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1.
Crit Pathw Cardiol ; 22(2): 45-49, 2023 06 01.
Article in English | MEDLINE | ID: mdl-37220658

ABSTRACT

OBJECTIVE: Emergency physicians are challenged to efficiently and reliably risk stratify patients presenting with chest pain (CP) to optimize diagnostic testing and avoid unnecessary hospital admissions. The objective of our study was to evaluate the impact of a HEART score-based decision aid (HSDA) integrated in the electronic health record on coronary computed tomography angiography (CCTA) utilization and diagnostic yield in adult emergency department (ED) CP patients with suspected acute coronary syndrome. METHODS: We conducted a before and after study to determine whether implementation of a mandatory computerized HSDA would reduce CCTA utilization in ED CP patients and improve the diagnostic yield of obstructive coronary artery disease (CAD) (≥50%). We included all adult ED CP patients with suspected acute coronary syndrome during the first 6 months of 2018 (before) and 2020 (after) at a large academic center. CCTA utilization and obstructive CAD yield were compared in patients before and after implementing the HSDA using χ2 tests. Secondarily, we assessed the association of HEART scores and CCTA results. RESULTS: Of the 3095 CP patients during the before study period, 733 underwent CCTA. Of the 2692 CP patients during the after study period, 339 underwent CCTA. CCTA utilization before and after HSDA was 23.4% [95% confidence interval (95% CI), 22.2-25.2] and 12.6% (95% CI, 11.4-13.0), respectively; mean difference was 11.1% (95% CI, 0.9-13.0). Among 1072 patients undergoing CCTA, mean (SD) age and percent females before versus after HSDA were 54 (11) versus 56 (11) years and 50% versus 49%, respectively. We included 1014 patients (686 before and 328 after) for the yield analysis. Obstructive CAD was present in 15% (95% CI, 12.7-17.9) and 20.1% (95% CI, 16.1-24.7) before and after HSDA, respectively; mean difference was 4.9% (95% CI, 0.1-10.1). CONCLUSIONS: Implementation of a mandatory electronic health record HSDA aid reduced ED CCTA utilization by half and improved the diagnostic yield.


Subject(s)
Acute Coronary Syndrome , Coronary Artery Disease , Adult , Female , Humans , Computed Tomography Angiography , Heart , Chest Pain , Emergency Service, Hospital , Decision Support Techniques
2.
Ir Vet J ; 75(1): 1, 2022 Jan 05.
Article in English | MEDLINE | ID: mdl-34986879

ABSTRACT

BACKGROUND: Legislation pertaining to canine ownership in Ireland maintains a one-health perspective by establishing a minimum standard of care for dogs while safeguarding human health and wellbeing. However, public awareness of this legislation has not been measured. The goals of this study were first, to estimate and compare the level of awareness, among dog owners and non-dog owners, that eight responsibilities of dog owners are prescribed by law in Ireland. Second, to determine if gender modifies differences in awareness between owners and non-owners, and third to determine whether gender itself is independently associated with awareness of the legal specification of these dog ownership responsibilities. RESULTS: We conducted a cross-sectional study of 679 University College Dublin employees. Exposure information included participants' dog ownership status, gender, age, and education level. Among dog owners and non-dog owners, we estimated and compared the prevalences of persons with self-reported awareness that each of eight dog ownership responsibilities are prescribed by law in Ireland: Dog fouling in a public place, the leashing and muzzling of certain breeds, holding a dog license, straying of dogs, safeguarding health and welfare of dogs, dog abandonment, prohibition on tail docking of puppies and the mandatory wearing of identification. The prevalence of awareness was low among both dog owners and non-dog owners with substantial awareness (≥ 80%) of only three responsibilities: Those pertaining to fouling, licensing and muzzling and leashing. Awareness that more than one responsibility was specified by law was also poor with only 17.9% (95% CI: 15.1-20.9%) of participants aware of all eight and dog owners essentially just as likely (54%; 95% CI: 49-58%) to be aware of more than one as non-dog owners. For most dog ownership responsibilities, differences in prevalence (PD) of awareness between owners and non-owners and females and males were trivial (PD < 10%). Similarly for most responsibilities, gender did not modify awareness PDs between owners and non-owners. CONCLUSIONS: In this well-educated university community, self-reported awareness that these eight responsibilities of dog owners are prescribed by law in Ireland is poor with essentially no difference between dog owners and non-dog owners or males and females. Awareness was higher for those responsibilities which, when not discharged, result in direct negative consequences to humans compared to those that result in direct negative consequences to dogs. It is likely that awareness of the legal status of these eight responsibilities of dog owners among the general public in Ireland is even less than observed in this study.

4.
Ir Vet J ; 70: 29, 2017.
Article in English | MEDLINE | ID: mdl-28944041

ABSTRACT

BACKGROUND: Pet cat and dog obesity contributes to increased risk of several diseases, including cancer and diabetes mellitus as well as a worsening of orthopaedic problems, and a reduction in survival rate. This study aims to develop a better understanding of cat and dog owners' self-reported beliefs and factors that influence owner behaviour around feeding and exercising their pet cat or dog, as there is a lack of in-depth understanding in this area. Seven focus group discussions, with 43 pet owners in total, were conducted. RESULTS: Pet owners often reported a perceived a low level of control over feeding; often undermined by other people feeding of their pet, their pets begging for food, and their pets attitude towards food. Treats were used in the absence of owner control over pet begging and emotional attachment, and to influence pet behaviour. The majority of participants had positive attitudes to pet exercise, which could be related to pet specific requirements, especially differences in cats and dogs. There were some negative experiences of stress associated with dog walking and fears over aggressive confrontations with other dogs. CONCLUSION: Feeding one's pet is influenced by beliefs about pet specific needs, pet food and pet health, pet owners' perceived control over feeding, and the implications for the pet owner. Pet exercise is influenced by beliefs about pet specific exercise needs, and the implications of exercising one's pet for the pet owner. Understanding owner behaviours on feeding and exercise allows for a more targeted approach to preventing and treating pet obesity.

5.
Public Underst Sci ; 26(7): 872-888, 2017 10.
Article in English | MEDLINE | ID: mdl-26941211

ABSTRACT

Societal adaptation to flooding is a critical component of contemporary flood policy. Using content analysis, this article identifies how two major flooding episodes (2009 and 2014) are framed in the Irish broadsheet news media. The article considers the extent to which these frames reflect shifts in contemporary flood policy away from protection towards risk management, and the possible implications for adaptation to living with flood risk. Frames help us make sense of the social world, and within the media, framing is an essential tool for communication. Five frames were identified: flood resistance and structural defences, politicisation of flood risk, citizen as risk manager, citizen as victim and emerging trade-offs. These frames suggest that public debates on flood management do not fully reflect shifts in contemporary flood policy, with negative implications for the direction of societal adaptation. Greater discussion is required on the influence of the media on achieving policy objectives.


Subject(s)
Communication , Floods , Newspapers as Topic , Public Opinion , Risk Management , Government Regulation , Ireland
6.
PeerJ ; 3: e1196, 2015.
Article in English | MEDLINE | ID: mdl-26312187

ABSTRACT

Background. Failure among pet owners to neuter their pets results in increased straying and overpopulation problems. Variations in neutering levels can be explained by cultural differences, differences in economic status in rural and urban locations, and owner perceptions about their pet. There are also differences between male and female pet owners. There is no research pertaining to Irish pet owner attitudes towards neutering their pets. This paper identified the perceptions of a sample of Irish cat and dog owners that influenced their decisions on pet neutering. Methods. This study was conducted using social science (qualitative) methods, including an interview-administered survey questionnaire and focus group discussions. Data was coded and managed using Nvivo 8 qualitative data analysis software. Results. Focus groups were conducted with 43 pet (cats and dogs) owners. Two major categories relating to the decision to neuter were identified: (1) enabling perceptions in the decision to neuter (subcategories were: controlling unwanted pet behaviour; positive perceptions regarding pet health and welfare outcomes; perceived owner responsibility; pet function; and the influence of veterinary advice), and (2) disabling perceptions in the decision to neuter (subcategories were: perceived financial cost of neutering; perceived adequacy of existing controls; and negative perceptions regarding pet health and welfare outcomes). Discussion. Pet owner sense of responsibility and control are two central issues to the decision to neuter their pets. Understanding how pet owners feel about topics such as pet neutering, can help improve initiatives aimed at emphasising the responsibility of population control of cats and dogs.

7.
Ir Vet J ; 69: 2, 2015.
Article in English | MEDLINE | ID: mdl-26862390

ABSTRACT

BACKGROUND: Currently, there is growing interest in developing ante and post mortem meat inspection (MI) to incorporate measures of pig health and welfare for use as a diagnostic tool on pig farms. However, the success of the development of the MI process requires stakeholder engagement with the process. Knowledge gaps and issues of trust can undermine the effective exchange and utilisation of information across the supply chain. A social science research methodology was employed to establish stakeholder perspectives towards the development of MI to include measures of pig health and welfare. In this paper the findings of semi-structured telephone interviews with 18 pig producers from the Republic of Ireland and Northern Ireland are presented. RESULTS: Producers recognised the benefit of the utilisation of MI data as a health and welfare diagnostic tool. This acknowledgment, however, was undermined for some by dissatisfaction with the current system of MI information feedback, by trust and fairness concerns, and by concerns regarding the extent to which data would be used in the producers' interests. Tolerance of certain animal welfare issues may also have a negative impact on how producers viewed the potential of MI data. The private veterinary practitioner was viewed as playing a vital role in assisting them with the interpretation of MI data for herd health planning. CONCLUSIONS: The development of positive relationships based on trust, commitment and satisfaction across the supply chain may help build a positive environment for the effective utilisation of MI data in improving pig health and welfare. The utilisation of MI as a diagnostic tool would benefit from the development of a communication strategy aimed at building positive relationships between stakeholders in the pig industry.

8.
J Allergy Clin Immunol ; 130(5): 1167-1174.e10, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22818765

ABSTRACT

BACKGROUND: One explanation for the high burden of allergic and autoimmune diseases in industrialized countries is inappropriate immune development under modern environmental conditions. There is increasing evidence that the process of immune deviation already begins in utero, but the underlying immunologic mechanisms are not clear. OBJECTIVE: We sought to identify differences in the function of neonatal antigen-presenting cells (APCs) in children born in settings that are more traditional versus those of modern societies. METHODS: Cord blood mononuclear cells were collected from newborns from Papua New Guinea (PNG; traditional) and Australia (modern) and compared for differences in APCs and T-cell phenotype and function. RESULTS: Australian cord naive T cells (CD4(+)CD25(-)CD127(+) cells) showed an enhanced and more rapid proliferative response in an autologous, APC-dependent culture system, a result of differences in neonatal APCs rather than T-cell function. This included an increased capacity to process antigen and to upregulate activation markers after stimulation. In contrast, resting PNG APCs exhibited higher baseline levels of activation and inhibitory markers and were less responsive or nonresponsive to stimulation in vitro. CONCLUSIONS: This study supports the hypothesis that prenatal environments can influence the developing immune system in utero. Children born under modern environmental conditions exhibit increased APC reactivity at birth compared with children born under traditional environmental conditions. The functionally more quiescent nature of PNG neonatal APCs might protect against the development of harmful inflammatory responses in early life.


Subject(s)
Antigen-Presenting Cells/immunology , T-Lymphocyte Subsets/immunology , T-Lymphocytes/immunology , Adult , Antigens, CD/metabolism , Australia , Cells, Cultured , Child , Demography , Environmental Exposure/adverse effects , Female , Humans , Immunophenotyping , Industry , Infant, Newborn , Life Style , Lymphocyte Activation , Papua New Guinea , Young Adult
9.
PLoS One ; 7(5): e36793, 2012.
Article in English | MEDLINE | ID: mdl-22649499

ABSTRACT

Studies addressing the ontogeny of the innate immune system in early life have reported mainly on Toll-like receptor (TLR) responses in infants living in high-income countries, with little or even no information on other pattern recognition receptors or on early life innate immune responses in children living under very different environmental conditions in less-developed parts of the world. In this study, we describe whole blood innate immune responses to both Toll-like and nucleotide-binding oligomerization domain (NOD)-like receptor agonists including the widely used vaccine adjuvant 'alum' in a group of Papua New Guinean infants aged 1-3 (n = 18), 4-6 (n = 18), 7-12 (n = 21) and 13-18 (n = 10) months old. Depending on the ligands and cytokines studied, different age-related patterns were found: alum-induced IL-1ß and CXCL8 responses were found to significantly decline with increasing age; inflammatory (IL-6, IL-1ß, IFN-γ) responses to TLR2 and TLR3 agonists increased; and IL-10 responses remained constant or increased during infancy, while TNF-α responses either declined or remained the same. We report for the first time that whole blood innate immune responses to the vaccine adjuvant alum decrease with age in infancy; a finding that may imply that the adjuvant effect of alum in pediatric vaccines could be age-related. Our findings further suggest that patterns of innate immune development may vary between geographically diverse populations, which in line with the 'hygiene hypothesis' particularly involves persistence of innate IL-10 responses in populations experiencing higher infectious pressure.


Subject(s)
Carrier Proteins/physiology , Immune System/growth & development , Immunity, Innate/physiology , Inflammasomes/metabolism , Toll-Like Receptors/physiology , Age Factors , Alum Compounds , Cells, Cultured , Cross-Sectional Studies , Humans , Infant , Inflammasomes/physiology , Interferon-gamma/blood , Interleukin-10/blood , Interleukin-1beta/blood , Interleukin-6/blood , Leukocytes, Mononuclear , NLR Family, Pyrin Domain-Containing 3 Protein , Papua New Guinea , Statistics, Nonparametric , Toll-Like Receptors/agonists , Tumor Necrosis Factor-alpha/blood
10.
J Interpers Violence ; 27(17): 3514-31, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22610827

ABSTRACT

Intimate partner violence is endemic in parts of the African continent. A small scale survey (n = 229) was conducted in 2009 in Northern Liberia, West Africa, to determine the prevalence and nature of intimate partner violence, and the cultural beliefs and gender norms that underpin respondent experiences and views towards intimate partner violence. Results show widespread experience of intimate partner violence among the respondent group, including physical abuse, sexual and verbal, and economic abuse. Acceptance of the situation was identified by most respondents as a way of responding to violence, and arises from the lack of financial and legal supports for women within the community. Despite the range of abuses experienced, beliefs about the power position of men in Liberian society provide evidence to reflect the predominance of certain cultural beliefs in framing respondents' perceptions of gender relations. The article concludes with a discussion on the possible impact of Liberia's recent conflict in contributing to the perpetuation and normalization of intimate partner violence. Further large scale research in this area is required.


Subject(s)
Attitude to Health/ethnology , Cultural Characteristics , Social Values/ethnology , Spouse Abuse/ethnology , Women's Health/ethnology , Adult , Coercion , Female , Humans , Interpersonal Relations , Liberia/epidemiology , Male , Middle Aged , Prevalence , Risk Factors , Sexual Partners , Social Perception , Young Adult
11.
Pediatr Infect Dis J ; 31(3): 243-8, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22189528

ABSTRACT

BACKGROUND: The aim of this study was to examine the relationship between nasopharyngeal pneumococcal colonization in early life and the subsequent development of pneumococcal-specific T cell responses. METHODS: Pernasal swabs were collected from Papua New Guinean infants at the ages of 1 and 2 weeks (n = 279). At 9 months, in vitro cellular immune responses to choline-binding protein A (n = 132), pneumococcal surface protein A (n = 132), pneumolysin (n = 99), and the pneumococcal conjugate vaccine carrier CRM197 were determined. Responses were compared based on the children's carriage status within the first 2 weeks of life. RESULTS: Within the first 2 weeks of life, 40% of the study children carried Streptococcus pneumoniae. Early carriage was associated with lower interferon-γ and interleukin 10 responses to pneumococcal proteins at age 9 months when children had not received pneumococcal conjugate vaccines during the study period. CONCLUSIONS: Early pneumococcal carriage may result in enhanced disease susceptibility and suboptimal vaccine responses by modulating the development of pneumococcal immune responses.


Subject(s)
Antigens, Bacterial/immunology , Bacterial Proteins/immunology , Carrier State/immunology , Immunity, Cellular , Streptococcal Infections/immunology , Streptococcus pneumoniae/immunology , Disease Susceptibility , Female , Humans , Infant , Infant, Newborn , Male , Nasopharynx/microbiology , Papua New Guinea , Pneumococcal Vaccines/administration & dosage , Pneumococcal Vaccines/immunology , Pregnancy , T-Lymphocytes/immunology
12.
Pediatr Allergy Immunol ; 23(2): 173-80, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22192086

ABSTRACT

BACKGROUND: Environmental changes, including declining microbial exposure, have been linked with the rising incidence of allergic and autoimmune diseases in 'western' populations. This potentially occurs by altering early development of immuno-regulatory pathways including T regulatory cells (T(reg)). There is now increasing evidence that such conditioning begins in utero. METHODS: We compared neonatal T(reg) from children born under typical western conditions (Australia, AUS) with those of neonates born under more traditional conditions of high microbial burden (Papua New Guinea, PNG). RESULTS: The frequency of neonatal T(reg), defined as CD4(+) Foxp3(+) CD127(-) CD25(+/high) was found to be higher in the cord blood of AUS compared to PNG newborns. However, cord T(reg) suppressive function in a small subset of children was qualitatively similar between PNG and AUS newborns in both a T(reg) depletion assay and a T(reg) supplementation assay. CONCLUSIONS: These findings do not support the hypothesis that living in a 'western' versus more traditional environment leads to poor induction or suppressive function of neonatal T(reg). However, environmentally-induced immuno-regulation may potentially occur via alternative mechanisms in PNG newborns that should now be investigated further.


Subject(s)
Infant, Newborn/immunology , T-Lymphocytes, Regulatory/immunology , Australia , Female , Flow Cytometry , Humans , Infant, Newborn/blood , Male , Papua New Guinea
13.
Ir Vet J ; 64(1): 7, 2011 Mar 31.
Article in English | MEDLINE | ID: mdl-21777494

ABSTRACT

Part 1 of the study described the development of a Hazard Analysis and Critical Control Point (HACCP) based programme and accompanying handbook for the control of mastitis. This paper describes the implementation and evaluation of customised HACCP-based programmes, which were developed from the handbook and assessed on six Irish dairy farms. Both quantitative and qualitative (action research) research methodologies were used to measure the success of implementation and efficacy of control of sub-clinical mastitis as measured by Somatic Cell Counts (SCC) and the degree of compliance by farmers in adopting and maintaining recommendations throughout the course of the study period. No overall differences in SCC before and during the implementation of the study were found when all six farms were considered together. Three of the six study farms experienced a significant decrease in herd milk recorded SCC during the implementation of the control programme. An essential part of the study was achieving initial agreement on recommendations as well as ongoing monitoring of compliance during the study. This pilot study shows that HACCP can be implemented on farms as a means of working towards the control of mastitis and that farmer attitude, and understanding of mastitis are crucial in terms of motivation irrespective of practical approaches used to manage mastitis.

14.
Vaccine ; 29(33): 5414-20, 2011 Jul 26.
Article in English | MEDLINE | ID: mdl-21645573

ABSTRACT

Concerns about the risk of inducing immune deviation-associated "neonatal tolerance" as described in mice have restricted the widespread adoption of neonatal vaccination. The aim of this study was to demonstrate the immunological feasibility of neonatal pneumococcal conjugate vaccination (PCV) which could potentially protect high-risk infants in resource poor countries against severe pneumococcal disease and mortality in the early critical period of life. Papua New Guinean infants were randomized to be vaccinated with the 7-valent PCV (7vPCV) at birth, 1 and 2 months (neonatal group, n=104) or at 1, 2 and 3 months of age (infant group, n=105), or to not receive 7vPCV at all (control group, n=109). Analysis of vaccine responses at 3 and 9 months of age demonstrated persistently higher type-1 (IFN-γ) and type-2 (IL-5 and IL-13) T-cell responses to the protein carrier CRM(197) and IgG antibody titres to 7vPCV serotypes in children vaccinated with 7vPCV according to either schedule as compared to unvaccinated children. In a comprehensive immuno-phenotypic analysis at 9 months of age, no differences in the quantity or quality of vaccine-specific T cell memory responses were found between neonatal vaccinations versus children given their first PCV dose at one month. Hospitalization rates in the first month of life did not differ between children vaccinated with PCV at birth or not. These findings demonstrate that neonatal 7vPCV vaccination is safe and not associated with immunological tolerance. Neonatal immunisation schedules should therefore be considered in high-risk areas where this may result in improved vaccine coverage and the earliest possible protection against pneumococcal disease and death.


Subject(s)
Immune Tolerance , Pneumococcal Vaccines/administration & dosage , Pneumococcal Vaccines/immunology , T-Lymphocytes/immunology , Age Factors , Antibodies, Bacterial/blood , Female , Heptavalent Pneumococcal Conjugate Vaccine , Humans , Immunoglobulin G/blood , Infant , Infant, Newborn , Interferon-gamma/metabolism , Interleukin-13/metabolism , Interleukin-5/metabolism , Leukocytes, Mononuclear/immunology , Papua New Guinea , Pneumococcal Vaccines/adverse effects , Pregnancy
15.
J Allergy Clin Immunol ; 124(3): 544-50, 550.e1-2, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19500827

ABSTRACT

BACKGROUND: The protective effect of Mycobacterium bovis BCG vaccination against infection and atopy varies between populations. OBJECTIVE: To identify differences in neonatal responses to BCG between diverse populations and study longitudinal associations with memory T-cell responses. METHODS: Cord blood mononuclear cells were collected from Papua New Guinean (PNG) and Western Australian (WA) newborns. Toll-like receptor (TLR)-2, TLR4, and TLR9 mRNA expression and in vitro BCG-stimulated (+/-IFN-gamma priming) innate cytokine responses were compared. When PNG infants were 3 months old, PBMCs were stimulated in vitro with Mycobacterium-purified protein derivative (PPD) to determine memory T-cell responses. RESULTS: BCG-induced IL-10 and IFN-gamma responses were significantly higher in cord blood mononuclear cells of PNG newborns, and TLR2 and TLR9 expression was significantly higher and TLR4 expression lower compared with WA newborns. High neonatal IL-10 and low IFN-gamma responses to BCG were found to promote the development of PPD-memory T(H)2 responses in infancy, whereas neonatal BCG-TNFalpha responses inhibited the development of PPD-IL 10 responses. When primed with IFN-gamma, BCG-induced TNF-alpha, IL-12p70, and in particular IFN-gamma responses were enhanced to a significantly higher extent in WA than in PNG newborns. In response to IFN-gamma priming and BCG stimulation, natural killer cells of WA newborns produced IFN-gamma, whereas natural killer cells of PNG newborns contributed only indirectly to this response. CONCLUSION: Neonatal BCG-related innate immune responses control the differentiation of T(H) memory responses and vary between populations. This may explain differences in the effects of BCG vaccination between populations.


Subject(s)
BCG Vaccine/immunology , Cytokines/immunology , Killer Cells, Natural/immunology , Leukocytes, Mononuclear/immunology , T-Lymphocytes, Helper-Inducer/immunology , Antiviral Agents/metabolism , Antiviral Agents/pharmacology , Cells, Cultured , Cytokines/drug effects , Female , Humans , Infant, Newborn , Interferon-gamma/metabolism , Interferon-gamma/pharmacology , Killer Cells, Natural/metabolism , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/metabolism , Linear Models , Longitudinal Studies , Male , Multivariate Analysis , Toll-Like Receptor 2/immunology , Toll-Like Receptor 2/metabolism , Toll-Like Receptor 4/immunology , Toll-Like Receptor 4/metabolism , Toll-Like Receptor 9/immunology , Toll-Like Receptor 9/metabolism , Tuberculin
16.
Vaccine ; 27(9): 1340-7, 2009 Feb 25.
Article in English | MEDLINE | ID: mdl-19150378

ABSTRACT

The effects of neonatal immunization with 7-valent pneumococcal conjugate vaccine (7vPCV) on development of T-cell memory and general immune maturation were studied in a cohort of Papua New Guinean newborns. Neonatal 7vPCV priming (followed by a dose at 1 and 2 months of age) was associated with enhanced Th2, but not Th1, cytokine responses to CRM(197) compared to 7vPCV at 1 and 2 months of age only. T cell responses to non-7vPCV vaccine antigens were similar in all groups, but TLR-mediated IL-6 and IL-10 responses were enhanced in 7vPCV vaccinated compared to controls. Neonatal 7vPCV vaccination primes T cell responses with a polarization towards Th2 with no bystander effects on other T cell responses.


Subject(s)
Pneumococcal Vaccines/therapeutic use , T-Lymphocytes/immunology , Th2 Cells/immunology , Cesarean Section , Cytokines/biosynthesis , Cytokines/genetics , Drug Administration Schedule , Female , Humans , Infant, Newborn , Infant, Small for Gestational Age/immunology , Papua New Guinea , Pneumococcal Vaccines/administration & dosage , Pregnancy , Pregnancy Complications/immunology , RNA, Bacterial/genetics , RNA, Bacterial/isolation & purification , Reverse Transcriptase Polymerase Chain Reaction , Streptococcus pneumoniae/genetics , T-Lymphocytes/drug effects , Viral Vaccines/administration & dosage
17.
J Immunol ; 176(8): 4766-77, 2006 Apr 15.
Article in English | MEDLINE | ID: mdl-16585570

ABSTRACT

Atopic diseases are associated with hyperexpression of Th2 cytokines by allergen-specific T memory cells. However, clinical trials with recently developed Th2 inhibitors in atopics have proven disappointing, suggesting underlying complexities in atopy pathogenesis which are not satisfactorily explained via the classical Th1/Th2 paradigm. One likely possibility is that additional Th2-associated genes which are central to disease pathogenesis remain unidentified. The aim of the present study was to identify such novel Th2-associated genes in recall responses to the inhalant allergen house dust mite. In contrast to earlier human microarray studies in atopy which focused on mitogen-activated T cell lines and clones, we concentrated on PBMC-derived primary T cells stimulated under more physiological conditions of low dose allergen exposure. We screened initially for allergen-induced gene activation by microarray, and validated novel genes in independent panels of subjects by quantitative RT-PCR. Kinetic analysis of allergen responses in PBMC revealed an early wave of novel atopy-associated genes involved in signaling which were coexpressed with IL-4 and IL-4R, followed by a later wave of genes encoding the classical Th2 effector cytokines. We further demonstrate that these novel activation-associated Th2 genes up-regulate in response to another atopy-associated physiological stimulus bacterial superantigen, but remain quiescent in nonphysiological responses in primary T cells or cell lines driven by potent mitogens, which may account for their failure to be detected in earlier microarray studies.


Subject(s)
Immunologic Memory/genetics , Th2 Cells/immunology , Administration, Inhalation , Adolescent , Adult , Allergens/administration & dosage , Animals , Antigens, Dermatophagoides/administration & dosage , Child , Cytokines/genetics , Gene Expression , Gene Expression Profiling , Humans , Hypersensitivity, Immediate/genetics , Hypersensitivity, Immediate/immunology , In Vitro Techniques , Kinetics , Middle Aged , Mites/immunology , Oligonucleotide Array Sequence Analysis , Th1 Cells/immunology
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