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Bringing together insights from feminist political economy and everyday financialization, this paper explores the complex nature of women’s pension decisions. Women in the UK experience structural constraints originating from a pension system which ignores socially reproductive activities, and they face limitations in pension planning due to prevalent gender norms. Both aspects have a significant impact on women’s long-term financial wellbeing and yet little attention has been paid to how they operate within these constraints, ultimately leading to women’s behaviors being construed as passive or irrational. Drawing on 61 interviews, our paper conceptualizes pension practices adopted by women through gendered finance rationality, defined as variegated financial practices shaped by the gendered context in which they arise. Rather than being irrational or passive victims of an unequal welfare system, women actively engage with the limitations of the pension system and seek out asset strategies which seem more suited to their life trajectories, but implicitly reinforce gendered wealth inequalities.

Later life relationships and in particular the role of sex within them, have often been neglected in research due to assumptions of decline and sexlessness. We contribute to a growing body of work which counters these stereotypes by examining sexual scripts within the socio-cultural context of later life relationships. We analyzed open-text comments from the English Longitudinal Study of Aging (ELSA) collected as part of a self-completion questionnaire. In Wave 6, 1065 participants (M age 67.5, SD 9.6 years) and in Wave 8, 922 participants (M age 69.1, SD 9.01 years) responded to an open-text box question. Across both waves, 38% of respondents were men and 62% were women. The analysis used a coding template developed from existing literature and adjusted to accommodate emerging topics. A gendered analysis of the interrelated topics of relationships, sex and sexuality resulted in themes which illustrate similarities and differences in how men and women negotiate sex in later life relationships. The findings confirm that sex remains integral to intimacy in later life relationships for many men and women. However, they also demonstrate that norms of age and gender interact to shape sex and relationship practices in later life. These norms limit some people's experiences, for example, preventing them from seeking new relationships, as well as creating challenges for intimacy in partnerships. These findings extend the theoretical understanding of relationships and sex in later life.

Purpose To identify molecular features that distinguish individuals with shared clinical features of granulomatous uveitis. Design Cross-sectional observational study. Participants Four eyes from patients with active granulomatous uveitis. Methods We performed single-cell RNA sequencing with antigen-receptor sequence analysis to obtain an unbiased gene expression survey of ocular immune cells and to identify clonally expanded lymphocytes. Main Outcomes Measures For each inflamed eye, we measured the proportion of distinct immune cell types, the amount of B- or T-cell clonal expansion, and the transcriptional profile of T and B cells. Results Each individual showed robust clonal expansion arising from a single T- or B-cell lineage, suggesting distinct, antigen-driven pathogenic processes in each patient. This variability in clonal expansion was mirrored by individual variability in CD4 T-cell populations, whereas ocular CD8 T cells and B cells were more similar transcriptionally among patients. Finally, ocular B cells displayed evidence of class switching and plasmablast differentiation within the ocular microenvironment, providing additional support for antigen-driven immune responses in granulomatous uveitis. Conclusions Collectively, our study identified both conserved and individualized features of granulomatous uveitis, illuminating parallel pathophysiologic mechanisms and suggesting that future personalized therapeutic approaches may be warranted.

In the UK, individuals are increasingly responsible for achieving an adequate retirement income, yet many people are not saving enough for later life. While we understand some of the structures tha...

Metagenomic next-generation sequencing is a powerful method for pathogen detection that combines advanced genome sequencing technology with cutting-edge bioinformatics to analyze microbial populations. Metagenomic next-generation sequencing has the potential to identify uncommon, unculturable, and even previously unidentified pathogens from a clinical isolate. Of particular interest to ophthalmology, this robust data extraction can occur from very small volume clinical samples. Here we discuss the opportunities and limitations of this technique and their current and future application to ophthalmic diagnostics.

Interest in co-research with older adults has grown in the past 20 years, yet few published studies have addressed why and how older people have been involved as partners in research. This article presents a systematic review of the literature, examining the aims and challenges of co-research and the ways in which older adults can be involved in research. Systematic searches covering several databases were conducted, yielding a total of 3,293 articles, with 27 papers reviewed which involved older people as co-researchers across more than one stage of the research cycle. We find that co-research with older people offers improved understandings of the issues facing older people; more inclusive and responsive policy, practice and service design; and opportunities for co-researchers to develop new skills whilst giving voice to marginalised groups of older people. The analysis highlights the different ways in which older adults can be involved across phases of research, and identifies ethical, methodological and practical challenges encountered in the process. Involving older adults as co-researchers, while labour intensive and practically challenging, holds promise as an underdeveloped resource for social gerontology, as well as older people themselves. The paper identifies four pathways for improving and extending co-research: developing diversified structures of involvement, supporting co-researchers, embedding research rigour and ensuring co-ownership of change.

Background\ud IgE to α-Gal is a cause of mammalian meat allergy and has been linked to tick bites in North America, Australia, and Eurasia. Reports from the developing world indicate that α-Gal sensitization is prevalent but has been little investigated.\ud \ud Objective\ud We sought evidence for the cause(s) of α-Gal sensitization and lack of reported meat allergy among children in less developed settings in Ecuador and Kenya.\ud \ud Methods\ud IgE to α-Gal and total IgE were assessed in children from Ecuador (n = 599) and Kenya (n = 254) and compared with children with (n = 42) and without known (n = 63) mammalian meat allergy from the southeastern United States. Information on diet, potential risk factors, and helminth infections was available for children from Ecuador. IgG4 to α-Gal and antibodies to regionally representative parasites were assessed in a subset of children.\ud \ud Results\ud In Ecuador (32%) and Kenya (54%), α-Gal specific IgE was prevalent, but levels were lower than in children with meat allergy from the United States. Sensitization was associated with rural living, antibody markers of Ascaris exposure, and total IgE, but not active infections with Ascaris or Trichuris species. In Ecuador, 87.5% reported consuming beef at least once per week, including 83.9% of those who had α-Gal specific IgE. Levels of α-Gal specific IgG4 were not high in Ecuador, but were greater than in children from the United States.\ud \ud Conclusions\ud These results suggest that in areas of the developing world with endemic parasitism, α-Gal sensitization is (1) common, (2) associated with Ascaris exposure, and (3) distinguished by a low percentage of specific/total IgE compared with individuals with meat allergy in the United States.

Purpose To report the successful use of tofacitinib in the treatment of refractory ocular mucous membrane pemphigoid (MMP). Observations Two patients with ocular MMP presented with refractory disease after failure of multiple therapies. Treatment with tofacitinib led to durable control of conjunctival inflammation within 8 weeks and no apparent progression of sub-conjunctival fibrosis. One patient maintained absence of apparent disease activity over 16 months of follow-up. Cessation of tofacitinib in the other patient led to disease relapse which was reversed by re-initiation of therapy. Conclusions and importance Small molecule inhibitors of Janus kinases, such as tofacitinib, may offer an effective treatment option for refractory ocular MMP.

While behavioural economists posit that ‘present bias’ influences adults' propensity to save, we know very little about the cultural frameworks and internalised rationalities that people apply in real life contexts when making pension choices. This paper investigates how people anticipate the future when they make decisions about workplace pensions, considering whether they think about later life at all; if so, how they conceptualise it; and how these views shape their saving behaviour. These are important questions in the UK where private pension saving is essential to provide for old age, yet an estimated 12 million people do not invest enough for income adequacy in later life. We investigate this issue through in-depth interviews with 42 full time employees aged between 20 and 50 years, working for three large employers – a privileged group facing relatively few structural barriers to saving. Later life was considered to be a distinct and uncertain phase in the long-term future, and thinking about it was uncomfortable. Most participants were unable to imagine what retirement might be like for them. People's thoughts about the future were disconnected from their pension saving decisions, even for those who were saving at higher levels. Instead people focussed on what they can afford in the present, prioritising stability and current standard of life over long-term saving; even the people who save do so because they feel they can afford to without jeopardising their standard of living. We expect that if those in our sample with their relative advantages did not connect their present pension actions to their long term futures, this disconnect may be amplified in less privileged and more precarious groups, who have many more demands on their immediate income and far more uncertain futures. We argue that what has previously been identified as an unconscious ‘present bias’ is instead a conscious and culturally constructed mechanism that embeds everyday structural privileges into long-term savings.

An archaeological evaluation was undertaken at Mill Green, Cannock, Staffordshire, ahead of a new development for which a planning application has been submitted to Cannock District Council. The main aims of this evaluation were to establish the presence or absence of archaeological remains and to determine their character, date, extent and distribution. 21 trenches, 50m in length and 2.10m width, were excavated, at a 2% trenching strategy, and the findings recorded. The archaeological evaluation revealed that little existed on the site and that no features of archaeologically significance were found. Modern features included clay ceramic drainage pipes, potential Geotech pits, and two linear field boundaries, probably those last noted on the 1841 mapping of the site. No evidence of the postulated mill, or any associated features were noted and based on this and previous investigations across the site it is suggested that no activity occurred here until the clearance of woodland in the medieval period.

Females of child-bearing age are more resistant to infectious disease and have an increased risk of systemic lupus erythematosus (SLE). We hypothesized that estrogen-induced gene expression could establish an immunoactivated state which would render enhanced defense against infection, but may be deleterious in autoimmune development. Using peripheral blood mononuclear cells (PBMCs), we demonstrate enhanced responses with immunogen stimulation in the presence of 17β-estradiol (E2) and gene array analyses reveal toll-like receptor 8 (TLR8) as an E2-responsive candidate gene. TLR8 expression levels are up-regulated in SLE and PBMCs stimulated with TLR8 agonist display a female sex-biased, E2-sensitive response. Moreover, we identify a putative ERα-binding region near the TLR8 locus and blocking ERα expression significantly decreases E2-mediated TLR8 induction. Our findings characterize TLR8 as a novel estrogen target gene that can lower the inflammatory threshold and implicate an IFNα-independent inflammatory mechanism that could contribute to higher SLE incidence in women.

Background Red meat allergy has historically been understood as a rare disease of atopic children, but the discovery of the “α-Gal syndrome,” which relates to IgE to the oligosaccharide galactose-α-1,3-galactose (α-Gal), has challenged that notion. Objective To describe the clinical and immunologic characteristics of a large group of subjects with self-reported allergy to mammalian meat. Methods This was an observational study of 261 children and adults (range, 5-82 years) who presented for evaluation for allergic reactions to mammalian meat. Results were based on serum assays and a detailed questionnaire. Results α-Gal specific IgE ≥ 0.35 IU/mL was detected in 245 subjects and symptom onset occurred ≥2 hours after eating mammalian meat in 211 (81%). Component testing supported a diagnosis of α-Gal syndrome in 95%, pork-cat syndrome in 1.9%, and primary beef allergy in 1.1%. Urticaria was reported by 93%, anaphylaxis by 60%, and gastrointestinal symptoms by 64%. Levels of IgE and IgG specific to α-Gal were similar in subjects who reported early- or delayed-onset symptoms, and in those with and without anaphylaxis. Levels of α-Gal specific IgE and severity of reactions were similar among those with and without traditional atopy, and among children (n = 35) and adults (n = 226). Blood group B trended toward being under-represented among α-Gal-sensitized subjects; however, α-Gal specific IgE titers were high in symptomatic cases with B-antigen. Conclusions The α-Gal syndrome is a regionally common form of food allergy that has a characteristic but not universal delay in symptom onset, includes gastrointestinal symptoms, can develop at any time in life, and is equally common in otherwise nonatopic individuals.

Determination of metabolic changes that occur following the development of and after red meat challenge in alpha-gal allergic individuals will aid in biomarkers for patient identification and targeted therapeutic development.

BACKGROUND: Although sensitization to indoor allergens is strongly associated with asthma, there are questions as to how this relates to asthma symptoms.OBJECTIVE: We sought to study the relevance ...

Purpose: To compare organ specific cancer incidence risks for standard and complex external beam radiotherapy (including cone beam CT verification) following breast conservation surgery for early breast cancer. Method: Doses from breast radiotherapy and kilovoltage cone beam CT(CBCT) exposures were obtained from thermoluminescent dosimeter measurements in an anthropomorphic phantom in which the positions of radiosensitive organs were delineated. Five treatment deliveries were investigated: (i) conventional tangential field whole breast radiotherapy (WBRT), (ii) noncoplanar conformal delivery applicable to accelerated partial beast irradiation (APBI), (iii) two-volume simultaneous integrated boost (SIB) treatment, (iv) forward planned three-volume SIB, and (v) inverse-planned three volume SIB. Conformal and intensity modulated radiotherapy methods were used to plan the complex treatments. Techniques spanned the range from simple methods appropriate for patient cohorts with a low cancer recurrence risk to complex plans relevant to cohorts with high recurrence risk. Delineated organs at risk included brain, salivary glands, thyroid, contralateral breast, left and right lung, esophagus, stomach, liver, colon, and bladder. Biological Effects of Ionizing Radiation (BEIR) VII cancer incidence models were applied to the measured mean organdoses to determine lifetime attributable risk (LAR) for ages at exposure from 35 to 80 yr according to radiotherapy techniques, and included dose from the CBCTimaging. Results: All LAR decreased with age at exposure and were lowest for brain, thyroid, liver, and bladder (

Rationale: IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose (α-gal) are common in the southeastern United States. These antibodies, which are induced by ectoparasitic ticks, can give rise to positive skin tests or serum assays with cat extract. Objectives: To evaluate the relationship between IgE antibodies to α-gal and asthma, and compare this with the relationship between asthma and IgE antibodies to Fel d 1 and other protein allergens. Methods: Patients being investigated for recurrent anaphylaxis, angioedema, or acute urticaria underwent spirometry, exhaled nitric oxide, questionnaires, and serum IgE antibody assays. The results were compared with control subjects and cohorts from the emergency department in Virginia (n = 130), northern Sweden (n = 963), and rural Kenya (n = 131). Measurements and Main Results: Patients in Virginia with high-titer IgE antibodies to α-gal had normal lung function, low levels of exhaled nitric oxide, and low prevalence of asthma symptoms. Among patients in the emergency department and children in Kenya, there was no association between IgE antibodies to α-gal and asthma (odds ratios, 1.04 and 0.75, respectively). In Sweden, IgE antibodies to cat were closely correlated with IgE antibodies to Fel d 1 (r = 0.83) and to asthma (P < 0.001). Conclusions: These results provide a model of an ectoparasite-induced specific IgE response that can increase total serum IgE without creating a risk for asthma, and further evidence that the main allergens that are causally related to asthma are those that are inhaled.

Background: Chronic Kidney Disease (CKD) is associated with the development of serious co-morbidities. Patients with CKD are encouraged to adhere to regimens to lower this risk. This study aimed to explore the experiences of patients attempting to integrate lifestyle changes into their lives. Method: Face-to-face recorded interviews were conducted with nine consenting patients with CKD Stage 4 under the care of a consultant nephrologist. Each recording was analysed by two independent investigators using thematic analysis. Results: Five themes emerged: Self in relation to others, Control, Adherence, Beliefs about treatment and illness and Uncertainty. Participants highlighted the importance of personal support and recounted their sense of being a burden on close family. They described how they approached disclosure about their condition, their beliefs regarding treatment and their decision making processes and how these factors impacted on adherence to behaviour change. Conclusion: Practical support from family and healthcare professionals, a willingness to disclose their condition and help to make good decisions in difficult circumstances were identified as important factors in supporting success with behaviour change.

Purpose To establish planning solutions for a concomitant three-level radiation dose distribution to the breast using linear accelerator- or tomotherapy-based intensity-modulated radiotherapy (IMRT), for the U.K. Intensity Modulated and Partial Organ (IMPORT) High trial. Methods and Materials Computed tomography data sets for 9 patients undergoing breast conservation surgery with implanted tumor bed gold markers were used to prepare three-level dose distributions encompassing the whole breast (36 Gy), partial breast (40 Gy), and tumor bed boost (48 or 53 Gy) treated concomitantly in 15 fractions within 3 weeks. Forward and inverse planned IMRT and tomotherapy were investigated as solutions. A standard electron field was compared with a photon field arrangement encompassing the tumor bed boost volume. The out-of-field doses were measured for all methods. Results Dose–volume constraints of volume >90% receiving 32.4 Gy and volume >95% receiving 50.4 Gy for the whole breast and tumor bed were achieved. The constraint of volume >90% receiving 36 Gy for the partial breast was fulfilled in the inverse IMRT and tomotherapy plans and in 7 of 9 cases of a forward planned IMRT distribution. An electron boost to the tumor bed was inadequate in 8 of 9 cases. The IMRT methods delivered a greater whole body dose than the standard breast tangents. A contralateral lung volume >2.5 Gy was increased in the inverse IMRT and tomotherapy plans, although it did not exceed the constraint. Conclusion We have demonstrated a set of widely applicable solutions that fulfilled the stringent clinical trial requirements for the delivery of a concomitant three-level dose distribution to the breast.

Background Although associated allergies are common and the mechanism may include long-term exposure to allergens, measurement of serum specific IgE levels has not been studied in pediatric eosinophilic esophagitis (EE). Objective To compare the results of serum IgE testing, patch testing, and epicutaneous skin testing to measure allergic sensitization in pediatric patients with EE. Methods In a cross-sectional study of 53 pediatric patients with EE, relevant history was obtained by questionnaire, and patch testing to foods was performed. Food and inhalant sensitivities were also assessed using skin prick testing and serum specific IgE measurement. Streptavidin CAP was used to measure specific IgE to cross-reactive carbohydrate determinants and Helicobacter pylori . Results The overall prevalence of food and inhalant sensitization was 80%, with higher total IgE levels in sensitized vs nonsensitized patients (median, 150 vs 13 IU/mL; P P = .001). Patch test results were interpreted as positive in 39% of patients (rye, wheat, and soy were the most common). Conclusions Most, but not all, patients with EE are highly atopic individuals with frequent allergic sensitivities. Thus, serum IgE measurement of low-titer IgE antibody may be useful in identifying relevant food sensitivities and in distinguishing subgroups of patients with EE, making a more directed approach to food avoidance possible.

Anti-galactose-α-1,3-galactose IgE from allergic patients does not bind α-galactosylated glycans on intact therapeutic antibody Fc domains

Background Reports from several African countries have noted an increasing prevalence of asthma in areas of extensive urbanization. Objective To investigate the relevance of allergen-specific sensitization and body mass index (BMI) to asthma/wheezing and exercise-induced bronchospasm (EIB) among children from affluent and poorer communities within a large town in Ghana. Methods Children with physician-diagnosed asthma and/or current wheezing aged 9–16 years (n=99; cases) from three schools with differing socio-economic backgrounds [urban affluent (UA), urban poor (UP) or suburban/rural (SR)] were recruited from a cross-sectional study (n=1848) in Kumasi, Ghana, and matched according to age, sex and area of residence with non-asthmatic/non-wheezy controls. We assayed sera for IgE antibodies to mite, cat, dog, cockroach, Ascaris and galactose-α-1,3-galactose. Results Children from the UA school had the lowest total serum IgE. However, cases from the UA school had a higher prevalence and mean titre of sIgE to mite (71.4%, 21.2 IU/mL) when compared with controls (14.3%, 0.8 IU/mL) or cases from UP (30%, 0.8 IU/mL) and SR community (47.8%, 1.6 IU/mL). While similar findings were observed with EIB in the whole population, among cases there was no difference in IgE antibody prevalence or titre between children with or without EIB. BMI was higher among UA children with and without asthma; in UP and SR communities, children with EIB (n=14) had a significantly higher BMI compared with children with asthma/wheezing without EIB (n=38) (18.2 vs. 16.4, respectively, P

Transition onto haemodialysis is a time of increased psychosocial difficulty, yet, many renal patients exhibit personal resilience in continuing to lead productive lives. Using a positive psychological methodology, this qualitative study aims to identify factors identified by patients as helpful in the transition onto haemodialysis. Semi-structured interviews were undertaken with 10 patients within six months of starting haemodialysis. Interpretive content analysis identified three main themes (each with subthemes) in patients' accounts-preparation, cognitive style and social support. Limited differences arose between patients who underwent a gradual versus acute transition onto haemodialysis. Themes are discussed with reference to implications for practice development.

IgE to mammalian allergens can contribute significantly to asthma risk. Studying the details of the relationship between animal sensitization and asthma is simpler in an environment where mite, fungal, and cockroach allergens make little or no contribution to asthma risk. Methods: Quantitative assays for IgE to eight allergens were carried out on 963 sera from 19-year-olds in a population-based cohort in northern Sweden, and associations with questionnaire data from ages 7, 12, and 19 on asthma symptoms, diagnosis, and treatment were tested. Results: Overall, 79 (53%) of the students with a physician diagnosis of asthma were positive to one or more of the mammalian allergens (cat, dog, or horse danders) tested. Of the allergens assessed, only mammalian allergens, birch, and timothy grass pollen showed a significant relationship with asthma diagnosis. Multivariate analysis showed that high titer (>17.5 IU/ml) IgE to any mammalian allergen had the strongest relationship with asthma at age 19 (odds ratio 5.1 [3.0-8.6]). Furthermore, IgE to mammalian allergens gave an odds ratio of 8.5 [4.9-15] for asthma that started before age 12 and was still present at age 19. Sensitization to Fel d 1 and Fel d 4 was strongly associated with asthma and significantly reduced in cat owners. Conclusions: Sensitization to cat and dog related allergens, and specifically to the components Fel d 1 and Fel d 4, is a major risk factor for the persistence and severity of asthma in an area where these are the only significant perennial allergens.

Background: Chronic kidney disease (CKD) is associated with the development of serious co-morbidities. Patients with CKD are encouraged to adhere to regimens to lower this risk, encompassing dietary change, drug treatments and regular attendance at hospital. Engagement in self-management behaviours has been found to improve fluid management, self efficacy and nutritional outcomes (Campbell et al., 2008). Few published studies to date, have explored the patient's experience of implementing these changes. This qualitative study using semi-structured interviews aiming to explore the experiences of patients attempting to effect dietary, drug and life changes inherent in living with CKD stage 4 as recommended by their renal healthcare team. Method: The study (approved by the Cambridgeshire 1 Research Ethics Committee) was conducted in a large National Health Service teaching hospital renal unit, which provides care for more than 1100 CKD patients of multi-ethnic origin. A purposive sampling technique was adopted to recruit patients. Face-to-face recorded interviews were conducted with consented patients with CKD stage 4 under the care of a consultant nephrologist to explore their views on recommended lifestyle and dietary changes. Each recording was transcribed verbatim and analysed by two independent investigators using thematic analysis. Recruitment continued until saturation of themes occurred. Results: Nine participants were recruited. The average age was 76 years; four were male; and ethnicity included Indian Asian, other Asian, white Jewish and white British. Five themes emerged: Self in relation to others, Control, Adherence, Beliefs about treatment and illness and Uncertainty. Participants highlighted the importance of personal support and recounted their sense of being a burden on close family. They described how they approached disclosing their condition, their beliefs regarding their dietary and drug treatment and dietary decision-making processes in difficult circumstances and how, together, these factors impacted on adherence to behaviour change. Discussion: Several studies (Molzahn et al., 2008) highlight the importance of both emotional and practical support and this study associated support, particularly of a practical nature (such as changing what food was bought and eaten by the whole family), to enabling patients to adhere to recommended lifestyle changes. The sense of burden on friends and family, that patients described, is also a common finding and, in this study, it was shown to lead to concealment about the condition. Eating out and travelling was particularly difficult when trying to adhere, although patients felt unable to tell people about their dietary restrictions in an attempt to maintain control. Conversely, those who were able to disclose felt it enabled friends and family to work around these dietary restrictions and therefore support adherence. Making dietary decisions in difficult circumstances was a common problem. Krespi et al. (2004) found that participants used self-management techniques to manage these circumstances and describe ‘getting around’ dietary ‘rules’ by consuming alternative food or eating minimal amounts of ‘forbidden’ food. This study mirrored these findings precisely and also highlighted other techniques such as discovering ‘tricks’ that allowed them to adhere to dietary recommendations at the same time as attempting to be less of a burden on family and friends. Conclusions: Healthcare professionals should look to provide and encourage practical support from a variety of sources and promote a willingness in patients to disclose their condition to others. Dietitians should address good dietary decision-making in difficult circumstances such as eating out and travelling as an important factor helping adherence to recommended behaviour changes. References: Campbell, K.L., Ash, S. & Bauer, J.D. (2008) The impact of nutrition intervention on quality of life in pre-dialysis chronic kidney disease patients. Clin. Nutr.27, 537–544. Krespi, R., Bone, M., Ahmad, R., Worthington, B. & Salmon, P. (2004) Haemodialysis patients’ beliefs about renal failure and its treatment. Patient Educ. Couns.53, 189–196. Molzahn, A.E., Bruce, A. & Sheilds, L. (2008) Learning from stories of people with chronic kidney disease. Nephrol. Nurs. J.35, 13–20.

In 2009, we reported a novel form of delayed anaphylaxis to red meat related to serum IgE antibodies to the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal). Although patients were remarkably consistent in their description of a 3- to 6-hour delay between eating mammalian meat and the appearance of symptoms, this delay has not been demonstrated under observed studies.We sought to formally document the time course of clinical symptoms after the ingestion of mammalian meat in subjects with IgE to alpha-gal and to monitor ex vivo for the appearance of markers of an allergic reaction.Open food challenges were performed with mammalian meat in 12 subjects with a history of severe urticarial reactions 3 to 6 hours after eating beef, pork, or lamb, as well as in 13 control subjects. Blood samples were taken hourly during each challenge.Ten of 12 subjects with IgE to alpha-gal had clinical evidence of a reaction during the food challenge (vs none of the control subjects, P.001). The reactions occurred 3 to 7 hours after the initial ingestion of mammalian meat and ranged from urticaria to anaphylaxis. Tryptase levels were positive in 3 challenges. Basophil activation, as measured by increased expression of CD63, correlated with the appearance of clinical symptoms.The results presented provide clear evidence of an IgE-mediated food allergy that occurs several hours after ingestion of the inciting allergen. Moreover, here we report that in vivo basophil activation during a food challenge occurs in the same time frame as clinical symptoms and likely reflects the appearance of the antigen in the bloodstream.

Current understanding of the effects of reducing exposure to cat allergens is limited. It has also become clear that there are different forms of immune response to cat allergens.To investigate changes in skin tests and cat specific IgG and IgE antibodies when students from a home with a cat move to a college dormitory.Ninety-seven college students participated in a prospective study that consisted of allergy skin prick testing and serum measurement of IgE and IgG antibodies to cat at the beginning and end of one academic year in college. A subgroup returned for follow-up at the end of 2 years.Among 97 students, 33% had IgG antibodies to Fel d 1 but no evidence of sensitization, 25% had positive skin test results and/or serum IgE antibodies, and 42% had negative skin test results and no detectable serum antibodies. Among the non-cat sensitized students with IgG antibodies, the titers decreased during 8 months (P = .002). Titers of IgG4 to Fel d 1 also decreased (P.001). Among the sensitized students, no change in IgE antibodies to cat occurred in 8 months (P = .20), whereas Fel d 1 specific IgG antibodies decreased (P.001). Thus, ratios of IgG to IgE decreased highly significantly (P = .007). Among the students with negative skin test results who returned for follow-up (n = 56), none developed positive skin test results or serum IgE antibodies.Under conditions of marked decrease in exposure, no participants developed new-onset sensitization. Among the individuals sensitized at study entry, there were major decreases in the ratio of IgG to IgE.

Background Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by significant gender bias. Previous studies have demonstrated the contributions of hormones, particularly estrogen (E2), to SLE pathogenesis. E2 has been shown to regulate the expression of multiple genes through ligand activation of estrogen receptors (ER) α and β. While many ER-target genes have been previously described, many others remain to be characterized. In this work, we examined ZAS3 and toll-like receptors (TLRs) as potential targets of E2-mediated regulation. ZAS3 is a member of the ZAS family of zinc-finger transcription factors and is thought to be involved in controlling cellular growth and inflammation (1). Furthermore, recent work with large patient cohorts has shown that TLRs appear to have a strong association as SLE susceptibility markers. TLRs have also been of interest as potential autoimmune response triggers (2). Objectives Since sex hormones have been shown to play a significant role in SLE pathogenesis, we examined the effects of estrogen on gene expression in peripheral blood mononuclear cells (PBMCs) from premenopausal healthy individuals and SLE patients. Methods RNA was isolated from the peripheral blood of SLE patients and healthy donors. In addition, PBMCs were isolated and treated with a physiological dose of testosterone, E2, and/or TLR agonists. Western blotting and real-time RT-PCR of protein and mRNA expression were then analyzed, respectively. Nuclear extracts were isolated for EMSA analysis from E2-treated lymphocyte cell lines. Results In whole blood, SLE patients expressed higher levels of ZAS3 and all endosome-associated TLRs: TLR3, TLR7, TLR8, and TLR9. Also, E2-induced expression of endosomal TLRs and ZAS3 was confirmed in healthy PBMCs in vitro , while no effects were observed with testosterone treatment. EMSA analysis with intronic estrogen receptor response element probes within the ZAS3 region revealed that ERα binds directly and that E2 stimulation enhanced complex formation. Using TLR agonists to treat these cells, we identified an autocrine loop with positive feedback over TLR expression. This mechanism was observed in all endosomal TLRs. Furthermore, we discovered that TLR8 agonist stimulation of PBMCs accentuates TLR8 expression in the presence of estrogen. Not only was an enhanced response with E2 and TLR8 agonist observed, but female PBMCs were more sensitive to this effect. Conclusions Thus, the E2/ERα-mediated stimulation of ZAS3 expression occurs through direct, genomic interactions with intragenic enhancing elements. Furthermore, primary human PBMCs display heightened expression of endosome-associated TLRs in response to E2. Taken together, we propose that estrogen-induced upregulation of ZAS3 and endosomal TLRs, along with the TLR autocrine loop, lowers the inflammatory threshold. These novel mechanisms could explain, in part, the gender bias in SLE. 1. Hong JW, Allen CE, Wu LC. Inhibition of NF-kappaB by ZAS3, a zinc-finger protein that also binds to the kappaB motif. Proc Natl Acad Sci U S A 2003;100(21):12301-6. 2. Li M, Zhou Y, Feng G, Su SB. The critical role of Toll-like receptor signaling pathways in the induction and progression of autoimmune diseases. Curr Mol Med 2009;9(3):365-74. Disclosure of Interest None Declared

The relevance of allergic sensitization, as judged by titers of serum IgE antibodies, to the risk of an asthma exacerbation caused by rhinovirus is unclear.We sought to examine the prevalence of rhinovirus infections in relation to the atopic status of children treated for wheezing in Costa Rica, a country with an increased asthma burden.The children enrolled (n= 287) were 7 through 12 years old. They included 96 with acute wheezing, 65 with stable asthma, and 126 nonasthmatic control subjects. PCR methods, including gene sequencing to identify rhinovirus strains, were used to identify viral pathogens in nasal washes. Results were examined in relation to wheezing, IgE, allergen-specific IgE antibody, and fraction of exhaled nitric oxide levels.Sixty-four percent of wheezing children compared with 13% of children with stable asthma and 13% of nonasthmatic control subjects had positive test results for rhinovirus (P.001 for both comparisons). Among wheezing subjects, 75% of the rhinoviruses detected were group C strains. High titers of IgE antibodies to dust mite allergen (especially Dermatophagoides species) were common and correlated significantly with total IgE and fraction of exhaled nitric oxide levels. The greatest risk for wheezing was observed among children with titers of IgE antibodies to dust mite of 17.5 IU/mL or greater who tested positive for rhinovirus (odds ratio for wheezing, 31.5; 95% CI, 8.3-108; P.001).High titers of IgE antibody to dust mite allergen were common and significantly increased the risk for acute wheezing provoked by rhinovirus among asthmatic children.