishing routine immunization should be the foremost priority. IAP strongly recommends to Government of India (GOI) to take urgent measures to attain coverage of a minimum of 90% against all UIP antigens in all the states by the end of 2008. In view of the need to simultaneously raise immunity levels to protect against WPVs 1, 3 and cVDPV2, IPV may be given immediate consideration as an additional tool. IPV will be essential in the postWPVeradication phase; it can play a useful role even in the current WPV eradication phase. IAP urges the GOI to urgently sort out various issues associated with implementation of the proposal to use IPV. More transparency is needed on cases of vaccine associated paralytic poliomyelitis (VAPP). Further improvement in stool collection rates is also warranted to minimize the tally of compatible cases. IAP urges the social mobilization network to address the issues of waning interest and shifting focus and negative media coverage. Alternate tactics like reduced numbers of SIAs applied in the low transmission season, along with IPVDTP combination vaccine in RI can also be considered. IAP believes it will be risky to stop vaccination against poliomyelitis in postWPV eradication phase. The best option is to gradually introduce IPV starting now, so that a switch to IPV following high-performance national immunization days (NIDs) can be made to ensure sustained high immunity against all polioviruses, wild and vaccine derived. IAP requests the global polio eradication initiative (GPEI) to continue relevant research to inform on various aspects related to polio eradication, defined as zero incidence of any poliovirus infection. IAP also urges GOI to take immediate measures for improvement of environmental sanitation.

An Extracellular Subtilase Switch for Immune Priming in Arabidopsis

PubMed Central

Mauch-Mani, Brigitte; Gil, Ma José; Vera, Pablo

2013-01-01

In higher eukaryotes, induced resistance associates with acquisition of a priming state of the cells for a more effective activation of innate immunity; however, the nature of the components for mounting this type of immunological memory is not well known. We identified an extracellular subtilase from Arabidopsis, SBT3.3, the overexpression of which enhances innate immune responses while the loss of function compromises them. SBT3.3 expression initiates a durable autoinduction mechanism that promotes chromatin remodeling and activates a salicylic acid(SA)-dependent mechanism of priming of defense genes for amplified response. Moreover, SBT3.3 expression-sensitized plants for enhanced expression of the OXI1 kinase gene and activation of MAP kinases following pathogen attack, providing additional clues for the regulation of immune priming by SBT3.3. Conversely, in sbt3.3 mutant plants pathogen-mediated induction of SA-related defense gene expression is drastically reduced and activation of MAP kinases inhibited. Moreover, chromatin remodeling of defense-related genes normally associated with activation of an immune priming response appear inhibited in sbt3.3 plants, further indicating the importance of the extracellular SBT3.3 subtilase in the establishment of immune priming. Our results also point to an epigenetic control in the regulation of plant immunity, since SBT3.3 is up-regulated and priming activated when epigenetic control is impeded. SBT3.3 represents a new regulator of primed immunity. PMID:23818851

An extracellular subtilase switch for immune priming in Arabidopsis.

PubMed

Ramírez, Vicente; López, Ana; Mauch-Mani, Brigitte; Gil, Ma José; Vera, Pablo

2013-01-01

In higher eukaryotes, induced resistance associates with acquisition of a priming state of the cells for a more effective activation of innate immunity; however, the nature of the components for mounting this type of immunological memory is not well known. We identified an extracellular subtilase from Arabidopsis, SBT3.3, the overexpression of which enhances innate immune responses while the loss of function compromises them. SBT3.3 expression initiates a durable autoinduction mechanism that promotes chromatin remodeling and activates a salicylic acid(SA)-dependent mechanism of priming of defense genes for amplified response. Moreover, SBT3.3 expression-sensitized plants for enhanced expression of the OXI1 kinase gene and activation of MAP kinases following pathogen attack, providing additional clues for the regulation of immune priming by SBT3.3. Conversely, in sbt3.3 mutant plants pathogen-mediated induction of SA-related defense gene expression is drastically reduced and activation of MAP kinases inhibited. Moreover, chromatin remodeling of defense-related genes normally associated with activation of an immune priming response appear inhibited in sbt3.3 plants, further indicating the importance of the extracellular SBT3.3 subtilase in the establishment of immune priming. Our results also point to an epigenetic control in the regulation of plant immunity, since SBT3.3 is up-regulated and priming activated when epigenetic control is impeded. SBT3.3 represents a new regulator of primed immunity.

Plant immunity triggered by microbial molecular signatures.

PubMed

Zhang, Jie; Zhou, Jian-Min

2010-09-01

Pathogen/microbe-associated molecular patterns (PAMPs/MAMPs) are recognized by host cell surface-localized pattern-recognition receptors (PRRs) to activate plant immunity. PAMP-triggered immunity (PTI) constitutes the first layer of plant immunity that restricts pathogen proliferation. PTI signaling components often are targeted by various Pseudomonas syringae virulence effector proteins, resulting in diminished plant defenses and increased bacterial virulence. Some of the proteins targeted by pathogen effectors have evolved to sense the effector activity by associating with cytoplasmic immune receptors classically known as resistance proteins. This allows plants to activate a second layer of immunity termed effector-triggered immunity (ETI). Recent studies on PTI regulation and P. syringae effector targets have uncovered new components in PTI signaling. Although MAP kinase (MAPK) cascades have been considered crucial for PTI, emerging evidence indicates that a MAPK-independent pathway also plays an important role in PTI signaling.

Age-specific strategies for immunization reminders and recalls: a registry-based randomized trial.

PubMed

Dombkowski, Kevin J; Costello, Lauren E; Harrington, Laura B; Dong, Shiming; Kolasa, Maureen; Clark, Sarah J

2014-07-01

Although previous studies have found reminder/recall to be effective in increasing immunization rates, little guidance exists regarding the specific ages at which it is optimal to send reminder/recall notices. To assess the relative effectiveness of centralized reminder/recall strategies targeting age-specific vaccination milestones among children in urban areas during June 2008-June 2009. Three reminder/recall strategies used capabilities of the Michigan Care Improvement Registry (MCIR), a statewide immunization information system: a 7-month recall strategy, a 12-month reminder strategy, and a 19-month recall strategy. Eligible children were randomized to notification (intervention) or no notification groups (control). Primary study outcomes included MCIR-recorded immunization activity (administration of ≥1 new dose, entry of ≥1 historic dose, entry of immunization waiver) within 60 days following each notification cycle. A total of 10,175 children were included: 2,072 for the 7-month recall, 3,502 for the 12-month reminder, and 4,601 for the 19-month recall. Immunization activity was similar between notification versus no notification groups at both 7 and 12 months. Significantly more 19-month-old children in the recall group (26%) had immunization activity compared to their counterparts who did not receive a recall notification (19%). Although recall notifications can positively affect immunization activity, the effect may vary by targeted age group. Many 7- and 12-month-olds had immunization activity following reminder/recall; however, levels of activity were similar irrespective of notification, suggesting that these groups were likely to receive medical care or immunization services without prompting. Copyright © 2014 American Journal of Preventive Medicine. All rights reserved.

22 CFR 40.25 - Certain aliens involved in serious criminal activity who have asserted immunity from prosecution...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Certain aliens involved in serious criminal activity who have asserted immunity from prosecution. [Reserved] 40.25 Section 40.25 Foreign Relations... Certain aliens involved in serious criminal activity who have asserted immunity from prosecution...

22 CFR 40.25 - Certain aliens involved in serious criminal activity who have asserted immunity from prosecution...

Code of Federal Regulations, 2013 CFR

2013-04-01

... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Certain aliens involved in serious criminal activity who have asserted immunity from prosecution. [Reserved] 40.25 Section 40.25 Foreign Relations... Certain aliens involved in serious criminal activity who have asserted immunity from prosecution...

22 CFR 40.25 - Certain aliens involved in serious criminal activity who have asserted immunity from prosecution...

Code of Federal Regulations, 2011 CFR

2011-04-01

... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Certain aliens involved in serious criminal activity who have asserted immunity from prosecution. [Reserved] 40.25 Section 40.25 Foreign Relations... Certain aliens involved in serious criminal activity who have asserted immunity from prosecution...

22 CFR 40.25 - Certain aliens involved in serious criminal activity who have asserted immunity from prosecution...

Code of Federal Regulations, 2012 CFR

2012-04-01

... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Certain aliens involved in serious criminal activity who have asserted immunity from prosecution. [Reserved] 40.25 Section 40.25 Foreign Relations... Certain aliens involved in serious criminal activity who have asserted immunity from prosecution...

22 CFR 40.25 - Certain aliens involved in serious criminal activity who have asserted immunity from prosecution...

Code of Federal Regulations, 2014 CFR

2014-04-01

... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Certain aliens involved in serious criminal activity who have asserted immunity from prosecution. [Reserved] 40.25 Section 40.25 Foreign Relations... Certain aliens involved in serious criminal activity who have asserted immunity from prosecution...

Cytosolic nucleic acid sensors and innate immune regulation.

PubMed

Ori, Daisuke; Murase, Motoya; Kawai, Taro

2017-03-04

During viral and bacterial infections, pathogen-derived cytosolic nucleic acids are recognized by the intracellular RNA sensors retinoic acid-inducible gene I and melanoma-differentiated gene 5 and intracellular DNA sensors, including cyclic-di-GMP-AMP synthase, absent in melanoma 2, interferon (IFN)-gamma inducible protein 16, polymerase III, and so on. Binding of intracellular nucleic acids to these sensors activates downstream signaling cascades, resulting in the production of type I IFNs and pro-inflammatory cytokines to induce appropriate systematic immune responses. While these sensors also recognize endogenous nucleic acids and activate immune responses, they can discriminate between self- and non-self-nucleic acids. However, dysfunction of these sensors or failure of regulatory mechanisms causes aberrant activation of immune response and autoimmune disorders. In this review, we focus on how intracellular immune sensors recognize exogenous nucleic acids and activate the innate immune system, and furthermore, how autoimmune diseases result from dysfunction of these sensors.

Innate Immune Regulations and Liver Ischemia Reperfusion Injury

PubMed Central

Lu, Ling; Zhou, Haoming; Ni, Ming; Wang, Xuehao; Busuttil, Ronald; Kupiec-Weglinski, Jerzy; Zhai, Yuan

2016-01-01

Liver ischemia reperfusion activates innate immune system to drive the full development of inflammatory hepatocellular injury. Damage-associated molecular patterns (DAMPs) stimulate myeloid and dendritic cells via pattern recognition receptors (PRRs) to initiate the immune response. Complex intracellular signaling network transduces inflammatory signaling to regulate both innate immune cell activation and parenchymal cell death. Recent studies have revealed that DAMPs may trigger not only proinflammatory, but also immune regulatory responses by activating different PRRs or distinctive intracellular signaling pathways or in special cell populations. Additionally, tissue injury milieu activates PRR-independent receptors which also regulate inflammatory disease processes. Thus, the innate immune mechanism of liver IRI involves diverse molecular and cellular interactions, subjected to both endogenous and exogenous regulation in different cells. A better understanding of these complicated regulatory pathways/network is imperative for us in designing safe and effective therapeutic strategy to ameliorate liver IRI in patients. PMID:27861288

Teachers' Guide for Aviation Education. For Use in Grades Two through Six. Communication Arts, Science, Social Studies, Health, Career Education.

ERIC Educational Resources Information Center

Federal Aviation Administration (DOT), Washington, DC.

Provided in this guide is an array of supplementary activities centered around the topic of aviation. Although the activities are designed for students in grades 2 to 6, teachers are encouraged to adapt them to other grade levels or to the individual abilities of students. The activities are presented in five parts by subject area and within these…

Experimentally-induced immune activation in natural hosts of SIV induces significant increases in viral replication and CD4+ T cell depletion

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

Ribeiro, Ruy M

2008-01-01

Chronically SIVagm-infected African green monkeys (AGMs) have a remarkably stable non-pathogenic disease course, with levels of immune activation in chronic SIVagm infection similar to those observed in uninfected monkeys and stable viral loads (VLs) for long periods of time. In vivo administration of lipopolysaccharide (LPS) or an IL-2/diphtheria toxin fusion protein (Ontak) to chronically SIVagm-infected AGMs triggered increases in immune activation and subsequently of viral replication and depletion of intestinal CD4{sup +} T cells. Our study indicates that circulating microbial products can increase viral replication by inducing immune activation and increasing the number of viral target cells, thus demonstrating thatmore » immune activation and T cell prolifeation are key factors in AIDS pathogenesis.« less

Annual Progress Report - Fiscal Year 1982

DTIC Science & Technology

1982-10-01

activity . A published method developed in our laboratory for determining tne antibacterial activity of mouse peritoneal phagocytes in vivo (1) has been...EDITOR’S NOTE This FY 1982 Annual Progress report is a general review of research activities of the U. S. Army Medical Research Institute of Infectious...years earlier. Passive immunization, active immunization using killed or living attenuated whole agent, or immunization with sub-unit antigens achieved

Surveying the Views of Pupils Attending Supplementary Schools in England

ERIC Educational Resources Information Center

Strand, Steve

2007-01-01

Background: Supplementary schooling broadly refers to extra schooling organized by and for particular ethnic groups outside of mainstream provision. Purpose: This is the first study to systematically explore the attitudes of pupils attending supplementary schools in England and the largest ever UK study of supplementary schools and their pupils.…

System-level determinants of immunization coverage disparities among health districts in Burkina Faso: a multiple case study.

PubMed

Haddad, Slim; Bicaba, Abel; Feletto, Marta; Taminy, Elie; Kabore, Moussa; Ouédraogo, Boubacar; Contreras, Gisèle; Larocque, Renée; Fournier, Pierre

2009-10-14

Despite rapid and tangible progress in vaccine coverage and in premature mortality rates registered in sub-Saharan Africa, inequities to access remain firmly entrenched, large pockets of low vaccination coverage persist, and coverage often varies considerably across regions, districts, and health facilities' areas of responsibility. This paper focuses on system-related factors that can explain disparities in immunization coverage among districts in Burkina Faso. A multiple-case study was conducted of six districts representative of different immunization trends and overall performance. A participative process that involved local experts and key actors led to a focus on key factors that could possibly determine the efficiency and efficacy of district vaccination services: occurrence of disease outbreaks and immunization days, overall district management performance, resources available for vaccination services, and institutional elements. The methodology, geared toward reconstructing the evolution of vaccine services performance from 2000 to 2006, is based on data from documents and from individual and group interviews in each of the six health districts. The process of interpreting results brought together the field personnel and the research team. The districts that perform best are those that assemble a set of favourable conditions. However, the leadership of the district medical officer (DMO) appears to be the main conduit and the rallying point for these conditions. Typically, strong leadership that is recognized by the field teams ensures smooth operation of the vaccination services, promotes the emergence of new initiatives and offers some protection against risks related to outbreaks of epidemics or supplementary activities that can hinder routine functioning. The same is true for the ability of nurse managers and their teams to cope with new situations (epidemics, shortages of certain stocks). The discourse on factors that determine the performance or breakdown of local health care systems in lower and middle income countries remains largely concentrated on technocratic and financial considerations, targeting institutional reforms, availability of resources, or accessibility of health services. The leadership role of those responsible for the district, and more broadly, of those we label "the human factor", in the performance of local health care systems is mentioned only marginally. This study shows that strong and committed leadership promotes an effective mobilization of teams and creates the conditions for good performance in districts, even when they have only limited access to supports provided by external partners. ABSTRACT IN FRENCH: See the full article online for a translation of this abstract in French.

Use of Dedicated Mobile Teams and Polio Volunteer Community Mobilizers to Increase Access to Zero-Dose Oral Poliovirus Vaccine and Routine Childhood Immunizations in Settlements at High Risk for Polio Transmission in Northern Nigeria.

PubMed

Ongwae, Kennedy M; Bawa, Samuel B; Shuaib, Faisal; Braka, Fiona; Corkum, Melissa; Isa, Hammanyero K

2017-07-01

The Polio Eradication Initiative in Nigeria, which started >20 years ago, faced many challenges, including initial denial, resistance from communities, and prolonged regional safety concerns. These challenges led into the structuring of the response including the development of the National Emergency Action Plan, improved partner coordination and government engagement, and the establishment of a Polio Emergency Operations Centre. Although monthly supplementary immunization activities (SIAs) continued, the targeting of settlements at high risk for polio transmission with routine immunization (RI) and other selected primary healthcare (PHC) services using dedicated mobile teams and volunteer community mobilizers (VCMs) became a key strategy for interrupting polio transmission in the high-risk areas. These efforts could have contributed to the wild poliovirus-free 2-year period between 24 July 2014 and 11 August 2016, when 2 cases of the virus were reported from Borno State, Northern Nigeria. A narrative analysis of polio-related program and other official documents was conducted to identify the relevant human resources and their role in the Polio Eradication Initiative and in RI. The data used in the article was obtained from United Nations Children's Fund (UNICEF) and World Health Organization project reports and a draft evaluation report of the dedicated mobile teams approach in Northern Nigeria. The data from 6 of the states that commenced the provision of polio, RI, and other selected PHC services using the dedicated mobile teams approach in 2014 showed an overall increase in the percentage of children aged 12-23 months in the settlements at high risk for polio transmission with a RI card seen, from 23% to 56%, and an overall increase in fully immunized children aged 12-23 months, from 19% to 55%. The number of newborns given the first dose of oral poliovirus vaccine (OPV) according to the RI schedule and the number of children given zero-dose OPV with the assistance of the VCMs similarly increased between 2013 and 2015. In 2015, VCMs helped track 167 092 newborns and also linked 156 537 infants aged <1 year to RI services in the 6 states. The analysis illustrates that polio personnel in Northern Nigeria are used in increasing access to zero-dose OPV, RI, and selected PHC services. The increase in the services generated represented the increasing role of the dedicated mobile teams and polio VCMs in strengthening RI. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Use of Dedicated Mobile Teams and Polio Volunteer Community Mobilizers to Increase Access to Zero-Dose Oral Poliovirus Vaccine and Routine Childhood Immunizations in Settlements at High Risk for Polio Transmission in Northern Nigeria

PubMed Central

Bawa, Samuel B.; Shuaib, Faisal; Braka, Fiona; Corkum, Melissa; Isa, Hammanyero K.

2017-01-01

Abstract Background The Polio Eradication Initiative in Nigeria, which started >20 years ago, faced many challenges, including initial denial, resistance from communities, and prolonged regional safety concerns. These challenges led into the structuring of the response including the development of the National Emergency Action Plan, improved partner coordination and government engagement, and the establishment of a Polio Emergency Operations Centre. Although monthly supplementary immunization activities (SIAs) continued, the targeting of settlements at high risk for polio transmission with routine immunization (RI) and other selected primary healthcare (PHC) services using dedicated mobile teams and volunteer community mobilizers (VCMs) became a key strategy for interrupting polio transmission in the high-risk areas. These efforts could have contributed to the wild poliovirus–free 2-year period between 24 July 2014 and 11 August 2016, when 2 cases of the virus were reported from Borno State, Northern Nigeria. Methods A narrative analysis of polio-related program and other official documents was conducted to identify the relevant human resources and their role in the Polio Eradication Initiative and in RI. The data used in the article was obtained from United Nations Children's Fund (UNICEF) and World Health Organization project reports and a draft evaluation report of the dedicated mobile teams approach in Northern Nigeria. Results The data from 6 of the states that commenced the provision of polio, RI, and other selected PHC services using the dedicated mobile teams approach in 2014 showed an overall increase in the percentage of children aged 12–23 months in the settlements at high risk for polio transmission with a RI card seen, from 23% to 56%, and an overall increase in fully immunized children aged 12–23 months, from 19% to 55%. The number of newborns given the first dose of oral poliovirus vaccine (OPV) according to the RI schedule and the number of children given zero-dose OPV with the assistance of the VCMs similarly increased between 2013 and 2015. In 2015, VCMs helped track 167 092 newborns and also linked 156 537 infants aged <1 year to RI services in the 6 states. Conclusions The analysis illustrates that polio personnel in Northern Nigeria are used in increasing access to zero-dose OPV, RI, and selected PHC services. The increase in the services generated represented the increasing role of the dedicated mobile teams and polio VCMs in strengthening RI. PMID:28838155

The immune complex CTA1-DD/IgG adjuvant specifically targets connective tissue mast cells through FcγRIIIA and augments anti-HPV immunity after nasal immunization.

PubMed

Fang, Y; Zhang, T; Lidell, L; Xu, X; Lycke, N; Xiang, Z

2013-11-01

We have previously reported that CTA1-DD/IgG immune complexes augment antibody responses in a mast cell-dependent manner following intranasal (IN) immunizations. However, from a safety perspective, mast cell activation could preclude clinical use. Therefore, we have extended these studies and demonstrate that CTA1-DD/IgG immune complexes administered IN did not trigger an anaphylactic reaction. Importantly, CTA1-DD/IgE immune complexes did not activate mast cells. Interestingly, only connective tissue, but not mucosal, mast cells could be activated by CTA1-DD/IgG immune complexes. This effect was mediated by FcγRIIIA, only expressed on connective tissue mast cells, and found in the nasal submucosa. FcγRIIIA-deficient mice had compromised responses to immunization adjuvanted by CTA1-DD/IgG. Proof-of-concept studies revealed that IN immunized mice with human papillomavirus (HPV) type 16 L1 virus-like particles (VLP) and CTA1-DD/IgG immune complexes demonstrated strong and sustained specific antibody titers in serum and vaginal secretions. From a mast cell perspective, CTA1-DD/IgG immune complexes appear to be safe and effective mucosal adjuvants.

Passive immunization of mice pups through oral immunization of dams with a plant-derived vaccine.

PubMed

Walmsley, Amanda M; Kirk, Dwayne D; Mason, Hugh S

2003-03-03

Passive immunization plays an important role in protecting young mammals against pathogens before the maturation of their own immune systems. Although many reports have shown active immunization of animals and human through the use of plant-derived vaccines, only one report has given evidence of passive immunization of offspring through oral immunization of parents using plant-derived vaccines. In this case, a challenge alone provided the evidence of passive immunization and the mechanism through which this occurred was not investigated. This report describes the first step in elucidating the mechanism of passive immunization of offspring through actively immunizing the female parent through an orally delivered, plant-derived vaccine. The authors found passive immunization of offspring was caused by transfer of antigen-specific IgG through either transplacental transfer or ingesting colostrum. Future studies will investigate the roles of transplacental antibody transfer and ingesting colostrum in passive immunization and the possible involvement of IgA in this immunization route.

Immune response in a wild bird is predicted by oxidative status, but does not cause oxidative stress.

PubMed

Cram, Dominic L; Blount, Jonathan D; York, Jennifer E; Young, Andrew J

2015-01-01

The immune system provides vital protection against pathogens, but extensive evidence suggests that mounting immune responses can entail survival and fecundity costs. The physiological mechanisms that underpin these costs remain poorly understood, despite their potentially important role in shaping life-histories. Recent studies involving laboratory models highlight the possibility that oxidative stress could mediate these costs, as immune-activation can increase the production of reactive oxygen species leading to oxidative stress. However, this hypothesis has rarely been tested in free-ranging wild populations, where natural oxidative statuses and compensatory strategies may moderate immune responses and their impacts on oxidative status. Furthermore, the possibility that individuals scale their immune responses according to their oxidative status, conceivably to mitigate such costs, remains virtually unexplored. Here, we experimentally investigate the effects of a phytohaemagglutinin (PHA) immune-challenge on oxidative status in wild male and female white-browed sparrow weavers, Plocepasser mahali. We also establish whether baseline oxidative status prior to challenge predicts the scale of the immune responses. Contrary to previous work on captive animals, our findings suggest that PHA-induced immune-activation does not elicit oxidative stress. Compared with controls (n = 25 birds), PHA-injected birds (n = 27 birds) showed no evidence of a differential change in markers of oxidative damage or enzymatic and non-enzymatic antioxidant protection 24 hours after challenge. We did, however, find that the activity of a key antioxidant enzyme (superoxide dismutase, SOD) prior to immune-activation predicted the scale of the resulting swelling: birds with stronger initial SOD activity subsequently produced smaller swellings. Our findings (i) suggest that wild birds can mount immune responses without suffering from systemic oxidative stress, and (ii) lend support to biomedical evidence that baseline oxidative status can impact the scale of immune responses; a possibility not yet recognised in ecological studies of immunity.

Immune Response in a Wild Bird Is Predicted by Oxidative Status, but Does Not Cause Oxidative Stress

PubMed Central

Cram, Dominic L.; Blount, Jonathan D.; York, Jennifer E.; Young, Andrew J.

2015-01-01

The immune system provides vital protection against pathogens, but extensive evidence suggests that mounting immune responses can entail survival and fecundity costs. The physiological mechanisms that underpin these costs remain poorly understood, despite their potentially important role in shaping life-histories. Recent studies involving laboratory models highlight the possibility that oxidative stress could mediate these costs, as immune-activation can increase the production of reactive oxygen species leading to oxidative stress. However, this hypothesis has rarely been tested in free-ranging wild populations, where natural oxidative statuses and compensatory strategies may moderate immune responses and their impacts on oxidative status. Furthermore, the possibility that individuals scale their immune responses according to their oxidative status, conceivably to mitigate such costs, remains virtually unexplored. Here, we experimentally investigate the effects of a phytohaemagglutinin (PHA) immune-challenge on oxidative status in wild male and female white-browed sparrow weavers, Plocepasser mahali. We also establish whether baseline oxidative status prior to challenge predicts the scale of the immune responses. Contrary to previous work on captive animals, our findings suggest that PHA-induced immune-activation does not elicit oxidative stress. Compared with controls (n = 25 birds), PHA-injected birds (n = 27 birds) showed no evidence of a differential change in markers of oxidative damage or enzymatic and non-enzymatic antioxidant protection 24 hours after challenge. We did, however, find that the activity of a key antioxidant enzyme (superoxide dismutase, SOD) prior to immune-activation predicted the scale of the resulting swelling: birds with stronger initial SOD activity subsequently produced smaller swellings. Our findings (i) suggest that wild birds can mount immune responses without suffering from systemic oxidative stress, and (ii) lend support to biomedical evidence that baseline oxidative status can impact the scale of immune responses; a possibility not yet recognised in ecological studies of immunity. PMID:25815888

Hypothalamic-Pituitary-Adrenal Hypofunction in Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS) as a Consequence of Activated Immune-Inflammatory and Oxidative and Nitrosative Pathways.

PubMed

Morris, Gerwyn; Anderson, George; Maes, Michael

2017-11-01

There is evidence that immune-inflammatory and oxidative and nitrosative stress (O&NS) pathways play a role in the pathophysiology of myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS). There is also evidence that these neuroimmune diseases are accompanied by hypothalamic-pituitary-adrenal (HPA) axis hypoactivity as indicated by lowered baseline glucocorticoid levels. This paper aims to review the bidirectional communications between immune-inflammatory and O&NS pathways and HPA axis hypoactivity in ME/CFS, considering two possibilities: (a) Activation of immune-inflammatory pathways is secondary to HPA axis hypofunction via attenuated negative feedback mechanisms, or (b) chronic activated immune-inflammatory and O&NS pathways play a causative role in HPA axis hypoactivity. Electronic databases, i.e., PUBMED, Scopus, and Google Scholar, were used as sources for this narrative review by using keywords CFS, ME, cortisol, ACTH, CRH, HPA axis, glucocorticoid receptor, cytokines, immune, immunity, inflammation, and O&NS. Findings show that activation of immune-inflammatory and O&NS pathways in ME/CFS are probably not secondary to HPA axis hypoactivity and that activation of these pathways may underpin HPA axis hypofunction in ME/CFS. Mechanistic explanations comprise increased levels of tumor necrosis factor-α, T regulatory responses with elevated levels of interleukin-10 and transforming growth factor-β, elevated levels of nitric oxide, and viral/bacterial-mediated mechanisms. HPA axis hypoactivity in ME/CFS is most likely a consequence and not a cause of a wide variety of activated immune-inflammatory and O&NS pathways in that illness.

Trans-generational Immune Priming Protects the Eggs Only against Gram-Positive Bacteria in the Mealworm Beetle

PubMed Central

Dubuffet, Aurore; Zanchi, Caroline; Boutet, Gwendoline; Moreau, Jérôme; Teixeira, Maria; Moret, Yannick

2015-01-01

In many vertebrates and invertebrates, offspring whose mothers have been exposed to pathogens can exhibit increased levels of immune activity and/or increased survival to infection. Such phenomena, called “Trans-generational immune priming” (TGIP) are expected to provide immune protection to the offspring. As the offspring and their mother may share the same environment, and consequently similar microbial threats, we expect the immune molecules present in the progeny to be specific to the microbes that immune challenged the mother. We provide evidence in the mealworm beetle Tenebrio molitor that the antimicrobial activity found in the eggs is only active against Gram-positive bacteria, even when females were exposed to Gram-negative bacteria or fungi. Fungi were weak inducers of TGIP while we obtained similar levels of anti-Gram-positive activity using different bacteria for the maternal challenge. Furthermore, we have identified an antibacterial peptide from the defensin family, the tenecin 1, which spectrum of activity is exclusively directed toward Gram-positive bacteria as potential contributor to this antimicrobial activity. We conclude that maternal transfer of antimicrobial activity in the eggs of T. molitor might have evolved from persistent Gram-positive bacterial pathogens between insect generations. PMID:26430786

Dual regulation of gene expression mediated by extended MAPK activation and salicylic acid contributes to robust innate immunity in Arabidopsis thaliana.

PubMed

Tsuda, Kenichi; Mine, Akira; Bethke, Gerit; Igarashi, Daisuke; Botanga, Christopher J; Tsuda, Yayoi; Glazebrook, Jane; Sato, Masanao; Katagiri, Fumiaki

2013-01-01

Network robustness is a crucial property of the plant immune signaling network because pathogens are under a strong selection pressure to perturb plant network components to dampen plant immune responses. Nevertheless, modulation of network robustness is an area of network biology that has rarely been explored. While two modes of plant immunity, Effector-Triggered Immunity (ETI) and Pattern-Triggered Immunity (PTI), extensively share signaling machinery, the network output is much more robust against perturbations during ETI than PTI, suggesting modulation of network robustness. Here, we report a molecular mechanism underlying the modulation of the network robustness in Arabidopsis thaliana. The salicylic acid (SA) signaling sector regulates a major portion of the plant immune response and is important in immunity against biotrophic and hemibiotrophic pathogens. In Arabidopsis, SA signaling was required for the proper regulation of the vast majority of SA-responsive genes during PTI. However, during ETI, regulation of most SA-responsive genes, including the canonical SA marker gene PR1, could be controlled by SA-independent mechanisms as well as by SA. The activation of the two immune-related MAPKs, MPK3 and MPK6, persisted for several hours during ETI but less than one hour during PTI. Sustained MAPK activation was sufficient to confer SA-independent regulation of most SA-responsive genes. Furthermore, the MPK3 and SA signaling sectors were compensatory to each other for inhibition of bacterial growth as well as for PR1 expression during ETI. These results indicate that the duration of the MAPK activation is a critical determinant for modulation of robustness of the immune signaling network. Our findings with the plant immune signaling network imply that the robustness level of a biological network can be modulated by the activities of network components.

Protective antitumor activity through dendritic cell immunization is mediated by NK cell as well as CTL activation.

PubMed

Kim, K D; Kim, J K; Kim, S J; Choe, I S; Chung, T H; Choe, Y K; Lim, J S

1999-08-01

Dendritic cells (DCs) are potent professional antigen-presenting cells (APC) capable of inducing the primary T cell response to antigen. Although tumor cells express target antigens, they are incapable of stimulating a tumor-specific immune response due to a defect in the costimulatory signal that is required for optimal activation of T cells. In this work, we describe a new approach using tumor-DC coculture to improve the antigen presenting capacity of tumor cells, which does not require a source of tumor-associated antigen. Immunization of a weakly immunogenic and progressive tumor cocultured with bone marrow-derived DCs generated an effective tumor vaccine. Immunization with the cocultured DCs was able to induce complete protective immunity against tumor challenges and was effective for the induction of tumor-specific CTL (cytotoxic T lymphocyte) activity. Furthermore, high NK cell activity was observed in mice in which tumors were rejected. In addition, immunization with tumor-pulsed DCs induced delayed tumor growth, but not tumor eradication in tumor-bearing mice. Our results demonstrate that coculture of DCs with tumors generated antitumor immunity due to the NK cell activation as well as tumor-specific T cell. This approach would be useful for designing tumor vaccines using DCs when the information about tumor antigens is limited.

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Early infections by myxoma virus of young rabbits (Oryctolagus cuniculus) protected by maternal antibodies activate their immune system and enhance herd immunity in wild populations.

PubMed

Marchandeau, Stéphane; Pontier, Dominique; Guitton, Jean-Sébastien; Letty, Jérôme; Fouchet, David; Aubineau, Jacky; Berger, Francis; Léonard, Yves; Roobrouck, Alain; Gelfi, Jacqueline; Peralta, Brigitte; Bertagnoli, Stéphane

2014-03-04

The role of maternal antibodies is to protect newborns against acute early infection by pathogens. This can be achieved either by preventing any infection or by allowing attenuated infections associated with activation of the immune system, the two strategies being based on different cost/benefit ratios. We carried out an epidemiological survey of myxomatosis, which is a highly lethal infectious disease, in two distant wild populations of rabbits to describe the epidemiological pattern of the disease. Detection of specific IgM and IgG enabled us to describe the pattern of immunity. We show that maternal immunity attenuates early infection of juveniles and enables activation of their immune system. This mechanism associated with steady circulation of the myxoma virus in both populations, which induces frequent reinfections of immune rabbits, leads to the maintenance of high immunity levels within populations. Thus, myxomatosis has a low impact, with most infections being asymptomatic. This work shows that infection of young rabbits protected by maternal antibodies induces attenuated disease and activates their immune system. This may play a major role in reducing the impact of a highly lethal disease when ecological conditions enable permanent circulation of the pathogen.

Early infections by myxoma virus of young rabbits (Oryctolagus cuniculus) protected by maternal antibodies activate their immune system and enhance herd immunity in wild populations

PubMed Central

2014-01-01

The role of maternal antibodies is to protect newborns against acute early infection by pathogens. This can be achieved either by preventing any infection or by allowing attenuated infections associated with activation of the immune system, the two strategies being based on different cost/benefit ratios. We carried out an epidemiological survey of myxomatosis, which is a highly lethal infectious disease, in two distant wild populations of rabbits to describe the epidemiological pattern of the disease. Detection of specific IgM and IgG enabled us to describe the pattern of immunity. We show that maternal immunity attenuates early infection of juveniles and enables activation of their immune system. This mechanism associated with steady circulation of the myxoma virus in both populations, which induces frequent reinfections of immune rabbits, leads to the maintenance of high immunity levels within populations. Thus, myxomatosis has a low impact, with most infections being asymptomatic. This work shows that infection of young rabbits protected by maternal antibodies induces attenuated disease and activates their immune system. This may play a major role in reducing the impact of a highly lethal disease when ecological conditions enable permanent circulation of the pathogen. PMID:24589193

An overiew of non medical prescribing across one strategic health authority: a questionnaire survey.

PubMed

Courtenay, Molly; Carey, Nicola; Stenner, Karen

2012-06-01

Over 50,000 non-medical healthcare professionals across the United Kingdom now have prescribing capabilities. However, there is no evidence available with regards to the extent to which non-medical prescribing (NMP) has been implemented within organisations across a strategic health authority (SHA). The aim of the study was to provide an overview of NMP across one SHA. NMP leads across one SHA were asked to supply the email addresses of NMPs within their organisation. One thousand five hundred and eighty five NMPs were contacted and invited to complete an on-line descriptive questionnaire survey, 883 (55.7%) participants responded. Data was collected between November 2010 and February 2011. The majority of NMPs were based in primary care and worked in a team of 2 or more. Nurse independent supplementary prescribers were the largest group (590 or 68.6%) compared to community practitioner prescribers (198 or 22.4%), pharmacist independent supplementary prescribers (35 or 4%), and allied health professionals and optometrist independent and/or supplementary prescribers (8 or 0.9%). Nearly all (over 90%) of nurse independent supplementary prescribers prescribed medicines. Approximately a third of pharmacist independent supplementary prescribers, allied health professionals, and community practitioner prescribers did not prescribe. Clinical governance procedures were largely in place, although fewer procedures were reported by community practitioner prescribers. General practice nurses prescribed the most items. Factors affecting prescribing practice were: employer, the level of experience prior to becoming a non-medical prescriber, existence of governance procedures and support for the prescribing role (p < 0.001). NMP in this strategic health authority reflects national development of this relatively new role in that the majority of non-medical prescribers were nurses based in primary care, with fewer pharmacist and allied health professional prescribers. This workforce is contributing to medicines management activities in a range of care settings. If non-medical prescibers are to maximise their contribution, robust governance and support from healthcare organisations is essential. The continued use of supplementary prescribing is questionable if maximum efficiency is sought. These are important points that need to be considered by those responsible for developing non-medical prescribing in the United Kingdom and other countries around the world.

Inbred decorated crickets exhibit higher measures of macroparasitic immunity than outbred individuals.

PubMed

Gershman, S N; Barnett, C A; Pettinger, A M; Weddle, C B; Hunt, J; Sakaluk, S K

2010-09-01

Inbreeding is assumed to have negative effects on fitness, including the reduced ability to withstand immune challenges. We examined the immunological consequences of inbreeding in decorated crickets, Gryllodes sigillatus, by comparing lytic activity, phenoloxidase (PO) activity, and encapsulation ability of crickets from eight inbred lines with that of crickets from the outbred founder population. Surprisingly, crickets from inbred lines had a greater encapsulation ability compared with crickets from the outbred population. We suggest that because inbred crickets have reduced reproductive effort, they may, therefore, have the option of devoting more resources to this form of immunity than outbred individuals. We also found that both inbred and outbred females had higher immunity than males in PO activity and implant darkness. This result supports the hypothesis that females should devote more effort to somatic maintenance and immunity than males. PO activity and implant darkness were heritable in both males and females, but lytic activity was only heritable in females. Males and females differed in the heritability of, and genetic correlations among, immune traits, suggesting that differences in selective pressures on males and females may have resulted in a sexual conflict over optimal immune trait values.

The role of the immune system in central nervous system plasticity after acute injury.

PubMed

Peruzzotti-Jametti, Luca; Donegá, Matteo; Giusto, Elena; Mallucci, Giulia; Marchetti, Bianca; Pluchino, Stefano

2014-12-26

Acute brain injuries cause rapid cell death that activates bidirectional crosstalk between the injured brain and the immune system. In the acute phase, the damaged CNS activates resident and circulating immune cells via the local and systemic release of soluble mediators. This early immune activation is necessary to confine the injured tissue and foster the clearance of cellular debris, thus bringing the inflammatory reaction to a close. In the chronic phase, a sustained immune activation has been described in many CNS disorders, and the degree of this prolonged response has variable effects on spontaneous brain regenerative processes. The challenge for treating acute CNS damage is to understand how to optimally engage and modify these immune responses, thus providing new strategies that will compensate for tissue lost to injury. Herein we have reviewed the available information regarding the role and function of the innate and adaptive immune responses in influencing CNS plasticity during the acute and chronic phases of after injury. We have examined how CNS damage evolves along the activation of main cellular and molecular pathways that are associated with intrinsic repair, neuronal functional plasticity and facilitation of tissue reorganization. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Interactions between adipose tissue and the immune system in health and malnutrition.

PubMed

Wensveen, Felix M; Valentić, Sonja; Šestan, Marko; Wensveen, Tamara Turk; Polić, Bojan

2015-09-01

Adipose tissue provides the body with a storage depot of nutrients that is drained during times of starvation and replenished when food sources are abundant. As such, it is the primary sensor for nutrient availability in the milieu of an organism, which it communicates to the body through the excretion of hormones. Adipose tissue regulates a multitude of body functions associated with metabolism, such as gluconeogenesis, feeding and nutrient uptake. The immune system forms a vital layer of protection against micro-organisms that try to gain access to the nutrients contained in the body. Because infections need to be resolved as quickly as possible, speed is favored over energy-efficiency in an immune response. Especially when immune cells are activated, they switch to fast, but energy-inefficient anaerobic respiration to fulfill their energetic needs. Despite the necessity for an effective immune system, it is not given free rein in its energy expenditure. Signals derived from adipose tissue limit immune cell numbers and activity under conditions of nutrient shortage, whereas they allow proper immune cell activity when food sources are sufficiently available. When excessive fat accumulation occurs, such as in diet-induced obesity, adipose tissue becomes the site of pathological immune cell activation, causing chronic low-grade systemic inflammation. Obesity is therefore associated with a number of disorders in which the immune system plays a central role, such as atherosclerosis and non-alcoholic steatohepatitis. In this review, we will discuss the way in which adipose tissue regulates activity of the immune system under healthy and pathological conditions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Immune modulation following immunization with polyvalent vaccines in dogs.

PubMed

Strasser, Alois; May, Bettina; Teltscher, Andrea; Wistrela, Eva; Niedermüller, Hans

2003-08-15

A decline in T-cell-mediated immunity and transient state of immunosuppression after immunization has been reported in dogs. Nevertheless, dogs are still routinely vaccinated with polyvalent live vaccines and severe disease does not generally occur. In order to investigate these effects on the canine immune system and to elucidate possible mechanisms we determined the following immune parameters in the blood of 33 clinically sound German shepherd dogs before and after standard vaccination with a polyvalent vaccine against distemper, parvovirus, viral hepatitis, leptospirosis, kennel cough and rabies: white and differential blood cell count, the serum concentrations and/or activities of IL-1, IL-2, IFN-gamma, TNF-alpha, neopterin and IgG, natural killer (NK) cell activity, bactericidal activity and complement hemolytic activity, lymphocyte proliferation test (LPT) and nitroblue tetrazolium test (NBT). Our major findings were that significant postvaccinal decreases in T-cell mitogenic response to PHA and in neutrophil function and neopterin serum concentration were accompanied by simultaneous increase in plasma IgG and hemolytic complement activity. This suggests a transient shift in the balance between cell-mediated and humoral (T(H)1/T(H)2) immunity rather than immunosuppression. These results do not imply that dogs should not receive live vaccines, as the response to vaccines just seems to create a state of altered homeostasis when immunization elicits protection by humoral and cell-mediated immunity. However, these recognized compromises of immune function should be considered and vaccines still be applied only in healthy animals and strictly according to the rules and regulations given by the manufacturer.

A key requirement for CD300f in innate immune responses of eosinophils in colitis.

PubMed

Moshkovits, I; Reichman, H; Karo-Atar, D; Rozenberg, P; Zigmond, E; Haberman, Y; Ben Baruch-Morgenstern, N; Lampinen, M; Carlson, M; Itan, M; Denson, L A; Varol, C; Munitz, A

2017-01-01

Eosinophils are traditionally studied in the context of type 2 immune responses. However, recent studies highlight key innate immune functions for eosinophils especially in colonic inflammation. Surprisingly, molecular pathways regulating innate immune activities of eosinophil are largely unknown. We have recently shown that the CD300f is highly expressed by colonic eosinophils. Nonetheless, the role of CD300f in governing innate immune eosinophil activities is ill-defined. RNA sequencing of 162 pediatric Crohn's disease patients revealed upregulation of multiple Cd300 family members, which correlated with the presence of severe ulcerations and inflammation. Increased expression of CD300 family receptors was also observed in active ulcerative colitis (UC) and in mice following induction of experimental colitis. Specifically, the expression of CD300f was dynamically regulated in monocytes and eosinophils. Dextran sodium sulfate (DSS)-treated Cd300f -/- mice exhibit attenuated disease activity and histopathology in comparison with DSS-treated wild type (WT). Decreased disease activity in Cd300f -/- mice was accompanied with reduced inflammatory cell infiltration and nearly abolished production of pro-inflammatory cytokines. Monocyte depletion and chimeric bone marrow transfer experiments revealed a cell-specific requirement for CD300f in innate immune activation of eosinophils. Collectively, we uncover a new pathway regulating innate immune activities of eosinophils, a finding with significant implications in eosinophil-associated gastrointestinal diseases.

Spatiotemporally restricted arenavirus replication induces immune surveillance and type I interferon-dependent tumour regression

PubMed Central

Kalkavan, Halime; Sharma, Piyush; Kasper, Stefan; Helfrich, Iris; Pandyra, Aleksandra A.; Gassa, Asmae; Virchow, Isabel; Flatz, Lukas; Brandenburg, Tim; Namineni, Sukumar; Heikenwalder, Mathias; Höchst, Bastian; Knolle, Percy A.; Wollmann, Guido; von Laer, Dorothee; Drexler, Ingo; Rathbun, Jessica; Cannon, Paula M.; Scheu, Stefanie; Bauer, Jens; Chauhan, Jagat; Häussinger, Dieter; Willimsky, Gerald; Löhning, Max; Schadendorf, Dirk; Brandau, Sven; Schuler, Martin; Lang, Philipp A.; Lang, Karl S.

2017-01-01

Immune-mediated effector molecules can limit cancer growth, but lack of sustained immune activation in the tumour microenvironment restricts antitumour immunity. New therapeutic approaches that induce a strong and prolonged immune activation would represent a major immunotherapeutic advance. Here we show that the arenaviruses lymphocytic choriomeningitis virus (LCMV) and the clinically used Junin virus vaccine (Candid#1) preferentially replicate in tumour cells in a variety of murine and human cancer models. Viral replication leads to prolonged local immune activation, rapid regression of localized and metastatic cancers, and long-term disease control. Mechanistically, LCMV induces antitumour immunity, which depends on the recruitment of interferon-producing Ly6C+ monocytes and additionally enhances tumour-specific CD8+ T cells. In comparison with other clinically evaluated oncolytic viruses and to PD-1 blockade, LCMV treatment shows promising antitumoural benefits. In conclusion, therapeutically administered arenavirus replicates in cancer cells and induces tumour regression by enhancing local immune responses. PMID:28248314

A Xanthomonas uridine 5'-monophosphate transferase inhibits plant immune kinases.

PubMed

Feng, Feng; Yang, Fan; Rong, Wei; Wu, Xiaogang; Zhang, Jie; Chen, She; He, Chaozu; Zhou, Jian-Min

2012-04-15

Plant innate immunity is activated on the detection of pathogen-associated molecular patterns (PAMPs) at the cell surface, or of pathogen effector proteins inside the plant cell. Together, PAMP-triggered immunity and effector-triggered immunity constitute powerful defences against various phytopathogens. Pathogenic bacteria inject a variety of effector proteins into the host cell to assist infection or propagation. A number of effector proteins have been shown to inhibit plant immunity, but the biochemical basis remains unknown for the vast majority of these effectors. Here we show that the Xanthomonas campestris pathovar campestris type III effector AvrAC enhances virulence and inhibits plant immunity by specifically targeting Arabidopsis BIK1 and RIPK, two receptor-like cytoplasmic kinases known to mediate immune signalling. AvrAC is a uridylyl transferase that adds uridine 5'-monophosphate to and conceals conserved phosphorylation sites in the activation loop of BIK1 and RIPK, reducing their kinase activity and consequently inhibiting downstream signalling.

Subverting Toll-Like Receptor Signaling by Bacterial Pathogens

PubMed Central

McGuire, Victoria A.; Arthur, J. Simon C.

2015-01-01

Pathogenic bacteria are detected by pattern-recognition receptors (PRRs) expressed on innate immune cells, which activate intracellular signal transduction pathways to elicit an immune response. Toll-like receptors are, perhaps, the most studied of the PRRs and can activate the mitogen-activated protein kinase (MAPK) and Nuclear Factor-κB (NF-κB) pathways. These pathways are critical for mounting an effective immune response. In order to evade detection and promote virulence, many pathogens subvert the host immune response by targeting components of these signal transduction pathways. This mini-review highlights the diverse mechanisms that bacterial pathogens have evolved to manipulate the innate immune response, with a particular focus on those that target MAPK and NF-κB signaling pathways. Understanding the elaborate strategies that pathogens employ to subvert the immune response not only highlights the importance of these proteins in mounting effective immune responses, but may also identify novel approaches for treatment or prevention of infection. PMID:26648936

Toll-like receptors and intestinal defence: molecular basis and therapeutic implications.

PubMed

Cario, Elke

2003-07-07

Toll-like receptors (TLRs) play a principle role in distinct pathogen recognition and in the initiation of innate immune responses of the intestinal mucosa. Activated innate immunity interconnects downstream with adaptive immunity in complex feedback regulatory loops. Intestinal disease might result from inappropriate activation of the mucosal immune system driven by TLRs in response to normal luminal flora.

Age-associated changes in monocyte and innate immune activation markers occur more rapidly in HIV infected women.

PubMed

Martin, Genevieve E; Gouillou, Maelenn; Hearps, Anna C; Angelovich, Thomas A; Cheng, Allen C; Lynch, Fiona; Cheng, Wan-Jung; Paukovics, Geza; Palmer, Clovis S; Novak, Richard M; Jaworowski, Anthony; Landay, Alan L; Crowe, Suzanne M

2013-01-01

Aging is associated with immune dysfunction and the related development of conditions with an inflammatory pathogenesis. Some of these immune changes are also observed in HIV infection, but the interaction between immune changes with aging and HIV infection are unknown. Whilst sex differences in innate immunity are recognized, little research into innate immune aging has been performed on women. This cross-sectional study of HIV positive and negative women used whole blood flow cytometric analysis to characterize monocyte and CD8(+) T cell subsets. Plasma markers of innate immune activation were measured using standard ELISA-based assays. HIV positive women exhibited elevated plasma levels of the innate immune activation markers CXCL10 (p<0.001), soluble CD163 (sCD163, p = 0.001), sCD14 (p = 0.022), neopterin (p = 0.029) and an increased proportion of CD16(+) monocytes (p = 0.009) compared to uninfected controls. Levels of the innate immune aging biomarkers sCD163 and the proportion of CD16(+) monocytes were equivalent to those observed in HIV negative women aged 14.5 and 10.6 years older, respectively. CXCL10 increased with age at an accelerated rate in HIV positive women (p = 0.002) suggesting a synergistic effect between HIV and aging on innate immune activation. Multivariable modeling indicated that age-related increases in innate immune biomarkers CXCL10 and sCD163 are independent of senescent changes in CD8(+) T lymphocytes. Quantifying the impact of HIV on immune aging reveals that HIV infection in women confers the equivalent of a 10-14 year increase in the levels of innate immune aging markers. These changes may contribute to the increased risk of inflammatory age-related diseases in HIV positive women.

In situ vaccine, immunological memory and cancer cure.

PubMed

Tsung, Kangla; Norton, Jeffrey A

2016-01-01

As surgery is able to remove primary tumors and limit metastases, the major challenge in cancer management is the prevention of post-resection recurrence and metastases. From the immune point of view, tumor resection removes the supply of tumor antigens that maintain an active concomitant antitumor immunity elicited by the primary tumor, and may also signal for deposition of immunological memory against future metastases. However, the natural course of this antitumor immunity in many cancer patients following complete tumor resection may not be favorable because protection is often lost after 1-3 years. Recent studies suggest that chemotherapy is able to activate this pre-existing antitumor immunity, and tumor resection following immune activation may lead to higher levels of immunological memory against future tumor antigens (in the form of metastases). Interleukin-12 added to chemotherapy mimics the function of a vaccine adjuvant in that it helps to enhance the antitumor immunity activated by chemotherapy and leaves a much stronger antitumor immune memory. This finding, when applied to cancer management, may help to maintain a strong and long lasting antitumor immunity following complete tumor resection, thus eliminating post-surgery recurrence and metastases.

Extending the Cortical Grasping Network: Pre-supplementary Motor Neuron Activity During Vision and Grasping of Objects.

PubMed

Lanzilotto, Marco; Livi, Alessandro; Maranesi, Monica; Gerbella, Marzio; Barz, Falk; Ruther, Patrick; Fogassi, Leonardo; Rizzolatti, Giacomo; Bonini, Luca

2016-12-01

Grasping relies on a network of parieto-frontal areas lying on the dorsolateral and dorsomedial parts of the hemispheres. However, the initiation and sequencing of voluntary actions also requires the contribution of mesial premotor regions, particularly the pre-supplementary motor area F6. We recorded 233 F6 neurons from 2 monkeys with chronic linear multishank neural probes during reaching-grasping visuomotor tasks. We showed that F6 neurons play a role in the control of forelimb movements and some of them (26%) exhibit visual and/or motor specificity for the target object. Interestingly, area F6 neurons form 2 functionally distinct populations, showing either visually-triggered or movement-related bursts of activity, in contrast to the sustained visual-to-motor activity displayed by ventral premotor area F5 neurons recorded in the same animals and with the same task during previous studies. These findings suggest that F6 plays a role in object grasping and extend existing models of the cortical grasping network. © The Author 2016. Published by Oxford University Press.

Structurally well-defined macrophage activating factor derived from vitamin D3-binding protein has a potent adjuvant activity for immunization.

PubMed

Yamamoto, N; Naraparaju, V R

1998-06-01

Freund's adjuvant produced severe inflammation that augments development of antibodies. Thus, mixed administration of antigens with adjuvant was not required as long as inflammation was induced in the hosts. Since macrophage activation for phagocytosis and antigen processing is the first step of antibody development, inflammation-primed macrophage activation plays a major role in immune development. Therefore, macrophage activating factor should act as an adjuvant for immunization. The inflammation-primed macrophage activation process is the major macrophage activating cascade that requires participation of serum vitamin D3-binding protein (DBP; human DBP is known as Gc protein) and glycosidases of B and T lymphocytes. Stepwise incubation of Gc protein with immobilized beta-galactosidase and sialidase efficiently generated the most potent macrophage activating factor (designated GcMAF) we have ever encountered. Administration of GcMAF (20 or 100 pg/mouse) resulted in stimulation of the progenitor cells for extensive mitogenesis and activation of macrophages. Administration of GcMAF (100 pg/mouse) along with immunization of mice with sheep red blood cells (SRBC) produced a large number of anti-SRBC antibody secreting splenic cells in 2-4 days. Thus, GcMAF has a potent adjuvant activity for immunization. Although malignant tumours are poorly immunogenic, 4 days after GcMAF-primed immunization of mice with heat-killed Ehrlich ascites tumour cells, the ascites tumour was no longer transplantable in these mice.

Glycogen synthase kinase 3β promotes liver innate immune activation by restraining AMP-activated protein kinase activation.

PubMed

Zhou, Haoming; Wang, Han; Ni, Ming; Yue, Shi; Xia, Yongxiang; Busuttil, Ronald W; Kupiec-Weglinski, Jerzy W; Lu, Ling; Wang, Xuehao; Zhai, Yuan

2018-07-01

Glycogen synthase kinase 3β (Gsk3β [Gsk3b]) is a ubiquitously expressed kinase with distinctive functions in different types of cells. Although its roles in regulating innate immune activation and ischaemia and reperfusion injuries (IRIs) have been well documented, the underlying mechanisms remain ambiguous, in part because of the lack of cell-specific tools in vivo. We created a myeloid-specific Gsk3b knockout (KO) strain to study the function of Gsk3β in macrophages in a murine liver partial warm ischaemia model. Compared with controls, myeloid Gsk3b KO mice were protected from IRI, with diminished proinflammatory but enhanced anti-inflammatory immune responses in livers. In bone marrow-derived macrophages, Gsk3β deficiency resulted in an early reduction of Tnf gene transcription but sustained increase of Il10 gene transcription on Toll-like receptor 4 stimulation in vitro. These effects were associated with enhanced AMP-activated protein kinase (AMPK) activation, which led to an accelerated and higher level of induction of the novel innate immune negative regulator small heterodimer partner (SHP [Nr0b2]). The regulatory function of Gsk3β on AMPK activation and SHP induction was confirmed in wild-type bone marrow-derived macrophages with a Gsk3 inhibitor. Furthermore, we found that this immune regulatory mechanism was independent of Gsk3β Ser9 phosphorylation and the phosphoinositide 3-kinase-Akt signalling pathway. In vivo, myeloid Gsk3β deficiency facilitated SHP upregulation by ischaemia-reperfusion in liver macrophages. Treatment of Gsk3b KO mice with either AMPK inhibitor or SHP small interfering RNA before the onset of liver ischaemia restored liver proinflammatory immune activation and IRI in these otherwise protected hosts. Additionally, pharmacological activation of AMPK protected wild-type mice from liver IRI, with reduced proinflammatory immune activation. Inhibition of the AMPK-SHP pathway by liver ischaemia was demonstrated in tumour resection patients. Gsk3β promotes innate proinflammatory immune activation by restraining AMPK activation. Glycogen synthase kinase 3β promotes macrophage inflammatory activation by inhibiting the immune regulatory signalling of AMP-activated protein kinase and the induction of small heterodimer partner. Therefore, therapeutic targeting of glycogen synthase kinase 3β enhances innate immune regulation and protects liver from ischaemia and reperfusion injury. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

A COMPARISON OF MASS MEDIA USAGE BY JUNIOR HIGH SCHOOL PUPILS OF EXTREME EDUCATIONAL ACHIEVEMENT AND MENTAL ABILITY.

ERIC Educational Resources Information Center

KINSELLA, PAUL J.

THE MOTION PICTURE, RADIO, AND TELEVISION ACTIVITIES AND INTERESTS OF JUNIOR HIGH SCHOOL STUDENTS WERE ASCERTAINED TO DETERMINE POSSIBILITIES FOR BETTER EDUCATIONAL UTILIZATION OF THESE MEDIA. THIS PROJECT WAS CONDUCTED AS A SUPPLEMENTARY ACTIVITY TO COOPERATIVE RESEARCH PROJECT 367, "A STUDY OF INTERESTS OF CHILDREN AND YOUTH" (ED 002…

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Suppression of Antigen-Specific Lymphocyte Activation in Simulated Microgravity

NASA Technical Reports Server (NTRS)

Cooper, David; Pride, Michael W.; Brown, Eric L.; Risin, Diana; Pellis, Neal R.

1999-01-01

Various parameters of immune suppression are observed in astronauts during and after spaceflight, and in isolated immune cells in true and simulated microgravity. Specifically, polyclonal activation of T cells is severely suppressed in true and simulated microgravity. These recent findings with various polyclonal activators suggests a suppression of oligoclonal lymphocyte activation in microgravity. We utilized rotating wall vessel (RWV) bioreactors that simulate aspects of microgravity for cell cultures to analyze three models of antigen-specific activation. A mixed-lymphocyte reaction (MLR), as a model for a primary immune response; a tetanus toxoid (TT) response and a B. burgdorferi (Bb) response, as models of a secondary immune response, were all suppressed in the RWV bioreactor. Our findings confirm that the suppression of activation observed with polyclonal models also encompasses oligoclonal antigen-specific activation.

Hypothesis: Leukocyte Endogenous Mediator/Endogenous Pyrogen/Lymphocyte-Activating Factor Modulates the Development of Nonspecific and Specific Immunity and Affects Nutritional Status

DTIC Science & Technology

1982-04-01

Hypothesis: leukocyte endogenous mediator/ endogenous pyrogen /lymphocyte-activating factor modulates the development of nonspecific and specific... endogenous pyrogen /lympho- NI cyte-activating factor (LEM/EP/LAF) integrates the host’s nonspecific and specific immune responses to infection by...mediator/ endogenous pyrogen /lymphocyte-activating factor, nonspecific and specific immunity, infection, metabolism, nutrition. Introduction LAF which lead

Signals of monocyte activation in patients with SLE.

PubMed Central

Kávai, M; Zsindely, A; Sonkoly, I; Major, M; Demján, I; Szegedi, G

1983-01-01

The Fc receptor mediated reaction, the beta-glucuronidase and the lactic dehydrogenase activities of monocytes and the serum lysozyme level were tested together with the circulating immune complex content of patients with systemic lupus erythematosus. Simultaneously with the increasing FC receptor-mediated reaction and the elevated enzyme activities of patient monocytes, the secretion of lysozyme and the immune complex content of the sera were higher than those of the controls. A positive correlation was demonstrated between the Fc receptor-mediated reaction, the beta-glucuronidase activity, the lysozyme secretion and the immune complex content of the sera. Thus, the monocytes of patients appeared to be activated by the circulating immune complexes. PMID:6839541

Platelets: versatile effector cells in hemostasis, inflammation, and the immune continuum

PubMed Central

Vieira-de-Abreu, Adriana; Campbell, Robert A.; Weyrich, Andrew S.

2015-01-01

Platelets are chief effector cells in hemostasis. In addition, however, their specializations include activities and intercellular interactions that make them key effectors in inflammation and in the continuum of innate and adaptive immunity. This review focuses on the immune features of human platelets and platelets from experimental animals and on interactions between inflammatory, immune, and hemostatic activities of these anucleate but complex and versatile cells. The experimental findings and evidence for physiologic immune functions include previously unrecognized biologic characteristics of platelets and are paralleled by new evidence for unique roles of platelets in inflammatory, immune, and thrombotic diseases. PMID:21818701

A neuro-immune model of Myalgic Encephalomyelitis/Chronic fatigue syndrome.

PubMed

Morris, Gerwyn; Maes, Michael

2013-12-01

This paper proposes a neuro-immune model for Myalgic Encephalomyelitis/Chronic fatigue syndrome (ME/CFS). A wide range of immunological and neurological abnormalities have been reported in people suffering from ME/CFS. They include abnormalities in proinflammatory cytokines, raised production of nuclear factor-κB, mitochondrial dysfunctions, autoimmune responses, autonomic disturbances and brain pathology. Raised levels of oxidative and nitrosative stress (O&NS), together with reduced levels of antioxidants are indicative of an immuno-inflammatory pathology. A number of different pathogens have been reported either as triggering or maintaining factors. Our model proposes that initial infection and immune activation caused by a number of possible pathogens leads to a state of chronic peripheral immune activation driven by activated O&NS pathways that lead to progressive damage of self epitopes even when the initial infection has been cleared. Subsequent activation of autoreactive T cells conspiring with O&NS pathways cause further damage and provoke chronic activation of immuno-inflammatory pathways. The subsequent upregulation of proinflammatory compounds may activate microglia via the vagus nerve. Elevated proinflammatory cytokines together with raised O&NS conspire to produce mitochondrial damage. The subsequent ATP deficit together with inflammation and O&NS are responsible for the landmark symptoms of ME/CFS, including post-exertional malaise. Raised levels of O&NS subsequently cause progressive elevation of autoimmune activity facilitated by molecular mimicry, bystander activation or epitope spreading. These processes provoke central nervous system (CNS) activation in an attempt to restore immune homeostatsis. This model proposes that the antagonistic activities of the CNS response to peripheral inflammation, O&NS and chronic immune activation are responsible for the remitting-relapsing nature of ME/CFS. Leads for future research are suggested based on this neuro-immune model.

A one-year community study of under-fives in rural Ethiopia: health and behavioural determinants of morbidity.

PubMed

Muhe, L; Byass, P; Freij, L; Sandström, A; Wall, S

1996-07-01

Based on a one-year weekly home surveillance study, morbidity patterns of 1,304 children under five years of age in a rural Ethiopian community were measured, together with nutritional and health behavioural determinants. Using Poisson regression models, the study showed that nutritional and health care factors make a significant impact on under-five morbidity. Gastroenteritis was particularly associated with child care factors, while acute respiratory infections were particularly associated with nutritional factors. Lack of immunization, low birthweight and pre-term delivery (more than one month early) were not found to have any independent effect on morbidity. Breast feeding was universal, but the introduction of supplementary foods was found to protect from excess morbidity. The study concludes by discussing possible applications of the results in intervention programmes.

In immune defense: redefining the role of the immune system in chronic disease.

PubMed

Rubinow, Katya B; Rubinow, David R

2017-03-01

The recognition of altered immune system function in many chronic disease states has proven to be a pivotal advance in biomedical research over the past decade. For many metabolic and mood disorders, this altered immune activity has been characterized as inflammation, with the attendant assumption that the immune response is aberrant. However, accumulating evidence challenges this assumption and suggests that the immune system may be mounting adaptive responses to chronic stressors. Further, the inordinate complexity of immune function renders a simplistic, binary model incapable of capturing critical mechanistic insights. In this perspective article, we propose alternative paradigms for understanding the role of the immune system in chronic disease. By invoking allostasis or systems biology rather than inflammation, we can ascribe greater functional significance to immune mediators, gain newfound appreciation of the adaptive facets of altered immune activity, and better avoid the potentially disastrous effects of translating erroneous assumptions into novel therapeutic strategies.

The interplay between immunity and aging in Drosophila.

PubMed

Garschall, Kathrin; Flatt, Thomas

2018-01-01

Here, we provide a brief review of the mechanistic connections between immunity and aging-a fundamental biological relationship that remains poorly understood-by considering two intertwined questions: how does aging affect immunity, and how does immunity affect aging? On the one hand, aging contributes to the deterioration of immune function and predisposes the organism to infections ("immuno-senescence"). On the other hand, excessive activation of the immune system can accelerate degenerative processes, cause inflammation and immunopathology, and thus promote aging ("inflammaging"). Interestingly, several recent lines of evidence support the hypothesis that restrained or curbed immune activity at old age (that is, optimized age-dependent immune homeostasis) might actually improve realized immune function and thereby promote longevity. We focus mainly on insights from Drosophila , a powerful genetic model system in which both immunity and aging have been extensively studied, and conclude by outlining several unresolved questions in the field.

Exosomes and their roles in immune regulation and cancer.

PubMed

Greening, David W; Gopal, Shashi K; Xu, Rong; Simpson, Richard J; Chen, Weisan

2015-04-01

Exosomes, a subset of extracellular vesicles (EVs), function as a mode of intercellular communication and molecular transfer. Exosomes facilitate the direct extracellular transfer of proteins, lipids, and miRNA/mRNA/DNAs between cells in vitro and in vivo. The immunological activities of exosomes affect immunoregulation mechanisms including modulating antigen presentation, immune activation, immune suppression, immune surveillance, and intercellular communication. Besides immune cells, cancer cells secrete immunologically active exosomes that influence both physiological and pathological processes. The observation that exosomes isolated from immune cells such as dendritic cells (DCs) modulate the immune response has enforced the way these membranous vesicles are being considered as potential immunotherapeutic reagents. Indeed, tumour- and immune cell-derived exosomes have been shown to carry tumour antigens and promote immunity, leading to eradication of established tumours by CD8(+) T cells and CD4(+) T cells, as well as directly suppressing tumour growth and resistance to malignant tumour development. Further understanding of these areas of exosome biology, and especially of molecular mechanisms involved in immune cell targeting, interaction and manipulation, is likely to provide significant insights into immunorecognition and therapeutic intervention. Here, we review the emerging roles of exosomes in immune regulation and the therapeutic potential in cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.

Food-mediated modulation of immunity in a phytophagous insect: An effect of nutrition rather than parasitic contamination.

PubMed

Vogelweith, Fanny; Moreau, Jérôme; Thiéry, Denis; Moret, Yannick

2015-06-01

Inherent to the cost of immunity, the immune system itself can exhibit tradeoffs between its arms. Phytophagous insects face a wide range of microbial and eukaryotic parasites, each activating different immune pathways that could compromise the activity of the others. Feeding larvae are primarily exposed to microbes, which growth is controlled by antibiotic secondary metabolites produced by the host plant. The resulting variation in abundance of microbes on plants is expected to differentially stimulate the insect antimicrobial immune defenses. Under the above tradeoff hypothesis, stimulation of the insect antimicrobial defenses is expected to compromise immune activity against eukaryote parasites. In the European grape berry moth, Eupoecilia ambiguella, immune effectors directed towards microbes are negatively correlated to those directed towards eukaryotic parasites among host plants. Here, we hypothesize this relationship is caused by a variable control of the microbial community among host plants by their antibiotic metabolites. To test this hypothesis, we first quantified antimicrobial activity in berries of several grape varieties. We then measured immune defenses of E. ambiguella larvae raised on artificial diets in which we mimicked levels of antimicrobial activity of grape berries using tetracycline to control the abundance of growing microbes. Another group of larvae was raised on artificial diets made of berry extracts only to control for the effect of nutrition. We found that controlling microbe abundance with tetracycline in diets did not explain variation in the immune function whereas the presence of berry extracts did. This suggests that variation in immune defenses of E. ambiguella among grape varieties is caused by nutritional difference among host plants rather than microbe abundance. Further study of the effects of berry compounds on larval immune parameters will be needed to explain the observed tradeoff among immune system components. Copyright © 2015 Elsevier Ltd. All rights reserved.

Seafood Products: Food Service Program Guide.

ERIC Educational Resources Information Center

Webb, Anita H.; And Others

The nine lessons and supplementary activities included in this seafood food service program guide are intended for use in secondary and postsecondary occupational home economics food service programs. Material covers nutrition, therapeutic diets, harvesting methods, quality assessment, fish cuts and forms, inspection, dressing, storage,…

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Summer Coursework and Completing College

ERIC Educational Resources Information Center

Attewell, Paul; Jang, Sou Hyun

2013-01-01

The summer school sessions that colleges offer their undergraduates are sometimes considered supplementary activities and are rarely perceived as central to a college's mission or effectiveness. However, analyses of college transcript data that tracked a nationally-representative sample of undergraduates for several years and through multiple…

Basic Scientific Principles of Diving

ERIC Educational Resources Information Center

MacLean, Don

1976-01-01

Described are some of the physical and physiological scientific principles related to diving. The article is written as supplementary information for a teacher and includes suggested activities, a keyed test, and a bibliography. This article complements one on Sea Lab II in the same issue. (MA)

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South Carolina Guide for Selling.

ERIC Educational Resources Information Center

Elliott, Ronald T.

This curriculum guide provides materials for a secondary course in salesmanship. It contains 6 units that cover 33 competencies. Each competency is presented in a standard format: performance objective, resources, teaching activities, evaluation, and supplementary materials, including an information sheet, exercises, and checklists. Units and…

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Immunity by equilibrium.

PubMed

Eberl, Gérard

2016-08-01

The classical model of immunity posits that the immune system reacts to pathogens and injury and restores homeostasis. Indeed, a century of research has uncovered the means and mechanisms by which the immune system recognizes danger and regulates its own activity. However, this classical model does not fully explain complex phenomena, such as tolerance, allergy, the increased prevalence of inflammatory pathologies in industrialized nations and immunity to multiple infections. In this Essay, I propose a model of immunity that is based on equilibrium, in which the healthy immune system is always active and in a state of dynamic equilibrium between antagonistic types of response. This equilibrium is regulated both by the internal milieu and by the microbial environment. As a result, alteration of the internal milieu or microbial environment leads to immune disequilibrium, which determines tolerance, protective immunity and inflammatory pathology.

Disparate Vitamin D Activity in the Prostate of Men with African Ancestry

DTIC Science & Technology

2015-10-01

the vitamin D receptor (VDR) and determined by several cytochrome P450 metabolism enzymes that bioactivate/inactivate the active form of the hormone...activity of vitamin D3 is mediated by the vitamin D receptor (VDR) and determined by several cytochrome P450 metabolism enzymes that bioactivate...Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT African American (AA) men are disproportionally affected by prostate cancer (PCa). AA men are not only at

Surface modification of nanoparticles enables selective evasion of phagocytic clearance by distinct macrophage phenotypes

NASA Astrophysics Data System (ADS)

Qie, Yaqing; Yuan, Hengfeng; von Roemeling, Christina A.; Chen, Yuanxin; Liu, Xiujie; Shih, Kevin D.; Knight, Joshua A.; Tun, Han W.; Wharen, Robert E.; Jiang, Wen; Kim, Betty Y. S.

2016-05-01

Nanomedicine is a burgeoning industry but an understanding of the interaction of nanomaterials with the immune system is critical for clinical translation. Macrophages play a fundamental role in the immune system by engulfing foreign particulates such as nanoparticles. When activated, macrophages form distinct phenotypic populations with unique immune functions, however the mechanism by which these polarized macrophages react to nanoparticles is unclear. Furthermore, strategies to selectively evade activated macrophage subpopulations are lacking. Here we demonstrate that stimulated macrophages possess higher phagocytic activities and that classically activated (M1) macrophages exhibit greater phagocytic capacity than alternatively activated (M2) macrophages. We show that modification of nanoparticles with polyethylene-glycol results in decreased clearance by all macrophage phenotypes, but importantly, coating nanoparticles with CD47 preferentially lowers phagocytic activity by the M1 phenotype. These results suggest that bio-inspired nanoparticle surface design may enable evasion of specific components of the immune system and provide a rational approach for developing immune tolerant nanomedicines.

Molecular Mechanisms Underlying β-Adrenergic Receptor-Mediated Cross-Talk between Sympathetic Neurons and Immune Cells

PubMed Central

Lorton, Dianne; Bellinger, Denise L.

2015-01-01

Cross-talk between the sympathetic nervous system (SNS) and immune system is vital for health and well-being. Infection, tissue injury and inflammation raise firing rates of sympathetic nerves, increasing their release of norepinephrine (NE) in lymphoid organs and tissues. NE stimulation of β2-adrenergic receptors (ARs) in immune cells activates the cAMP-protein kinase A (PKA) intracellular signaling pathway, a pathway that interfaces with other signaling pathways that regulate proliferation, differentiation, maturation and effector functions in immune cells. Immune–SNS cross-talk is required to maintain homeostasis under normal conditions, to develop an immune response of appropriate magnitude after injury or immune challenge, and subsequently restore homeostasis. Typically, β2-AR-induced cAMP is immunosuppressive. However, many studies report actions of β2-AR stimulation in immune cells that are inconsistent with typical cAMP–PKA signal transduction. Research during the last decade in non-immune organs, has unveiled novel alternative signaling mechanisms induced by β2-AR activation, such as a signaling switch from cAMP–PKA to mitogen-activated protein kinase (MAPK) pathways. If alternative signaling occurs in immune cells, it may explain inconsistent findings of sympathetic regulation of immune function. Here, we review β2-AR signaling, assess the available evidence for alternative signaling in immune cells, and provide insight into the circumstances necessary for “signal switching” in immune cells. PMID:25768345

Ginseng (Panax ginseng Meyer) oligopeptides regulate innate and adaptive immune responses in mice via increased macrophage phagocytosis capacity, NK cell activity and Th cells secretion.

PubMed

He, Li-Xia; Ren, Jin-Wei; Liu, Rui; Chen, Qi-He; Zhao, Jian; Wu, Xin; Zhang, Zhao-Feng; Wang, Jun-Bo; Pettinato, Giuseppe; Li, Yong

2017-10-01

Traditionally used as a restorative medicine, ginseng (Panax ginseng Meyer) has been the most widely used and acclaimed herb in Chinese communities for thousands of years. To investigate the immune-modulating activity of ginseng oligopeptides (GOP), 420 healthy female BALB/c mice were intragastrically administered distilled water (control), whey protein (0.15 g per kg body weight (BW)), and GOP 0.0375, 0.075, 0.15, 0.3 and 0.6 g per kg BW for 30 days. Blood samples from mice were collected from the ophthalmic venous plexus and then sacrificed by cervical dislocation. Seven assays were conducted to determine the immunomodulatory effects of GOP on innate and adaptive immune responses, followed by flow cytometry to investigate spleen T lymphocyte sub-populations, multiplex sandwich immunoassays to investigate serum cytokine and immunoglobulin levels, and ELISA to investigate intestinally secreted immunoglobulin to study the mechanism of GOP affecting the immune system. Our results showed that GOP was able to enhance innate and adaptive immune responses in mice by improving cell-mediated and humoral immunity, macrophage phagocytosis capacity and NK cell activity. Notably, the use of GOP revealed a better immune-modulating activity compared to whey protein. We conclude that the immune-modulating activity might be due to the increased macrophage phagocytosis capacity and NK cell activity, and the enhancement of T and Th cells, as well as IL-2, IL-6 and IL-12 secretion and IgA, IgG1 and IgG2b production. These results indicate that GOP could be considered a good candidate that may improve immune functions if used as a dietary supplement, with a dosage that ranges from 0.3 to 0.6 g per kg BW.

Increasing the immune activity of exosomes: the effect of miRNA-depleted exosome proteins on activating dendritic cell/cytokine-induced killer cells against pancreatic cancer.

PubMed

Que, Ri-Sheng; Lin, Cheng; Ding, Guo-Ping; Wu, Zheng-Rong; Cao, Li-Ping

2016-05-01

Tumor-derived exosomes were considered to be potential candidates for tumor vaccines because they are abundant in immune-regulating proteins, whereas tumor exosomal miRNAs may induce immune tolerance, thereby having an opposite immune function. This study was designed to separate exosomal protein and depleted exosomal microRNAs (miRNAs), increasing the immune activity of exosomes for activating dendritic cell/cytokine-induced killer cells (DC/CIKs) against pancreatic cancer (PC). PC-derived exosomes (PEs) were extracted from cultured PANC-1 cell supernatants and then ruptured; this was followed by ultrafiltered exosome lysates (UELs). DCs were stimulated with lipopolysaccharide (LPS), PE, and UEL, followed by co-culture with CIKs. The anti-tumor effects of DC/CIKs against PC were evaluated by proliferation and killing rates, tumor necrosis factor-α (TNF-α) and perforin secretion. Exosomal miRNAs were depleted after lysis and ultrafiltration, while 128 proteins were retained, including several immune-activating proteins. UEL-stimulated DC/CIKs showed a higher killing rate than LPS- and PE-stimulated DC/CIKs. miRNA-depleted exosome proteins may be promising agonists for specifically activating DC/CIKs against PC.

LINE1 contributes to autoimmunity through both RIG-I- and MDA5-mediated RNA sensing pathways.

PubMed

Zhao, Ke; Du, Juan; Peng, Yanfeng; Li, Peng; Wang, Shaohua; Wang, Yu; Hou, Jingwei; Kang, Jian; Zheng, Wenwen; Hua, Shucheng; Yu, Xiao-Fang

2018-06-01

Improper host immune activation leads to the development of the autoimmune disease Aicardi-Goutières syndrome (AGS), which is attributed to defined genetic mutations in such proteins as TREX1 and ADAR1. The mechanism of immune activation in AGS patients has not been thoroughly elucidated to date. In this study, we report that endogenous LINE1 components trigger IFNβ production in multiple human cell types, including those defective for cGAS/STING-mediated DNA sensing. In these cells, LINE1 DNA synthesis and retrotransposition were not required for LINE1-triggered immune activation, but RNA sensing pathways were essential. LINE1-triggered immune activation could be suppressed by diverse LINE1 inhibitors, including AGS-associated proteins targeting LINE1 RNA or proteins. However, AGS-associated ADAR1 or TREX1 mutants were defective in suppressing LINE1 retrotransposition or LINE1-triggered immune activation. Therefore, we have revealed a new function for LINE1 as an endogenous trigger of innate immune activation, which is important for understanding the molecular basis of IFN-based autoimmune diseases and may offer new intervention strategies. Copyright © 2018 Elsevier Ltd. All rights reserved.

siRNA and innate immunity.

PubMed

Robbins, Marjorie; Judge, Adam; MacLachlan, Ian

2009-06-01

Canonical small interfering RNA (siRNA) duplexes are potent activators of the mammalian innate immune system. The induction of innate immunity by siRNA is dependent on siRNA structure and sequence, method of delivery, and cell type. Synthetic siRNA in delivery vehicles that facilitate cellular uptake can induce high levels of inflammatory cytokines and interferons after systemic administration in mammals and in primary human blood cell cultures. This activation is predominantly mediated by immune cells, normally via a Toll-like receptor (TLR) pathway. The siRNA sequence dependency of these pathways varies with the type and location of the TLR involved. Alternatively nonimmune cell activation may also occur, typically resulting from siRNA interaction with cytoplasmic RNA sensors such as RIG1. As immune activation by siRNA-based drugs represents an undesirable side effect due to the considerable toxicities associated with excessive cytokine release in humans, understanding and abrogating this activity will be a critical component in the development of safe and effective therapeutics. This review describes the intracellular mechanisms of innate immune activation by siRNA, the design of appropriate sequences and chemical modification approaches, and suitable experimental methods for studying their effects, with a view toward reducing siRNA-mediated off-target effects.

Rivastigmine is Associated with Restoration of Left Frontal Brain Activity in Parkinson’s Disease

PubMed Central

Possin, Katherine L.; Kang, Gail A.; Guo, Christine; Fine, Eric M.; Trujillo, Andrew J.; Racine, Caroline A.; Wilheim, Reva; Johnson, Erica T.; Witt, Jennifer L.; Seeley, William W.; Miller, Bruce L.; Kramer, Joel H.

2013-01-01

Objective To investigate how acetylcholinesterase inhibitor (ChEI) treatment impacts brain function in Parkinson’s disease (PD). Methods Twelve patients with PD and either dementia or mild cognitive impairment underwent task-free functional magnetic resonance imaging before and after three months of ChEI treatment and were compared to 15 age and sex matched neurologically healthy controls. Regional spontaneous brain activity was measured using the fractional amplitude of low frequency fluctuations. Results At baseline, patients showed reduced spontaneous brain activity in regions important for motor control (e.g., caudate, supplementary motor area, precentral gyrus, thalamus), attention and executive functions (e.g., lateral prefrontal cortex), and episodic memory (e.g., precuneus, angular gyrus, hippocampus). After treatment, the patients showed a similar but less extensive pattern of reduced spontaneous brain activity relative to controls. Spontaneous brain activity deficits in the left premotor cortex, inferior frontal gyrus, and supplementary motor area were restored such that the activity was increased post-treatment compared to baseline and was no longer different from controls. Treatment-related increases in left premotor and inferior frontal cortex spontaneous brain activity correlated with parallel reaction time improvement on a test of controlled attention. Conclusions PD patients with cognitive impairment show numerous regions of decreased spontaneous brain function compared to controls, and rivastigmine is associated with performance-related normalization in left frontal cortex function. PMID:23847120

Supplementary motor area activation in patients with frontal lobe tumors and arteriovenous malformations.

PubMed

Sailor, Janet; Meyerand, M Elizabeth; Moritz, Chad H; Fine, Jason; Nelson, Lindsey; Badie, Behnam; Haughton, Victor M

2003-10-01

Some patients who undergo surgical resection of portions of the supplementary motor area (SMA) have severe postoperative motor and language deficits, whereas others have no deficits. We tested the hypothesis that in some patients with lesions affecting the SMA, the contralateral SMA exhibits some of the activation normally associated with the ipsilateral SMA. Functional MR imaging studies in seven healthy volunteers and 19 patients with frontal lobe tumors or arteriovenous malformations were reviewed retrospectively. The hemisphere in which the SMA activation predominated was tabulated for right and left motor tasks. The relative hemispheric dominance in the SMA for the right and left motor tasks was compared in the healthy and patient groups and with the location of the lesion in the patient group. None of the control subjects performing a right hand motor task activated predominantly the right SMA. Fifty percent of the patients with lesions overlapping the left SMA performing the right motor task activated predominantly the right SMA. Fifty-seven percent of control subjects performing the left hand motor task activated the left SMA predominantly. One hundred percent of patients with lesions overlapping the right frontal SMA performing the left motor task activated the left SMA predominantly. Differences between patients and controls were statistically significant. A lesion that contacts or overlaps the SMA is associated with an increased functional MR imaging response within the contralateral SMA.

The immunological capacity in the larvae of Pacific oyster Crassostrea gigas.

PubMed

Song, Xiaorui; Wang, Hao; Xin, Lusheng; Xu, Jiachao; Jia, Zhihao; Wang, Lingling; Song, Linsheng

2016-02-01

As the immune system has not fully developed during early developmental stages, bivalve larvae are more susceptible for pathogens, which frequently leads to the significant mortality in hatcheries. In the present study, the development of immune system and its response against bacteria challenge were investigated in order to characterize the repertoire of immunological capacity of Pacific oyster Crassostrea gigas during the ontogenesis. The phagocytosis was firstly observed in the early D-veliger larvae (17 hpf), especially in their velum site, which indicated the appearance of functional hemocytes during early D-veliger larvae stage. The whole-mount immunofluorescence assay of three pattern recognition receptors (integrin β-1, caspase-3 and C-type lectin 3) and one immune effector gene (IL17-5) was performed in blastula, early D-veliger and umbo larvae, suggested that velum and digestive gland were the potential sites of immune system in the larvae. The lowest activities of antioxidant enzymes (superoxide dismutase and catalase) and hydrolytic enzyme (lysozyme), as well as descended expression levels of 12 immune genes at the transition between embryogenesis and planktonic, indicated that the larvae at hatching (9 hpf) were in hypo-immunity. While the ascending activities of enzymes and expression levels of seven immune genes during the trochophore stage (15 hpf) suggested the initiation of immune system. The steadily increasing trend of all the 12 candidate genes at the early umbo larvae (120 h) hinted that the immune system was well developed at this stage. After bacterial challenge, some immune recognition (TLR4) and immune effector (IL17-5 and defh2) genes were activated in blastula stage (4 hpf), and other immune genes were up regulated in D-veliger larvae, indicating that the zygotic immune system could respond earlier against the bacterial challenge during its development. These results indicated that the cellular and humoral immune components appeared at trochophore stage, and the cellular immune system was activated with its occurrence, while the humoral immune system executed until the early umbo larval stage. The immune system emerged earlier to aid larvae in defending bacterial challenge during the early stages of oyster development. Copyright © 2016 Elsevier Ltd. All rights reserved.

Doyne lecture 2016: intraocular health and the many faces of inflammation

PubMed Central

Dick, A D

2017-01-01

Dogma for reasons of immune privilege including sequestration (sic) of ocular antigen, lack of lymphatic and immune competent cells in the vital tissues of the eye has long evaporated. Maintaining tissue and cellular health to preserve vision requires active immune responses to prevent damage and respond to danger. A priori the eye must contain immune competent cells, undergo immune surveillance to ensure homoeostasis as well as an ability to promote inflammation. By interrogating immune responses in non-infectious uveitis and compare with age-related macular degeneration (AMD), new concepts of intraocular immune health emerge. The role of macrophage polarisation in the two disorders is a tractable start. TNF-alpha regulation of macrophage responses in uveitis has a pivotal role, supported via experimental evidence and validated by recent trial data. Contrast this with the slow, insidious degeneration in atrophic AMD or in neovasular AMD, with the compelling genetic association with innate immunity and complement, highlights an ability to attenuate pathogenic immune responses and despite known inflammasome activation. Yolk sac-derived microglia maintains tissue immune health. The result of immune cell activation is environmentally dependent, for example, on retinal cell bioenergetics status, autophagy and oxidative stress, and alterations that skew interaction between macrophages and retinal pigment epithelium (RPE). For example, dead RPE eliciting macrophage VEGF secretion but exogenous IL-4 liberates an anti-angiogenic macrophage sFLT-1 response. Impaired autophagy or oxidative stress drives inflammasome activation, increases cytotoxicity, and accentuation of neovascular responses, yet exogenous inflammasome-derived cytokines, such as IL-18 and IL-33, attenuate responses. PMID:27636226

Immunosuppressive Effects of Natural α,β-Unsaturated Carbonyl-Based Compounds, and Their Analogs and Derivatives, on Immune Cells: A Review.

PubMed

Arshad, Laiba; Jantan, Ibrahim; Bukhari, Syed Nasir Abbas; Haque, Md Areeful

2017-01-01

The immune system is complex and pervasive as it functions to prevent or limit infections in the human body. In a healthy organism, the immune system and the redox balance of immune cells maintain homeostasis within the body. The failure to maintain the balance may lead to impaired immune response and either over activity or abnormally low activity of the immune cells resulting in autoimmune or immune deficiency diseases. Compounds containing α,β-unsaturated carbonyl-based moieties are often reactive. The reactivity of these groups is responsible for their diverse pharmacological activities, and the most important and widely studied include the natural compounds curcumin, chalcone, and zerumbone. Numerous studies have revealed the mainly immunosuppressive and anti-inflammatory activities of the aforesaid compounds. This review highlights the specific immunosuppressive effects of these natural α,β-unsaturated carbonyl-based compounds, and their analogs and derivatives on different types of immune cells of the innate (granulocytes, monocytes, macrophages, and dendritic cells) and adaptive (T cells, B cells, and natural killer cells) immune systems. The inhibitory effects of these compounds have been comprehensively studied on neutrophils, monocytes and macrophages but their effects on T cells, B cells, natural killer cells, and dendritic cells have not been well investigated. It is of paramount importance to continue generating experimental data on the mechanisms of action of α,β-unsaturated carbonyl-based compounds on immune cells to provide useful information for ensuing research to discover new immunomodulating agents.