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Silica nonwoven fabrics (SNF) prepared using electrospinning have high biocompatibility, thermal stability, and porosity that allows growing three-dimensional culture of cells. In this study, we used SNF to construct a three-dimensional artificial skin model consisting of epidermal and dermal layers with immortalized and primary human cell lines, creating a novel model that minimizes tissue shrinkage. As a result, SNF dermal/epidermal models have enhanced functions in the basement membrane, whereas Collagen dermal/epidermal models have advantages in keratinization and barrier functions. The SNF dermal/epidermal model with mechanical strength formed a basement membrane mimicking structure, suggesting the construction of a stable skin model. Next, we constructed three-dimensional skin models consisting of SNF and collagen. In the combination models, the expression of genes in the basement membrane was significantly increased compared with that in the Collagen dermal/epidermal model, and the gene for keratinization was increased compared with that in the SNF dermal/epidermal model. We believe that the combination model can be a biomimetic model that takes advantage of both SNF and collagen and can be applied to various basic research. Our new skin model is expected to be an alternative method for skin testing to improve the shrinkage of the collagen matrix gel.

To improve the accuracy of skin sensitization prediction of chemicals by conventional alternative methods using cells, it is important to reproduce the environment of skin in vitro, such as the crosstalk between keratinocytes and dendritic cells (DCs). We developed a skin sensitization test system based on the markers and criteria of the human cell line activation test (h-CLAT), which combines THP-1 cells as a surrogate for DCs and keratinized normal human epidermal keratinocytes (NHEK). After exposure to chemicals via keratinized NHEK, the cell surface expression of CD54 and CD86 on THP-1 was measured by flow cytometry. This co-culture system evaluated 2,4-dinitrochlorobenzene (DNCB), a typical sensitizer, as positive, lactic acid (LA), a non-sensitizer, as negative, and isoeugenol (IE), a prohapten that requires biological activation to acquire skin sensitization, as positive. However, the expression levels of CD54 and CD86 in DNCB-treated THP-1 were lower than those in normal h-CLAT. Therefore, we investigated the effects of the medium and secretion by NHEK cells on THP-1 cells. CD54 and CD86 expression was enhanced in monocultured THP-1 in the medium for keratinized NHEK and in the conditioned medium of keratinized NHEK. The increase in CD54 and CD86 by changes in the medium type was higher than that by the NHEK secretion; therefore, it was found that the medium composition has a large effect on the evaluation index among the experimental parameters in the co-culture system. It is necessary to find the optimal medium for immunotoxicity assessment in the co-culture system.

Background β‐Lactam allergy is over‐reported and this leads to greater healthcare costs. Allergy testing has inherent risks, yet patients who test negative may continue avoiding β‐lactams. Objective To evaluate the safety and diagnostic value of β‐lactams allergy testing locally and usage of antibiotics following negative testing. Methods We performed a retrospective medical record review and follow‐up survey of patients who underwent β‐lactam testing between 2010 and 2016 at the National Skin Centre, Singapore. Results We reviewed the records of 166 patients, with a total of 173 β‐lactam allergy labels. Eighty (46.2%) labels were to penicillin, 75 (43.1%) to amoxicillin/amoxicillin‐clavulanic acid, 11 (6.4%) to cephalexin, and 5 (2.9%) to others. Skin tests were performed in 142 patients and drug provocation tests (DPTs) in 141 patients. Eleven (6.6%) patients defaulted DPTs after skin testing. Out of 166 patients, 22 (13.3%) patients were proven allergic by either skin tests (16) or DPTs (6). Patients who tested positive had nonsevere reactions. Out of 155 patients who were conclusively evaluated, 133 (85.8%) were not allergic. Of these patients, 30 (22.6%) used the tested β‐lactam subsequently, with one reporting a mild reaction. Fifty‐one (38.3%) patients were uncontactable or uncertain if they consumed a β‐lactam since testing negative. Fifty‐two (39.1%) patients had no re‐exposure (35 had no indication, 17 were fearful of reactions). Conclusion Drug allergy testing was safe and removed inappropriate labels. Clinical Implication Allergy testing is efficacious, but fears of subsequent rechallenge should be addressed to maximize the effectiveness of allergy delabeling. Allergy testing is efficacious, but fears of subsequent rechallenge should be addressed to maximize the effectiveness of allergy delabeling.

The practice of elective penicillin skin testing could be compromised by the fact that patients, their parents, or their physicians remain reluctant to reuse penicillin-class antibiotics (PCAs) despite a negative evaluation by an allergist. This study addresses reuse of PCAs in a pediatric population after negative penicillin skin testing and drug challenge and factors associated with its reluctance. All children evaluated for a history of penicillin allergy at the CHU Sainte-Justine Allergy Clinic between January 1998 and June 2000 with negative skin testing and drug challenge were included in the study. A telephone survey was conducted between May and October 2002 to assess the perception of the initial reaction by the parents, subsequent use of antibiotics, and antibiotic-related adverse reactions. Among the 200 children selected, parents of 170 (85%) children completed the survey. Since the allergist evaluation, 130 (76%) children had received antibiotics. PCA was used in 59 (45%) children. Parents of 24 (18%) children refused PCAs because they still feared an adverse reaction. They were more likely to have been very frightened by their child's allergic reaction than other parents whose children had used PCAs (p = 0.008). Although elective penicillin skin testing is useful and safe in the pediatric population, a significant proportion of parents still refuse PCAs even though they are needed. Identification of parents that were very frightened by their children's allergic reactions and additional reassurance could improve this situation.

Anti-IgE therapy with omalizumab, a recombinant humanized monoclonal antibody, has anti-inflammatory effects in allergic asthma and rhinitis. Although omalizumab has been exceptionally safe, reactions after its administration have been reported. The goal of this study was to assess two patients who experienced apparent anaphylaxis after omalizumab administration. Two cases of apparent anaphylaxis after omalizumab administration are reported with diagnostic evaluation using skin testing and unique IgE and IgG anti-omalizumab serological assays. At the time of evaluation, both atopic asthmatic patients had total (free and bound) serum IgE levels of 199 kIU/L (100% free) and 200 kIU/L (80% free and 20% bound), respectively. Epicutaneous skin tests to omalizumab were negative at 150 mg/mL of omalizumab in both subjects and the nonexposed negative control subject. Intradermal skin tests were positive at 0.15 mg/mL in subject 1 and negative at 1.5 mg/mL of omalizumab in subject 2 and the control subject. Intradermal testing to polysorbate produced significant wheal/flare reaction in subject 2 but not in the negative control subject. Serological assays for IgE or IgG antibodies reactive with omalizumab were negative. The in vitro and in vivo immunologic data support the conclusion that the adverse reactions experienced by two patients after omalizumab administration after more than a year of successful omalizumab therapy for asthma were likely anaphylactoid in nature. Polysorbate, an excipient in omalizumab, is known to cause similar reactivity to other medicines and is the most likely cause of these reactions.

We investigated and modeled the temporal evolution of motion sickness in a highly dynamic sickening drive. Slalom maneuvers were performed in a passenger vehicle, resulting in lateral accelerations of 0.4 g at 0.2 Hz, to which participants were subjected as passengers for up to 30 min. Subjective motion sickness was recorded throughout the sickening drive using the MISC scale. In addition, physiological and postural responses were evaluated by recording head roll, galvanic skin response (GSR) and electrocardiography (ECG). Experiment 1 compared external vision (normal view through front and side car windows) to internal vision (obscured view through front and side windows). Experiment 2 tested hypersensitivity with a second exposure a few minutes after the first drive and tested repeatability of individuals’ sickness responses by measuring these two exposures three times in three successive sessions. An adapted form of Oman’s model of nausea was used to quantify sickness development, repeatability, and motion sickness hypersensitivity at an individual level. Internal vision was more sickening compared to external vision with a higher mean MISC (4.2 vs. 2.3), a higher MISC rate (0.59 vs. 0.10 min−1) and more dropouts (66% vs. 33%) for whom the experiment was terminated due to reaching a MISC level of 7 (moderate nausea). The adapted Oman model successfully captured the development of sickness, with a mean model error, including the decay during rest and hypersensitivity upon further exposure, of 11.3%. Importantly, we note that knowledge of an individuals’ previous motion sickness response to sickening stimuli increases individual modeling accuracy by a factor of 2 when compared to group-based modeling, indicating individual repeatability. Head roll did not vary significantly with motion sickness. ECG varied slightly with motion sickness and time. GSR clearly varied with motion sickness, where the tonic and phasic GSR increased 42.5% and 90%, respectively, above baseline at high MISC levels, but GSR also increased in time independent of motion sickness, accompanied with substantial scatter.

BackgroundEmotion processing deficits have been identified as a critical transdiagnostic factor that facilitates distress after trauma exposure. Limited skills in identifying and labelling emotional states (i.e. alexithymia) may present on the more automated (less conscious) end of the spectrum of emotional awareness and clarity. Individuals with alexithymia tend to exhibit a disconcordance between subjective experience and autonomic activity (e.g. where high levels of subjective emotional intensity are associated with low physiological arousal), which may exacerbate distress. Although there is a robust link between alexithymia and trauma exposure, no work to date has explored whether alexithymia is associated with emotional response disconcordance among trauma-exposed adults.MethodUsing a validated trauma script paradigm, the present study explored the impact of alexithymia on emotion response concordance [skin conductance (Galvanic Skin Response, GSR) and Total Mood Disturbance (TMD)] among 74 trauma-exposed adults recruited via a posttraumatic stress disorder (PTSD) treatment clinic and student research programme.ResultsUnlike posttraumatic symptom severity, age, sex, participant type and mood (which showed no effect on emotion response concordance), alexithymia was associated with heightened emotion response disconcordance between GSR and TMD [F(1, 37) = 8.93, p = 0.006], with low GSR being associated with high TMD. Observed effects of the trauma script were entirely accounted for by the interaction with alexithymia, such that those with alexithymia showed a negligible association between subjective and physiological states.ConclusionThis finding is paramount as it shows that a large proportion of trauma-exposed adults have a divergent emotion engagement profile.

Delayed drug hypersensitivity reactions are clinically diverse reactions that vary from isolated benign skin conditions that remit quickly with no or symptomatic treatment, drug discontinuation or even continued drug treatment, to the other extreme of severe cutaneous adverse reactions (SCARs) that are associated with presumed life-long memory T-cell responses, significant acute and long-term morbidity and mortality. Diagnostic “in clinic” approaches to delayed hypersensitivity reactions have included patch testing (PT), delayed intradermal testing (IDT) and drug challenges for milder reactions. Patch and IDT are, in general, performed no sooner than 4–6 weeks after resolution of the acute reaction at the maximum non-irritating concentrations. Functional in vitro and ex vivo assays have largely remained the province of research laboratories and include lymphocyte transformation test (LTT) and cytokine release enzyme linked ImmunoSpot (ELISpot) assay, an emerging diagnostic tool which uses cytokine release, typically IFN-γ, after the patient’s peripheral blood mononuclear cells are stimulated with the suspected drug(s). Genetic markers such as human leukocyte antigen have shown recent promise for both pre-prescription screening as well as pre-emptive and diagnostic testing strategies.

Background Emotions play a crucial role in shaping human interactions, decision‐making, and overall well‐being. Emotional assessment is particularly critical for older adults and individuals with Alzheimer's Disease and Alzheimer's Disease Related Dementias (AD/ADRD). Facial expressions are the gold standard of emotion detection in older adults. Due to the applicability in real‐world settings, emotion detection through wearable sensors will be of significant interest. We aim to capture emotional states and their underlying correlation with wearable sensors, considering facial expression as the gold standard. Our analysis can help develop an effective wearable emotion detection system for older adults and people with AD/ADRD. Method The study involved 50 older adults (range: 60‐75 years). They wore wearable sensors that captured physiological data. A facial recognition system analyzed their expressions in real time. Key features include Participant age, and quantified emotions such as Joy, Anger, Surprise, Fear, Contempt, Disgust, and Sadness, derived from facial expression analysis. Physiological signals captured using wearable devices include Galvanic Skin Response (GSR), Heart Rate (HR), Photoplethysmography (PPG). We showed a distribution of emotions for each participant, the baseline set by the iMotion's FACET module and samples outside the first standard deviation (Table 1). Result Figure 1 shows a Gaussian or Normal distribution of emotions that validates the number of active participants to be adequate for the study. Joy and Anger were the most frequent states. Figure 2 shows the correlation heatmap illustrating relationships between emotional evidence scores and physiological sensor data. Here, values closer to 1 refer to strong correlation and the sign refers to the relation. Joy showed a weak positive correlation with heart rate (r = 0.15, p < 0.05), while Fear was moderately correlated with GSR conductance (r = 0.35, p < 0.01). However, Contempt and Disgust exhibited minimal relationships with physiological data. Conclusion Our findings show that there was very little correlation between the facial expression and data captured from wearable sensors. These suggest that traditional statistical modeling may not effectively capture non‐linear dynamics in emotional data. Future research should explore machine learning techniques to better model these complexities and improve emotional detection accuracy.

Purpose of ReviewAn unconfirmed penicillin allergy is known to confer significant risk to patients. Only a small minority of patients labeled with penicillin allergy will be confirmed to be hypersensitive with the current reference standard test, an oral amoxicillin therapeutic dose challenge. Skin testing has been recommended prior to oral challenges to reduce the risk of severe acute challenge reactions. The rate of severe acute anaphylactic reactions with oral amoxicillin is currently extremely low. Unfortunately, penicillin skin testing, as commonly performed, has a high rate of false positive results.Recent FindingsEncouraging skin testing in all individuals with an unconfirmed penicillin allergy, prior to a confirmatory oral challenge, would be technically difficult, make testing all individuals with an unconfirmed penicillin allergy very unlikely, and ultimately increase the risk to patients because of suboptimal antibiotic use. Most patients, who are appropriate candidates for a direct oral amoxicillin challenge, to confirm current penicillin tolerance, can be safely identified by their clinical histories. Higher risk individuals, those with a history of anaphylaxis or other acute onset potentially IgE-mediated reaction such as hives within 6 h of the first dose of the last course of a penicillin, may benefit from properly performed puncture and intradermal skin testing, using commercially available penicilloyl-polylysine, prior to an oral challenge, if skin test negative.SummaryDirect oral amoxicillin challenges in low-risk individuals are well accepted by patients and a safe and effective part of penicillin allergy delabeling.