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This study challenges dominant, academic conceptualization of resilience in light of the Lower Elwha Klallam Tribe's (LEKT) experiences of ecosystem restoration. Resilience has gained traction in social science as a framework for a community's response to environmental, social, and political disturbances, the contours of which are not well understood in Indigenous contexts. Interviews with LEKT members on the Olympic Peninsula of Washington State reveal that colonial ecological violence associated with the damming of the Elwha River in the early half of the 20th century continues to shape contemporary possibilities for Klallam resurgence, sovereignty, and self‐determination. Cultural resurgence has been enhanced; but unanticipated burdens and heightened feelings of powerlessness and deprivation remain. Resilience‐based approaches to ecosystem restoration support aspects of Indigenous survival and collective continuance, but they are unlikely to support significant revitalization and self‐determined development unless the structural basis of ecological violence and Indigenous futurisms of resurgence, self‐determination, and sovereignty are addressed. [ABSTRACT FROM AUTHOR]

This article examines place-based poverty in Indian Country, emphasizing that reservation characteristics are influenced by the system of federal Indian policy that affects American Indian self-determination and antipoverty strategies within reservation boundaries. Using data from the American Community Survey five-year file, 2006-10, I model poverty rates using multivariate, nested regression along key dimensions associated with American Indian antipoverty strategies and place-based poverty. The results indicate that rates of female-headed households and opportunity structures, such as lack of work, contribute to higher rates of reservation poverty while gaming acts as a slight buffer against poverty. Surprisingly, natural-resource-related occupations, thought to be associated with expropriation of tribal resources, was not associated with higher poverty, while self-governance compacts, acting as a proxy for tribal autonomy, had no significant impact on poverty rates. As tribal governments seek to address poverty through strategies enabled by self-determination policies, there is a critical need for more comprehensive and reliable data to understand how and whether tribal governments can effectively adapt federal policies to specific reservation conditions. [ABSTRACT FROM AUTHOR]

It has been shown that losartan inhibits vasoconstriction through binding to the thromboxane A 2 receptors. We investigated whether Thromboxane A 2 -induced platelet aggregation can be inhibited by losartan and if this effect is present in losartan treated hypertensive patients. Platelet aggregation was measured in platelet rich plasma from healthy volunteers and hypertensive patients, with the use of an aggregometer. Losartan inhibited the effect of Thomboxane A 2 agonist (U46619)-induced platelet aggregation, with a pA 2 value of 48.9 μM and inhibited both second and first phases of Adenosine diphosphate-induced aggregation, from 109 ± 9 to 65 ± 10 mm and from 62± 8 to 0 mm. U46619’s and Adenosine diphosphate's concentration required to produce half-maximal response were higher in normotensive volunteers (EC 50 2.01 ± .3 μM and 2.6 ± .4 μM) compared to the hypertensive patients without treatment (EC 50 0.6 ± .2 μM and 2.0 ± .3 μM). The concentration required to produce half-maximal response in losartan treated patients was similar to the healthy volunteers(EC 50 1.7 ± .2 μM and 1.4 ± .3 μM), whereas in the lisinopril hypertension treated patients the concentrations used, were lower (EC 50 1.4 ± .3 μM and 2.11 ± .5 μM). Losartan plasma concentration of hypertensive patients was 60.3 ± 18.7 ng/ml. Computer analysis showed that losartan, Thromboxane A 2 and the Thromboxane A 2 receptor antagonist, SQ29548 have equivalent functional groups and spatial distribution. Conclusion. We suggest that losartan inhibits platelet aggregation through Thromboxane A 2 dependent and independent mechanisms. [ABSTRACT FROM AUTHOR]

Background Context: Opioids are commonly prescribed to treat spinal pain, especially those undergoing surgery. Cannabis has been suggested as an agent that can modulate opioid needs in these patients., Purpose: To investigate the effect of cannabis use on perioperative opioid requirement and revision surgery rate in patients undergoing lumbar fusion., Study Design: Retrospective cross-sectional study., Patient Sample: A total of 48,499 patients from PearlDiver national database who underwent posterior lumbar interbody fusion., Outcome Measures: Opioid-use rates, MME, length of stay, and revision rates., Methods: Using PearlDiver, we identified patients for posterior lumbar interbody fusion (PLIF), cannabis use disorder, revision lumbar fusion, demographics, and comorbidities. Cannabis users and non-users were propensity matched for age, sex, and tobacco use. Pre and postoperative cumulative morphine milli equivalence (MME) were calculated. Opioid-use rates, MME, length of stay (LOS), and revision rates were compared using univariate analysis. Revision rates were compared using Kaplan-Meyer log-rank analysis, and logistic and cox regression., Results: Of 48,499 patients undergoing PLIF, 3.4% were identified as chronic cannabis users. They were younger, and more likely to be male and use tobacco. They had a higher rate and amount of opioid use within 90-days preoperatively, and 90- and 365-days postoperatively, after controlling for age, sex, and tobacco use. Cannabis users had longer LOS (4.4 vs 4.0 days), and a higher rate of revision surgery (6.9% vs 3.2%). Log-rank analysis, as well as logistic and cox regression confirmed an increased revision rate. Concurrent tobacco and cannabis use also had an additive effect on revision rate to 8.1%, compared with those who used only cannabis (5.4%) or tobacco (4.5%)., Conclusions: Chronic cannabis use is associated with an increased preoperative and long-term postoperative opioid use, a longer length of stay, and an increased revision rate., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Coronavirus disease 2019 (COVID-19) patients can develop pulmonary fibrosis (PF), which is associated with impaired outcome. We assessed specific leukocytic transcriptome profiles associated with PF and the influence of early dexamethasone (DEXA) treatment on the clinical course of PF in critically ill COVID-19 patients., Methods: We performed a pre-post design study in 191 COVID-19 patients admitted to the Intensive Care Unit (ICU) spanning two treatment cohorts: the pre-DEXA- (n = 67) and the DEXA-cohort (n = 124). PF was identified based on radiological findings, worsening of ventilatory parameters and elevated circulating PIIINP levels. Longitudinal transcriptome profiles of 52 pre-DEXA patients were determined using RNA sequencing. Effects of prednisone treatment on clinical fibrosis parameters and outcomes were analyzed between PF- and no-PF-patients within both cohorts., Results: Transcriptome analyses revealed upregulation of inflammatory, coagulation and neutrophil extracellular trap-related pathways in PF-patients compared to no-PF patients. Key genes involved included PADI4, PDE4D, MMP8, CRISP3, and BCL2L15. Enrichment of several identified pathways was associated with impaired survival in a external cohort of patients with idiopathic pulmonary fibrosis. Following prednisone treatment, PF-related profiles reverted towards those observed in the no-PF-group. Likewise, PIIINP levels decreased significantly following prednisone treatment. PF incidence was 28% and 25% in the pre-DEXA- and DEXA-cohort, respectively (p = 0.61). ICU length-of-stay (pre-DEXA: 42 [29-49] vs. 18 [13-27] days, p < 0.001; DEXA: 42 [28-57] vs. 13 [7-24] days, p < 0.001) and mortality (pre-DEXA: 47% vs. 15%, p = 0.009; DEXA: 61% vs. 19%, p < 0.001) were higher in the PF-groups compared to the no-PF-groups within both cohorts. Early dexamethasone therapy did not influence these outcomes., Conclusions: ICU patients with COVID-19 who develop PF exhibit upregulated coagulation, inflammation, and neutrophil extracellular trap-related pathways as well as prolonged ICU length-of-stay and mortality. This study indicates that early dexamethasone treatment neither influences the incidence or clinical course of PF, nor clinical outcomes., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: With the expansion of animal production, parasitic helminths are gaining increasing economic importance. However, application of several established deworming agents can harm treated hosts and environment due to their low specificity. Furthermore, the number of parasite strains showing resistance is growing, while hardly any new anthelminthics are being developed. Here, we present a bioinformatics workflow designed to reduce the time and cost in the development of new strategies against parasites. The workflow includes quantitative transcriptomics and proteomics, 3D structure modeling, binding site prediction, and virtual ligand screening. Its use is demonstrated for Acanthocephala (thorny-headed worms) which are an emerging pest in fish aquaculture. We included three acanthocephalans (Pomphorhynchus laevis, Neoechinorhynchus agilis, Neoechinorhynchus buttnerae) from four fish species (common barbel, European eel, thinlip mullet, tambaqui)., Results: The workflow led to eleven highly specific candidate targets in acanthocephalans. The candidate targets showed constant and elevated transcript abundances across definitive and accidental hosts, suggestive of constitutive expression and functional importance. Hence, the impairment of the corresponding proteins should enable specific and effective killing of acanthocephalans. Candidate targets were also highly abundant in the acanthocephalan body wall, through which these gutless parasites take up nutrients. Thus, the candidate targets are likely to be accessible to compounds that are orally administered to fish. Virtual ligand screening led to ten compounds, of which five appeared to be especially promising according to ADMET, GHS, and RO5 criteria: tadalafil, pranazepide, piketoprofen, heliomycin, and the nematicide derquantel., Conclusions: The combination of genomics, transcriptomics, and proteomics led to a broadly applicable procedure for the cost- and time-saving identification of candidate target proteins in parasites. The ligands predicted to bind can now be further evaluated for their suitability in the control of acanthocephalans. The workflow has been deposited at the Galaxy workflow server under the URL tinyurl.com/yx72rda7 ., (© 2022. The Author(s).)

Background: A central question in parasitology is why parasites mature and reproduce in some host species but not in others. Yet, a better understanding of the inability of parasites to complete their life cycles in less suitable hosts may hold clues for their control. To shed light on the molecular basis of parasite (non-)maturation, we analyzed transcriptomes of thorny-headed worms (Acanthocephala: Pomphorhynchus laevis), and compared developmentally arrested worms excised from European eel (Anguilla anguilla) to developmentally unrestricted worms from barbel (Barbus barbus)., Results: Based on 20 RNA-Seq datasets, we demonstrate that transcriptomic profiles are more similar between P. laevis males and females from eel than between their counterparts from barbel. Impairment of sexual phenotype development was reflected in gene ontology enrichment analyses of genes having differential transcript abundances. Genes having reproduction- and energy-related annotations were found to be affected by parasitizing either eel or barbel. According to this, the molecular machinery of male and female acanthocephalans from the eel is less tailored to reproduction and more to coping with the less suitable environment provided by this host. The pattern was reversed in their counterparts from the definitive host, barbel., Conclusions: Comparative analysis of transcriptomes of developmentally arrested and reproducing parasites elucidates the challenges parasites encounter in hosts which are unsuitable for maturation and reproduction. By studying a gonochoric species, we were also able to highlight sex-specific traits. In fact, transcriptomic evidence for energy shortage in female acanthocephalans associates with their larger body size. Thus, energy metabolism and glycolysis should be promising targets for the treatment of acanthocephaliasis. Although inherently enabling a higher resolution in heterosexuals, the comparison of parasites from definitive hosts and less suitable hosts, in which the parasites merely survive, should be applicable to hermaphroditic helminths. This may open new perspectives in the control of other helminth pathogens of humans and livestock., (© 2022. The Author(s).)

Objectives: Pain is a known complication in persons with hemophilia (PWH) as a result of muscle and joint bleeding. Little is known regarding national Hemophilia Treatment Center (HTC) practice patterns related to pain management. The aim of this study was to: 1) Describe pain management practice patterns of HTC providers, 2) Identify gaps and areas of alignment with the CDC pain guidelines, and 3) Address educational opportunities for pain management. This survey is the first extensive description of multidisciplinary practice patterns of pain management for PWH., Methods: This descriptive study involved physicians, nurse practitioners, nurses, physical therapists, and social workers from federally funded Hemophilia Treatment Centers (HTC) eligible to complete an online survey exploring pain management practice patterns within the CDC pain guidelines., Results: Results of this survey shed light on areas of strength and cohesiveness between HTC providers, including the following: dedication to effective pain management, utilization of non-pharmacological pain options, trial of non-opioid medications first before opioids, maintaining follow-up with patients after opioid prescription initiation, recognizing and utilizing clinically important findings before prescribing opioids, and counseling their patients regarding potential risk factors., Conclusions: There remain opportunities to incorporate into clinical practice consistent use of tools such as formal screening questionnaires, opioid use agreements, written measurable goals, ongoing prescription monitoring, and written plans for discontinuation of opioid therapy. These results provide opportunities for improvement in education of HTC team members thus optimizing pain management in persons with bleeding disorders., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Academy of Pain Medicine.)

Thorny-headed worms (Acanthocephala) are endoparasites exploiting Mandibulata (Arthropoda) and Gnathostomata (Vertebrata). Despite their world-wide occurrence and economic relevance as a pest, genome and transcriptome assemblies have not been published before. However, such data might hold clues for a sustainable control of acanthocephalans in animal production. For this reason, we present the first draft of an acanthocephalan nuclear genome, besides the mitochondrial one, using the fish parasite Pomphorhynchus laevis (Palaeacanthocephala) as a model. Additionally, we have assembled and annotated the transcriptome of this species and the proteins encoded. A hybrid assembly of long and short reads resulted in a near-complete P. laevis draft genome of ca. 260 Mb, comprising a large repetitive portion of ca. 63%. Numbers of transcripts and translated proteins (35,683) were within the range of other members of the Rotifera-Acanthocephala clade. Our data additionally demonstrate a significant reorganization of the acanthocephalan gene repertoire. Thus, more than 20% of the usually conserved metazoan genes were lacking in P. laevis. Ontology analysis of the retained genes revealed many connections to the incorporation of carotinoids. These are probably taken up via the surface together with lipids, thus accounting for the orange coloration of P. laevis. Furthermore, we found transcripts and protein sequences to be more derived in P. laevis than in rotifers from Monogononta and Bdelloidea. This was especially the case in genes involved in energy metabolism, which might reflect the acanthocephalan ability to use the scarce oxygen in the host intestine for respiration and simultaneously carry out fermentation. Increased plasticity of the gene repertoire through the integration of foreign DNA into the nuclear genome seems to be another underpinning factor of the evolutionary success of acanthocephalans. In any case, energy-related genes and their proteins may be considered as candidate targets for the acanthocephalan control., Competing Interests: The authors have declared that no competing interests exist.

Heptatocellular (HCC) is a rapidly progressive fatal malignancy often presenting at an advanced stage at the time of initial diagnosis. Loco-regional therapies for early-stage HCC including surgical options (surgical resection and liver transplant) and percutaneous ablations could be potentially curative. Recent technological advances in percutaneous image-guided ablations have provided clinicians with a range of options which have proven to be equal to or better than surgical resection. For intermediate- and advanced-stage HCC, palliative therapies are available which significantly increase overall and progression-free survival. These palliative therapies include intra-arterial chemo- or radioembolization as monotherapy or in combination with percutaneous ablation or antiangiogenic drugs. Availability of a multitude of treatment options for various stages of HCC as well as conflicting data comparing their safety and efficacy presented in the several randomized controlled trials poses a significant challenge to hepatologists, surgeons, and interventional radiologists in selecting optimal therapy for their patients. The aim of this article is to review and discuss currently available therapies at each stage of HCC along with presenting clinical data published in most recent and relevant randomized controlled trials.

Peripheral artery disease (PAD) is associated with exercise impairment and greater thrombotic risk. We investigated whether clot formation and platelet aggregation assessed by thromboelastography and light-transmission aggregometry correlate with the severity of symptomatic PAD assessed by ambulatory function measures. We studied 40 symptomatic patients with PAD in whom severity of disease was assessed using ankle-brachial index, peak walking time (PWT), claudication onset time, peak oxygen uptake, daily ambulatory activity, and walking impairment questionnaire (WIQ) scores. Clot strength correlated negatively with peak oxygen uptake, PWT, WIQ distance, and stair-climbing scores. Time to clot formation did not correlate with exercise parameters. Platelet aggregation was negatively correlated with WIQ distance score and was positively correlated with PWT and peak oxygen uptake. In conclusion, clot strength and platelet aggregation correlated with objective and self-perceived ambulatory measures. Patients with PAD having more severe walking impairment may be likely to form stronger clots., (© The Author(s) 2014.)

Objectives: Patients with peripheral artery disease have walking impairment, greater thrombotic risk, and are often treated with exercise training. We sought to determine the effect of a 3-month-long exercise program on clot strength among patients with peripheral artery disease and intermittent claudication., Methods: Twenty-three symptomatic peripheral artery disease patients were randomly assigned to a walking exercise program or to an attention control group who performed light resistance exercise. We investigated the effect of exercise training on clot strength and time to clot formation was assessed by thromboelastography., Results: After 3 months of exercise, clot strength (maximal amplitude) and time to clot formation (R) did not change significantly from baseline, even after improvements in claudication onset time (p < 0.01) and peak walking time (p < 0.05). Furthermore, changes in clot formation parameters were not significantly different between groups. Among the 10 individuals demonstrating a reduction in clot strength (reduced maximal amplitude), one was a smoker (10%) compared to 9 of 13 non-responders (69%) whose maximal amplitude was unchanged or increased (p = 0.0097)., Conclusion: In this ancillary study, a 12-week walking program improved ambulatory function in peripheral artery disease patients with claudication, but does not modify clot strength or time to clot formation. Larger studies are needed to confirm these hypothesis generating findings and to determine whether a different amount or type of exercise may induce a change in clotting in this patient population.

Background and Objectives: Rivaroxaban, a new oral anti-Xa agent, has been approved for use without routine monitoring, but the lack of a predictable drug level measurement may hinder the management of anticoagulated patients. The aims of the project were to correlate a Anti-Factor Xa assay using commercial calibrators and controls (Riva Activity) with serum drug levels analyzed by HPLC-MS/MS (Riva MS) in patients currently receiving rivaroxaban, and secondly, to correlate the PT/PTT, thrombin generation (CAT assay) and Thromboelastograph (TEG) with the Riva activity and Riva MS., Methods: Recruited patients receiving rivaroxaban prospectively had a total of 3 blood samples taken at least 2 hours apart. Plasma was divided for measurement of PT/PTT, Riva activity, rivaroxaban HPCL-MS/MS, and thrombin generation. TEG activity was measured at one random time point for each patient. Correlation and linear regression evaluations were used to compare the different assays., Results: The cases were 22 patients on rivaroxaban, age 56+12.6, and 10 healthy controls. There was a strong correlation between Riva activity compared to serum Riva MS (r=0.99). We found a statistically significant correlation between PT/INR compared to serum measurements of Riva MS (r=0.68) and anti-Xa activity (r=0.69). The peak (r=-0.50) and lag time (r=0.57) CAT correlated with Riva MS measurements. There was no correlation between Riva MS and PTT, TEG R, TEG MA, Endogenous Thrombin potential., Conclusion: Riva anti-factor Xa activity assay measured with commercial calibrators and controls provides a reliable assessment of rivaroxaban serum levels for patients requiring measurement of anticoagulant activity. Correlation with other coagulation tests is not sufficiently strong to be used clinically., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Women with peripheral arterial disease (PAD) have more limited physical function than men but the mechanisms involved are not clear. We determined whether alterations in lipid components, such as decreased high-density lipoprotein cholesterol (HDL-C), are associated with worsening intermittent claudication (IC) in postmenopausal women with PAD. Our cross-sectional cohort study included 69 postmenopausal women with IC (Fontaine stage II). A treadmill test was used to measure initial claudication distance (ICD), absolute claudication distance (ACD), peak oxygen uptake, and ankle systolic blood pressure. High-density lipoprotein cholesterol correlated with ankle brachial index ([ABI]; R = .29, P = .019). No other lipid profile components were associated with exercise performance and hemodynamic measures. Among women with HDL-C <50 mg/dL (n = 43), the median peak oxygen uptake level was significantly lower (P = .021) relative to women with normal HDL-C >50 mg/dL (n = 26). Lower HDL-C levels are associated with worse ABI and decreased peak oxygen uptake in postmenopausal women with PAD.

PER.C6, a cell line derived from human embryonic retinal cells transformed with the Adenovirus Type 5 (Ad5) E1A and E1B genes, is used to produce E1-deleted Ad5 vectors such as the MRKAd5 HIV-1 gag vaccine. While whole, live PER.C6 cells are capable of growing as tumours when transplanted subcutaneously into immunodeficient nude mice at a high dosage, the process for vaccine production includes filtration steps and other methods which effectively preclude contamination by intact viable substrate cells. However, because of the neoplastic nature of this cell line, we carried out a series of investigations to assess the tumorigenic risk posed by residuals from the cell substrate in a vaccine. To address concerns about transmission of oncogenic DNA, we demonstrated that purified PER.C6 cellular DNA does not induce tumours in newborn hamsters or nude mice. To address concerns about other potential residuals, including hypothetical adventitious tumour viruses, we demonstrated that a PER.C6 cell lysate and a MRKAd5 HIV-1 gag vaccine produced on PER.C6 cells do not induce tumours in newborn hamsters or newborn rats. These results, in conjunction with the wide panel of viral safety tests performed on these cells, support the safety of the PER.C6 as a cell substrate for vaccine production.

While the heart size maintains a constant proportion to body size, heart function parameters, such as heart rate and cardiac output, show a more complex scaling pattern. How these phenomena affect the long-axis left ventricular (LV) function is unknown. We studied 10 mice, 15 rats, 6 rabbits, 8 mongrel dogs and 38 human volunteers. Doppler tissue echocardiography data were postprocessed to reconstruct mitral annulus (MA) peak systolic velocity and displacement. The relationship between MA peak velocity, MA displacement and LV ejection time, and LV end-diastolic volume (and mass) were fit to an allometric (power-law) equation Y=kMbeta. LV mass varied from 0.062 to 255 g, while end-diastolic volume varied from 0.014 to 205 ml. beta values of the relation between LV ejection time and LV end-diastolic volume and mass were 0.247+/-0.017 and 0.267+/-0.018, respectively. beta values of the relationship between MA displacement and LV end-diastolic volume and mass were 0.358+/-0.047 and 0.390+/-0.051 (P<0.023 versus beta of LV ejection time). beta values of the relationship between MA peak systolic velocity and LV end-diastolic volume and mass were 0.096+/-0.012 and 0.100+/-0.013, respectively (P<0.0001 versus 0). Finally, beta values of the relationship between the long-to-short axis displacement ratio and LV end-diastolic volume and mass were 0.077+/-0.017 and 0.086+/-0.019 (P<0.0001 versus 0). We conclude that MA velocity, displacement, and long-to-short axis displacement ratio scale allometrically to heart size. This reduces the relative long-axis contribution to heart function in small mammals.

Objective: The combination of push and sonde enteroscopy permits endoscopic evaluation to extend the distal small bowel. Our objective was to determine the yields of both push and sonde enteroscopy in patients with obscure GI bleeding., Methods: We retrospectively reviewed 553 small bowel examinations performed with an orally passed 135-cm pediatric colonoscope in combination with a 2750-cm per nasal sonde enteroscope to investigate the small bowel for sources of gastrointestinal bleeding of obscure origin., Results: The examination reached the distal jejunum or beyond in over 90% of patients undergoing both push and sonde enteroscopy. The yield of these combined studies was 58% for identifying a possible source of gastrointestinal blood loss. In 40% of the examinations, the abnormality was found distal to the limits of routine upper gastrointestinal endoscopy. In 26% of all examinations, the lesion was detectable only by sonde enteroscopy. The most common small bowel findings were mucosal vascular lesions (31% of all exams) and tumors (6%). No major endoscopic complications occurred, and patients tolerated the procedures well., Conclusions: The combination of push and sonde enteroscopy is a valuable tool in the evaluation of obscure gastrointestinal bleeding and may provide useful information necessary to formulate treatment plans aimed at cessation of bleeding.

The current status of screening mammography in the Tampa Bay area is evaluated by three parameters: accessibility, cost and quality, and the screening resources necessary to reach the National Cancer Institute's (NCI) cancer control goals for the year 2000 in this area are projected. Fifty-two mammographic facilities were surveyed comprising 64 units in Pinellas, Hillsborough, Pasco and Manatee Counties. The number of units is adequate to serve the current needs of the population eligible for screening; however, the number of facilities offering low-cost examinations is not adequate. Only a few facilities have documented quality assurance through the American College of Radiology. These results and those projected for the year 2000 suggest that new efforts will be necessary to meet the NCI-2000 goal for screening mammography. We have made recommendations to clinicians and radiologists for strategies to meet this challenge.

We describe the development of specific immunoassays for IgG4 protein and for allergen-specific IgG4 antibodies. We also measured the concentrations of IgG4 protein and determined the frequencies of detectable IgG4 antibodies to several common allergens in sera from adults and children with asthma and from nonallergic subjects. Serum concentrations of IgG4 protein increase with age but are not different in children with asthma and nonallergic children, nor does a raised serum concentration predict a severe clinical course in childhood asthma. IgG4 antibodies to milk and egg are common in children and adults and are more common in children with asthma than in nonallergic children less than 3 years of age. The presence of detectable IgG4 antibodies or a raised concentration of IgG4 protein in serum is not useful empirically as a diagnostic indicator of asthma but more likely results from antigen exposure occurring at mucosal surfaces.