Search

Iron-depleted donors are at increased risk of developing anemia; if these donors could be identified by a screening test, iron supplementation or decreased donation frequency could be considered. Tests to determine serum ferritin, blood hemoglobin, and erythrocyte (Erc)-zinc protoporphyrin concentrations were examined in 679 consecutive female blood donors to identify donors with non-anemic iron deficiency. The test to determine serum ferritin is expensive and slow, whereas the two latter tests are rapid and less costly and could therefore be used for screening. Women in the fertile age groups had the lowest average serum ferritin values. In all, 93 women (13.7%) had depleted iron stores, as indicated by serum ferritin concentrations less than 14 micrograms/L. In these women, a much better correlation was found between Erc-zinc protoporphyrin and serum ferritin (rs = -0.49, P less than 0.001) than between blood hemoglobin and serum ferritin (rs = 0.31, P less than 0.01). These findings suggest that measurement of Erc-zinc protoporphyrin is superior to that of blood hemoglobin in identifying donors with non-anemic iron deficiency.

Objective: To compare nursing homes (NHs) that report different staffing statistics on quality of care.Data Sources: Staffing information generated by California NHs on state cost reports and during onsite interviews. Data independently collected by research staff describing quality of care related to 27 care processes.Study Design: Two groups of NHs (n=21) that reported significantly different and stable staffing data from all data sources were compared on quality of care measures.Data Collection: Direct observation, resident and staff interview, and chart abstraction methods.Principal Findings: Staff in the highest staffed homes (n=6), according to state cost reports, reported significantly lower resident care loads during onsite interviews across day and evening shifts (7.6 residents per nurse aide [NA]) compared to the remaining homes that reported between 9 to 10 residents per NA (n=15). The highest-staffed homes performed significantly better on 13 of 16 care processes implemented by NAs compared to lower-staffed homes.Conclusion: The highest-staffed NHs reported significantly lower resident care loads on all staffing reports and provided better care than all other homes. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To demonstrate the reliability and feasibility of a standardized protocol to assess and score urinary incontinence care in nursing homes. DESIGN: Descriptive. SETTING: Eighteen nursing homes (NHs). PARTICIPANTS: Four hundred twenty-six incontinent residents. MEASUREMENTS: Resident interview data were used to score three quality indicators, and usable data were retrieved from 117 (27%) of 426 incontinent residents in 18 homes who were selected for interview based on evidence that they could accurately describe the care they received. Medical record data were used to score six quality indicators for a subset of 58 participants in five homes. RESULTS: Zero to 98% of the participants were scored as receiving care consistent with the intent of the indicator across the nine indicators. All NHs failed to provide chart documentation of an assessment to determine an incontinent resident's appropriateness for a scheduled toileting program (0% passed). The absence of an assessment to determine a resident's potential responsiveness to toileting assistance may explain why 103 incontinent residents who were documented on the Minimum Data Set as being on a scheduled toileting program reported that they received the same number of toileting assists per day (1.3) as the group of 114 incontinent residents who were not on a scheduled toileting program (1.0). The received toileting assistance frequencies reported by both groups were too low to maintain continence. CONCLUSION: The standardized quality assessment system generated scores for nine incontinence quality indicators with good interrater reliability and provided explicit scoring rules that can facilitate replication. The focus of the indicators on care processes that are under the control of NH staff make the protocol useful for external survey and internal quality improvement purposes. [ABSTRACT FROM AUTHOR]

Purpose: To determine if nursing homes that score in the lower 25th percentile (low prevalence) versus the upper 75th percentile (high prevalence) on each of two Minimum Data Set (MDS) incontinence quality indicators provide different incontinence care processesDesign: Cross-sectional.Subjects: 347 long-term residents in 14 skilled nursing facilities for the MDS "prevalence of incontinence" indicator and 432 residents in 16 skilled nursing facilities for the MDS "prevalence of incontinence without a toileting plan" indicator.Measures: Nine care processes related to incontinence were defined and operationalized into clinical indicators. Research staff assessed implementation of each care process on 3 consecutive 12-hour days (7 am to 7 pm ). The assessment included resident interviews, physical performance evaluations, and chart abstraction using standardized protocols.Results: Homes with lower prevalence rates on both MDS incontinence quality indicators (good outcomes) had a significantly higher proportion of participants with chart documentation of two relevant care processes: 1 an evaluation of the resident's incontinence history and 2 toileting assistance rendered by staff. However, interviews with incontinent residents capable of accurately reporting care activity occurrence showed no difference in toileting assistance frequency between homes in the upper and lower quartiles for either MDS incontinence indicator. Participants reported an average of 1.8 toileting assists per day across all homes with a narrow average frequency range between homes (1.6-2.0). These frequencies of toileting assistance are not sufficient to improve urinary incontinence. There was also no difference in the frequency of toileting assistance received by incontinent participants rated on the MDS as receiving scheduled toileting (n = 75, mean = 1.9 +/- 1.24) compared to incontinent residents rated on the MDS as not receiving scheduled toileting (n = 131, mean = 1.8 +/- 1.22). None of the homes provided chart documentation that supported staff decisions to place or not place a resident on a scheduled toileting program.Conclusions: The quality of incontinence assessment and treatment as documented by scheduled toileting interventions was poor across all homes, and the MDS incontinence quality indicators were not associated with clinically important differences in related care processes. Chart documentation that a resident was on a scheduled toileting program or received toileting assistance was not related to resident reports of the frequency of received assistance. [ABSTRACT FROM AUTHOR]

Aim: To assess the effectiveness of thermography, colorimetry, and oximetry at detecting temperature changes after erythema induction across diverse skin tones in healthy adults., Materials and Methods: Erythema was induced at the forearm and ulnar head (UH) using a cupping device. Temperature via thermal image, erythema value via colorimeter, and oxygen saturation via oximeter were collected immediately and 5-10 min (delayed) after cupping at both sites., Results: At the forearm, the delayed timepoint was significantly warmer than baseline. At the UH, the immediate timepoint was significantly colder than baseline. Erythema increased at both timepoints and both locations. The correlation between temperature change and erythema change was weak. Change in temperature did not differ between skin tone groups. The Intermediate Low Eumelanin skin tone group had more change in erythema compared to the Intermediate Mid (i.e., darkest) skin tone group immediately after cupping at the UH and at the delayed timepoint at the forearm., Conclusions: This study observed differences in the change of erythema across skin tones but did not observe differences in temperature across skin tones. Given high variability in results, it is premature to conclude thermal imaging works equally well across all skin tones. Further research is necessary to validate the effectiveness of thermal imaging in diverse populations. Results suggest visual erythema may be a problematic indicator as less erythema was consistently noted in participants with dark skin tones. The potential of technology to increase our ability to detect erythema warrants further investigation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Tissue Viability Society / Society of Tissue Viability. Published by Elsevier Ltd. All rights reserved.)

Objective: Examine pressure injury (PrI) pain severity, stability, and current treatment of PrI pain among nursing home (NH) residents using two assessment tools and a descriptive cohort study design., Background: PrI pain affects quality of life of NH residents yet, best assessment methods, stability of PrI pain, and how to take care of the pain are not well known., Methods: Data collected from 33 residents with PrI (stages 1-4) from 4 NHs. All PrI were staged and assessed using the Bates-Jensen Wound Assessment Tool (BWAT) to determine severity. Verbal Response Scale (VRS) and Pain Assessment in Advanced Dementia (PAINAD) were used to assess general and PrI pain 3 times a day for two days within one week. Data classified as: no, mild, moderate, or severe pain. Proportions of participants with different levels of PrI pain were calculated. T tests were conducted to examine differences across time; VRS and PAINAD were examined for agreement., Results: Participants were 74 % female, 49 % white, 58 % cognitively intact, 58 % functionally dependent, and had mean age of 82 years old. The majority (52 %; n = 17) were full thickness PrI, stage 3 (n = 5), stage 4 (n = 7), unstageable (n = 5). The majority of participants (82 %; n = 27) reported PrI pain on at least one of six assessments over the two days; with 57 % mild, 26 % moderate and 16 % severe pain. More severe pain occurred in afternoon. No differences existed across days. Although there was a positive relationship between VRS and PAINAD in pain assessments (r = 0.38, P<.05), the agreement between the two scales, as indicated by Cohen's kappa (K = 0.19, p=.28), was found to be poor. Of those with PrI pain, 22 % had pain documented in the Minimum Data Set (MDS). Only 42 % of participants who reported PrI pain received pain medication within 12 h of initial pain assessment. Out of 28 participants who received routine pain medication for general pain, 18 of them reported experiencing no pain., Conclusion: While VRS and PAINAD scores exhibited a relationship, their agreement was limited. Documentation of PrI pain on the Minimum Data Set (MDS) was found to be inadequate. Notably, 40 % of participants reported higher levels of PrI pain in the afternoon, suggesting this time may be opportune for PrI pain assessment and management. Interestingly, participants who received medication for general pain did not report PrI pain, suggesting that treatment of general pain may effectively alleviate PrI pain symptoms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Objective: To determine if subepidermal moisture (SEM) measures help detect and prevent intraoperative acquired pressure injuries (IAPIs) for prone-position surgery., Methods: In this clinical trial of patients (n = 39 preintervention, n = 48 intervention, 100 historical control) undergoing prone-position surgery, researchers examined the use of multidimensionally flexible silicone foam (MFSF) dressings applied preoperatively to patients' face, chest, and iliac crests. Visual skin assessments and SEM measures were obtained preoperatively, postoperatively, and daily for up to 5 days or until discharge. Electronic health record review included demographic, medical, and surgery data., Results: Of the 187 total participants, 76 (41%) were women. Participants' mean age was 61.0 ± 15.0 years, and 9.6% were Hispanic (n = 18), 9.6% were Asian (n = 18), 6.9% were Black or African American (n = 13), and 73.8% were White (n = 138). Participants had a mean Scott-Triggers IAPI risk score of 1.5 ± 1.1. Among those with no erythema preoperatively, fewer intervention participants exhibited postoperative erythema on their face and chest than did preintervention participants. Further, fewer intervention participants had SEM-defined IAPIs at all locations in comparison with preintervention participants. The MFSF dressings overcame IAPI risk factors of surgery length, skin tone, and body mass index with fewer IAPIs in intervention participants., Conclusions: Patients undergoing prone-position surgeries developed fewer IAPIs, and SEM measures indicated no damage when MFSF dressings were applied to sites preoperatively. The SEM measures detected more damage than visual assessment., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To examine the effectiveness of the ColorMeter DSM III (ColorMeter; Cortex Technology) at grouping individuals by skin tone and measuring erythema/skin discoloration after erythema induction across skin tones., Methods: This pre/post experimental study induced erythema on a convenience sample of 61 healthy adults. Skin tone at baseline was measured using the ColorMeter, Munsell Soil Color Chart 5YR (Munsell), and Pantone SkinTone Guide (Pantone) and compared with the Eumelanin Human Skin Colour Scale (Eumelanin Scale) groupings. Erythema and melanin values on the arm immediately and after recovery time were compared with baseline values. Melanin was measured at five body regions on the face and arm., Results: Participants were predominantly women (64% [n = 39] women, 36% [n = 22] men) and young (mean, 28.8 ± 14.3 years); 5% (n = 3) were Hispanic, 26% (n = 16) Asian, 29% (n = 18) Black, 38% (n = 23) White, and 7% (n = 4) identified with more than one race. ColorMeter lightness (L*) and melanin measures were strongly correlated with both Munsell and Pantone values. Munsell skin tone groups were not aligned with Eumelanin Scale groupings. Most participants were in the Eumelanin intermediate-low group, and this changed depending on which body location melanin value was used. The change in erythema from baseline did not differ significantly across skin tone groups at the ulnar head, but on the forearm at the delayed time point, significant differences existed between light and both medium and dark skin tone groups (P = .001; 95% CI, 0.04-0.37)., Conclusions: The ColorMeter provides an effective objective measure of skin tone and erythema/discoloration across various skin tones and may improve on current standards for detection. The proposed Eumelanin Scale-Modified provides additional sensitivity for persons with medium skin tones., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Recruitment to the local tissue and alerted phenotype are the hallmarks of basophils in chronic urticaria (CU). Chemokine receptors such as chemokine (C-C motif) receptor 4 (CCR4) or CCR8 have been studied in skin diseases, e.g., atopic dermatitis, but not in CU. In this study, we aimed to define CU's basophil homing potential and receptor profile and the effect of Omalizumab treatment on these. Unstimulated and activated (anti-IgE, fMLP, C5a, and Substance P) whole blood basophils from 11 Omalizumab-treated CU patients and 10 healthy subjects were investigated with flow cytometry. Unstimulated basophils in CU showed higher expression of the skin-associated (CCR8) and scavenger (CCX-CKR) receptors and lower expression of the lung-associated (CCR3) receptor in contrast to healthy ones. IgE-mediated activation increased the percentage of CCR8 and CCX-CKR in CU compared to healthy group and elevated the expression of the lung-associated chemokine receptor, XCR1, in all groups. A trend of augmented expression of the coagulation cascade (CD87) and fMLP (FPR1) receptors was seen on basophils in CU, while a tendency of reduced expression was seen for itch (IL-31RA) and immunotolerance (CD109) receptors. fMLP and C5a increased the expression of CCR4, CCR8, CCX-CKR, and CD87 and decreased CCR2 and CCR3, though no changes between the groups were found. In conclusion, CU basophils exhibit skin-homing potential amplified by IgE-mediated stimulation.

Background: Chronic urticaria (CU) is a skin condition driven by mast cells and basophils. The exact responsiveness profile of these cells, especially regarding the anti-IgE treatment, Omalizumab, is not fully investigated. We sought to characterize the surface activation profile of basophils in CU during Omalizumab treatment and their responsiveness to IgE and non-IgE stimulation., Methods: Whole blood basophils from 11 CU patients and 10 healthy controls were stimulated with either medium, anti-IgE, fMLP, C5a, or Substance P for 30 min and characterized by flow cytometry., Results: CU patients showed a broad range of basophil count as opposed to healthy subjects. An increased number of unstimulated CD69 + ( p  = 0.05), but not CD63 + basophils was observed in CU groups in comparison to healthy. The expression of CD203c and CD200R were comparable between all groups, whilst the FcεRI was reduced with the treatment. Both IgE and non-IgE mediated stimulations upregulated CD63, CD203c and CD200R, but not CD69 in all groups, however, no difference between the groups was observed. Among unstimulated basophils, expression of MRGPRX2 was higher in CU patients after Omalizumab treatment than in the healthy group (2.4% vs. 1.5%, p  = 0.01). The anti-IgE stimulation increased the number of MRGPRX2-expressing basophils in the CU group before and after omalizumab as compared to the healthy ( p  = 0.003; p  = 0.005). The fMLP and C5a stimulations showed a similar effect to the IgE-mediated stimulation. The MRGPRX2 ligand, Substance P did not activate basophils., Conclusion: CU basophils show increased expression of MRGPRX2 after IgE and non-IgE stimulation., Competing Interests: All authors declare no conflicts of interest., (© 2022 The Authors. Skin Health and Disease published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Mast cells (MCs) are distributed in tissues throughout the body and are highly involved in many physiological and pathophysiological processes. The potential and involvement of different MC phenotypes are still not well understood. MCs are present in blood vessel walls, but their specific phenotypic features are unknown. We aimed at characterizing MCs from human saphenous veins for localization, mediator content, and receptor expression. This was done in MCs from both healthy and varicose human saphenous veins (hSV and vSV, respectively). For both vSV and hSV, we found that vein MCs are mainly present in the tunica adventitia (99% MCs in adventitia) and that the population consists of both MC T and MC TC phenotypes (vSV: 55% MC T , hSV: 64% MC T ). The vein MCs contained high levels of histamine (vSV: 27 pg/MC, hSV: 55 pg/MC) and tryptase (vSV: 98 pg/MC, hSV: 111 pg/MC), indicating a strong potential for regulatory effects on blood vessels. The receptor expression of FcεRI, MRGPRX2, PTAFR, C3aR, and C5aR was found, even though the percentage of positive cells differed between vSV and hSV MCs. We conclude that vein MCs from the blood vessel wall have a high potential to affect the tissue around them.

Background: The basophil histamine release (HR) assay can be used for allergy diagnosis in addition to the conventional measurement of allergen-specific IgE (sIgE). Passive sensitization of basophils increases the versatility and allows testing the biological relevance of allergen-induced IgE cross-linking in any serum unbiased by the cellular component. However, not all the patient sera perform equally well and we hypothesized that the absolute level and fraction of sIgE affect the performance. Choosing birch pollen allergy as a model, we investigated the concentration of sIgE needed for successful passive sensitization using soluble- or matrix-fixed Bet v 1., Methods: Twenty-eight sera with Bet v 1 sIgE [7 sera within each allergy class (1: 0.1-0.70 kUA/L, 2: 0.71-3.50 kUA/L, 3: 3.51-17.50 kUA/L, and 4+: >17.50 kUA/L)] and a negative control serum pool were used to passively sensitize donor basophils, obtained from buffy coat blood ( n = 3). The cells were incubated (30 min) with a soluble allergen (rBet v 1 from 0.2 to 50 ng/ml), matrix-fixed allergen (ImmunoCAP™ containing recombinant Bet v 1), or phorbol 12-myristate 13-acetate (PMA)/ionomycin mixture (maximal HR) and released histamine was quantified fluorometrically., Results: The lowest level of Bet v 1 sIgE generating a detectable HR (HR > 10% of maximal release) in all the 3 runs was found to be 1.25 kUA/L (corresponding to allergy class 2, 0.71-3.50 kUA/L). Furthermore, sera from allergy classes 3 and 4+ ascertained a significant reproducible HR: 42/42 vs. 5/21 in allergy class 1 and 15/21 in allergy class 2. Using ImmunoCAP™s containing Bet v 1 as a matrix-fixed allergen system, similar results were obtained where the lowest sIgE concentration mediating an HR was 1.68 kUA/L and 7/7 for both allergy classes 3 and 4+., Conclusion: The results demonstrate that the IgE titer is strikingly robust in predicting the ability to sensitize basophils and produce a measurable HR., Competing Interests: PSS is head of research at RefLab. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Stoffersen, Skov, Poulsen and Jensen.)

The continued use of insecticides for public health and agriculture has led to widespread insecticide resistance and hampering of control methods. Insecticide resistance surveillance of mosquito populations is typically done through Centers for Disease Control and Prevention (CDC) bottle bioassays or World Health Organization (WHO) tube tests. However, these methods can result in a high degree of variability in mortality data due to variable insecticide contact with the insect, the relatively small numbers of organisms tested, extensive variation in mass between populations, and constantly changing environmental conditions, leading to variable outcomes. This paper presents the topical application bioassay, adapted as a high-throughput phenotypic bioassay for both mosquitoes and fruit flies, to test large numbers of insects along a range of insecticide concentrations. This assay 1) ensures consistent treatment and insecticide contact with every organism, 2) produces highly specific dose-response curves that account for differences in average mass between strains and sexes (which is particularly important for field-collected organisms), and 3) allows for the calculation of statistically rigorous median lethal doses (LD50), which are necessary for resistance ratio comparisons-an alternative surveillance approach from diagnostic dose mortality, which is also used for larvicide resistance surveillance. This assay will be a complementary tool for accurately phenotyping mosquito populations and, as illustrated using fruit flies, is easily adaptable for use with other insects. We argue that this assay will help fill the gap between genotypic and phenotypic insecticide resistance in multiple insect species.

Background: Polyethylene glycols (PEGs) are polymers of varying molecular weight (MW) used widely as excipients in drugs and other products, including the mRNA vaccines against coronavirus disease 2019. Allergy to PEGs is rare. Skin testing and graded challenge carries a high risk of inducing systemic reactions., Objective: We evaluated skin prick test (SPT) results and in vitro reactivity over time to different MW PEGs and assessed cross-sensitization patterns in PEG allergy., Methods: Ten patients with previously diagnosed PEG allergy underwent SPT twice with PEGs 26 months apart. Lower MW (PEG 300, 3000, 6000) were tested, followed by PEG 20,000, in stepwise, increasing concentrations. Cross-sensitization to polysorbate 80 and poloxamer 407 was assessed. SPT was performed in 16 healthy controls. In vitro basophil histamine release (HR) test and passive sensitization HR test were performed in patients and controls., Results: Patients previously testing positive on SPT to PEG 3000 and/or 6000 also tested positive to PEG 20,000. Patients with a longer interval since diagnosis tested negative to lower MW PEGs and positive mainly to higher concentrations of PEG 20,000. Three patients developed systemic urticaria during SPT. Eight patients showed cross-sensitization to poloxamer 407 and 3 to polysorbate 80. All controls tested negative. In vitro tests showed limited usefulness., Conclusions: Skin test reactivity to PEG can decrease over time, but titrated SPT with increasing concentrations of PEG 20,000 can be diagnostic when lower MW PEGs test negative. To avoid systemic reactions, stepwise SPT is mandatory., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Technologies have been developed to monitor changes in dermal oedema, indicative of the early signs of pressure ulcers. However, there is limited information on the effects of regional differences in tissue morphology on these sub-epidermal moisture (SEM) parameters. This study was designed to investigate the absolute SEM readings across different anatomical sites using a commercial device., Methods: Twenty-four healthy participants were recruited to evaluate basal SEM values at different bony prominences, sampled by an experienced operator., Results: Distinct differences were observed in unloaded SEM values across different anatomical sites, notably between the upper and lower extremities. A high degree of variability was observed in particular sites, such as the heels. Moreover, SEM values at certain locations revealed significant relationships with age, BMI and gender (p < 0.05)., Conclusion: The study revealed a high level of variability between and within anatomical sites in a healthy cohort of participants. Determining the changes in local skin and sub-dermal tissue status using SEM may require consideration of both site specific and individual demographic factors, with further research needed in cohorts at risk of pressure ulcers., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Skin is constantly exposed to mechanical and chemical insults, in the form of prolonged loading, overhydration or exposure to irritants. An array of non-invasive biophysical tools has been adopted to monitor the changes in skin response. The present study aims to identify a set of robust parameters sensitive to mechanical and chemical challenges to skin integrity., Materials and Methods: Eleven healthy participants were recruited to evaluate the skin response following mechanical loading, tape stripping, overhydration and chemical irritation. Forearm skin responses were recorded at baseline and at three time points following the insult. Measurements included transepidermal water loss, sub-epidermal moisture, erythema and laser Doppler imaging. Thresholds were informed by basal values, and the sensitivity of parameters to detect skin changes was evaluated., Results: High degree of variability in skin response was observed with selected biophysical parameters, such as sub-epidermal moisture, laser Doppler imaging and erythema, even in the absence of an applied insult. Temporal skin response revealed distinct response profiles during each evoked insult. Indeed, the sensitivity of the biophysical parameters was influenced by the threshold values and time point of measurement. Some statistically significant correlations were determined between the biophysical parameters., Conclusion: The study revealed that thresholds derived from single biophysical parameters were limited in detecting skin changes following insults. A complementary evaluation using combined parameters has the potential to provide a more sensitive assessment. Further research is required to identify robust biophysical parameters, to aid the early detection of skin damage in clinical settings., (© 2021 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

Human anaphylactic reactions largely involve an increase in vascular permeability, which is mainly controlled by endothelial cells (ECs). Due to the acute and serious nature of human anaphylaxis, in vivo studies of blood vessels must be replaced or supplemented with in vitro models. Therefore, we used a macromolecular tracer assay (MMTA) to investigate the EC permeability of three phenotypes of human ECs: artery (HAECs), vein (HSVECs) and microvessels from lung (HMLECs). ECs were stimulated with two fast-acting anaphylactic mediators (histamine and platelet-activating factor (PAF)) and one longer-lasting mediator (thrombin). At steady-state conditions, HSVEC monolayers were the most permeable and HMLEC the least (15.8% and 8.3% after 60 min, respectively). No response was found in ECs from artery or vein to any stimuli. ECs from microvessels reacted to stimulation with thrombin and also demonstrated a tendency of increased permeability for PAF. There was no reaction for histamine. This was not caused by missing receptor expression, as all three EC phenotypes expressed receptors for both PAF and histamine. The scarce response to fast-acting mediators illustrates that the MMTA is not suitable for investigating EC permeability to anaphylactic mediators.

The current observational study provides descriptive data on 270 pressure injuries (PrIs) among 142 racially/ethnically diverse nursing home (NH) residents over 16 weeks. Weekly assessments were conducted with the Bates-Jensen Wound Assessment Tool. NH data were obtained from public government websites. NH, resident, and PrI characteristics across race/ethnicity groups were compared using analysis of variance and chi-square. Participants were 62% female and 89% functionally dependent. More Black and Asian individuals had peripheral vascular disease. More Black individuals had persistent trunk and Stage 4 PrIs. Black and Hispanic individuals had normal skin color surrounding PrIs. More Asian individuals had PrIs surrounded by purple/red discolored skin. More Black individuals' heel PrIs were unstageable, necrotic, and showed no granulation. Black and Hispanic individuals exhibited more deep tissue injury. No NH or prevention differences existed. Health disparities found validate administrative data results. Differences in PrI characteristics should be further examined among diverse NH residents. [Journal of Gerontological Nursing, 47(3), 37-46.]., (Copyright 2021, SLACK Incorporated.)

Purpose: To describe relationships between subepidermal moisture (SEM) and visual skin assessment of pressure injury (PI) in children., Design: Prospective descriptive study., Subjects and Setting: Twenty-four participants aged 8 to 16 years recruited from a pediatric orthopedic unit in a children's hospital in Ireland., Methods: Subepidermal moisture measured with the SEM scanner (Bruin Biometrics, Los Angeles, California) ranged from 0 to 7 picoFarads [pF], and visual observation of trunk and heels occurred daily for 3 days after admission to the unit and/or after surgery. Skin was assessed for discoloration categorized as blanchable erythema, stage 1 PI, or deep tissue injury (DTI). Any open wound PI was classified as stage 2, 3, 4, or unstageable. Demographic, medical, and pain data were collected. Chi-square test, t tests, analysis of variance, and regression were used to describe data and examine relationships., Results: Participants were pediatric patients; 100% (n = 24) were white, 62% (n = 15) were female, 8 to 16 years of age (mean = 12.5 ± 2.5 years), and 29% (n = 7) had fractures and 71% (n = 17) surgery diagnoses. Blanchable erythema incidence was 21% (n = 5) and stage 1 PI incidence was 42% (n = 10); nearly all at heels. Deep tissue injury incidence was 4% (one sacral DTI). Stage 2 or greater PI incidence was 4% (one heel stage 2 PI). For skin that was assessed as normal in this pediatric population, SEM for trunk was 2.65 to 2.76 pF and for heels 2.37 to 2.41 pF. Subepidermal moisture for blanchable erythema and stage 1 PI was higher (range, 3.2-3.7 pF) and significant at trochanters and heels (left trochanter: P = .003; right trochanter: P = .02; right and left heels: P = .000). Nominal regression, controlling for participant and assessment day, showed SEM a predictor of erythema and stage 1 PI at heels. We also found that SEM was higher with pain (significant at sacrum and heels)., Conclusions: In this pediatric population, SEM values over skin assessed as normal are lower than SEM values reported for normal skin in adults, 2.37 to 2.76 pF. Subepidermal moisture was significantly higher for blanchable erythema and stage 1 PI at trochanters and heels, and with the presence of pain at sacrum and heels. We recommend that SEM should be examined for detecting PIs in pediatric populations; SEM and pain should be explored in larger pediatric and adult populations.

Background: Anaphylaxis includes mast cell (MC) activation, but less is known about downstream mechanisms (ie, vascular permeability controlled by endothelial cells [ECs]). The TNF-like weak inducer of apoptosis (TWEAK) and its sole receptor, fibroblast growth factor-inducible molecule 14 (Fn14), belong to the TNF superfamily and are involved in proinflammatory responses., Objective: We sought to investigate the role of TWEAK/Fn14 axis in anaphylaxis., Methods: In vivo vascular permeability and mouse models of passive systemic anaphylaxis (PSA) and active systemic anaphylaxis were applied to wild-type (WT), TWEAK- and Fn14-deficient mice (TWEAK -/- and Fn14 -/- , respectively). Primary bone marrow-derived mast cells (BMMCs) and ECs from WT and Fn14 -/- or TWEAK -/- mice were studied. The TWEAK/Fn14 axis was also investigated in human samples., Results: Mice with PSA and active systemic anaphylaxis had increased Fn14 and TWEAK expression in lung tissues and increased serum soluble TWEAK concentrations. TWEAK and Fn14 deficiencies prevent PSA-related symptoms, resulting in resistance to decreased body temperature, less severe reactions, and maintained physical activity. Numbers of MCs after PSA are similar between genotypes in different tissue regions, such as ear skin and the trachea, tongue, peritoneum, lungs, and bone marrow. Moreover, in vitro studies revealed no differences in degranulation or mediator release between WT and Fn14 -/- BMMCs after IgE-FcεRI stimulation. In vivo and in vitro histamine and platelet-activating factor administration increases Fn14 receptor expression in lungs and ECs. Moreover, Fn14 deficiency in ECs maintained in vitro impermeability when stimulated by mediators or activated BMMCs but not by TWEAK -/- BMMCs, indicating that Fn14 is crucial for endothelial barrier function. TWEAK/Fn14 deletion or TWEAK-blocking antibody prevented histamine/platelet-activating factor-induced vascular subcutaneous permeability. Circulating soluble TWEAK levels were increased in patients with anaphylaxis, and plasma from those patients increased Fn14 expression in ECs., Conclusion: The TWEAK/Fn14 axis participates in anaphylactic reactions. Inhibition of TWEAK/Fn14 interaction could be efficacious in anaphylaxis therapy., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Basophils and mast cells are known for their capability to release both preformed and newly synthesized inflammatory mediators. In this chapter, we describe how to stimulate and detect histamine released from basophils in whole blood, purified basophils, in vitro cultured mast cells, and in situ skin mast cells (the latter by microdialysis), using either a solid phase assay or flow cytometry. We also give an example of an activation protocol for basophil and mast cell cytokine release and discuss approaches for cytokine detection.

Basophils have been suggested to express low quantities of RNA, challenging the study of gene expression within these cells. However, the purification technique employed might have an impact on the quantity and quality of RNA purified from basophils. This chapter describes a method which gives an optimal RNA output using a TRIzol-based method in contrast to a commercial kit.

Scope: Allergies to lipid transfer proteins involve severe adverse reactions; thus, effective and sustainable therapies are desired. Previous attempts disrupting disulfide bonds failed to maintain immunogenicity; thus, the aim is to design novel hypoallergenic Pru p 3 variants and evaluate the applicability for treatment of peach allergy., Methods and Results: Pru p 3 proline variant (PV) designed using in silico mutagenesis, cysteine variant (CV), and wild-type Pru p 3 (WT) are purified from Escherichia coli. Variants display homogenous and stable protein conformations with an altered secondary structure in circular dichroism. PV shows enhanced long-term storage capacities compared to CV similar to the highly stable WT. Using sera of 33 peach allergic patients, IgE-binding activity is reduced by 97% (PV) and 71% (CV) compared to WT. Both molecules show strong hypoallergenicity in Pru p 3 ImmunoCAP cross-inhibition and histamine release assays. Immunogenicity of PV is demonstrated with a phosphate-based adjuvant formulation in a mouse model., Conclusions: An in silico approach is used to generate a PV without targeting disulfide bonds, T cell epitopes, or previously reported IgE epitopes of Pru p 3. PV is strongly hypoallergenic while structurally stable and immunogenic, thus representing a promising candidate for peach allergen immunotherapy., (© 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The Bates-Jensen Wound Assessment Tool (BWAT) is used to assess wound healing in clinical practice. The purpose of this study was to evaluate BWAT use among nursing home residents with pressure injury. Findings and reliability estimates from the BWAT related to pressure injury characteristics (stage, anatomic location) and natural history (resolved, persisted) among 142 ethnically and racially diverse residents are reported. In this prospective 16-week study, 305 pressure injuries among 142 participants (34% prevalence) are described by stage, anatomic location, and BWAT scores. Visual and subepidermal moisture assessments were obtained from sacrum, buttock, ischial, and heel ulcers weekly. Participants were 14% Asian, 28% Black, 18% Hispanic, 40% White with a mean age of 78 ± 14 years, and were 62% female; 80% functionally dependent (bed mobility extensive/total assistance) and at risk (Braden Scale score 14 ± 2.7). The reliability coefficient for BWAT score (all participants, all anatomic locations) was high (r = 0.90; p < 0.0001; n = 1,161 observations). Weighted Kappas for characteristics ranging from 0.46 (skin color surrounding wound) to 0.79 (undermining) were consistent for all participants. BWAT scores showed strongest agreement coefficients for stage 4 pressure injury (r = 0.69), pressure injuries among Asian and White ethnicity/racial groups (r = 0.89, and r = 0.91, respectively), and sacrum anatomic location (r = 0.92) indicating scores are better correlated to fair skin tones. Lower agreement coefficients were demonstrated for stage 2 pressure injury (r = 0.38) and pressure injuries among African American and Hispanic ethnicity/racial groups (r = 0.88 and 0.87, respectively). BWAT scores were significantly different by pressure injury stage (F = 496.7, df = 6, p < 0.001) and anatomic location (F = 33.76, df = 8, p < 0.001). BWAT score correlated with pressure injury natural history (ulcer resolved 18.4 ± 7.4, ulcer persisted 24.9 ± 10.0; F = 70.11, df = 2, p < 0.001), but not with comorbidities. The BWAT provides reliable, objective data for assessing pressure injury healing progress., (© 2019 by the Wound Healing Society.)

Introduction: Mast cells are the primary effector cells of allergy. This study aimed at characterizing human peripheral blood-derived mast cells (PBdMC) from peanut allergic and non-allergic subjects by investigating whether the molecular and stimulus-response profile of PBdMC discriminate between peanut allergic and healthy individuals., Methods: PBdMC were generated from eight peanut allergic and 10 non-allergic subjects. The molecular profile (cell surface receptor expression) was assessed using flow cytometry. The stimulus-response profile (histamine release induced by secretagogues, secretion of cytokines/chemokines and changes in miRNA expression following anti-IgE activation) was carried out with histamine release test, luminex multiplex assay and miRNA arrays., Results: Expression of activating receptors (FcϵRI, CD48, CD88, CD117, and C3aR) on PBdMC was not different among peanut allergic and non-allergic subjects. Likewise, inhibitory receptors (CD32, CD200R, CD300a, and siglec-8) displayed comparable levels of expression. Both groups of PBdMC were unresponsive to substance P, compound 48/80 and C5a but released comparable levels of histamine when stimulated with anti-IgE and C3a. Interestingly, among the secreted cytokines/chemokines (IL-8, IL-10, IL-13, IL-23, IL-31, IL-37, MCP-1, VEGF, GM-CSF) PBdMC from peanut allergic subjects showed a different secretion pattern of IL-31 compared to non-allergic subjects. Investigating miRNA expression from resting or activated PBdMC revealed no significantly difference between peanut allergic and non-allergic subjects., Conclusion: The molecular and stimulus-response profile revealed that PBdMC from peanut allergic subjects differently express IL-31 compared to non-allergic subjects. However, since only one altered parameter was found among 893 investigated, it is still questionable if the pathophysiological mechanisms of peanut allergy are revealed in PBdMC., (© 2018 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd.)

We examined subepidermal moisture (SEM) and visual skin assessment of heel pressure injury (PrI) among 417 nursing home residents in 19 facilities over 16 weeks. Participants were older (mean age 77 years), 58% were female, over half were ethnic minorities (29% African American, 12% Asian American, 21% Hispanic), and at risk for PrI (mean Braden Scale Risk score = 15.6). Blinded concurrent visual assessments and SEM measurements were obtained at heels weekly. Visual skin damage was categorised as normal, erythema, stage 1 PrI, deep tissue injury (DTI) or stage 2 or greater PrI. PrI incidence was 76%. Off-loading occurred with pillows (76% of residents) rather than heel boots (21%) and often for those with DTI (91%). Subepidermal moisture was measured with a device where higher readings indicate greater moisture (range: 0-70 tissue dielectric constant), with normal skin values significantly different from values in the presence of skin damage. Subepidermal moisture was associated with concurrent damage and damage 1 week later in generalised multinomial logistic models adjusting for age, diabetes and function. Subepidermal moisture detected DTI and differentiated those that resolved, remained and deteriorated over 16 weeks. Subepidermal moisture may be an objective method for detecting PrI., (© 2017 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Background: Allergy can be diagnosed using basophil tests. Several methods measuring basophil activation are available. This study aimed at comparing basophil activation test (BAT), histamine release assay (HR), and passive sensitization histamine release assay (passive HR) in the diagnosis of peanut allergy., Methods: BAT, HR, and passive HR were performed on 11 peanut-allergic and 14 nonallergic subjects. Blood was incubated with peanut extract or anti-IgE and tests were performed as follows: BAT-CD63 upregulation was assessed by flow cytometry; HR-released histamine was quantified by a glass fiber-based fluorometric method; passive HR-IgE-stripped donor basophils were incubated with participants' serum and histamine release was quantified as HR., Results: CDsens, a measure of basophil allergen sensitivity, was significantly higher for BAT (80.1±17.4) compared to HR (23.4±10.31) and passive HR (11.1±2.0). BAT, HR, and passive HR had a clinical sensitivity of 100%, 100%, and 82% and specificity of 100%, 100%, and 100%, respectively, when excluding inconclusive results. BAT identified 11 of 11 allergic patients, HR 10, and passive HR 9. Likewise, BAT recognized 12 of 14 nonallergic subjects, HR 10, and passive HR 13. However, the tests' diagnostic performances were not statistically different. Interestingly, nonreleasers in HR but not in BAT had lower basophil count compared to releasers (249 vs 630 counts/min)., Conclusion: BAT displayed a significantly higher CDsens compared to HR and passive HR. The basophil tests' diagnostic performances were not significantly different. Still, BAT could diagnose subjects with low basophil number in contrast to HR., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Anaphylaxis, the most serious and life-threatening allergic reaction, produces the release of inflammatory mediators by mast cells and basophils. Regulator of calcineurin 1 (Rcan1) is a negative regulator of mast-cell degranulation. The action of mediators leads to vasodilation and an increase in vascular permeability, causing great loss of intravascular volume in a short time. Nevertheless, the molecular basis remains unexplored on the vascular level. We investigated Rcan1 expression induced by histamine, platelet-activating factor (PAF), and epinephrine in primary human vein (HV)-/artery (HA)-derived endothelial cells (ECs) and human dermal microvascular ECs (HMVEC-D). Vascular permeability was analyzed in vitro in human ECs with forced Rcan1 expression using Transwell migration assays and in vivo using Rcan1 knockout mice. Histamine, but neither PAF nor epinephrine, induced Rcan1-4 mRNA and protein expression in primary HV-ECs, HA-ECs, and HMVEC-D through histamine receptor 1 (H1R). These effects were prevented by pharmacological inhibition of calcineurin with cyclosporine A. Moreover, intravenous histamine administration increased Rcan1 expression in lung tissues of mice undergoing experimental anaphylaxis. Functional in vitro assays showed that overexpression of Rcan1 promotes barrier integrity, suggesting a role played by this molecule in vascular permeability. Consistent with these findings, in vivo models of subcutaneous and intravenous histamine-mediated fluid extravasation showed increased response in skin, aorta, and lungs of Rcan1 -deficient mice compared with wild-type animals. These findings reveal that endothelial Rcan1 is synthesized in response to histamine through a calcineurin-sensitive pathway and may reduce barrier breakdown, thus contributing to the strengthening of the endothelium and resistance to anaphylaxis. These new insights underscore its potential role as a regulator of sensitivity to anaphylaxis in humans.

Anaphylaxis in humans is inherently difficult to study due to the acuteness of symptoms and the lack of biomarkers serving as risk predictors. Most cases are related to IgE sensitizations to foods, insect venoms, and drugs with mastocytosis patients forming a smaller risk group. However, identifying the relatively small fraction of persons at risk has been exceedingly difficult. In this review, we propose to describe anaphylaxis in a broader context than defined by IgE sensitization alone. Exposure to a trigger, such as an allergen, may lead to anaphylaxis, but in particular, the internal dose sensed by the immune system needs to be established. Moreover, intrinsic patient factors as well as the specific circumstances of the exposure, i.e., the extrinsic factors, need to be thoroughly accounted for. More controversially, other triggers of anaphylaxis, such as increased sensitivity to or reduced catabolism of histamine ("histamine intolerance") or mast cell activation syndrome also named mast cell activation disorder have been suggested, but still with very limited epidemiological evidence that a significant proportion of the observed reactions are caused by these alleged conditions. Thus, when all conditions are considered, it seems as if IgE-mediated reactions are responsible for the vast majority of anaphylactic conditions.

We examined the relationship between subepidermal moisture measured using surface electrical capacitance and visual skin assessment of pressure ulcers at the trunk location (sacral, ischial tuberosities) in 417 nursing home residents residing in 19 facilities. Participants were on average older (mean age of 77 years), 58% were female, over half were ethnic minorities (29% African American, 12% Asian American, and 21% Hispanic), and at risk for pressure ulcers (mean score for Braden Scale for Predicting Pressure Ulcer Risk of 15.6). Concurrent visual assessments and subepidermal moisture were obtained at the sacrum and right and left ischium weekly for 16 weeks. Visual assessment was categorized as normal, erythema, stage 1 pressure ulcer, Deep Tissue Injury or stage 2+ pressure ulcer using the National Pressure Ulcer Advisory Panel 2009 classification system. Incidence of any skin damage was 52%. Subepidermal moisture was measured with a dermal phase meter where higher readings indicate greater moisture (range: 0-70 tissue dielectric constant), with values increasing significantly with the presence of skin damage. Elevated subepidermal moisture values co-occurred with concurrent skin damage in generalized multinomial logistic models (to control for repeated observations) at the sacrum, adjusting for age and risk. Higher subepidermal moisture values were associated with visual damage 1 week later using similar models. Threshold values for subepidermal moisture were compared to visual ratings to predict skin damage 1 week later. Subepidermal moisture of 39 tissue dielectric constant units predicted 41% of future skin damage while visual ratings predicted 27%. Thus, this method of detecting early skin damage holds promise for clinicians, especially as it is objective and equally valid for all groups of patients., (© 2017 by the Wound Healing Society.)

Purpose: Benzoxazinoids (BXs) are a group of wholegrain phytochemicals with potential pharmacological properties; however, limited information exists on their absorption, metabolism, and excretion in humans. The aim of this study was to investigate the dose-dependent uptake and excretion of dietary BXs in a healthy population., Methods: Blood and urine were collected from 19 healthy participants from a crossover study after a washout, a LOW BX diet or HIGH BX diet, and analysed for 12 BXs and 4 phenoxazinone derivatives., Results: We found that the plasma BX level peaked approximately 3 h after food intake, whereas BXs in urine were present even at 36 h after consuming a meal. No phenoxazinone derivatives could be detected in either plasma or urine. The dominant BX metabolite in both plasma and urine was 2-β-D-glucopyranosyloxy-1,4-benzoxazin-3-one (HBOA-Glc), even though 2-β-D-glucopyranosyloxy-4-hydroxy-1,4-benzoxazin-3-one (DIBOA-Glc) was the major component in the diet., Conclusion: The dietary BX treatment correlated well with the plasma and urine levels, illustrating strong dose-dependent BX absorption, which also had a rapid washout, especially from the plasma compartment.

Objective: To identify characteristics associated with pressure ulcer (PrU) healing for individuals with spinal cord injury (SCI)., Design: Secondary analysis of a large clinical trial's data for healing PrUs in individuals with SCI; prospective Delphi process was conducted with SCI and/or PrU experts., Setting: Spinal cord injury centers., Participants: There were 629 screening and 162 treatment participants (N=791); 185 SCI clinicians/national PrU/wound care experts participated in the Delphi process., Interventions: None., Main Outcome Measure: PrU healing of 50% and 100% at weeks 4 and 12., Results: Poisson regression models using the top Delphi-recommended factors found that only ulcer stage consistently predicted 50% and 100% healing at weeks 4 and 12. Additionally, ischial/perineal location was associated with 33% higher likelihood of 50% healing at week 4. Patient noncompliance with treatment recommendations, the top-ranked Delphi factor, did not predict healing at week 4 or 12. Expanded models found that at week 4, baseline PrU size, PrU stage IV, PrU pain, and American Spinal Injury Association grade A significantly predicted 100% healing, while at week 12, only PrU stage (IV) significantly predicted 100% healing. Significant predictors of 50% healing at week 4 included baseline PrU size, stage, ischial/perianal location body mass index >30kg/m 2 , foul odor, and signs of infection. At week 12, PrU duration, paraplegia predicted 50% healing. SCI center identifiers consistently showed 2- to 5-fold variation in predicting 50% PrU healing at weeks 4 and 12., Conclusions: Delphi panel-recommended factors (eg, patient compliance) did not predict PrU healing. Reducing center-level variability in wound healing by learning from best practices should be a health system goal. PrU healing in SCI is still poorly understood, and future studies should focus on as yet unidentified or underappreciated factors., (Published by Elsevier Inc.)

Aims: To assess the feasibility of classifying skin tone using Munsell color chart values and to compare Munsell-based skin tone categories to ethnicity/race to predict pressure ulcer risk., Background: Pressure ulcer classification uses level of visible tissue damage, including skin discoloration over bony prominences. Prevention begins with early detection of damage. Skin discoloration in those with dark skin tones can be difficult to observe, hindering early detection., Design: Observational cohort of 417 nursing home residents from 19 nursing homes collected between 2009-2014, with weekly skin assessments for up to 16 weeks., Methods: Assessment included forearm and buttocks skin tone based on Munsell values (Dark, Medium, Light) at three time points, ethnicity/race medical record documentation, and weekly skin assessment on trunk and heels., Results: Inter-rater reliability was high for forearm and buttock values and skin tone. Mean Munsell buttocks values differed significantly by ethnicity/race. Across ethnicity/race, Munsell value ranges overlapped, with the greatest range among African Americans. Trunk pressure ulcer incidence varied by skin tone, regardless of ethnicity/race. In multinomial regression, skin tone was more predictive of skin damage than ethnicity/race for trunk locations but ethnicity/race was more predictive for heels., Conclusions: Given the overlap of Munsell values across ethnicity/race, color charts provide more objective measurement of skin tone than demographic categories. An objective measure of skin tone can improve pressure ulcer risk assessment among patients for whom current clinical guidelines are less effective., (© 2016 John Wiley & Sons Ltd.)

Background: Chlorhexidine is an effective disinfectant, which may cause severe allergic reactions. Plasma level of specific IgE to chlorhexidine (ImmunoCAP(®) ) has high estimated sensitivity and specificity when measured within 6 months of allergic reaction, but knowledge of the dynamics over longer time periods is lacking and it is unknown whether levels fall below <0.35 kUA/L in patients with previously elevated levels. It is also unclear whether re-exposure influences levels of specific IgE., Objective: To investigate the dynamics of specific IgE in chlorhexidine allergic patients with and without re-exposure., Methods: All patients diagnosed with chlorhexidine allergy in the Danish Anaesthesia Allergy Centre January 1999 to March 2015 were invited to participate. The study included blood samples from the time of reaction and time of investigation and blood samples drawn prospectively over several years., Results: Overall, 23 patients were included. Specific IgE within hours of reaction was available in eight patients and was >0.35 kUA/L in six of these. During allergy investigations, usually 2-4 months later, specific IgE was >0.35 kUA/L in 22 of 23 patients. In the following months/years specific IgE declined <0.35 kUA/L in 17 of 23 patients (most rapidly within 4 months). Nine re-exposures in the healthcare setting were reported by seven patients (35%). Most re-exposures caused symptoms and were followed by an increase in specific IgE. Two patients with specific IgE <0.35 kUA/L reacted upon re-exposure., Conclusions & Clinical Relevance: Time from reaction should be considered when interpreting specific IgE results. Specific IgE is >0.35 kUA/L in most patients at time of reaction but should be repeated after a few weeks/months if negative. The optimal sampling time seems to be >1 month and <4 months. A value <0.35 kUA/L neither excludes allergy nor implies loss of reactivity in previously sensitized patients. Re-exposures are common, often iatrogenic, and can cause a rebound in specific IgE., (© 2016 John Wiley & Sons Ltd.)