Skin prick testing does not reflect the presence of IgE against food allergens in adult eosinophilic esophagitis patients: a case study

Skin prick testing is widely used to predict the presence of allergen-specific IgE. In eosinophilic esophagitis patients, who frequently exhibit polysensitization and broad reactivity upon skin prick testing, this is commonly used to aid avoidance recommendations in the clinical management of their disease. We present here the predictive value of skin prick testing for the presence of allergen-specific IgE, in 12 patients, determined by immunoblot against the allergen extracts using individual-matched serum. Our results demonstrate a high degree of predictive value for aeroallergens but a poor predictive value for food allergens. This suggests that skin prick testing likely identifies IgE reactivity towards aeroallergens in adult eosinophilic esophagitis but this is not true for foods. Consequently, IgE immunoblotting might be required for determining food avoidance in these patients

Towards Training the Extended Voltage Manifold Computer (EVMC) using Particle Swarm Optimization

poster abstractExtended Analog Computers (EAC) have been explored as a substrate for unconventional computing techniques since the early 1990s. A particular strength of the technique is the near instantaneous speed it solves computational problems. However, application of the EAC and specific EAC classes, as the Extended Voltage Manifold Computer (EVMC), to real-world problems await the development of methods to program EACs. A property of the EVMC is that each output voltage can be described by a class of radial basis functions (RBF). Linking multiple EVMCs, a neural network called a radial basis function network (RBFN) can be implemented. The specific aim of this work is to develop the means to train EVMCs and networks of EVMC based RBFNs. The strategy employed in the present work is to develop a method using EVMCs implemented as finite element method (FEM) simulations to define the error state-space and error gradient of the untrained EVMC manifold. Once defined the EVMC simulation can be recursively configured to reduce the error in a Hebbian sense. Furthermore, particle swarm optimization (PSO) is being explored to improve the speed of convergence. FEM simulations were constructed using COMSOL Multiphysics to model EVMC manifolds in different states. In parallel, a particle swarm optimizer was altered to demonstrate training of simple RBF manifolds. Examination of FEM simulations verified the kernel function as hyperbolic and radially based. These preliminary findings indicated that the EVMC can be accurately modeled and manipulated using COMSOL, and PSO can be used once the error manifold is defined. From this we can take the possibility of improving the speed of training the EVMC via PSO. The next step to verify this possibility is to combine the COMSOL and Python codes to confirm the EVMC can be trained

Immune Sensitization in the Skin Is Enhanced by Antigen-Independent Effects of IgE

AbstractContact sensitivity responses require both effective immune sensitization following cutaneous exposure to chemical haptens and antigen-specific elicitation of inflammation upon subsequent hapten challenge. We report that antigen-independent effects of IgE antibodies can promote immune sensitization to haptens in the skin. Contact sensitivity was markedly impaired in IgE−/− mice but was restored by either transfer of sensitized cells from wild-type mice or administration of hapten-irrelevant IgE before sensitization. Moreover, IgE−/− mice exhibited impairment in the reduction of dendritic cell numbers in the epidermis after hapten exposure. Monomeric IgE has been reported to influence mast cell function. We observed diminished contact sensitivity in mice lacking FcϵRI or mast cells, and mRNA for several mast cell-associated genes was reduced in IgE−/− versus wild-type skin after hapten exposure. We speculate that levels of IgE normally present in mice favor immune sensitization via antigen-independent but FcϵRI-dependent effects on mast cells

Impact of anti‐immigrant rhetoric and policies on frontline health and social service providers in Southeast Michigan, U.S.A

Rising hostility towards immigrants characterised the 2016 Presidential election in the United States (US) and subsequent policy priorities by the new presidential administration. The political shift towards aggressive policies targeting undocumented immigrants is far‐reaching and extends into other communities that convive con—or coexist with—immigrant communities. Our study aims to examine the rippling effects of these anti‐immigrant policies and rhetoric on health and social service providers in Southeast Michigan who predominantly serve Latino immigrants. Between April and August 2018, we conducted in‐depth individual interviews in two Federally Qualified Health Centers and a non‐profit social service agency at a county health department. We interviewed 28 frontline health and social service providers. After coding and thematic analyses, we found that staff members’ experiences in supporting immigrant clients was congruent with definitions of secondary trauma stress and compassion fatigue, whereby exposure to clients’ trauma combined with job burden subsequently impacted the mental health of providers. Major themes included: (a) frontline staff experienced a mental and emotional burden in providing services to immigrant clients given the restrictive anti‐immigrant context; and (b) this burden was exacerbated by the increased difficulties in providing these services to their clients. Staff described psychological and emotional distress stemming from exposure to clients’ immigration‐related trauma and increased mental health needs. This distress was exacerbated by an increased demand to meet clients’ needs, which involved explaining or translating documents into English, assisting with legal paperwork, referring clients to mental health resources, addressing increased transportation barriers, and reestablishing trust with the community. Our findings add qualitative data on the mental health implications for frontline providers who support Latino immigrant clients impacted by immigration and highlights the need for further research and resources that address the workplace‐related stress generated by heightened immigration enforcement.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163387/2/hsc13012.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163387/1/hsc13012_am.pd

Trade-offs in marine protection : Multi-species interactions within a community-led temperate marine reserve

This study investigated the effects of a community-led temperate marine reserve in Lamlash Bay, Firth of Clyde, Scotland, on commercially important populations of European lobster (Homarus gammarus), brown crab (Cancer pagurus), and velvet swimming crabs (Necora puber). Potting surveys conducted over 4 years revealed significantly higher catch per unit effort (cpue 109% greater), weight per unit effort (wpue 189% greater), and carapace length (10-15 mm greater) in lobsters within the reserve compared with control sites. However, likely due to low levels of recruitment and increased fishing effort outside the reserve, lobster catches decreased in all areas during the final 2 years. Nevertheless, catch rates remained higher within the reserve across all years, suggesting the reserve buffered these wider declines. Additionally, lobster cpue and wpue declined with increasing distance from the boundaries of the marine reserve, a trend which tag-recapture data suggested were due to spillover. Catches of berried lobster were also twice as high within the reserve than outside, and the mean potential reproductive output per female was 22.1% greater. It was originally thought that higher densities of lobster within the reserve might lead to greater levels of aggression and physical damage. However, damage levels were solely related to body size, as large lobsters >110 mm had sustained over 218% more damage than smaller individuals. Interestingly, catches of adult lobsters were inversely correlated with those of juvenile lobsters, brown crabs, and velvet crabs, which may be evidence of competitive displacement and/or predation. Our findings provide evidence that temperate marine reserves can deliver fisheries and conservation benefits, and highlight the importance of investigating multispecies interactions, as the recovery of some species can have knock-on effects on others

Targeted Inactivation of the IL-4 Receptor α Chain I4R Motif Promotes Allergic Airway Inflammation

The insulin/interleukin-4 (IL-4) receptor (I4R) motif mediates the association of insulin receptor substrate (IRS)-2 with the interleukin-4 (IL-4)Rα chain and transduces mitogenic signals in response to IL-4. Its physiological functions were analyzed in mice with a germline point mutation that changed the motif's effector tyrosine residue into phenylalanine (Y500F). The Y500F mutation abrogated IRS-2 phosphorylation and impaired IL-4–induced CD4+ T lymphocyte proliferation but left unperturbed Stat6 activation, up-regulation of IL-4-responsive gene products, and Th cell differentiation under Th2 polarizing conditions. However, in vivo the Y500F mutation was associated with increased allergen-induced IgE production, airway responsiveness, tissue eosinophilia, and mucus production. These results define an important role for the I4R motif in regulating allergic inflammation

Experimental and Computational Studies of Single-Molecule Conductance of Ru(II) and Pt(II) trans-Bis(acetylide) Complexes

The single-molecule conductance of metal complexes of the general forms trans-Ru(C≡CArC≡CY)2(dppe)2 and trans-Pt(C≡CArC≡CY)2(PPh3)2 (Ar = 1,4-C6H2-2,5-(OC6H13)2; Y = 4-C5H4N, 4-C6H4SMe) have been determined using the STM I(s) technique. The complexes display high conductance (Y = 4-C5H4N, M = Ru (0.4 ± 0.18 nS), Pt (0.8 ± 0.5 nS); Y = 4-C6H5SMe, M = Ru (1.4 ± 0.4 nS), Pt (1.8 ± 0.6 nS)) for molecular structures of ca. 3 nm in length, which has been attributed to transport processes arising from tunneling through the tails of LUMO state

The targeted delivery of multicomponent cargos to cancer cells by nanoporous particle-supported lipid bilayers.

Encapsulation of drugs within nanocarriers that selectively target malignant cells promises to mitigate side effects of conventional chemotherapy and to enable delivery of the unique drug combinations needed for personalized medicine. To realize this potential, however, targeted nanocarriers must simultaneously overcome multiple challenges, including specificity, stability and a high capacity for disparate cargos. Here we report porous nanoparticle-supported lipid bilayers (protocells) that synergistically combine properties of liposomes and nanoporous particles. Protocells modified with a targeting peptide that binds to human hepatocellular carcinoma exhibit a 10,000-fold greater affinity for human hepatocellular carcinoma than for hepatocytes, endothelial cells or immune cells. Furthermore, protocells can be loaded with combinations of therapeutic (drugs, small interfering RNA and toxins) and diagnostic (quantum dots) agents and modified to promote endosomal escape and nuclear accumulation of selected cargos. The enormous capacity of the high-surface-area nanoporous core combined with the enhanced targeting efficacy enabled by the fluid supported lipid bilayer enable a single protocell loaded with a drug cocktail to kill a drug-resistant human hepatocellular carcinoma cell, representing a 10(6)-fold improvement over comparable liposomes

Type 2 cytokines sensitize human sensory neurons to itch-associated stimuli

IntroductionChronic itch is a central symptom of atopic dermatitis. Cutaneous afferent neurons express receptors interleukins (IL)-4, IL-13, and IL-33, which are type 2 cytokines that are elevated in atopic dermatitis. These neuronal cytokine receptors were found to be required in several murine models of itch. Prior exposure of neurons to either IL-4 or IL-33 increased their response to subsequent chemical pruritogens in mice but has not been previously examined in humans. The objective of the present study was to determine if type 2 cytokine stimulation sensitizes sensory neurons to future itch stimuli in a fully human ex vivo system.MethodsWe measured calcium flux from human dorsal root ganglia cultures from cadaveric donors in response to pruritogens following transient exposure to type 2 cytokines. We also measured their effect on neuronal calcium flux and changes in gene expression by RNA sequencing.ResultsType 2 cytokines (IL-4, IL-13, and IL-33) were capable of sensitizing human dorsal root ganglia neurons to both histaminergic and nonhistaminergic itch stimuli. Sensitization was observed after only 2 h of pruritogen incubation. We observed rapid neuronal calcium flux in a small subset of neurons directly in response to IL-4 and to IL-13, which was dependent on the presence of extracellular calcium. IL-4 and IL-13 induced a common signature of upregulated genes after 24 h of exposure that was unique from IL-33 and non-type 2 inflammatory stimuli.DiscussionThis study provides evidence of peripheral neuron sensitization by type 2 cytokines as well as broad transcriptomic effects in human sensory ganglia. These studies identify both unique and overlapping roles of these cytokines in sensory neurons